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Sample records for blood stage vaccine

  1. Whole organism blood stage vaccines against malaria.

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    Stanisic, Danielle I; Good, Michael F

    2015-12-22

    Despite a century of research focused on the development and implementation of effective control strategies, infection with the malaria parasite continues to result in significant morbidity and mortality worldwide. An effective malaria vaccine is considered by many to be the definitive solution. Yet, after decades of research, we are still without a vaccine that is capable of inducing robust, long lasting protection in naturally exposed individuals. Extensive sub-unit vaccine development focused on the blood stage of the malaria parasite has thus far yielded disappointing results. There is now a renewed focus on whole parasite vaccine strategies, particularly as they may overcome some of the inherent weaknesses deemed to be associated with the sub-unit approach. This review discusses the whole parasite vaccine strategy focusing on the blood stage of the malaria parasite, with an emphasis on recent advances and challenges in the development of killed and live attenuated vaccines. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Progress and prospects for blood-stage malaria vaccines.

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    Miura, Kazutoyo

    2016-06-01

    There have been significant decreases in malaria mortality and morbidity in the last 10-15 years, and the most advanced pre-erythrocytic malaria vaccine, RTS,S, received a positive opinion from European regulators in July 2015. However, no blood-stage vaccine has reached a phase III trial. The first part of this review summarizes the pros and cons of various assays and models that have been and will be used to predict the efficacy of blood-stage vaccines. In the second part, blood-stage vaccine candidates that showed some efficacy in human clinical trials or controlled human malaria infection models are discussed. Then, candidates under clinical investigation are described in the third part, and other novel candidates and strategies are reviewed in the last part.

  3. Blood-stage malaria vaccines: post-genome strategies for the identification of novel vaccine candidates.

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    Ntege, Edward H; Takashima, Eizo; Morita, Masayuki; Nagaoka, Hikaru; Ishino, Tomoko; Tsuboi, Takafumi

    2017-08-01

    An efficacious malaria vaccine is necessary to advance the current control measures towards malaria elimination. To-date, only RTS,S/AS01, a leading pre-erythrocytic stage vaccine completed phase 3 trials, but with an efficacy of 28-36% in children, and 18-26% in infants, that waned over time. Blood-stage malaria vaccines protect against disease, and are considered effective targets for the logical design of next generation vaccines to improve the RTS,S field efficacy. Therefore, novel blood-stage vaccine candidate discovery efforts are critical, albeit with several challenges including, high polymorphisms in vaccine antigens, poor understanding of targets of naturally protective immunity, and difficulties in the expression of high AT-rich plasmodial proteins. Areas covered: PubMed ( www.ncbi.nlm.nih.gov/pubmed ) was searched to review the progress and future prospects of malaria vaccine research and development. We focused on post-genome vaccine candidate discovery, malaria vaccine development, sequence diversity, pre-clinical and clinical trials. Expert commentary: Post-genome high-throughput technologies using wheat germ cell-free protein synthesis technology and immuno-profiling with sera from malaria patients with clearly defined outcomes are highlighted to overcome current challenges of malaria vaccine candidate discovery.

  4. Molecular Basis of Allele-Specific Efficacy of a Blood-Stage Malaria Vaccine: Vaccine Development Implications

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    Ouattara, Amed; Takala-Harrison, Shannon; Thera, Mahamadou A.; Coulibaly, Drissa; Niangaly, Amadou; Saye, Renion; Tolo, Youssouf; Dutta, Sheetij; Heppner, D. Gray; Soisson, Lorraine; Diggs, Carter L.; Vekemans, Johan; Cohen, Joe; Blackwelder, William C.; Dube, Tina; Laurens, Matthew B.; Doumbo, Ogobara K.; Plowe, Christopher V.

    2013-01-01

    The disappointing efficacy of blood-stage malaria vaccines may be explained in part by allele-specific immune responses that are directed against polymorphic epitopes on blood-stage antigens. FMP2.1/AS02A, a blood-stage candidate vaccine based on apical membrane antigen 1 (AMA1) from the 3D7 strain of Plasmodium falciparum, had allele-specific efficacy against clinical malaria in a phase II trial in Malian children. We assessed the cross-protective efficacy of the malaria vaccine and inferred which polymorphic amino acid positions in AMA1 were the targets of protective allele-specific immune responses. FMP2.1/AS02A had the highest efficacy against AMA1 alleles that were identical to the 3D7 vaccine-type allele at 8 highly polymorphic amino acid positions in the cluster 1 loop (c1L) but differed from 3D7 elsewhere in the molecule. Comparison of the incidence of vaccine-type alleles before and after vaccination in the malaria vaccine and control groups and examination of the patterns of allele change at polymorphic positions in consecutive malaria episodes suggest that the highly polymorphic amino acid position 197 in c1L was the most critical determinant of allele-specific efficacy. These results indicate that a multivalent AMA1 vaccine with broad efficacy could include only a limited set of key alleles of this extremely polymorphic antigen. PMID:23204168

  5. A whole parasite vaccine to control the blood stages of Plasmodium: the case for lateral thinking.

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    Good, Michael F

    2011-08-01

    Now, 27 years following the cloning of malaria antigens with the promise of the rapid development of a malaria vaccine, we face significant obstacles that are belatedly being addressed. Poor immunogenicity of subunit vaccine antigens and significant antigenic diversity of target epitopes represent major hurdles for which there are no clear strategies for a way forward within the current paradigm. Thus, a different paradigm - a vaccine that uses the whole organism - is now being examined. Although most advances in this approach relate to a vaccine for the pre-erythrocytic stages (sporozoites, liver stages), this opinion paper will outline the possibilities of developing a whole parasite vaccine for the blood stage and address some of the challenges for this strategy, which are entirely different to the challenges for a subunit vaccine. It is the view of the author that both vaccine paradigms should be pursued, but that success will come more quickly using the paranormal approach of exposing individuals to ultra-low doses of whole attenuated or killed parasites. Copyright © 2011. Published by Elsevier Ltd.

  6. A Field Trial to Assess a Blood-Stage Malaria Vaccine

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    Thera, Mahamadou A.; Doumbo, Ogobara K.; Coulibaly, Drissa; Laurens, Matthew B.; Ouattara, Amed; Kone, Abdoulaye K.; Guindo, Ando B.; Traore, Karim; Traore, Idrissa; Kouriba, Bourema; Diallo, Dapa A.; Diarra, Issa; Daou, Modibo; Dolo, Amagana; Tolo, Youssouf; Sissoko, Mahamadou S.; Niangaly, Amadou; Sissoko, Mady; Takala-Harrison, Shannon; Lyke, Kirsten E.; Wu, Yukun; Blackwelder, William C.; Godeaux, Olivier; Vekemans, Johan; Dubois, Marie-Claude; Ballou, W. Ripley; Cohen, Joe; Thompson, Darby; Dube, Tina; Soisson, Lorraine; Diggs, Carter L.; House, Brent; Lanar, David E.; Dutta, Sheetij; Heppner, D. Gray; Plowe, Christopher V.

    2011-01-01

    BACKGROUND Blood-stage malaria vaccines are intended to prevent clinical disease. The malaria vaccine FMP2.1/AS02A, a recombinant protein based on apical membrane antigen 1 (AMA1) from the 3D7 strain of Plasmodium falciparum, has previously been shown to have immunogenicity and acceptable safety in Malian adults and children. METHODS In a double-blind, randomized trial, we immunized 400 Malian children with either the malaria vaccine or a control (rabies) vaccine and followed them for 6 months. The primary end point was clinical malaria, defined as fever and at least 2500 parasites per cubic millimeter of blood. A secondary end point was clinical malaria caused by parasites with the AMA1 DNA sequence found in the vaccine strain. RESULTS The cumulative incidence of the primary end point was 48.4% in the malaria-vaccine group and 54.4% in the control group; efficacy against the primary end point was 17.4% (hazard ratio for the primary end point, 0.83; 95% confidence interval [CI], 0.63 to 1.09; P = 0.18). Efficacy against the first and subsequent episodes of clinical malaria, as defined on the basis of various parasite-density thresholds, was approximately 20%. Efficacy against clinical malaria caused by parasites with AMA1 corresponding to that of the vaccine strain was 64.3% (hazard ratio, 0.36; 95% CI, 0.08 to 0.86; P = 0.03). Local reactions and fever after vaccination were more frequent with the malaria vaccine. CONCLUSIONS On the basis of the primary end point, the malaria vaccine did not provide significant protection against clinical malaria, but on the basis of secondary results, it may have strain-specific efficacy. If this finding is confirmed, AMA1 might be useful in a multicomponent malaria vaccine. PMID:21916638

  7. The evolutionary consequences of blood-stage vaccination on the rodent malaria Plasmodium chabaudi.

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    Victoria C Barclay

    Full Text Available Malaria vaccine developers are concerned that antigenic escape will erode vaccine efficacy. Evolutionary theorists have raised the possibility that some types of vaccine could also create conditions favoring the evolution of more virulent pathogens. Such evolution would put unvaccinated people at greater risk of severe disease. Here we test the impact of vaccination with a single highly purified antigen on the malaria parasite Plasmodium chabaudi evolving in laboratory mice. The antigen we used, AMA-1, is a component of several candidate malaria vaccines currently in various stages of trials in humans. We first found that a more virulent clone was less readily controlled by AMA-1-induced immunity than its less virulent progenitor. Replicated parasites were then serially passaged through control or AMA-1 vaccinated mice and evaluated after 10 and 21 rounds of selection. We found no evidence of evolution at the ama-1 locus. Instead, virulence evolved; AMA-1-selected parasites induced greater anemia in naïve mice than both control and ancestral parasites. Our data suggest that recombinant blood stage malaria vaccines can drive the evolution of more virulent malaria parasites.

  8. A semi-synthetic whole parasite vaccine designed to protect against blood stage malaria.

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    Giddam, Ashwini Kumar; Reiman, Jennifer M; Zaman, Mehfuz; Skwarczynski, Mariusz; Toth, Istvan; Good, Michael F

    2016-10-15

    Although attenuated malaria parasitized red blood cells (pRBCs) are promising vaccine candidates, their application in humans may be restricted for ethical and regulatory reasons. Therefore, we developed an organic microparticle-based delivery platform as a whole parasite malaria-antigen carrier to mimic pRBCs. Killed blood stage parasites were encapsulated within liposomes that are targeted to antigen presenting cells (APCs). Mannosylated lipid core peptides (MLCPs) were used as targeting ligands for the liposome-encapsulated parasite antigens. MLCP-liposomes, but not unmannosylated liposomes, were taken-up efficiently by APCs which then significantly upregulated expression of MHC-ll and costimulatory molecules, CD80 and CD86. Two such vaccines using rodent model systems were constructed - one with Plasmodium chabaudi and the other with P. yoelii. MLCP-liposome vaccines were able to control the parasite burden and extended the survival of mice. Thus, we have demonstrated an alternative delivery system to attenuated pRBCs with similar vaccine efficacy and added clinical advantages. Such liposomes are promising candidates for a human malaria vaccine. Attenuated whole parasite-based vaccines, by incorporating all parasite antigens, are very promising candidates, but issues relating to production, storage and safety concerns are significantly slowing their development. We therefore developed a semi-synthetic whole parasite malaria vaccine that is easily manufactured and stored. Two such prototype vaccines (a P. chabaudi and a P. yoelii vaccine) have been constructed. They are non-infectious, highly immunogenic and give good protection profiles. This semi-synthetic delivery platform is an exciting strategy to accelerate the development of a licensed malaria vaccine. Moreover, this strategy can be potentially applied to a wide range of pathogens. Copyright © 2016 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.

  9. Phase 1 study of a combination AMA1 blood stage malaria vaccine in Malian children.

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    Alassane Dicko

    2008-02-01

    Full Text Available Apical Membrane Antigen-1 (AMA1 is one of the leading blood stage malaria vaccine candidates. AMA1-C1/Alhydrogel consists of an equal mixture of recombinant AMA1 from FVO and 3D7 clones of P. falciparum, adsorbed onto Alhydrogel. A Phase 1 study in semi-immune adults in Mali showed that the vaccine was safe and immunogenic, with higher antibody responses in those who received the 80 microg dose. The aim of this study was to assess the safety and immunogenicity of this vaccine in young children in a malaria endemic area.This was a Phase 1 dose escalating study in 36 healthy children aged 2-3 years started in March 2006 in Donéguébougou, Mali. Eighteen children in the first cohort were randomized 2 ratio 1 to receive either 20 microg AMA1-C1/Alhydrogel or Haemophilus influenzae type b Hiberix vaccine. Two weeks later 18 children in the second cohort were randomized 2 ratio 1 to receive either 80 microg AMA1-C1/Alhydrogel or Haemophilus influenzae type b Hiberix vaccine. Vaccinations were administered on Days 0 and 28 and participants were examined on Days 1, 2, 3, 7, and 14 after vaccination and then about every two months. Results to Day 154 are reported in this manuscript.Of 36 volunteers enrolled, 33 received both vaccinations. There were 9 adverse events related to the vaccination in subjects who received AMA1-C1 vaccine and 7 in those who received Hiberix. All were mild to moderate. No vaccine-related serious or grade 3 adverse events were observed. There was no increase in adverse events with increasing dose of vaccine or number of immunizations. In subjects who received the test vaccine, antibodies to AMA1 increased on Day 14 and peaked at Day 42, with changes from baseline significantly different from subjects who received control vaccine.AMA-C1 vaccine is well tolerated and immunogenic in children in this endemic area although the antibody response was short lived.Clinicaltrials.gov NCT00341250.

  10. Anaemia in a phase 2 study of a blood stage falciparum malaria vaccine

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    Guindo Aldiouma

    2011-01-01

    Full Text Available Abstract Background A Phase 1-2b study of the blood stage malaria vaccine AMA1-C1/Alhydrogel was conducted in 336 children in Donéguébougou and Bancoumana, Mali. In the Phase 2 portion of the study (n = 300, no impact on parasite density or clinical malaria was seen; however, children who received the study vaccine had a higher frequency of anaemia (defined as haemoglobin Methods To further investigate the possible impact of vaccination on anaemia, additional analyses were conducted including patients from the Phase 1 portion of the study and controlling for baseline haemoglobin, haemoglobin types S or C, alpha-thalassaemia, G6PD deficiency, and age. A multiplicative intensity model was used, which generalizes Cox regression to allow for multiple events. Frailty effects for each subject were used to account for correlation of multiple anaemia events within the same subject. Intensity rates were calculated with reference to calendar time instead of time after randomization in order to account for staggered enrollment and seasonal effects of malaria incidence. Associations of anaemia with anti-AMA1 antibody were further explored using a similar analysis. Results A strong effect of vaccine on the incidence of anaemia (risk ratio [AMA1-C1 to comparator (Hiberix]= 2.01, 95% confidence interval [1.26,3.20] was demonstrated even after adjusting for baseline haemoglobin, haemoglobinopathies, and age, and using more sophisticated statistical models. Anti-AMA1 antibody levels were not associated with this effect. Conclusions While these additional analyses show a robust effect of vaccination on anaemia, this is an intensive exploration of secondary results and should, therefore, be interpreted with caution. Possible mechanisms of the apparent adverse effect on haemoglobin of vaccination with AMA1-C1/Alhydrogel and implications for blood stage vaccine development are discussed. The potential impact on malaria-associated anaemia should be closely

  11. Strain-specific Plasmodium falciparum growth inhibition among Malian children immunized with a blood-stage malaria vaccine.

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    Laurens, Matthew B; Kouriba, Bourema; Bergmann-Leitner, Elke; Angov, Evelina; Coulibaly, Drissa; Diarra, Issa; Daou, Modibo; Niangaly, Amadou; Blackwelder, William C; Wu, Yukun; Cohen, Joe; Ballou, W Ripley; Vekemans, Johan; Lanar, David E; Dutta, Sheetij; Diggs, Carter; Soisson, Lorraine; Heppner, D Gray; Doumbo, Ogobara K; Plowe, Christopher V; Thera, Mahamadou A

    2017-01-01

    The blood-stage malaria vaccine FMP2.1/AS02A, comprised of recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1) and the adjuvant system AS02A, had strain-specific efficacy against clinical malaria caused by P. falciparum with the vaccine strain 3D7 AMA1 sequence. To evaluate a potential correlate of protection, we measured the ability of participant sera to inhibit growth of 3D7 and FVO strains in vitro using high-throughput growth inhibition assay (GIA) testing. Sera from 400 children randomized to receive either malaria vaccine or a control rabies vaccine were assessed at baseline and over two annual malaria transmission seasons after immunization. Baseline GIA against vaccine strain 3D7 and FVO strain was similar in both groups, but more children in the malaria vaccine group than in the control group had 3D7 and FVO GIA activity ≥15% 30 days after the last vaccination (day 90) (49% vs. 16%, pvaccine group was 7.4 times the mean increase in the control group (pvaccination (day 364) and did not correlate with efficacy in the extended efficacy time period to day 730. In Cox proportional hazards regression models with time-varying covariates, there was a slight suggestion of an association between 3D7 GIA activity and increased risk of clinical malaria between day 90 and day 240. We conclude that vaccination with this AMA1-based malaria vaccine increased inhibition of parasite growth, but this increase was not associated with allele-specific efficacy in the first malaria season. These results provide a framework for testing functional immune correlates of protection against clinical malaria in field trials, and will help to guide similar analyses for next-generation malaria vaccines. Clinical trials registry: This clinical trial was registered on clinicaltrials.gov, registry number NCT00460525.

  12. Strain-specific Plasmodium falciparum growth inhibition among Malian children immunized with a blood-stage malaria vaccine.

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    Matthew B Laurens

    Full Text Available The blood-stage malaria vaccine FMP2.1/AS02A, comprised of recombinant Plasmodium falciparum apical membrane antigen 1 (AMA1 and the adjuvant system AS02A, had strain-specific efficacy against clinical malaria caused by P. falciparum with the vaccine strain 3D7 AMA1 sequence. To evaluate a potential correlate of protection, we measured the ability of participant sera to inhibit growth of 3D7 and FVO strains in vitro using high-throughput growth inhibition assay (GIA testing. Sera from 400 children randomized to receive either malaria vaccine or a control rabies vaccine were assessed at baseline and over two annual malaria transmission seasons after immunization. Baseline GIA against vaccine strain 3D7 and FVO strain was similar in both groups, but more children in the malaria vaccine group than in the control group had 3D7 and FVO GIA activity ≥15% 30 days after the last vaccination (day 90 (49% vs. 16%, p<0.0001; and 71.8% vs. 60.4%, p = 0.02. From baseline to day 90, 3D7 GIA in the vaccine group was 7.4 times the mean increase in the control group (p<0.0001. In AMA1 vaccinees, 3D7 GIA activity subsequently returned to baseline one year after vaccination (day 364 and did not correlate with efficacy in the extended efficacy time period to day 730. In Cox proportional hazards regression models with time-varying covariates, there was a slight suggestion of an association between 3D7 GIA activity and increased risk of clinical malaria between day 90 and day 240. We conclude that vaccination with this AMA1-based malaria vaccine increased inhibition of parasite growth, but this increase was not associated with allele-specific efficacy in the first malaria season. These results provide a framework for testing functional immune correlates of protection against clinical malaria in field trials, and will help to guide similar analyses for next-generation malaria vaccines. Clinical trials registry: This clinical trial was registered on clinicaltrials

  13. Impact of the RTS,S malaria vaccine candidate on naturally acquired antibody responses to multiple asexual blood stage antigens.

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    Joseph J Campo

    Full Text Available Partial protective efficacy lasting up to 43 months after vaccination with the RTS,S malaria vaccine has been reported in one cohort (C1 of a Phase IIb trial in Mozambique, but waning efficacy was observed in a smaller contemporaneous cohort (C2. We hypothesized that low dose exposure to asexual stage parasites resulting from partial pre-erythrocytic protection afforded by RTS,S may contribute to long-term vaccine efficacy to clinical disease, which was not observed in C2 due to intense active detection of infection and treatment.Serum collected 6 months post-vaccination was screened for antibodies to asexual blood stage antigens AMA-1, MSP-1(42, EBA-175, DBL-α and variant surface antigens of the R29 laboratory strain (VSA(R29. Effect of IgG on the prospective hazard of clinical malaria was estimated. No difference was observed in antibody levels between RTS,S and control vaccine when all children aged 1-4 years at enrollment in both C1 and C2 were analyzed together, and no effects were observed between cohort and vaccine group. RTS,S-vaccinated children <2 years of age at enrollment had lower levels of IgG for AMA-1 and MSP-1(42 (p<0.01, all antigens, while no differences were observed in children ≥2 years. Lower risk of clinical malaria was associated with high IgG to EBA-175 and VSA(R29 in C2 only (Hazard Ratio [HR]: 0.76, 95% CI 0.66-0.88; HR: 0.75, 95% CI 0.62-0.92, respectively.Vaccination with RTS,S modestly reduces anti-AMA-1 and anti-MSP-1 antibodies in very young children. However, for antigens associated with lower risk of clinical malaria, there were no vaccine group or cohort-specific effects, and age did not influence antibody levels between treatment groups for these antigens. The antigens tested do not explain the difference in protective efficacy in C1 and C2. Other less-characterized antigens or VSA may be important to protection.ClinicalTrials.gov NCT00197041.

  14. RTS,S vaccination is associated with serologic evidence of decreased exposure to Plasmodium falciparum liver- and blood-stage parasites.

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    Campo, Joe J; Aponte, John J; Skinner, Jeff; Nakajima, Rie; Molina, Douglas M; Liang, Li; Sacarlal, Jahit; Alonso, Pedro L; Crompton, Peter D; Felgner, Philip L; Dobaño, Carlota

    2015-03-01

    The leading malaria vaccine candidate, RTS,S, targets the sporozoite and liver stages of the Plasmodium falciparum life cycle, yet it provides partial protection against disease associated with the subsequent blood stage of infection. Antibodies against the vaccine target, the circumsporozoite protein, have not shown sufficient correlation with risk of clinical malaria to serve as a surrogate for protection. The mechanism by which a vaccine that targets the asymptomatic sporozoite and liver stages protects against disease caused by blood-stage parasites remains unclear. We hypothesized that vaccination with RTS,S protects from blood-stage disease by reducing the number of parasites emerging from the liver, leading to prolonged exposure to subclinical levels of blood-stage parasites that go undetected and untreated, which in turn boosts pre-existing antibody-mediated blood-stage immunity. To test this hypothesis, we compared antibody responses to 824 P. falciparum antigens by protein array in Mozambican children 6 months after receiving a full course of RTS,S (n = 291) versus comparator vaccine (n = 297) in a Phase IIb trial. Moreover, we used a nested case-control design to compare antibody responses of children who did or did not experience febrile malaria. Unexpectedly, we found that the breadth and magnitude of the antibody response to both liver and asexual blood-stage antigens was significantly lower in RTS,S vaccinees, with the exception of only four antigens, including the RTS,S circumsporozoite antigen. Contrary to our initial hypothesis, these findings suggest that RTS,S confers protection against clinical malaria by blocking sporozoite invasion of hepatocytes, thereby reducing exposure to the blood-stage parasites that cause disease. We also found that antibody profiles 6 months after vaccination did not distinguish protected and susceptible children during the subsequent 12-month follow-up period but were strongly associated with exposure. Together

  15. A Plasmodium vivax Plasmid DNA- and Adenovirus-Vectored Malaria Vaccine Encoding Blood-Stage Antigens AMA1 and MSP142in a Prime/Boost Heterologous Immunization Regimen Partially Protects Aotus Monkeys against Blood-Stage Challenge.

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    Obaldia, Nicanor; Stockelman, Michael G; Otero, William; Cockrill, Jennifer A; Ganeshan, Harini; Abot, Esteban N; Zhang, Jianfeng; Limbach, Keith; Charoenvit, Yupin; Doolan, Denise L; Tang, De-Chu C; Richie, Thomas L

    2017-04-01

    Malaria is caused by parasites of the genus Plasmodium , which are transmitted to humans by the bites of Anopheles mosquitoes. After the elimination of Plasmodium falciparum , it is predicted that Plasmodium vivax will remain an important cause of morbidity and mortality outside Africa, stressing the importance of developing a vaccine against P. vivax malaria. In this study, we assessed the immunogenicity and protective efficacy of two P. vivax antigens, apical membrane antigen 1 (AMA1) and the 42-kDa C-terminal fragment of merozoite surface protein 1 (MSP1 42 ) in a plasmid recombinant DNA prime/adenoviral (Ad) vector boost regimen in Aotus monkeys. Groups of 4 to 5 monkeys were immunized with plasmid DNA alone, Ad alone, prime/boost regimens with each antigen, prime/boost regimens with both antigens, and empty vector controls and then subjected to blood-stage challenge. The heterologous immunization regimen with the antigen pair was more protective than either antigen alone or both antigens delivered with a single vaccine platform, on the basis of their ability to induce the longest prepatent period and the longest time to the peak level of parasitemia, the lowest peak and mean levels of parasitemia, the smallest area under the parasitemia curve, and the highest self-cure rate. Overall, prechallenge MSP1 42 antibody titers strongly correlated with a decreased parasite burden. Nevertheless, a significant proportion of immunized animals developed anemia. In conclusion, the P. vivax plasmid DNA/Ad serotype 5 vaccine encoding blood-stage parasite antigens AMA1 and MSP1 42 in a heterologous prime/boost immunization regimen provided significant protection against blood-stage challenge in Aotus monkeys, indicating the suitability of these antigens and this regimen for further development. Copyright © 2017 American Society for Microbiology.

  16. Blood stage malaria vaccine eliciting high antigen-specific antibody concentrations confers no protection to young children in Western Kenya.

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    Bernhards R Ogutu

    Full Text Available The antigen, falciparum malaria protein 1 (FMP1, represents the 42-kDa C-terminal fragment of merozoite surface protein-1 (MSP-1 of the 3D7 clone of P. falciparum. Formulated with AS02 (a proprietary Adjuvant System, it constitutes the FMP1/AS02 candidate malaria vaccine. We evaluated this vaccine's safety, immunogenicity, and efficacy in African children.A randomised, double-blind, Phase IIb, comparator-controlled trial.The trial was conducted in 13 field stations of one mile radii within Kombewa Division, Nyanza Province, Western Kenya, an area of holoendemic transmission of P. falciparum. We enrolled 400 children aged 12-47 months in general good health.Children were randomised in a 1ratio1 fashion to receive either FMP1/AS02 (50 microg or Rabipur(R rabies vaccine. Vaccinations were administered on a 0, 1, and 2 month schedule. The primary study endpoint was time to first clinical episode of P. falciparum malaria (temperature >/=37.5 degrees C with asexual parasitaemia of >/=50,000 parasites/microL of blood occurring between 14 days and six months after a third dose. Case detection was both active and passive. Safety and immunogenicity were evaluated for eight months after first immunisations; vaccine efficacy (VE was measured over a six-month period following third vaccinations.374 of 400 children received all three doses and completed six months of follow-up. FMP1/AS02 had a good safety profile and was well-tolerated but more reactogenic than the comparator. Geometric mean anti-MSP-1(42 antibody concentrations increased from1.3 microg/mL to 27.3 microg/mL in the FMP1/AS02 recipients, but were unchanged in controls. 97 children in the FMP1/AS02 group and 98 controls had a primary endpoint episode. Overall VE was 5.1% (95% CI: -26% to +28%; p-value = 0.7.FMP1/AS02 is not a promising candidate for further development as a monovalent malaria vaccine. Future MSP-1(42 vaccine development should focus on other formulations and antigen constructs

  17. Cross-stage immunity for malaria vaccine development.

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    Nahrendorf, Wiebke; Scholzen, Anja; Sauerwein, Robert W; Langhorne, Jean

    2015-12-22

    A vaccine against malaria is urgently needed for control and eventual eradication. Different approaches are pursued to induce either sterile immunity directed against pre-erythrocytic parasites or to mimic naturally acquired immunity by controlling blood-stage parasite densities and disease severity. Pre-erythrocytic and blood-stage malaria vaccines are often seen as opposing tactics, but it is likely that they have to be combined into a multi-stage malaria vaccine to be optimally safe and effective. Since many antigenic targets are shared between liver- and blood-stage parasites, malaria vaccines have the potential to elicit cross-stage protection with immune mechanisms against both stages complementing and enhancing each other. Here we discuss evidence from pre-erythrocytic and blood-stage subunit and whole parasite vaccination approaches that show that protection against malaria is not necessarily stage-specific. Parasites arresting at late liver-stages especially, can induce powerful blood-stage immunity, and similarly exposure to blood-stage parasites can afford pre-erythrocytic immunity. The incorporation of a blood-stage component into a multi-stage malaria vaccine would hence not only combat breakthrough infections in the blood should the pre-erythrocytic component fail to induce sterile protection, but would also actively enhance the pre-erythrocytic potency of this vaccine. We therefore advocate that future studies should concentrate on the identification of cross-stage protective malaria antigens, which can empower multi-stage malaria vaccine development. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. New candidate vaccines against blood-stage Plasmodium falciparum malaria: prime-boost immunization regimens incorporating human and simian adenoviral vectors and poxviral vectors expressing an optimized antigen based on merozoite surface protein 1

    NARCIS (Netherlands)

    Goodman, Anna L.; Epp, C.; Moss, D.; Holder, A. A.; Wilson, J. M.; Gao, G. P.; Long, C. A.; Remarque, E. J.; Thomas, A. W.; Ammendola, V.; Colloca, S.; Dicks, M. D. J.; Biswas, S.; Seibel, D.; van Duivenvoorde, L. M.; Gilbert, S. C.; Hill, A. V. S.; Draper, S. J.

    2010-01-01

    Although merozoite surface protein 1 (MSP-1) is a leading candidate vaccine antigen for blood-stage malaria, its efficacy in clinical trials has been limited in part by antigenic polymorphism and potentially by the inability of protein-in-adjuvant vaccines to induce strong cellular immunity. Here we

  19. Phase 1 trial of AMA1-C1/Alhydrogel plus CPG 7909: an asexual blood-stage vaccine for Plasmodium falciparum malaria.

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    Gregory E D Mullen

    2008-08-01

    Full Text Available Apical Membrane Antigen 1 (AMA1, a polymorphic merozoite surface protein, is a leading blood-stage malaria vaccine candidate. This is the first reported use in humans of an investigational vaccine, AMA1-C1/Alhydrogel, with the novel adjuvant CPG 7909.A phase 1 trial was conducted at the University of Rochester with 75 malaria-naive volunteers to assess the safety and immunogenicity of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine. Participants were sequentially enrolled and randomized within dose escalating cohorts to receive three vaccinations on days 0, 28 and 56 of either 20 microg of AMA1-C1/Alhydrogel+564 microg CPG 7909 (n = 15, 80 microg of AMA1-C1/Alhydrogel (n = 30, or 80 microg of AMA1-C1/Alhydrogel+564 microg CPG 7909 (n = 30.Local and systemic adverse events were significantly more likely to be of higher severity with the addition of CPG 7909. Anti-AMA1 immunoglobulin G (IgG were detected by enzyme-linked immunosorbent assay (ELISA, and the immune sera of volunteers that received 20 microg or 80 microg of AMA1-C1/Alhydrogel+CPG 7909 had up to 14 fold significant increases in anti-AMA1 antibody concentration compared to 80 microg of AMA1-C1/Alhydrogel alone. The addition of CPG 7909 to the AMA1-C1/Alhydrogel vaccine in humans also elicited AMA1 specific immune IgG that significantly and dramatically increased the in vitro growth inhibition of homologous parasites to levels as high as 96% inhibition.The safety profile of the AMA1-C1/Alhydrogel+CPG 7909 malaria vaccine is acceptable, given the significant increase in immunogenicity observed. Further clinical development is ongoing.ClinicalTrials.gov NCT00344539.

  20. Phase 1 study in malaria naïve adults of BSAM2/Alhydrogel®+CPG 7909, a blood stage vaccine against P. falciparum malaria.

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    Ruth D Ellis

    Full Text Available A Phase 1 dose escalating study was conducted in malaria naïve adults to assess the safety, reactogenicity, and immunogenicity of the blood stage malaria vaccine BSAM2/Alhydrogel®+ CPG 7909. BSAM2 is a combination of the FVO and 3D7 alleles of recombinant AMA1 and MSP1(42, with equal amounts by weight of each of the four proteins mixed, bound to Alhydrogel®, and administered with the adjuvant CPG 7909. Thirty (30 volunteers were enrolled in two dose groups, with 15 volunteers receiving up to three doses of 40 µg total protein at Days 0, 56, and 180, and 15 volunteers receiving up to three doses of 160 µg protein on the same schedule. Most related adverse events were mild or moderate, but 4 volunteers experienced severe systemic reactions and two were withdrawn from vaccinations due to adverse events. Geometric mean antibody levels after two vaccinations with the high dose formulation were 136 µg/ml for AMA1 and 78 µg/ml for MSP1(42. Antibody responses were not significantly different in the high dose versus low dose groups and did not further increase after third vaccination. In vitro growth inhibition was demonstrated and was closely correlated with anti-AMA1 antibody responses. A Phase 1b trial in malaria-exposed adults is being conducted.Clinicaltrials.gov NCT00889616.

  1. Identification of Plasmodium falciparum reticulocyte binding protein homologue 5-interacting protein, PfRipr, as a highly conserved blood-stage malaria vaccine candidate.

    Science.gov (United States)

    Ntege, Edward H; Arisue, Nobuko; Ito, Daisuke; Hasegawa, Tomoyuki; Palacpac, Nirianne M Q; Egwang, Thomas G; Horii, Toshihiro; Takashima, Eizo; Tsuboi, Takafumi

    2016-11-04

    Genetic variability in Plasmodium falciparum malaria parasites hampers current malaria vaccine development efforts. Here, we hypothesize that to address the impact of genetic variability on vaccine efficacy in clinical trials, conserved antigen targets should be selected to achieve robust host immunity across multiple falciparum strains. Therefore, suitable vaccine antigens should be assessed for levels of polymorphism and genetic diversity. Using a total of one hundred and two clinical isolates from a region of high malaria transmission in Uganda, we analyzed extent of polymorphism and genetic diversity in four recently reported novel blood-stage malaria vaccine candidate proteins: Rh5 interacting protein (PfRipr), GPI anchored micronemal antigen (PfGAMA), rhoptry-associated leucine zipper-like protein 1 (PfRALP1) and Duffy binding-like merozoite surface protein 1 (PfMSPDBL1). In addition, utilizing the wheat germ cell-free system, we expressed recombinant proteins for the four candidates based on P. falciparum laboratory strain 3D7 sequences, immunized rabbits to obtain specific antibodies (Abs) and performed functional growth inhibition assay (GIA). The GIA activity of the raised Abs was demonstrated using both homologous 3D7 and heterologous FVO strains in vitro. Both pfripr and pfralp1 are less polymorphic but the latter is comparatively more diverse, with varied number of regions having insertions and deletions, asparagine and 6-mer repeats in the coding sequences. Pfgama and pfmspdbl1 are polymorphic and genetically diverse among the isolates with antibodies against the 3D7-based recombinant PfGAMA and PfMSPDBL1 inhibiting merozoite invasion only in the 3D7 but not FVO strain. Moreover, although Abs against the 3D7-based recombinant PfRipr and PfRALP1 proteins potently inhibited merozoite invasion of both 3D7 and FVO, the GIA activity of anti-PfRipr was much higher than that of anti-PfRALP1. Thus, PfRipr is regarded as a promising blood-stage vaccine

  2. Effect of the pre-erythrocytic candidate malaria vaccine RTS,S/AS01E on blood stage immunity in young children

    DEFF Research Database (Denmark)

    Bejon, Philip; Cook, Jackie; Bergmann-Leitner, Elke

    2011-01-01

    -linked immunosorbent assay, antibodies to 4 Plasmodium falciparum merozoite antigens (AMA-1, MSP-1(42), EBA-175, and MSP-3) and by growth inhibitory activity (GIA) using 2 parasite clones (FV0 and 3D7) at 4 times on 860 children who were randomized to receive with RTS,S/AS01(E) or a control vaccine. Results. Antibody...... concentrations to AMA-1, EBA-175, and MSP-1(42) decreased with age during the first year of life, then increased to 32 months of age. Anti-MSP-3 antibody concentrations gradually increased, and GIA gradually decreased up to 32 months. Vaccination with RTS,S/AS01(E) resulted in modest reductions in AMA-1, EBA-175......, MSP-1(42), and MSP-3 antibody concentrations and no significant change in GIA. Increasing anti-merozoite antibody concentrations and GIA were prospectively associated with increased risk of clinical malaria. Conclusions. Vaccination with RTS,S/AS01E reduces exposure to blood-stage parasites and, thus...

  3. Phase 1b randomized trial and follow-up study in Uganda of the blood-stage malaria vaccine candidate BK-SE36.

    Directory of Open Access Journals (Sweden)

    Nirianne Marie Q Palacpac

    Full Text Available BACKGROUND: Up to now a malaria vaccine remains elusive. The Plasmodium falciparum serine repeat antigen-5 formulated with aluminum hydroxyl gel (BK-SE36 is a blood-stage malaria vaccine candidate that has undergone phase 1a trial in malaria-naive Japanese adults. We have now assessed the safety and immunogenicity of BK-SE36 in a malaria endemic area in Northern Uganda. METHODS: We performed a two-stage, randomized, single-blinded, placebo-controlled phase 1b trial (Current Controlled trials ISRCTN71619711. A computer-generated sequence randomized healthy subjects for 2 subcutaneous injections at 21-day intervals in Stage1 (21-40 year-olds to 1-mL BK-SE36 (BKSE1.0 (n = 36 or saline (n = 20 and in Stage2 (6-20 year-olds to BKSE1.0 (n = 33, 0.5-mL BK-SE36 (BKSE0.5 (n = 33, or saline (n = 18. Subjects and laboratory personnel were blinded. Safety and antibody responses 21-days post-second vaccination (Day42 were assessed. Post-trial, to compare the risk of malaria episodes 130-365 days post-second vaccination, Stage2 subjects were age-matched to 50 control individuals. RESULTS: Nearly all subjects who received BK-SE36 had induration (Stage1, n = 33, 92%; Stage2, n = 63, 96% as a local adverse event. No serious adverse event related to BK-SE36 was reported. Pre-existing anti-SE36 antibody titers negatively correlated with vaccination-induced antibody response. At Day42, change in antibody titers was significant for seronegative adults (1.95-fold higher than baseline [95% CI, 1.56-2.43], p = 0.004 and 6-10 year-olds (5.71-fold [95% CI, 2.38-13.72], p = 0.002 vaccinated with BKSE1.0. Immunogenicity response to BKSE0.5 was low and not significant (1.55-fold [95% CI, 1.24-1.94], p = 0.75. In the ancillary analysis, cumulative incidence of first malaria episodes with ≥5000 parasites/µL was 7 cases/33 subjects in BKSE1.0 and 10 cases/33 subjects in BKSE0.5 vs. 29 cases/66 subjects in the control group. Risk ratio

  4. Polymorphism in liver-stage malaria vaccine candidate proteins: immune evasion and implications for vaccine design.

    Science.gov (United States)

    Flanagan, Katie L; Wilson, Kirsty L; Plebanski, Magdalena

    2016-01-01

    The pre-erythrocytic stage of infection by malaria parasites represents a key target for vaccines that aim to eradicate malaria. Two important broad immune evasion strategies that can interfere with vaccine efficacy include the induction of dendritic cell (DC) dysfunction and regulatory T cells (Tregs) by blood-stage malaria parasites, leading to inefficient priming of T cells targeting liver-stage infections. The parasite also uses 'surgical strike' strategies, whereby polymorphism in pre-erythrocytic antigens can interfere with host immunity. Specifically, we review how even single amino acid changes in T cell epitopes can lead to loss of binding to major histocompatibility complex (MHC), lack of cross-reactivity, or antagonism and immune interference, where simultaneous or sequential stimulation with related variants of the same T cell epitope can cause T cell anergy or the conversion of effector to immunosuppressive T cell phenotypes.

  5. A phase 1 trial of MSP2-C1, a blood-stage malaria vaccine containing 2 isoforms of MSP2 formulated with Montanide® ISA 720.

    Directory of Open Access Journals (Sweden)

    James S McCarthy

    Full Text Available In a previous Phase 1/2b malaria vaccine trial testing the 3D7 isoform of the malaria vaccine candidate Merozoite surface protein 2 (MSP2, parasite densities in children were reduced by 62%. However, breakthrough parasitemias were disproportionately of the alternate dimorphic form of MSP2, the FC27 genotype. We therefore undertook a dose-escalating, double-blinded, placebo-controlled Phase 1 trial in healthy, malaria-naïve adults of MSP2-C1, a vaccine containing recombinant forms of the two families of msp2 alleles, 3D7 and FC27 (EcMSP2-3D7 and EcMSP2-FC27, formulated in equal amounts with Montanide® ISA 720 as a water-in-oil emulsion.The trial was designed to include three dose cohorts (10, 40, and 80 µg, each with twelve subjects receiving the vaccine and three control subjects receiving Montanide® ISA 720 adjuvant emulsion alone, in a schedule of three doses at 12-week intervals. Due to unexpected local reactogenicity and concern regarding vaccine stability, the trial was terminated after the second immunisation of the cohort receiving the 40 µg dose; no subjects received the 80 µg dose. Immunization induced significant IgG responses to both isoforms of MSP2 in the 10 µg and 40 µg dose cohorts, with antibody levels by ELISA higher in the 40 µg cohort. Vaccine-induced antibodies recognised native protein by Western blots of parasite protein extracts and by immunofluorescence microscopy. Although the induced anti-MSP2 antibodies did not directly inhibit parasite growth in vitro, IgG from the majority of individuals tested caused significant antibody-dependent cellular inhibition (ADCI of parasite growth.As the majority of subjects vaccinated with MSP2-C1 developed an antibody responses to both forms of MSP2, and that these antibodies mediated ADCI provide further support for MSP2 as a malaria vaccine candidate. However, in view of the reactogenicity of this formulation, further clinical development of MSP2-C1 will require formulation

  6. Report of a consultation on the optimization of clinical challenge trials for evaluation of candidate blood stage malaria vaccines, 18-19 March 2009, Bethesda, MD, USA.

    NARCIS (Netherlands)

    Moorthy, V.S.; Diggs, C.; Ferro, S.; Good, M.F.; Herrera, S.; Hill, A.V.; Imoukhuede, E.B.; Kumar, S.; Loucq, C.; Marsh, K.; Ockenhouse, C.F.; Richie, T.L.; Sauerwein, R.W.

    2009-01-01

    Development and optimization of first generation malaria vaccine candidates has been facilitated by the existence of a well-established Plasmodium falciparum clinical challenge model in which infectious sporozoites are administered to human subjects via mosquito bite. While ideal for testing

  7. Multi-stage subunit vaccines against Mycobacterium tuberculosis: an alternative to the BCG vaccine or a BCG-prime boost?

    Science.gov (United States)

    Khademi, Farzad; Derakhshan, Mohammad; Yousefi-Avarvand, Arshid; Tafaghodi, Mohsen; Soleimanpour, Saman

    2018-01-01

    More than two billion people are latently infected with Mycobacterium tuberculosis. Most tuberculosis (TB)-subunit vaccines currently in various stages of clinical trials are designed for prevention of active TB, but not to prevent reactivation of latent TB-infection. Thus, there is an urgent need for an effective multi-stage vaccine based on early-expressed and latently-expressed antigens that prevents both acute and latent infections. Areas covered: Here, we reviewed the published pre-clinical and clinical studies of multi-stage subunit vaccines against TB, and the protective capacities of the vaccines were compared with BCG, either alone or in combination with different vaccine delivery systems/adjuvants. The results revealed that multi-stage subunit vaccines induced a wide variety of immune-responses to all forms of TB, including CD8 + T-cell-mediated cytolytic and IFN-γ responses comparable to those induced by the BCG. They could potentially be used as a booster vaccine to improve the efficacy of the BCG. Expert commentary: Multi-stage TB-vaccines could boost BCG-primed immunity, decrease bacterial loads and provide efficient protection against progressive TB-infection, especially in the latent phase. These types of vaccines administered before and after TB-infection can act as pre-exposure, post-exposure and even therapeutic vaccines. In the near future, these vaccines could provide a new generation of prime-vaccines or BCG prime-boosters.

  8. Flying vaccinator; a transgenic mosquito delivers a Leishmania vaccine via blood feeding.

    Science.gov (United States)

    Yamamoto, D S; Nagumo, H; Yoshida, S

    2010-06-01

    'Flying vaccinator' is the concept of using genetically engineered hematophagous insects to deliver vaccines. Here we show the generation of a transgenic anopheline mosquito that expresses the Leishmania vaccine candidate, SP15, fused to monomeric red fluorescent protein (mDsRed) in its salivary glands. Importantly, mice bitten repeatedly by the transgenic mosquitoes raised anti-SP15 antibodies, indicating delivery of SP15 via blood feeding with its immunogenicity intact. Thus, this technology makes possible the generation of transgenic mosquitoes that match the original concept of a 'flying vaccinator'. However, medical safety issues and concerns about informed consent mitigate the use of the 'flying vaccinator' as a method to deliver vaccines. We propose that this expression system could be applied to elucidate saliva-malaria sporozoite interactions.

  9. Analysis of a Multi-component Multi-stage Malaria Vaccine Candidate--Tackling the Cocktail Challenge.

    Directory of Open Access Journals (Sweden)

    Alexander Boes

    Full Text Available Combining key antigens from the different stages of the P. falciparum life cycle in the context of a multi-stage-specific cocktail offers a promising approach towards the development of a malaria vaccine ideally capable of preventing initial infection, the clinical manifestation as well as the transmission of the disease. To investigate the potential of such an approach we combined proteins and domains (11 in total from the pre-erythrocytic, blood and sexual stages of P. falciparum into a cocktail of four different components recombinantly produced in plants. After immunization of rabbits we determined the domain-specific antibody titers as well as component-specific antibody concentrations and correlated them with stage specific in vitro efficacy. Using purified rabbit immune IgG we observed strong inhibition in functional in vitro assays addressing the pre-erythrocytic (up to 80%, blood (up to 90% and sexual parasite stages (100%. Based on the component-specific antibody concentrations we calculated the IC50 values for the pre-erythrocytic stage (17-25 μg/ml, the blood stage (40-60 μg/ml and the sexual stage (1.75 μg/ml. While the results underline the feasibility of a multi-stage vaccine cocktail, the analysis of component-specific efficacy indicates significant differences in IC50 requirements for stage-specific antibody concentrations providing valuable insights into this complex scenario and will thereby improve future approaches towards malaria vaccine cocktail development regarding the selection of suitable antigens and the ratios of components, to fine tune overall and stage-specific efficacy.

  10. Extended Safety, Immunogenicity and Efficacy of a Blood-Stage Malaria Vaccine in Malian Children: 24-Month Follow-Up of a Randomized, Double-Blinded Phase 2 Trial

    Science.gov (United States)

    Laurens, Matthew B.; Thera, Mahamadou A.; Coulibaly, Drissa; Ouattara, Amed; Kone, Abdoulaye K.; Guindo, Ando B.; Traore, Karim; Traore, Idrissa; Kouriba, Bourema; Diallo, Dapa A.; Diarra, Issa; Daou, Modibo; Dolo, Amagana; Tolo, Youssouf; Sissoko, Mahamadou S.; Niangaly, Amadou; Sissoko, Mady; Takala-Harrison, Shannon; Lyke, Kirsten E.; Wu, Yukun; Blackwelder, William C.; Godeaux, Olivier; Vekemans, Johan; Dubois, Marie-Claude; Ballou, W. Ripley; Cohen, Joe; Dube, Tina; Soisson, Lorraine; Diggs, Carter L.; House, Brent; Bennett, Jason W.; Lanar, David E.; Dutta, Sheetij; Heppner, D. Gray; Plowe, Christopher V.; Doumbo, Ogobara K.

    2013-01-01

    Background The FMP2.1/AS02A candidate malaria vaccine was tested in a Phase 2 study in Mali. Based on results from the first eight months of follow-up, the vaccine appeared well-tolerated and immunogenic. It had no significant efficacy based on the primary endpoint, clinical malaria, but marginal efficacy against clinical malaria in secondary analyses, and high allele-specific efficacy. Extended follow-up was conducted to evaluate extended safety, immunogenicity and efficacy. Methods A randomized, double-blinded trial of safety, immunogenicity and efficacy of the candidate Plasmodium falciparum apical membrane antigen 1 (AMA1) vaccine FMP2.1/AS02A was conducted in Bandiagara, Mali. Children aged 1–6 years were randomized in a 1∶1 ratio to receive FMP2.1/AS02A or control rabies vaccine on days 0, 30 and 60. Using active and passive surveillance, clinical malaria and adverse events as well as antibodies against P. falciparum AMA1 were monitored for 24 months after the first vaccination, spanning two malaria seasons. Findings 400 children were enrolled. Serious adverse events occurred in nine participants in the FMP2.1/AS02A group and three in the control group; none was considered related to study vaccination. After two years, anti-AMA1 immune responses remained significantly higher in the FMP2.1/AS02A group than in the control group. For the entire 24-month follow-up period, vaccine efficacy was 7.6% (p = 0.51) against first clinical malaria episodes and 9.9% (p = 0.19) against all malaria episodes. For the final 16-month follow-up period, vaccine efficacy was 0.9% (p = 0.98) against all malaria episodes. Allele-specific efficacy seen in the first malaria season did not extend into the second season of follow-up. Interpretation Allele-specific vaccine efficacy was not sustained in the second malaria season, despite continued high levels of anti-AMA1 antibodies. This study presents an opportunity to evaluate correlates of partial protection against

  11. Extended safety, immunogenicity and efficacy of a blood-stage malaria vaccine in malian children: 24-month follow-up of a randomized, double-blinded phase 2 trial.

    Directory of Open Access Journals (Sweden)

    Matthew B Laurens

    Full Text Available The FMP2.1/AS02A candidate malaria vaccine was tested in a Phase 2 study in Mali. Based on results from the first eight months of follow-up, the vaccine appeared well-tolerated and immunogenic. It had no significant efficacy based on the primary endpoint, clinical malaria, but marginal efficacy against clinical malaria in secondary analyses, and high allele-specific efficacy. Extended follow-up was conducted to evaluate extended safety, immunogenicity and efficacy.A randomized, double-blinded trial of safety, immunogenicity and efficacy of the candidate Plasmodium falciparum apical membrane antigen 1 (AMA1 vaccine FMP2.1/AS02A was conducted in Bandiagara, Mali. Children aged 1-6 years were randomized in a 1∶1 ratio to receive FMP2.1/AS02A or control rabies vaccine on days 0, 30 and 60. Using active and passive surveillance, clinical malaria and adverse events as well as antibodies against P. falciparum AMA1 were monitored for 24 months after the first vaccination, spanning two malaria seasons.400 children were enrolled. Serious adverse events occurred in nine participants in the FMP2.1/AS02A group and three in the control group; none was considered related to study vaccination. After two years, anti-AMA1 immune responses remained significantly higher in the FMP2.1/AS02A group than in the control group. For the entire 24-month follow-up period, vaccine efficacy was 7.6% (p = 0.51 against first clinical malaria episodes and 9.9% (p = 0.19 against all malaria episodes. For the final 16-month follow-up period, vaccine efficacy was 0.9% (p = 0.98 against all malaria episodes. Allele-specific efficacy seen in the first malaria season did not extend into the second season of follow-up.Allele-specific vaccine efficacy was not sustained in the second malaria season, despite continued high levels of anti-AMA1 antibodies. This study presents an opportunity to evaluate correlates of partial protection against clinical malaria that waned during

  12. 42 CFR 410.63 - Hepatitis B vaccine and blood clotting factors: Conditions.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Hepatitis B vaccine and blood clotting factors... Other Health Services § 410.63 Hepatitis B vaccine and blood clotting factors: Conditions... under § 410.10, subject to the specified conditions: (a) Hepatitis B vaccine: Conditions. Effective...

  13. Multi-stage subunit vaccine development against Mycobacterium paratuberculosis and Johne’s disease in ruminants

    DEFF Research Database (Denmark)

    Jungersen, Gregers

    paratuberculosis provide only partial protection and interfere with diagnostic tests for JD and surveillance for bovine TB. In contrast, recombinant subunit vaccines can be designed to be used without compromising control of bTB and Map. Taking advantage of data from mouse TB studies, and early Map vaccination......- and field-studies we developed a vaccine with a single recombinant fusion protein comprising four acute-stage antigens (Ags) and one latent-stage Ag formulated in adjuvant (FET-vaccine). In post-exposure vaccination of calves and goats with necropsy 8-12 months post inoculation, we determined...... in macrophages. The disease progression is very slow with neonatal animals being the most susceptible to infection, but without development of detectable IFN-γ responses for months after infection and rarely with clinical disease before the second or third year of life. Available whole cell vaccines against...

  14. Development of a Multi-Stage Vaccine against Paratuberculosis in Cattle

    DEFF Research Database (Denmark)

    Thakur, Aneesh

    of quantitative real-time PCR (qPCR) for the evaluation of microbial load in tissues and vaccine efficacy (Article 4). Costimulation of vaccine-induced ex vivo T cells significantly increased IFN-γ levels following use of anti-CD28 and anti-CD49d antibodies (Article 2). Recombinant interleukin IL-12 (rIL-12) also...... to considerable economic losses to farming community. Paratuberculosis is a staged infection in which young calves acquire the infection in the first months of life, may progress into a prolonged asymptomatic stage of about 2-5 years and may eventually become clinically infected animals. Vaccination with whole......-cell live or inactivated vaccines prevents or delays the development of clinical stage of the disease but does not eliminate MAP and is usually accompanied by interference with bovine tuberculosis diagnostics as well as local tissue damage. Subunit vaccines with well-defined antigens in combination...

  15. Gene expression profiles are different in venous and capillary blood: Implications for vaccine studies.

    Science.gov (United States)

    Stein, D F; O'Connor, D; Blohmke, C J; Sadarangani, M; Pollard, A J

    2016-10-17

    Detailed analysis of the immunological pathways leading to robust vaccine responses has become possible with the application of systems biology, including transcriptomic analysis. Venous blood is usually obtained for such studies but others have obtained capillary blood (e.g. finger-prick). Capillary samples are practically advantageous, especially in children. The aim of this study was to compare gene expression profiles in venous and capillary blood before, 12h and 24h after vaccination with 23-valent pneumococcal polysaccharide or trivalent inactivated seasonal influenza vaccines. Gene expression at baseline was markedly different between venous and capillary samples, with 4940 genes differentially expressed, and followed a different pattern of changes after vaccination. At baseline, multiple pathways were upregulated in venous compared to capillary blood, including transforming growth factor-beta receptor signalling and toll-like receptor cascades. After vaccination with the influenza vaccine, there was enrichment for T and NK cell related signatures in capillary blood, and monocyte signatures in venous blood. By contrast, after vaccination with the pneumococcal vaccination, there was enrichment of dendritic cells, monocytes and interferon related signatures in capillary blood, whilst at 24h there was enrichment for T and NK cell related signatures in venous blood. These data show differences between venous and capillary gene expression both at baseline, and post vaccination, which may impact on the conclusions regarding immunological mechanisms drawn from studies using these different sampling methodologies. Copyright © 2016 Elsevier Ltd. All rights reserved.

  16. Persistence and immunogenicity of chemically attenuated blood stage Plasmodium falciparum in Aotus monkeys.

    Science.gov (United States)

    De, Sai Lata; Stanisic, Danielle I; van Breda, Karin; Bellete, Bernadette; Harris, Ivor; McCallum, Fiona; Edstein, Michael D; Good, Michael F

    2016-08-01

    Malaria is a disease caused by a protozoan of the Plasmodium genus and results in 0.5-0.7million deaths per year. Increasing drug resistance of the parasite and insecticide resistance of mosquitoes necessitate alternative control measures. Numerous vaccine candidates have been identified but none have been able to induce robust, long-lived protection when evaluated in malaria endemic regions. Rodent studies have demonstrated that chemically attenuated blood stage parasites can persist at sub-patent levels and induce homologous and heterologous protection against malaria. Parasite-specific cellular responses were detected, with protection dependent on CD4+ T cells. To investigate this vaccine approach for Plasmodium falciparum, we characterised the persistence and immunogenicity of chemically attenuated P. falciparum FVO strain parasites (CAPs) in non-splenectomised Aotus nancymaae monkeys following administration of a single dose. Control monkeys received either normal red blood cells or wild-type parasites followed by drug treatment. Chemical attenuation was performed using tafuramycin A, which irreversibly binds to DNA. CAPs were detected in the peripheral blood for up to 2days following inoculation as determined by thick blood smears, and for up to 8days as determined by quantitative PCR. Parasite-specific IgG was not detected in monkeys that received CAPs; however, in vitro parasite-specific T cell proliferation was observed. Following challenge, the CAP monkeys developed an infection; however, one CAP monkey and the infection and drug-cure monkeys showed partial or complete resistance. These experiments lay the groundwork for further assessment of CAPs as a potential vaccine against malaria. Copyright © 2016 Australian Society for Parasitology. Published by Elsevier Ltd. All rights reserved.

  17. Live Vaccine Strain Francisella tularensis is Detectable at the Inoculation Site but Not in Blood after Vaccination Against Tularemia

    National Research Council Canada - National Science Library

    Hepburn, Matthew J; Purcell, Bret K; Lawler, James V; Coyne, Susan R; Petitt, Patricia L; Sellers, Karen D; Norwood, David A; Ulrich, Melanie P

    2006-01-01

    ...) for the detection of F. tularensis in human clinical samples. Methods. Blood and skin swab samples were prospectively collected from volunteers who received the LVS tularemia vaccine at baseline (negative controls...

  18. Malaria transmission blocking immunity and sexual stage vaccines for interrupting malaria transmission in Latin America

    Science.gov (United States)

    Arévalo-Herrera, Myriam; Solarte, Yezid; Marin, Catherin; Santos, Mariana; Castellanos, Jenniffer; Beier, John C; Valencia, Sócrates Herrera

    2016-01-01

    Malaria is a vector-borne disease that is considered to be one of the most serious public health problems due to its high global mortality and morbidity rates. Although multiple strategies for controlling malaria have been used, many have had limited impact due to the appearance and rapid dissemination of mosquito resistance to insecticides, parasite resistance to multiple antimalarial drug, and the lack of sustainability. Individuals in endemic areas that have been permanently exposed to the parasite develop specific immune responses capable of diminishing parasite burden and the clinical manifestations of the disease, including blocking of parasite transmission to the mosquito vector. This is referred to as transmission blocking (TB) immunity (TBI) and is mediated by specific antibodies and other factors ingested during the blood meal that inhibit parasite development in the mosquito. These antibodies recognize proteins expressed on either gametocytes or parasite stages that develop in the mosquito midgut and are considered to be potential malaria vaccine candidates. Although these candidates, collectively called TB vaccines (TBV), would not directly stop malaria from infecting individuals, but would stop transmission from infected person to non-infected person. Here, we review the progress that has been achieved in TBI studies and the development of TBV and we highlight their potential usefulness in areas of low endemicity such as Latin America. PMID:21881775

  19. Malaria transmission blocking immunity and sexual stage vaccines for interrupting malaria transmission in Latin America

    Directory of Open Access Journals (Sweden)

    Myriam Arévalo-Herrera

    2011-08-01

    Full Text Available Malaria is a vector-borne disease that is considered to be one of the most serious public health problems due to its high global mortality and morbidity rates. Although multiple strategies for controlling malaria have been used, many have had limited impact due to the appearance and rapid dissemination of mosquito resistance to insecticides, parasite resistance to multiple antimalarial drug, and the lack of sustainability. Individuals in endemic areas that have been permanently exposed to the parasite develop specific immune responses capable of diminishing parasite burden and the clinical manifestations of the disease, including blocking of parasite transmission to the mosquito vector. This is referred to as transmission blocking (TB immunity (TBI and is mediated by specific antibodies and other factors ingested during the blood meal that inhibit parasite development in the mosquito. These antibodies recognize proteins expressed on either gametocytes or parasite stages that develop in the mosquito midgut and are considered to be potential malaria vaccine candidates. Although these candidates, collectively called TB vaccines (TBV, would not directly stop malaria from infecting individuals, but would stop transmission from infected person to non-infected person. Here, we review the progress that has been achieved in TBI studies and the development of TBV and we highlight their potential usefulness in areas of low endemicity such as Latin America.

  20. [Our experience with 1 mg BCG vaccine instillation in T1 stage cancer of the bladder].

    Science.gov (United States)

    Rivera, P; Orio, M; Hinostroza, J; Venegas, P; Pastor, P; Gorena, M; Lagos, M; Pinochet, R

    1999-10-01

    We studied 67 patients with bladder cancer in stage T1, with terminated BCG treatment and in pursuit. No stage Ta neither carcinoma in situ was included. The protocol was: beginning of treatment upon retiring vesical catheter, instilation of 1 mg of liofilized BCG vaccine (16 x 10(6) bacilles) in 40-50 ml of intravesical saline solution. A weekly instilation during the first month. An instilation each 15 days during the second and third month and one monthly until complete 12 months of treatment. Also was carried out an study of T lymphocites and cytokines. The average followup of the 67 patients treated was 51.3 months. 17 patients relapses (25.4%). A 33% were grade 3 and 27% grade 2. Like complications there was a case of inguinal TBC adenititis, 2 TBC prostatitis, 2 TBC cistitis and 5 cases of slight disuric syndrome. The study of subpopulations of lymphocites in peripheral blood demonstrated a significant increase of CD3 and CD4/CD8 ratio. The interleukin 2 measurement in serum also increased significantly after the BCG instilations. Our protocol gets similar results to the higher doses, but with minimal complications diminishing the relapses of the tumors in stage T1. A monthly maintenance dose would help to maintain immunity.

  1. Post-exposure vaccination with multi-stage vaccine significantly reduce map level in tissues without interference in diagnostics

    DEFF Research Database (Denmark)

    Thakur, Aneesh; Aagaard, Claus; Melvang, Heidi Mikkelsen

    A new (Fet11) vaccine against paratuberculosis based on recombinant antigens from acute and latent stages of Map infection was developed to be used without interference with diagnostic tests for bovine TB and Johne’s disease. Calves were orally inoculated with 2x10E10 live Map in their third week...... of life and randomly assigned to four groups of seven calves each. One group was left unvaccinated, while other calves were post-exposure vaccinated with either a whole-cell vaccine at 16 weeks, or Fet11 vaccine at 3 and 7, or 16 and 20 weeks of age, respectively. Antibody responses were measured by ID...... Screen® ELISA and individual vaccine protein ELISAs along with FACS and IFN-γ responses to PPDj and to individual vaccine proteins. At termination 8 or 12 months of age, Map burden in a number of gut tissues was determined by quantitative IS900 PCR and histopathology. Fet11 vaccination of calves at 16...

  2. PREVENTION OF BLOOD LOSS IN THIRD STAGE OF LABOUR BY PLACENTAL BLOOD DRAINAGE- A CLINICAL STUDY

    Directory of Open Access Journals (Sweden)

    B. K. Dutta

    2017-12-01

    Full Text Available BACKGROUND Placental cord drainage is a simple, safe and non-invasive method which reduces the duration and blood loss in the third stage of labour thereby preventing PPH. This method is of great use in day to day obstetric practices not requiring any extra effort, cost or equipment, so this type of practice is more relevant in rural areas. The objectives of the study were1. To evaluate the effectiveness of placental blood drainage via umbilical cord in reducing duration and blood loss in third stage of labour. 2. Reducing the incidence of postpartum haemorrhage. 3. Decreasing the complications in third stage of labour and reduce maternal mortality. MATERIALS AND METHODS This study was carried out in 100 full term pregnant women admitted in the labour room in Gauhati medical college and hospital in the department of obstetrics and gynaecology since 1st August 2007 to 30th August 2008. Cases were divided into two. Study group and control group. RESULTS In control group the average duration of third stage was 7.41 minutes and in study group 5.57 minutes and p value was <0.001 which is very highly significant. The blood loss in third stage of labour was more in case of control group, the mean blood loss in control was 169.48 ml and study group was 110.38 ml after delivery of placenta. The post-partum haemorrhage was present in 2% of cases in control group while in study group it was present in 0% case. CONCLUSION Placental blood drainage is one of the additional components in active management of third stage of labour, which is safe, simple and non-invasive method. It reduces the duration of third stage of labour, amount of blood loss and decreases the duration of placental separation time.

  3. Effect of Vaccination with Irradiated Third Stage Larvae of Haemonchus Contortus

    International Nuclear Information System (INIS)

    Beriajaya; Sukardji, P.

    2000-01-01

    The objective of this study was to determine the effect of vaccination with irradiated third stage larvae of Haemonchus contortus on immune responses in sheep. A number of 15 young male thin-tail sheep freed of worms were divided into 3 groups of 5. The first group was vaccinated with 50.000 irradiated third larvae of H. contortus . The second group was vaccinated as group 1 but without challenged. The third group was not vaccinated but challenged as group 1. Observations were carried out on egg counts, worn counts, total serum protein and antibody titer against H. contortus. The results showed there was no significant differences (P>0.05) on egg counts, worn counts and antibody titer, but a significant difference was seen on value of serum protein between vaccinated group and non vaccinated group. The results showed no protective immunity which is showed in worn counts of vaccinated and non vaccinated groups. Key word: Haemonchus contortus, irradiated larvae, sheep, vaccine

  4. Antibody response to pneumococcal vaccine in patients with early stage Hodgkin's disease

    DEFF Research Database (Denmark)

    Frederiksen, B.; Specht, L.; Henrichsen, J.

    1989-01-01

    Antibody response to pneumococcal vaccination was studied in 76 patients with Hodgkin's disease (HD) before, during and at different time intervals after cessation of therapy. All patients were in pathological stage I and II following explorative laparatomy with splenectomy. The increase in antib......Antibody response to pneumococcal vaccination was studied in 76 patients with Hodgkin's disease (HD) before, during and at different time intervals after cessation of therapy. All patients were in pathological stage I and II following explorative laparatomy with splenectomy. The increase...... in antibody response was compared to the findings in 12 healthy volunteers with the aim of establishing the optimal time for vaccination. Serum antibodies against 6 of the pneumococcal polysaccharide antigens (types 1, 4, 7F, 14, 18C and 23F) contained in the vaccine were determined by an ELISA. Antibody...

  5. An essential malaria protein defines the architecture of blood-stage and transmission-stage parasites.

    Science.gov (United States)

    Absalon, Sabrina; Robbins, Jonathan A; Dvorin, Jeffrey D

    2016-04-28

    Blood-stage replication of the human malaria parasite Plasmodium falciparum occurs via schizogony, wherein daughter parasites are formed by a specialized cytokinesis known as segmentation. Here we identify a parasite protein, which we name P. falciparum Merozoite Organizing Protein (PfMOP), as essential for cytokinesis of blood-stage parasites. We show that, following PfMOP knockdown, parasites undergo incomplete segmentation resulting in a residual agglomerate of partially divided cells. While organelles develop normally, the structural scaffold of daughter parasites, the inner membrane complex (IMC), fails to form in this agglomerate causing flawed segmentation. In PfMOP-deficient gametocytes, the IMC formation defect causes maturation arrest with aberrant morphology and death. Our results provide insight into the mechanisms of replication and maturation of malaria parasites.

  6. Antibody response to pneumococcal vaccine in patients with early stage Hodgkin's disease

    DEFF Research Database (Denmark)

    Frederiksen, B.; Specht, L.; Henrichsen, J.

    1989-01-01

    Antibody response to pneumococcal vaccination was studied in 76 patients with Hodgkin's disease (HD) before, during and at different time intervals after cessation of therapy. All patients were in pathological stage I and II following explorative laparatomy with splenectomy. The increase in antib......Antibody response to pneumococcal vaccination was studied in 76 patients with Hodgkin's disease (HD) before, during and at different time intervals after cessation of therapy. All patients were in pathological stage I and II following explorative laparatomy with splenectomy. The increase...

  7. Immunity to viral haemorrhagic septicaemia (VHS) following DNA vaccination of rainbow trout at an early life-stage

    DEFF Research Database (Denmark)

    Lorenzen, Niels; Lorenzen, Ellen; Einer-Jensen, Katja

    2001-01-01

    -vaccination respectively, revealed that a highly protective and lasting immunity was established shortly after vaccination, in accordance with earlier experiments with larger fish. The defence mechanisms activated by the DNA vaccine are thus functional at an early life-stage in rainbow trout....

  8. A novel multi-stage subunit vaccine against paratuberculosis induces significant immunity and reduces bacterial burden in tissues (P4304)

    DEFF Research Database (Denmark)

    Thakur, Aneesh; Aagaard, Claus; Riber, Ulla

    2013-01-01

    Effective control of paratuberculosis is hindered by lack of a vaccine preventing infection, transmission and without diagnostic interference with tuberculosis. We have developed a novel multi-stage recombinant subunit vaccine in which a fusion of four early expressed MAP antigens is combined...... with a MAP protein expressed in latent infection (FET11 vaccine). FET11 vaccine proteins were formulated with CAF01 adjuvant and injected to MAP challenged calves at two different ages. 28 calves divided into two FET11 vaccine groups, a commercial vaccine and a control group were used in the study...... and followed for a year. The FET11 vaccine induced a significant T cell response against constituent vaccine proteins characterized by a high percentage of CD4+ T cells and participation of polyfunctional CD4+ T cells. Of the two different age groups, late FET11 vaccination conferred protective immunity...

  9. Adjuvant dendritic cell vaccination induces tumor-specific immune responses in the majority of stage III melanoma patients

    NARCIS (Netherlands)

    Boudewijns, Steve; Bol, Kalijn F.; Schreibelt, Gerty; Westdorp, Harm; Textor, Johannes C.; van Rossum, Michelle M.; Scharenborg, Nicole M.; de Boer, Annemiek J.; van de Rakt, Mandy W. M. M.; Pots, Jeanne M.; van Oorschot, Tom G. M.; Duiveman-de Boer, Tjitske; Olde Nordkamp, Michel A.; van Meeteren, Wilmy S. E. C.; van der Graaf, Winette T. A.; Bonenkamp, Johannes J.; de Wilt, Johannes H. W.; Aarntzen, Erik H. J. G.; Punt, Cornelis J. A.; Gerritsen, Winald R.; Figdor, Carl G.; de Vries, I. Jolanda M.

    2016-01-01

    Purpose: To determine the effectiveness of adjuvant dendritic cell (DC) vaccination to induce tumor-specific immunological responses in stage III melanoma patients. Experimental design: Retrospective analysis of stage III melanoma patients, vaccinated with autologous monocyte-derived DC loaded with

  10. Adjuvant dendritic cell vaccination induces tumor-specific immune responses in the majority of stage III melanoma patients

    NARCIS (Netherlands)

    Boudewijns, S; Bol, K.F.; Schreibelt, G.; Westdorp, H.; Textor, J.C.; Rossum, M.M. van; Scharenborg, N.M.; Boer, A.J. de; Rakt, M.W.M.M. van de; Pots, J.M.; Oorschot, T.G.M. van; Boer, T. de; Nordkamp, M.A. Olde; Meeteren, W.S. van; Graaf, W.T.A. van der; Bonenkamp, J.J.; Wilt, J.H.W. de; Aarntzen, E.H.J.G.; Punt, C.J.A.; Gerritsen, W.R.; Figdor, C.G.; Vries, I.J.M. de

    2016-01-01

    PURPOSE: To determine the effectiveness of adjuvant dendritic cell (DC) vaccination to induce tumor-specific immunological responses in stage III melanoma patients. EXPERIMENTAL DESIGN: Retrospective analysis of stage III melanoma patients, vaccinated with autologous monocyte-derived DC loaded with

  11. Plasmodium falciparum Liver Stage Infection and Transition to Stable Blood Stage Infection in Liver-Humanized and Blood-Humanized FRGN KO Mice Enables Testing of Blood Stage Inhibitory Antibodies (Reticulocyte-Binding Protein Homolog 5 In Vivo

    Directory of Open Access Journals (Sweden)

    Lander Foquet

    2018-03-01

    Full Text Available The invention of liver-humanized mouse models has made it possible to directly study the preerythrocytic stages of Plasmodium falciparum. In contrast, the current models to directly study blood stage infection in vivo are extremely limited. Humanization of the mouse blood stream is achievable by frequent injections of human red blood cells (hRBCs and is currently the only system with which to study human malaria blood stage infections in a small animal model. Infections have been primarily achieved by direct injection of P. falciparum-infected RBCs but as such, this modality of infection does not model the natural route of infection by mosquito bite and lacks the transition of parasites from liver stage infection to blood stage infection. Including these life cycle transition points in a small animal model is of relevance for testing therapeutic interventions. To this end, we used FRGN KO mice that were engrafted with human hepatocytes and performed a blood exchange under immune modulation to engraft the animals with more than 50% hRBCs. These mice were infected by mosquito bite with sporozoite stages of a luciferase-expressing P. falciparum parasite, resulting in noninvasively measurable liver stage burden by in vivo bioluminescent imaging (IVIS at days 5–7 postinfection. Transition to blood stage infection was observed by IVIS from day 8 onward and then blood stage parasitemia increased with a kinetic similar to that observed in controlled human malaria infection. To assess the utility of this model, we tested whether a monoclonal antibody targeting the erythrocyte invasion ligand reticulocyte-binding protein homolog 5 (with known growth inhibitory activity in vitro was capable of blocking blood stage infection in vivo when parasites emerge from the liver and found it highly effective. Together, these results show that a combined liver-humanized and blood-humanized FRGN mouse model infected with luciferase-expressing P. falciparum will be a

  12. CD8+ T cells from a novel T cell receptor transgenic mouse induce liver-stage immunity that can be boosted by blood-stage infection in rodent malaria.

    Directory of Open Access Journals (Sweden)

    Lei Shong Lau

    2014-05-01

    Full Text Available To follow the fate of CD8+ T cells responsive to Plasmodium berghei ANKA (PbA infection, we generated an MHC I-restricted TCR transgenic mouse line against this pathogen. T cells from this line, termed PbT-I T cells, were able to respond to blood-stage infection by PbA and two other rodent malaria species, P. yoelii XNL and P. chabaudi AS. These PbT-I T cells were also able to respond to sporozoites and to protect mice from liver-stage infection. Examination of the requirements for priming after intravenous administration of irradiated sporozoites, an effective vaccination approach, showed that the spleen rather than the liver was the main site of priming and that responses depended on CD8α+ dendritic cells. Importantly, sequential exposure to irradiated sporozoites followed two days later by blood-stage infection led to augmented PbT-I T cell expansion. These findings indicate that PbT-I T cells are a highly versatile tool for studying multiple stages and species of rodent malaria and suggest that cross-stage reactive CD8+ T cells may be utilized in liver-stage vaccine design to enable boosting by blood-stage infections.

  13. Novel dendritic cell-based vaccination in late stage melanoma.

    Science.gov (United States)

    Schneble, Erika J; Yu, Xianzhong; Wagner, T E; Peoples, George E

    2014-01-01

    Dendritic cells (DCs) are professional antigen-presenting cells (APCs) that play an important role in stimulating an immune response of both CD4(+) T helper cells and CD8(+) cytotoxic T lymphocytes (CTLs). As such, DCs have been studied extensively in cancer immunotherapy for their capability to induce a specific anti-tumor response when loaded with tumor antigens. However, when the most relevant antigens of a tumor remain to be identified, alternative approaches are required. Formation of a dentritoma, a fused DC and tumor cells hybrid, is one strategy. Although initial studies of these hybrid cells are promising, several limitations interfere with its clinical and commercial application. Here we present early experience in clinical trials and an alternative approach to manufacturing this DC/tumor cell hybrid for use in the treatment of late stage and metastatic melanoma.

  14. Deconvoluting heme biosynthesis to target blood-stage malaria parasites

    Science.gov (United States)

    Sigala, Paul A; Crowley, Jan R; Henderson, Jeffrey P; Goldberg, Daniel E

    2015-01-01

    Heme metabolism is central to blood-stage infection by the malaria parasite Plasmodium falciparum. Parasites retain a heme biosynthesis pathway but do not require its activity during infection of heme-rich erythrocytes, where they can scavenge host heme to meet metabolic needs. Nevertheless, heme biosynthesis in parasite-infected erythrocytes can be potently stimulated by exogenous 5-aminolevulinic acid (ALA), resulting in accumulation of the phototoxic intermediate protoporphyrin IX (PPIX). Here we use photodynamic imaging, mass spectrometry, parasite gene disruption, and chemical probes to reveal that vestigial host enzymes in the cytoplasm of Plasmodium-infected erythrocytes contribute to ALA-stimulated heme biosynthesis and that ALA uptake depends on parasite-established permeability pathways. We show that PPIX accumulation in infected erythrocytes can be harnessed for antimalarial chemotherapy using luminol-based chemiluminescence and combinatorial stimulation by low-dose artemisinin to photoactivate PPIX to produce cytotoxic reactive oxygen. This photodynamic strategy has the advantage of exploiting host enzymes refractory to resistance-conferring mutations. DOI: http://dx.doi.org/10.7554/eLife.09143.001 PMID:26173178

  15. A Recombinant Multi-Stage Vaccine against Paratuberculosis Significantly Reduces Bacterial Level in Tissues without Interference in Diagnostics

    DEFF Research Database (Denmark)

    Jungersen, Gregers; Thakur, Aneesh; Aagaard, C.

    A new (FET11) recombinant vaccine against paratuberculosis was developed based on recombinant antigens from acute and latent stages of Mycobacterium avium subsp. paratuberculosis (Map) infection. In two experiments 28 calves and 15 goats were orally inoculated with live Map in their third week...... of life and post-exposure vaccinated at different times after inoculation or with different vaccine constructs. In contrast to common whole-cells vaccination, the FET11 vaccine did not interfere with tests for paratuberculosis or bovine tuberculosis as no measurable antibody responses by ID Screen® ELISA...... PCR and revealed significantly reduced levels of Map and reduced histopathology. Diagnostic tests for antibody responses and cell-mediated immune responses, used as surrogates of infection, corroborated the observed vaccine efficacy: Five of seven non‐vaccinated calves seroconverted in ID Screen...

  16. CCR study: evidence for benefit of TARP vaccine for men with early stage prostate cancer | Center for Cancer Research

    Science.gov (United States)

    Results from a pilot clinical trial found that TARP, or T-cell receptor gamma chain alternate reading frame protein, vaccination slowed prostate-specific antigen (PSA) rise in the majority of patients with early stage prostate cancer.

  17. Chemical rescue of malaria parasites lacking an apicoplast defines organelle function in blood-stage Plasmodium falciparum.

    Science.gov (United States)

    Yeh, Ellen; DeRisi, Joseph L

    2011-08-01

    Plasmodium spp parasites harbor an unusual plastid organelle called the apicoplast. Due to its prokaryotic origin and essential function, the apicoplast is a key target for development of new anti-malarials. Over 500 proteins are predicted to localize to this organelle and several prokaryotic biochemical pathways have been annotated, yet the essential role of the apicoplast during human infection remains a mystery. Previous work showed that treatment with fosmidomycin, an inhibitor of non-mevalonate isoprenoid precursor biosynthesis in the apicoplast, inhibits the growth of blood-stage P. falciparum. Herein, we demonstrate that fosmidomycin inhibition can be chemically rescued by supplementation with isopentenyl pyrophosphate (IPP), the pathway product. Surprisingly, IPP supplementation also completely reverses death following treatment with antibiotics that cause loss of the apicoplast. We show that antibiotic-treated parasites rescued with IPP over multiple cycles specifically lose their apicoplast genome and fail to process or localize organelle proteins, rendering them functionally apicoplast-minus. Despite the loss of this essential organelle, these apicoplast-minus auxotrophs can be grown indefinitely in asexual blood stage culture but are entirely dependent on exogenous IPP for survival. These findings indicate that isoprenoid precursor biosynthesis is the only essential function of the apicoplast during blood-stage growth. Moreover, apicoplast-minus P. falciparum strains will be a powerful tool for further investigation of apicoplast biology as well as drug and vaccine development.

  18. Shape-Shifted Red Blood Cells: A Novel Red Blood Cell Stage?

    Science.gov (United States)

    Chico, Verónica; Puente-Marin, Sara; Nombela, Iván; Ciordia, Sergio; Mena, María Carmen; Carracedo, Begoña; Villena, Alberto; Mercado, Luis; Coll, Julio; Ortega-Villaizan, María Del Mar

    2018-04-19

    Primitive nucleated erythroid cells in the bloodstream have long been suggested to be more similar to nucleated red cells of fish, amphibians, and birds than the red cells of fetal and adult mammals. Rainbow trout Ficoll-purified red blood cells (RBCs) cultured in vitro undergo morphological changes, especially when exposed to stress, and enter a new cell stage that we have coined shape-shifted RBCs (shRBCs). We have characterized these shRBCs using transmission electron microscopy (TEM) micrographs, Wright⁻Giemsa staining, cell marker immunostaining, and transcriptomic and proteomic evaluation. shRBCs showed reduced density of the cytoplasm, hemoglobin loss, decondensed chromatin in the nucleus, and striking expression of the B lymphocyte molecular marker IgM. In addition, shRBCs shared some features of mammalian primitive pyrenocytes (extruded nucleus surrounded by a thin rim of cytoplasm and phosphatidylserine (PS) exposure on cell surface). These shRBCs were transiently observed in heat-stressed rainbow trout bloodstream for three days. Functional network analysis of combined transcriptomic and proteomic studies resulted in the identification of proteins involved in pathways related to the regulation of cell morphogenesis involved in differentiation, cellular response to stress, and immune system process. In addition, shRBCs increased interleukin 8 (IL8), interleukin 1 β (IL1β), interferon ɣ (IFNɣ), and natural killer enhancing factor (NKEF) protein production in response to viral hemorrhagic septicemia virus (VHSV). In conclusion, shRBCs may represent a novel cell stage that participates in roles related to immune response mediation, homeostasis, and the differentiation and development of blood cells.

  19. Exploring the Limitations of Peripheral Blood Transcriptional Biomarkers in Predicting Influenza Vaccine Responsiveness

    Directory of Open Access Journals (Sweden)

    Luca Marchetti

    2017-01-01

    Full Text Available Systems biology has been recently applied to vaccinology to better understand immunological responses to the influenza vaccine. Particular attention has been paid to the identification of early signatures capable of predicting vaccine immunogenicity. Building from previous studies, we employed a recently established algorithm for signature-based clustering of expression profiles, SCUDO, to provide new insights into why blood-derived transcriptome biomarkers often fail to predict the seroresponse to the influenza virus vaccination. Specifically, preexisting immunity against one or more vaccine antigens, which was found to negatively affect the seroresponse, was identified as a confounding factor able to decouple early transcriptome from later antibody responses, resulting in the degradation of a biomarker predictive power. Finally, the broadly accepted definition of seroresponse to influenza virus vaccine, represented by the maximum response across the vaccine-targeted strains, was compared to a composite measure integrating the responses against all strains. This analysis revealed that composite measures provide a more accurate assessment of the seroresponse to multicomponent influenza vaccines.

  20. Phase II Study of HER-2/neu Intracellular Domain Peptide-Based Vaccine Administered to Stage IV HER2 Positive Breast Cancer Patients Receiving Trastuzumab

    National Research Council Canada - National Science Library

    Disis, Mary L

    2006-01-01

    The primary purpose of this grant is to determine the overall survival benefit in Stage IV HER2 positive breast cancer patients vaccinated with a HER2 ICD peptide-based vaccine while receiving maintenance trastuzumab...

  1. Phase II Study of HER-2/neu Intracellular Domain Peptide-Based Vaccine Administered to Stage IV HER2 Positive Breast Cancer Patients Receiving Trastuzumab

    National Research Council Canada - National Science Library

    Disis, Mary L

    2007-01-01

    The primary purpose of this grant is to determine the overall survival benefit in Stage IV HER2 positive breast cancer patients vaccinated with a HER2 ICD peptide-based vaccine while receiving maintenance trastuzumab...

  2. Salivary gland thrombostasin isoforms differentially regulate blood uptake of horn flies fed on control- and thrombostasin-vaccinated cattle.

    Science.gov (United States)

    Cupp, Mary S; Cupp, Eddie W; Navarre, Christine; Zhang, Dunhua; Yue, Xin; Todd, Latora; Panangala, Victor

    2010-07-01

    Thrombostasin (TS) is an anticlotting protein found in saliva of Haematobia irritans (horn flies). The polymorphic nature of the ts gene was first associated with success of horn flies blood feeding on a laboratory host, New Zealand White rabbits. In this study, we report results of similar studies testing blood uptake of horn flies feeding on a natural host, cattle. These studies confirmed the association of ts genotype with blood uptake of horn flies and showed that it was host species specific. In contrast to rabbits, blood uptake volumes of homozygous ts10 horn flies were lower than those of other ts genotypes when fed on control (ovalbumin-vaccinated) cattle. Cattle vaccinated with recombinant protein isoforms, rTS9 or rTB8, resisted horn fly feeding by yielding lower blood volumes compared with flies feeding on control cattle. The specific impact of vaccination, however, varied by ts genotype of flies. Cattle vaccinated with isoform rTS9 resisted flies of ts2, ts9, and tb8 genotype. Vaccination with isoform rTB8 produced resistance to ts8, ts9, and tb8 genotype flies. Horn flies of genotype ts10 were not affected by vaccination with either TS isoform and fed as well on rTS9- and rTB8-vaccinated as on control-vaccinated cattle. These experimental results confirm the efficacy of vaccines targeting horn fly salivary proteins and provide new insight into the dynamics of horn fly-cattle interactions in nature.

  3. CIMAvax-EGF®: Therapeutic Vaccine Against Non-small Cell Lung Cancer in Advanced Stages

    Directory of Open Access Journals (Sweden)

    Diana Rosa Fernández Ruiz

    2017-02-01

    Full Text Available Biotechnology is one of the scientific activities deployed by the Cuban State, which shows greater results and impact on the of the Cuban population health. It has increased the therapeutic repertoire in dealing with oncological diseases with products such as CIMAvax-EGF®, the first therapeutic vaccine of its kind, from the Molecular Immunology Center, against non-small cell lung cancer in advanced stages IIIB IV. The application of this product already extends to Primary Health Care with encouraging results, by prolonging the survival of patients with higher quality of life.

  4. White blood cell differential count of maturation stages in bone marrow smear using dual-stage convolutional neural networks.

    Directory of Open Access Journals (Sweden)

    Jin Woo Choi

    Full Text Available The white blood cell differential count of the bone marrow provides information concerning the distribution of immature and mature cells within maturation stages. The results of such examinations are important for the diagnosis of various diseases and for follow-up care after chemotherapy. However, manual, labor-intensive methods to determine the differential count lead to inter- and intra-variations among the results obtained by hematologists. Therefore, an automated system to conduct the white blood cell differential count is highly desirable, but several difficulties hinder progress. There are variations in the white blood cells of each maturation stage, small inter-class differences within each stage, and variations in images because of the different acquisition and staining processes. Moreover, a large number of classes need to be classified for bone marrow smear analysis, and the high density of touching cells in bone marrow smears renders difficult the segmentation of single cells, which is crucial to traditional image processing and machine learning. Few studies have attempted to discriminate bone marrow cells, and even these have either discriminated only a few classes or yielded insufficient performance. In this study, we propose an automated white blood cell differential counting system from bone marrow smear images using a dual-stage convolutional neural network (CNN. A total of 2,174 patch images were collected for training and testing. The dual-stage CNN classified images into 10 classes of the myeloid and erythroid maturation series, and achieved an accuracy of 97.06%, a precision of 97.13%, a recall of 97.06%, and an F-1 score of 97.1%. The proposed method not only showed high classification performance, but also successfully classified raw images without single cell segmentation and manual feature extraction by implementing CNN. Moreover, it demonstrated rotation and location invariance. These results highlight the promise of

  5. White blood cell differential count of maturation stages in bone marrow smear using dual-stage convolutional neural networks.

    Science.gov (United States)

    Choi, Jin Woo; Ku, Yunseo; Yoo, Byeong Wook; Kim, Jung-Ah; Lee, Dong Soon; Chai, Young Jun; Kong, Hyoun-Joong; Kim, Hee Chan

    2017-01-01

    The white blood cell differential count of the bone marrow provides information concerning the distribution of immature and mature cells within maturation stages. The results of such examinations are important for the diagnosis of various diseases and for follow-up care after chemotherapy. However, manual, labor-intensive methods to determine the differential count lead to inter- and intra-variations among the results obtained by hematologists. Therefore, an automated system to conduct the white blood cell differential count is highly desirable, but several difficulties hinder progress. There are variations in the white blood cells of each maturation stage, small inter-class differences within each stage, and variations in images because of the different acquisition and staining processes. Moreover, a large number of classes need to be classified for bone marrow smear analysis, and the high density of touching cells in bone marrow smears renders difficult the segmentation of single cells, which is crucial to traditional image processing and machine learning. Few studies have attempted to discriminate bone marrow cells, and even these have either discriminated only a few classes or yielded insufficient performance. In this study, we propose an automated white blood cell differential counting system from bone marrow smear images using a dual-stage convolutional neural network (CNN). A total of 2,174 patch images were collected for training and testing. The dual-stage CNN classified images into 10 classes of the myeloid and erythroid maturation series, and achieved an accuracy of 97.06%, a precision of 97.13%, a recall of 97.06%, and an F-1 score of 97.1%. The proposed method not only showed high classification performance, but also successfully classified raw images without single cell segmentation and manual feature extraction by implementing CNN. Moreover, it demonstrated rotation and location invariance. These results highlight the promise of the proposed method

  6. Frederick National Lab Rallies to Meet Demand for Zika Vaccine | FNLCR Staging

    Science.gov (United States)

    The Frederick National Laboratory for Cancer Research’s Vaccine Pilot Plant, part of the Vaccine Clinical Materials Program (VCMP), is helping researchers produce investigational Zika vaccines for a new round of clinical trials. The plant has been

  7. Application of solid-phase radioimmunoassay in determining antibodies to Aujeszky's disease virus in blood serum of vaccinated pigs

    International Nuclear Information System (INIS)

    Rodak, L.; Smid, B.; Valicek, L.

    1983-01-01

    In the blood sera of pigs vaccinated with inactivated vaccines manufactured by three different manufacturers the RIA method was used to determine the specific antibodies to the virus of Aujeszky's disease. In certain groups of vaccinated pigs the results of the RIA examination are unfavourably affected by the bond of antibodies to the cellular antigenous determinants. This proves that following vaccination antibodies are formed not only against the viral antigen but also against the antigens of cells on which the vaccination virus is propagated. These shortcomings are eliminated by the use of suitable cellular cultures for the preparation of viral and control antigens. Antigens are applicable for RIA and for ELISA examinations of blood sera of infected and vaccinated pigs. The advantages are described of the RIA and ELISA methods as compared with the virus neutralization test. (author)

  8. Earlier stages of colorectal cancer detected with immunochemical faecal occult blood tests

    NARCIS (Netherlands)

    van Rossum, L. G. M.; van Rijn, A. F.; van Munster, I. P.; Jansen, J. B. M. J.; Fockens, P.; Laheij, R. J. F.; Dekker, E.

    2009-01-01

    Background: The aim of colorectal cancer screening is to improve prognosis by the detection of early cancer and precursor stages. We compared the stage distribution of asymptomatic colorectal cancer patients detected by a positive immunochemical or guaiac-based faecal occult blood test (FOBT) with

  9. [Oral polio vaccine in infants does not interfere in detection of enterovirus in blood].

    Science.gov (United States)

    González, Marcela; Sandoval, Carmen; Valenzuela, Patricia; Montecinos, Luisa; Martínez, Constanza; Godoy, Paula; Abarca, Katia

    2013-12-01

    There is not known if a viraemia post-oral polio vaccine (OPV) is detectable by modern molecular techniques. Such viraemia could affect the performance of the real time-polymerase chain reaction (PCR) for non polio enterovirus (EV) detection, technique of growing clinical use for the study of febrile infants. To determine viraemia post-first dose of OPV in healthy infants, by molecular techniques. 50 infants less than three months without previous VPO were randomized in 5 groups: a control group with pre-vaccination blood sample (BS), group 1 BS at day 2, group 2 BS at day 4, group 3, BS at day 6 and group 4, BS at day 8 post-vaccination. Conventional and specific PCR for poliovirus and real time PCR for non polio EV were performed in BS and in OPV samples. No genetic material of poliovirus was detected in any infant, while in 9 of them (18%) non polio EV was identified. Real time PCR for EV did not amplify poliovirus from OPV samples. Results suggest that no post VPO viraemia detectable by molecular methods exists. Considering that real time PCR for EV does not allow to identify polio virus, no false positives of the test are expected as a result of a recent VPO vaccination. We documented presence of non polio EV in blood of healthy asymptomatic infants.

  10. A novel Pfs38 protein complex on the surface of Plasmodium falciparum blood-stage merozoites

    DEFF Research Database (Denmark)

    Paul, Gourab; Deshmukh, Arunaditya; Kaur, Inderjeet

    2017-01-01

    BACKGROUND: The Plasmodium genome encodes for a number of 6-Cys proteins that contain a module of six cysteine residues forming three intramolecular disulphide bonds. These proteins have been well characterized at transmission as well as hepatic stages of the parasite life cycle. In the present...... the development of a multi-sub-unit malaria vaccine based on some of these protein complexes on merozoite surface....

  11. Canine Distemper Viral Inclusions in Blood Cells of Four Vaccinated Dogs

    OpenAIRE

    McLaughlin, Bruce G.; Adams, Pamela S.; Cornell, William D.; Elkins, A. Darrel

    1985-01-01

    Four cases of canine distemper were detected by the presence of numerous cytoplasmic inclusions in various circulating blood cells. Fluorescent antibody techniques and electron microscopy confirmed the identity of the viral inclusions. The cases occurred in the same geographic area and within a short time span. All four dogs had been vaccinated against canine distemper, but stress or other factors may have compromised their immune status. The possibility of an unusually virulent virus strain ...

  12. Evaluation of blood monocyte and lymphocyte population in broiler chicken after vaccination and experimental challenge with Newcastle disease virus.

    Science.gov (United States)

    Taebipour, Mohammad Jafar; Dadras, Habibollah; Nazifi, Saeed; Afsar, Mina; Ansari-Lari, Maryam

    2017-08-01

    In the present study, after vaccination and challenge with Newcastle disease virus, changes in the population of blood monocytes and lymphocytes of broiler chickens were evaluated using flow cytometry. 300 apparently healthy 1-day-old Cobb broiler chicks were divided randomly into four experimental groups (n=75). At 20days of age the chicks in group 1 and 2 were vaccinated with live B1 ND vaccine. Those in group 2 were additionally injected with a killed vaccine simultaneously and group 3 chicks received only the adjuvant of the killed vaccine. The birds in groups 1, 2 and 3 were challenged with a velogenic ND virus and those in group 4 were treated as control. Sampling was done on days 1,2,3,7 after vaccination and also on 1, 2, 3,7,14, 21 post challenge days. In this study percentage of B cell population was increased after vaccination and challenge in vaccinated birds, but CD3+ cells were decreased after vaccination and challenge, which showed B cells have more expansion than T cells. The CD4+ cell percentage in vaccinated birds was always lower than control birds. However, the percentage of CD8+ cells in vaccinated birds was increased. Results indicate increased CMI with the live NDV vaccination. In this study CD4/CD8 ratio in control birds was about 1.5 at 30days of age and it was slightly lower in vaccinated and challenged birds. The percentage of monocytes in vaccinated birds was significantly higher than control birds from 3days post vaccination to the end of the experiment. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Christophers’ stage durations and effect of interrupted blood meal in the mosquito Aedes caspius (Diptera: Culicidae

    Directory of Open Access Journals (Sweden)

    Carron A.

    2007-09-01

    Full Text Available Christophers’ stages durations and effect of interrupted blood meal were investigated in laboratory to study the gonotrophic cycle of Aedes caspius (Pallas, 1771. A first experiment was done with replete females (full blood meal and females with an interrupted blood meal. Females were then regularly dissected, the durations of Christophers’ stages I, II, III, IV, V were up to 8, 8, 32, 8, 48 h, respectively. A second experiment was done with replete females, females with an interrupted blood meal and females with an interrupted blood meal completed 24 h later. Interrupted females matured 21 ± 5 follicles, interrupted-completed females 92 ± 11, and replete females 120 ± 8 follicles.

  14. A nurse-led intervention improved blood-borne virus testing and vaccination in Victorian prisons.

    Science.gov (United States)

    Winter, Rebecca J; White, Bethany; Kinner, Stuart A; Stoové, Mark; Guy, Rebecca; Hellard, Margaret E

    2016-12-01

    Testing is the first step in treatment and care for blood-borne viruses (BBVs) and sexually transmitted infections (STIs). As new treatments for viral hepatitis emerge, it is important to document effective models for BBV/STI testing. A nurse-led intervention was implemented across three prisons in Victoria to improve BBV/STI testing. We evaluated the impact of the intervention on BBV/STI testing rates and hepatitis B (HBV) vaccination for reception prisoners. BBV/STI testing and HBV vaccination data were collected from the medical files of 100 consecutive reception prisoners at three prisons (n=300) prior to and after the intervention was implemented. BBV testing increased significantly from 21% of prisoners to 62% post-intervention. Testing for some STIs increased significantly, but remained low: 5% to 17% for chlamydia and 1% to 5% for gonorrhoea. HBV vaccination increased significantly from 2% to 19%. The nurse-led intervention resulted in substantially increased testing and vaccination, demonstrating the benefits of a concerted effort to improve BBV and STI management in correctional settings. The availability of new treatments for hepatitis C has precipitated expansion of treatment in prisons. Improving the testing rate of prisoners, the first step in the treatment cascade, will maximise the benefits. © 2016 Public Health Association of Australia.

  15. Vaccination and blood sampling acceptability during Ramadan fasting month: A cross-sectional study in Conakry, Guinea.

    Science.gov (United States)

    Peiffer-Smadja, Nathan; Ouedraogo, Ramatou; D'Ortenzio, Eric; Cissé, Papa Ndiaga; Zeggani, Zahra; Beavogui, Abdoul Habib; Faye, Sylvain Landry; Le Marcis, Frédéric; Yazdanpanah, Yazdan; Nguyen, Vinh-Kim

    2017-05-02

    There are few data on the acceptability of vaccination or blood sampling during Ramadan fasting month in Muslim countries. This could impact vaccination campaigns, clinical trials or healthcare during Ramadan. Using a semi-structured questionnaire, we conducted a cross-sectional study on 201 practising Muslims and 10 religious leaders in Conakry, Guinea in the wake of the recent epidemic Ebola epidemic. Acceptability of vaccination and blood sampling during Ramadan were investigated as well as reasons for refusal. Vaccination was judged acceptable during Ramadan by 46% (93/201, 95% CI 0.40-0.53) of practising Muslims versus 80% (8/10, 95% CI 0.49-0.94) of religious leaders (p=0.11). Blood sampling was judged acceptable during Ramadan by 54% (108/201, 95% CI 0.47-0.60) of practising Muslims versus 80% (8/10, 95% CI 0.49-0.94) of religious leaders (p=0.19). The percentage of participants that judged both blood sampling and vaccination acceptable during Ramadan was 40% (81/201, 95% CI 0.34-0.47) for practising Muslims versus 80% (8/10, 95% CI 0.49-0.94) for religious leaders (p=0.048). The most common reasons for refusal of vaccination or blood sampling were that nothing should enter or leave the body during Ramadan (43%), that adverse events could lead to breaking the fast (32%), that blood should not be seen during Ramadan (9%) and that the Quran explicitly forbids it (9%). Although most Muslims leaders and scientists consider that injections including immunization and blood sampling should be authorized during Ramadan, many Muslims in our study judged vaccination or blood sampling unacceptable when fasting. Widely available recommendations on healthcare during Ramadan would be useful to inform Muslims. Copyright © 2017. Published by Elsevier Ltd.

  16. Blunting the knife: development of vaccines targeting digestive proteases of blood-feeding helminth parasites.

    Science.gov (United States)

    Pearson, Mark S; Ranjit, Najju; Loukas, Alex

    2010-08-01

    Proteases are pivotal to parasitism, mediating biological processes crucial to worm survival including larval migration through tissue, immune evasion/modulation and nutrient acquisition by the adult parasite. In haematophagous parasites, many of these proteolytic enzymes are secreted from the intestine (nematodes) or gastrodermis (trematodes) where they act to degrade host haemoglobin and serum proteins as part of the feeding process. These proteases are exposed to components of the immune system of the host when the worms ingest blood, and therefore present targets for the development of anti-helminth vaccines. The protective effects of current vaccine antigens against nematodes that infect humans (hookworm) and livestock (barber's pole worm) are based on haemoglobin-degrading intestinal proteases and act largely as a result of the neutralisation of these proteases by antibodies that are ingested with the blood-meal. In this review, we survey the current status of helminth proteases that show promise as vaccines and describe their vital contribution to a parasitic existence.

  17. Induction of cell death on Plasmodium falciparum asexual blood stages by Solanum nudum steroids

    DEFF Research Database (Denmark)

    López, Mary Luz; Vommaro, Rossiane; Zalis, Mariano

    2010-01-01

    -87 μM. However, their mode of action is unknown. Steroids regulate important cellular functions including cell growth, differentiation and death. Thus, the aim of this work was to determine the effects of S. nudum compounds on P. falciparum asexual blood stages and their association with cell death. We....... The Mitochondria presented no morphological alterations and the nuclei showed no abnormal chromatin condensation. By the use of S. nudum compounds, cell death in P. falciparum was evident by a decrease in mitochondrial membrane potential, DNA fragmentation and cytoplasmic acidification. The asexual blood stages...... of P. falciparum showed some apoptotic-like and autophagic-like cell death characteristics induced by SNs treatment....

  18. Flow cytometric readout based on Mitotracker Red CMXRos staining of live asexual blood stage malarial parasites reliably assesses antibody dependent cellular inhibition

    DEFF Research Database (Denmark)

    Jogdand, Prajakta S; Singh, Susheel K; Christiansen, Michael

    2012-01-01

    asynchronous and tightly synchronized asexual blood stage cultures of Plasmodium falciparum were stained with CMXRos and subjected to detection by flow cytometry and fluorescence microscopy. The parasite counts obtained by flow cytometry were compared to standard microscopic counts obtained through examination......ABSTRACT: BACKGROUND: Functional in vitro assays could provide insights into the efficacy of malaria vaccine candidates. For estimating the anti-parasite effect induced by a vaccine candidate, an accurate determination of live parasite count is an essential component of most in vitro bioassays....... Although traditionally parasites are counted microscopically, a faster, more accurate and less subjective method for counting parasites is desirable. In this study mitochondrial dye (Mitotracker Red CMXRos) was used for obtaining reliable live parasite counts through flow cytometry. METHODS: Both...

  19. The Heme Biosynthesis Pathway Is Essential for Plasmodium falciparum Development in Mosquito Stage but Not in Blood Stages*

    Science.gov (United States)

    Ke, Hangjun; Sigala, Paul A.; Miura, Kazutoyo; Morrisey, Joanne M.; Mather, Michael W.; Crowley, Jan R.; Henderson, Jeffrey P.; Goldberg, Daniel E.; Long, Carole A.; Vaidya, Akhil B.

    2014-01-01

    Heme is an essential cofactor for aerobic organisms. Its redox chemistry is central to a variety of biological functions mediated by hemoproteins. In blood stages, malaria parasites consume most of the hemoglobin inside the infected erythrocytes, forming nontoxic hemozoin crystals from large quantities of heme released during digestion. At the same time, the parasites possess a heme de novo biosynthetic pathway. This pathway in the human malaria parasite Plasmodium falciparum has been considered essential and is proposed as a potential drug target. However, we successfully disrupted the first and last genes of the pathway, individually and in combination. These knock-out parasite lines, lacking 5-aminolevulinic acid synthase and/or ferrochelatase (FC), grew normally in blood-stage culture and exhibited no changes in sensitivity to heme-related antimalarial drugs. We developed a sensitive LC-MS/MS assay to monitor stable isotope incorporation into heme from its precursor 5-[13C4]aminolevulinic acid, and this assay confirmed that de novo heme synthesis was ablated in FC knock-out parasites. Disrupting the FC gene also caused no defects in gametocyte generation or maturation but resulted in a greater than 70% reduction in male gamete formation and completely prevented oocyst formation in female Anopheles stephensi mosquitoes. Our data demonstrate that the heme biosynthesis pathway is not essential for asexual blood-stage growth of P. falciparum parasites but is required for mosquito transmission. Drug inhibition of pathway activity is therefore unlikely to provide successful antimalarial therapy. These data also suggest the existence of a parasite mechanism for scavenging host heme to meet metabolic needs. PMID:25352601

  20. A cell-based systems biology assessment of human blood to monitor immune responses after influenza vaccination.

    Science.gov (United States)

    Hoek, Kristen L; Samir, Parimal; Howard, Leigh M; Niu, Xinnan; Prasad, Nripesh; Galassie, Allison; Liu, Qi; Allos, Tara M; Floyd, Kyle A; Guo, Yan; Shyr, Yu; Levy, Shawn E; Joyce, Sebastian; Edwards, Kathryn M; Link, Andrew J

    2015-01-01

    Systems biology is an approach to comprehensively study complex interactions within a biological system. Most published systems vaccinology studies have utilized whole blood or peripheral blood mononuclear cells (PBMC) to monitor the immune response after vaccination. Because human blood is comprised of multiple hematopoietic cell types, the potential for masking responses of under-represented cell populations is increased when analyzing whole blood or PBMC. To investigate the contribution of individual cell types to the immune response after vaccination, we established a rapid and efficient method to purify human T and B cells, natural killer (NK) cells, myeloid dendritic cells (mDC), monocytes, and neutrophils from fresh venous blood. Purified cells were fractionated and processed in a single day. RNA-Seq and quantitative shotgun proteomics were performed to determine expression profiles for each cell type prior to and after inactivated seasonal influenza vaccination. Our results show that transcriptomic and proteomic profiles generated from purified immune cells differ significantly from PBMC. Differential expression analysis for each immune cell type also shows unique transcriptomic and proteomic expression profiles as well as changing biological networks at early time points after vaccination. This cell type-specific information provides a more comprehensive approach to monitor vaccine responses.

  1. A Cell-Based Systems Biology Assessment of Human Blood to Monitor Immune Responses after Influenza Vaccination

    Science.gov (United States)

    Hoek, Kristen L.; Samir, Parimal; Howard, Leigh M.; Niu, Xinnan; Prasad, Nripesh; Galassie, Allison; Liu, Qi; Allos, Tara M.; Floyd, Kyle A.; Guo, Yan; Shyr, Yu; Levy, Shawn E.; Joyce, Sebastian; Edwards, Kathryn M.; Link, Andrew J.

    2015-01-01

    Systems biology is an approach to comprehensively study complex interactions within a biological system. Most published systems vaccinology studies have utilized whole blood or peripheral blood mononuclear cells (PBMC) to monitor the immune response after vaccination. Because human blood is comprised of multiple hematopoietic cell types, the potential for masking responses of under-represented cell populations is increased when analyzing whole blood or PBMC. To investigate the contribution of individual cell types to the immune response after vaccination, we established a rapid and efficient method to purify human T and B cells, natural killer (NK) cells, myeloid dendritic cells (mDC), monocytes, and neutrophils from fresh venous blood. Purified cells were fractionated and processed in a single day. RNA-Seq and quantitative shotgun proteomics were performed to determine expression profiles for each cell type prior to and after inactivated seasonal influenza vaccination. Our results show that transcriptomic and proteomic profiles generated from purified immune cells differ significantly from PBMC. Differential expression analysis for each immune cell type also shows unique transcriptomic and proteomic expression profiles as well as changing biological networks at early time points after vaccination. This cell type-specific information provides a more comprehensive approach to monitor vaccine responses. PMID:25706537

  2. ABO blood type correlates with survival on prostate cancer vaccine therapy.

    Science.gov (United States)

    Muthana, Saddam M; Gulley, James L; Hodge, James W; Schlom, Jeffrey; Gildersleeve, Jeffrey C

    2015-10-13

    Immunotherapies for cancer are transforming patient care, but clinical responses vary considerably from patient to patient. Simple, inexpensive strategies to target treatment to likely responders could substantially improve efficacy while simultaneously reducing health care costs, but identification of reliable biomarkers has proven challenging. Previously, we found that pre-treatment serum IgM to blood group A (BG-A) correlated with survival for patients treated with PROSTVAC-VF, a therapeutic cancer vaccine in phase III clinical trials for the treatment of prostate cancer. These results suggested that ABO blood type might influence efficacy. Unfortunately, blood types were not available in the clinical records for all but 8 patients and insufficient amounts of sera were left for standard blood typing methods. To test the hypothesis, therefore, we developed a new glycan microarray-based method for determining ABO blood type. The method requires only 4 μL of serum, provides 97% accuracy, and allows simultaneous profiling of many other serum anti-glycan antibodies. After validation with 220 healthy subjects of known blood type, the method was then applied to 74 PROSTVAC-VF patients and 37 control patients from a phase II trial. In this retrospective study, we found that type B and O PROSTVAC-VF patients demonstrated markedly improved clinical outcomes relative to A and AB patients, including longer median survival, longer median survival relative to Halabi predicted survival, and improved overall survival via Kaplan-Meier survival analysis (p = 0.006). Consequently, blood type may provide an inexpensive screen to pre-select patients likely to benefit from PROSTVAC-VF therapy.

  3. Liver-inherent immune system: its role in blood-stage malaria.

    Science.gov (United States)

    Wunderlich, Frank; Al-Quraishy, Saleh; Dkhil, Mohamed A

    2014-01-01

    The liver is well known as that organ which is obligately required for the intrahepatocyte development of the pre-erythrocytic stages of the malaria-causative agent Plasmodium. However, largely neglected is the fact that the liver is also a central player of the host defense against the morbidity- and mortality-causing blood stages of the malaria parasites. Indeed, the liver is equipped with a unique immune system that acts locally, however, with systemic impact. Its main "antipodal" functions are to recognize and to generate effective immunoreactivity against pathogens on the one hand, and to generate tolerance to avoid immunoreactivity with "self" and harmless substances as dietary compounds on the other hand. This review provides an introductory survey of the liver-inherent immune system: its pathogen recognition receptors including Toll-like receptors (TLRs) and its major cell constituents with their different facilities to fight and eliminate pathogens. Then, evidence is presented that the liver is also an essential organ to overcome blood-stage malaria. Finally, we discuss effector responses of the liver-inherent immune system directed against blood-stage malaria: activation of TLRs, acute phase response, phagocytic activity, cytokine-mediated pro- and anti-inflammatory responses, generation of "protective" autoimmunity by extrathymic T cells and B-1 cells, and T cell-mediated repair of liver injuries mainly produced by malaria-induced overreactions of the liver-inherent immune system.

  4. Leidos Biomed Supports Clinical Trials for Vaccine Against Mosquito-borne Chikungunya | FNLCR Staging

    Science.gov (United States)

    An experimental vaccine for mosquito-borne chikungunya is being tested at sites in the Caribbean as part of a phase II clinical trial being managed by the Frederick National Lab. No vaccine or treatment currently exists for the viral disease, which c

  5. Effects of Concord grape juice on ambulatory blood pressure in prehypertension and stage 1 hypertension123

    Science.gov (United States)

    Dohadwala, Mustali M; Hamburg, Naomi M; Holbrook, Monika; Kim, Brian H; Duess, Mai-Ann; Levit, Aaron; Titas, Megan; Chung, William B; Vincent, Felix B; Caiano, Tara L; Frame, Alissa A; Keaney, John F

    2010-01-01

    Background: Consumption of flavonoid-containing foods may be useful for the management of hypertension. Objective: We investigated whether 100% Concord grape juice lowers blood pressure in patients with prehypertension and stage 1 hypertension. Design: We conducted a double-blind crossover study to compare the effects of grape juice (7 mL · kg−1 · d−1) and matched placebo beverage on 24-h ambulatory blood pressure, stress-induced changes in blood pressure, and biochemical profile. Participants consumed each beverage for 8 wk with a 4-wk rest period between beverages. They ceased consumption of grapes and other flavonoid-containing beverages throughout the study. Results: We enrolled 64 otherwise healthy patients taking no antihypertensive medications (31% women, 42% black, age 43 ± 12 y). Baseline mean (±SD) cuff blood pressure was 138 ± 7 (systolic)/82 ± 7 (diastolic) mm Hg. No effects on the primary endpoint of 24-h mean systolic blood pressure, diastolic blood pressure, or stress-induced changes in blood pressure were observed. A secondary endpoint was nocturnal dip in systolic pressure. At baseline, nocturnal pressure was 8.3 ± 7.1% lower at night than during daytime. The mean nocturnal dip increased 1.4 percentage points after grape juice and decreased 2.3 percentage points after placebo (P = 0.005). Fasting blood glucose was 91 ± 10 mg/dL at baseline for the entire cohort. Glucose decreased 2 mg/dL after consumption of grape juice and increased 1 mg/dL after consuming the placebo (P = 0.03). Conclusions: We observed no effect of grape juice on ambulatory blood pressure in this cohort of relatively healthy individuals with modestly elevated blood pressure. Secondary analyses suggested favorable effects on nocturnal dip and glucose homeostasis that may merit further investigation. This trial was registered at clinicaltrials.gov as NCT00302809. PMID:20844075

  6. Disruption of transitional stages in 24-h blood pressure in renal transplant recipients

    Directory of Open Access Journals (Sweden)

    Marcelo E Katz

    2012-03-01

    Full Text Available Patients with kidney replacement exhibit disrupted circadian rhythms. Most studies measuring blood pressure use the dipper/non-dipper classification, which does not consider analysis of transitional stages between low and high blood pressure, confidence intervals nor shifts in the time of peak, while assuming subjective onsets of night and day phases. In order to better understand the nature of daily variation of blood pressure in these patients, we analyzed 24h recordings from 41 renal transplant recipients using the non-symmetrical double-logistic fitting assessment which does not assume abruptness nor symmetry in ascending and descending stages of the blood pressure profile, and a cosine best-fitting regression method (Cosinor. Compared with matched controls, double-logistic fitting showed that the times for most of transitional stages (ascending systolic and descending systolic, diastolic and mean arterial pressure had a wider distribution along the 24 h. The proportion of individuals without daily blood pressure rhythm in the transplanted group was larger only for systolic arterial pressure, and the amplitude showed no significant difference. Furthermore, the transplant recipient group had a less pronounced slope in descending systolic and ascending mean blood pressure. Cosinor analysis confirmed the phase related changes, showing a wider distribution of times of peak (acrophases. We conclude that daily disruptions in renal transplant recipients can be explained not only by absence in diurnal variation, but also in changes in waveform-related parameters of the rhythm, and that distortions in the phase of the rhythm are the most consistent finding for the patients.

  7. Towards an RTS,S-based, multi-stage, multi-antigen vaccine against falciparum malaria: progress at the Walter Reed Army Institute of Research

    NARCIS (Netherlands)

    Heppner, D. Gray; Kester, Kent E.; Ockenhouse, Christian F.; Tornieporth, Nadia; Ofori, Opokua; Lyon, Jeffrey A.; Stewart, V. Ann; Dubois, Patrice; Lanar, David E.; Krzych, Urszula; Moris, Philippe; Angov, Evelina; Cummings, James F.; Leach, Amanda; Hall, B. Ted; Dutta, Sheetij; Schwenk, Robert; Hillier, Collette; Barbosa, Arnoldo; Ware, Lisa A.; Nair, Lalitha; Darko, Christian A.; Withers, Mark R.; Ogutu, Bernhards; Polhemus, Mark E.; Fukuda, Mark; Pichyangkul, Sathit; Gettyacamin, Montip; Diggs, Carter; Soisson, Lorraine; Milman, Jessica; Dubois, Marie-Claude; Garçon, Nathalie; Tucker, Kathryn; Wittes, Janet; Plowe, Christopher V.; Thera, Mahamadou A.; Duombo, Ogobara K.; Pau, Maria G.; Goudsmit, Jaap; Ballou, W. Ripley; Cohen, Joe

    2005-01-01

    The goal of the Malaria Vaccine Program at the Walter Reed Army Institute of Research (WRAIR) is to develop a licensed multi-antigen, multi-stage vaccine against Plasmodium falciparum able to prevent all symptomatic manifestations of malaria by preventing parasitemia. A secondary goal is to limit

  8. Phase II Study of HER-2/Neu Intracellular Domain Peptide-Based Vaccine Administered to Stage IV HER2 Positive Breast Cancer Patients Receiving Trastuzumab

    National Research Council Canada - National Science Library

    Disis, Mary L

    2005-01-01

    .... This proposal outlines a Phase II clinical trial designed to estimate survival in Stage IV HER2 positive breast cancer patients with no evidence of disease and receiving trastuzumab and a HER2 ICD peptide based vaccine...

  9. Interferon-gamma--central mediator of protective immune responses against the pre-erythrocytic and blood stage of malaria.

    NARCIS (Netherlands)

    McCall, M.B.B.; Sauerwein, R.W.

    2010-01-01

    Immune responses against Plasmodium parasites, the causative organisms of malaria, are traditionally dichotomized into pre-erythrocytic and blood-stage components. Whereas the central role of cellular responses in pre-erythrocytic immunity is well established, protection against blood-stage

  10. Immunological memory to blood-stage malaria infection is controlled by the histamine releasing factor (HRF) of the parasite.

    Science.gov (United States)

    Demarta-Gatsi, Claudia; Peronet, Roger; Smith, Leanna; Thiberge, Sabine; Ménard, Robert; Mécheri, Salaheddine

    2017-08-22

    While most subunit malaria vaccines provide only limited efficacy, pre-erythrocytic and erythrocytic genetically attenuated parasites (GAP) have been shown to confer complete sterilizing immunity. We recently generated a Plasmodium berghei (PbNK65) parasite that lacks a secreted factor, the histamine releasing factor (HRF) (PbNK65 hrfΔ), and induces in infected mice a self-resolving blood stage infection accompanied by a long lasting immunity. Here, we explore the immunological mechanisms underlying the anti-parasite protective properties of the mutant PbNK65 hrfΔ and demonstrate that in addition to an up-regulation of IL-6 production, CD4 + but not CD8 + T effector lymphocytes are indispensable for the clearance of malaria infection. Maintenance of T cell-associated protection is associated with the reduction in CD4 + PD-1 + and CD8 + PD-1 + T cell numbers. A higher number of central and effector memory B cells in mutant-infected mice also plays a pivotal role in protection. Importantly, we also demonstrate that prior infection with WT parasites followed by a drug cure does not prevent the induction of PbNK65 hrfΔ-induced protection, suggesting that such protection in humans may be efficient even in individuals that have been infected and who repeatedly received antimalarial drugs.

  11. Subunit vaccine consisting of multi-stage antigens has high protective efficacy against Mycobacterium tuberculosis infection in mice.

    Directory of Open Access Journals (Sweden)

    Qi Xin

    Full Text Available To search for more effective tuberculosis (TB subunit vaccines, antigens expressed in different growth stages of Mycobacterium tuberculosis (M. tuberculosis, such as RpfE (Rv2450c produced in the stage of resuscitation, Mtb10.4 (Rv0288, Mtb8.4 (Rv1174c, ESAT6 (Rv3875, Ag85B (Rv1886c mainly secreted by replicating bacilli, and HspX (Rv2031c highly expressed in dormant bacilli, were selected to construct six fusion proteins: ESAT6-Ag85B-MPT64190-198-Mtb8.4 (EAMM, Mtb10.4-HspX (MH, ESAT6-Mtb8.4, Mtb10.4-Ag85B, ESAT6-Ag85B, and ESAT6-RpfE. The six fusion proteins were separately emulsified in an adjuvant composed of N,N'-dimethyl-N, N'-dioctadecylammonium bromide (DDA, polyribocytidylic acid (poly I:C and gelatin to construct subunit vaccines, and their protective effects against M. tuberculosis infection were evaluated in C57BL/6 mice. Furthermore, the boosting effects of EAMM and MH in the adjuvant of DDA plus trehalose 6,6'-dimycolate (TDM on BCG-induced immunity were also evaluated. It was found that the six proteins were stably produced in E. coli and successfully purified by chromatography. Among them, EAMM presented the most effective protection against M. tuberculosis. Interestingly, the mice that received EAMM+MH had significantly lower bacterial counts in the lungs and spleens than the single protein vaccinated groups, and had the same effect as those that received BCG. In addition, EAMM and MH could improve BCG-primed protective efficacy against M. tuberculosis infection in mice. In conclusion, the combination of EAMM and MH containing antigens from both replicating and dormant stages of the bacilli could induce robust immunity against M. tuberculosis infection in mice and may serve as promising subunit vaccine candidate.

  12. Assessment of safety and reproductive performance after vaccination with a modified live-virus PRRS genotype 1 vaccine in pregnant sows at various stages of gestation.

    Science.gov (United States)

    Stadler, Julia; Zoels, Susanne; Eddicks, Matthias; Kraft, Christian; Ritzmann, Mathias; Ladinig, Andrea

    2016-07-19

    The objective of the present study was to assess safety and efficacy of a new modified live-virus porcine reproductive and respiratory syndrome (PRRS) genotype 1 vaccine in pregnant sows at various stages of gestation under field conditions. A total of 505 sows and gilts were allocated to two treatment groups and maintained in separate facilities. Animals of group 1 were vaccinated with a commercial modified live genotype 1 PRRSV vaccine (control product, CP), while animals of group 2 were immunized with a new modified live genotype 1 PRRSV vaccine (investigational veterinary product, IVP) (ReproCyc® PRRS EU, Boehringer Ingelheim Vetmedica GmbH). Injection site reactions were noted to be significantly less frequent in the IVP group compared to the CP group for pain (p=0.039), redness (p=0.030), heat (p=0.016) and swelling (p=0.002). The mean total number of piglets alive at weaning did not differ significantly between both study groups (10.6 vs. 11.0, p=0.375). However, pre-weaning mortality was significantly higher (p=0.005) in piglets from the CP group (14.1% vs. 10.9%). Analyses of reproductive performance data for both groups did not result in statistically significant differences between CP group and IVP group for number of piglets alive (12.7 and 12.6, respectively), healthy live (11.9 and 11.8), weak (0.7 and 0.5), stillborn (1.0 and 0.8) and mummified piglets (0.3 and 0.2) per litter. No differences were detected between both groups for piglet birth weights, while body weights at weaning (7.2kg vs. 6.6kg, p=0.026) and average daily gain (0.2445kg vs. 0.2211kg, p=0.037) were significantly higher in piglets from the IVP group. In conclusion, the administration of a single dose of ReproCyc® PRRS EU to sows and gilts at various stages of gestation confirmed non-inferiority to a commercial PRRS vaccine regarding safety and efficacy parameters under field conditions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  13. Adjuvant Autologous Melanoma Vaccine for Macroscopic Stage III Disease: Survival, Biomarkers, and Improved Response to CTLA-4 Blockade

    Directory of Open Access Journals (Sweden)

    Michal Lotem

    2016-01-01

    Full Text Available Background. There is not yet an agreed adjuvant treatment for melanoma patients with American Joint Committee on Cancer stages III B and C. We report administration of an autologous melanoma vaccine to prevent disease recurrence. Patients and Methods. 126 patients received eight doses of irradiated autologous melanoma cells conjugated to dinitrophenyl and mixed with BCG. Delayed type hypersensitivity (DTH response to unmodified melanoma cells was determined on the vaccine days 5 and 8. Gene expression analysis was performed on 35 tumors from patients with good or poor survival. Results. Median overall survival was 88 months with a 5-year survival of 54%. Patients attaining a strong DTH response had a significantly better (p=0.0001 5-year overall survival of 75% compared with 44% in patients without a strong response. Gene expression array linked a 50-gene signature to prognosis, including a cluster of four cancer testis antigens: CTAG2 (NY-ESO-2, MAGEA1, SSX1, and SSX4. Thirty-five patients, who received an autologous vaccine, followed by ipilimumab for progressive disease, had a significantly improved 3-year survival of 46% compared with 19% in nonvaccinated patients treated with ipilimumab alone (p=0.007. Conclusion. Improved survival in patients attaining a strong DTH and increased response rate with subsequent ipilimumab suggests that the autologous vaccine confers protective immunity.

  14. Screening inhibitors of P. berghei blood stages using bioluminescent reporter parasites.

    Science.gov (United States)

    Lin, Jing-Wen; Sajid, Mohammed; Ramesar, Jai; Khan, Shahid M; Janse, Chris J; Franke-Fayard, Blandine

    2013-01-01

    We describe two improved assays for in vitro and in vivo screening of inhibitors and chemicals for antimalarial activity against blood stages of the rodent malaria parasite, Plasmodium berghei. These assays are based on the determination of bioluminescence in small blood samples that is produced by reporter parasites expressing luciferase. Luciferase production increases as the parasite develops in a red blood cell and as the numbers of parasites increase during an infection. In the first assay, in vitro drug luminescence (ITDL) assay, the in vitro development of ring-stage parasites into mature schizonts in the presence and absence of candidate inhibitor(s) is quantified by measuring luciferase activity after the parasites have been allowed to mature into schizonts in culture. In the second assay, the in vivo drug luminescence (IVDL) assay, in vivo parasite growth (using a standard 4-day suppressive drug test) is quantified by measuring the luciferase activity of circulating parasites in samples of tail blood of drug-treated mice.

  15. Assessment of humoral immune responses to blood-stage malaria antigens following ChAd63-MVA immunization, controlled human malaria infection and natural exposure.

    Directory of Open Access Journals (Sweden)

    Sumi Biswas

    Full Text Available The development of protective vaccines against many difficult infectious pathogens will necessitate the induction of effective antibody responses. Here we assess humoral immune responses against two antigens from the blood-stage merozoite of the Plasmodium falciparum human malaria parasite--MSP1 and AMA1. These antigens were delivered to healthy malaria-naïve adult volunteers in Phase Ia clinical trials using recombinant replication-deficient viral vectors--ChAd63 to prime the immune response and MVA to boost. In subsequent Phase IIa clinical trials, immunized volunteers underwent controlled human malaria infection (CHMI with P. falciparum to assess vaccine efficacy, whereby all but one volunteer developed low-density blood-stage parasitemia. Here we assess serum antibody responses against both the MSP1 and AMA1 antigens following i ChAd63-MVA immunization, ii immunization and CHMI, and iii primary malaria exposure in the context of CHMI in unimmunized control volunteers. Responses were also assessed in a cohort of naturally-immune Kenyan adults to provide comparison with those induced by a lifetime of natural malaria exposure. Serum antibody responses against MSP1 and AMA1 were characterized in terms of i total IgG responses before and after CHMI, ii responses to allelic variants of MSP1 and AMA1, iii functional growth inhibitory activity (GIA, iv IgG avidity, and v isotype responses (IgG1-4, IgA and IgM. These data provide the first in-depth assessment of the quality of adenovirus-MVA vaccine-induced antibody responses in humans, along with assessment of how these responses are modulated by subsequent low-density parasite exposure. Notable differences were observed in qualitative aspects of the human antibody responses against these malaria antigens depending on the means of their induction and/or exposure of the host to the malaria parasite. Given the continued clinical development of viral vectored vaccines for malaria and a range of other

  16. FNL Scientists Introduce Concept That Could Help the Immune System Respond to Vaccines | FNLCR Staging

    Science.gov (United States)

    Scientists have discovered an efficient and straightforward model to manipulate RNA nanoparticles, a new concept that could help trigger desirable activation of the immune system with vaccines and therapies. A multi-institutional team of researchers

  17. Cerebral oxygen metabolism and cerebral blood flow in man during light sleep (stage 2)

    DEFF Research Database (Denmark)

    Madsen, P L; Schmidt, J F; Holm, S

    1991-01-01

    We measured cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) during light sleep (stage 2) in 8 young healthy volunteers using the Kety-Schmidt technique with 133Xe as the inert gas. Measurements were performed during wakefulness and light sleep as verified by standard...... polysomnography. Unlike our previous study in man showing a highly significant 25% decrease in CMRO2 during deep sleep (stage 3-4) we found a modest but statistically significant decrease of 5% in CMRO2 during stage 2 sleep. Deep and light sleep are both characterized by an almost complete lack of mental activity....... They differ in respect of arousal threshold as a stronger stimulus is required to awaken a subject from deep sleep as compared to light sleep. Our results suggest that during non-rapid eye movement sleep cerebral metabolism and thereby cerebral synaptic activity is correlated to cerebral readiness rather than...

  18. A multi-stage malaria vaccine candidate targeting both transmission and asexual parasite life-cycle stages

    DEFF Research Database (Denmark)

    Theisen, Michael; Roeffen, Will; Singh, Susheel K

    2014-01-01

    that combine antigens from both stages may provide direct protection and indirect benefit by reducing the force of infection. We constructed a chimeric antigen composed of a fragment of the Plasmodium falciparum (Pf) glutamate-rich protein fused in frame to a correctly folded fragment of Pfs48/45. The chimera...... was produced in Lactococcus lactis and induced robust antibody responses in rodents to the individual components. Specific antibodies showed strong transmission blocking activity against multiple Pf-strains in the standard membrane feeding assay and functional activity against asexual stages in the antibody...

  19. Vaccinations

    Science.gov (United States)

    ... will not work well for all pets. Your veterinarian will determine a vaccination schedule most appropriate for ... programs, but in some instances may help your veterinarian determine if your pet has a reasonable expectation ...

  20. Beneficiary characteristics and vaccinations in the end-stage renal disease Medicare beneficiary population, an analysis of claims data 2006-2015.

    Science.gov (United States)

    Shen, Angela K; Kelman, Jeffrey A; Warnock, Rob; Zhang, Weiwei; Brereton, Stephaeno; McKean, Stephen; Wernecke, Michael; Chu, Steve; Gellin, Bruce G

    2017-12-19

    The Advisory Committee on Immunization Practices (ACIP) routinely recommends three vaccines - influenza, hepatitis B, and pneumococcal vaccines - for End-Stage Renal Disease (ESRD) dialysis patients. We sought to assess vaccination coverage among fee-for-service (FFS) Medicare beneficiaries with ESRD who received Part B dialysis services at any point from January 1, 2006 through December 31, 2015 (through June 30, 2016 for influenza). To assess influenza vaccination rates in a given influenza season, we restricted the population to beneficiaries who were continuously enrolled in Medicare Parts A and B throughout all twelve months of that season. To assess hepatitis B and pneumococcal vaccine coverage following dialysis initiation, we developed a Kaplan-Meier curve for all patients who began dialysis between 2006 and 2015. For influenza vaccination, we identified an average of approximately 325,000 ESRD dialysis beneficiaries enrolled through each influenza season from 2006-2015. Seasonal influenza vaccination rates steadily increased during the 10-year period, from 52% in 2006-2007 to 71% in 2015-2016. The greatest increases in influenza vaccination appear in non-white beneficiaries with overall utilization in non-whites higher than in whites (p vaccinations, we identified over 350,000 ESRD dialysis beneficiaries who began dialysis over the 10-year study window. The probability of receiving a hepatitis B vaccine within the first three years of entering into the ESRD program was higher (77%) than the probability of receiving any pneumococcal vaccine (53%). 45% of ESRD patients completed at least one dose of the two hepatitis B series (three-dose or four-dose) at any time during the study period. Opportunities exist at regional and facility levels to improve vaccination coverage. Compliance to ACIP recommendations may directly affect risk for ESRD dialysis patients for complications from diseases that can be mitigated by vaccination. Published by Elsevier Ltd.

  1. Gold nanoparticle-enabled blood test for early stage cancer detection and risk assessment.

    Science.gov (United States)

    Zheng, Tianyu; Pierre-Pierre, Nickisha; Yan, Xin; Huo, Qun; Almodovar, Alvin J O; Valerio, Felipe; Rivera-Ramirez, Inoel; Griffith, Elizabeth; Decker, David D; Chen, Sixue; Zhu, Ning

    2015-04-01

    When citrate ligands-capped gold nanoparticles are mixed with blood sera, a protein corona is formed on the nanoparticle surface due to the adsorption of various proteins in the blood to the nanoparticles. Using a two-step gold nanoparticle-enabled dynamic light scattering assay, we discovered that the amount of human immunoglobulin G (IgG) in the gold nanoparticle protein corona is increased in prostate cancer patients compared to noncancer controls. Two pilot studies conducted on blood serum samples collected at Florida Hospital and obtained from Prostate Cancer Biorespository Network (PCBN) revealed that the test has a 90-95% specificity and 50% sensitivity in detecting early stage prostate cancer, representing a significant improvement over the current PSA test. The increased amount of human IgG found in the protein corona is believed to be associated with the autoantibodies produced in cancer patients as part of the immunodefense against tumor. Proteomic analysis of the nanoparticle protein corona revealed molecular profile differences between cancer and noncancer serum samples. Autoantibodies and natural antibodies produced in cancer patients in response to tumorigenesis have been found and detected in the blood of many cancer types. The test may be applicable for early detection and risk assessment of a broad spectrum of cancer. This new blood test is simple, low cost, requires only a few drops of blood sample, and the results are obtained within minutes. The test is well suited for screening purpose. More extensive studies are being conducted to further evaluate and validate the clinical potential of the new test.

  2. Blood transfusion and survival after surgery for Stage I and II breast cancer

    International Nuclear Information System (INIS)

    Herman, K.; Kolodziejski, L.

    1993-01-01

    The records of 690 Stage I and II breast cancer patients (31% of them with transfusions), who underwent mastectomy with axillary dissection were examined whether perioperative blood transfusion might be detrimental to survival. The overall 5- and 1-year survival rates for 477 patients who had not received transfusions were 75% and 63% respectively, compared with 66% and 49% for those who had transfusions (p=0.005). There was no significant difference between the group in any other of the most important prognostic factors. An analysis of the subpopulation of patients with favorable prognostic factors yielded similar results. A multivariate analysis indicated that blood transfusion was one of the four variables significantly related to survival. (author)

  3. Cerebral oxygen metabolism and cerebral blood flow in man during light sleep (stage 2)

    DEFF Research Database (Denmark)

    Madsen, P L; Schmidt, J F; Holm, S

    1991-01-01

    We measured cerebral blood flow (CBF) and cerebral metabolic rate of oxygen (CMRO2) during light sleep (stage 2) in 8 young healthy volunteers using the Kety-Schmidt technique with 133Xe as the inert gas. Measurements were performed during wakefulness and light sleep as verified by standard....... They differ in respect of arousal threshold as a stronger stimulus is required to awaken a subject from deep sleep as compared to light sleep. Our results suggest that during non-rapid eye movement sleep cerebral metabolism and thereby cerebral synaptic activity is correlated to cerebral readiness rather than...

  4. Decreased mitochondrial DNA content in blood samples of patients with stage I breast cancer

    Directory of Open Access Journals (Sweden)

    Fokas Emmanouil

    2009-12-01

    Full Text Available Abstract Background Alterations of mitochondrial DNA (mtDNA have been implicated in carcinogenesis. We developed an accurate multiplex quantitative real-time PCR for synchronized determination of mtDNA and nuclear DNA (nDNA. We sought to investigate whether mtDNA content in the peripheral blood of breast cancer patients is associated with clinical and pathological parameters. Methods Peripheral blood samples were collected from 60 patients with breast cancer and 51 age-matched healthy individuals as control. DNA was extracted from peripheral blood for the quantification of mtDNA and nDNA, using a one-step multiplex real-time PCR. A FAM labeled MGB probe and primers were used to amplify the mtDNA sequence of the ATP 8 gene, and a VIC labeled MGB probe and primers were employed to amplify the glyceraldehyde-3-phosphate-dehydrogenase gene. mtDNA content was correlated with tumor stage, menstruation status, and age of patients as well as lymph node status and the expression of estrogen receptor (ER, progesterone receptor (PR and Her-2/neu protein. Results The content of mtDNA in stage I breast cancer patients was significantly lower than in other stages (overall P = 0.023. Reduced mtDNA was found often in post menopausal cancer group (P = 0.024. No difference in mtDNA content, in regards to age (p = 0.564, lymph node involvement (p = 0.673, ER (p = 0.877, PR (p = 0.763, and Her-2/neu expression (p = 0.335, was observed. Conclusion Early detection of breast cancer has proved difficult and current detection methods are inadequate. In the present study, decreased mtDNA content in the peripheral blood of patients with breast cancer was strongly associated with stage I. The use of mtDNA may have diagnostic value and further studies are required to validate it as a potential biomarker for early detection of breast cancer.

  5. The Predictive Value of Inflammation-Related Peripheral Blood Measurements in Cancer Staging and Prognosis

    Directory of Open Access Journals (Sweden)

    Joanna L. Sylman

    2018-03-01

    Full Text Available In this review, we discuss the interaction between cancer and markers of inflammation (such as levels of inflammatory cells and proteins in the circulation, and the potential benefits of routinely monitoring these markers in peripheral blood measurement assays. Next, we discuss the prognostic value and limitations of using inflammatory markers such as neutrophil-to-lymphocyte and platelet-to-lymphocyte ratios and C-reactive protein measurements. Furthermore, the review discusses the benefits of combining multiple types of measurements and longitudinal tracking to improve staging and prognosis prediction of patients with cancer, and the ability of novel in silico frameworks to leverage this high-dimensional data.

  6. Staging of malignant lymphoma with three-station black-blood fast short-inversion time inversion recovery (STIR).

    Science.gov (United States)

    Amano, Yasuo; Tajika, Kenji; Uchiyama, Nachiko; Takahama, Katsuya; Dan, Kazuo; Kumazaki, Tatsuo

    2003-04-01

    The purpose of this study was to assess the usefulness of three-station black-blood fast short-inversion time inversion recovery (STIR) imaging in detecting and staging malignant lymphoma. Seventeen patients with malignant lymphoma were examined with a 1.5T imager. The findings and stagings determined with three-station black-blood fast STIR imaging were compared with reference standards (e.g., computed tomography [CT] findings and clinical stagings). Three-station black-blood fast STIR imaging provided a fat-suppressed T2-weighted imaging contrast with fewer flow artifacts and revealed nodal involvement as well as bone marrow and spleen involvement to an extent comparable with CT. Especially notable was the excellent specificity (94%) of this imaging technique. Regarding disease staging, significant agreement was observed between clinical staging (k=0.60) and staging as evaluated by three-station black-blood fast STIR, although the detection of lymphadenopathy in the thorax was relatively poor. The average time required for this imaging was approximately 30 min. Three-station black-blood fast STIR MR imaging may be useful as a staging tool for malignant lymphoma because this imaging technique reveals lymphoma lesions, which determine the staging, without radiation exposure or the use of contrast agents.

  7. DENGUE VACCINES.

    Science.gov (United States)

    Thisyakorn, Usa; Thisyakorn, Chule

    2015-01-01

    The uniqueness of the dengue viruses (DENVs) and the spectrum of disease resulting from infection have made dengue vaccine development difficult. Several vaccine candidates are currently being evaluated in clinical studies. The candidate currently at the most advanced clinical development stage, a live-attenuated tetravalent vaccine based on the chimeric yellow fever-dengue virus (CYD-TDV), has progressed to Phase 3 efficacy studies. Several other live-attenuated vaccines, as well as subunit, DNA, and purified inactivated vaccine candidates are at earlier stages of clinical development. Additional technological approaches, such as virus-vectored and Virus-Like Particles (VLP)-based vaccines are under evaluation in preclinical studies.

  8. Relationship Between Uterine and Ovarian Arterial Blood Flow Measured by Doppler Sonography at Different Stages of Puberty

    Directory of Open Access Journals (Sweden)

    Reza Golestani

    2008-03-01

    Conclusion: Uterine and ovarian arterial blood flow, measured by Doppler sonography, was not useful for the evaluation of pubertal stages. However, it should be investigated with a greater sample size.

  9. Application of solid-phase radioimmunoassay in determining antibodies to Aujeszky's disease virus in blood serum of vaccinated pigs

    Energy Technology Data Exchange (ETDEWEB)

    Rodak, L.; Smid, B.; Valicek, L. (Vyzkumny Ustav Veterinarniho Lekarstvi, Brno-Medlanky (Czechoslovakia))

    1983-11-01

    In the blood sera of pigs vaccinated with inactivated vaccines manufactured by three different manufacturers the RIA method was used to determine the specific antibodies to the virus of Aujeszky's disease. In certain groups of vaccinated pigs the results of the RIA examination are unfavourably affected by the bond of antibodies to the cellular antigenous determinants. This proves that following vaccination antibodies are formed not only against the viral antigen but also against the antigens of cells on which the vaccination virus is propagated. These shortcomings are eliminated by the use of suitable cellular cultures for the preparation of viral and control antigens. Antigens are applicable for RIA and for ELISA examinations of blood sera of infected and vaccinated pigs. The advantages are described of the RIA and ELISA methods as compared with the virus neutralization test.

  10. Humoral and cellular immunity to Plasmodium falciparum merozoite surface protein 1 and protection from infection with blood-stage parasites.

    Science.gov (United States)

    Moormann, Ann M; Sumba, Peter Odada; Chelimo, Kiprotich; Fang, Hua; Tisch, Daniel J; Dent, Arlene E; John, Chandy C; Long, Carole A; Vulule, John; Kazura, James W

    2013-07-01

     Acquired immunity to malaria develops with increasing age and repeated infections. Understanding immune correlates of protection from malaria would facilitate vaccine development and identification of biomarkers that reflect changes in susceptibility resulting from ongoing malaria control efforts.  The relationship between immunoglobulin G (IgG) antibody and both interferon γ (IFN-γ) and interleukin 10 (IL-10) responses to the 42-kD C-terminal fragment of Plasmodium falciparum merozoite surface protein 1 (MSP142) and the risk of (re)infection were examined following drug-mediated clearance of parasitemia in 94 adults and 95 children in an area of holoendemicity of western Kenya.  Positive IFN-γ enzyme-linked immunosorbent assay (ELISA) and enzyme-linked immunosorbent spot assay (ELISPOT) responses to MSP142 3D7 were associated with delayed time to (re)infection, whereas high-titer IgG antibodies to MSP142 3D7 or FVO alleles were not independently predictive of the risk of (re)infection. When IFN-γ and IL-10 responses were both present, the protective effect of IFN-γ was abrogated. A Cox proportional hazard model including IFN-γ, IL-10, MSP142 3D7 IgG antibody responses, hemoglobin S genotype, age, and infection status at baseline showed that the time to blood-stage infection correlated positively with IFN-γ responses and negatively with IL-10 responses, younger age, and asymptomatic parasitemia.  Evaluating combined allele-specific cellular and humoral immunity elicited by malaria provides a more informative measure of protection relative to evaluation of either measure alone.

  11. IFN-γ and TNF-α producing CD4+ T-cells in the blood after Mycoplasma hyosynoviae challenge of vaccinated pigs

    DEFF Research Database (Denmark)

    Riber, Ulla; Hansen, Mette Sif; Lauritsen, Klara Tølbøll

    In a vaccine trial against Mycoplasma hyosynoviae infection, pigs were vaccinated with formalin fixed whole-cell-antigen formulated with adjuvant DDA/TDB (SSI). Placebo pigs received adjuvant with saline. Vaccinations were performed at five and eight weeks of age, followed by an intranasal M....... hyosynoviae challenge inoculation three weeks later. Vaccination induced both antibodies and a cell-mediated immune response (CMI) in vaccinated pigs compared to placebo pigs as shown by M. hyosynoviae antigen (Ag) specific IFN-γ response in an IL-18 potentiated whole-blood IFN-γ stimulation assay (mean IFN......-γ level 1936 pg/ml vs. 82 pg/ml (p=0.0001)). A central memory T cell phenotype with polyfunctional capacity to produce all three cytokines IFN-γ, TNF-α and IL-2 has recently been linked to development of vaccine induced protection in several infections. In a subset of seven vaccinated pigs and four...

  12. Vaccine Pipeline Has Grown During The Past Two Decades With More Early-Stage Trials From Small And Medium-Size Companies.

    Science.gov (United States)

    Hwang, Thomas J; Kesselheim, Aaron S

    2016-02-01

    Many serious diseases lack safe and effective vaccines. Using a large commercial database, we examined trends in global vaccine research and development and found that the proportion of new vaccine candidates entering all stages of clinical development increased by 3-5 percentage points over the past two decades. Small and medium-size companies accounted for nearly twice as many new Phase I vaccine trials compared to large companies, but late-stage (Phase III) vaccine trials were dominated by large companies. There were no significant differences between vaccines and drugs in the probability of success in clinical trials or in profitability. Small and medium-size companies, including spin-outs from academic research centers, play an important role in innovative research and discovery. Our findings suggest that policy making targeted at smaller companies, such as prizes or opportunities for public-private partnerships, could support the development of new vaccines, particularly those targeting unmet medical needs and emerging public health threats. Project HOPE—The People-to-People Health Foundation, Inc.

  13. Investigation of the immature stage of the cord blood banks and their regulation in China.

    Science.gov (United States)

    Liu, Yinliang

    2008-12-01

    Cord blood banks (CBBs) collect umbilical cord blood and isolate therefrom the stem cells which may be transplanted into patients serving treatment of many kinds of serious diseases. As one kind of health resource, CBBs need regulation to guarantee its fair development and safe application. During the past decade, several CBBs have been established in China and related measures have been administered to regulate their establishment and manipulation. How about the actual situation of CBBs in China, including, how are they regulated and what are the problems with the CBBs in practice? Upon introduction to cord blood and the CBBs, this paper investigates the practical situation of the CBBs in China and their regulation, and explores the corresponding problems which need to be dealt with. It is held that the CBB system in China is still at an initial stage, not only for its establishment and operation, but for its regulation as well; and, therefore, justification of a more sustainable CBB system for a better development is needed in China.

  14. Systematic Analysis of Blood Cell Transcriptome in End-Stage Chronic Respiratory Diseases

    Science.gov (United States)

    Botturi, Karine; Reynaud-Gaubert, Martine; Mussot, Sacha; Stern, Marc; Danner-Boucher, Isabelle; Mornex, Jean-François; Pison, Christophe; Dromer, Claire; Kessler, Romain; Dahan, Marcel; Brugière, Olivier; Le Pavec, Jérôme; Perros, Frédéric; Humbert, Marc; Gomez, Carine; Brouard, Sophie; Magnan, Antoine

    2014-01-01

    Background End-stage chronic respiratory diseases (CRD) have systemic consequences, such as weight loss and susceptibility to infection. However the mechanisms of such dysfunctions are as yet poorly explained. We hypothesized that the genes putatively involved in these mechanisms would emerge from a systematic analysis of blood mRNA profiles from pre-transplant patients with cystic fibrosis (CF), pulmonary hypertension (PAH), and chronic obstructive pulmonary disease (COPD). Methods Whole blood was first collected from 13 patients with PAH, 23 patients with CF, and 28 Healthy Controls (HC). Microarray results were validated by quantitative PCR on a second and independent group (7PAH, 9CF, and 11HC). Twelve pre-transplant COPD patients were added to validate the common signature shared by patients with CRD for all causes. To further clarify a role for hypoxia in the candidate gene dysregulation, peripheral blood mononuclear cells from HC were analysed for their mRNA profile under hypoxia. Results Unsupervised hierarchical clustering allowed the identification of 3 gene signatures related to CRD. One was common to CF and PAH, another specific to CF, and the final one was specific to PAH. With the common signature, we validated T-Cell Factor 7 (TCF-7) and Interleukin 7 Receptor (IL-7R), two genes related to T lymphocyte activation, as being under-expressed. We showed a strong impact of the hypoxia on modulation of TCF-7 and IL-7R expression in PBMCs from HC under hypoxia or PBMCs from CRD. In addition, we identified and validated genes upregulated in PAH or CF, including Lectin Galactoside-binding Soluble 3 and Toll Like Receptor 4, respectively. Conclusions Systematic analysis of blood cell transcriptome in CRD patients identified common and specific signatures relevant to the systemic pathologies. TCF-7 and IL-7R were downregulated whatever the cause of CRD and this could play a role in the higher susceptibility to infection of these patients. PMID:25329529

  15. The impact of Rotavirus mass vaccination on hospitalization rates, nosocomial Rotavirus gastroenteritis and secondary blood stream infections.

    Science.gov (United States)

    Zlamy, Manuela; Kofler, Sabine; Orth, Dorothea; Würzner, Reinhard; Heinz-Erian, Peter; Streng, Andrea; Prelog, Martina

    2013-03-01

    The aim of the study was to evaluate the effects of universal mass vaccination (UMV) against rotavirus (RV) on the hospitalization rates, nosocomial RV infections and RV-gastroenteritis (GE)-associated secondary blood stream infections (BSI). The retrospective evaluation (2002-2009) by chart analysis included all clinically diagnosed and microbiologically confirmed RV-GE cases in a large tertiary care hospital in Austria. The pre-vaccination period (2002-2005) was compared with the recommended and early funded (2006-2007) and the funded (2008-2009) vaccination periods. Primary outcomes were RV-GE-associated hospitalizations, secondary outcomes nosocomial RV disease, secondary BSI and direct hospitalization costs for children and their accompanying persons. In 1,532 children with RV-GE, a significant reduction by 73.9% of hospitalized RV-GE cases per year could be observed between the pre-vaccination and the funded vaccination period, which was most pronounced in the age groups 0-11 months (by 87.8%), 6-10 years (by 84.2%) and 11-18 years (88.9%). In the funded vaccination period, a reduction by 71.9% of nosocomial RV-GE cases per year was found compared to the pre-vaccination period. Fatalities due to nosocomial RV-GE were only observed in the pre-vaccination period (3 cases). Direct costs of hospitalized, community-acquired RV-GE cases per year were reduced by 72.7% in the funded vaccination period. The reduction of direct costs for patients (by 86.9%) and accompanying persons (86.2%) was most pronounced in the age group 0-11 months. UMV may have contributed to the significant decrease of RV-GE-associated hospitalizations, to a reduction in nosocomial RV infections and RV-associated morbidity due to secondary BSI and reduced direct hospitalization costs. The reduction in nosocomial cases is an important aspect considering severe disease courses in hospitalized patients with co-morbidities and death due to nosocomial RV-GE.

  16. Timeliness and completeness of measles vaccination among children in rural areas of Guangxi, China: A stratified three-stage cluster survey

    Directory of Open Access Journals (Sweden)

    Xianyan Tang

    2017-07-01

    Full Text Available Background: Large-scale outbreaks of measles occurred in 2013 and 2014 in rural Guangxi, a region in Southwest China with high coverage for measles-containing vaccine (MCV. This study aimed to estimate the timely vaccination coverage, the timely-and-complete vaccination coverage, and the median delay period for MCV among children aged 18–54 months in rural Guangxi. Methods: Based on quartiles of measles incidence during 2011–2013, a stratified three-stage cluster survey was conducted from June through August 2015. Using weighted estimation and finite population correction, vaccination coverage and 95% confidence intervals (CIs were calculated. Weighted Kaplan–Meier analyses were used to estimate the median delay periods for the first (MCV1 and second (MCV2 doses of the vaccine. Results: A total of 1216 children were surveyed. The timely vaccination coverage rate was 58.4% (95% CI, 54.9%–62.0% for MCV1, and 76.9% (95% CI, 73.6%–80.0% for MCV2. The timely-and-complete vaccination coverage rate was 47.4% (95% CI, 44.0%–51.0%. The median delay period was 32 (95% CI, 27–38 days for MCV1, and 159 (95% CI, 118–195 days for MCV2. Conclusions: The timeliness and completeness of measles vaccination was low, and the median delay period was long among children in rural Guangxi. Incorporating the timeliness and completeness into official routine vaccination coverage statistics may help appraise the coverage of vaccination in China.

  17. Timeliness and completeness of measles vaccination among children in rural areas of Guangxi, China: A stratified three-stage cluster survey.

    Science.gov (United States)

    Tang, Xianyan; Geater, Alan; McNeil, Edward; Zhou, Hongxia; Deng, Qiuyun; Dong, Aihu

    2017-07-01

    Large-scale outbreaks of measles occurred in 2013 and 2014 in rural Guangxi, a region in Southwest China with high coverage for measles-containing vaccine (MCV). This study aimed to estimate the timely vaccination coverage, the timely-and-complete vaccination coverage, and the median delay period for MCV among children aged 18-54 months in rural Guangxi. Based on quartiles of measles incidence during 2011-2013, a stratified three-stage cluster survey was conducted from June through August 2015. Using weighted estimation and finite population correction, vaccination coverage and 95% confidence intervals (CIs) were calculated. Weighted Kaplan-Meier analyses were used to estimate the median delay periods for the first (MCV1) and second (MCV2) doses of the vaccine. A total of 1216 children were surveyed. The timely vaccination coverage rate was 58.4% (95% CI, 54.9%-62.0%) for MCV1, and 76.9% (95% CI, 73.6%-80.0%) for MCV2. The timely-and-complete vaccination coverage rate was 47.4% (95% CI, 44.0%-51.0%). The median delay period was 32 (95% CI, 27-38) days for MCV1, and 159 (95% CI, 118-195) days for MCV2. The timeliness and completeness of measles vaccination was low, and the median delay period was long among children in rural Guangxi. Incorporating the timeliness and completeness into official routine vaccination coverage statistics may help appraise the coverage of vaccination in China. Copyright © 2017 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

  18. Analysis of peripheral blood immune cells after prophylactic immunization with HPV-16/18 ASO4-adjuvanted vaccine

    Directory of Open Access Journals (Sweden)

    Iwona Hus

    2015-04-01

    Full Text Available Persistent infection with oncogenic types of human papillomavirus (HPV is a causal factor for more than 99% of cervical cancers. Recently, prophylactic vaccines have been developed to prevent infections with cancer-associated HPV types (HPV16 and HPV18. The aim of this study was to analyze the changes in the immune system that occur within four weeks of the first dose of HPV-16/18 ASO4-adjuvanted vaccine. Assessment of the percentages of selected cell populations in peripheral blood of 20 healthy volunteers vaccinated with Cervarix was performed using flow cytometry. The analysis revealed an increase in the proportion of activated B and CD4+ T helper cells and an absence of significant differences in cytotoxic CD8+ T lymphocytes, indicating activation of the humoral response after vaccination, without a significant effect on cellular response. There were no significant changes in the NK cell population, and there was a reduction of the percentage of NKT-like cells, which may result from expiry of the primary response at the time of analysis. The presented results are preliminary, and in the context of the increasing use of the anti-HPV vaccine, it would be worth continuing the study in larger groups of patients and at earlier and later time points in combination with the measurement of specific anti-HPV16 and -HPV18 antibody levels. Such an assessment could therefore contribute not only to better understanding of the exact mechanism of action of the vaccine, but also to defining the immunological parameters that determine its effectiveness.

  19. Blood lactate minimum of rats during swimming test using three incremental stages

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    Mariana de Souza Sena

    2015-09-01

    Full Text Available AbstractThe purpose of this study was to determine the lactate minimum intensity (LMI by swimming LACmintest using three incremental stages (LACmintest3 and to evaluate its sensitivity to changes in aerobic fitness (AF. Twenty Wistar rats performed: LACmintest3 (1: induction of hyperlactacidemia and incremental phase (4%, 5% and 6.5% of bw; Constant loads tests on (2 and above (3 the LMI. Half of the animals were subjected to training with the individual LMI and the tests were performed again. The mean exercise load in LACmintest3 was 5.04 ± 0.13% bw at 5.08 ± 0.55 mmol L-1 blood lactate minimum (BLM. There was a stabilize and disproportionate increase of blood lactate in tests 2 and 3, respectively. After the training period, the mean BLM was lower in the trained animals. The LACmintest3 seems to be a good indicator of LMI and responsive to changes in AF in rats subjected to swim training.

  20. Caveolins and flotillin-2 are present in the blood stages of Plasmodium vivax.

    Science.gov (United States)

    Bracho, Carmen; Dunia, Irene; Romano, Mirtha; Raposo, Graça; De La Rosa, Mercedes; Benedetti, Ennio-Lucio; Pérez, Hilda A

    2006-07-01

    Blood stages of Plasmodium vivax induce the development of caveolae and caveola-vesicle complexes (CVC) in the membrane of their host erythrocyte. Caveolae are found in almost all types of cells and are involved in endogenous processes as calcium and cholesterol homeostasis, cell signalling, transporting, ligand internalization and transcytosis of serum components. Major structural components of caveolae are the proteins caveolins and flotillins. The functional role of caveolae in the P. vivax-infected erythrocyte is not properly understood. As these organelles have been shown to contain malaria antigens, it has been suggested that they are involved in the transport and release of specific parasite antigens from the infected erythrocyte and in the uptake of plasma proteins. Using specific antibodies to classical caveolae proteins and an immunolocalization approach, we found caveolin-2, caveolin-3, and flotillin-2 in the vesicle profiles and some CVC of P. vivax-infected erythrocytes. Caveolin-1-3 were not found in uninfected erythrocytes. This is the first report of identification and localization of caveolins in the CVC present in erythrocytes infected with P. vivax, thereby providing evidence of the role of this particular organelle in the protein-trafficking pathway that connect parasite-encoded proteins with the erythrocyte cytoplasm and the cell surface throughout the asexual blood cycle of vivax malaria parasite.

  1. SOME BIOCHEMICAL BLOOD CONSTANTS EVOLUTION IN REPORT TO THE TRAINING SCHEDULE STAGE IN SPORT HORSES

    Directory of Open Access Journals (Sweden)

    FLAVIA BOCHIS

    2008-10-01

    Full Text Available To determine whether a clinical examination was adequate to assess the fitness of horses in a fence course riding, and to characterize the relationship between a clinical assessment of the horse's fitness, training schedule stage and its blood biochemistry, 22 horses were monitored before (S1, during training, immediately after warming-up (S2 and after an E level fence obstacle course ride (S3. The blood samples were taken from the jugular vein in the above three mentioned phases, for the determination of total protein (g/dl, nitrogen (mg/dl, glucose (mg/dl, lactic acid (nmol/l, calcium (mg/dl, cholesterol (mg/dl and phosphorus (mg/dl. The intend of the paper is to present the obtained results as a reference study for the appropriate use by clinicians, sport horses owners and trainers in view to have a solid base in evaluation, for the adequate protection of health and welfare of the jumper horses competitors.

  2. Association of "Elevated Blood Pressure" and "Stage 1 Hypertension" With Cardiovascular Mortality Among an Asian Population.

    Science.gov (United States)

    Talaei, Mohammad; Hosseini, Naeimeh; Koh, Angela S; Yuan, Jian-Min; Koh, Woon-Puay

    2018-04-10

    The new American College of Cardiology/American Heart Association high blood pressure (BP) guidelines in the United States have lowered definition of hypertension by defining normal as systolic/diastolic BP hypertension as systolic between 130 and 139 mm Hg or diastolic between 80 and 89 mm Hg. We investigated the association between the new hypertension definition and cardiovascular disease mortality among Chinese in Singapore. We used data from 30 636 participants of a population-based cohort, the SCHS (Singapore Chinese Health Study), who had BPs measured using a standard protocol at ages 46 to 85 years between 1994 and 2005. Information on lifestyle factors was collected at recruitment (1993-1998) and follow-up 1 interviews (1999 and 2004). Mortality was identified via nationwide registry linkage up to December 31, 2016. Neither elevated BP (hazard ratio, 0.89; 95% confidence interval, 0.74-1.07) nor stage 1 hypertension (hazard ratio, 0.94; 95% confidence interval, 0.81-1.11) was associated with increased risk of cardiovascular mortality compared with normal BP in the whole cohort. Stage 1 hypertension was associated with increased cardiovascular risk only in those hypertension may not be associated with increased cardiovascular mortality across all ages among Chinese in Singapore, but that the at-risk subpopulation is limited to those <65 years of age and without a prior cardiovascular disease. © 2018 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley.

  3. MALVAC 2012 scientific forum: accelerating development of second-generation malaria vaccines

    Science.gov (United States)

    2012-01-01

    The World Health Organization (WHO) convened a malaria vaccines committee (MALVAC) scientific forum from 20 to 21 February 2012 in Geneva, Switzerland, to review the global malaria vaccine portfolio, to gain consensus on approaches to accelerate second-generation malaria vaccine development, and to discuss the need to update the vision and strategic goal of the Malaria Vaccine Technology Roadmap. This article summarizes the forum, which included reviews of leading Plasmodium falciparum vaccine candidates for pre-erythrocytic vaccines, blood-stage vaccines, and transmission-blocking vaccines. Other major topics included vaccine candidates against Plasmodium vivax, clinical trial site capacity development in Africa, trial design considerations for a second-generation malaria vaccine, adjuvant selection, and regulatory oversight functions including vaccine licensure. PMID:23140365

  4. Gene encoding erythrocyte binding ligand linked to blood stage multiplication rate phenotype in Plasmodium yoelii yoelii.

    Science.gov (United States)

    Pattaradilokrat, Sittiporn; Culleton, Richard L; Cheesman, Sandra J; Carter, Richard

    2009-04-28

    Variation in the multiplication rate of blood stage malaria parasites is often positively correlated with the severity of the disease they cause. The rodent malaria parasite Plasmodium yoelii yoelii has strains with marked differences in multiplication rate and pathogenicity in the blood. We have used genetic analysis by linkage group selection (LGS) to identify genes that determine differences in multiplication rate. Genetic crosses were generated between genetically unrelated, fast- (17XYM) and slowly multiplying (33XC) clones of P. y. yoelii. The uncloned progenies of these crosses were placed under multiplication rate selection in blood infections in mice. The selected progenies were screened for reduction in intensity of quantitative genetic markers of the slowly multiplying parent. A small number of strongly selected markers formed a linkage group on P. y. yoelii chromosome 13. Of these, that most strongly selected marked the gene encoding the P. yoelii erythrocyte binding ligand (pyebl), which has been independently identified by Otsuki and colleagues [Otsuki H, et al. (2009) Proc Natl Acad Sci USA 106:10.1073/pnas.0811313106] as a major determinant of virulence in these parasites. In an analysis of a previous genetic cross in P. y. yoelii, pyebl alleles of fast- and slowly multiplying parents segregated with the fast and slow multiplication rate phenotype in the cloned recombinant progeny, implying the involvement of the pyebl locus in determining the multiplication rate. Our genome-wide LGS analysis also indicated effects of at least 1 other locus on multiplication rate, as did the findings of Otsuki and colleagues on virulence in P. y. yoelii.

  5. Comparison of blood and brain mercury levels in infant monkeys exposed to methylmercury or vaccines containing thimerosal.

    Science.gov (United States)

    Burbacher, Thomas M; Shen, Danny D; Liberato, Noelle; Grant, Kimberly S; Cernichiari, Elsa; Clarkson, Thomas

    2005-08-01

    Thimerosal is a preservative that has been used in manufacturing vaccines since the 1930s. Reports have indicated that infants can receive ethylmercury (in the form of thimerosal) at or above the U.S. Environmental Protection Agency guidelines for methylmercury exposure, depending on the exact vaccinations, schedule, and size of the infant. In this study we compared the systemic disposition and brain distribution of total and inorganic mercury in infant monkeys after thimerosal exposure with those exposed to MeHg. Monkeys were exposed to MeHg (via oral gavage) or vaccines containing thimerosal (via intramuscular injection) at birth and 1, 2, and 3 weeks of age. Total blood Hg levels were determined 2, 4, and 7 days after each exposure. Total and inorganic brain Hg levels were assessed 2, 4, 7, or 28 days after the last exposure. The initial and terminal half-life of Hg in blood after thimerosal exposure was 2.1 and 8.6 days, respectively, which are significantly shorter than the elimination half-life of Hg after MeHg exposure at 21.5 days. Brain concentrations of total Hg were significantly lower by approximately 3-fold for the thimerosal-exposed monkeys when compared with the MeHg infants, whereas the average brain-to-blood concentration ratio was slightly higher for the thimerosal-exposed monkeys (3.5 +/- 0.5 vs. 2.5 +/- 0.3). A higher percentage of the total Hg in the brain was in the form of inorganic Hg for the thimerosal-exposed monkeys (34% vs. 7%). The results indicate that MeHg is not a suitable reference for risk assessment from exposure to thimerosal-derived Hg. Knowledge of the toxicokinetics and developmental toxicity of thimerosal is needed to afford a meaningful assessment of the developmental effects of thimerosal-containing vaccines.

  6. Quantitation of antibody-secreting cells in the blood after vaccination with Haemophilus influenzae type b conjugate vaccine

    DEFF Research Database (Denmark)

    Barington, T; Heilmann, C; Andersen, V

    1990-01-01

    The human B-lymphocyte response to protein-conjugated polysaccharide antigens has not previously been studied at the cellular level. In order to do so, we developed and evaluated haemolytic plaque-forming cell assays detecting Haemophilus influenzae type b (Hib) capsular polysaccharide...... capsular polysaccharides from Hib and pneumococci. The predominance of IgA AbSC in response to both conjugate and pure polysaccharide vaccines is probably due to reactivation of the same clones of IgA-committed memory B cells originally primed at the mucosa by natural exposure to the polysaccharide...

  7. DNA from pre-erythrocytic stage malaria parasites is detectable by PCR in the faeces and blood of hosts.

    Science.gov (United States)

    Abkallo, Hussein M; Liu, Weimin; Hokama, Sarina; Ferreira, Pedro E; Nakazawa, Shusuke; Maeno, Yoshimasa; Quang, Nguyen T; Kobayashi, Nobuyuki; Kaneko, Osamu; Huffman, Michael A; Kawai, Satoru; Marchand, Ron P; Carter, Richard; Hahn, Beatrice H; Culleton, Richard

    2014-06-01

    Following the bite of an infective mosquito, malaria parasites first invade the liver where they develop and replicate for a number of days before being released into the bloodstream where they invade red blood cells and cause disease. The biology of the liver stages of malaria parasites is relatively poorly understood due to the inaccessibility of the parasites to sampling during this phase of their life cycle. Here we report the detection in blood and faecal samples of malaria parasite DNA throughout their development in the livers of mice and before the parasites begin their growth in the blood circulation. It is shown that parasite DNA derived from pre-erythrocytic stage parasites reaches the faeces via the bile. We then show that different primate malaria species can be detected by PCR in blood and faecal samples from naturally infected captive macaque monkeys. These results demonstrate that pre-erythrocytic parasites can be detected and quantified in experimentally infected animals. Furthermore, these results have important implications for both molecular epidemiology and phylogenetics of malaria parasites. In the former case, individuals who are malaria parasite negative by microscopy, but PCR positive for parasite DNA in their blood, are considered to be "sub-microscopic" blood stage parasite carriers. We now propose that PCR positivity is not necessarily an indicator of the presence of blood stage parasites, as the DNA could derive from pre-erythrocytic parasites. Similarly, in the case of molecular phylogenetics based on DNA sequences alone, we argue that DNA amplified from blood or faeces does not necessarily come from a parasite species that infects the red blood cells of that particular host. Copyright © 2014 Australian Society for Parasitology Inc. Published by Elsevier Ltd. All rights reserved.

  8. The dog that did not bark: malaria vaccines without antibodies.

    NARCIS (Netherlands)

    Heppner, D.G.; Schwenk, R.J.; Arnot, D.; Sauerwein, R.W.; Luty, A.J.F.

    2007-01-01

    To date, the only pre-blood stage vaccine to confer protection against malaria in field trials elicits both antigen-specific antibody and T-cell responses. Recent clinical trials of new heterologous prime-boost malaria vaccine regimens using DNA, fowlpox or MVA, have chiefly elicited T-cell

  9. Distribution of kappa and lambda light chain isotypes among human blood immunoglobulin-secreting cells after vaccination with pneumococcal polysaccharides

    DEFF Research Database (Denmark)

    Heilmann, C; Barington, T

    1989-01-01

    The light chain isotype of immunoglobulin-secreting blood cells was investigated by means of monolayer plaque-forming cell assays allowing direct immunofluorescence staining for cytoplasmic kappa and lambda light chains in centre cells. The study revealed that cultured, polyclonally activated...... pokeweed mitogen (PWM) and Epstein-Barr virus (EBV), IgM-, IgG- and IgA-secreting cells expressed the kappa light chain isotype in approximately 65% of the cells. IgM- and IgG-secreting cells induced by vaccination with pneumococcal polysaccharides had a similar percentage of kappa light chain......-containing cells. In contrast, IgA-secreting cells induced by vaccination with pneumococcal polysaccharides showed a different (bimodal) distribution as regards expression of kappa light chain. The majority (56%) of the investigated individuals expressed kappa light chain in approximately 50% of the cells...

  10. Screening and hit evaluation of a chemical library against blood-stage Plasmodium falciparum.

    Science.gov (United States)

    Avery, Vicky M; Bashyam, Sridevi; Burrows, Jeremy N; Duffy, Sandra; Papadatos, George; Puthukkuti, Shyni; Sambandan, Yuvaraj; Singh, Shivendra; Spangenberg, Thomas; Waterson, David; Willis, Paul

    2014-05-27

    In view of the need to continuously feed the pipeline with new anti-malarial agents adapted to differentiated and more stringent target product profiles (e.g., new modes of action, transmission-blocking activity or long-duration chemo-protection), a chemical library consisting of more than 250,000 compounds has been evaluated in a blood-stage Plasmodium falciparum growth inhibition assay and further assessed for chemical diversity and novelty. The selection cascade used for the triaging of hits from the chemical library started with a robust three-step in vitro assay followed by an in silico analysis of the resulting confirmed hits. Upon reaching the predefined requirements for selectivity and potency, the set of hits was subjected to computational analysis to assess chemical properties and diversity. Furthermore, known marketed anti-malarial drugs were co-clustered acting as 'signposts' in the chemical space defined by the hits. Then, in cerebro evaluation of the chemical structures was performed to identify scaffolds that currently are or have been the focus of anti-malarial medicinal chemistry programmes. Next, prioritization according to relaxed physicochemical parameters took place, along with the search for structural analogues. Ultimately, synthesis of novel chemotypes with desired properties was performed and the resulting compounds were subsequently retested in a P. falciparum growth inhibition assay. This screening campaign led to a 1.25% primary hit rate, which decreased to 0.77% upon confirmatory repeat screening. With the predefined potency (EC₅₀  10) criteria, 178 compounds progressed to the next steps where chemical diversity, physicochemical properties and novelty assessment were taken into account. This resulted in the selection of 15 distinct chemical series. A selection cascade was applied to prioritize hits resulting from the screening of a medium-sized chemical library against blood-stage P. falciparum. Emphasis was placed on chemical

  11. Inflammatory Gene Expression in Whole Peripheral Blood at Early Stages of Sporadic Amyotrophic Lateral Sclerosis

    Directory of Open Access Journals (Sweden)

    Pol Andrés-Benito

    2017-10-01

    Full Text Available ObjectiveCharacterization of altered expression of selected transcripts linked to inflammation in the peripheral blood of sporadic amyotrophic lateral sclerosis (sALS patients at early stage of disease to increase knowledge about peripheral inflammatory response in sALS.MethodsRNA expression levels of 45 genes were assessed by RT-qPCR in 22 sALS cases in parallel with 13 age-matched controls. Clinical and serum parameters were assessed at the same time.ResultsUpregulation of genes coding for factors involved in leukocyte extravasation (ITGB2, INPP5D, SELL, and ICAM1 and extracellular matrix remodeling (MMP9 and TIMP2, as well as downregulation of certain chemokines (CCL5 and CXC5R, anti-inflammatory cytokines (IL10, TGFB2, and IL10RA, pro-inflammatory cytokines (IL-6, and T-cell regulators (CD2 and TRBC1 was found in sALS cases independently of gender, clinical symptoms at onset (spinal, respiratory, or bulbar, progression, peripheral leukocyte number, and integrity of RNA. MMP9 levels positively correlated with age, whereas CCR5, CCL5, and TRBC1 negatively correlated with age in sALS but not in controls. Relatively higher TNFA expression levels correlate with higher creatinine kinase protein levels in plasma.ConclusionPresent findings show early inflammatory responses characterized by upregulation of factors enabling extravasation of leukocytes and extracellular matrix remodeling in blood in sALS cases, in addition to increased TNFA levels paralleling skeletal muscle damage.

  12. Effect of dialysis on cerebral blood flow in depressive end-stage renal disease patients

    International Nuclear Information System (INIS)

    Nam, Hyun-Yeol; Kim, Seong-Jang; Song, Sang-Heon

    2011-01-01

    The aim of this study was to investigate regional cerebral blood flow (rCBF) changes of end-stage renal disease (ESRD) patients with depressive symptoms during dialysis. Fourteen patients with ESRD underwent Tc-99m ethylcysteinate dimer (Tc-99m ECD) brain single photon emission computed tomography (SPECT) and were evaluated the severity of depressive mood at pre-dialytic period and at least 6 months after dialysis initiation. rCBF was analyzed using statistical parametric mapping (SPM) in brain SPECT image. The responder was defined as a decrease of ≥25% in Hamilton Depression Rating Scale (HDRS) score from baseline HDRS score. Pre-dialysis brain SPECT did not show any rCBF differences between responders and non-responders. The follow-up brain SPECT revealed a significant higher perfusion in left middle temporal gyrus of responder group when compared with non-responder (hemisphere coordinate X, Y, Z; -58, -2, -16, peak Z=3.36, p=0.046). In responder, a significant increase in rCBF was found in right parahippocampal gyrus (hemisphere coordinate X, Y, Z; 30, -40, -14, peak Z=3.51, p=0.043). In non-responder, there were significant decreases in rCBF in left superior frontal gyrus (hemisphere coordinate X, Y, Z; -22, 30, 42, peak Z=3.86, p=0.032) and right orbitofrontal cortex (hemisphere coordinate X, Y, Z; 10, 58, -6, peak Z=3.81, p=0.046). The present findings showed the characteristic patterns of rCBF changes in depressive ESRD patients having maintenance dialysis. Further investigations in brain blood flow and glucose metabolism are needed to elucidate the effect of dialysis itself and the difference of according to dialysis modality in patients having depression and ESRD. (author)

  13. Biomarkers for early and late stage chronic allograft nephropathy by proteogenomic profiling of peripheral blood.

    Directory of Open Access Journals (Sweden)

    Sunil M Kurian

    2009-07-01

    Full Text Available Despite significant improvements in life expectancy of kidney transplant patients due to advances in surgery and immunosuppression, Chronic Allograft Nephropathy (CAN remains a daunting problem. A complex network of cellular mechanisms in both graft and peripheral immune compartments complicates the non-invasive diagnosis of CAN, which still requires biopsy histology. This is compounded by non-immunological factors contributing to graft injury. There is a pressing need to identify and validate minimally invasive biomarkers for CAN to serve as early predictors of graft loss and as metrics for managing long-term immunosuppression.We used DNA microarrays, tandem mass spectroscopy proteomics and bioinformatics to identify genomic and proteomic markers of mild and moderate/severe CAN in peripheral blood of two distinct cohorts (n = 77 total of kidney transplant patients with biopsy-documented histology.Gene expression profiles reveal over 2400 genes for mild CAN, and over 700 for moderate/severe CAN. A consensus analysis reveals 393 (mild and 63 (moderate/severe final candidates as CAN markers with predictive accuracy of 80% (mild and 92% (moderate/severe. Proteomic profiles show over 500 candidates each, for both stages of CAN including 302 proteins unique to mild and 509 unique to moderate/severe CAN.This study identifies several unique signatures of transcript and protein biomarkers with high predictive accuracies for mild and moderate/severe CAN, the most common cause of late allograft failure. These biomarkers are the necessary first step to a proteogenomic classification of CAN based on peripheral blood profiling and will be the targets of a prospective clinical validation study.

  14. Mature Liver Stages of Cloned Plasmodium Falciparum Share Epitopes with Proteins from Sporozoites and Asexual Blood Stages

    Science.gov (United States)

    1988-05-01

    hatural mosquito flora co- purified with the sporozoites used for seeding the liver cultures. ln-"rour study, mature liver schizonts were shown to...liver cells are inherently difficult. Human hepatocyte cultures are frequently contaminated with the natural mosquito flora co-purified with the...Seances de l’Acedemie des Sciences (Paris) 294, 511 DRUILHE P., PUEBLA R.M.. MILTGEN F., PE.RKN L. & GENTILINI M. (1984) Species- and stage- specific

  15. An Oral DNA Vaccine Encoding Endoglin Eradicates Breast Tumors by Blocking Their Blood Supply

    National Research Council Canada - National Science Library

    Reisfeld, Ralph A

    2005-01-01

    .... These cells overexpress a glycoprotein called endoglin which stimulates such vessels. We successfully constructed and evaluated an oral endoglin-based DNA vaccine and demonstrated its capability to induce a robust CD8...

  16. Blocking Blood Supply to Breast Carcinoma with a DNA Vaccine Encoding VEGF Receptor-2

    National Research Council Canada - National Science Library

    Xiang, Rong

    2003-01-01

    Proof of concept was established for the hypothesis driving this project indicating that effective suppression of tumor angiogenesis can be achieved with a DNA vaccine encoding murine VEGF receptor-2 (FLK-l...

  17. Blocking Blood Supply to Breast Carcinoma with a DNA Vaccine Encoding VEGF Receptor-2

    National Research Council Canada - National Science Library

    Xiang, Rong

    2004-01-01

    .... In our second fiscal year, we demonstrated proof of concept indicating that effective suppression of tumor angiogenesis can be achieved with a DNA vaccine encoding either muring VEGF receptor-2 (Flk-1...

  18. An Oral DNA Vaccine Encoding Endoglin Eradicates Breast Tumors by Blocking Their Blood Supply

    National Research Council Canada - National Science Library

    Reisfeld, Ralph A

    2007-01-01

    In an effort to meet the urgent need for the development of novel and effective treatments for metastatic breast cancer, we developed and evaluated a novel, oral DNA vaccine targeting endoglin (CD105...

  19. Response of tumour necrosis factor alpha (TNF ) in blood and spleen mice that vaccinated with P.berghei radiation

    International Nuclear Information System (INIS)

    Darlina; Tur R; Teja K

    2015-01-01

    Tumor necrosis factor is a glycoprotein derived from helper T lymphocytes that play an important role in the body's response against malaria infection. However, TNF-α has double play that is on appropriate levels will provide protection and healing, while at excessive levels which may be a response to hyperparasitemia. Thus investigated the expression of TNF alpha secreted blood lymphocytes and spleen cells the mice that's infected with 1 x 10 7 P.berghei infectious or inactivated by radiation. Levels of TNF alpha serum and spleen cell culture medium was monitored on days 2, 7, 14 post infection. Monitoring of parasite growth every two days for 60 days. Determination of TNF alpha levels were measure using ELISA. The results showed parasitaemia mice infected with 175 Gy irradiated parasites have pre patent period of 16 days longer than the control (non-irradiated parasites) with low parasitaemia. TNF alpha concentration that secreted spleen cells of mice vaccinated higher than control mice. Concentration of TNF alpha that secreted blood lymphocyte of mice vaccinated lower than control mice. It was concluded that the secretion of TNF alpha by blood lymphocytes caused more pathogenic factors of the parasite, while the secretion of TNF alpha in spleen due to an immune response against the parasite. (author)

  20. Blood borne infections in sport: risks of transmission, methods of prevention, and recommendations for hepatitis B vaccination.

    Science.gov (United States)

    Kordi, R; Wallace, W A

    2004-12-01

    Athletes are at risk of blood borne infections through bleeding injuries or injection of drugs with contaminated syringes. Prevention should focus on reducing non-sport associated risky behaviour, as well as dealing appropriately with bleeding injuries. The risk of transmission of hepatitis B virus is particularly high in athletes in contact and collision sports, those who live in or travel to endemic regions, injecting drug abusers, and those who practice first aid when there is no healthcare practitioner available. It is recommended that such athletes, and also adolescent athletes, should be vaccinated against the virus as a routine.

  1. Th1/Th2 balance in the liver and hepatic lymph nodes of vaccinated and unvaccinated sheep during acute stages of infection with Fasciola hepatica.

    Science.gov (United States)

    Pacheco, I L; Abril, N; Morales-Prieto, N; Bautista, M J; Zafra, R; Escamilla, A; Ruiz, M T; Martínez-Moreno, A; Pérez, J

    2017-04-30

    The expression of IFNγ and IL4 was quantified using q-PCR in the liver and hepatic lymph nodes (HLN) of sheep during early stages of infection with Fasciola hepatica (1, 3, 9 and 18days post-infection, dpi). A group of animals (Group 1) were vaccinated with Fasciola hepatica recombinant cathepsin L1 (FhCL1) in montanide 70 VG prior to infection, a second group (group 2) was used as infected control and a third (group 3) was used as uninfected control. To study vaccine efficacy three additional groups were sacrificed 19 weeks post-infection (group 4 immunized with CL1, group 5 with the adjuvant and group 6 was used as infected control). The vaccinated group did not show significant fluke reduction compared to the adjuvant group and infected control group. IL4 expression was observed to increase at 9 dpi and was further elevated at 18 dpi in the liver and HLN of vaccinated and infected control groups compared to the uninfected group. IFNγ expression exhibited different dynamics in the liver and HLN compared to IL4; thus, in the liver this cytokine increased at 9 dpi in the vaccinated and at 18 dpi in vaccinated and infected control groups, while in the HLN it decreased gradually and significantly from 1 dpi onwards. These results suggest that a marked Th2 polarization is present from 9 dpi in HLN and from 18 dpi in the liver. The increase of IFNγ in the liver may correspond with tissue damage response with granuloma formation. The FhCL1 vaccine did not alter the Th1/Th2 balance when compared to unvaccinated and infected sheep. The study of IFNγ and IL4 in the various tissue compartments in sheep could facilitate selection of new adjuvants inducing a strong Th1 response for a more rationale vaccine formulation. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. [Predictive study of HBsAg in different stages of neonatal venous blood on failure of blocking HBV mother to infant transmission].

    Science.gov (United States)

    Yi, Wei; Li, Ming-Hui; Hu, Yu-Hong; Liu, Feng; Zhang, Yang-Li; Liu, Xue-Jing; Hao, Hong-Xiao; Song, Shu-Jing; Liu, Ying; Li, Xing-Hong; Sun, Ji-Yun; Liu, Min; Cheng, Jun; Xie, Yao

    2011-10-01

    In this study, we discuss the predictive value of different content of HBsAg in different stages of neotal venous blood on failure of blocking mother to infant transmission of HBV. 150 infants born of chronically HBV infected mothers who were positive of both HBsAg and HBeAg and who also had a HBV DNA virus load above 10(5) copies/ml were enrolled. These infants were given hepatitis B virus immune globin (HBIG) 200 IU immediately after birth and were given hepatitis B vaccine 10 or 20 microg at brith, 1 month and 6 months after birth. HBV serological index of these infants were test at birth, 1 month and 7 months after birth respectively. Different content of HBsAg in different stages of neonatal venus blood were analyzed to predict the failure of blocking mother to infant transmission of HBV. 11 infants failed in blocking of HBV mother to infant transmission. The positive rate of HBsAg at birth, 1 month and 7 months after birth were 41.26%, 10.49% and 7.69% respectively, and were 97.90%, 65.73% and 13.29% of HBeAg. The positive predictive value of HBsAg > or = 0.05 and HBsAg > or = 1 IU/ml at birth were 18.64% and 70% respectively, and were 73.33% and 100% one month after birth. Infants with HBsAg > or = 1 IU/ml at birth should be suspicious of failure on blocking HBV mother-to-infant transmission and it should be more credible if the infant has HBsAg > or = 1 IU/ml one month after birth. How to improve the blocking rate of neonates who were positive of HBsAg at birth and one month after birth should be the focus of our future research.

  3. Effect of selected local medicinal plants on the asexual blood stage of chloroquine resistant Plasmodium falciparum.

    Science.gov (United States)

    Mohd Abd Razak, Mohd Ridzuan; Afzan, Adlin; Ali, Rosnani; Amir Jalaluddin, Nur Fasihah; Wasiman, Mohd Isa; Shiekh Zahari, Siti Habsah; Abdullah, Noor Rain; Ismail, Zakiah

    2014-12-15

    The development of resistant to current antimalarial drugs is a major challenge in achieving malaria elimination status in many countries. Therefore there is a need for new antimalarial drugs. Medicinal plants have always been the major source for the search of new antimalarial drugs. The aim of this study was to screen selected Malaysian medicinal plants for their antiplasmodial properties. Each part of the plants were processed, defatted by hexane and sequentially extracted with dichloromethane, methanol and water. The antiplasmodial activities of 54 plant extracts from 14 species were determined by Plasmodium falciparum Histidine Rich Protein II ELISA technique. In order to determine the selectivity index (SI), all plant extracts demonstrating a good antiplasmodial activity were tested for their cytotoxicity activity against normal Madin-Darby Bovine Kidney (MDBK) cell lines by 3-(4, 5-Dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium bromide (MTT) assay. Twenty three extracts derived from Curcuma zedoaria (rhizome), Curcuma aeruginosa (rhizome), Alpinia galanga (rhizome), Morinda elliptica (leaf), Curcuma mangga (rhizome), Elephantopus scaber (leaf), Vitex negundo (leaf), Brucea javanica (leaf, root and seed), Annona muricata (leaf), Cinnamomun iners (leaf) and Vernonia amygdalina (leaf) showed promising antiplasmodial activities against the blood stage chloroquine resistant P. falciparum (EC50 toxicity effect to MDBK cells in vitro (SI ≥10). The extracts belonging to eleven plant species were able to perturb the growth of chloroquine resistant P. falciparum effectively. The findings justified the bioassay guided fractionation on these plants for the search of potent antimalarial compounds or formulation of standardized extracts which may enhance the antimalarial effect in vitro and in vivo.

  4. Nebivolol reduces central blood pressure in stage I hypertensive patients: experimental single cohort study

    Directory of Open Access Journals (Sweden)

    Renan Oliveira Vaz-de-Melo

    Full Text Available CONTEXT AND OBJECTIVES: Assessment of central blood pressure (BP has grown substantially over recent years because evidence has shown that central BP is more relevant to cardiovascular outcomes than peripheral BP. Thus, different classes of antihypertensive drugs have different effects on central BP despite similar reductions in brachial BP. The aim of this study was to investigate the effect of nebivolol, a β-blocker with vasodilator properties, on the biochemical and hemodynamic parameters of hypertensive patients.DESIGN AND SETTING: Experimental single cohort study conducted in the outpatient clinic of a university hospital.METHODS: Twenty-six patients were recruited. All of them underwent biochemical and hemodynamic evaluation (BP, heart rate (HR, central BP and augmentation index before and after 3 months of using nebivolol.RESULTS: 88.5% of the patients were male; their mean age was 49.7 ± 9.3 years and most of them were overweight (29.6 ± 3.1 kg/m2 with large abdominal waist (102.1 ± 7.2 cm. There were significant decreases in peripheral systolic BP (P = 0.0020, diastolic BP (P = 0.0049, HR (P < 0.0001 and central BP (129.9 ± 12.3 versus 122.3 ± 10.3 mmHg; P = 0.0083 after treatment, in comparison with the baseline values. There was no statistical difference in the augmentation index or in the biochemical parameters, from before to after the treatment.CONCLUSIONS: Nebivolol use seems to be associated with significant reduction of central BP in stage I hypertensive patients, in addition to reductions in brachial systolic and diastolic BP.

  5. The cytosolic glyoxalases of Plasmodium falciparum are dispensable during asexual blood-stage development

    Directory of Open Access Journals (Sweden)

    Cletus A. Wezena

    2017-11-01

    Full Text Available The enzymes glyoxalase 1 and 2 (Glo1 and Glo2 are found in most eukaryotes and catalyze the glutathione-dependent conversion of 2-oxoaldehydes to 2-hydroxycarboxylic acids. Four glyoxalases are encoded in the genome of the malaria parasite Plasmodium falciparum, the cytosolic enzymes PfGlo1 and PfcGlo2, the apicoplast enzyme PftGlo2, and an inactive Glo1-like protein that also carries an apicoplast-targeting sequence. Inhibition or knockout of the Plasmodium glyoxalases was hypothesized to lead to an accumulation of 2-oxoaldehydes and advanced glycation end-products (AGE in the host-parasite unit and to result in parasite death. Here, we generated clonal P. falciparum strain 3D7 knockout lines for PFGLO1 and PFcGLO2 using the CRISPR-Cas9 system. Although 3D7Δglo1 knockout clones had an increased susceptibility to external glyoxal, all 3D7Δglo1 and 3D7Δcglo2 knockout lines were viable and showed no significant growth phenotype under standard growth conditions. Furthermore, the lack of PfcGlo2, but not PfGlo1, increased gametocyte commitment in the knockout lines. In summary, PfGlo1 and PfcGlo2 are dispensable during asexual blood-stage development while the loss of PfcGlo2 may induce the formation of transmissible gametocytes. These combined data show that PfGlo1 and PfcGlo2 are most likely not suited as targets for selective drug development.

  6. Blocking Blood Supply to Breast Carcinoma With a DNA Vaccine Encoding VEGF Receptor-2

    Science.gov (United States)

    2006-03-01

    vaccination: an update. Methods Mol Med 2003;87:377–90. 14. Ambrosini G, Adida C, Altieri DC. A novel anti- apoptosis gene, survivin, expressed in cancer...endothelial cells. Biochem Biophys Res Commun 1999;264:781–8. 26. O’Connor DS, Schechner JS, Adida C, et al. Control of apoptosis during angiogenesis by...minigene DNA vaccine protects mice from tumors of different origins by inducing a T cell-mediated suppression of tumor angiogenesis. From the Department of

  7. In vitro marker gene expression analyses in human peripheral blood mononuclear cells: A tool to assess safety of influenza vaccines in humans.

    Science.gov (United States)

    Sasaki, Eita; Momose, Haruka; Hiradate, Yuki; Ishii, Ken J; Mizukami, Takuo; Hamaguchi, Isao

    2018-12-01

    Vaccines are inoculated in healthy individuals from children to the elderly, and thus high levels of safety and consistency of vaccine quality in each lot must meet the required specifications by using preclinical and lot release testing. Because vaccines are inoculated into humans, recapitulation of biological reactions in humans should be considered for test methods. We have developed a new method to evaluate the safety of influenza vaccines using biomarker gene expression in mouse and rat models. Some biomarker genes are already known to be expressed in human lymphocytes, macrophages and dendritic cells; therefore, we considered some of these genes might be common biomarkers for human and mice to evaluate influenza vaccine safety. In this study, we used human peripheral blood mononuclear cells (PBMC) as a primary assessment tool to confirm the usefulness of potential marker genes in humans. Analysis of marker gene expression in PBMC revealed biomarker gene expressions were dose-relatedly increased in toxic reference influenza vaccine (RE)-stimulated PBMC. Although some marker genes showed increased expression in hemagglutinin split vaccine-stimulated PBMC, their expression levels were lower than that of RE in PBMC from two different donors. Many marker gene expressions correlated with chemokine production. Marker genes such as IRF7 were associated with other Type 1 interferon (IFN)-associated signals and were highly expressed in the CD304 + plasmacytoid dendritic cell (pDC) population. These results suggest PBMC and their marker genes may be useful for vaccine safety evaluation in humans.

  8. Poor validity of self-reported HBV vaccination among young heroin users in Spain supports the policy "don't ask, draw a blood sample, vaccinate and try to schedule another visit".

    Science.gov (United States)

    de la Fuente, Luis; Toro, Carlos; Brugal, M Teresa; Vallejo, Fernando; Soriano, Vicente; Barrio, Gregorio; Ballesta, Rosario; Bravo, María J

    2007-01-01

    To assess the validity of self-reported hepatitis B virus vaccination status in young heroin users. Cross-sectional study among 949 street-recruited young injection heroin users (IHUs) and non-injection heroin users (NIHUs) in Madrid, Barcelona and Seville. Face-to-face interviews and dried blood spot tested for anti-HBc and anti-HBs. The validity of self-reported vaccination status was assessed comparing with the serological status. The percentage of agreement with the kappa (kappa) statistic and the positive predictive value were calculated. The percentage of agreement between self-reported and serologic vaccination status was 51.9% overall, with little difference by city (53.1% in Barcelona, 49.0% in Madrid and 51.5% in Seville) or between IHUs (51.3%) and NIHUs (53.0%). All the kappa scores were lower than 0.1. The positive predictive value of self-reports was less than 25% in all categories analysed, except in the city of Barcelona (37%). Among those who indicated that they had been vaccinated, 31% were actually susceptible. In areas with a high prevalence of infection and rising coverage of vaccination the policy "don't ask, take a blood sample, give a dose of vaccine and try to schedule another visit" should be recommended in clinical practice.

  9. Effects of end-stage renal disease and dialysis modalities on blood ammonia level.

    Science.gov (United States)

    Vaziri, Nosratola D; Khazaeli, Mahyar; Nunes, Ane C F; Harley, Kevin T; Said, Hyder; Alipour, Omeed; Lau, Wei Ling; Pahl, Madeleine V

    2017-07-01

    Uremia results in a characteristic breath odor (uremic fetor) which is largely due to its high ammonia content. Earlier studies have shown a strong correlation between breath ammonia and blood urea levels and a 10-fold reduction in breath ammonia after hemodialysis in patients with chronic kidney disease. Potential sources of breath ammonia include: (i) local ammonia production from hydrolysis of urea in the oropharyngeal and respiratory tracts by bacterial flora, and (ii) release of circulating blood ammonia by the lungs. While the effects of uremia and hemodialysis on breath ammonia are well known their effects on blood ammonia are unknown and were explored here. Blood samples were obtained from 23 hemodialysis patients (immediately before and after dialysis), 14 peritoneal dialysis patients, and 10 healthy controls. Blood levels of ammonia, creatinine, urea, and electrolytes were measured. No significant difference was found in baseline blood ammonia between hemodialysis, peritoneal dialysis and control groups. Hemodialysis procedure led to a significant reduction in urea concentration (P ammonia level in 10 of the 23 patients studied. Change in blood ammonia pre- and post-hemodialysis correlated with change in serum bicarbonate levels (r = 0.61, P ammonia levels after dialysis, there was a strong correlation with drop in mean arterial pressure (r = 0.88, P ammonia compared to the patients who manifested a fall in blood ammonia (124 ± 8 vs. 136 ± 6 mmHg respectively, P = 0.27). Fall in blood urea following hemodialysis in ESRD patients was paradoxically accompanied by a modest rise in blood ammonia levels in 43% of the patients studied, contrasting prior reported effects of hemodialysis on breath ammonia. In this subgroup of patients, changes in blood ammonia during hemodialysis correlated with rise in blood bicarbonate and fall in mean arterial blood pressure. © 2016 International Society for Hemodialysis.

  10. Changes in peripheral blood level of regulatory T cells in patients with malignant melanoma during treatment with dendritic cell vaccination and low-dose IL-2

    DEFF Research Database (Denmark)

    Bjoern, J; Brimnes, M K; Andersen, M H

    2011-01-01

    In this study, changes in peripheral blood regulatory T cell (Treg) levels were evaluated in 46 progressive patients with melanoma treated with a dendritic cell-based vaccine and concomitant low-dose IFN-α and IL-2. The regulatory subset of CD4 T cells, characterized by CD25(high) , was prospecti......In this study, changes in peripheral blood regulatory T cell (Treg) levels were evaluated in 46 progressive patients with melanoma treated with a dendritic cell-based vaccine and concomitant low-dose IFN-α and IL-2. The regulatory subset of CD4 T cells, characterized by CD25(high...

  11. Malaria vaccines and human immune responses.

    Science.gov (United States)

    Long, Carole A; Zavala, Fidel

    2016-08-01

    Despite reductions in malaria episodes and deaths over the past decade, there is still significant need for more effective tools to combat this serious global disease. The positive results with the Phase III trial of RTS,S directed to the circumsporozoite protein of Plasmodium falciparum have established that a vaccine against malaria can provide partial protection to children in endemic areas, but its limited efficacy and relatively short window of protection mandate that new generations of more efficacious vaccines must be sought. Evidence shows that anti-parasite immune responses can control infection against other stages as well, but translating these experimental findings into vaccines for blood stages has been disappointing and clinical efforts to test a transmission blocking vaccine are just beginning. Difficulties include the biological complexity of the organism with a large array of stage-specific genes many of which in the erythrocytic stages are antigenically diverse. In addition, it appears necessary to elicit high and long-lasting antibody titers, address the redundant pathways of merozoite invasion, and still seek surrogate markers of protective immunity. Most vaccine studies have focused on a single or a few antigens with an apparent functional role, but this is likely to be too restrictive, and broad, multi-antigen, multi-stage vaccines need further investigation. Finally, novel tools and biological insights involving parasite sexual stages and the mosquito vector will provide new avenues for reducing or blocking malaria transmission. Published by Elsevier Ltd.

  12. Sex bias in response to hepatitis B vaccination in end-stage renal disease patients: Meta-analysis.

    Science.gov (United States)

    Khedmat, Hossein; Aghaei, Aghdas; Ghamar-Chehreh, Mohammad Ebrahim; Agah, Shahram

    2016-01-06

    To systematically review the literature for studies investigating the potential effect of gender of dialysis patients on the immunogenicity of hepatitis B virus vaccines. Literature searches were conducted by the MEDLINE and Google Scholar. The key words used included "hepatitis B (HB)", "vaccine", "dialysis", "hemodialysis", "sex", "male" and "female". Data of seroresponse to HB vaccine in clinical trials regarding sex of the recipients have been achieved and analyzed. Finally data from 19 clinical trials have been pooled and analyzed. Analysis of response to HB vaccination in our dialysis population showed males significantly respond less to hepatitis B vaccination (P = 0.002, Z = 3.08) with no significant heterogeneity detected [P = 0.766; heterogeneity χ(2) = 14.30 (df = 19); I (2) = 0%]. A reanalysis of the pooled data was conducted regarding the dialysis mode to evaluate potential differential impact of sex on HB vaccine response. Hemodialysis was the only subgroup that showed a significant difference regarding dialysis mode in response to HB vaccination regarding sex (P = 0.042, Z = 2.03). This Meta-analysis showed significant effect for the sex of chronic kidney disease and dialysis patients on the immunogenicity of HB vaccine. This sex discrimination was most prominent among hemodialysis patients.

  13. Dramatic impact of blood transfusion on cancer-specific survival after radical cystectomy irrespective of tumor stage.

    Science.gov (United States)

    Buchner, Alexander; Grimm, Tobias; Schneevoigt, Birte-Swantje; Wittmann, Georg; Kretschmer, Alexander; Jokisch, Friedrich; Grabbert, Markus; Apfelbeck, Maria; Schulz, Gerald; Gratzke, Christian; Stief, Christian G; Karl, Alexander

    2017-04-01

    The aim of the present study was to determine the influence of intraoperative and postoperative blood transfusion on cancer-specific outcome. Follow-up data were collected from 722 patients undergoing radical cystectomy for urothelial carcinoma of the bladder (UCB) between 2004 and 2014. Median follow-up was 26 months (interquartile range 12-61 months). Outcome was analyzed in relation to the amount of intraoperative and postoperative blood transfusion and different tumor stages. The primary endpoint was cancer-specific survival (CSS) after cystectomy. Kaplan-Meier analysis with log-rank test and Cox regression models were used. Intraoperative blood transfusion was given in 36% (263/722) and postoperative blood transfusion in 18% (132/722). In patients with and without intraoperative blood transfusion, 5 year CSS was 48% and 67%, respectively (p blood transfusion, 5 year CSS was 48% and 63%, respectively (p transfused red blood cell (RBC) units [intraoperatively: hazard ratio (HR) = 1.08, 95% confidence interval (CI) 1.01-1.15, p = .023; postoperatively: HR = 1.14, 95% CI 1.07-1.21, p transfusions was also found in favorable subgroups (pT1 tumor, hemoglobin ≥13 mg/dl, p = .004) and in a high-volume surgeon subgroup (n = 244, p Blood transfusions during and after radical cystectomy were independent prognostic factors for CSS in this retrospective study. Therefore, efforts should be made to reduce the necessity of intraoperative and postoperative blood transfusion in cystectomy patients.

  14. Retinal blood flow is increased in type 1 diabetes mellitus patients with advanced stages of retinopathy

    NARCIS (Netherlands)

    Nguyen, Hoang-Ton; van Duinkerken, Eelco; Verbraak, Frank D.; Polak, Bettine C. P.; Ringens, Peter J.; Diamant, Michaela; Moll, Annette C.

    2016-01-01

    Diabetic retinopathy (DRP) is a common microvascular complication seen in patients with type 1 diabetes mellitus (T1DM). The effects of T1DM and concomitant (proliferative) DRP on retinal blood flow are currently unclear. Therefore, we measured retinal vascular blood flow in T1DM patients with and

  15. Generation of genetically attenuated blood-stage malaria parasites; characterizing growth and virulence in a rodent model of malaria

    NARCIS (Netherlands)

    Lin, Jingwen

    2013-01-01

    Despite intense efforts over the past 50 years to develop a vaccine, there is currently no licensed malaria vaccine available. The limited success in inducing sufficient protection against malaria with subunit-vaccines has renewed an interest in whole-parasite vaccination strategies. While

  16. Acanthocheilonema viteae: Vaccination of jirds with irradiation-attenuated stage-3 larvae and with exported larval antigens

    International Nuclear Information System (INIS)

    Lucius, R.; Textor, G.; Kern, A.; Kirsten, C.

    1991-01-01

    Jirds (Meriones unguiculatus) were immunized with irradiated (35 krad) stage-3 larvae (L3) of Acanthocheilonema viteae. The induced resistance against homologous challenge infection and the antibody response of the animals were studied. Immunization with 3, 2, or 1 dose of 50 irradiated L3 induced approximately 90% resistance. Immunization with a single dose of only 5 irradiated L3 resulted in 60.8% protection while immunization with a single dose of 25 L3 induced 94.1% protection. The protection induced with 3 doses of 50 irradiated L3 did not decrease significantly during a period of 6 months. Sera of a proportion, but not all resistant jirds, contained antibodies against the surface of vector derived L3 as defined by IFAT. No surface antigens of microfilariae or adult worms were recognized by the sera. Vaccinated animals had antibody responses against antigens in the inner organs of L3 and in the cuticle and reproductive organs of adult worms as shown by IFAT. Immunoblotting with SDS-PAGE-separated L3 antigens and L3-CSN revealed that all sera contained antibodies against two exported antigens of 205 and 68 kDa, and against a nonexported antigen of 18 kDa. The 205-kDa antigen easily degraded into fragments of 165, 140, 125, and 105 kDa which were recognized by resistant jird sera. Various antigens of adult worms, but relatively few antigens of microfilariae, were also recognized. To test the relevance of exported antigens of L3 to resistance, jirds were immunized with L3-CSN together with a mild adjuvant. This immunization induced 67.7% resistance against challenge infection and sera of the immunized animals recognized the 205- and 68-kDa antigens of L3

  17. Flow cytometric readout based on Mitotracker Red CMXRos staining of live asexual blood stage malarial parasites reliably assesses antibody dependent cellular inhibition

    Directory of Open Access Journals (Sweden)

    Jogdand Prajakta S

    2012-07-01

    Full Text Available Abstract Background Functional in vitro assays could provide insights into the efficacy of malaria vaccine candidates. For estimating the anti-parasite effect induced by a vaccine candidate, an accurate determination of live parasite count is an essential component of most in vitro bioassays. Although traditionally parasites are counted microscopically, a faster, more accurate and less subjective method for counting parasites is desirable. In this study mitochondrial dye (Mitotracker Red CMXRos was used for obtaining reliable live parasite counts through flow cytometry. Methods Both asynchronous and tightly synchronized asexual blood stage cultures of Plasmodium falciparum were stained with CMXRos and subjected to detection by flow cytometry and fluorescence microscopy. The parasite counts obtained by flow cytometry were compared to standard microscopic counts obtained through examination of Giemsa-stained thin smears. A comparison of the ability of CMXRos to stain live and compromised parasites (induced by either medium starvation or by anti-malarial drug treatment was carried out. Finally, parasite counts obtained by CMXRos staining through flow cytometry were used to determine specific growth inhibition index (SGI in an antibody-dependent cellular inhibition (ADCI assay. Results Mitotracker Red CMXRos can reliably detect live intra-erythrocytic stages of P. falciparum. Comparison between staining of live with compromised parasites shows that CMXRos predominantly stains live parasites with functional mitochondria. Parasite counts obtained by CMXRos staining and flow cytometry were highly reproducible and can reliably determine the ability of IgG from hyper-immune individuals to inhibit parasite growth in presence of monocytes in ADCI assay. Further, a dose-dependent parasite growth inhibitory effect could be detected for both total IgG purified from hyper-immune sera and affinity purified IgGs against the N-terminal non-repeat region of GLURP

  18. Flow cytometric readout based on Mitotracker Red CMXRos staining of live asexual blood stage malarial parasites reliably assesses antibody dependent cellular inhibition.

    Science.gov (United States)

    Jogdand, Prajakta S; Singh, Susheel K; Christiansen, Michael; Dziegiel, Morten H; Singh, Subhash; Theisen, Michael

    2012-07-20

    Functional in vitro assays could provide insights into the efficacy of malaria vaccine candidates. For estimating the anti-parasite effect induced by a vaccine candidate, an accurate determination of live parasite count is an essential component of most in vitro bioassays. Although traditionally parasites are counted microscopically, a faster, more accurate and less subjective method for counting parasites is desirable. In this study mitochondrial dye (Mitotracker Red CMXRos) was used for obtaining reliable live parasite counts through flow cytometry. Both asynchronous and tightly synchronized asexual blood stage cultures of Plasmodium falciparum were stained with CMXRos and subjected to detection by flow cytometry and fluorescence microscopy. The parasite counts obtained by flow cytometry were compared to standard microscopic counts obtained through examination of Giemsa-stained thin smears. A comparison of the ability of CMXRos to stain live and compromised parasites (induced by either medium starvation or by anti-malarial drug treatment) was carried out. Finally, parasite counts obtained by CMXRos staining through flow cytometry were used to determine specific growth inhibition index (SGI) in an antibody-dependent cellular inhibition (ADCI) assay. Mitotracker Red CMXRos can reliably detect live intra-erythrocytic stages of P. falciparum. Comparison between staining of live with compromised parasites shows that CMXRos predominantly stains live parasites with functional mitochondria. Parasite counts obtained by CMXRos staining and flow cytometry were highly reproducible and can reliably determine the ability of IgG from hyper-immune individuals to inhibit parasite growth in presence of monocytes in ADCI assay. Further, a dose-dependent parasite growth inhibitory effect could be detected for both total IgG purified from hyper-immune sera and affinity purified IgGs against the N-terminal non-repeat region of GLURP in ADCI assays coupled with determination of

  19. A Global Survey of ATPase Activity in Plasmodium falciparum Asexual Blood Stages and Gametocytes

    Energy Technology Data Exchange (ETDEWEB)

    Ortega, Corrie; Frando, Andrew; Webb-Robertson, Bobbie-Jo; Anderson, Lindsey N.; Fleck, Neil; Flannery, Erika L.; Fishbaugher, Matthew; Murphree, Taylor A.; Hansen, Joshua R.; Smith, Richard D.; Kappe, Stefan H. I.; Wright, Aaron T.; Grundner, Christoph

    2017-10-27

    Effective malaria control and elimination in hyperendemic areas of the world will require treatment of disease-causing Plasmodium falciparum (Pf) blood stage infection but also blocking parasite transmission from humans to mosquito to prevent disease spread. Numerous antimalarial drugs have become ineffective due to parasite drug resistance and many currently used therapies do not kill gametocytes, highly specialized sexual parasite stages with distinct physiology that are necessary for transmission from the human host to the mosquito vector. Further confounding next generation drug development against Pf is the lack of known biochemical activity for most parasite gene products as well as the unknown metabolic needs of non-replicating gametocyte. Here, we take a systematic activity-based proteomics approach to survey the large and druggable ATPase family that is associated with replicating blood stage asexual parasites and transmissible gametocytes. We experimentally confirm existing annotation and predict ATPase function for 38 uncharacterized proteins. ATPase activity broadly changes during the transition from asexual schizonts to gametocytes, indicating altered metabolism and regulatory roles of ATPases specific for each lifecycle stage. By mapping the activity of ATPases associated with gametocytogenesis, we assign biochemical activity to a large number of uncharacterized proteins and identify new candidate transmission blocking targets.

  20. Retinal blood flow is increased in type 1 diabetes mellitus patients with advanced stages of retinopathy.

    Science.gov (United States)

    Nguyen, Hoang-Ton; van Duinkerken, Eelco; Verbraak, Frank D; Polak, Bettine C P; Ringens, Peter J; Diamant, Michaela; Moll, Annette C

    2016-05-26

    Diabetic retinopathy (DRP) is a common microvascular complication seen in patients with type 1 diabetes mellitus (T1DM). The effects of T1DM and concomitant (proliferative) DRP on retinal blood flow are currently unclear. Therefore, we measured retinal vascular blood flow in T1DM patients with and without DRP and non-diabetic controls. We further assessed the acute effects of panretinal photocoagulation on retinal microvascular bloodflow in eight patients with diabetes. Thirty-three T1DM patients with proliferative DRP, previously treated with panretinal photocoagulation (pDRP), 11 T1DM patients with untreated non-proliferative retinopathy (npDRP) and 32 T1DM patients without DRP (nDRP) were compared with 44 non-diabetic gender-matched controls. Using scanning laser Doppler flowmetry (HRF, Heidelberg) blood flow in the retinal microvasculature was measured temporal and nasal of the optic disc and averaged into one flow value per eye. The right eye was used as a default for further analyses. Eight patients with novel proliferative retinopathy (4 T1DM and 4 with type 2 diabetes) were measured before and several months after photocoagulation. Between-group differences in retinal blood flow were assessed using ANOVA corrected for multiple comparisons (Bonferroni). Retinal blood flow was higher in the treated pDRP compared with the nDRP group and controls (all P Bonferroni retinopathy, blood flow did not significantly change before and after panretinal photocoagulation (P > 0.05). Using regression analysis, no variables were found as predictors of retinal blood flow. In comparison with controls and nDRP patients, retinal blood flow significantly increased in the pDRP group, which previously underwent photocoagulation treatment, but not in the npDRP patients. These changes may be a consequence of a failing vascular autoregulation in advanced diabetic retinopathy.

  1. Induction of antigen-specific antibody response in human pheripheral blood lymphocytes in vitro by a dog kidney cell vaccine against rabies virus (DKCV).

    NARCIS (Netherlands)

    F.G.C.M. Uytdehaag (Fons); A.D.M.E. Osterhaus (Albert); H.G. Loggen; R.H.J. Bakker (Roland); J.A.A.M. van Asten (Jack); J.G. Kreeftenberg; P. van der Marel; G. van Steenis (Bert)

    1983-01-01

    textabstractIn the present report an in vitro method for obtaining a secondary human antibody response to a dog kidney cell vaccine against rabies virus (DKCV) is described. Cultures of peripheral blood mononuclear cells from normal rabies-immune and nonimmune donors were stimulated in vitro by

  2. Mechanisms of stage-transcending protection following immunization of mice with late liver stage-arresting genetically attenuated malaria parasites.

    Directory of Open Access Journals (Sweden)

    Brandon K Sack

    2015-05-01

    Full Text Available Malaria, caused by Plasmodium parasite infection, continues to be one of the leading causes of worldwide morbidity and mortality. Development of an effective vaccine has been encumbered by the complex life cycle of the parasite that has distinct pre-erythrocytic and erythrocytic stages of infection in the mammalian host. Historically, malaria vaccine development efforts have targeted each stage in isolation. An ideal vaccine, however, would target multiple life cycle stages with multiple arms of the immune system and be capable of eliminating initial infection in the liver, the subsequent blood stage infection, and would prevent further parasite transmission. We have previously shown that immunization of mice with Plasmodium yoelii genetically attenuated parasites (GAP that arrest late in liver stage development elicits stage-transcending protection against both a sporozoite challenge and a direct blood stage challenge. Here, we show that this immunization strategy engenders both T- and B-cell responses that are essential for stage-transcending protection, but the relative importance of each is determined by the host genetic background. Furthermore, potent anti-blood stage antibodies elicited after GAP immunization rely heavily on FC-mediated functions including complement fixation and FC receptor binding. These protective antibodies recognize the merozoite surface but do not appear to recognize the immunodominant merozoite surface protein-1. The antigen(s targeted by stage-transcending immunity are present in both the late liver stages and blood stage parasites. The data clearly show that GAP-engendered protective immune responses can target shared antigens of pre-erythrocytic and erythrocytic parasite life cycle stages. As such, this model constitutes a powerful tool to identify novel, protective and stage-transcending T and B cell targets for incorporation into a multi-stage subunit vaccine.

  3. Relative blood volume monitoring during hemodialysis in end stage renal disease patients.

    Science.gov (United States)

    Ion Titapiccolo, Jasmine; Ferrario, Manuela; Garzotto, Francesco; Cruz, Dinna; Moissl, Ulrich; Tetta, Ciro; Ronco, Claudio; Signorini, Maria G; Cerutti, Sergio

    2010-01-01

    A crucial point in the haemodialysis (HD) treatment is the reliable assessment of hydration status. An inadequate removed volume may lead to chronic fluid overload which can lead to hypertension, left ventricular hypertrophy and heart failure. Therefore, the estimation of the hydration state and the management of a well-tolerated water removal is an important challenge. This exploratory study aims at identifying new parameters obtained from continuous Blood Volume Monitoring (BVM) allowing a qualitative evaluation of hydration status for verifying the adequacy of HD setting parameters (e.g UFR, target dry weight). The percentage of blood volume reduction (BVR%) during HD was compared against a gold standard method for hydration status assessment. The slope of the first 30 minute of blood volume reduction (BVR) was proposed as a useful parameter to identify overhydrated patients.

  4. Intra-subject variability of snoring sounds in relation to body position, sleep stage, and blood oxygen level.

    Science.gov (United States)

    Azarbarzin, Ali; Moussavi, Zahra

    2013-04-01

    In a multidimensional feature space, the snoring sounds can extend from a very compact cluster to highly distinct clusters. In this study, we investigated the cause of snoring sound's variation within the snorers. It is known that a change in body position and sleep stage can affect snoring during sleep but it is unclear whether positional, sleep state, and blood oxygen level variations cause the snoring sounds to have different characteristics, and if it does how significant that effect would be. We extracted 12 characteristic features from snoring sound segments of 57 snorers and transformed them into a 4-D feature space using principal component analysis (PCA). Then, they were grouped based on the body position (side, supine, and prone), sleep stage (NREM, REM, and Arousal), and blood oxygen level (Normal and Desaturation). The probability density function of the transformed features was calculated for each class of categorical variables. The distance between the class-densities were calculated to determine which of these parameters affects the snoring sounds significantly. Analysis of Variance (ANOVA) was run for each categorical variable. The results show that the positional change has the highest effect on the snoring sounds; it results in forming distinct clusters of snoring sounds. Also, sleep state and blood oxygen level variation have been found to moderately affect the snoring sounds.

  5. A prime-boost immunization regimen based on a simian adenovirus 36 vectored multi-stage malaria vaccine induces protective immunity in mice.

    Science.gov (United States)

    Fonseca, Jairo A; McCaffery, Jessica N; Kashentseva, Elena; Singh, Balwan; Dmitriev, Igor P; Curiel, David T; Moreno, Alberto

    2017-05-31

    Malaria remains a considerable burden on public health. In 2015, the WHO estimates there were 212 million malaria cases causing nearly 429,000 deaths globally. A highly effective malaria vaccine is needed to reduce the burden of this disease. We have developed an experimental vaccine candidate (PyCMP) based on pre-erythrocytic (CSP) and erythrocytic (MSP1) stage antigens derived from the rodent malaria parasite P. yoelii. Our protein-based vaccine construct induces protective antibodies and CD4 + T cell responses. Based on evidence that viral vectors increase CD8 + T cell-mediated immunity, we also have tested heterologous prime-boost immunization regimens that included human adenovirus serotype 5 vector (Ad5), obtaining protective CD8 + T cell responses. While Ad5 is commonly used for vaccine studies, the high prevalence of pre-existing immunity to Ad5 severely compromises its utility. Here, we report the use of the novel simian adenovirus 36 (SAd36) as a candidate for a vectored malaria vaccine since this virus is not known to infect humans, and it is not neutralized by anti-Ad5 antibodies. Our study shows that the recombinant SAd36PyCMP can enhance specific CD8 + T cell response and elicit similar antibody titers when compared to an immunization regimen including the recombinant Ad5PyCMP. The robust immune responses induced by SAd36PyCMP are translated into a lower parasite load following P. yoelii infectious challenge when compared to mice immunized with Ad5PyCMP. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Longitudinal observations on circadian blood pressure variation in chronic kidney disease stages 3-5

    DEFF Research Database (Denmark)

    Elung-Jensen, T.; Strandgaard, S.; Kamper, Anne-Lise

    2008-01-01

    BACKGROUND: It has been suggested that status as a 'non-dipper' determined from 24-h blood pressure (BP) recordings is associated with increased risk of end-organ damage but little is known about the consistency of dipper status in renal patients. The present post hoc analysis evaluated dipper/no...

  7. Longitudinal observations on circadian blood pressure variation in chronic kidney disease stages 3-5

    DEFF Research Database (Denmark)

    Elung-Jensen, T.; Strandgaard, S.; Kamper, Anne-Lise

    2008-01-01

    /non-dipper status prospectively in a study on dosage of enalapril in progressive chronic kidney disease (CKD) stages 3-5. METHODS: In 34 patients, 24-h ambulatory BP (A&D TM2421) was measured at baseline and every 4 months for 1 year or until the need for renal replacement therapy. For each BP recording patients...

  8. Engineering of Genetically Arrested Parasites (GAPs) For a Precision Malaria Vaccine.

    Science.gov (United States)

    Kreutzfeld, Oriana; Müller, Katja; Matuschewski, Kai

    2017-01-01

    Continuous stage conversion and swift changes in the antigenic repertoire in response to acquired immunity are hallmarks of complex eukaryotic pathogens, including Plasmodium species, the causative agents of malaria. Efficient elimination of Plasmodium liver stages prior to blood infection is one of the most promising malaria vaccine strategies. Here, we describe different genetically arrested parasites (GAPs) that have been engineered in Plasmodium berghei, P. yoelii and P. falciparum and compare their vaccine potential. A better understanding of the immunological mechanisms of prime and boost by arrested sporozoites and experimental strategies to enhance vaccine efficacy by further engineering existing GAPs into a more immunogenic form hold promise for continuous improvements of GAP-based vaccines. A critical hurdle for vaccines that elicit long-lasting protection against malaria, such as GAPs, is safety and efficacy in vulnerable populations. Vaccine research should focus on solutions toward turning malaria into a vaccine-preventable disease, which would offer an exciting new path of malaria control.

  9. Roles of IFN-γ and γδ T cells in protective immunity against blood-stage malaria

    Directory of Open Access Journals (Sweden)

    Shin-Ichi eInoue

    2013-08-01

    Full Text Available Malaria is caused by infection with Plasmodium parasites. Various studies with knockout mice have indicated that IFN-γ plays essential roles in protective immunity against blood-stage Plasmodium infection. However, after Plasmodium infection, increased IFN-γ production by various types of cells is involved not only in protective immunity, but also in immunopathology. Recent reports have shown that IFN-γ acts as a pro-inflammatory cytokine to induce not only the activation of macrophages, but also the generation of uncommon myelolymphoid progenitor cells after Plasmodium infection. However, the effects of IFN-γ on hematopoietic stem cells and progenitor cells are unclear. Therefore, the regulation of hematopoiesis by IFN-γ during Plasmodium infection remains to be clarified. Although there are conflicting reports concerning the significance of γδ T cells in protective immunity against Plasmodium infection, γδ T cells may respond to infection and produce IFN-γ as innate immune cells in the early phase of blood-stage malaria. Our recent studies have shown that γδ T cells express CD40 ligand and produce IFN-γ after Plasmodium infection, resulting in the enhancement of dendritic cell activation as part of the immune response to eliminate Plasmodium parasites. These data suggest that the function of γδ T cells is similar to that of NK cells. Although several reports suggest that γδ T cells have the potential to act as memory cells for various infections, it remains to be determined whether memory γδ T cells are generated by Plasmodium infection and whether memory γδ T cells can contribute to the host defense against re-infection with Plasmodium. Here, we summarize and discuss the effects of IFN-γ and the various functions of γδ T cells in blood-stage Plasmodium infection.

  10. Vaccines against malaria.

    Science.gov (United States)

    Hill, Adrian V S

    2011-10-12

    There is no licenced vaccine against any human parasitic disease and Plasmodium falciparum malaria, a major cause of infectious mortality, presents a great challenge to vaccine developers. This has led to the assessment of a wide variety of approaches to malaria vaccine design and development, assisted by the availability of a safe challenge model for small-scale efficacy testing of vaccine candidates. Malaria vaccine development has been at the forefront of assessing many new vaccine technologies including novel adjuvants, vectored prime-boost regimes and the concept of community vaccination to block malaria transmission. Most current vaccine candidates target a single stage of the parasite's life cycle and vaccines against the early pre-erythrocytic stages have shown most success. A protein in adjuvant vaccine, working through antibodies against sporozoites, and viral vector vaccines targeting the intracellular liver-stage parasite with cellular immunity show partial efficacy in humans, and the anti-sporozoite vaccine is currently in phase III trials. However, a more effective malaria vaccine suitable for widespread cost-effective deployment is likely to require a multi-component vaccine targeting more than one life cycle stage. The most attractive near-term approach to develop such a product is to combine existing partially effective pre-erythrocytic vaccine candidates.

  11. Gene expression patterns in CD4+ peripheral blood cells in healthy subjects and stage IV melanoma patients.

    Science.gov (United States)

    Felts, Sara J; Van Keulen, Virginia P; Scheid, Adam D; Allen, Kathleen S; Bradshaw, Renee K; Jen, Jin; Peikert, Tobias; Middha, Sumit; Zhang, Yuji; Block, Matthew S; Markovic, Svetomir N; Pease, Larry R

    2015-11-01

    Melanoma patients exhibit changes in immune responsiveness in the local tumor environment, draining lymph nodes, and peripheral blood. Immune-targeting therapies are revolutionizing melanoma patient care increasingly, and studies show that patients derive clinical benefit from these newer agents. Nonetheless, predicting which patients will benefit from these costly therapies remains a challenge. In an effort to capture individual differences in immune responsiveness, we are analyzing patterns of gene expression in human peripheral blood cells using RNAseq. Focusing on CD4+ peripheral blood cells, we describe multiple categories of immune regulating genes, which are expressed in highly ordered patterns shared by cohorts of healthy subjects and stage IV melanoma patients. Despite displaying conservation in overall transcriptome structure, CD4+ peripheral blood cells from melanoma patients differ quantitatively from healthy subjects in the expression of more than 2000 genes. Moreover, 1300 differentially expressed genes are found in transcript response patterns following activation of CD4+ cells ex vivo, suggesting that widespread functional discrepancies differentiate the immune systems of healthy subjects and melanoma patients. While our analysis reveals that the transcriptome architecture characteristic of healthy subjects is maintained in cancer patients, the genes expressed differentially among individuals and across cohorts provide opportunities for understanding variable immune states as well as response potentials, thus establishing a foundation for predicting individual responses to stimuli such as immunotherapeutic agents.

  12. Larval stages of the bluefin tuna blood fluke Cardicola opisthorchis (Trematoda: Aporocotylidae) found from Terebella sp. (Polychaeta: Terebellidae).

    Science.gov (United States)

    Sugihara, Yukitaka; Yamada, Toshiyuki; Tamaki, Akio; Yamanishi, Ryohei; Kanai, Kinya

    2014-04-01

    We found aporocotylid larval stages (sporocysts and cercariae) from five individuals of terebellid polychaete Terebella sp., which were collected from seabed substrate and ropes and floats attached to tuna cages in a tuna farm on the coast of Tsushima Island, Nagasaki, Japan. Nucleotide sequences of the regions of internal transcribed spacer 2 ribosomal DNA and 28S ribosomal DNA from these larval stages were 100% identical to those of Cardicola opisthorchis registered in GenBank. C. opisthorchis is a pathogen causing blood fluke infection of Pacific bluefin tuna Thunnus orientalis, which is considered to have a significant impact on the Japanese Pacific bluefin tuna aquaculture industry. This is the first description of the intermediate host of C. opisthorchis. This indicates that the life cycle of C. opisthorchis is completed within tuna farms in this area. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

  13. The Plasmodium falciparum var gene transcription strategy at the onset of blood stage infection in a human volunteer

    DEFF Research Database (Denmark)

    Wang, Christian W; Hermsen, Cornelus C; Sauerwein, Robert W

    2009-01-01

    transcript distribution of var genes in a P. falciparum-infected non-immune individual and show that the initial expression of PfEMP1 is based on a strategy that allows all or most variants of PfEMP1s to be expressed by the parasite population at the onset of the blood stage infection.......The var genes encode a family of adhesion receptor proteins, Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1), which profoundly influence malaria pathogenesis. Only a single var gene is transcribed and one PfEMP1 expressed per P.falciparum parasite. Here we present the in vivo...

  14. Biochemical and Haematological Blood Parameters at Different Stages of Lactation in Cows

    Directory of Open Access Journals (Sweden)

    Cristian Ovidiu COROIAN

    2017-05-01

    Full Text Available The health status of cows is evaluated and depending on haematological and biochemical profile of blood. Nutrition is the main technological factor that can produce profound changes in the metabolic profile in animals (Dhiman et al., 1991; Khaled et al., 1999; Ingvartsen, 2006. Blood parameters analyze can lead to identify if there are errors in nutrition of lactating cows (Payne et al., 1970. The aim of this study was the evaluation of metabolic and biochemical changes that occur during colostrum period and in terms of number of lactations in cows. The biological material was represented by a total of 60 heads of dairy cows from a family farm from Sălaj County, Romania. The cows are all from Holstein breed and presented no clinical signs of any specific pathology. Blood samples were collected from the jugular vein of each cow and analyzed. 10 individuals from each of the six lactations have been randomly selected. Haematological and biochemical parameters showed variations depending on factors analyzed here. In lactation 1 Hb was 7.55±3.05 (g/dl, while in lactation 6 the value was 12.5±2.10 (g/dl. RBC ranged as follows: in lactation 1 - 28.50±2.05 and in lactation 6 - 30.02±2.05. Lymphocytes varied within very wide limits under the influence of lactation: in lactation 1 - 2.8±1.56 and in lactation 6 - 7.55±1.80. The number of lactations and lactation rank have influenced blood biochemical and hematological parameters in dairy cows. Biochemical parameters are influenced by post-partum day, showing the lowest values in the early days of colostral period and the highest in the last few days of the same period.

  15. Persistent positive metaiodobenzylguanidine scans after autologous peripheral blood stem cell transplantation may indicate maturation of stage 4 neuroblastoma.

    Science.gov (United States)

    Okamoto, Yasuhiro; Kodama, Yuichi; Nishikawa, Takuro; Rindiarti, Almitra; Tanabe, Takayuki; Nakagawa, Shunsuke; Yoshioka, Takako; Takumi, Koji; Kaji, Tatsuru; Kawano, Yoshifumi

    2017-04-01

    Metaiodobenzylguanidine (MIBG) scans are sensitive testing tools for neuroblastoma. Persistent positive MIBG scans in patients with stage 3 neuroblastoma have previously been found to indicate maturation rather than regression. We assessed the significance of this finding in stage 4 neuroblastoma in the present study. Fifteen consecutive pediatric patients with stage 4 neuroblastoma treated between 2004 and 2014 at the Kagoshima University Hospital were retrospectively examined. Treatment involved a combination of multiagent chemotherapy, resection, autologous peripheral blood stem cell transplantation (PBSCT), radiotherapy, and maintenance therapy with retinoic acid. The MIBG uptake in each patient during treatment was assessed using a Curie score. The 5-year event-free and overall survival rates in 15 patients were 38.9% and 58.7%, respectively. Four patients with persistent positive MIBG scans who underwent autologous PBSCT but experienced decreased 123 I-MIBG uptake during the clinical course survived without progression, and their event-free survival (EFS) was significantly superior to that of patients who showed negative MIBG scans after PBSCT (5-year EFS rate: 18.2%, p = 0.0176). Therefore, persistent positive MIBG scans with gradually decreased uptake after PBSCT do not always indicate neuroblastoma progression, and may instead indicate tumor maturation in some selected cases, if not all cases, of stage 4 neuroblastoma.

  16. Hd86 mRNA expression profile in Hyalomma scupense life stages, could it contribute to explain anti-tick vaccine effect discrepancy between adult and immature instars?

    Science.gov (United States)

    Ben Said, Mourad; Galaï, Yousr; Ben Ahmed, Melika; Gharbi, Mohamed; de la Fuente, José; Jedidi, Mohamed; Darghouth, Mohamed Aziz

    2013-11-15

    Bm86 midgut protein has been used in order to control ticks of the Hyalomma genus. Previous studies demonstrated the inefficacity of this antigen in the control of Hyalomma scupense, whereas recombinant Hd86 antigen, the Bm86 ortholog in H. scupense produced in Pichia pastoris, was protective against larval H. scupense tick stage infestations but ineffective in the control of the adult stage. One possible explanation for this result is the variation in Hd86 expression levels between these two developmental stages. To test this hypothesis, Hd86 mRNA levels were characterized in H. scupense developmental stages. The expression profile of Hd86 demonstrated a significant variation between tick life stages and showed a significant reduction in the number of transcripts during feeding and, particularly after molting to adults. The most interesting result was noted after molting of engorged nymphs in unfed adults where the expression levels decreased significantly by 12.78 (10.77-17.39) (pstages might explain, in part, the discrepancy of the Hd86 vaccine efficacy against these two life stages of H. scupense. Copyright © 2013 Elsevier B.V. All rights reserved.

  17. Comparative testing of six antigen-based malaria vaccine candidates directed toward merozoite-stage Plasmodium falciparum

    DEFF Research Database (Denmark)

    Arnot, David E; Cavanagh, David R; Remarque, Edmond J

    2008-01-01

    Immunogenicity testing of Plasmodium falciparum antigens being considered as malaria vaccine candidates was undertaken in rabbits. The antigens compared were recombinant baculovirus MSP-1(19) and five Pichia pastoris candidates, including two versions of MSP-1(19), AMA-1 (domains I and II), AMA-1......G concentrations. The two P. pastoris-produced MSP-1(19)-induced IgGs conferred the lowest growth inhibition. Comparative analysis of immunogenicity of vaccine antigens can be used to prioritize candidates before moving to expensive GMP production and clinical testing. The assays used have given discriminating...

  18. Status of a Unique Vaccine against hCG for Contraception and Advanced Stage Cancers expressing ectopically hCG

    OpenAIRE

    Talwar GP; Singh P; Gupta JC

    2015-01-01

    Dear Egon!br God bless you on your 95th Birthday! May you complete 100 years.br Being submitted in your honor is a brief article on my continuing work to make available a unique vaccine preventing pregnancy in women without blocking ovulation, her normal production of sex steroid hormones and retaining her regular menstrual cycles and bleeding profiles.br The vaccine is directed at the Human chorionic gonadotropin (hCG), which emerges following fertilization of the egg [1]. Healthy, non-p...

  19. Malaria vaccine research and development: the role of the WHO MALVAC committee

    Science.gov (United States)

    2013-01-01

    The WHO Malaria Vaccine Advisory Committee (MALVAC) provides advice to WHO on strategic priorities, activities and technical issues related to global efforts to develop vaccines against malaria. MALVAC convened a series of meetings to obtain expert, impartial consensus views on the priorities and best practice for vaccine-related research and development strategies. The technical areas covered during these consultations included: guidance on clinical trial design for candidate sporozoite and asexual blood stage vaccines; measures of efficacy of malaria vaccines in Phase IIb and Phase III trials; standardization of immunoassays; the challenges of developing assays and designing trials for interventions against malaria transmission; modelling impact of anti-malarial interventions; whole organism malaria vaccines, and Plasmodium vivax vaccine-related research and evaluation. These informed discussions and opinions are summarized here to provide guidance on harmonization of strategies to help ensure high standards of practice and comparability between centres and the outcome of vaccine trials. PMID:24112689

  20. Benih Keturunan Induk Ikan Nila yang Divaksinasi pada Tingkat Kematangan Gonad-2 Lebih Tahan Terhadap Infeksi Streptococcus agalactiae (RESISTANCE OF TILAPIA (OREOCHRIMIS NILOTICUS FRY VACCINATED AT DIFFERENT GONADAL DEVELOPMENTAL STAGES TOWARD STREPTOCO

    Directory of Open Access Journals (Sweden)

    Khairun Nissa

    2016-11-01

    Full Text Available The aim of this study was to evaluate the effectiveness of vaccination based on gonad maturationstages on tilapia brood stocks in which the released antibodies was able to be transferred to the seed.Vaccine composed with whole cells and extracellular product (ECP was injected at stage 2 and stage 3 ofthe gonad development stages at concentration of 109 CFU mL1 as much as 4 mL to 1 kg of brood fish.Control fish was unvaccinated treatment. Challenge study at seed was conducted by immersing S. agalactiaefor 30 minutes at 7, 14, 21, and 28 days post hatching (DPH in 107 CFU/mL. Antibody levels on broodstocks, eggs, and body fluids of seed, and relative percentage survival (RPS of seed post challenge studywere evaluated. The results showed that stage 2 of gonad developmental stages was found on 7 days postinitial spawning and stage 3 found on 14 days post initial spawning of brood fish. Vaccinated done in stage 2 of gonad developmental stages gave immunoglobulin serum in brood (0,166±0,001, egg (0,165±0,002,and seed aged 7, 14, 21, and 28 days post hatching (0,164±0,002, 0,162±0,005, 0,155±0,006, and 0,14±0,008respectively were significantly higher (P<0,05 compared to other treatment. Challenged test that doneby immersing with S. agalactiae suspension on larval aged 7, 14, 21, and 28 days had highest RPS(95,24%, 83,33%, 72,22%, and 56,02% respectively formed on seed from brood stock vaccination in gonaddevelopment stage 2. Vaccination in tilapia brood stocks at stage 2 of gonad developmental stages gavehighest protection by maternal immunity to the seed against S. agalactiae.

  1. Remarkable stability in patterns of blood-stage gene expression during episodes of non-lethal Plasmodium yoelii malaria.

    Science.gov (United States)

    Cernetich-Ott, Amy; Daly, Thomas M; Vaidya, Akhil B; Bergman, Lawrence W; Burns, James M

    2012-08-06

    Microarray studies using in vitro cultures of synchronized, blood-stage Plasmodium falciparum malaria parasites have revealed a 'just-in-time' cascade of gene expression with some indication that these transcriptional patterns remain stable even in the presence of external stressors. However, direct analysis of transcription in P. falciparum blood-stage parasites obtained from the blood of infected patients suggests that parasite gene expression may be modulated by factors present in the in vivo environment of the host. The aim of this study was to examine changes in gene expression of the rodent malaria parasite, Plasmodium yoelii 17X, while varying the in vivo setting of replication. Using P. yoelii 17X parasites replicating in vivo, differential gene expression in parasites isolated from individual mice, from independent infections, during ascending, peak and descending parasitaemia and in the presence and absence of host antibody responses was examined using P. yoelii DNA microarrays. A genome-wide analysis to identify coordinated changes in groups of genes associated with specific biological pathways was a primary focus, although an analysis of the expression patterns of two multi-gene families in P. yoelii, the yir and pyst-a families, was also completed. Across experimental conditions, transcription was surprisingly stable with little evidence for distinct transcriptional states or for consistent changes in specific pathways. Differential gene expression was greatest when comparing differences due to parasite load and/or host cell availability. However, the number of differentially expressed genes was generally low. Of genes that were differentially expressed, many involved biologically diverse pathways. There was little to no differential expression of members of the yir and pyst-a multigene families that encode polymorphic proteins associated with the membrane of infected erythrocytes. However, a relatively large number of these genes were expressed during

  2. [Prognostic significance of leukocyte count in the venous blood in the acute stage of cerebral aneurism rupture].

    Science.gov (United States)

    Kalinkin, A A; Petrikov, S S; Khamidova, L T; Krylov, V V

    To determine a prognostic role of leukocyte count in the venous blood in the acute stage of cerebral aneurysm (CA) rupture. Fifty-one patients with CA rupture, aged from 20 to 65 years, hospitalized in the first 72 h over the period from 01.10.12 to 01.02.16 were examined. The severity of disease and anatomical form of hemorrhage was corresponded to III-IV degree on the W. Hunt - R. Hess scale and Fisher scale. All patients underwent surgery. Outcomes after open and endovascular surgeries were similar. Normal leukocyte number in the venous blood at admission was identified in 12 (24%) of patients (on average 7.3±1.4·109/L), leukocytosis in 39 (76%) (14.3±3.1·109/L) (pLeukocyte number in the acute stage of CA rupture was correlated with the frequency and severity of the vessel spasm. In 28 (55%) of patients with ischemic lesions of the brain matter, mean leukocyte number in the first 72 h after hemorrhage was higher by 2-24% (3±4.8·109/L) compared to patients without ischemia (11.9±2.5·109/L) (p=0.06). The level of leukocytes in survivors was lower by 3 - 28% (122±3.4·109/L) compared to patients with fatal outcome and patients with severe neurological deficit after the surgery (14.5±3.9·109/L) (p>0.05). The increase in leukocyte number in the venous blood in the first 72 h after CA rupture ≥10,1·109/L is a reliable risk factor of marked vessel spasm. The level of leukocytes in patients with cerebral ischemia and poor prognosis in the first 72h after aneurysmal hemorrhage was higher by 2-28% compared to survivors without neurological impairment or mild neurological deficit.

  3. Distinct kinetics of memory B-cell and plasma-cell responses in peripheral blood following a blood-stage Plasmodium chabaudi infection in mice.

    Directory of Open Access Journals (Sweden)

    Eunice W Nduati

    2010-11-01

    Full Text Available B cell and plasma cell responses take place in lymphoid organs, but because of the inaccessibility of these organs, analyses of human responses are largely performed using peripheral blood mononuclear cells (PBMC. To determine whether PBMC are a useful source of memory B cells and plasma cells in malaria, and whether they reflect Plasmodium-specific B cell responses in spleen or bone marrow, we have investigated these components of the humoral response in PBMC using a model of Plasmodium chabaudi blood-stage infections in C57BL/6 mice. We detected memory B cells, defined as isotype-switched IgD(- IgM(- CD19(+ B cells, and low numbers of Plasmodium chabaudi Merozoite Surface Protein-1 (MSP1-specific memory B cells, in PBMC at all time points sampled for up to 90 days following primary or secondary infection. By contrast, we only detected CD138(+ plasma cells and MSP1-specific antibody-secreting cells within a narrow time frame following primary (days 10 to 25 or secondary (day 10 infection. CD138(+ plasma cells in PBMC at these times expressed CD19, B220 and MHC class II, suggesting that they were not dislodged bone-marrow long-lived plasma cells, but newly differentiated migratory plasmablasts migrating to the bone marrow; thus reflective of an ongoing or developing immune response. Our data indicates that PBMC can be a useful source for malaria-specific memory B cells and plasma cells, but extrapolation of the results to human malaria infections suggests that timing of sampling, particularly for plasma cells, may be critical. Studies should therefore include multiple sampling points, and at times of infection/immunisation when the B-cell phenotypes of interest are likely to be found in peripheral blood.

  4. Effects of dietary Centella asiatica (L.) Urban on growth performance, nutrient digestibility, blood composition in piglets vaccinated with Mycoplasma hyopneumoniae.

    Science.gov (United States)

    Maneewan, Chamroon; Mekbungwan, Apichai; Charerntantanakul, Wasin; Yamauchi, Kohsho; Yamauchi, Koh-en

    2014-05-01

    To investigate the effects of Centella asiatica (L.) on growth performance, nutrient digestibility and blood composition in piglets, 32 nursery pigs were fed 0.0, 0.5, 1.0 and 2.0% dietary C. asiatica (L.) from 15 to 90 kg BW. At 30 kg BW, nutrient digestibility was measured and at 35 kg BW piglets were vaccinated with Mycoplasma hyopneumoniae. Hematological parameters were checked at 40 and 80 kg BW. Compared with the control, growth performance was not affected. The ether extract, ash and calcium digestibility were lower at 0.5%, and dry matter, crude protein, crude fat, phosphorus and energy digestibility were lower at 1.0% (Phyopneumoniae did not differ except that at 40 kg the cholesterol of 0.5% was lower (Phyopneumoniae-specific antibodies tended to be higher with increasing levels of C. asiatica (L.) (Pmycoplasma immunity to M. hyopneumoniae might suggest that C. asiatica (L.) has no function to elevate body weight but has the potential to enhance innate immunity. © 2014 Japanese Society of Animal Science.

  5. IPP-rich milk protein hydrolysate lowers blood pressure in subjects with stage 1 hypertension, a randomized controlled trial

    Directory of Open Access Journals (Sweden)

    Kloek Joris

    2010-11-01

    Full Text Available Abstract Background Milk derived peptides have been identified as potential antihypertensive agents. The primary objective was to investigate the effectiveness of IPP-rich milk protein hydrolysates (MPH on reducing blood pressure (BP as well as to investigate safety parameters and tolerability. The secondary objective was to confirm or falsify ACE inhibition as the mechanism underlying BP reductions by measuring plasma renin activity and angiotensin I and II. Methods We conducted a randomized, placebo-controlled, double blind, crossover study including 70 Caucasian subjects with prehypertension or stage 1 hypertension. Study treatments consisted of daily consumption of two capsules MPH1 (each containing 7.5 mg Isoleucine-Proline-Proline; IPP, MPH2 (each containing 6.6 mg Methionine-Alanine-Proline, 2.3 mg Leucine-Proline-Proline, 1.8 mg IPP, or placebo (containing cellulose for 4 weeks. Results In subjects with stage 1 hypertension, MPH1 lowered systolic BP by 3.8 mm Hg (P = 0.0080 and diastolic BP by 2.3 mm Hg (P = 0.0065 compared with placebo. In prehypertensive subjects, the differences in BP between MPH1 and placebo were not significant. MPH2 did not change BP significantly compared with placebo in stage I hypertensive or prehypertensive subjects. Intake of MPHs was well tolerated and safe. No treatment differences in hematology, clinical laboratory parameters or adverse effects were observed. No significant differences between MPHs and placebo were found in plasma renin activity, or angiotensin I and II. Conclusions MPH1, containing IPP and no minerals, exerts clinically relevant BP lowering effects in subjects with stage 1 hypertension. It may be included in lifestyle changes aiming to prevent or reduce high BP. Trial registration ClinicalTrials.gov NCT00471263

  6. High-Sensitivity Troponin: A Clinical Blood Biomarker for Staging Cardiomyopathy in Fabry Disease.

    Science.gov (United States)

    Seydelmann, Nora; Liu, Dan; Krämer, Johannes; Drechsler, Christiane; Hu, Kai; Nordbeck, Peter; Schneider, Andreas; Störk, Stefan; Bijnens, Bart; Ertl, Georg; Wanner, Christoph; Weidemann, Frank

    2016-05-31

    High-sensitivity troponin (hs-TNT), a biomarker of myocardial damage, might be useful for assessing fibrosis in Fabry cardiomyopathy. We performed a prospective analysis of hs-TNT as a biomarker for myocardial changes in Fabry patients and a retrospective longitudinal follow-up study to assess longitudinal hs-TNT changes relative to fibrosis and cardiomyopathy progression. For the prospective analysis, hs-TNT from 75 consecutive patients with genetically confirmed Fabry disease was analyzed relative to typical Fabry-associated echocardiographic findings and total myocardial fibrosis as measured by late gadolinium enhancement (LE) on magnetic resonance imaging. Longitudinal data (3.9±2.0 years), including hs-TNT, LE, and echocardiographic findings from 58 Fabry patients, were retrospectively collected. Hs-TNT level positively correlated with LE (linear correlation coefficient, 0.72; odds ratio, 32.81 [95% CI, 3.56-302.59]; P=0.002); patients with elevated baseline hs-TNT (>14 ng/L) showed significantly increased LE (median: baseline, 1.9 [1.1-3.3] %; follow-up, 3.2 [2.3-4.9] %; PFabry disease and a qualified predictor of cardiomyopathy progression. Thus, hs-TNT could be helpful for staging and follow-up of Fabry patients. © 2016 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

  7. Preoperative Monocyte-to-Lymphocyte Ratio in Peripheral Blood Predicts Stages, Metastasis, and Histological Grades in Patients with Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Jiangdong Xiang

    2017-02-01

    dehydrogenase were found between the low-MLR group (MLR ≤ 0.23 and the high-MLR group (MLR > 0.23. Correspondingly, dramatic differences were observed between the two groups in OS. CONCLUSION: Our results show that the peripheral blood MLR before surgery could be a significant predictor of advanced stages, advanced pathologic grades, and positive lymphatic metastasis in ovarian cancer patients.

  8. Nucleated red blood cells and early EEG: predicting Sarnat stage and two year outcome.

    LENUS (Irish Health Repository)

    Walsh, B H

    2012-01-31

    AIMS: Hypoxic Ischaemic Encephalopathy (HIE) causes characteristic changes of the electroencephalogram (EEG), and a raised Nucleated Red Blood Cell (NRBC) count compared to controls. We wished to examine whether combining these markers could improve their ability to predict HIE severity in the first 24h. METHODS: Term infants with HIE were recruited. NRBC count and continuous multi-channel EEG were recorded within the first 24h. Neurological assessment was carried out at 24 months. A control population with NRBC counts in the first 24h was recruited. RESULTS: 44 infants with HIE and 43 control infants were recruited. Of the HIE population 39 completed a 2 year follow-up. The median NRBC count differed significantly between the controls and those with HIE (3\\/100 WBC [range of 0-11] vs 12.3\\/100 WBC [0-240]) (p<0.001). Within the HIE population the median NRBC count was significantly greater in infants with moderate\\/severe HIE than mild (16\\/100 WBC [range of 0-240] vs 8\\/100 WBC [1-23]) (p=0.016), and among infants with abnormal outcome compared to normal (21.3\\/100 WBC [1-239.8] vs 8.3\\/100 WBC [0-50])(p=0.03). The predictive ability of EEG changed with time post-delivery, therefore results are given at both 12 and 24h of age. At both time points the combined marker had a stronger correlation than EEG alone; with HIE severity (12h: r=0.661 vs r=0.622), (24h: r=0.645 vs r=0.598), and with outcome at 2 years (12h: r=0.756 vs r=0.652), (24h: r=0.802 vs r=0.746). CONCLUSION: Combining early EEG and NRBC count to predict HIE severity and neurological outcome, improved the predictive ability of either in isolation.

  9. IFNAR1-Signalling Obstructs ICOS-mediated Humoral Immunity during Non-lethal Blood-Stage Plasmodium Infection

    Science.gov (United States)

    Sebina, Ismail; James, Kylie R.; Soon, Megan S. F.; Best, Shannon E.; Montes de Oca, Marcela; Amante, Fiona H.; Thomas, Bryce S.; Beattie, Lynette; Souza-Fonseca-Guimaraes, Fernando; Smyth, Mark J.; Hertzog, Paul J.; Hill, Geoffrey R.; Engwerda, Christian R.

    2016-01-01

    Parasite-specific antibodies protect against blood-stage Plasmodium infection. However, in malaria-endemic regions, it takes many months for naturally-exposed individuals to develop robust humoral immunity. Explanations for this have focused on antigenic variation by Plasmodium, but have considered less whether host production of parasite-specific antibody is sub-optimal. In particular, it is unclear whether host immune factors might limit antibody responses. Here, we explored the effect of Type I Interferon signalling via IFNAR1 on CD4+ T-cell and B-cell responses in two non-lethal murine models of malaria, P. chabaudi chabaudi AS (PcAS) and P. yoelii 17XNL (Py17XNL) infection. Firstly, we demonstrated that CD4+ T-cells and ICOS-signalling were crucial for generating germinal centre (GC) B-cells, plasmablasts and parasite-specific antibodies, and likewise that T follicular helper (Tfh) cell responses relied on B cells. Next, we found that IFNAR1-signalling impeded the resolution of non-lethal blood-stage infection, which was associated with impaired production of parasite-specific IgM and several IgG sub-classes. Consistent with this, GC B-cell formation, Ig-class switching, plasmablast and Tfh differentiation were all impaired by IFNAR1-signalling. IFNAR1-signalling proceeded via conventional dendritic cells, and acted early by limiting activation, proliferation and ICOS expression by CD4+ T-cells, by restricting the localization of activated CD4+ T-cells adjacent to and within B-cell areas of the spleen, and by simultaneously suppressing Th1 and Tfh responses. Finally, IFNAR1-deficiency accelerated humoral immune responses and parasite control by boosting ICOS-signalling. Thus, we provide evidence of a host innate cytokine response that impedes the onset of humoral immunity during experimental malaria. PMID:27812214

  10. Subcompartmentalisation of proteins in the rhoptries correlates with ordered events of erythrocyte invasion by the blood stage malaria parasite.

    Directory of Open Access Journals (Sweden)

    Elizabeth S Zuccala

    Full Text Available Host cell infection by apicomplexan parasites plays an essential role in lifecycle progression for these obligate intracellular pathogens. For most species, including the etiological agents of malaria and toxoplasmosis, infection requires active host-cell invasion dependent on formation of a tight junction - the organising interface between parasite and host cell during entry. Formation of this structure is not, however, shared across all Apicomplexa or indeed all parasite lifecycle stages. Here, using an in silico integrative genomic search and endogenous gene-tagging strategy, we sought to characterise proteins that function specifically during junction-dependent invasion, a class of proteins we term invasins to distinguish them from adhesins that function in species specific host-cell recognition. High-definition imaging of tagged Plasmodium falciparum invasins localised proteins to multiple cellular compartments of the blood stage merozoite. This includes several that localise to distinct subcompartments within the rhoptries. While originating from the same organelle, however, each has very different dynamics during invasion. Apical Sushi Protein and Rhoptry Neck protein 2 release early, following the junction, whilst a novel rhoptry protein PFF0645c releases only after invasion is complete. This supports the idea that organisation of proteins within a secretory organelle determines the order and destination of protein secretion and provides a localisation-based classification strategy for predicting invasin function during apicomplexan parasite invasion.

  11. Prevalence, clinical staging and risk for blood-borne transmission of Chagas disease among Latin American migrants in Geneva, Switzerland.

    Science.gov (United States)

    Jackson, Yves; Gétaz, Laurent; Wolff, Hans; Holst, Marylise; Mauris, Anne; Tardin, Aglaé; Sztajzel, Juan; Besse, Valérie; Loutan, Louis; Gaspoz, Jean-Michel; Jannin, Jean; Albajar Vinas, Pedro; Luquetti, Alejandro; Chappuis, François

    2010-02-02

    Migration of Latin Americans to the USA, Canada and Europe has modified Chagas disease distribution, but data on imported cases and on risks of local transmission remain scarce. We assessed the prevalence and risk factors for Chagas disease, staged the disease and evaluated attitudes towards blood transfusion and organ transplant among Latin American migrants in Geneva, Switzerland. This cross-sectional study included all consecutive Latin American migrants seeking medical care at a primary care facility or attending two Latino churches. After completing a questionnaire, they were screened for Chagas disease with two serological tests (Biomérieux ELISA cruzi; Biokit Bioelisa Chagas). Infected subjects underwent a complete medical work-up. Predictive factors for infection were assessed by univariate and multivariate logistic regression analysis.1012 persons (females: 83%; mean age: 37.2 [SD 11.3] years, Bolivians: 48% [n = 485]) were recruited. 96% had no residency permit. Chagas disease was diagnosed with two positive serological tests in 130 patients (12.8%; 95%CI 10.8%-14.9%), including 127 Bolivians (26.2%; 95%CI 22.3%-30.1%). All patients were in the chronic phase, including 11.3% with cardiac and 0.8% with digestive complications. Predictive factors for infection were Bolivian origin (OR 33.2; 95%CI 7.5-147.5), reported maternal infection with T. cruzi (OR 6.9; 95%CI 1.9-24.3), and age older than 35 years (OR 6.7; 95%CI 2.4-18.8). While 22 (16.9%) infected subjects had already donated blood, 24 (18.5%) and 34 (26.2%) considered donating blood and organs outside Latin America, respectively. Chagas disease is highly prevalent among Bolivian migrants in Switzerland. Chronic cardiac and digestive complications were substantial. Screening of individuals at risk should be implemented in nonendemic countries and must include undocumented migrants.

  12. Novel approaches to identify protective malaria vaccine candidates

    Directory of Open Access Journals (Sweden)

    Wan Ni eChia

    2014-11-01

    Full Text Available Efforts to develop vaccines against malaria have been the focus of substantial research activities for decades. Several categories of candidate vaccines are currently being developed for protection against malaria, based on antigens corresponding to the pre-erythrocytic, blood-stage or sexual stages of the parasite. Long lasting sterile protection from Plasmodium falciparum sporozoite challenge has been observed in human following vaccination with whole parasite formulations, clearly demonstrating that a protective immune response targeting predominantly the pre-erythrocytic stages can develop against malaria. However, most of vaccine candidates currently being investigated, which are mostly subunits vaccines, have not been able to induce substantial (>50% protection thus far. This is due to the fact that the antigens responsible for protection against the different parasite stages are still yet to be known and relevant correlates of protection have remained elusive. For a vaccine to be developed in a timely manner, novel approaches are required. In this article, we review the novel approaches that have been developed to identify the antigens for the development of an effective malaria vaccine.

  13. Development and regulation of cell-mediated immune responses to the blood stages of malaria: implications for vaccine research.

    Science.gov (United States)

    Good, Michael F; Xu, Huji; Wykes, Michelle; Engwerda, Christian R

    2005-01-01

    The immune response to the malaria parasite is complex and poorly understood. Although antibodies and T cells can control parasite growth in model systems, natural immunity to malaria in regions of high endemicity takes several years to develop. Variation and polymorphism of antibody target antigens are known to impede immune responses, but these factors alone cannot account for the slow acquisition of immunity. In human and animal model systems, cell-mediated responses can control parasite growth effectively, but such responses are regulated by parasite load via direct effects on dendritic cells and possibly on T and B cells as well. Furthermore, high parasite load is associated with pathology, and cell-mediated responses may also harm the host. Inflammatory cytokines have been implicated in the pathogenesis of cerebral malaria, anemia, weight loss, and respiratory distress in malaria. Immunity without pathology requires rapid parasite clearance, effective regulation of the inflammatory anti-parasite effects of cellular responses, and the eventual development of a repertoire of antibodies effective against multiple strains. Data suggest that this may be hastened by exposure to malaria antigens in low dose, leading to augmented cellular immunity and rapid parasite clearance.

  14. Pneumococcal polysaccharide vaccination elicits IgG anti-AB blood group antibodies in healthy individuals and patients with Type I diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Wendelin Wolfram

    2016-11-01

    Full Text Available Hypothesis: Blood group antibodies are natural antibodies that develop early in life in response to cross-reactive environmental antigens in the absence of antigen encounter. Even later in life structural similarities in saccharide composition between environmental antigens such as bacterial polysaccharides and blood group A/B antigens could lead to changes in serum levels, IgM/IgG isotype and affinity maturation of blood group anti-A/B antibodies. We adressed the question whether immunization with pneumococcal polysaccharide (PnP vaccine (PPV Pneumovax®23 could have such an effect in patients with with type I diabetes mellitus (DM I, an autoimmune disease where an aberrant immune response to microbial antigens likely plays a role.Methods: Anti-PnP IgM and IgG responses were determined by ELISA and the Diamed-ID Micro Typing System was used to screen anti-A/B antibody titer before and after Pneumovax®23 immunization in 28 healthy individuals and 16 patients with DM I. In addition, surface plasmon resonance (SPR technology using the Biacore® device and a synthetic blood group A/B trisaccharide as the antigen was applied to investigate IgM and IgG anti-A/B antibodies and to measure antibody binding dynamics. Results: All healthy individuals and DM I patients responded with anti-PnP IgM and IgG antibody production four to six weeks after Pneumovax®23 (Pn23 immunization, while no increase in blood group anti-A/B antibody titer was observed when measured by the Diamed-ID Micro Typing System. Interestingly, isotype-specific testing by SPR-technology revealed an increase in blood group anti-A/B IgG, but not IgM, following Pn23 immunization in both patients and controls. No change in binding characteristics of blood group anti-A/B antibodies could be detected following Pn23 vaccination, supporting the assumption of an increase in IgG antibody titer with no or very little affinity maturation.Conclusion: The study provides evidence for epitope sharing

  15. Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination

    DEFF Research Database (Denmark)

    Burgdorf, Stefan; Claesson, Mogens; Nielsen, Hans

    2009-01-01

    of responding patients. The aim of this study was to evaluate cytokine and biomarker responses in patients with colorectal cancer treated with a cancer vaccine based on dendritic cells pulsed with an allogeneic melanoma cell lysate. Material and methods. Plasma and serum samples were collected prior......Introduction. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction...... to vaccination and continuously during treatment. GM-CSF, IL-2, IL-6, TNF-alpha, IFN-gamma, IL-4, IL-8, IL-1b, IL-5, IL-10, IL-12, MIP-1b, IP-10 and Eotaxin were analyzed in a multiplex assay with a Luminex 100 instrument. CEA and TIMP-1 were analysed on ELISA platforms. Results. Patients achieving stable...

  16. Tuberculosis contact investigation with a new, specific blood test in a low-incidence population containing a high proportion of BCG-vaccinated persons

    Directory of Open Access Journals (Sweden)

    Meywald-Walter K

    2006-05-01

    Full Text Available Abstract Background BCG-vaccination can confound tuberculin skin test (TST reactions in the diagnosis of latent tuberculosis infection. Methods We compared the TST with a Mycobacterium tuberculosis specific whole blood interferon-gamma assay (QuantiFERON®-TB-Gold In Tube; QFT-G during ongoing investigations among close contacts of sputum smear positive source cases in Hamburg, Germany. Results During a 6-month period, 309 contacts (mean age 28.5 ± 10.5 years from a total of 15 source cases underwent both TST and QFT-G testing. Of those, 157 (50.8% had received BCG vaccination and 84 (27.2% had migrated to Germany from a total of 25 different high prevalence countries (i.e. >20 cases/100,000. For the TST, the positive response rate was 44.3% (137/309, whilst only 31 (10% showed a positive QFT-G result. The overall agreement between the TST and the QFT-G was low (κ = 0.2, with 95% CI 0.14.-0.23, and positive TST reactions were closely associated with prior BCG vaccination (OR 24.7; 95% CI 11.7–52.5. In contrast, there was good agreement between TST and QFT-G in non-vaccinated persons (κ = 0.58, with 95% CI 0.4–0.68, increasing to 0.68 (95% CI 0.46–0.81, if a 10-mm cut off for the TST was used instead of the standard 5 mm recommended in Germany. Conclusion The QFT-G assay was unaffected by BCG vaccination status, unlike the TST. In close contacts who were BCG-vaccinated, the QFT-G assay appeared to be a more specific indicator of latent tuberculosis infection than the TST, and similarly sensitive in unvaccinated contacts. In BCG-vaccinated close contacts, measurement of IFN-gamma responses of lymphocytes stimulated with M. tuberculosis-specific antigen should be recommended as a basis for the decision on whether to perform subsequent chest X-ray examinations or to start treatment for latent tuberculosis infection.

  17. MALARIA VACCINE: MYTH OR REALITY?

    African Journals Online (AJOL)

    Femi Olaleye

    stage antigens. VACCINE DEVELOPMENT. The skill involved in development of vaccines has always been the use of a whole organism or a fraction of it. Non- ... Human vaccine trials are also reported to have been successful. (Amador et. al., 1992). Erythrocyte Stage Antigens SPF 66. This is the first synthetically produced.

  18. The effects of stair climbing on arterial stiffness, blood pressure, and leg strength in postmenopausal women with stage 2 hypertension.

    Science.gov (United States)

    Wong, Alexei; Figueroa, Arturo; Son, Won-Mok; Chernykh, Oksana; Park, Song-Young

    2018-02-12

    Menopause is accompanied by a progressive arterial stiffening associated with increases in blood pressure (BP) and decline in muscular function. It is crucial to prevent or reduce the negative effects of menopause on vascular and muscular function by implementing appropriate lifestyle interventions, such as exercise training. We examined the effects of a stair climbing (SC) regimen on arterial stiffness (pulse wave velocity [PWV]), BP, and leg strength in postmenopausal women with stage 2 hypertension. Using a parallel experimental design, participants were randomly assigned to either SC (n = 21) or nonexercising control group (n = 20) for 12 weeks. Participants in the SC group trained 4 d/wk, climbing 192 steps 2 to 5 times/d. Participants' brachial-to-ankle PWV (baPWV), BP, and leg strength were measured at baseline and after 12 weeks of their assigned intervention. There was a significant group by time interaction (P hypertensive postmenopausal women. The decrease in arterial stiffness partially explained the improvements in SBP and leg strength. SC may be an effective intervention in the prevention and treatment of menopause/aging-related vascular complications and muscle weakness.

  19. Blood

    Science.gov (United States)

    ... production of red blood cells, including: Iron deficiency anemia. Iron deficiency anemia is the most common type of anemia and ... inflammatory bowel disease are especially likely to have iron deficiency anemia. Anemia due to chronic disease. People with chronic ...

  20. Antibody responses to a panel of Plasmodium falciparum malaria blood-stage antigens in relation to clinical disease outcome in Sudan

    DEFF Research Database (Denmark)

    Iriemenam, Nnaemeka C; Khirelsied, Atif H; Nasr, Amre

    2009-01-01

    have analysed immunoglobulin G profiles to six leading blood-stage antigens in relation to clinical malaria outcome in a hospital-based study in Sudan. Our results revealed a linear association with anti-AMA-1-IgG1 antibodies in children

  1. The effect of early initiation of breast feeding on the amount of vaginal blood loss during the fourth stage of labor.

    Science.gov (United States)

    Sobhy, Soheir Ibrahim; Mohame, Nabaweya Aly

    2004-01-01

    Post partum hemorrhage is a major problem that jeopardizes maternal health. Its prevention can save mothers' life postnatal, through early initiation of breast-feeding. So, the study aimed to explore the effect of early initiation of breast feeding on the amount of vaginal blood loss during the fourth stage of labor. A convenient sample of one hundred primiparae was selected from the delivery unit & post partum unit of El-Shatby Maternity University Hospital in Alexandria. The study subjects were divided equally into experimental group (early breast feeding group) and control group (late breast feeding group). Two tools were developed and used for data collection. A specially designed interview questionnaire was used during early first stage of labor to collect data about general characteristics of the study subjects. An observational checklist was used during the fourth stage of labor to collect data about uterine characteristics, number of feeds and the amount of blood loss. The early breast-feeding group started feeding immediately after placental delivery, while late breast feeding group started breast- feeding after the first two hours postnatally. The amounts of blood loss for both groups were calculated. The findings of the study revealed that early initiation & increased frequency of breast-feeding could decrease the amount of blood loss during the fourth stage of labor. Therefore, maternity and pediatric nurses have to encourage mothers to start breast-feeding early. They have to explain how breast-feeding is beneficial for both mother and child.

  2. HPV vaccine

    Science.gov (United States)

    Vaccine - HPV; Immunization - HPV; Gardasil; HPV2; HPV4; Vaccine to prevent cervical cancer; Genital warts - HPV vaccine; Cervical dysplasia - HPV vaccine; Cervical cancer - HPV vaccine; Cancer of the cervix - HPV vaccine; Abnormal ...

  3. Blood Interferon Signatures Putatively Link Lack of Protection Conferred by the RTS,S Recombinant Malaria Vaccine to an Antigen-specific IgE Response [version 2; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Darawan Rinchai

    2017-07-01

    Full Text Available Malaria remains a major cause of mortality and morbidity worldwide. Progress has been made in recent years with the development of vaccines that could pave the way towards protection of hundreds of millions of exposed individuals. Here we used a modular repertoire approach to re-analyze a publically available microarray blood transcriptome dataset monitoring the response to malaria vaccination. We report the seminal identification of interferon signatures in the blood of subjects on days 1, 3 and 14 following administration of the third dose of the RTS,S recombinant malaria vaccine. These signatures at day 1 correlate with protection, and at days 3 and 14 to susceptibility to subsequent challenge of study subjects with live parasites. In addition we putatively link the decreased abundance of interferon-inducible transcripts observed at days 3 and 14 post-vaccination with the elicitation of an antigen-specific IgE response in a subset of vaccine recipients that failed to be protected by the RTS,S vaccine. Furthermore, profiling of antigen-specific levels of IgE in a Mozambican cohort of malaria-exposed children vaccinated with RTS,S identified an association between elevated baseline IgE levels and subsequent development of naturally acquired malaria infection during follow up. Taken together these findings warrant further investigation of the role of antigen-specific IgE in conferring susceptibility to malaria infection.

  4. Cytokine responses of CD4+ T cells during a Plasmodium chabaudi chabaudi (ER blood-stage infection in mice initiated by the natural route of infection

    Directory of Open Access Journals (Sweden)

    Butcher Geoffrey

    2007-06-01

    Full Text Available Abstract Background Investigation of host responses to blood stages of Plasmodium spp, and the immunopathology associated with this phase of the life cycle are often performed on mice infected directly with infected red blood cells. Thus, the effects of mosquito bites and the pre-erythrocytic stages of the parasite, which would be present in natural infection, are ignored In this paper, Plasmodium chabaudi chabaudi infections of mice injected directly with infected red blood cells were compared with those of mice infected by the bites of infected mosquitoes, in order to determine whether the courses of primary infection and splenic CD4 T cell responses are similar. Methods C57Bl/6 mice were injected with red blood cells infected with P. chabaudi (ER or infected via the bite of Anopheles stephensi mosquitoes. Parasitaemia were monitored by Giemsa-stained thin blood films. Total spleen cells, CD4+ T cells, and cytokine production (IFN-γ, IL-2, IL-4, IL-10 were analysed by flow cytometry. In some experiments, mice were subjected to bites of uninfected mosquitoes prior to infectious bites in order to determine whether mosquito bites per se could affect a subsequent P. chabaudi infection. Results P. chabaudi (ER infections initiated by mosquito bite were characterized by lower parasitaemia of shorter duration than those observed after direct blood challenge. However, splenomegaly was comparable suggesting that parasitaemia alone does not account for the increase in spleen size. Total numbers of CD4 T cells and those producing IFN-γ, IL-10 and IL-2 were reduced in comparison to direct blood challenge. By contrast, the reduction in IL-4 producing cells was less marked suggesting that there is a proportionally lower Th1-like response in mice infected via infectious mosquitoes. Strikingly, pre-exposure to bites of uninfected mosquitoes reduced the magnitude and duration of the subsequent mosquito-transmitted infection still further, but enhanced the

  5. [Intervention of chronic hepatitis B liver fibrosis patients in different stages by syndrome typing and different activating blood removing stasis methods: a clinical study].

    Science.gov (United States)

    Liu, Shi-yi; Zhang, Yin-qiang; Liu, Yan-ling; Guo, Peng; Zhou, Chun-mei

    2013-11-01

    To observe the clinical efficacy of treating chronic hepatitis B liver fibrosis (CHBLF) in different stages by syndrome typing and different activating blood removing stasis methods (ABRSM). Totally 100 CHBLF patients of vital qi deficiency blood stasis syndrome (VQDBSS) treated at the Department of Liver Diseases, Xiyuan Hospital, China Academy of Chinese Medical Sciences from July 2008 to December 2011, were randomly assigned to the treatment group and the control group, 50 in each group. Those in the treatment group were treated by self-formulated decoctions for activating blood nourishing blood (ABNB), activating blood removing stasis (ABRS), and activating blood softening hard mass (ABSHM) according to their stages of disease conditions (mild, moderate, and severe). Those in the control group were treated with Compound Biejia Ruangan Tablet (CBRT). Integrals of Chinese medical syndromes, liver functions [mainly including alanine aminotransferase (ALT), albumin/globulin (A/ G)], ultrasonographic examinations of liver (mainly including echoes of liver, width of spleens, width of portal vein), four indicators of serum hepatic fibrosis [including serum hyaluronic acid (HA), laminin (LN), type IV collagen (IV-C), type III collagen peptide (P-III-P)] were statistically analyzed. The therapeutic course was 6 months for all. Compared with before treatment in the same group, the integrals of Chinese medical syndromes both decreased after treatment in the two groups (P serum biochemical indicators.

  6. Effects of single and combined Mycoplasma gallisepticum vaccinations on blood electrolytes and acid-base balance in commercial egg-laying hens.

    Science.gov (United States)

    Olanrewaju, H A; Collier, S D; Branton, S L

    2011-02-01

    A previous study from our laboratory on F-strain Mycoplasma gallisepticum-inoculated layers showed a significant increase in arterial partial pressure of oxygen (pO(2)), which is generally associated with an oxygen-dependent improvement in tissue oxygenation. The aim of this study was to determine whether a killed (bacterin) and live TS-11-strain M. gallisepticum (TS-11-MG) vaccine treatment combination could further enhance the arterial pO(2) levels in layer chickens. The experiment was conducted in 2 trials and arranged in a completely randomized experimental design with 4 treatments. The treatments consisted of a control M. gallisepticum, bacterin, TS-11-MG, and bacterin + TS-11-MG combined, with all treatments receiving the R low strain of MG at 30 wk of age (WOA). In each of the 2 trials, 160 one-day-old MG-free pullets were raised to 10 WOA and were transported to a poultry disease isolation facility. Sixteen isolation units were divided into 4 treatment groups, and each of the 4 treatment groups had 4 replication units, with 10 birds/unit (40 birds/treatment). Venous blood samples were collected at the termination of the study at 56 WOA. The TS-11-MG-vaccinated chickens had a higher (P ≤ 0.05) blood pO(2) and a lower (P ≤ 0.05) partial pressure of CO(2) when compared with the control and combined MG-vaccinated groups. However, no significant blood pO(2) differences were observed between the bacterin and TS-11-MG treatment groups. Hematocrit and blood concentrations of hemoglobin were not statistically different among treatments, but were numerically higher in the TS-11-MG treatment group. There was a significant (P ≤ 0.05) treatment effect on blood concentrations of Na(+), Ca(2+), and anion, but no significant effect on glucose, cholesterol, triglyceride, or osmolality. These data suggest that the inoculation of layers with TS-11-MG was more effective in elevating pO(2) than was inoculation with TS-11-MG + bacterin combined.

  7. Changes in cytokine and biomarker blood levels in patients with colorectal cancer during dendritic cell-based vaccination

    DEFF Research Database (Denmark)

    Burgdorf, Stefan K; Claesson, Mogens Helweg; Nielsen, Hans J

    2009-01-01

    Introduction. Immunotherapy based on dendritic cell vaccination has exciting perspectives for treatment of cancer. In order to clarify immunological mechanisms during vaccination it is essential with intensive monitoring of the responses. This may lead to optimization of treatment and prediction...... of responding patients. The aim of this study was to evaluate cytokine and biomarker responses in patients with colorectal cancer treated with a cancer vaccine based on dendritic cells pulsed with an allogeneic melanoma cell lysate. Material and methods. Plasma and serum samples were collected prior...... disease showed increasing levels of plasma GM-CSF, TNF-alpha, IFN-gamma, IL-2, and IL-5. Patients with progressive disease showed significant increase in CEA and TIMP-1 levels, while patients with stable disease showed relatively unaltered levels. Conclusion. The increased levels of key pro...

  8. Features of intra- and extra-cranial blood flow in patients with essential hypertension stage II according to smoking status

    Directory of Open Access Journals (Sweden)

    V. V. Syvolap

    2014-04-01

    Full Text Available Today diseases of the cardiovascular system are called the problem number 1in the world, including Ukraine. Every year more than 500 thousand Ukrainians dye from CVDs, i.e. 1370 people on average dye every day. Smoking is one of the most serious threats to health, especially with regard to cardiovascular disease. Every year, smoking kills more than 1.2 million people in Europe (of which 450 thousand - due to cardiovascular diseases and about 650 thousand people of the EU countries (including from cardiovascular problems - 185 thousand. Analysis of the literature suggests paucity and contradictory information about changes in the functional status of the various systems of the body while smoking. The aim of the work was to study the peculiarities of cerebral hemodynamics in patients with hypertension stage II depending on smoking status. Material and methods. We examined 100 patients with essential hypertension stage II low additional cardiovascular risk, 53 men and 47 women. Depending on the smoking status (at least 10 years, all patients were divided into 2 groups: a group of smokers included 30 patients, in the group of non-smokers there were 70 patients. To assess cerebral hemodynamic Doppler ultrasound and duplex scanning methods were used. Statistical processing of the material was performed using the software package Statistica 6.0 («Statsoft», USA, № license AXXR712D833214FAN5. Results and discussion. Analysis of the data shows the predominance of authentic vascular resistance index in the right CCA by 3.3% (p = 0.033, in the right MCA by 8.5% (p = 0.05, in the left MCA by 7.1% (p = 0.042 in hypertensive patients with smoking status, compared with non-smoking hypertensive patients. In smokers with hypertension statistically significant increasing of the indicator "reserve vasoconstriction" by 4.63 times (p = 0.029 in the left ICA and by 3.01 times (p = 0.031 in the right ICA was also found compared with data rates in nonsmokers

  9. Progressive rise in red blood cell distribution width predicts mortality and cardiovascular events in end-stage renal disease patients.

    Science.gov (United States)

    Yoon, Hye Eun; Kim, Sung Jun; Hwang, Hyeon Seok; Chung, Sungjin; Yang, Chul Woo; Shin, Seok Joon

    2015-01-01

    Red blood cell distribution width (RDW) is a robust marker of adverse clinical outcomes in various populations. However, the clinical significance of a progressive rise in RDW is undetermined in end-stage renal disease (ESRD) patients. The purpose of this study was to determine the prognostic importance of a change in RDW in ESRD patients. Three hundred twenty-six incident dialysis patients were retrospectively analyzed. Temporal changes in RDW during 12 months after dialysis initiation were assessed by calculating the coefficients by linear regression. Patients were divided into two groups: an RDW-decreased group who had negative coefficient values (n = 177) and an RDW-increased group who had positive values (n = 149). The associations between rising RDW and mortality and cardiovascular (CV) events were investigated. During a median follow-up of 2.7 years (range, 1.0-7.7 years), 75 deaths (24.0%) and 60 non-fatal CV events (18.4%) occurred. The event-free survival rate for the composite of end-points was lower in the RDW-increased group (P = 0.004). After categorizing patients according to baseline RDW, the event-free survival rate was lowest in patients with a baseline RDW >14.9% and increased RDW, and highest in patients with a baseline RDW ≤14.9% and decreased RDW (P = 0.02). In multivariate analysis, rising RDW was independently associated with the composite of end-points (hazard ratio = 1.75, P = 0.007), whereas the baseline RDW was not. This study shows that a progressive rise in RDW independently predicted mortality and CV events in ESRD patients. Rising RDW could be an additive predictor for adverse CV outcomes ESRD patients.

  10. Physical activity and sedentary behaviour at different life stages and adult blood pressure in the 1958 British cohort.

    Science.gov (United States)

    Pouliou, Theodora; Ki, Myung; Law, Catherine; Li, Leah; Power, Chris

    2012-02-01

    To investigate whether physical activity or sedentary behaviour at different life stages is associated with blood pressure (BP) in mid-adulthood; activity levels have accumulative associations with BP; and adult body mass index (BMI) mediates associations. Information on activity and television-viewing was available at several ages (23, 33, 42, 45 years) and BP at 45 years for the 1958 British birth cohort (n = 9927). Associations were examined with and without adjustment for covariates. Active adults, generally, had lower mean systolic and diastolic BP and risk of hypertension than nonactive, although varying by age. After adjustment for covariates, systolic and diastolic BP for active men at 23 years or at 45 years were 1-2 mmHg lower; similar associations were seen for women active at 33 years. Some but not all associations attenuated with further adjustment for BMI: odds ratio (OR) for hypertension associated with 23 years activity changed from 0.82 [95% confidence interval (CI) 0.74, 0.91] to 0.79 (0.70, 0.90) after BMI adjustment. Independent associations of activity at more than one age were found, such that prevalence of hypertension was higher in men active at 23 years but not at 45 years, than men sustaining activity (39 vs. 31%). Sitting at work was unrelated to BP, but there was a trend of higher BP with greater television-viewing: for example risk of hypertension was higher by 10-12% per h/day television-viewing at 45 years after adjustment for covariates, attenuating after allowance for BMI. Our study suggests that there are benefits to BP of becoming and sustaining active lifestyles and minimizing television-viewing over many years of adulthood, with a mediating role for BMI.

  11. Heart rate response to blood pressure variations: sympathetic activation versus baroreflex response in patients with end-stage renal disease.

    Science.gov (United States)

    Sapoznikov, Dan; Dranitzki Elhalel, Michal; Rubinger, Dvora

    2013-01-01

    Continuous systolic blood pressure (SBP) and interbeat intervals (IBI) recordings reveal sequences of consecutive beats in which SBP and heart rate change in opposite direction, representing negative feedback baroreflex mechanisms, as well as sequences in which SBP and heart rate change in the same direction (non-baroreflex), believed to represent feedforward control mechanisms. The present study was undertaken to assess the relationship between baroreflex and non-baroreflex sequences in end stage renal insufficiency. Continuous beat-to-beat SBP and IBI monitoring was performed in patients on chronic hemodialysis (HD, n=72), in age-matched patients after renal transplantation (TX, n=41) and healthy (control) individuals (C, n=34). The proportion of baroreflex and nonbaroreflex episodes and the b coefficients (the regression line slope of SBP-IBI correlation) were determined using a newly developed 1 minute sliding window method, the classical sequence technique and the "Z" coefficient method. Analysis using the 1 minute sliding window showed an increased proportion of baroreflex episodes in controls and HD, and predominance of nonbaroreflex episodes in TX. An increased proportion of nonbaroreflex episodes in TX patients relative to HD was also revealed by the "Z" method. Baroreflex and nonbaroreflex b coefficients obtained by all methods were markedly decreased in HD. This alteration was reversed at least partly in TX. In HD, both baroreflex and nonbaroreflex b coefficients were inversely correlated to age and CRP levels; in TX, the nonbaroreflex b coefficient was influenced by the type of calcineurin inhibitor. Renal status affects the contribution of baroreflex and nonbaroreflex mechanisms and the strength of SBP-IBI relationship. The predominant contribution of nonbaroreflex mechanisms in TX may be suggestive of enhanced central sympathetic control. Our data may be relevant for understanding of the pathogenesis and selection of appropriate treatment of post

  12. Glycaemic, blood pressure and lipid goal attainment and chronic kidney disease stage of type 2 diabetic patients treated in primary care practices.

    Science.gov (United States)

    Corcillo, Antonella; Pivin, Edward; Lalubin, Fabrice; Pitteloud, Nelly; Burnier, Michel; Zanchi, Anne

    2017-07-11

    The prevalence of chronic kidney disease and diabetes is rising in Europe. These patients are at high cardiovascular and renal risk and need a challenging multifactorial therapeutic approach. The goal of this cross-sectional study was to examine the treatment and attainments of goals related to cardiovascular risk factors within chronic kidney disease stages in type 2 diabetic patients followed up by primary care physicians in Switzerland. Each participating physician entered into a web database the anonymised data of up to 15 consecutive diabetic patients attending her/his office between December 2013 and June 2014. Diabetes, hypertension and lipid lowering therapies were analysed, as well as glycated haemoglobin (HbA1c), blood pressure and low-density lipoprotein-cholesterol (LDL-c) levels and goal attainments by KDIGO chronic kidney disease stage 1 to 4. A total of 1359 patients (mean age 66.5±12.4 years) were included by 109 primary care physicians. Chronic kidney disease stages 0-2, 3a, 3 b and 4 were present in 77.6%, 13.9%, 6.1%, and 2.4%, respectively. Average HbA1c was independent of chronic kidney disease stage and close to 7%; more than half of the patients reached the HbA1c goal. Eighty-four percent of patients were hypertensive and only 18.2% reached the then current Swiss or American Diabetes Association 2013 blood pressure goals. Despite loosening of blood pressure goals in 2015, only half of the patients reached them and most needed multiple therapies. Increased body mass index and advanced chronic kidney disease stage decreased the chance of reaching blood pressure goals. Lipid lowering therapy was prescribed in 62.1% of cases, with average LDL-c levels similar across chronic kidney disease stages. Only 42% of patients reached the LDL-c goal of primary prevention and 32% reached primary care physicians in Switzerland. Goal attainments for HbA1c and LDL-c were not influenced by chronic kidney disease stages, in contrast to blood pressure. Reaching

  13. Blood Pressure Test

    Science.gov (United States)

    ... pressure monitors may have some limitations. Tracking your blood pressure readings It can be helpful in diagnosing or ... more Stage 2 high blood pressure (hypertension) Elevated blood pressure and stages 1 and 2 high blood pressure ( ...

  14. Malaria parasite-synthesized heme is essential in the mosquito and liver stages and complements host heme in the blood stages of infection.

    Directory of Open Access Journals (Sweden)

    Viswanathan Arun Nagaraj

    Full Text Available Heme metabolism is central to malaria parasite biology. The parasite acquires heme from host hemoglobin in the intraerythrocytic stages and stores it as hemozoin to prevent free heme toxicity. The parasite can also synthesize heme de novo, and all the enzymes in the pathway are characterized. To study the role of the dual heme sources in malaria parasite growth and development, we knocked out the first enzyme, δ-aminolevulinate synthase (ALAS, and the last enzyme, ferrochelatase (FC, in the heme-biosynthetic pathway of Plasmodium berghei (Pb. The wild-type and knockout (KO parasites had similar intraerythrocytic growth patterns in mice. We carried out in vitro radiolabeling of heme in Pb-infected mouse reticulocytes and Plasmodium falciparum-infected human RBCs using [4-(14C] aminolevulinic acid (ALA. We found that the parasites incorporated both host hemoglobin-heme and parasite-synthesized heme into hemozoin and mitochondrial cytochromes. The similar fates of the two heme sources suggest that they may serve as backup mechanisms to provide heme in the intraerythrocytic stages. Nevertheless, the de novo pathway is absolutely essential for parasite development in the mosquito and liver stages. PbKO parasites formed drastically reduced oocysts and did not form sporozoites in the salivary glands. Oocyst production in PbALASKO parasites recovered when mosquitoes received an ALA supplement. PbALASKO sporozoites could infect mice only when the mice received an ALA supplement. Our results indicate the potential for new therapeutic interventions targeting the heme-biosynthetic pathway in the parasite during the mosquito and liver stages.

  15. The Subcellular Location of Ovalbumin in Plasmodium berghei Blood Stages Influences the Magnitude of T-Cell Responses

    Science.gov (United States)

    Lin, Jing-Wen; Shaw, Tovah N.; Annoura, Takeshi; Fougère, Aurélie; Bouchier, Pascale; Chevalley-Maurel, Séverine; Kroeze, Hans; Franke-Fayard, Blandine; Janse, Chris J.; Couper, Kevin N.

    2014-01-01

    Model antigens are frequently introduced into pathogens to study determinants that influence T-cell responses to infections. To address whether an antigen's subcellular location influences the nature and magnitude of antigen-specific T-cell responses, we generated Plasmodium berghei parasites expressing the model antigen ovalbumin (OVA) either in the parasite cytoplasm or on the parasitophorous vacuole membrane (PVM). For cytosolic expression, OVA alone or conjugated to mCherry was expressed from a strong constitutive promoter (OVAhsp70 or OVA::mCherryhsp70); for PVM expression, OVA was fused to HEP17/EXP1 (OVA::Hep17hep17). Unexpectedly, OVA expression in OVAhsp70 parasites was very low, but when OVA was fused to mCherry (OVA::mCherryhsp70), it was highly expressed. OVA expression in OVA::Hep17hep17 parasites was strong but significantly less than that in OVA::mCherryhsp70 parasites. These transgenic parasites were used to examine the effects of antigen subcellular location and expression level on the development of T-cell responses during blood-stage infections. While all OVA-expressing parasites induced activation and proliferation of OVA-specific CD8+ T cells (OT-I) and CD4+ T cells (OT-II), the level of activation varied: OVA::Hep17hep17 parasites induced significantly stronger splenic and intracerebral OT-I and OT-II responses than those of OVA::mCherryhsp70 parasites, but OVA::mCherryhsp70 parasites promoted stronger OT-I and OT-II responses than those of OVAhsp70 parasites. Despite lower OVA expression levels, OVA::Hep17hep17 parasites induced stronger T-cell responses than those of OVA::mCherryhsp70 parasites. These results indicate that unconjugated cytosolic OVA is not stably expressed in Plasmodium parasites and, importantly, that its cellular location and expression level influence both the induction and magnitude of parasite-specific T-cell responses. These parasites represent useful tools for studying the development and function of antigen

  16. Development of vaccines for Plasmodium vivax malaria.

    Science.gov (United States)

    Mueller, Ivo; Shakri, Ahmad Rushdi; Chitnis, Chetan E

    2015-12-22

    Plasmodium vivax continues to cause significant morbidity outside Africa with more than 50% of malaria cases in many parts of South and South-east Asia, Pacific islands, Central and South America being attributed to P. vivax infections. The unique biology of P. vivax, including its ability to form latent hypnozoites that emerge months to years later to cause blood stage infections, early appearance of gametocytes before clinical symptoms are apparent and a shorter development cycle in the vector makes elimination of P. vivax using standard control tools difficult. The availability of an effective vaccine that provides protection and prevents transmission would be a valuable tool in efforts to eliminate P. vivax. Here, we review the latest developments related to P. vivax malaria vaccines and discuss the challenges as well as directions toward the goal of developing highly efficacious vaccines against P. vivax malaria. Copyright © 2015. Published by Elsevier Ltd.

  17. Protracted sterile protection with Plasmodium yoelii pre-erythrocytic genetically attenuated parasite malaria vaccines is independent of significant liver-stage persistence and is mediated by CD8+ T cells.

    Science.gov (United States)

    Tarun, Alice S; Dumpit, Ronald F; Camargo, Nelly; Labaied, Mehdi; Liu, Pu; Takagi, Akihide; Wang, Ruobing; Kappe, Stefan H I

    2007-08-15

    Irradiation-attenuated sporozoite vaccinations confer sterile protection against malaria infection in animal models and humans. Persistent, nonreplicating parasite forms in the liver are presumably necessary for the maintenance of sterile immunity. A novel vaccine approach uses genetically attenuated parasites (GAPs) that undergo arrested development during liver infection. The fate of GAPs after immunization, their persistence in vaccinated animals, and the immune mechanisms that mediate protection are unknown. To examine the developmental defects of genetically attenuated liver stages in vivo, we created deletions of the UIS3 and UIS4 loci in the Plasmodium yoelii rodent malaria model (Pyuis3[-] and Pyuis4[-]). The low 50% infectious dose of P. yoelii in BALB/c mice provides the most sensitive infectivity model. We show that P. yoelii GAPs reach the liver, invade hepatocytes, and develop a parasitophorous vacuole but do not significantly persist 40 h after infection. A single dose of Pyuis4(-) sporozoites conferred complete protection, but full protection by Pyuis3(-) sporozoites required at least 2 immunizations. CD8(+) T cells were essential for protection, but CD4(+) T cells were not. Our results show that genetically distinct GAPs confer different degrees of protective efficacy and that live vaccine persistence in the liver is not necessary to sustain long-lasting protection. These findings have important implications for the development of a P. falciparum GAP malaria vaccine.

  18. Comparative effect of fixed dose combination of Amlodipine + Bisoprolol versus Amlodipine and Bisoprolol alone on blood pressure in stage-2 essential hypertensive patients.

    Directory of Open Access Journals (Sweden)

    Shirure PA,Tadvi NA, Bajait CS, Baig MS, Gade PR

    2012-09-01

    Full Text Available Background: Employment of low dose combinations of two antihypertensives, with different mode of action has gained acceptance worldwide for the treatment of mild to moderate hypertension. However, most studies in hypertensive disease have focused on monotherapy. The combination therapy in the treatment of hypertension is largely extrapolated from these monotherapy studies. Objectives: To study and compare the effect of amlodipine, bisoprolol and fixed dose combination of amlodipine + bisoprolol on blood pressure in stage-2 essential hypertensive patients. Methods: The present study was carried out in Department of Pharmacology in collaboration with Department of Medicine at Government Medical College and Hospital, Aurangabad. Results and Conclusion : Amlodipine + bisoprolol in fixed dose combination have showed significant blood pressure control in patients of stage-2 essential hypertension and the antihypertensive effect was greater than individual monotherapy study groups.

  19. Distinct patterns of blood-stage parasite antigens detected by plasma IgG subclasses from individuals with different level of exposure to Plasmodium falciparum infections

    DEFF Research Database (Denmark)

    Olesen, Cathrine Holm; Brahimi, Karima; Vandahl, Brian

    2010-01-01

    then gradually develop into protective response dominated by cytophilic IgG1 and IgG3 antibodies. METHODS: Naturally occurring IgG antibodies against P. falciparum blood-stage antigens were analysed from plasma samples collected from four groups of individuals differing in age and level of exposure to P....... falciparum infections. Western Blot profiling of blood-stage parasite antigens displaying reactivity with individual plasma samples in terms of their subclass specificities was conducted. Parasite antigens detected by IgG were grouped based on their apparent molecular sizes resolved by SDS-PAGE as high...... groups of individuals with different levels of exposure to P. falciparum infections. RESULTS: IgG4 and IgM antibodies in plasma samples from all groups detected very few parasite antigens. IgG2 antibodies from all groups detected a common pattern of high molecular weight parasite antigens. Cytophilic Ig...

  20. A high force of plasmodium vivax blood-stage infection drives the rapid acquisition of immunity in papua new guinean children.

    Directory of Open Access Journals (Sweden)

    Cristian Koepfli

    Full Text Available When both parasite species are co-endemic, Plasmodium vivax incidence peaks in younger children compared to P. falciparum. To identify differences in the number of blood stage infections of these species and its potential link to acquisition of immunity, we have estimated the molecular force of blood-stage infection of P. vivax ((molFOB, i.e. the number of genetically distinct blood-stage infections over time, and compared it to previously reported values for P. falciparum.P. vivax (molFOB was estimated by high resolution genotyping parasites in samples collected over 16 months in a cohort of 264 Papua New Guinean children living in an area highly endemic for P. falciparum and P. vivax. In this cohort, P. vivax episodes decreased three-fold over the age range of 1-4.5 years.On average, children acquired 14.0 new P. vivax blood-stage clones/child/year-at-risk. While the incidence of clinical P. vivax illness was strongly associated with mol FOB (incidence rate ratio (IRR = 1.99, 95% confidence interval (CI95 [1.80, 2.19], (molFOB did not change with age. The incidence of P. vivax showed a faster decrease with age in children with high (IRR = 0.49, CI95 [0.38, 0.64] p<0.001 compared to those with low exposure (IRR = 0.63, CI95[0.43, 0.93] p = 0.02.P. vivax (molFOB is considerably higher than P. falciparum (molFOB (5.5 clones/child/year-at-risk. The high number of P. vivax clones that infect children in early childhood contribute to the rapid acquisition of immunity against clinical P. vivax malaria.

  1. Nicotine vaccines for smoking cessation-present and future

    Directory of Open Access Journals (Sweden)

    Richa

    2013-01-01

    Full Text Available Background: Worldwide tobacco is the leading cause of preventable death. Anew treatment in smoking cessation and relapse prevention is nicotine vaccination which is based on active immunization against the nicotine molecule. This article aimed to review the mechanism of action, current status of research and future aspects for the development of vaccines against nicotine. Materials & Method: The literature search of publications indexed was carried out in PubMed, Medline, Google scholar databases. Total 25 animal trials, human trials under various phases of clinical trials, unpublished document and cross-sectional survey were reviewed. Results: This immunization will act on immune system to produce nicotine-specific antibodies that sequester nicotine in the blood stream, after inhaling tobacco products. Nicotine vaccines are irreversible, provide protection over years and need booster injections. Efficiency of the vaccines is directly related to the antibody levels which help to optimize the vaccine effect. Nicotine vaccines are today in an advanced stage of clinical evaluation trials. Conclusions: Though, nicotine vaccine has considerable therapeutic potential, they do not target the non pharmacological factors that maintain tobacco dependence. So combination of nicotine vaccine with behavioral interventions would be effective mode to motivate abstinence from tobacco use.

  2. Developmental stages of fish blood flukes, Cardicola forsteri and Cardicola opisthorchis (Trematoda: Aporocotylidae), in their polychaete intermediate hosts collected at Pacific bluefin tuna culture sites in Japan.

    Science.gov (United States)

    Ogawa, Kazuo; Shirakashi, Sho; Tani, Kazuki; Shin, Sang Phil; Ishimaru, Katsuya; Honryo, Tomoki; Sugihara, Yukitaka; Uchida, Hiro'omi

    2017-02-01

    Farming of Pacific bluefin tuna (PBT), Thunnus orientalis, is a rapidly growing industry in Japan. Aporocotylid blood flukes of the genus Cardicola comprising C. orientalis, C. opisthorchis and C. forsteri are parasites of economic importance for PBT farming. Recently, terebellid polychaetes have been identified as the intermediate hosts for all these parasites. We collected infected polychaetes, Terebella sp., the intermediate host of C. opisthorchis, from ropes and floats attached to tuna cages in Tsushima, Nagasaki Prefecture, Japan. Also, Neoamphitrite vigintipes (formerly as Amphitrite sp. sensu Shirakashi et al., 2016), the intermediate host of C. forsteri, were collected from culture cages in Kushimoto, Wakayama Prefecture, Japan. The terebellid intermediate hosts harbored the sporocysts and cercariae in their body cavity. Developmental stages of these blood flukes were molecularly identified using species specific PCR primers. In this paper, we describe the cercaria and sporocyst stages of C. opisthorchis and C. forsteri and compare their morphological characteristics among three Cardicola blood flukes infecting PBT. We also discuss phylogenetic relations of the six genera of the terebellid intermediate hosts (Artacama, Lanassa, Longicarpus, Terebella, Nicolea and Neoamphitrite) of blood flukes infecting marine fishes, based on their morphological characters. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  3. Adjuvant ganglioside GM2-KLH/QS-21 vaccination versus observation after resection of primary tumor > 1.5 mm in patients with stage II melanoma

    DEFF Research Database (Denmark)

    Eggermont, Alexander M M; Suciu, Stefan; Rutkowski, Piotr

    2013-01-01

    The GM2 ganglioside is an antigen expressed in the majority of melanomas. The GM2-KLH/QS-21 vaccine induces high immunoglobulin M (IgM) and IgG antibody responses. The EORTC 18961 trial compared the efficacy of GM2-KLH/QS-21 vaccination versus observation....

  4. Vaccines as Epidemic Insurance

    Directory of Open Access Journals (Sweden)

    Mark V. Pauly

    2017-10-01

    Full Text Available This paper explores the relationship between the research for and development of vaccines against global pandemics and insurance. It shows that development in advance of pandemics of a portfolio of effective and government-approved vaccines does have some insurance properties: it requires incurring costs that are certain (the costs of discovering, developing, and testing vaccines in return for protection against large losses (if a pandemic treatable with one of the vaccines occurs but also with the possibility of no benefit (from a vaccine against a disease that never reaches the pandemic stage. It then argues that insurance against the latter event might usefully be offered to organizations developing vaccines, and explores the benefits of insurance payments to or on behalf of countries who suffer from unpredictable pandemics. These ideas are then related to recent government, industry, and philanthropic efforts to develop better policies to make vaccines against pandemics available on a timely basis.

  5. MALARIA VACCINE: MYTH OR REALITY?

    African Journals Online (AJOL)

    Femi Olaleye

    first synthetic vaccine (Spf 66) made up in part by the CSP- 1. Human vaccine trials are also reported to have been successful. (Amador et. al., 1992). Erythrocyte Stage Antigens SPF 66. This is the first synthetically produced malaria vaccine. It is made up of a combination of three peptides (35.1, 55.1 and 83.1) whose ...

  6. Identification of Stages of Erythroid Differentiation in Bone Marrow and Erythrocyte Subpopulations in Blood Circulation that Are Preferentially Lost in Autoimmune Hemolytic Anemia in Mouse

    Science.gov (United States)

    Chatterjee, Sreoshi; Bhardwaj, Nitin; Saxena, Rajiv K.

    2016-01-01

    Repeated weekly injections of rat erythrocytes produced autoimmune hemolytic anemia (AIHA) in C57BL/6 mice after 5–6 weeks. Using the double in vivo biotinylation (DIB) technique, recently developed in our laboratory, turnover of erythrocyte cohorts of different age groups during AIHA was monitored. Results indicate a significant decline in the proportion of reticulocytes, young and intermediate age groups of erythrocytes, but a significant increase in the proportion of old erythrocytes in blood circulation. Binding of the autoantibody was relatively higher to the young erythrocytes and higher levels of intracellular reactive oxygen species (ROS) were also seen in these cells. Erythropoietic activity in the bone marrows and the spleen of AIHA induced mice was examined by monitoring the relative proportion of erythroid cells at various stages of differentiation in these organs. Cells at different stages of differentiation were enumerated flow cytometrically by double staining with anti-Ter119 and anti-transferrin receptor (CD71) monoclonal antibodies. Erythroid cells in bone marrow declined significantly in AIHA induced mice, erythroblast C being most affected (50% decline). Erythroblast C also recorded high intracellular ROS level along with increased levels of membrane-bound autoantibody. No such decline was observed in spleen. A model of AIHA has been proposed indicating that binding of autoantibodies may not be a sufficient condition for destruction of erythroid cells in bone marrow and in blood circulation. Last stage of erythropoietic differentiation in bone marrow and early stages of erythrocytes in blood circulation are specifically susceptible to removal in AIHA. PMID:27870894

  7. Identification of Stages of Erythroid Differentiation in Bone Marrow and Erythrocyte Subpopulations in Blood Circulation that Are Preferentially Lost in Autoimmune Hemolytic Anemia in Mouse.

    Directory of Open Access Journals (Sweden)

    Sreoshi Chatterjee

    Full Text Available Repeated weekly injections of rat erythrocytes produced autoimmune hemolytic anemia (AIHA in C57BL/6 mice after 5-6 weeks. Using the double in vivo biotinylation (DIB technique, recently developed in our laboratory, turnover of erythrocyte cohorts of different age groups during AIHA was monitored. Results indicate a significant decline in the proportion of reticulocytes, young and intermediate age groups of erythrocytes, but a significant increase in the proportion of old erythrocytes in blood circulation. Binding of the autoantibody was relatively higher to the young erythrocytes and higher levels of intracellular reactive oxygen species (ROS were also seen in these cells. Erythropoietic activity in the bone marrows and the spleen of AIHA induced mice was examined by monitoring the relative proportion of erythroid cells at various stages of differentiation in these organs. Cells at different stages of differentiation were enumerated flow cytometrically by double staining with anti-Ter119 and anti-transferrin receptor (CD71 monoclonal antibodies. Erythroid cells in bone marrow declined significantly in AIHA induced mice, erythroblast C being most affected (50% decline. Erythroblast C also recorded high intracellular ROS level along with increased levels of membrane-bound autoantibody. No such decline was observed in spleen. A model of AIHA has been proposed indicating that binding of autoantibodies may not be a sufficient condition for destruction of erythroid cells in bone marrow and in blood circulation. Last stage of erythropoietic differentiation in bone marrow and early stages of erythrocytes in blood circulation are specifically susceptible to removal in AIHA.

  8. Daily blueberry consumption improves blood pressure and arterial stiffness in postmenopausal women with pre- and stage 1-hypertension: a randomized, double-blind, placebo-controlled clinical trial.

    Science.gov (United States)

    Johnson, Sarah A; Figueroa, Arturo; Navaei, Negin; Wong, Alexei; Kalfon, Roy; Ormsbee, Lauren T; Feresin, Rafaela G; Elam, Marcus L; Hooshmand, Shirin; Payton, Mark E; Arjmandi, Bahram H

    2015-03-01

    Postmenopausal women have a high prevalence of hypertension and often develop arterial stiffness thereby increasing cardiovascular disease risk. Although antihypertensive drug therapies exist, increasing numbers of people prefer natural therapies. In vivo studies and a limited number of clinical studies have demonstrated the antihypertensive and vascular-protective effects of blueberries. To examine the effects of daily blueberry consumption for 8 weeks on blood pressure and arterial stiffness in postmenopausal women with pre- and stage 1-hypertension. This was an 8-week, randomized, double-blind, placebo-controlled clinical trial. Forty-eight postmenopausal women with pre- and stage 1-hypertension recruited from the greater Tallahassee, FL, area participated. Participants were randomly assigned to receive either 22 g freeze-dried blueberry powder or 22 g control powder. Resting brachial systolic and diastolic blood pressures were evaluated and arterial stiffness was assessed using carotid-femoral pulse wave velocity and brachial-ankle pulse wave velocity. C-reactive protein, nitric oxide, and superoxide dismutase were measured at baseline, 4 weeks, and 8 weeks. Statistical analysis was performed using a split plot model of repeated measures analysis of variance. After 8 weeks, systolic blood pressure and diastolic blood pressure (131±17 mm Hg [Pblueberry powder group, whereas there were no changes in the group receiving the control powder. Nitric oxide levels were greater (15.35±11.16 μmol/L; Pblueberry powder group at 8 weeks compared with baseline values (9.11±7.95 μmol/L), whereas there were no changes in the control group. Daily blueberry consumption may reduce blood pressure and arterial stiffness, which may be due, in part, to increased nitric oxide production. Copyright © 2015 Academy of Nutrition and Dietetics. Published by Elsevier Inc. All rights reserved.

  9. Atypical hodgkin and reed-sternberg cells in peripheral blood of a patient with advanced stage of Hodgkin's disease - a case report

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    Milošević Rajko

    2003-01-01

    Full Text Available The occurrence of abnormal Hodgkin's and Reed-Sternberg cells in the peripheral blood in a patient suffering from Hodgkin's disease has been noticed exceptionally rare in a previous period, and especially rare in last ten years primarily due to successfull treatment of this disease. The presence of atypical mononuclear cells in peripheral blood which cytomorphologically resembled Reed-Sternberg cells was registered in 8 patients till 1966. During the last decade, the presence of atypical mononuclear cells in the peripheral blood was used for their isolation cultivation, and detailed immunophenotypic and genetic analysis. The analysis of mononuclear cells in rare patients with Hodgkin's disease was established that they belong to the B-lymphoid cells with expression of CD30 and CD15 antigens. The examination of presence of Hodgkin's cells in the peripheral blood of patients with Hodgkin's disease is important for patients with advanced stage of the disease in which autologous stem cell transplantation and high dose chmeotherapy is planned. The authors present a 33-year-old patient, who noticed enlarged neck lymph nodes in September 2000, high temperature and loss in weight. On physical examination enlarged neck lymph nodes 5x8 cm and hepatosplenomegaly were found. There was anemia and thrombo-cytopenia, and normal WBC count with 24% of lymphoid elements in differential formula. On histologic examination of lymph nodes Hodgkin¢s disease, type nodular sclerosis with mixed cellularity was found. Histology of bone marrow showed nodal lymphomatous infiltration. Immunohistochemistry with monoclonal antibodies of concentrate of peripheral blood cells showed expression of CD30+ and CD15+, immunophenotypically and morphologically matching Reed-Sternberg cells. Cytogentic analysis of mononuclear cells of the bone marrow showed normal karyotype. The patient was in clinical stage IV/V of the disease and chemotherapy with 9 cycles of ABVD+Mp protocol was

  10. Immunological changes in canine peripheral blood leukocytes triggered by immunization with first or second generation vaccines against canine visceral leishmaniasis.

    Science.gov (United States)

    Araújo, Márcio Sobreira Silva; de Andrade, Renata Aline; Sathler-Avelar, Renato; Magalhães, Camila Paula; Carvalho, Andréa Teixeira; Andrade, Mariléia Chaves; Campolina, Sabrina Sidney; Mello, Maria Norma; Vianna, Leonardo Rocha; Mayrink, Wilson; Reis, Alexandre Barbosa; Malaquias, Luiz Cosme Cotta; Rocha, Luciana Morais; Martins-Filho, Olindo Assis

    2011-05-15

    In this study, we summarized the major phenotypic/functional aspects of circulating leukocytes following canine immunization with Leishvaccine and Leishmune®. Our findings showed that Leishvaccine triggered early changes in the innate immunity (neutrophils and eosinophils) with late alterations on monocytes. Conversely, Leishmune(®) induced early phenotypic changes in both, neutrophils and monocytes. Moreover, Leishvaccine triggered mixed activation-related phenotypic changes on T-cells (CD4+ and CD8+ and B-lymphocytes, whereas Leishmune(®) promoted a selective response, mainly associated with CD8+ T-cell activation. Mixed cytokine profile (IFN-γ/IL-4) was observed in Leishvaccine immunized dogs whereas a selective pro-inflammatory pattern (IFN-γ/NO) was induced by Leishmune® vaccination. The distinct immunological profile triggered by Leishvaccine and Leishmune® may be a direct consequence of the distinct biochemical composition of these immunobiological, i.e. complex versus purified Leishmania antigen along with Bacillus Calmette-Guérin (BCG) versus saponin adjuvant. Both immunobiologicals are able to activate phagocytes and CD8+ T-cells and therefore could be considered as a putative vaccines against canine visceral leishmaniasis (CVL). Copyright © 2011 Elsevier B.V. All rights reserved.

  11. Safety and immunogenicity of RTS,S/AS01 malaria vaccine in infants and children with WHO stage 1 or 2 HIV disease: a randomised, double-blind, controlled trial.

    Science.gov (United States)

    Otieno, Lucas; Oneko, Martina; Otieno, Walter; Abuodha, Joseph; Owino, Emmanuel; Odero, Chris; Mendoza, Yolanda Guerra; Andagalu, Ben; Awino, Norbert; Ivinson, Karen; Heerwegh, Dirk; Otsyula, Nekoye; Oziemkowska, Maria; Usuf, Effua Abigail; Otieno, Allan; Otieno, Kephas; Leboulleux, Didier; Leach, Amanda; Oyieko, Janet; Slutsker, Laurence; Lievens, Marc; Cowden, Jessica; Lapierre, Didier; Kariuki, Simon; Ogutu, Bernhards; Vekemans, Johan; Hamel, Mary J

    2016-10-01

    Malaria remains a major global public health concern, especially in sub-Saharan Africa. The RTS,S/AS01 malaria candidate vaccine was reviewed by the European Medicines Agency and received a positive scientific opinion; WHO subsequently recommended pilot implementation in sub-Saharan African countries. Because malaria and HIV overlap geographically, HIV-infected children should be considered for RTS,S/AS01 vaccination. We therefore aimed to assess the safety of RTS,S/AS01 in HIV-infected children at two sites in western Kenya. We did a randomised, double-blind, controlled trial at the clinical trial sites of the Kenya Medical Research Institute (KEMRI)-Walter Reed Army Institute of research in Kisumu and the KEMRI/US Centers for Disease Control and Prevention in Siaya. Eligible participants were infants and children aged from 6 weeks to 17 months with WHO stage 1 or 2 HIV disease (documented positive by DNA PCR), whether or not they were receiving antiretroviral therapy (ART). We randomly assigned participants (1:1) to receive three doses of either RTS,S/AS01 or rabies vaccine (both 0·5 mL per dose by intramuscular injection), given once per month at 0, 1, and 2 months. We did the treatment allocation using a web-based central randomisation system stratified by age (6 weeks-4 months, 5-17 months), and by baseline CD4% (vaccine recipient, their parent or carer, the funder, and investigators responsible for the assessment of endpoints were all masked to treatment allocation (only staff responsible for the preparation and administration of the vaccines were aware of the assignment and these individuals played no other role in the study). We provided ART, even if the participants were not receiving ART before the study, and daily co-trimoxazole for prevention of opportunistic infections. The primary outcome was the occurrence of serious adverse events until 14 months after dose 1 of the vaccine, assessed in the intention-to-treat population. This trial was registered

  12. Circulation of HIV antigen in blood according to stage of infection, risk group, age and geographic origin

    NARCIS (Netherlands)

    Goudsmit, J.; Paul, D. A.

    1987-01-01

    Human immunodeficiency virus antigen (HIV-ag) was determined by enzyme immunoassay (EIA) in HIV-antibody (anti-HIV) positive as well as pre-anti-HIV seroconversion sera and the results analysed according to stage of infection, risk group, age and geographic origin. Eleven (19%) of 58 homosexual men

  13. Black blood T1rho MR imaging may diagnose early stage liver fibrosis: a proof-of-principle study with rat biliary duct ligation model.

    Science.gov (United States)

    Koon, Chi-Man; Zhang, Xin; Chen, Weitian; Chu, Eagle Siu Hong; San Lau, Clara Bik; Wáng, Yì-Xiáng J

    2016-08-01

    To explore black blood T1rho (T1ρ) liver imaging and investigate the earliest stage when biliary duct ligation (BDL) induced liver fibrosis can be diagnosed. MR was performed at 3 Tesla. A T1ρ prepared 2D fast spin echo (FSE) sequence with acquisition of four spin lock times (TSLs: 1, 10, 30, and 50 msec) and spin-lock frequency of 500 Hz was applied. Inherent black blood effect of FSE and double inversion recovery (DIR) achieved blood signal suppression, and 3 axial sections per liver were obtained. Male Sprague-Dawley rats were scanned at baseline (n=32), and on day-3 (n=13), day-5 (n=11), day-7 (n=10), day-10 (n=4) respectively after BDL. Hematoxylin-eosin (HE) and picrosirius red staining liver histology was obtained at these time points. The physiological liver parenchyma T1ρ was 38.38±1.53 msec (range, 36.05-41.53 msec). Liver T1ρ value elevated progressively after BDL. On day-10 after BDL all experimental animals can be separated from normal liver based on T1ρ measurement with lowest value being 42.82 msec. Day-7 and day-10 liver resembled METAVIR stage-F1/F2 fibrosis, and fibrous area counted for 0.22%±0.13% and 0.38%±0.44% of liver parenchyma area, respectively. This study provides the first proof-of-principle that T1ρ might diagnose early stage liver fibrosis.

  14. Distinct patterns of blood-stage parasite antigens detected by plasma IgG subclasses from individuals with different level of exposure to Plasmodium falciparum infections

    Directory of Open Access Journals (Sweden)

    Højrup Peter

    2010-10-01

    Full Text Available Abstract Background In endemic regions naturally acquired immunity against Plasmodium falciparum develops as a function of age and exposure to parasite infections and is known to be mediated by IgG. The targets of protective antibodies remain to be fully defined. Several immunoepidemiological studies have indicated an association of cytophilic anti-parasite IgG with protection against malaria. It has been hypothesized that the initial antibody responses against parasite antigens upon first few Plasmodium falciparum infections is dominated by non-protective IgG2/IgG4 and IgM antibodies, which then gradually develop into protective response dominated by cytophilic IgG1 and IgG3 antibodies. Methods Naturally occurring IgG antibodies against P. falciparum blood-stage antigens were analysed from plasma samples collected from four groups of individuals differing in age and level of exposure to P. falciparum infections. Western Blot profiling of blood-stage parasite antigens displaying reactivity with individual plasma samples in terms of their subclass specificities was conducted. Parasite antigens detected by IgG were grouped based on their apparent molecular sizes resolved by SDS-PAGE as high molecular weight (≥ 70 kDa or low molecular weight (P. falciparum infections. Results IgG4 and IgM antibodies in plasma samples from all groups detected very few parasite antigens. IgG2 antibodies from all groups detected a common pattern of high molecular weight parasite antigens. Cytophilic IgG subclasses in plasma samples from individuals with higher levels of exposure to P. falciparum infections distinctly detected higher numbers of low molecular weight parasite antigens. Conclusions In the present study, there was no evidence for switching of antibody responses from non-cytophilic to cytophilic subclasses against blood-stage parasite antigens as a likely mechanism for induction of protective immunity against malaria.

  15. No effect of human serum and erythrocytes enriched in n-3 fatty acids by oral intake on Plasmodium falciparum blood stage parasites in vitro

    DEFF Research Database (Denmark)

    Abu-Zeid, Y A; Hansen, H S; Jakobsen, P H

    1993-01-01

    To examine the effect of n-3 polyunsaturated fatty acids (n-3 PUFA) on the erythrocytic growth of Plasmodium falciparum, serum and erythrocytes were separated from blood of a healthy donor before and after he had taken fish oil capsules for 8 days. Such intake supplied an amount of eicosapentaenoic...... acid (EPA, 20:5n-3) of 3.5 g/d and docosahexaenoic acid (DHA, 22:6n-3) of 2.5 g/d and 24 mg/d of total tocopherol. Post-intake fish oil serum (post-s) and erythrocytes (post-e) were tested in vitro for inhibitory activity against blood stages of P. falciparum compared with pre-intake serum (pre...

  16. The Impact of Hemodialysis Frequency and Duration on Blood Pressure Management and Quality of Life in End-Stage Renal Disease Patients

    Science.gov (United States)

    Shafiee, Mohammad Ali; Chamanian, Pouyan; Shaker, Pouyan; Shahideh, Yasmin; Broumand, Behrooz

    2017-01-01

    Cardiovascular complications are the most prominent causes of morbidity and mortality among chronic kidney disease (CKD) and end-stage renal disease (ESRD) patients undergoing standard hemodialysis (HD) therapy. Cardiovascular disease risk is increased significantly through persistent hypertension and blood pressure (BP) fluctuation, which are the most common complications of CKD. It was hypothesized that an extended approach with lengthier and more frequent dialysis sessions, referred to in this paper as “extended hemodialysis” (EHD), can potentially lower and stabilize blood pressure, and consequently reduce the rate of morbidity and mortality. A greater reduction of volume (salt and water) with higher frequency can improve patient quality of life (QOL). Eleven papers, including clinical trials and systematic reviews were chosen and analyzed. The extracted data was used to evaluate the change in blood pressure levels between standard HD and EHD. Overall, the studies showed that EHD resulted in improved blood pressure management; therefore, we concluded that there will be a decrease in cardiovascular disease risk, stroke, and morbidity and mortality rate. There will be also an improvement in patient QOL due to beneficial effects of the EHD. PMID:28869490

  17. Features of cerebral blood flow, cardiac arrhythmias and conduction disturbances in patients with essential hypertension stage II associated with occlusive and stenotic lesions of brachiocephalic arteries

    Directory of Open Access Journals (Sweden)

    Vizir V.A.

    2015-09-01

    Full Text Available Arterial hypertension is the most common disease of the cardiovascular system in industrially advanced countries. With the aim to determine the characteristics of cerebral blood flow, disorders of cardiac rhythm and conduction in patients with stage 2 hypertension associated with stenotic and occlusive lesions of brachiocephalic arteries, cerebral blood flow indicators were studied in 87 patients using duplex scanning of extracranial arteries and Holter ECG monitoring. It was established that linear blood flow velocity was considerably decreased in the basins of the internal and common carotid artery; cerebral blood flow asymmetry was present in the course of the internal carotid artery. Evidence-based differences in structure of arrhythmias were revealed by single and paired ventricular extrasystoles, as well as episodes of unstable ventricular tachycardia. All this indicates the progressive decrease of elasticity and tonicity of vessel walls, intensified rigidity and sinuosity of carotid arteries, more severe disorders of cardiac rhythm and conduction in case of simultaneous hypertension and atherosclerotic lesion of brachiocephalic arteries.

  18. 'Who's who' in renal sphaerosporids (Bivalvulida: Myxozoa) from common carp, Prussian carp and goldfish - molecular identification of cryptic species, blood stages and new members of Sphaerospora sensu stricto

    Czech Academy of Sciences Publication Activity Database

    Holzer, Astrid S.; Bartošová, Pavla; Pecková, Hana; Tyml, Tomáš; Atkinson, S.; Bartholomew, J.; Sipos, D.; Eszterbauer, E.; Dyková, Iva

    2013-01-01

    Roč. 140, JAN 2013 (2013), s. 46-60 ISSN 0031-1820 R&D Projects: GA ČR(CZ) GPP506/11/P724; GA ČR GBP505/12/G112 Grant - others:Hungarian Scientifc Research Fund(HU) OTKA K75873 Institutional research plan: CEZ:AV0Z60220518 Institutional support: RVO:60077344 Keywords : Sphaerospora * Myxozoa * cyprinid * morphometry * cryptic speciation * ribosomal DNA * molecular identification * blood stages * multi-species infection Subject RIV: GJ - Animal Vermins ; Diseases, Veterinary Medicine Impact factor: 2.350, year: 2013

  19. The influence of Maloprim chemoprophylaxis on cellular and humoral immune responses to Plasmodium falciparum asexual blood stage antigens in schoolchildren living in a malaria endemic area of Mozambique

    DEFF Research Database (Denmark)

    Hogh, B; Thompson, R; Lobo, V

    1994-01-01

    We examined the impact of chemoprophylaxis on the cellular and humoral immune responses to polypeptides of the asexual Plasmodium falciparum blood stage antigens, the glutamate rich protein GLURP and Pf155/RESA, both of which in previous field studies have been identified as potentially protective...... chemoprophylaxis successfully reduced the parasite rate during the rainy season from 43% to 4%, and during the dry season from 18% to 0%. Chemoprophylaxis may therefore have a useful role in combination with another partially effective malaria control measure such as insecticide-impregnated bed nets or a malaria...

  20. Intravenous Infusion of Magnesium Chloride Improves Epicenter Blood Flow during the Acute Stage of Contusive Spinal Cord Injury in Rats

    Science.gov (United States)

    Muradov, Johongir M.

    2013-01-01

    Abstract Vasospasm, hemorrhage, and loss of microvessels at the site of contusive or compressive spinal cord injury lead to infarction and initiate secondary degeneration. Here, we used intravenous injection of endothelial-binding lectin followed by histology to show that the number of perfused microvessels at the injury site is decreased by 80–90% as early as 20 min following a moderate T9 contusion in adult female rats. Hemorrhage within the spinal cord also was maximal at 20 min, consistent with its vasoconstrictive actions in the central nervous system (CNS). Microvascular blood flow recovered to up to 50% of normal volume in the injury penumbra by 6 h, but not at the epicenter. A comparison with an endothelial cell marker suggested that many microvessels fail to be reperfused up to 48 h post-injury. The ischemia was probably caused by vasospasm of vessels penetrating the parenchyma, because repeated Doppler measurements over the spinal cord showed a doubling of total blood flow over the first 12 h. Moreover, intravenous infusion of magnesium chloride, used clinically to treat CNS vasospasm, greatly improved the number of perfused microvessels at 24 and 48 h. The magnesium treatment seemed safe as it did not increase hemorrhage, despite the improved parenchymal blood flow. However, the treatment did not reduce acute microvessel, motor neuron or oligodendrocyte loss, and when infused for 7 days did not affect functional recovery or spared epicenter white matter over a 4 week period. These data suggest that microvascular blood flow can be restored with a clinically relevant treatment following spinal cord injury. PMID:23302047

  1. Results of a study of the reactogenic and immunogenic properties of live anti-poliomyelitis vaccine.

    Science.gov (United States)

    SMORODINTSEV, A A; DAVIDENKOVA, E F; DROBYSHEVSKA YA, A I; ILYENKO, V I; GOREV, N E; KURNOSOVA, L M; KLYUCHAREVA, T E

    1959-01-01

    The authors have studied the harmlessness and immunogenic properties of live poliomyelitis vaccine made in Leningrad from Sabin strains of low pathogenicity for monkeys. More than 20 000 children of pre-school (6 months to 3 years) and school age (7-14 years) were each given 100 000 tissue-culture infective doses of virus of types 1, 2 and 3, injected either in three stages at monthly intervals in the form of monovaccines, or in two stages, a monovaccine of type 1 being followed after a month's interval by injection of a divalent vaccine of types 2 and 3. The vaccination caused no symptoms of lesions of the central nervous system or other organs. In the blood of the inoculated children there was a regular build-up of virus-neutralizing antibodies to the serotypes mentioned, the intensity of which depended on the antibody level before vaccination and was in a constant relationship to the multiplication of the virus in the intestinal canal. The antibody titre was maintained at high levels for 6-9 months after immunization and fell a little after 12-18 months. The vaccinal virus is easily transferred from vaccinated children to contact groups, which are gradually vaccinated by this natural means.Lengthy and numerous passages of vaccinal strains through the intestinal canal of normal, susceptible children showed that strains may periodically appear which have a higher neurotropic activity for monkeys. This activity, however, did not increase in subsequent passage and returned to the initial level.

  2. Towards functional antibody-based vaccines to prevent pre-erythrocytic malaria infection.

    Science.gov (United States)

    Sack, Brandon; Kappe, Stefan H I; Sather, D Noah

    2017-05-01

    An effective malaria vaccine would be considered a milestone of modern medicine, yet has so far eluded research and development efforts. This can be attributed to the extreme complexity of the malaria parasites, presenting with a multi-stage life cycle, high genome complexity and the parasite's sophisticated immune evasion measures, particularly antigenic variation during pathogenic blood stage infection. However, the pre-erythrocytic (PE) early infection forms of the parasite exhibit relatively invariant proteomes, and are attractive vaccine targets as they offer multiple points of immune system attack. Areas covered: We cover the current state of and roadblocks to the development of an effective, antibody-based PE vaccine, including current vaccine candidates, limited biological knowledge, genetic heterogeneity, parasite complexity, and suboptimal preclinical models as well as the power of early stage clinical models. Expert commentary: PE vaccines will need to elicit broad and durable immunity to prevent infection. This could be achievable if recent innovations in studying the parasites' infection biology, rational vaccine selection and design as well as adjuvant formulation are combined in a synergistic and multipronged approach. Improved preclinical assays as well as the iterative testing of vaccine candidates in controlled human malaria infection trials will further accelerate this effort.

  3. Changes in some pro-and anti-inflammatory cytokines produced by bovine peripheral blood mononuclear cells following foot and mouth disease vaccination

    Directory of Open Access Journals (Sweden)

    N. Delirezh

    2016-09-01

    Full Text Available Interleukin (IL-17 is exclusively produced by CD4 helper T-cells upon activation. It most often acts as a pro-inflammatory cytokine, which stimulates the release of pro-inflammatory cytokines IL-6, IL-8, TNF-α, and granulocyte-macrophage colony-stimulating factor (GM-CSF. In this study, we studied the in-vitro IL-17 response to specific antigens and a variety of mitogens and compared the IL-17 response to IL-2, IL-4, IL-5, IL-6, IL-10, and IFN-γ responses. We used a foot and mouth disease (FMD vaccine as specific antigens and mitogens (phytohemagglutinin [PHA], pokeweed mitogen [PWM], and concanavalin A [Con A] to stimulate peripheral blood mononuclear cells (PBMCs of vaccinated calves. Cell culture supernatant was harvested and analyzed for cytokines, using commercially available bovine ELISA kits. The mitogens induced a significant increase in IL-17 production. IL-17 was produced at high levels in response to the T cell-stimulated mitogens, PHA, and Con A, and at low levels in response to PWM mitogens. In contrast, level of the produced IL-17 cytokines in response to the FMDV antigens was lower as compared to those produced by mitogens. The FMDV antigens and mitogens significantly increased IL-17 production. There was not a correlation between IL-17 production and type-1 cytokine, IFN-γ, and IL-2, while there was a correlation between type-2 cytokine, IL-4, and IL-5 at either cytokine level produced by PBMCs stimulated by FMDV antigens. Moreover, there was an interaction between IL-17 and IL-6, that is, as IL-6 cytokine level elevated or diminished, IL-17 cytokine level increased or decreased, as well.

  4. Prevalence of Pertussis Antibodies in Maternal Blood, Cord Serum, and Infants From Mothers With and Those Without Tdap Booster Vaccination During Pregnancy in Argentina.

    Science.gov (United States)

    Fallo, Aurelia A; Neyro, Silvina E; Manonelles, Gabriela V; Lara, Claudia; Hozbor, Daniela; Zintgraff, Jonathan; Mazzeo, Silvina; Davison, Héctor E; González, Susana; Zapulla, Estella; Canle, Oscar; Huespe, Miguel; Galas, Marcelo; López, Eduardo L

    2018-02-19

    Morbidity and mortality rates for pertussis in infants are high because disease often occurs before the onset of routine immunization or in those who do not complete a primary immunization series. Pertussis immunization is recommended during pregnancy to achieve antibody levels sufficient to protect young infants. To our knowledge, no previous reports of maternal pertussis immunization results in Latin America exist in the literature. This study compared pertussis antibody levels in newborns from mothers who received or did not receive a tetanus-diphtheria-acellular pertussis vaccination (TdapV) during pregnancy. Each mother's level of immunoglobulin G antibodies against pertussis toxin (IgG-PT) was measured with a validated, specific enzyme-linked immunosorbent assay (ELISA). Paired mother and cord serum samples were compared in 105 mothers with and 99 mothers without a TdapV. At birth, the mothers with and those without a TdapV had serum IgG-PT geometric mean concentrations (GMCs) of 35.1 and 9.8 ELISA units (EU)/mL, respectively (P Vaccination timing did not affect the IgG-PT GMC at birth. Placental antibody transference efficiencies (measured as the ratio of the cord blood GMC to the maternal GMC) were 1.46 and 1.18 for mothers with and those without a TdapV, respectively. The IgG-PT GMCs were 17.7 EU/mL in 36 infants in their first month of life and 11.6 EU/mL in 32 infants in their second month of life. Women who received a TdapV during pregnancy had significantly a higher serum/cord IgG-PT concentration at birth than mothers who did not receive a TdapV. Timing of the immunization was not correlated with antibody concentrations. Infants born to immunized mothers had significantly higher antibody levels during their first 2 months of life.

  5. Three-dimensional visualisation of developmental stages of an apicomplexan fish blood parasite in its invertebrate host

    Directory of Open Access Journals (Sweden)

    Hayes Polly M

    2011-11-01

    Full Text Available Abstract Background Although widely used in medicine, the application of three-dimensional (3D imaging to parasitology appears limited to date. In this study, developmental stages of a marine fish haemogregarine, Haemogregarina curvata (Apicomplexa: Adeleorina, were investigated in their leech vector, Zeylanicobdella arugamensis; this involved 3D visualisation of brightfield and confocal microscopy images of histological sections through infected leech salivary gland cells. Findings 3D assessment demonstrated the morphology of the haemogregarine stages, their spatial layout, and their relationship with enlarged host cells showing reduced cellular content. Haemogregarine meronts, located marginally within leech salivary gland cells, had small tail-like connections to the host cell limiting membrane; this parasite-host cell interface was not visible in two-dimensional (2D light micrographs and no records of a similar connection in apicomplexan development have been traced. Conclusions This is likely the first account of the use of 3D visualisation to study developmental stages of an apicomplexan parasite in its invertebrate vector. Elucidation of the extent of development of the haemogregarine within the leech salivary cells, together with the unusual connections between meronts and the host cell membrane, illustrates the future potential of 3D visualisation in parasite-vector biology.

  6. Cancer vaccines: from research to clinical practice

    National Research Council Canada - National Science Library

    Bot, Adrian; Obrocea, Mihail; Marincola, Francesco M

    2011-01-01

    ..., for both solid and blood borne cancers. Cancer Vaccines: Challenges and Opportunities in Translation is the first text in the field to bring immunotherapy treatments from the laboratory trial to the bedside for the practicing oncologist. Cancer Vaccines...

  7. Communicating vaccine safety during the development and introduction of vaccines.

    Science.gov (United States)

    Kochhar, Sonali

    2015-01-01

    Vaccines are the best defense available against infectious diseases. Vaccine safety is of major focus for regulatory bodies, vaccine manufacturers, public health authorities, health care providers and the public as vaccines are often given to healthy children and adults as well as to pregnant woman. Safety assessment is critical at all stages of vaccine development. Effective, clear and consistent communication of the risks and benefits of vaccines and advocacy during all stages of clinical research (including the preparation, approvals, conduct of clinical trials through the post marketing phase) is critically important. This needs to be done for all major stakeholders (e.g. community members, Study Team, Health Care Providers, Ministry of Health, Regulators, Ethics Committee members, Public Health Authorities and Policy Makers). Improved stakeholder alignment would help to address some of the concerns that may affect the clinical research, licensing of vaccines and their wide-spread use in immunization programs around the world.

  8. β-Hydroxybutyrate (BHB) and glucose concentrations in the blood of dairy calves as influenced by age, vaccination stress, weaning, and starter intake including evaluation of BHB and glucose markers of starter intake.

    Science.gov (United States)

    Suarez-Mena, F X; Hu, W; Dennis, T S; Hill, T M; Schlotterbeck, R L

    2017-04-01

    The objective of this research was to determine how blood β-hydroxybutyrate (BHB) and glucose are affected by age, time of day, stress, weaning, forced intake restriction, and voluntary starter intake in calves between 1 and 9 wk of age, and to evaluate if either is an acceptable proxy for starter intake. Holstein calves were fed a 27% crude protein, 17% fat milk replacer at 660 g of dry matter daily along with free-choice starter and water. Calves were weaned on d 42. Jugular blood was sampled at 0800, 1200, and 1600 h, and within 5 min of sampling BHB, and glucose concentrations were estimated using test strips (Nova Max Plus meter, Nova Biomedical Corporation, Waltham, MA). Age effects and time of day were estimated by sampling blood weekly (d 6, 13, 20, 27, 34, 41, and 48). To determine vaccination stress, a Pasteurella vaccine was administered after blood sampling at 0800 h on d 36. Effect of voluntary starter intake was tested by selecting calves for low and high intakes (d 35 to 39) and sampling on d 40, 41, 43, and 44. Starter intake restriction was tested by restricting intake in half of the calves and sampling on d 60 and 61. Data were analyzed with repeated measurements in a mixed model procedure with either within-calf effect (day or week) or within-calf effects (hour, and day or week) included in the model. Time of day did not affect blood BHB and glucose in the first 6 wk. Blood BHB was greater in wk 7 versus wk 1 to 6. Blood glucose was greater in the first 5 wk compared with wk 6 and 7. Blood BHB increased and glucose decreased with increasing starter intake. Blood BHB declined due to vaccination, but glucose was unaffected. Starter intake restriction reduced BHB for 3 d and glucose for 2 d after restriction. Both were affected by time of day. Around weaning (d 40 to 44), BHB and glucose increased with increasing starter intake. In this research, neither blood BHB nor glucose was a good proxy for starter intake. Blood BHB was positively and glucose

  9. The march toward malaria vaccines.

    Science.gov (United States)

    Hoffman, Stephen L; Vekemans, Johan; Richie, Thomas L; Duffy, Patrick E

    2015-11-27

    In 2013 there were an estimated 584,000 deaths and 198 million clinical illnesses due to malaria, the majority in sub-Saharan Africa. Vaccines would be the ideal addition to the existing armamentarium of anti-malaria tools. However, malaria is caused by parasites, and parasites are much more complex in terms of their biology than the viruses and bacteria for which we have vaccines, passing through multiple stages of development in the human host, each stage expressing hundreds of unique antigens. This complexity makes it more difficult to develop a vaccine for parasites than for viruses and bacteria, since an immune response targeting one stage may not offer protection against a later stage, because different antigens are the targets of protective immunity at different stages. Furthermore, depending on the life cycle stage and whether the parasite is extra- or intra-cellular, antibody and/or cellular immune responses provide protection. It is thus not surprising that there is no vaccine on the market for prevention of malaria, or any human parasitic infection. In fact, no vaccine for any disease with this breadth of targets and immune responses exists. In this limited review, we focus on four approaches to malaria vaccines, (1) a recombinant protein with adjuvant vaccine aimed at Plasmodium falciparum (Pf) pre-erythrocytic stages of the parasite cycle (RTS,S/AS01), (2) whole sporozoite vaccines aimed at Pf pre-erythrocytic stages (PfSPZ Vaccine and PfSPZ-CVac), (3) prime boost vaccines that include recombinant DNA, viruses and bacteria, and protein with adjuvant aimed primarily at Pf pre-erythrocytic, but also asexual erythrocytic stages, and (4) recombinant protein with adjuvant vaccines aimed at Pf and Plasmodium vivax sexual erythrocytic and mosquito stages. We recognize that we are not covering all approaches to malaria vaccine development, or most of the critically important work on development of vaccines against P. vivax, the second most important cause of

  10. Distinct patterns of blood-stage parasite antigens detected by plasma IgG subclasses from individuals with different level of exposure to Plasmodium falciparum infections.

    Science.gov (United States)

    Olesen, Cathrine Holm; Brahimi, Karima; Vandahl, Brian; Lousada-Dietrich, Susana; Jogdand, Prajakta S; Vestergaard, Lasse S; Dodoo, Daniel; Højrup, Peter; Christiansen, Michael; Larsen, Severin Olesen; Singh, Subhash; Theisen, Michael

    2010-10-26

    In endemic regions naturally acquired immunity against Plasmodium falciparum develops as a function of age and exposure to parasite infections and is known to be mediated by IgG. The targets of protective antibodies remain to be fully defined. Several immunoepidemiological studies have indicated an association of cytophilic anti-parasite IgG with protection against malaria. It has been hypothesized that the initial antibody responses against parasite antigens upon first few Plasmodium falciparum infections is dominated by non-protective IgG2/IgG4 and IgM antibodies, which then gradually develop into protective response dominated by cytophilic IgG1 and IgG3 antibodies. Naturally occurring IgG antibodies against P. falciparum blood-stage antigens were analysed from plasma samples collected from four groups of individuals differing in age and level of exposure to P. falciparum infections. Western Blot profiling of blood-stage parasite antigens displaying reactivity with individual plasma samples in terms of their subclass specificities was conducted. Parasite antigens detected by IgG were grouped based on their apparent molecular sizes resolved by SDS-PAGE as high molecular weight (≥ 70 kDa) or low molecular weight (immunity against malaria.

  11. Vaccines (immunizations) - overview

    Science.gov (United States)

    Vaccinations; Immunizations; Immunize; Vaccine shots; Prevention - vaccine ... component) of the vaccine. VACCINE SCHEDULE The recommended vaccination (immunization) schedule is updated every 12 months by ...

  12. Vaccine hesitancy

    Science.gov (United States)

    Dubé, Eve; Laberge, Caroline; Guay, Maryse; Bramadat, Paul; Roy, Réal; Bettinger, Julie A.

    2013-01-01

    Despite being recognized as one of the most successful public health measures, vaccination is perceived as unsafe and unnecessary by a growing number of individuals. Lack of confidence in vaccines is now considered a threat to the success of vaccination programs. Vaccine hesitancy is believed to be responsible for decreasing vaccine coverage and an increasing risk of vaccine-preventable disease outbreaks and epidemics. This review provides an overview of the phenomenon of vaccine hesitancy. First, we will characterize vaccine hesitancy and suggest the possible causes of the apparent increase in vaccine hesitancy in the developed world. Then we will look at determinants of individual decision-making about vaccination. PMID:23584253

  13. Towards clinical development of a Pfs48/45-based transmission blocking malaria vaccine

    DEFF Research Database (Denmark)

    Theisen, Michael; Jore, Matthijs M; Sauerwein, Robert

    2017-01-01

    Introduction: Malaria is a devastating vector-borne disease caused by the Plasmodium parasite, resulting in almost 0.5 million casualties per year. The parasite has a complex life-cycle that includes asexual replication in human red blood cells, causing symptomatic malaria, and sexual stages which...... are essential for the transmission to the mosquito vector. A vaccine targeting the sexual stages of the parasite and thus blocking transmission will be instrumental for the eradication of malaria. One of the leading transmission blocking vaccine candidates is the sexual stage antigen Pfs48/45. Areas covered......: PubMed was searched to review the progress and future prospects for clinical development of a Pfs48/45-based subunit vaccine. We will focus on biological function, naturally acquired immunity, functional activity of specific antibodies, sequence diversity, production of recombinant protein...

  14. Vaccines against malaria.

    Science.gov (United States)

    Ouattara, Amed; Laurens, Matthew B

    2015-03-15

    Despite global efforts to control malaria, the illness remains a significant public health threat. Currently, there is no licensed vaccine against malaria, but an efficacious vaccine would represent an important public health tool for successful malaria elimination. Malaria vaccine development continues to be hindered by a poor understanding of antimalarial immunity, a lack of an immune correlate of protection, and the genetic diversity of malaria parasites. Current vaccine development efforts largely target Plasmodium falciparum parasites in the pre-erythrocytic and erythrocytic stages, with some research on transmission-blocking vaccines against asexual stages and vaccines against pregnancy-associated malaria. The leading pre-erythrocytic vaccine candidate is RTS,S, and early results of ongoing Phase 3 testing show overall efficacy of 46% against clinical malaria. The next steps for malaria vaccine development will focus on the design of a product that is efficacious against the highly diverse strains of malaria and the identification of a correlate of protection against disease. © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  15. [Mercury in vaccines].

    Science.gov (United States)

    Hessel, Luc

    2003-01-01

    Thiomersal, also called thimerosal, is an ethyl mercury derivative used as a preservative to prevent bacterial contamination of multidose vaccine vials after they have been opened. Exposure to low doses of thiomersal has essentially been associated with hypersensitivity reactions. Nevertheless there is no evidence that allergy to thiomersal could be induced by thiomersal-containing vaccines. Allergy to thiomersal is usually of delayed-hypersensitivity type, but its detection through cutaneous tests is not very reliable. Hypersensitivity to thiomersal is not considered as a contraindication to the use of thiomersal-containing vaccines. In 1999 in the USA, thiomersal was present in approximately 30 different childhood vaccines, whereas there were only 2 in France. Although there were no evidence of neurological toxicity in infants related to the use of thiomersal-containing vaccines, the FDA considered that the cumulative dose of mercury received by young infants following vaccination was high enough (although lower than the FDA threshold for methyl mercury) to request vaccine manufacturers to remove thiomersal from vaccine formulations. Since 2002, all childhood vaccines used in Europe and the USA are thiomersal-free or contain only minute amounts of thiomersal. Recently published studies have shown that the mercury levels in the blood, faeces and urine of children who had received thiomersal-containing vaccines were much lower than those accepted by the American Environmental Protection Agency. It has also been demonstrated that the elimination of mercury in children was much faster than what was expected on the basis of studies conducted with methyl mercury originating from food. Recently, the hypothesis that mercury contained in vaccines could be the cause of autism and other neurological developmental disorders created a new debate in the medical community and the general public. To date, none of the epidemiological studies conducted in Europe and elsewhere

  16. Moving towards improved vaccines for Toxoplasma gondii.

    Science.gov (United States)

    Li, Yawen; Zhou, Huaiyu

    2018-03-01

    Toxoplasma gondii is an intracellular parasitic protozoan that infects almost all warm-blooded animals and humans, resulting in threats to public health and economic losses. Despite continuous research efforts, there are still very few effective strategies against toxoplasmosis. In the past few years, numerous vaccination experiments have been performed to control T. gondii infection. Areas covered: In this review, the authors summarize the development of T. gondii vaccines with proper adjuvants, ranging from live or live-attenuated vaccines to protein vaccines, DNA vaccines, epitope vaccines and novel vaccines. They also highlight the challenges involved in the development of T. gondii vaccines, including specific impediments and shortcomings. Expert opinion: Moving towards the development of effective vaccines against T. gondii is not only a tedious mission but also a difficult challenge. Future studies should consider new approaches and strategies for vaccine development, particularly novel vaccines and genetic adjuvants, as well as optimizing immunization protocols and evaluation criteria.

  17. Tissue reduction of map numbers after post-exposure vaccination with single latency antigen is improved by combination with acute-stage antigens in goats

    DEFF Research Database (Denmark)

    Thakur, Aneesh; Aagaard, C.; Melvang, Heidi Mikkelsen

    compared to unvaccinated control goats. FET11 and FET13 vaccination, however, provided significantly protection with absent or very low Map numbers in tissues. No goats seroconverted in ID Screen® ELISA, except for a single goat in the unvaccinated control group at last sampling prior to euthanasia. PPDj...

  18. The infection staging and profile of genotypic distribution and drug resistance mutation among the human immunodeficiency virus-1 infected blood donors from five Chinese blood centers, 2012-2014.

    Directory of Open Access Journals (Sweden)

    Peibin Zeng

    Full Text Available The increasing complexity and diversity of the human immunodeficiency virus-1 (HIV-1 infections challenge the disease control and anti-retrovirus treatment in China. The infection stages and molecular characteristics of HIV-1 from infected Chinese blood donors were examined to shed light on the HIV genotype distribution and the status of drug resistance mutations (DRMs in the changing HIV epidemic in China. Western blot (WB confirmed HIV-1 positive plasma samples were collected from blood donors at five Chinese blood centers from April 16, 2012, through June 30, 2014. The HIV infection stages were determined using the Lag-avidity assay. HIV Pol regions including whole protease and partial reverse transcriptase (RT were amplified and sequenced to establish the profile of genotype distribution and drug resistance mutations (DRMs. Viral loads were determined using the ROCHE COBAS system. Of the 259 HIV-1 positive samples tested by the Lag-avidity assay, 23.6% (61/259 were identified as recent infections. A total of 205 amplified sequences displayed the following genotype distributions: circulating recombinant form (CRF 07_BC (61.5%, CRF08_BC (8.3%, CRF01_AE (20%, B (6.3%, and 01B (3.9%. There was no significant difference in genotype distribution between recent and long-term infections. 31 DRMs were identified from 27 samples including four protease inhibitors (PIs accessory DRMs, two PIs major DRMs (M46I, two nucleoside RT inhibitors DRMs (K219R and K70Q, and 23 nonnucleoside RT inhibitors DRMs. 27 samples had DRMs, yielding a drug resistance prevalence of 13.2% (27/205. Our findings provide important information for developing strategies for comprehensive HIV control and improving anti-retroviral treatment in China.

  19. A phase 2b randomized, controlled trial of the efficacy of the GMZ2 malaria vaccine in African children

    DEFF Research Database (Denmark)

    Sirima, Sodiomon B; Mordmüller, Benjamin; Milligan, Paul

    2016-01-01

    BACKGROUND: GMZ2 is a recombinant protein malaria vaccine, comprising two blood-stage antigens of Plasmodium falciparum, glutamate-rich protein and merozoite surface protein 3. We assessed efficacy of GMZ2 in children in Burkina Faso, Gabon, Ghana and Uganda. METHODS: Children 12-60months old wer...

  20. The blood level of transforming growth factor-beta rises in the early stages of acute protein and energy deficit in the weanling mouse.

    Science.gov (United States)

    Monk, Jennifer M; Woodward, Bill

    2010-03-01

    Plasma transforming growth factor (TGF)-beta levels are high in the advanced stages of acute (wasting) pre-pubescent deficits of protein and energy. Consequently, this potently anti-inflammatory cytokine may help to sustain the depression of inflammatory immune competence in acute malnutrition. Our objective was to determine if plasma TGF-beta levels rise during the early stages of acute malnutrition and, secondarily, to confirm the elevation reported previously in advanced weight loss. In two experiments, male and female C57BL/6J mice, initially 19 d old, consumed ad libitum a complete purified diet (group C), or in restricted daily quantities (group R) or had free access to an isoenergetic low-protein diet (group LP). TGF-beta bioactivity in platelet-poor plasma was determined via inhibition of Mv1Lu mink lung cell proliferation after 3 d (Expt 1, early stage) or 14 d (Expt 2, advanced stage) of dietary intervention. At 3 d, mean plasma TGF-beta bioactivities were 802 (C), 2952 (R) and 4678 (LP) pg/ml, and after 14 d mean bioactivities were 1786 (C), 5360 (R) and 5735 (LP) pg/ml. At both time points, the malnourished groups differed from age-matched controls (P blood TGF-beta concentration, and this cytokine joins corticosterone and IL-10 as a third anti-inflammatory hormone temporally positioned to contribute to the initiation (and maintenance) of malnutrition-associated immune depression. This investigation contributes new insight into the active anti-inflammatory form of immune competence that appears to prevail in acute pre-pubescent malnutrition.

  1. Dengue virus vaccine development.

    Science.gov (United States)

    Yauch, Lauren E; Shresta, Sujan

    2014-01-01

    Dengue virus (DENV) is a significant cause of morbidity and mortality in tropical and subtropical regions, causing hundreds of millions of infections each year. Infections range from asymptomatic to a self-limited febrile illness, dengue fever (DF), to the life-threatening dengue hemorrhagic fever/dengue shock syndrome (DHF/DSS). The expanding of the habitat of DENV-transmitting mosquitoes has resulted in dramatic increases in the number of cases over the past 50 years, and recent outbreaks have occurred in the United States. Developing a dengue vaccine is a global health priority. DENV vaccine development is challenging due to the existence of four serotypes of the virus (DENV1-4), which a vaccine must protect against. Additionally, the adaptive immune response to DENV may be both protective and pathogenic upon subsequent infection, and the precise features of protective versus pathogenic immune responses to DENV are unknown, complicating vaccine development. Numerous vaccine candidates, including live attenuated, inactivated, recombinant subunit, DNA, and viral vectored vaccines, are in various stages of clinical development, from preclinical to phase 3. This review will discuss the adaptive immune response to DENV, dengue vaccine challenges, animal models used to test dengue vaccine candidates, and historical and current dengue vaccine approaches. © 2014 Elsevier Inc. All rights reserved.

  2. Expression, Purification and Characterization of GMZ2'.10C, a Complex Disulphide-Bonded Fusion Protein Vaccine Candidate against the Asexual and Sexual Life-Stages of the Malaria-Causing Plasmodium falciparum Parasite

    DEFF Research Database (Denmark)

    Mistarz, Ulrik H; Singh, Susheel K; Nguyen, Tam T T N

    2017-01-01

    for a multi-stage malaria vaccine that targets both transmission and asexual life-cycle stages of the parasite. METHODS: GMZ2'.10C was produced in Lactococcus lactis and purified using either an immunoaffinity purification (IP) or a conventional purification (CP) method. Protein purity and stability......-GMZ2'.10C. CP-GMZ2'.10C and IP-GMZ2'.10C both elicited a high titer of transmission blocking (TB) antibodies in rodents. The intricate disulphide-bond connectivity of C-terminus Pfs48/45 was analysed by tandem mass spectrometry and was established for GMZ2'.10C and two reference fusion proteins...

  3. Lymphocyte populations and apoptosis of peripheral blood B and T lymphocytes in children with end stage renal disease.

    Science.gov (United States)

    Saad, Khaled; Elsayh, Khalid I; Zahran, Asmaa M; Sobhy, Karema M

    2014-05-01

    End stage renal disease (ESRD) is a worldwide devastating health problem due to its increased prevalence in the population and high association with several pathologic conditions including immunodeficiency, which makes a significant contribution to morbidity and mortality. The present study aimed at analysis of T and B lymphocyte subpopulation and the detection of flowcytometric apoptosis markers on peripheral B and T lymphocytes in a cohort of children with ESRD. A case-control study was conducted on 28 children with ESRD. In addition, 30 age and sex matched healthy children were included as a control group. We used Annexin V-FITC binding assay as a sensitive probe for identifying cells undergoing apoptosis. Circulating neutrophils, T and B lymphocytes were lower in patient group. In addition, apoptotic B and T lymphocytes occurred more frequently in children with ESRD than in the control group. Our finding of low numbers of circulating neutrophils, T and B lymphocytes, and increased portion of apoptotic B and T lymphocytes in children with ESRD, may emphasize the fact that these derangements are the main mechanisms responsible for the impairment of the immune system in ESRD children, also it adds to the fact that both cellular and humoral immunity affected in ESRD children. Finally, uremia and increased peripheral lymphocyte apoptosis were the major causes of lymphocyte populations' depletion in our ESRD patients.

  4. The Effects of Vaccination and Immunity on Bacterial Infection Dynamics In Vivo

    Science.gov (United States)

    Coward, Chris; Restif, Olivier; Dybowski, Richard; Grant, Andrew J.; Maskell, Duncan J.; Mastroeni, Pietro

    2014-01-01

    Salmonella enterica infections are a significant global health issue, and development of vaccines against these bacteria requires an improved understanding of how vaccination affects the growth and spread of the bacteria within the host. We have combined in vivo tracking of molecularly tagged bacterial subpopulations with mathematical modelling to gain a novel insight into how different classes of vaccines and branches of the immune response protect against secondary Salmonella enterica infections of the mouse. We have found that a live Salmonella vaccine significantly reduced bacteraemia during a secondary challenge and restrained inter-organ spread of the bacteria in the systemic organs. Further, fitting mechanistic models to the data indicated that live vaccine immunisation enhanced both the bacterial killing in the very early stages of the infection and bacteriostatic control over the first day post-challenge. T-cell immunity induced by this vaccine is not necessary for the enhanced bacteriostasis but is required for subsequent bactericidal clearance of Salmonella in the blood and tissues. Conversely, a non-living vaccine while able to enhance initial blood clearance and killing of virulent secondary challenge bacteria, was unable to alter the subsequent bacterial growth rate in the systemic organs, did not prevent the resurgence of extensive bacteraemia and failed to control the spread of the bacteria in the body. PMID:25233077

  5. The effects of vaccination and immunity on bacterial infection dynamics in vivo.

    Directory of Open Access Journals (Sweden)

    Chris Coward

    2014-09-01

    Full Text Available Salmonella enterica infections are a significant global health issue, and development of vaccines against these bacteria requires an improved understanding of how vaccination affects the growth and spread of the bacteria within the host. We have combined in vivo tracking of molecularly tagged bacterial subpopulations with mathematical modelling to gain a novel insight into how different classes of vaccines and branches of the immune response protect against secondary Salmonella enterica infections of the mouse. We have found that a live Salmonella vaccine significantly reduced bacteraemia during a secondary challenge and restrained inter-organ spread of the bacteria in the systemic organs. Further, fitting mechanistic models to the data indicated that live vaccine immunisation enhanced both the bacterial killing in the very early stages of the infection and bacteriostatic control over the first day post-challenge. T-cell immunity induced by this vaccine is not necessary for the enhanced bacteriostasis but is required for subsequent bactericidal clearance of Salmonella in the blood and tissues. Conversely, a non-living vaccine while able to enhance initial blood clearance and killing of virulent secondary challenge bacteria, was unable to alter the subsequent bacterial growth rate in the systemic organs, did not prevent the resurgence of extensive bacteraemia and failed to control the spread of the bacteria in the body.

  6. The influence of Maloprim chemoprophylaxis on cellular and humoral immune responses to Plasmodium falciparum asexual blood stage antigens in schoolchildren living in a malaria endemic area of Mozambique

    DEFF Research Database (Denmark)

    Hogh, B; Thompson, R; Lobo, V

    1994-01-01

    We examined the impact of chemoprophylaxis on the cellular and humoral immune responses to polypeptides of the asexual Plasmodium falciparum blood stage antigens, the glutamate rich protein GLURP and Pf155/RESA, both of which in previous field studies have been identified as potentially protective...... antigens. The study was carried out in the Escola Primária de Lingamo, a primary school in a suburban area of Maputo, Mozambique. A cohort of 392 schoolchildren (aged 7-12 years) was randomly allocated to two equal groups, one receiving chemoprophylaxis with dapsone/pyrimethamine (Maloprim), the other...... receiving placebo every week from December 1989 to November 1990. The groups were then followed until November 1991 without chemoprophylaxis. Cellular responses to immunodominant epitopes from Pf155/RESA and GLURP, and to non malaria antigens C. albicans and PPD, were assessed by lymphocyte proliferation...

  7. Next generation vaccines.

    Science.gov (United States)

    Riedmann, Eva M

    2011-07-01

    In February this year, about 100 delegates gathered for three days in Vienna (Austria) for the Next Generation Vaccines conference. The meeting held in the Vienna Hilton Hotel from 23rd-25th February 2011 had a strong focus on biotech and industry. The conference organizer Jacob Fleming managed to put together a versatile program ranging from the future generation of vaccines to manufacturing, vaccine distribution and delivery, to regulatory and public health issues. Carefully selected top industry experts presented first-hand experience and shared solutions for overcoming the latest challenges in the field of vaccinology. The program also included several case study presentations on novel vaccine candidates in different stages of development. An interactive pre-conference workshop as well as interactive panel discussions during the meeting allowed all delegates to gain new knowledge and become involved in lively discussions on timely, interesting and sometimes controversial topics related to vaccines.

  8. Malaria resistance genes are associated with the levels of IgG subclasses directed against Plasmodium falciparum blood-stage antigens in Burkina Faso

    Directory of Open Access Journals (Sweden)

    Afridi Sarwat

    2012-09-01

    Full Text Available Abstract Background HBB, IL4, IL12, TNF, LTA, NCR3 and FCGR2A polymorphisms have been associated with malaria resistance in humans, whereas cytophilic immunoglobulin G (IgG antibodies are thought to play a critical role in immune protection against asexual blood stages of the parasite. Furthermore, HBB, IL4, TNF, and FCGR2A have been associated with both malaria resistance and IgG levels. This suggests that some malaria resistance genes influence the levels of IgG subclass antibodies. Methods In this study, the effect of HBB, IL4, IL12, TNF, LTA, NCR3 and FCGR2A polymorphisms on the levels of IgG responses against Plasmodium falciparum blood-stage extract was investigated in 220 individuals living in Burkina Faso. The Pearson’s correlation coefficient among IgG subclasses was determined. A family-based approach was used to assess the association of polymorphisms with anti-P. falciparum IgG, IgG1, IgG2, IgG3 and IgG4 levels. Results After applying a multiple test correction, several polymorphisms were associated with IgG subclass or IgG levels. There was an association of i haemoglobin C with IgG levels; ii the FcγRIIa H/R131 with IgG2 and IgG3 levels; iii TNF-863 with IgG3 levels; iv TNF-857 with IgG levels; and, v TNF1304 with IgG3, IgG4, and IgG levels. Conclusion Taken together, the results support the hypothesis that some polymorphisms affect malaria resistance through their effect on the acquired immune response, and pave the way towards further comprehension of genetic control of an individual’s humoral response against malaria.

  9. Relationship between red blood cell transfusion requirements and severity of renal disease during the acute stage of hemolytic uremic syndrome.

    Science.gov (United States)

    Cobeñas, Carlos J; Bresso, Paula S; Lombardi, Laura L; Amoreo, Oscar R; Ruscasso, Javier D; Spizzirri, Ana P; Del C Suarez, Ângela; Zalba, Javier H; Rahman, Ricardo C; Risso, Paula

    2015-12-01

    We performed a retrospective evaluation of patients with diarrhea-associated hemolytic uremic syndrome (D + HUS) with the aims of: (1) determining the rate of red blood cell (RBC) transfusions; (2) establishing the relationship between need for RBC transfusion and severity of renal involvement; (3) determining whether precise measurements of lactic dehydrogenase (LDH) levels can predict the rate of hemolysis and severity of renal disease. A total of 288 patients with D + HUS were retrospectively divided into three groups based on dialysis treatment: group 1, no dialysis treatment (144 patients); group 2, dialysis for 1-10 days (67 patients); group 3, dialysis for ≥11 days (77 patients). Of the patients in groups 1, 2 and 3, 73.6, 86.5 and 83.1%, respectively, required at least one RBC transfusion. The number of RBC transfusions in groups 1, 2 and 3 was 163, 107 and 162, respectively. Comparison of the groups revealed that the number of RBC transfusions was significantly higher in patients in groups 2 and 3 than in those in group 1 (p = 0.0001). Most RBC transfusions (94.2%) occurred during the first 2 weeks of the disease. The median peak LDH level was 2091 U/l in 32 patients with no RBC transfusion (group A), 3900 U/l in 73 patients with one transfusion (group B) and 6378 U/l in 62 patients with two or more transfusions (group C). Patients who received two or more RBC transfusions had a significantly higher median peak LDH level than those who did not receive RBC transfusions or received only one transfusion. This difference was also observed between patients who received only one RBC transfusion and those who did not receive any transfusions (p 10 days of dialysis (group 3) had the highest LDH levels, followed by patients with 1-10 days of dialysis (group 2) and then by patients with no dialysis requirements (group 1) (p < 0.00001). The rate of RBC transfusion was higher in patients with the most severe renal injury, and most were performed during the

  10. Plasmodium yoelii blood-stage primes macrophage-mediated innate immune response through modulation of toll-like receptor signalling

    Directory of Open Access Journals (Sweden)

    Fu Yong

    2012-04-01

    Full Text Available Abstract Background Toll-like receptors (TLRs signalling is reported to be primed by the infection of human malaria parasite, Plasmodium falciparum. However, little is known about the regulation of macrophages TLR signalling by the infection of lethal or non-lethal strain of rodent malaria parasites. Methods BALB/c mice were infected with non-lethal strain Plasmodium yoelii 17XNL or lethal strain P. yoelii 17XL. Peritoneal macrophages were isolated to study its immune response to pRBC lysate, and TLRs (TLR2, TLR4, and TLR9 agonists, and the expression of TLRs and intracellular signalling molecules were also investigated by flow cytometry and semi-quantitive RT-PCR. Results The reactivity of peritoneal macrophages from the mice infected with lethal strain P. y 17XL or non-lethal strain P. y 17XNL were enhanced to pRBC lysate, and TLR2, TLR4, and TLR9 agonists at one, three and five days post-infection. Of all the tested TLRs, only TLR2 was up-regulated on peritoneal macrophages of mice infected with either strain. However, transcription of intracellular signalling molecules MyD88, IRAK-1, and TRAF-6 was significantly up-regulated in peritoneal macrophages from mice infected either with P. yoelii 17XL or P. yoelii 17XNL at one, three and five days post-infection. However, the enhanced TLRs response of macrophage from P. yoelii 17XNL-infected mice persisted for a much longer time than that from P. yoelii 17XL-infected mice. Conclusion Both P. yoelii 17XL and 17XNL strains could enhance the response of peritoneal macrophages to pRBC lysate and TLR agonists, through up-regulating the expression of TLR2 and intracellular signalling molecules MyD88, IRAK-1, and TRAF-6. In addition, prolonged high response of macrophage from P. yoelii 17XNL-infected mice might be associated with the more efficiently controlling of P. yoelii 17XNL growth in mice at early stage.

  11. Acceptability of study procedures (self-collected introital swabs, blood draws and stool sample collection) by students 10-16 years for an HPV vaccine effectiveness study: a pilot study.

    Science.gov (United States)

    Nakalembe, Miriam; Mutyaba, Twaha; Mirembe, Florence

    2016-03-16

    A cohort study was planned to evaluate vaccine immunogenicity and effect of malaria and helminth co-infections on the bivalent Human papilloma virus (HPV) vaccine. The study would involve self collected introital swabs, blood draws and stool sample collection. We therefore conducted a pilot study to assess the acceptability of these procedures among the students and their parents. A cross-sectional study among forty four students from two purposively selected primary schools of Western Uganda. Exit interviews and two focus group discussions (FGD) (for parents) were conducted. Acceptability was measured by willingness to undergo the procedures again, recommending the procedures to others as well as proportion of introital swabs positive for β globulin. FGD determined acceptability of the parents and explored opinions and perceptions that would influence their decisions. HPV-16/18 and β globulin deoxyribonucleic acid (DNA) were analysed using a polymerase chain reaction (PCR) kit. All the students (100%) in the study were willing to provide a self- collected introital swab and a stool sample as well as recommending their friends while (86.3%) were willing for blood draws. There were 40/44 (90.1%) self collected introital swabs that had positive result for human β globulin though none of them was positive for HPV-16/18. In the FGD, it emerged that parents concerns were on the blood draws and introital swab collection which were addressed. The study procedures were highly acceptable among this study population of students and their parents. Follow-up to assess HPV vaccine effectiveness and factors that may influence the vaccine in this age group is feasible.

  12. Panels of tumor-derived RNA markers in peripheral blood of patients with non-small cell lung cancer: their dependence on age, gender and clinical stages.

    Science.gov (United States)

    Chian, Chih-Feng; Hwang, Yi-Ting; Terng, Harn-Jing; Lee, Shih-Chun; Chao, Tsui-Yi; Chang, Hung; Ho, Ching-Liang; Wu, Yi-Ying; Perng, Wann-Cherng

    2016-08-02

    Peripheral blood mononuclear cell (PBMC)-derived gene signatures were investigated for their potential use in the early detection of non-small cell lung cancer (NSCLC). In our study, 187 patients with NSCLC and 310 age- and gender-matched controls, and an independent set containing 29 patients for validation were included. Eight significant NSCLC-associated genes were identified, including DUSP6, EIF2S3, GRB2, MDM2, NF1, POLDIP2, RNF4, and WEE1. The logistic model containing these significant markers was able to distinguish subjects with NSCLC from controls with an excellent performance, 80.7% sensitivity, 90.6% specificity, and an area under the receiver operating characteristic curve (AUC) of 0.924. Repeated random sub-sampling for 100 times was used to validate the performance of classification training models with an average AUC of 0.92. Additional cross-validation using the independent set resulted in the sensitivity 75.86%. Furthermore, six age/gender-dependent genes: CPEB4, EIF2S3, GRB2, MCM4, RNF4, and STAT2 were identified using age and gender stratification approach. STAT2 and WEE1 were explored as stage-dependent using stage-stratified subpopulation. We conclude that these logistic models using different signatures for total and stratified samples are potential complementary tools for assessing the risk of NSCLC.

  13. Iyengar Yoga versus Enhanced Usual Care on Blood Pressure in Patients with Prehypertension to Stage I Hypertension: a Randomized Controlled Trial.

    Science.gov (United States)

    Cohen, Debbie L; Bloedon, Leanne T; Rothman, Rand L; Farrar, John T; Galantino, Mary Lou; Volger, Sheri; Mayor, Christine; Szapary, Phillipe O; Townsend, Raymond R

    2011-01-01

    The prevalence of prehypertension and Stage 1 hypertension continues to increase despite being amenable to non-pharmacologic interventions. Iyengar yoga (IY) has been purported to reduce blood pressure (BP) though evidence from randomized trials is lacking. We conducted a randomized controlled trial to assess the effects of 12 weeks of IY versus enhanced usual care (EUC) (based on individual dietary adjustment) on 24-h ambulatory BP in yoga-naïve adults with untreated prehypertension or Stage 1 hypertension. In total, 26 and 31 subjects in the IY and EUC arms, respectively, completed the study. There were no differences in BP between the groups at 6 and 12 weeks. In the EUC group, 24-h systolic BP (SBP), diastolic BP (DBP) and mean arterial pressure (MAP) significantly decreased by 5, 3 and 3 mmHg, respectively, from baseline at 6 weeks (P IY group, 24 h SBP was reduced by 6 mmHg at 12 weeks compared to baseline (P = .05). 24 h DBP (P IY group at 12 weeks. Twelve weeks of IY produces clinically meaningful improvements in 24 h SBP and DBP. Larger studies are needed to establish the long term efficacy, acceptability, utility and potential mechanisms of IY to control BP.

  14. Elevated global cerebral blood flow, oxygen extraction fraction and unchanged metabolic rate of oxygen in young adults with end-stage renal disease: an MRI study

    Energy Technology Data Exchange (ETDEWEB)

    Zheng, Gang; Lou, Yaxian; Pan, Zhiying; Liu, Ya [Medical School of Nanjing University, Department of Medical Imaging, Jinling Hospital, Nanjing, Jiangsu (China); Nanjing University of Aeronautics and Astronautics, College of Aivil Aviation, Nanjing, Jiangsu (China); Wen, Jiqiu; Li, Xue; Zhang, Zhe [Medical School of Nanjing University, National Clinical Research Center of Kidney Diseases, Jinling Hospital, Nanjing, Jiangsu (China); Lu, Hanzhang [University of Texas Southwestern Medical Center, Advanced Imaging Research Center, Dallas, TX (United States); Liu, Wei [Siemens Shenzhen Magnetic Resonance Ltd., Shenzhen, Guangdong (China); Liu, Hui [Siemens MR NEA Collaboration, Siemens Ltd., Shanghai (China); Chen, Huijuan; Kong, Xiang; Luo, Song; Jiang, Xiaolu; Zhang, Zongjun; Zhang, Long Jiang; Lu, Guang Ming [Medical School of Nanjing University, Department of Medical Imaging, Jinling Hospital, Nanjing, Jiangsu (China)

    2016-06-15

    To noninvasively assess global cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO{sub 2}) in young adults with end-stage renal disease (ESRD). Thirty-six patients and 38 healthy volunteers were included and took part in MR examinations, blood and neuropsychological tests. CBF and OEF were measured by phase-contrast and T2-relaxation-under-spin-tagging MRI techniques, respectively. CMRO{sub 2} was computed from CBF, OEF and hematocrit according to Fick's principle. Correlations were performed between MR measurements, blood biochemistry measurements and neuropsychological test scores. Compared with controls, ESRD patients had elevated CBF (72.9 ± 12.5 vs. 63.8 ± 8.5 ml min{sup -1} 100 g{sup -1}, P < 0.001), elevated OEF (47.2 ± 10.2 vs. 35.8 ± 5.4 %, P < 0.001), but unaffected CMRO{sub 2} (199.5 ± 36.4 vs. 193.8 ± 28.6 μmol O{sub 2} min{sup -1} 100 g{sup -1}, P = 0.879). Hematocrit negatively correlated with CBF (r = -0.640, P < 0.001) and OEF (r = -0.701, P < 0.001), but not with CMRO{sub 2}. Altered neuropsychological test scores of ESRD patients were associated with OEF and CBF, but not with CMRO{sub 2}. There were weak relationships between eGFR and hematocrit (r = 0.308, P = 0.068) or CBF (r = 0.318, P = 0.059). Our findings suggested that anaemic young adults with ESRD may afford higher CBF and OEF to maintain a normal CMRO{sub 2}. Despite this compensatory process, however, cognitive function was still impaired and its severity was correlated with their CBF and OEF abnormality. (orig.)

  15. Elevated global cerebral blood flow, oxygen extraction fraction and unchanged metabolic rate of oxygen in young adults with end-stage renal disease: an MRI study

    International Nuclear Information System (INIS)

    Zheng, Gang; Lou, Yaxian; Pan, Zhiying; Liu, Ya; Wen, Jiqiu; Li, Xue; Zhang, Zhe; Lu, Hanzhang; Liu, Wei; Liu, Hui; Chen, Huijuan; Kong, Xiang; Luo, Song; Jiang, Xiaolu; Zhang, Zongjun; Zhang, Long Jiang; Lu, Guang Ming

    2016-01-01

    To noninvasively assess global cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO 2 ) in young adults with end-stage renal disease (ESRD). Thirty-six patients and 38 healthy volunteers were included and took part in MR examinations, blood and neuropsychological tests. CBF and OEF were measured by phase-contrast and T2-relaxation-under-spin-tagging MRI techniques, respectively. CMRO 2 was computed from CBF, OEF and hematocrit according to Fick's principle. Correlations were performed between MR measurements, blood biochemistry measurements and neuropsychological test scores. Compared with controls, ESRD patients had elevated CBF (72.9 ± 12.5 vs. 63.8 ± 8.5 ml min -1 100 g -1 , P < 0.001), elevated OEF (47.2 ± 10.2 vs. 35.8 ± 5.4 %, P < 0.001), but unaffected CMRO 2 (199.5 ± 36.4 vs. 193.8 ± 28.6 μmol O 2 min -1 100 g -1 , P = 0.879). Hematocrit negatively correlated with CBF (r = -0.640, P < 0.001) and OEF (r = -0.701, P < 0.001), but not with CMRO 2 . Altered neuropsychological test scores of ESRD patients were associated with OEF and CBF, but not with CMRO 2 . There were weak relationships between eGFR and hematocrit (r = 0.308, P = 0.068) or CBF (r = 0.318, P = 0.059). Our findings suggested that anaemic young adults with ESRD may afford higher CBF and OEF to maintain a normal CMRO 2 . Despite this compensatory process, however, cognitive function was still impaired and its severity was correlated with their CBF and OEF abnormality. (orig.)

  16. Green revolution vaccines, edible vaccines

    African Journals Online (AJOL)

    Admin

    Diabetes. Key words: Edible vaccines, oral vaccines, antigen expression, food vaccines. INTRODUCTION. Vaccination involves the stimulation of the immune system to prepare it for the event of an invasion from a particular pathogen for which the immune system has been primed (Arntzen, 1997). The release of vaccine is.

  17. Long-lasting complete response status of advanced stage IV gall bladder cancer and colon cancer after combined treatment including autologous formalin-fixed tumor vaccine: two case reports.

    Science.gov (United States)

    Imaoka, Yuki; Kuranishi, Fumito; Miyazaki, Tsubasa; Yasuda, Hiroko; Ohno, Tadao

    2017-09-11

    The prognosis of advanced (stage IV) cancer of the digestive organs is very poor. We have previously reported a case of advanced breast cancer with bone metastasis that was successfully treated with combined treatments including autologous formalin-fixed tumor vaccine (AFTV). Herein, we report the success of this approach in advanced stage IV (heavily metastasized) cases of gall bladder cancer and colon cancer. Case 1: A 61-year-old woman with stage IV gall bladder cancer (liver metastasis and lymph node metastasis) underwent surgery in May 2011, including partial resection of the liver. She was treated with AFTV as the first-line adjuvant therapy, followed by conventional chemotherapy. This patient is still alive without any recurrence, as confirmed with computed tomography, for more than 5 years. Case 2: A 64-year-old man with stage IV colon cancer (multiple para-aortic lymph node metastases and direct abdominal wall invasion) underwent non-curative surgery in May 2006. Following conventional chemotherapy, two courses of AFTV and radiation therapy were administered sequentially. This patient has had no recurrence for more than 5 years. We report the success of combination therapy including AFTV in cases of liver-metastasized gall bladder cancer and abdominal wall-metastasized colon cancer. Both patients experienced long-lasting, complete remission. Therefore, combination therapies including AFTV should be considered in patients with advanced cancer of the digestive organs.

  18. Leptospirosis vaccines

    Directory of Open Access Journals (Sweden)

    Jin Li

    2007-12-01

    Full Text Available Abstract Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the recent advancements of recombinant outer membrane protein (OMP vaccines, lipopolysaccharide (LPS vaccines, inactivated vaccines, attenuated vaccines and DNA vaccines against leptospirosis are reviewed. A comparison of these vaccines may lead to development of new potential methods to combat leptospirosis and facilitate the leptospirosis vaccine research. Moreover, a vaccine ontology database was built for the scientists working on the leptospirosis vaccines as a starting tool.

  19. Polio Vaccine

    Science.gov (United States)

    ... IBS) Home Family Health Infants and Toddlers Polio Vaccine Polio Vaccine Share Print What is polio? Poliomyelitis (polio) is ... each year. Fortunately, the use of the polio vaccine has made the disease very rare in most ...

  20. Measles Vaccination

    Science.gov (United States)

    ... World Health Organization Pan American Health Organization Measles Vaccination Pronounced (MEE-zills) Recommend on Facebook Tweet Share ... also be up to date on their MMR vaccination. The MMR vaccine is very safe and effective. ...

  1. A phase 2b randomized, controlled trial of the efficacy of the GMZ2 malaria vaccine in African children.

    Science.gov (United States)

    Sirima, Sodiomon B; Mordmüller, Benjamin; Milligan, Paul; Ngoa, Ulysse Ateba; Kironde, Fred; Atuguba, Frank; Tiono, Alfred B; Issifou, Saadou; Kaddumukasa, Mark; Bangre, Oscar; Flach, Clare; Christiansen, Michael; Bang, Peter; Chilengi, Roma; Jepsen, Søren; Kremsner, Peter G; Theisen, Michael

    2016-08-31

    GMZ2 is a recombinant protein malaria vaccine, comprising two blood-stage antigens of Plasmodium falciparum, glutamate-rich protein and merozoite surface protein 3. We assessed efficacy of GMZ2 in children in Burkina Faso, Gabon, Ghana and Uganda. Children 12-60months old were randomized to receive three injections of either 100μg GMZ2 adjuvanted with aluminum hydroxide or a control vaccine (rabies) four weeks apart and were followed up for six months to measure the incidence of malaria defined as fever or history of fever and a parasite density ⩾5000/μL. A cohort of 1849 children were randomized, 1735 received three doses of vaccine (868 GMZ2, 867 control-vaccine). There were 641 malaria episodes in the GMZ2/Alum group and 720 in the control group. In the ATP analysis, vaccine efficacy (VE), adjusted for age and site was 14% (95% confidence interval [CI]: 3.6%, 23%, p-value=0.009). In the ITT analysis, age-adjusted VE was 11.3% (95% CI 2.5%, 19%, p-value=0.013). VE was higher in older children. In GMZ2-vaccinated children, the incidence of malaria decreased with increasing vaccine-induced anti-GMZ2 IgG concentration. There were 32 cases of severe malaria (18 in the rabies vaccine group and 14 in the GMZ2 group), VE 27% (95% CI -44%, 63%). GMZ2 is the first blood-stage malaria vaccine to be evaluated in a large multicenter trial. GMZ2 was well tolerated and immunogenic, and reduced the incidence of malaria, but efficacy would need to be substantially improved, using a more immunogenic formulation, for the vaccine to have a public health role. Copyright © 2016 Elsevier Ltd. All rights reserved.

  2. Clinical Significance of T Lymphocyte Subset Changes After First Line Chemotherapy in Peripheral Blood from Patients with Advanced Stage Adenocarcinoma Cell Lung Cancer

    Directory of Open Access Journals (Sweden)

    Xiang YAN

    2012-03-01

    Full Text Available Background and objective The immune function disorder relates closely to the occurrence, metastasis, and prognosis of cancer. T lymphocyte subsets take an important role in immune function. We identified the dynamic changes of the immune system by investigating the levels of T lymphocyte subsets in peripheral blood of lung cancer patients with advanced stage adenocarcinoma undergoing first line chemotherapy. The results aided the search for rational chemo-immunotherapy strategies in lung cancer treatment. Methods Samples from 49 patients with pathologically demonstrated advanced stage adenocarcinoma cell lung cancer were compared with those from 33 healthy donors. Subsequently, the patients were separately treated with Docetaxol-based or Pemetrexed-based therapy. Peripheral blood samples at different time points after therapy were analyzed by flowcytometry. The lymphocyte subsets of the total lymphocytes were compared. Independent sample t test was used for the quantitative data analysis. Results The percentage of CD3+, CD3+CD4+, CD4+CD25+ cells of the lung cancer patients significantly varied from those of the healthy donors, the P values are 0.012, 0.034 and 0.006 separately. The CD3+ and CD3+CD4+ levels increased significantly on the 4th and 7th-10th day post-chemotherapy, which return to normal levels on the 21th day. The CD3+ level increased significantly both in the treatment group on all time points, while the CD3+, CD3+CD4+, CD4+/CD8+ levels significantly increased and the CD3+CD8+, CD8+CD28- levels significantly decreased on the 4th day in Pemetrexed group. The CD3+CD4+ levels increased significantly on the 4th and 7th-10th day and the CD3+CD8+, CD8+CD28- levels decreased on the 4th day in partial response group. Conclusion The immune function of advanced stage adenocarcinoma cell lung cancer patients was evidently suppressed, and was restored at the 4th day, followed by a reduction at the 21st day after chemotherapy. On the 4th day

  3. Vaccine-Mediated Mechanisms Controlling Replication of Francisella tularensis in Human Peripheral Blood Mononuclear Cells Using a Co-culture System

    Directory of Open Access Journals (Sweden)

    Kjell Eneslätt

    2018-02-01

    Full Text Available Cell-mediated immunity (CMI is normally required for efficient protection against intracellular infections, however, identification of correlates is challenging and they are generally lacking. Francisella tularensis is a highly virulent, facultative intracellular bacterium and CMI is critically required for protection against the pathogen, but how this is effectuated in humans is poorly understood. To understand the protective mechanisms, we established an in vitro co-culture assay to identify how control of infection of F. tularensis is accomplished by human cells and hypothesized that the model will mimic in vivo immune mechanisms. Non-adherent peripheral blood mononuclear cells (PBMCs were expanded with antigen and added to cultures with adherent PBMC infected with the human vaccine strain, LVS, or the highly virulent SCHU S4 strain. Intracellular numbers of F. tularensis was followed for 72 h and secreted and intracellular cytokines were analyzed. Addition of PBMC expanded from naïve individuals, i.e., those with no record of immunization to F. tularensis, generally resulted in little or no control of intracellular bacterial growth, whereas addition of PBMC from a majority of F. tularensis-immune individuals executed static and sometimes cidal effects on intracellular bacteria. Regardless of infecting strain, statistical differences between the two groups were significant, P < 0.05. Secretion of 11 cytokines was analyzed after 72 h of infection and significant differences with regard to secretion of IFN-γ, TNF, and MIP-1β was observed between immune and naïve individuals for LVS-infected cultures. Also, in LVS-infected cultures, CD4 T cells from vaccinees, but not CD8 T cells, showed significantly higher expression of IFN-γ, MIP-1β, TNF, and CD107a than cells from naïve individuals. The co-culture system appears to identify correlates of immunity that are relevant for the understanding of mechanisms of the protective host immunity to

  4. 'He is now like a brother, I can even give him some blood'--relational ethics and material exchanges in a malaria vaccine 'trial community' in The Gambia.

    Science.gov (United States)

    Geissler, P Wenzel; Kelly, Ann; Imoukhuede, Babatunde; Pool, Robert

    2008-09-01

    This paper explores social relations within the 'trial community' (staff and volunteers) of a Malaria Vaccine Trial (MVT), implemented by the Medical Research Council (MRC) in The Gambia between 2001 and 2004. It situates ethical concerns with medical research within the everyday life of scientific fieldwork. Based upon discussions with volunteers and staff, we explore processes of mediation between scientific project and study population, and between formal ethics, local ethical debates and everyday practice. We observe that material contact and substantial transactions, notably of blood and medicine, are central to the construction of the MVT. These transactions are guided by a concrete and relational form of ethics, which contrasts with the abstract and vertical formal ethical principles underwriting the scientific study protocol. The success of the MVT owed much to these kinship-like ethics. One possible conclusion from these observations is that research ethics should be understood, not just as a quasi-legal frame but also as an open, searching movement, much in the same way that kinship is not merely a juridical institution and a prescriptive frame of rules, but a network made through relational work. However, this conclusion raises new problems: by contrasting formal, abstract principles to intimate, immediate relations, and economic justice to personal morality, we accept that the order of medical research is moved further out of the public and political, and into the domains of either quasi-legal claims or of private morality. Irrespective of the undeniable importance of clear-cut rules and of good face-to-face relations, a third essential foundation of medical research ethics is the democratically constituted public sphere, including equitable health services, and transparent institutions to facilitate open debate and regulate particular interests. Ultimately, the ethics of global science can rely neither on principles nor trust but requires citizenship

  5. A Phase II pilot trial to evaluate safety and efficacy of ferroquine against early Plasmodium falciparum in an induced blood-stage malaria infection study.

    Science.gov (United States)

    McCarthy, James S; Rückle, Thomas; Djeriou, Elhadj; Cantalloube, Cathy; Ter-Minassian, Daniel; Baker, Mark; O'Rourke, Peter; Griffin, Paul; Marquart, Louise; Hooft van Huijsduijnen, Rob; Möhrle, Jörg J

    2016-09-13

    Ferroquine (SSR97193) is a candidate anti-malarial currently undergoing clinical trials for malaria. To better understand its pharmacokinetic (PK) and pharmacodynamic (PD) parameters the compound was tested in the experimentally induced blood stage malaria infection model in volunteers. Male and non-pregnant female aged 18-50 years were screened for this phase II, controlled, single-centre clinical trial. Subjects were inoculated with ~1800 viable Plasmodium falciparum 3D7A-infected human erythrocytes, and treated with a single-dose of 800 mg ferroquine. Blood samples were taken at defined time-points to measure PK and PD parameters. The blood concentration of ferroquine and its active metabolite, SSR97213, were measured on dry blood spot samples by ultra-performance liquid chromatography with tandem mass spectrometry (LC-MS/MS). Parasitaemia and emergence of gametocytes were monitored by quantitative PCR. Safety was determined by recording adverse events and monitoring clinical laboratory assessments during the course of the study. Eight subjects were enrolled into the study, inoculated with infected erythrocytes and treated with 800 mg ferroquine. Ferroquine was rapidly absorbed with maximal exposure after 4-8 and 4-12 h exposure for SSR97213. Non-compartmental PK analysis resulted in estimates for half-lives of 10.9 and 23.8 days for ferroquine and SSR97213, respectively. Parasite clearance as reported by parasite reduction ratio was 162.9 (95 % CI 141-188) corresponding to a parasite clearance half-life of 6.5 h (95 % CI: 6.4-6.7 h). PK/PD modelling resulted in a predicted minimal parasiticidal concentration of 20 ng/mL, and the single dosing tested in this study was predicted to maintain an exposure above this threshold for 454 h (37.8 days). Although ferroquine was overall well tolerated, transient elevated transaminase levels were observed in three subjects. Paracetamol was the only concomitant treatment among the two out of these three subjects

  6. Impact on malaria parasite multiplication rates in infected volunteers of the protein-in-adjuvant vaccine AMA1-C1/Alhydrogel+CPG 7909.

    Directory of Open Access Journals (Sweden)

    Christopher J A Duncan

    Full Text Available Inhibition of parasite growth is a major objective of blood-stage malaria vaccines. The in vitro assay of parasite growth inhibitory activity (GIA is widely used as a surrogate marker for malaria vaccine efficacy in the down-selection of candidate blood-stage vaccines. Here we report the first study to examine the relationship between in vivo Plasmodium falciparum growth rates and in vitro GIA in humans experimentally infected with blood-stage malaria.In this phase I/IIa open-label clinical trial five healthy malaria-naive volunteers were immunised with AMA1/C1-Alhydrogel+CPG 7909, and together with three unvaccinated controls were challenged by intravenous inoculation of P. falciparum infected erythrocytes.A significant correlation was observed between parasite multiplication rate in 48 hours (PMR and both vaccine-induced growth-inhibitory activity (Pearson r = -0.93 [95% CI: -1.0, -0.27] P = 0.02 and AMA1 antibody titres in the vaccine group (Pearson r = -0.93 [95% CI: -0.99, -0.25] P = 0.02. However immunisation failed to reduce overall mean PMR in the vaccine group in comparison to the controls (vaccinee 16 fold [95% CI: 12, 22], control 17 fold [CI: 0, 65] P = 0.70. Therefore no impact on pre-patent period was observed (vaccine group median 8.5 days [range 7.5-9], control group median 9 days [range 7-9].Despite the first observation in human experimental malaria infection of a significant association between vaccine-induced in vitro growth inhibitory activity and in vivo parasite multiplication rate, this did not translate into any observable clinically relevant vaccine effect in this small group of volunteers.ClinicalTrials.gov [NCT00984763].

  7. Impact on Malaria Parasite Multiplication Rates in Infected Volunteers of the Protein-in-Adjuvant Vaccine AMA1-C1/Alhydrogel+CPG 7909

    Science.gov (United States)

    Duncan, Christopher J. A.; Sheehy, Susanne H.; Ewer, Katie J.; Douglas, Alexander D.; Collins, Katharine A.; Halstead, Fenella D.; Elias, Sean C.; Lillie, Patrick J.; Rausch, Kelly; Aebig, Joan; Miura, Kazutoyo; Edwards, Nick J.; Poulton, Ian D.; Hunt-Cooke, Angela; Porter, David W.; Thompson, Fiona M.; Rowland, Ros; Draper, Simon J.; Gilbert, Sarah C.; Fay, Michael P.; Long, Carole A.; Zhu, Daming; Wu, Yimin; Martin, Laura B.; Anderson, Charles F.; Lawrie, Alison M.; Hill, Adrian V. S.; Ellis, Ruth D.

    2011-01-01

    Background Inhibition of parasite growth is a major objective of blood-stage malaria vaccines. The in vitro assay of parasite growth inhibitory activity (GIA) is widely used as a surrogate marker for malaria vaccine efficacy in the down-selection of candidate blood-stage vaccines. Here we report the first study to examine the relationship between in vivo Plasmodium falciparum growth rates and in vitro GIA in humans experimentally infected with blood-stage malaria. Methods In this phase I/IIa open-label clinical trial five healthy malaria-naive volunteers were immunised with AMA1/C1-Alhydrogel+CPG 7909, and together with three unvaccinated controls were challenged by intravenous inoculation of P. falciparum infected erythrocytes. Results A significant correlation was observed between parasite multiplication rate in 48 hours (PMR) and both vaccine-induced growth-inhibitory activity (Pearson r = −0.93 [95% CI: −1.0, −0.27] P = 0.02) and AMA1 antibody titres in the vaccine group (Pearson r = −0.93 [95% CI: −0.99, −0.25] P = 0.02). However immunisation failed to reduce overall mean PMR in the vaccine group in comparison to the controls (vaccinee 16 fold [95% CI: 12, 22], control 17 fold [CI: 0, 65] P = 0.70). Therefore no impact on pre-patent period was observed (vaccine group median 8.5 days [range 7.5–9], control group median 9 days [range 7–9]). Conclusions Despite the first observation in human experimental malaria infection of a significant association between vaccine-induced in vitro growth inhibitory activity and in vivo parasite multiplication rate, this did not translate into any observable clinically relevant vaccine effect in this small group of volunteers. Trial Registration ClinicalTrials.gov [NCT00984763] PMID:21799809

  8. Phase II Study of a HER-2/neu Intracellular Domain Peptide-Based Vaccine Administered to Stage IV HER2 Positive Breast Cancer Patients Receiving Trastuzumab

    Science.gov (United States)

    2010-05-01

    cells may be superior to IFNg-secreting Th1 cells alone in the prevention of tumor relapse. Th17 is a subset of CD4 Th cytokine recently reported and has...last Annual Report we have presented data to our Medical Monitor on June 22 , 2009 and December 30, 2009. Our next Data Safety Monitoring Plan...toxoid response (C), after immunization were associated with a decrease in serum TGF-beta levels. X axis: IFNg secretion (post-pre vaccine); Y axis

  9. Vaccination elicits a prominent acute phase response in horses.

    Science.gov (United States)

    Andersen, Susanne A; Petersen, Henrik H; Ersbøll, Annette K; Falk-Rønne, Jørgen; Jacobsen, Stine

    2012-02-01

    European and American guidelines for vaccination against tetanus and influenza in horses recommend annual and annual/semi-annual vaccinations, respectively, against the two pathogens. Too-frequent vaccination may, however, have adverse effects, among other things because an inflammatory response is elicited with subsequent alterations in homeostasis. The objective of the study was to compare the acute phase response (APR) in 10 horses following administration of two different types of vaccines, namely, an inactivated Immune Stimulating COMplex (ISCOM) vaccine and a live recombinant vector vaccine. Blood was sampled before and after vaccination to measure levels of serum amyloid A (SAA), fibrinogen, white blood cell counts (WBC) and iron. Vaccination induced a prominent APR with increased WBC, elevated blood levels of SAA and fibrinogen, and decreased serum iron concentrations. The ISCOM vaccine caused significantly (Phorse owners about convalescence after vaccination. Copyright © 2011 Elsevier Ltd. All rights reserved.

  10. Implementation workshop of WHO guidelines on evaluation of malaria vaccines: Current regulatory concepts and issues related to vaccine quality, Pretoria, South Africa 07 Nov 2014.

    Science.gov (United States)

    Ho, Mei Mei; Baca-Estrada, Maria; Conrad, Christoph; Karikari-Boateng, Eric; Kang, Hye-Na

    2015-08-26

    The current World Health Organization (WHO) guidelines on the quality, safety and efficacy of recombinant malaria vaccines targeting the pre-erythrocytic and blood stages of Plasmodium falciparum were adopted by the WHO Expert Committee on Biological Standardization in 2012 to provide guidance on the quality, nonclinical and clinical aspects of recombinant malaria vaccines. A WHO workshop was organised to facilitate implementation into African (national/regional) regulatory practices, of the regulatory evaluation principles outlined in the guidelines regarding quality aspects. The workshop was used also to share knowledge and experience on regulatory topics of chemistry, manufacturing and control with a focus on vaccines through presentations and an interactive discussion using a case study approach. The basic principles and concepts of vaccine quality including consistency of production, quality control and manufacturing process were presented and discussed in the meeting. By reviewing and practicing a case study, better understanding on the relationship between consistency of production and batch release tests of an adjuvanted pre-erythrocytic recombinant malaria vaccine was reached. The case study exercise was considered very useful to understand regulatory evaluation principles of vaccines and a suggestion was made to WHO to provide such practices also through its Global Learning Opportunities for Vaccine Quality programme. Crown Copyright © 2015. Published by Elsevier Ltd. All rights reserved.

  11. Double-blind, placebo-controlled first in human study to investigate an oral vaccine aimed to elicit an immune reaction against the VEGF-Receptor 2 in patients with stage IV and locally advanced pancreatic cancer

    International Nuclear Information System (INIS)

    Niethammer, Andreas G; Springer, Marco; Grenacher, Lars; Buchler, Markus W; Koch, Moritz; Weitz, Jürgen; Haefeli, Walter E; Schmitz-Winnenthal, Friedrich H; Lubenau, Heinz; Mikus, Gerd; Knebel, Philipp; Hohmann, Nicolas; Leowardi, Christine; Beckhove, Philipp; Akhisaroglu, Mustafa; Ge, Yingzi

    2012-01-01

    The investigational oral DNA vaccine VXM01 targets the vascular endothelial growth factor receptor 2 (VEGFR-2) and uses Salmonella typhi Ty21a as a vector. The immune reaction elicited by VXM01 is expected to disrupt the tumor neovasculature and, consequently, inhibit tumor growth. VXM01 potentially combines the advantages of anti-angiogenic therapy and active immunotherapy. This phase I trial examines the safety, tolerability, and immunological and clinical responses to VXM01. The randomized, placebo-controlled, double blind dose-escalation study includes up to 45 patients with locally advanced and stage IV pancreatic cancer. The patients will receive four doses of VXM01 or placebo in addition to gemcitabine as standard of care. Doses from 10 6 cfu up to 10 10 cfu of VXM01 will be evaluated in the study. An independent data safety monitoring board (DSMB) will be involved in the dose-escalation decisions. In addition to safety as primary endpoint, the VXM01-specific immune reaction, as well as clinical response parameters will be evaluated. The results of this study shall provide the first data regarding the safety and immunogenicity of the oral anti-VEGFR-2 vaccine VXM01 in cancer patients. They will also define the recommended dose for phase II and provide the basis for further clinical evaluation, which may also include additional cancer indications. EudraCT No.: 2011-000222-29, NCT01486329, ISRCTN68809279

  12. Iyengar Yoga versus Enhanced Usual Care on Blood Pressure in Patients with Prehypertension to Stage I Hypertension: a Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Debbie L. Cohen

    2011-01-01

    Full Text Available The prevalence of prehypertension and Stage 1 hypertension continues to increase despite being amenable to non-pharmacologic interventions. Iyengar yoga (IY has been purported to reduce blood pressure (BP though evidence from randomized trials is lacking. We conducted a randomized controlled trial to assess the effects of 12 weeks of IY versus enhanced usual care (EUC (based on individual dietary adjustment on 24-h ambulatory BP in yoga-naïve adults with untreated prehypertension or Stage 1 hypertension. In total, 26 and 31 subjects in the IY and EUC arms, respectively, completed the study. There were no differences in BP between the groups at 6 and 12 weeks. In the EUC group, 24-h systolic BP (SBP, diastolic BP (DBP and mean arterial pressure (MAP significantly decreased by 5, 3 and 3 mmHg, respectively, from baseline at 6 weeks (P < .05, but were no longer significant at 12 weeks. In the IY group, 24 h SBP was reduced by 6 mmHg at 12 weeks compared to baseline (P = .05. 24 h DBP (P < .01 and MAP (P < .05 decreased significantly each by 5 mmHg. No differences were observed in catecholamine or cortisol metabolism to explain the decrease in BP in the IY group at 12 weeks. Twelve weeks of IY produces clinically meaningful improvements in 24 h SBP and DBP. Larger studies are needed to establish the long term efficacy, acceptability, utility and potential mechanisms of IY to control BP.

  13. Polytopic vaccination with a live-attenuated dengue vaccine enhances B-cell and T-cell activation, but not neutralizing antibodies

    Directory of Open Access Journals (Sweden)

    Taweewun Hunsawong

    2017-03-01

    Full Text Available Dengue, caused by dengue viruses (DENVs, is the most common arboviral disease of humans. Several dengue vaccine candidates are at different stages of clinical development and one has been licensed. Inoculation with live-attenuated DENV constructs is an approach that has been used by vaccine developers. Unfortunately, the simultaneous injection of all four attenuated DENV serotypes (DENV1-4 into a single injection site (monotopic vaccination has been postulated to result in interference in the replication of some serotypes in favor of others, an important obstacle in obtaining a balanced immune response against all serotypes. Here, we demonstrate the virus replicative and immunostimulatory effects of polytopic monovalent dengue vaccination (PV in which, each of the four components of the tetravalent vaccine is simultaneously delivered to four different sites versus the more traditional monotopic tetravalent vaccination (MV in a non-human primate (NHP model. With the exception of DENV-2, there was no significant difference in detectable viral RNA levels between PV and MV inoculation. Interestingly, longer periods of detection and higher viral RNA levels were seen in the lymph nodes of NHPs inoculated PV compared to MV. Induction of lymph node dendritic cell maturation and of blood T- and B-cell activation showed different kinetics in PV inoculated NHPs compared to MV. The MV inoculated group showed earlier maturation of dendritic cells and activation of B and T cells compared to PV inoculated NHPs. A similar kinetic difference was also observed in the cytokine response: MV induced earlier cytokine responses compared to PV. However, similar levels of DENV neutralizing antibodies were observed in PV and MV NHPs. These findings indicate that cellular immune response after vaccination may be affected by the location of inoculation. Design of vaccine delivery may need to take into account the effects of locations of vaccine delivery of multiples

  14. DNA Vaccines

    Indian Academy of Sciences (India)

    DNA vaccine, immune response, antibodies, infectious diseases. GENERAL I ARTICLE. DNA Vaccines. P N Rangarajan. History of Vaccine Development. The year 1996 marked the 200th anniversary of the first vaccine developed against smallpox by Edward Jenner. In the now- famous 1796 experiment, Jenner scratched ...

  15. Vaccination, seizures and 'vaccine damage'.

    Science.gov (United States)

    Brown, Natasha J; Berkovic, Samuel F; Scheffer, Ingrid E

    2007-04-01

    Concerns about the safety of vaccination have plagued the community, with reduction in vaccine uptake resulting in increased risk of epidemics. Vaccination has been implicated in the cause of febrile seizures, 'vaccine encephalopathy' and autistic spectrum disorders. Evaluation of alleged associations is complicated by evolution in the vaccination field. This review focuses on the risk of seizures following vaccination and the alleged associations of vaccination with vaccine encephalopathy and also with autism spectrum disorders. Over the last decade the introduction of new vaccines such as the acellular pertussis vaccine has produced a reduction in seizures following vaccination, the outcome of which was benign even with older vaccines. New evidence emerged in 2006 showing that cases of alleged 'vaccine encephalopathy' are due to mutations within a sodium channel gene. The weight of epidemiological evidence does not support a relationship between vaccination and childhood epileptic encephalopathies or autism spectrum disorders. Vaccines are safer than ever before, but the challenge remains to convey this message to society in such a way that produces change in attitudes to vaccination and subsequent increase in vaccine coverage.

  16. In vivo approaches reveal a key role for DCs in CD4+ T cell activation and parasite clearance during the acute phase of experimental blood-stage malaria.

    Directory of Open Access Journals (Sweden)

    Henrique Borges da Silva

    2015-02-01

    Full Text Available Dendritic cells (DCs are phagocytes that are highly specialized for antigen presentation. Heterogeneous populations of macrophages and DCs form a phagocyte network inside the red pulp (RP of the spleen, which is a major site for the control of blood-borne infections such as malaria. However, the dynamics of splenic DCs during Plasmodium infections are poorly understood, limiting our knowledge regarding their protective role in malaria. Here, we used in vivo experimental approaches that enabled us to deplete or visualize DCs in order to clarify these issues. To elucidate the roles of DCs and marginal zone macrophages in the protection against blood-stage malaria, we infected DTx (diphtheria toxin-treated C57BL/6.CD11c-DTR mice, as well as C57BL/6 mice treated with low doses of clodronate liposomes (ClLip, with Plasmodium chabaudi AS (Pc parasites. The first evidence suggesting that DCs could contribute directly to parasite clearance was an early effect of the DTx treatment, but not of the ClLip treatment, in parasitemia control. DCs were also required for CD4+ T cell responses during infection. The phagocytosis of infected red blood cells (iRBCs by splenic DCs was analyzed by confocal intravital microscopy, as well as by flow cytometry and immunofluorescence, at three distinct phases of Pc malaria: at the first encounter, at pre-crisis concomitant with parasitemia growth and at crisis when the parasitemia decline coincides with spleen closure. In vivo and ex vivo imaging of the spleen revealed that DCs actively phagocytize iRBCs and interact with CD4+ T cells both in T cell-rich areas and in the RP. Subcapsular RP DCs were highly efficient in the recognition and capture of iRBCs during pre-crisis, while complete DC maturation was only achieved during crisis. These findings indicate that, beyond their classical role in antigen presentation, DCs also contribute to the direct elimination of iRBCs during acute Plasmodium infection.

  17. Two-stage, in silico deconvolution of the lymphocyte compartment of the peripheral whole blood transcriptome in the context of acute kidney allograft rejection.

    Science.gov (United States)

    Shannon, Casey P; Balshaw, Robert; Ng, Raymond T; Wilson-McManus, Janet E; Keown, Paul; McMaster, Robert; McManus, Bruce M; Landsberg, David; Isbel, Nicole M; Knoll, Greg; Tebbutt, Scott J

    2014-01-01

    Acute rejection is a major complication of solid organ transplantation that prevents the long-term assimilation of the allograft. Various populations of lymphocytes are principal mediators of this process, infiltrating graft tissues and driving cell-mediated cytotoxicity. Understanding the lymphocyte-specific biology associated with rejection is therefore critical. Measuring genome-wide changes in transcript abundance in peripheral whole blood cells can deliver a comprehensive view of the status of the immune system. The heterogeneous nature of the tissue significantly affects the sensitivity and interpretability of traditional analyses, however. Experimental separation of cell types is an obvious solution, but is often impractical and, more worrying, may affect expression, leading to spurious results. Statistical deconvolution of the cell type-specific signal is an attractive alternative, but existing approaches still present some challenges, particularly in a clinical research setting. Obtaining time-matched sample composition to biologically interesting, phenotypically homogeneous cell sub-populations is costly and adds significant complexity to study design. We used a two-stage, in silico deconvolution approach that first predicts sample composition to biologically meaningful and homogeneous leukocyte sub-populations, and then performs cell type-specific differential expression analysis in these same sub-populations, from peripheral whole blood expression data. We applied this approach to a peripheral whole blood expression study of kidney allograft rejection. The patterns of differential composition uncovered are consistent with previous studies carried out using flow cytometry and provide a relevant biological context when interpreting cell type-specific differential expression results. We identified cell type-specific differential expression in a variety of leukocyte sub-populations at the time of rejection. The tissue-specificity of these differentially

  18. Two-stage, in silico deconvolution of the lymphocyte compartment of the peripheral whole blood transcriptome in the context of acute kidney allograft rejection.

    Directory of Open Access Journals (Sweden)

    Casey P Shannon

    Full Text Available Acute rejection is a major complication of solid organ transplantation that prevents the long-term assimilation of the allograft. Various populations of lymphocytes are principal mediators of this process, infiltrating graft tissues and driving cell-mediated cytotoxicity. Understanding the lymphocyte-specific biology associated with rejection is therefore critical. Measuring genome-wide changes in transcript abundance in peripheral whole blood cells can deliver a comprehensive view of the status of the immune system. The heterogeneous nature of the tissue significantly affects the sensitivity and interpretability of traditional analyses, however. Experimental separation of cell types is an obvious solution, but is often impractical and, more worrying, may affect expression, leading to spurious results. Statistical deconvolution of the cell type-specific signal is an attractive alternative, but existing approaches still present some challenges, particularly in a clinical research setting. Obtaining time-matched sample composition to biologically interesting, phenotypically homogeneous cell sub-populations is costly and adds significant complexity to study design. We used a two-stage, in silico deconvolution approach that first predicts sample composition to biologically meaningful and homogeneous leukocyte sub-populations, and then performs cell type-specific differential expression analysis in these same sub-populations, from peripheral whole blood expression data. We applied this approach to a peripheral whole blood expression study of kidney allograft rejection. The patterns of differential composition uncovered are consistent with previous studies carried out using flow cytometry and provide a relevant biological context when interpreting cell type-specific differential expression results. We identified cell type-specific differential expression in a variety of leukocyte sub-populations at the time of rejection. The tissue-specificity of

  19. Thyroid hormones in milk and blood of lactating donkeys as affected by stage of lactation and dietary supplementation with trace elements.

    Science.gov (United States)

    Todini, Luca; Salimei, Elisabetta; Malfatti, Alessandro; Ferraro, Stefano; Fantuz, Francesco

    2012-05-01

    The traditional utilization of donkeys (Equus asinus) as dairy animals has recently attracted substantial scientific interest with regard to human nutrition. Donkey milk is well tolerated by infants with cows' milk allergy, useful in the treatment of human immune-related diseases, in the prevention of atherosclerosis, and in-vitro studies showed an anti-proliferative effect. Active 3-3'-5-triiodothyronine (T3) in colostrum and milk could play different physiological roles, systemic and paracrine, for both the mother and the suckling offspring. The aim was to evaluate whether thyroid hormones (TH) concentrations in milk and blood of lactating donkeys change with the advancing lactation and whether they can be affected by dietary supplementation with several trace elements, some of them directly involved with TH synthesis (I), metabolism (Se) and action (Zn). Sixteen lactating jennies were divided into two groups (CTL and TE). Mixed feed for TE was added with Zn, Fe, Cu, Mn, I, Se and Co. Every 2 weeks milk and blood samples were collected at 11·00. Total concentrations of T3 in milk (T3M) and T3 and T4 in plasma (T3P and T4P) were assayed using ELISA kits, validated for the donkey species. T3M was not correlated with TH concentrations in blood, did not change with the stage of lactation, and was significantly higher in TE (4·09 ± 0·07 ng/ml, mean ± SE) than in CTL group (3·89 ± 0·08 ng/ml). T4P (81·8 ± 5·2 ng/ml) and T3P (15·2 ± 1 ng/ml) significantly changed with time, but were not significantly affected by dietary treatment. T3P/T4P ratio was significantly lower in TE group. This study indicates that in donkey milk the concentration of T3, a human-like bioactive compound, can be affected by trace elements intake.

  20. Molecular and Cellular Dynamics in the Skin, the Lymph Nodes, and the Blood of the Immune Response to Intradermal Injection of Modified Vaccinia Ankara Vaccine

    Directory of Open Access Journals (Sweden)

    Pierre Rosenbaum

    2018-04-01

    Full Text Available New vaccine design approaches would be greatly facilitated by a better understanding of the early systemic changes, and those that occur at the site of injection, responsible for the installation of a durable and oriented protective response. We performed a detailed characterization of very early infection and host response events following the intradermal administration of the modified vaccinia virus Ankara as a live attenuated vaccine model in non-human primates. Integrated analysis of the data obtained from in vivo imaging, histology, flow cytometry, multiplex cytokine, and transcriptomic analysis using tools derived from systems biology, such as co-expression networks, showed a strong early local and systemic inflammatory response that peaked at 24 h, which was then progressively replaced by an adaptive response during the installation of the host response to the vaccine. Granulocytes, macrophages, and monocytoid cells were massively recruited during the local innate response in association with local productions of GM-CSF, IL-1β, MIP1α, MIP1β, and TNFα. We also observed a rapid and transient granulocyte recruitment and the release of IL-6 and IL-1RA, followed by a persistent phase involving inflammatory monocytes. This systemic inflammation was confirmed by molecular signatures, such as upregulations of IL-6 and TNF pathways and acute phase response signaling. Such comprehensive approaches improve our understanding of the spatiotemporal orchestration of vaccine-elicited immune response, in a live-attenuated vaccine model, and thus contribute to rational vaccine development.

  1. DNA VACCINES

    OpenAIRE

    Aksu, Burak

    2016-01-01

    Traditionally, protection against infectious diseases has relied on the use of attenuated or killed vaccines. However, many such vaccines are inadequate for reason of efficacy, safety, and cost effectiveness. Live-attenuated vaccines may be immunosuppressive, cause disease if not attenuated sufficiently, or provide limited immunity if too much attenuated. A major concern regarding the use of live vaccines is the possibility of outgrowth of more virulent organisms. Killed vaccines are often un...

  2. Hepatitis Vaccines

    OpenAIRE

    Sina Ogholikhan; Kathleen B. Schwarz

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B ...

  3. Liver Stage specific response among Endemic Populations: Diet & Immunity

    Directory of Open Access Journals (Sweden)

    Sarat Kumar Dalai

    2015-03-01

    Full Text Available Developing effective anti-malarial vaccine has been a challenge for long. Various factors including complex life cycle of parasite and lack of knowledge of stage specific critical antigens are some of the reasons. Moreover, inadequate understanding of the immune responses vis-à-vis sterile protection induced naturally by Plasmodia infection has further compounded the problem. It has been shown that people living in endemic areas take years to develop protective immunity to blood stage infection. But hardly anyone believes that immunity to liver-stage infection could be developed. Various experimental model studies using attenuated parasite suggest that liver stage immunity might exist among endemic populations. This could be induced because of the attenuation of parasite in liver by various compounds present in the diet of endemic populations.

  4. The effect of triploidy and vaccination on neutrophils and B-cells in the peripheral blood and head kidney of 0+ and 1+ Atlantic salmon (Salmo salar L.) post-smolts.

    Science.gov (United States)

    Fraser, Thomas W K; Rønneseth, Anita; Haugland, Gyri T; Fjelldal, Per Gunnar; Mayer, Ian; Wergeland, Heidrun I

    2012-07-01

    Sterile triploid fish are being used in aquaculture to prevent early unwanted sexual maturation and the genetic interaction between wild and cultured fish; however, triploid fish are typically considered to be more susceptible to disease than diploid counterparts. Proportions of leucocytes from the head kidney and peripheral blood were identified using monoclonal antibodies and flow cytometry in triploid and diploid, vaccinated and unvaccinated, out-of-season (0+) and 1+ Atlantic salmon (Salmo salar L.) three weeks post seawater transfer. Triploid 1+ fish were significantly (PAtlantic salmon post-smolts. Copyright © 2012 Elsevier Ltd. All rights reserved.

  5. Zika Virus Vaccine Development.

    Science.gov (United States)

    Morabito, Kaitlyn M; Graham, Barney S

    2017-12-16

    The emergence of Zika virus in Brazil and its association with microcephaly and Guillain-Barré syndrome led to accelerated vaccine development efforts. Based on prior flavivirus vaccine development programs, knowledge of flavivirus particle structure, definition of E dimers as the key antigenic target, and deep understanding of neutralizing mechanisms, multiple vaccine strategies have advanced to the stage of clinical evaluation with unprecedented speed. These include nucleic acid (DNA and messenger RNA), whole-inactivated virus, live-attenuated or chimeric virus, and protein or viruslike particle vaccines. Within a year from the declaration by the World Health Organization of Zika virus as a Public Health Emergency of International Concern, multiple vaccine candidates entered clinical trials, now totaling 7 products with an additional 40-plus candidate vaccines in preclinical development. The rapid progress in vaccine development demonstrates the capacity of governments, public health organizations, and the scientific community to respond to pandemic threats when sufficient prior knowledge exists, emergency funding is made available, and interagency cooperation is achieved and serves as a paradigm for preparing for future emerging infectious diseases. Published by Oxford University Press for the Infectious Diseases Society of America 2017. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  6. [mRNA Expressions of T-bet, GATA-3, ROR γt and Foxp3 in peripheral blood of patients with chronic lymphocytic leukemia in different stages].

    Science.gov (United States)

    Yu, Jing-Jing; Chen, Gang; Pang, Nan-Nan; Guo, Xin-Hong; Wang, Lei; Zhao, Fang; Tan, Ming-Fang; Qu, Jian-Hua

    2015-02-01

    This study was to investigate the mRNA expression of T-bet, GATA-3, ROR γt and Foxp3 mRNA in peripheral blood of patients with chronic lymphocytic leukemia (CLL) in different stages and explore their potential role in the pathogenesis and clinical diagnosis. A total of 46 newly diagnosed and untreated patients with CLL was chosen as patient group, including 16 patients in the stage of Binet A, 15 in the stage of Binet B, and 15 in the stage of Binet C; 20 healthy persons were selected as controls. The quantitative fluorescence PCR was adopted to detect the mRNA expression of T-bet, GATA-3, RORγt and Foxp3 in peripheral blood mononuclear cell (PBMNC). (1) The expression of T-bet mRNA in patient group was lower than that in normal controls (P ROR γt, Foxp3 in CLL patients group were higher than that in normal controls (P < 0.05), and the ratio of T-bet/GATA-3 and RORγt/Foxp3 in CLL in patient group were lower than that in normal controls(P < 0.05); (2) The later the stage, the higher the mRNA expression of GATA-3 and Foxp3. The mRNA expression of GATA-3 in stage Binet B and stage Binet C of CLL patients were higher than that in stage Binet A (P < 0.05),and the mRNA expression of Foxp3 in stage Binet C was higher than that in stage of Binet A and Binet B (P < 0.05); the later the stage, the lower the ratio of T-bet/GATA-3 and RORγt/Foxp3. The ratio of T-bet/GATA-3 in stage of Binet A CLL patients was higher than that in stage Binet C (P < 0.05) and the ratio of RORγt/Foxp3 in stage of Binet A and stage of Binet B were higher than that in stage Binet C (P < 0.05). This study found in the level of transcription factors in CLL patients that with the process of disease, the balance shifts from Th1/Th2 and Th17/Treg to Th17 and Treg, and Treg cell may play a critical immunosuppressive role in the development of CLL.

  7. THE RHEOLOGICAL PROPERTIES OF BLOOD IN THE MOST ACUTE STAGE OF ISCHEMIC STROKE AND THEIR RELATION TO THE SEVERITY OF NEUROLOGICAL IMPAIRMENT

    Directory of Open Access Journals (Sweden)

    M. N. Azhermacheva

    2013-01-01

    Full Text Available The study evaluated the rheological parameters of blood: blood viscosity, plasma viscosity, hematocrit, red blood cell aggregation and deformability. The severity of the patients was assessed by clinical scales:Glasgowcoma scale, the scale NIHSS, Barthel index. The study found that in the acute phase of ischemic stroke increased blood viscosity by increasing red blood cell aggregation and reduced erythrocyte deformability. The increase in the viscosity of the blood in acute ischemic stroke is accompanied by increased severity of neurological disorders.

  8. Vaccine Hesitancy.

    Science.gov (United States)

    Jacobson, Robert M; St Sauver, Jennifer L; Finney Rutten, Lila J

    2015-11-01

    Vaccine refusal received a lot of press with the 2015 Disneyland measles outbreak, but vaccine refusal is only a fraction of a much larger problem of vaccine delay and hesitancy. Opposition to vaccination dates back to the 1800 s, Edward Jenner, and the first vaccine ever. It has never gone away despite the public's growing scientific sophistication. A variety of factors contribute to modern vaccine hesitancy, including the layperson's heuristic thinking when it comes to balancing risks and benefits as well as a number of other features of vaccination, including falling victim to its own success. Vaccine hesitancy is pervasive, affecting a quarter to a third of US parents. Clinicians report that they routinely receive requests to delay vaccines and that they routinely acquiesce. Vaccine rates vary by state and locale and by specific vaccine, and vaccine hesitancy results in personal risk and in the failure to achieve or sustain herd immunity to protect others who have contraindications to the vaccine or fail to generate immunity to the vaccine. Clinicians should adopt a variety of practices to combat vaccine hesitancy, including a variety of population health management approaches that go beyond the usual call to educate patients, clinicians, and the public. Strategies include using every visit to vaccinate, the creation of standing orders or nursing protocols to provide vaccination without clinical encounters, and adopting the practice of stating clear recommendations. Up-to-date, trusted resources exist to support clinicians' efforts in adopting these approaches to reduce vaccine hesitancy and its impact. Copyright © 2015 Mayo Foundation for Medical Education and Research. Published by Elsevier Inc. All rights reserved.

  9. The immunological effects of oral polio vaccine provided with BCG vaccine at birth

    DEFF Research Database (Denmark)

    Jensen, Kristoffer Jarlov; Karkov, Hanne Sophie; Lund, Najaaraq

    2014-01-01

    BACKGROUND: Vaccines may have non-specific effects. An observational study from Guinea-Bissau suggested that oral polio vaccine at birth (OPV0) provided with Bacillus Calmette-Guérin (BCG) vaccine was associated with down-regulation of the immune response to BCG vaccine 6 weeks later. Based...... BCG alone at birth, and subsequently randomised to have a blood sample taken at 2, 4 or 6 weeks post-randomisation. Excreted levels of cytokines (IL-2, IL-5, IL-10, TNF-α and IFN-γ) were measured from whole blood in vitro stimulations with a panel of recall vaccine antigens (BCG, PPD, OPV), mitogen...

  10. Comparative analysis between RQ-PCR and digital droplet PCR of BCL2/IGH gene rearrangement in the peripheral blood and bone marrow of early stage follicular lymphoma.

    Science.gov (United States)

    Cavalli, Marzia; De Novi, Lucia Anna; Della Starza, Irene; Cappelli, Luca Vincenzo; Nunes, Vittorio; Pulsoni, Alessandro; Del Giudice, Ilaria; Guarini, Anna; Foà, Robin

    2017-05-01

    BCL2/IGH rearrangements were analysed by polymerase chain reaction (PCR) at diagnosis in paired peripheral blood (PB) and bone marrow (BM) samples from 67 patients with stage I/II follicular lymphoma (FL). Real time quantitative PCR (RQ-PCR) and digital droplet PCR (ddPCR) were performed in cases with a major breakpoint region (MBR+) at diagnosis and after localized radiotherapy and rituximab administration in order to investigate the applicability of ddPCR. The overall ddPCR/RQ-PCR concordance was 81·9% (113/138 samples) and 97·5% in the 40/138 with quantifiable disease (RQ-PCR≥10 -5 ). At baseline, ddPCR allowed the recovery of a MBR+ marker in 8/18 (44·4%) samples that resulted MBR-negative/minor cluster region-negative/minor BCL2-negative by qualitative PCR. Moreover, the tumour burden at diagnosis significantly predicted progression-free survival (PSF) only when quantified by ddPCR. Paired PB and BM samples analysis demonstrated a high concordance in the detection of BCL2/IGH+ cells by qualitative and quantitative methods; in particular, 40/62 samples were positive by ddPCR (25 PB+/BM+; 9 PB+/BM-; 6 PB-/BM+), with 34/40 (85%) identified by the study of PB only. In conclusion, in localized FL, ddPCR is a promising tool for monitoring minimal residual disease (MRD) that is at least comparable to RQ-PCR and potentially more accurate. PB is a suitable source for serial BCL2/IGH MRD assessments, regardless of the methodology utilized. © 2017 John Wiley & Sons Ltd.

  11. Dynamic Observation on Opening of the Blood-Brain Barrier in the Primary Stage of Severely Scalded Rabbits, a Multimodal Study.

    Science.gov (United States)

    Hu, Jun; Zhang, Yanwei; Ding, Shiyi; Li, Haitao

    2016-01-01

    The aim of this study was to characterize the opening of the blood-brain barrier (BBB) in the primary stage of 50% total burn surface area in third degree scalded rabbits. Thirty healthy male New Zealand white rabbits were randomly assigned to 1, 2, 3 and 4 hours post scald groups and an untreated control were used to establish a 50% total burn surface area third degree scalded model. I-labeled bovine serum albumin was used as a tracer to identify the earliest time point of BBB opening after a severe scald. Dual source CT and magnetic resonance imaging were used to visualize cerebral changes in vivo. Samples taken from the bilateral frontal, temporal, posterior cortex, cerebellum, brain stem, and basal ganglia were examined by light microscopy and transmission electron microscopy. Transmission electron microscopy observations confirmed that BBB had begun to open at 2 hours post scald. Intracellular edema of basal lamina and gliocytes, and the breakdown and an indistinct appearance of the tight junction of vascular endotheliocytes were observed at 3 hours post scald. A marked increase of I-labeled bovine serum albumin intake was recorded at 3 hours post scald in all parts of the brain. Significantly reduced apparent diffusion coefficient values calculated from diffusion-weighted imaging were measured at 4 hours post scald within region of interests in all parts of the brain applied on apparent diffusion coefficient images. No significant alteration was seen in CT, diffusion-weighted imaging, T1 or T2 weighted images. Opening of the BBB had begun at 2 hours post scald; ie, before the occurrence of edema. The results of this study suggest that opening of the BBB might be a prerequisite for brain edema.

  12. Cerebral blood flow of patients with age-associated memory impairment and the early stage of Alzheimer`s disease. A study by SPECT using the ARG method

    Energy Technology Data Exchange (ETDEWEB)

    Ishiwata, Akiko; Kitamura, Shin; Nagazumi, Atushi; Terashi, Akiro [Nippon Medical School, Tokyo (Japan)

    1998-04-01

    In order to further understand the pathology of Alzheimer`s disease (AD), we have utilized image analysis in diagnosing the early stages of AD in patients with cognitive disorders. CT and MRI, however, have not been feasible since only atrophy is seen and it is difficult to differentiate the changes in AD from age associated changes. In this study we tried to determine whether regional cerebral blood flow (rCBF) measurements using single photon emission CT (SPECT) are feasible for the early diagnosis of AD. Regional CBF (rCBF) was measured using SPECT in three subject groups: Age-associated memory impairment (AAMI, n=9), mild AD (n=16), and normal aged patients (mean age=68.3; n=20). The subjects were then observed for three years. The region of interest (ROI) for the medial temporal lobe was set at OM-30deg to cover the maximum area of the hippocampus. The absolute values of rCBF in the frontal, temporal, and parietal lobes and the cerebellum were significantly lower in the mild AD subjects than in the normal aged subjects. A significant decrease in rCBF was also seen in the medial temporal lobe in both the AD and the AAMI subjects compared to the normal controls. During the three years of follow up, no cases of dementia were seen in the AAMI subjects. However, there were two patients who appeared to have difficulty in adapting to daily life due to amnesia, one with a decrease in rCBF of the medial temporal lobe on the second SPECT, and the other showing a low rCBF the first time. This study suggests that AAMI subjects may comprise both AD and normal subjects. Therefore a more prospective study is needed. (author)

  13. Cerebral blood flow of patients with age-associated memory impairment and the early stage of Alzheimer's disease. A study by SPECT using the ARG method

    International Nuclear Information System (INIS)

    Ishiwata, Akiko; Kitamura, Shin; Nagazumi, Atushi; Terashi, Akiro

    1998-01-01

    In order to further understand the pathology of Alzheimer's disease (AD), we have utilized image analysis in diagnosing the early stages of AD in patients with cognitive disorders. CT and MRI, however, have not been feasible since only atrophy is seen and it is difficult to differentiate the changes in AD from age associated changes. In this study we tried to determine whether regional cerebral blood flow (rCBF) measurements using single photon emission CT (SPECT) are feasible for the early diagnosis of AD. Regional CBF (rCBF) was measured using SPECT in three subject groups: Age-associated memory impairment (AAMI, n=9), mild AD (n=16), and normal aged patients (mean age=68.3; n=20). The subjects were then observed for three years. The region of interest (ROI) for the medial temporal lobe was set at OM-30deg to cover the maximum area of the hippocampus. The absolute values of rCBF in the frontal, temporal, and parietal lobes and the cerebellum were significantly lower in the mild AD subjects than in the normal aged subjects. A significant decrease in rCBF was also seen in the medial temporal lobe in both the AD and the AAMI subjects compared to the normal controls. During the three years of follow up, no cases of dementia were seen in the AAMI subjects. However, there were two patients who appeared to have difficulty in adapting to daily life due to amnesia, one with a decrease in rCBF of the medial temporal lobe on the second SPECT, and the other showing a low rCBF the first time. This study suggests that AAMI subjects may comprise both AD and normal subjects. Therefore a more prospective study is needed. (author)

  14. LIVE ATTENUATED VACCINES FOR THE IMMUNOPROPHYLAXIS

    Directory of Open Access Journals (Sweden)

    O. A. Shamsutdinova

    2017-01-01

    Full Text Available The review focuses on the history of the production of live antiviral vaccines and their use for the prevention of infectious diseases. It was noted that before the beginning of the 20th century, only three live vaccines were developed and put into practice — against smallpox, rabies, plague. The discovery of D. Enders, T.H. Weller and F.Ch. Robins of the ability of the polio virus, and then of a number of other viruses, to reproduce in vitro in cell cultures of various types, greatly expanded the studies on the production of attenuated strains of viruses for live vaccines. The historical stages of obtaining and introducing live vaccines for the prevention of smallpox, poliomyelitis, measles, rubella, and mumps are highlighted. Arguments in favor of the use of associated vaccine preparations for the prevention of viral infections are presented. Various variants of the strategy and tactics of using live vaccines, which are used for specific prevention of viral infections in different countries, are described. The review provides information on technological methods for obtaining antiviral vaccines. The publications testifying to the development of specific reactions in immunized vaccine strains of measles, mumps, poliomyelitis and rubella viruses, such as aseptic meningitis (vaccine strains of mumps virus, acute arthritis (vaccine rubella virus strains, temperature reactions, rash (vaccine strains of the virus Measles, vaccine-associated paralytic poliomyelitis (VAPP vaccine vaccine poliovirus. It is particularly noted that the long experience of vaccine prevention both in Russia and abroad convincingly shows that the risk of developing post-vaccination complications is incommensurably lower than the risk of causing harm to health from the corresponding infections. It is concluded that despite introduction of new third and fourth generation vaccines into practice, live attenuated vaccines do not lose their significance and are used in vaccine

  15. Dengue vaccines: implications for dengue control.

    Science.gov (United States)

    Robinson, Matthew L; Durbin, Anna P

    2017-10-01

    Dengue, the most common arbovirus, is an increasingly significant cause of morbidity worldwide. After decades of research, an approved tetravalent dengue vaccine is finally available. Models constructed using recently available vaccine efficacy data allow for a data-driven discussion of the potential impact of dengue vaccine deployment on global control. Phase 3 efficacy trials demonstrated that the approved dengue vaccine, chimeric yellow fever-dengue-tetravalent dengue vaccine, has an efficacy of 60% against dengue illness of any severity. However, among dengue unexposed recipients, vaccination offers limited efficacy and may increase dengue severity. The WHO consequently recommends dengue vaccination for populations in which 70% of intended recipients are dengue seropositive. Models predict that routine childhood dengue vaccine may reduce dengue burden, but over time, population-level impact may be limited. Additional vaccine candidates in late-stage development may not suffer from the same limitations as chimeric yellow fever-dengue-tetravalent dengue vaccine. The efficacy and safety profile of the recently approved dengue vaccine is favorable only in previously dengue exposed recipients, which limits its potential for global control. Future work must evaluate the approved vaccine's long-term durability, efficacy of other late phase vaccine candidates, and potential for vector control efforts to work synergistically with vaccine deployment.

  16. Anthrax Vaccine

    Science.gov (United States)

    ... anthrax vaccine causes long-term health problems.Independent civilian committees have not found anthrax vaccination to be ... doctor, or get the person to a doctor right away. Tell your doctor what happened, the date ...

  17. Vaccine Safety

    Science.gov (United States)

    ... Search Form Controls Cancel Submit Search The CDC Vaccine Safety Note: Javascript is disabled or is not ... CDC.gov . Recommend on Facebook Tweet Share Compartir Vaccine Adverse Events Reporting System (VAERS) New website and ...

  18. Vaccine Finder

    Science.gov (United States)

    ... list . Showing availability for 6,604 locations. Influenza Vaccine Recommended for everyone greater than or equal to ... which one may be right for you! Flu Vaccines Protects again influenza, commonly called flu, a respiratory ...

  19. Stability testing of vaccines: Developing Countries Vaccine Manufacturers' Network (DCVMN) perspective.

    Science.gov (United States)

    Jadhav, Suresh S; Dogar, Vikas; Gautam, Manish; Gairola, Sunil

    2009-11-01

    Stability testing is an integral part of the vaccine manufacturing process and is crucial for the success of immunization programs. WHO (World Health Organization) has recently published guidelines on the stability testing of vaccines. These guidelines enlist scientific basis and principles for stability testing at various stages like development, pre-clinical, clinical, licensing, lot release and post-licensure monitoring. DCVMN (Developing Countries Vaccine Manufacturers' Network) is an international body of developing countries vaccine manufacturers and has viewpoints on technical and administrative issues in stability testing of vaccines. We here highlight viewpoints, possible roles and global expectations of DCVMN in the area of stability testing of vaccines.

  20. ROTAVIRUS VACCINES

    OpenAIRE

    Kang, G

    2006-01-01

    Rotavirus, the most common cause of severe diarrhea and a leading cause of mortality in children, has been a priority target for vaccine development for the past several years. The first rotavirus vaccine licensed in the United States was withdrawn because of an association of the vaccine with intussusception. However, the need for a vaccine is greatest in the developing world, because the benefits of preventing deaths due to rotavirus disease are substantially greater than the risk of intuss...

  1. Oral lipid-based nanoformulation of tafenoquine enhanced bioavailability and blood stage antimalarial efficacy and led to a reduction in human red blood cell loss in mice

    Directory of Open Access Journals (Sweden)

    Melariri P

    2015-02-01

    Full Text Available Paula Melariri,1 Lonji Kalombo,2 Patric Nkuna,2 Admire Dube,2,3 Rose Hayeshi,2 Benhards Ogutu,4,5 Liezl Gibhard,6 Carmen deKock,6 Peter Smith,6 Lubbe Wiesner,6 Hulda Swai2 1Polymers and Composites, Material Science and Manufacturing, Council for Scientific and Industrial Research, Port Elizabeth, South Africa; 2Polymer and Composites, Material Science and Manufacturing, Council for Scientific and Industrial Research, Pretoria, South Africa; 3School of Pharmacy, University of the Western Cape, Bellville, South Africa; 4Centre for Research in Therapeutic Sciences, Strathmore University, Nairobi, Kenya; 5Centre for Clinical Research, Kenya Medical Research Institute, Nairobi, Kenya; 6Division of Pharmacology, University of Cape Town Medical School, Groote Schuur Hospital, Cape Town, South Africa Abstract: Tafenoquine (TQ, a new synthetic analog of primaquine, has relatively poor bioavailability and associated toxicity in glucose-6-phosphate dehydrogenase (G6PD-deficient individuals. A microemulsion formulation of TQ (MTQ with sizes <20 nm improved the solubility of TQ and enhanced the oral bioavailability from 55% to 99% in healthy mice (area under the curve 0 to infinity: 11,368±1,232 and 23,842±872 min·µmol/L for reference TQ and MTQ, respectively. Average parasitemia in Plasmodium berghei-infected mice was four- to tenfold lower in the MTQ-treated group. In vitro antiplasmodial activities against chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum indicated no change in half maximal inhibitory concentration, suggesting that the microemulsion did not affect the inherent activity of TQ. In a humanized mouse model of G6PD deficiency, we observed reduction in toxicity of TQ as delivered by MTQ at low but efficacious concentrations of TQ. We hereby report an enhancement in the solubility, bioavailibility, and efficacy of TQ against blood stages of Plasmodium parasites without a corresponding increase in toxicity

  2. Effects of dexamethasone treatment and respiratory vaccination on rectal temperature, complete blood count, and functional capacities of neutrophils in beef steers

    Science.gov (United States)

    The objective of this research was to examine the effects of dexamethasone (DEX) treatment on various aspects of immunity following administration of a multivalent respiratory vaccine, using a model intended to mimic acute versus chronic stress. Angus × Hereford steers (n = 32; 209 ± 8 kg) were str...

  3. Contraceptive Vaccines

    Directory of Open Access Journals (Sweden)

    M.V. Supotnitsky

    2014-02-01

    Full Text Available Researches to develop vaccines with contraceptive effect are being carried out since the 1920s. Since 1972, the contraceptive vaccines are one of the priority programs of the World Health Organization (WHO Special Programme of Research, Development and Research Training in Human Reproduction. Rockefeller Foundation participates in implementing the program. Openly declared objective of creating such vaccines — the regulation of the population in the Third World countries. There are currently three main directions of contraceptive vaccine design: 1 vaccines targeted at blocking the production of gametes; 2 impairing their function; 3 violating the fertilization process. Contraceptive vaccines for more than 10 years are widely used to reduce fertility and castration of wild and domestic animals. In the commercial realization there are veterinary vaccines Equity®, Improvac®, GonaCon®, Repro-BLOC (based on gonadotropin-releasing hormone; SpayVac™ and IVT-PZP® (based on zona pellucida antigens. Clinical studies have shown effective contraceptive action (in women of vaccines, in which human chorionic gonadotropin is used as an antigen. At the same time, there are found the side effects of such vaccines: for vaccines containing gonadotropin-releasing hormone and luteinizing hormone as antigenic components — castration, impotence; for vaccines containing follicle stimulating hormone — oligospermia; zona pellucida antigens — irreversible oophoritis. This paper discusses approaches to detection of sterilizing components in vaccines intended for mass prevention of infectious diseases, not reported by manufacturers, and the consequences of their use. Hidden use of contraceptive vaccines, which already took place, can be detected: 1 by the presence of antibodies to their antigenic components (in unvaccinated by contraceptive vaccines people such antibodies do not exist, except infertility cases; 2 by change in the hormonal levels of the

  4. Immune reactivity in early life stages of sea-cage cultured Pacific bluefin tuna naturally infected with blood flukes from genus Cardicola (Trematoda: Aporocotylidae).

    Science.gov (United States)

    Pennacchi, Ylenia; Shirakashi, Sho; Nowak, Barbara F; Bridle, Andrew R

    2016-11-01

    Pacific bluefin tuna (PBT), Thunnus orientalis, due to its high average price on the market is an economically valuable fish species. Infections by blood flukes from the genus Cardicola (Trematoda: Aporocotylidae) represent a growing concern for the cage culture of bluefin tuna in Japan, Australia and Southern Europe. The accumulation of numerous Cardicola eggs in the fish gills causes severe pathology that has been linked to mortality in PBT juveniles up to one year old. The only effective treatment used to mitigate the infection is the oral administration of the antihelminthic drug praziquantel (PZQ) to the affected fish. However, with the need to minimise therapeutic drug use in aquaculture it is hoped that immunoprophylaxis can provide a future alternative to protect the PBT juveniles against Cardicola infection. Currently, little is known of the host immune response to these parasites and of their infection dynamics. In this study, using real-time qPCR we aimed to quantitatively detect C. orientalis and C. opisthorchis DNA within the gills and heart of cultured PBT juveniles and to investigate the host immune response at the transcriptional level in the gills. The research focused mainly during early stages of infection soon after young PBT were transferred to culture cages (from 14 to 77 days post-transfer). An increase (up to 11-fold) of immune-related genes, namely IgM, MHC-I, TCR-β and IL-1β was observed in the PBT gills infected with Cardicola spp. (28-77 days post-transfer). Furthermore, IgM (19-fold increase) and MHC-I (11.5-fold increase) transcription was strongly up-regulated in gill samples of PBT infected with C. orientalis relative to uninfected fish but not in fish infected with C. opisthorchis. Cardicola-specific DNA was first detected in the host 14 days post-transfer (DPT) to sea-cages which was 55 days earlier than the first detection of parasite eggs and adults by microscopy. Oral administration of PZQ did not have an immediate effect

  5. Third-stage Gnathostoma spinigerum larva excretory secretory antigens modulate function of Fc gamma receptor I-mediated monocytes in peripheral blood mononuclear cell culture.

    Science.gov (United States)

    Benjathummarak, Surachet; Kumsiri, Ratchanok; Nuamtanong, Supaporn; Kalambaheti, Thareerat; Waikagul, Jitra; Viseshakul, Nareerat; Maneerat, Yaowapa

    2016-01-01

    Third (infective)-stage Gnathostoma spinigerum larvae (L3) mainly cause human gnathostomiasis. G. spinigerum L3 migrate throughout the subcutaneous tissues, vital organs, and central nervous system and can cause various pathogenesis including sudden death. Interestingly, G. spinigerum L3 can survive and evade host cellular immunity for months or years. The effects of G. spinigerum excretory-secretory (ES) products involved in larval migration and immune-evasive strategies are unknown. Monocytes are innate immune cells that act as phagocytic and antigen-presenting cells and also play roles against helminthic infections via a complex interplay between other immune cells. Fc gamma receptor I (FcγRI) is a high-affinity receptor that is particularly expressed on monocytes, macrophages, and dendritic cells. The cross-linking of FcγRI and antigen-antibody complex initiates signal transduction cascades in phagocytosis, cytokine production, and antibody-dependent cell-mediated cytotoxicity (ADCC). This study investigated whether ES antigen (ESA) from G. spinigerum L3 affects monocyte functions. Cultures of normal peripheral blood mononuclear cells (PBMC) separated from healthy buffy coats were used as a human immune cell model. ESA was prepared from G. spinigerum L3 culture. Using Real-Time quantitative reverse transcription-polymerase chain reaction (qRT-PCR), the effect of ESA to down-regulate FcγRI mRNA expression in monocytes during 90 min of observation was not well delineated. Flow cytometry analysis revealed a significant phenotypic-decreased FcγRI expression on the monocyte surface at 12 hours (h) of cultivation with the ESA (p = 0.033). Significantly reduced monocyte-mediated phagocytosis capacity was consistently observed after 12 h of ESA pretreatment (p = 0.001). Our results suggest that G. spinigerum ESA modulates monocyte function via depletion of FcγRI expression. This study provides preliminary information for future in-depth studies to

  6. FLU VACCINATION

    CERN Document Server

    2007-01-01

    People working on the CERN site who wish to be vaccinated may go to the Infirmary (ground-floor, bldg. 57), with their vaccine, without a prior appointment. The vaccine can be reimbursed directly by Uniqa providing you attach the receipt and the prescription that you will receive from the Medical Service the day of your injection at the infirmary. Ideally, the vaccination should take place between 1st October and 30th November 2007 (preferably between 14:00 and 16:00). CERN staff aged 50 or over are recommended to have influenza vaccinations. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and those convalescing from serious medical problems or after serious surgical operations. The Medical Service will not administer vaccines for family members or retired staff members, who must contact their normal family doctor. Medical Service

  7. Daily Plasmodium yoelii infective mosquito bites do not generate protection or suppress previous immunity against the liver stage

    Directory of Open Access Journals (Sweden)

    Wong Kurt A

    2011-04-01

    Full Text Available Abstract Background Human populations that are naturally subjected to Plasmodium infection do not acquire complete protection against the liver stage of this parasite despite prolonged and frequent exposure. However, sterile immunity against Plasmodium liver stage can be achieved after repeated exposure to radiation attenuated sporozoites. The reasons for this different response remain largely unknown, but a suppressive effect of blood stage Plasmodium infection has been proposed as a cause for the lack of liver stage protection. Methods Using Plasmodium yoelii 17XNL, the response generated in mice subjected to daily infective bites from normal or irradiated mosquitoes was compared. The effect of daily-infected mosquito bites on mice that were previously immunized against P. yoelii liver stage was also studied. Results It was observed that while the bites of normal infected mosquitoes do not generate strong antibody responses and protection, the bites of irradiated mosquitoes result in high levels of anti-sporozoite antibodies and protection against liver stage Plasmodium infection. Exposure to daily infected mosquito bites did not eliminate the protection acquired previously with a experimental liver stage vaccine. Conclusions Liver stage immunity generated by irradiated versus normal P. yoelii infected mosquitoes is essentially different, probably because of the blood stage infection that follows normal mosquito bites, but not irradiated. While infective mosquito bites do not induce a protective liver stage response, they also do not interfere with previously acquired liver stage protective responses, even if they induce a complete blood stage infection. Considering that the recently generated anti-malaria vaccines induce only partial protection against infection, it is encouraging that, at least in mouse models, immunity is not negatively affected by subsequent exposure and infection with the parasite.

  8. Effects of the DASH-JUMP dietary intervention in Japanese participants with high-normal blood pressure and stage 1 hypertension: an open-label single-arm trial

    OpenAIRE

    Kawamura, Atsuko; Kajiya, Katsuko; Kishi, Hiroko; Inagaki, Junko; Mitarai, Makoto; Oda, Hiroshi; Umemoto, Seiji; Kobayashi, Sei

    2016-01-01

    The Dietary Approaches to Stop Hypertension (DASH) diet is recommended by the American Heart Association to lower blood pressure (BP); however, its effects in Japanese participants have not been rigorously studied. We assessed the effects of the DASH-Japan Ube Modified diet Program (DASH-JUMP), a modified DASH diet, on cardiometabolic and inflammatory biomarkers in Japanese participants with untreated high-normal BP or stage 1 hypertension. Fifty-eight participants (30 men and 28 women; mean ...

  9. An assessment in rodents of the pathological and immunopathological consequence of multiple vaccinations and challenge with radiation-attenuated malaria parasites (blood forms and sporozoites)

    International Nuclear Information System (INIS)

    Boonpucknavig, S.

    1982-06-01

    Multiple vaccination with irradiated merozoites of Plasmodium berghei resulted in high levels of circulating antibody but a low degree of protection to challenge with normal merozoites. On the other hand, the multiple vaccinations and the challenge resulted in severe immunopathological reactions shortly after the immunization or challenge. These reactions were seen in the liver, kidneys and spleen and included the accumulation of mononuclear cells, severe coagulative necrosis of liver cells and proliferative changes in the splenic white pulp and in the glomeruli. The pathological reactions were more severe than in non-immunized animals but the parasitemia was lower and less malarial antigen was detected in Kupfer Cells of the liver, the sinusoidal cells of the spleen and the reticuloendothelial cells in the interstitial tissue of the kidney. Vaccination with irradiated sporozoites of P. berghei resulted in good protection to challenge with normal sporozoites even before circulating anti-sporozoite antibody could be detected. Only mild pathological changes were associated with up to 4 immunizations followed by challenge and these were largely limited to the liver, and were reversible. Sporozoite antigens were detected in the spleen and immune complexes in the glomeruli for 2-4 weeks following challenge but not later. Immunized mice however often developed some lobular pneumonia of the lung but the severity of this did not increase with challenge

  10. Access to Liver Transplantation in Different ABO-Blood Groups and "Exceptions Points" in a Model for End-Stage Liver Disease Allocation System: A Brazilian Single-Center Study.

    Science.gov (United States)

    Martino, R B; Waisberg, D R; Dias, A P M; Inoue, V B S; Arantes, R M; Haddad, L B P; Rocha-Santos, V; Pinheiro, R S N; Nacif, L S; D'Albuquerque, L A C

    2018-04-01

    In the Model for End-Stage Liver Disease (MELD) system, patients with "MELD exceptions" points may have unfair privilege in the competition for liver grafts. Furthermore, organ distribution following identical ABO blood types may also result in unjust organ allocation. The aim of this study was to investigate access to liver transplantation in a tertiary Brazilian center, regarding "MELD exceptions" situations and among ABO-blood groups. A total of 465 adult patients on the liver waitlist from August 2015 to August 2016 were followed up until August 2017. Patients were divided into groups according to ABO-blood type and presence of "exceptions points." No differences in outcomes were observed among ABO-blood groups. However, patients from B and AB blood types spent less time on the list than patients from A and O groups (median, 46, 176, 415, and 401 days, respectively; P = .03). "Exceptions points" were granted for 141 patients (30.1%), hepatocellular carcinoma being the most common reason (52.4%). Patients with "exceptions points" showed higher transplantation rate, lower mortality on the list, and lower delta-MELD than non-exceptions patients (56.7% vs 19.1% [P blood types, despite shorter time on the waitlist for AB and B groups. The current MELD exception system provides advantages for candidates with "exception points," resulting in superior outcomes compared with those without exceptions. Copyright © 2018 Elsevier Inc. All rights reserved.

  11. A Research Agenda for Malaria Eradication: Vaccines

    Science.gov (United States)

    2011-01-01

    Vaccines could be a crucial component of efforts to eradicate malaria. Current attempts to develop malaria vaccines are primarily focused on Plasmodium falciparum and are directed towards reducing morbidity and mortality. Continued support for these efforts is essential, but if malaria vaccines are to be used as part of a repertoire of tools for elimination or eradication of malaria, they will need to have an impact on malaria transmission. We introduce the concept of “vaccines that interrupt malaria transmission” (VIMT), which includes not only “classical” transmission-blocking vaccines that target the sexual and mosquito stages but also pre-erythrocytic and asexual stage vaccines that have an effect on transmission. VIMT may also include vaccines that target the vector to disrupt parasite development in the mosquito. Importantly, if eradication is to be achieved, malaria vaccine development efforts will need to target other malaria parasite species, especially Plasmodium vivax, where novel therapeutic vaccines against hypnozoites or preventive vaccines with effect against multiple stages could have enormous impact. A target product profile (TPP) for VIMT is proposed and a research agenda to address current knowledge gaps and develop tools necessary for design and development of VIMT is presented. PMID:21311586

  12. [Guidelines for vaccination of immunocompromised individuals].

    Science.gov (United States)

    Wiedermann, Ursula; Sitte, Harald H; Burgmann, Heinz; Eser, Alexander; Falb, Petra; Holzmann, Heidemarie; Kitchen, Maria; Köller, Marcus; Kollaritsch, Herwig; Kundi, Michael; Lassmann, Hans; Mutz, Ingomar; Pickl, Winfried F; Riedl, Elisabeth; Sibilia, Maria; Thalhammer, Florian; Tucek, Barbara; Zenz, Werner; Zwiauer, Karl

    2016-08-01

    Immunosuppression of various origins is associated with an increased risk of infection; therefore the prevention of infectious diseases by vaccination is especially important in immunocompromised patients. However, the response to vaccinations is often reduced in these risk groups and the application of live vaccines is contraindicated during immunosuppression.In the following expert statement, recommendations for vaccination were created on the basis of current evidence and theoretical/immunological considerations. A first, general part elaborates on efficacy and safety of vaccinations during immunosuppression, modes of action of immunosuppressive medications and recommended time intervals between immunosuppressive treatments and vaccinations. A core piece of this part is a graduation of immunosuppression into three stages, i. e. no relevant immunosuppression, mild to moderate and severe immunosuppression and the assignment of various medications (including biologicals) to one of those stages; this is followed by an overview of possible and necessary vaccinations in each of those stages.The second part gives detailed vaccination guidelines for common diseases and therapies associated with immunosuppression. Primary immune deficiencies, chronic kidney disease, diabetes mellitus, solid and hematological tumors, hematopoetic stem cell transplantation, transplantation of solid organs, aspenia, rheumatological-, gastroenterologic-, dermatologic-, neurologic diseases, biologicals during pregnancy and HIV infection are dealt with.These vaccination guidelines, compiled for the first time in Austria, aim to be of practical help for physicians to facilitate and improve vaccination coverage in immunocompromised patients and their household members and contact persons.

  13. Toward the development of effective transmission-blocking vaccines for malaria.

    Science.gov (United States)

    Nikolaeva, Daria; Draper, Simon J; Biswas, Sumi

    2015-05-01

    The continued global burden of malaria can in part be attributed to a complex lifecycle, with both human hosts and mosquito vectors serving as transmission reservoirs. In preclinical models of vaccine-induced immunity, antibodies to parasite sexual-stage antigens, ingested in the mosquito blood meal, can inhibit parasite survival in the insect midgut as judged by ex vivo functional studies such as the membrane feeding assay. In an era of renewed political momentum for malaria elimination and eradication campaigns, such observations have fueled support for the development and implementation of so-called transmission-blocking vaccines. While leading candidates are being evaluated using a variety of promising vaccine platforms, the field is also beginning to capitalize on global '-omics' data for the rational genome-based selection and unbiased characterization of parasite and mosquito proteins to expand the candidate list. This review covers the progress and prospects of these recent developments.

  14. Development of malaria transmission-blocking vaccines: from concept to product.

    Science.gov (United States)

    Wu, Yimin; Sinden, Robert E; Churcher, Thomas S; Tsuboi, Takafumi; Yusibov, Vidadi

    2015-06-01

    Despite decades of effort battling against malaria, the disease is still a major cause of morbidity and mortality. Transmission-blocking vaccines (TBVs) that target sexual stage parasite development could be an integral part of measures for malaria elimination. In the 1950s, Huff et al. first demonstrated the induction of transmission-blocking immunity in chickens by repeated immunizations with Plasmodium gallinaceum-infected red blood cells. Since then, significant progress has been made in identification of parasite antigens responsible for transmission-blocking activity. Recombinant technologies accelerated evaluation of these antigens as vaccine candidates, and it is possible to induce effective transmission-blocking immunity in humans both by natural infection and now by immunization with recombinant vaccines. This chapter reviews the efforts to produce TBVs, summarizes the current status and advances and discusses the remaining challenges and approaches. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Human vaccination against RH5 induces neutralizing antimalarial antibodies that inhibit RH5 invasion complex interactions

    DEFF Research Database (Denmark)

    Payne, Ruth O; Silk, Sarah E; Elias, Sean C

    2017-01-01

    The development of a highly effective vaccine remains a key strategic goal to aid the control and eventual eradication of Plasmodium falciparum malaria. In recent years, the reticulocyte-binding protein homolog 5 (RH5) has emerged as the most promising blood-stage P. falciparum candidate antigen......-deficient chimpanzee adenovirus serotype 63 (ChAd63), and the attenuated orthopoxvirus modified vaccinia virus Ankara (MVA), encoding RH5 from the 3D7 clone of P. falciparum. Vaccines were administered i.m. in a heterologous prime-boost regimen using an 8-week interval and were well tolerated. Vaccine-induced anti-RH5...... serum antibodies exhibited cross-strain functional growth inhibition activity (GIA) in vitro, targeted linear and conformational epitopes within RH5, and inhibited key interactions within the RH5 invasion complex. This is the first time to our knowledge that substantial RH5-specific responses have been...

  16. Comparative efficacy of pre-erythrocytic whole organism vaccine strategies against the malaria parasite.

    Science.gov (United States)

    Friesen, Johannes; Matuschewski, Kai

    2011-09-16

    Despite major efforts over the past 50 years to develop a malaria vaccine, no product has been licensed yet. Irradiated sporozoites are the benchmark for an experimental live-attenuated malaria vaccine that induces potent protection against re-infection in humans and animal models. Lasting protection can also be elicited by parasite attenuation via tailored genetic modification or drug cover leading to renewed interest in whole-organism vaccination strategies. In this study, we systematically compared the protective efficacy of different whole-organism vaccination approaches in the Plasmodium berghei/C57bl/6 rodent malaria model. We applied blood stage parasitemia and quantitative RT-PCR of liver parasite loads as two complementary primary endpoints of a malaria challenge infection. We were able to demonstrate similar potency of genetic attenuation, i.e., uis3(-) and p36p(-) parasites, and prophylactic drug cover, i.e., azithromycin, pyrimethamine, primaquine and chloroquine, during sporozoite exposure in comparison to irradiated sporozoites. Importantly, when animals were covered with the antibiotic azithromycin during sporozoite exposure we observed superior protection. On the other end, immunizations with heat-killed and over-irradiated sporozoites failed to confer any detectable protection. Together, we show that systematic pre-clinical evaluation and quantification of vaccine efficacy is vital for identification of the most potent whole organism anti-malaria vaccine strategy. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Status of vaccine research and development of vaccines for malaria.

    Science.gov (United States)

    Birkett, Ashley J

    2016-06-03

    Despite recent progress in reducing deaths attributable to malaria, it continues to claim approximately 500,000 lives per year and is associated with approximately 200 million infections. New tools, including safe and effective vaccines, are needed to ensure that the gains of the last 15 years are leveraged toward achieving the ultimate goal of malaria parasite eradication. In 2015, the European Medicines Agency announced the adoption of a positive opinion for the malaria vaccine candidate most advanced in development, RTS,S/AS01, which provides modest protection against clinical malaria; in early 2016, WHO recommended large-scale pilot implementations of RTS,S in settings of moderate-to-high malaria transmission. In alignment with these advancements, the community goals and preferred product characteristics for next-generation vaccines have been updated to inform the development of vaccines that are highly efficacious in preventing clinical malaria, and those needed to accelerate parasite elimination. Next-generation vaccines, targeting all stages of the parasite lifecycle, are in early-stage development with the most advanced in Phase 2 trials. Importantly, progress is being made in the definition of feasible regulatory pathways to accelerate timelines, including for vaccines designed to interrupt transmission of parasites from humans to mosquitoes. The continued absence of financially lucrative, high-income markets to drive investment in malaria vaccine development points to continued heavy reliance on public and philanthropic funding. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  18. Hepatitis Vaccines

    Science.gov (United States)

    Ogholikhan, Sina; Schwarz, Kathleen B.

    2016-01-01

    Viral hepatitis is a serious health problem all over the world. However, the reduction of the morbidity and mortality due to vaccinations against hepatitis A and hepatitis B has been a major component in the overall reduction in vaccine preventable diseases. We will discuss the epidemiology, vaccine development, and post-vaccination effects of the hepatitis A and B virus. In addition, we discuss attempts to provide hepatitis D vaccine for the 350 million individuals infected with hepatitis B globally. Given the lack of a hepatitis C vaccine, the many challenges facing the production of a hepatitis C vaccine will be shown, along with current and former vaccination trials. As there is no current FDA-approved hepatitis E vaccine, we will present vaccination data that is available in the rest of the world. Finally, we will discuss the existing challenges and questions facing future endeavors for each of the hepatitis viruses, with efforts continuing to focus on dramatically reducing the morbidity and mortality associated with these serious infections of the liver. PMID:26978406

  19. [Laser doppler estimation of the influence of tobacco-smoking on the blood microcirculation in the periodont at the patients with the different stages of periodontal diseases].

    Science.gov (United States)

    Grudianov, A I; Kemulariia, I V

    2010-01-01

    Smoking appears to be one of the most significant risk factors in the development and progression of periodontal disease. Smoking is also a risk factor in the development of peripheral vascular diseases. Blood vessels in smokers are fewer and are subjected to stenosis. Clinically, it is well known that bleeding on probing, gingival exudates and redness and swelling in gingival sites of smokers are less than in non-smokers. According to previous studies, there is a relative increase in gingival blood flow immediately after smoking, while gingival blood flow itself is considerably decreased in healthy smokers in comparison with non-smokers. In this investigation, we used laser Doppler flowmetry to study gingival microcirculation in smokers with light, moderate and heavy periodontitis in comparison with non-smokers with the same diseases. Our results show, that smoking decreases gingival blood flow in smokers with periodontitis comparing to non-smokers with periodontitis. Immediately after smoking there is an increase in gingival microcirculation. In 30 minutes we observed a marked decrease in gingival blood flow in all groups, followed by gradual restoration of blood flow rate, registered before smoking. This restoration took 1.5-2 hrs in group with light periodontitis, 2 hrs in group with moderate periodontitis and more than 2 hrs in group with heavy periodontitis. We suppose, that constant changes in blood supply of periodontal tissue caused by smoking may contribute to higher prevalence and faster progression of inflammatory periodontal diseases in smokers.

  20. Arterial spin labeling perfusion-weighted MR imaging: correlation of tumor blood flow with pathological degree of tumor differentiation, clinical stage and nodal metastasis of head and neck squamous cell carcinoma.

    Science.gov (United States)

    Abdel Razek, Ahmed Abdel Khalek; Nada, Nadia

    2018-05-01

    The prognostic parameters of head and neck squamous cell carcinoma (HNSCC) include the pathological degree of tumor differentiation, clinical staging, and presence of metastatic cervical lymph nodes. To correlate tumor blood flow (TBF) acquired from arterial spin labeling (ASL) perfusion-weighted MR imaging with pathological degree of tumor differentiation, clinical stage, and nodal metastasis of HNSCC. Retrospective analysis of 43 patients (31 male, 12 female with a mean age of 65 years) with HNSCC that underwent ASL of head and neck and TBF of HNSCC was calculated. Tumor staging and metastatic lymph nodes were determined. The stages of HNSCC were stage 1 (n = 7), stage II (n = 12), stage III (n = 11) and stage IV (n = 13). Metastatic cervical lymph nodes were seen in 24 patients. The degree of tumor differentiation was determined through pathological examination. The mean TBF of poorly and undifferentiated HNSCC (157.4 ± 6.7 mL/100 g/min) was significantly different (P = 0.001) than that of well-to-moderately differentiated (142.5 ± 5.7 mL/100 g/min) HNSCC. The cut-off TBF used to differentiate well-moderately differentiated from poorly and undifferentiated HNSCC was 152 mL/100 g/min with an area under the curve of 0.658 and accuracy of 88.4%. The mean TBF of stages I, II (146.10 ± 9.1 mL/100 g/min) was significantly different (P = 0.014) than that of stages III, IV (153.33 ± 9.3 mL/100 g/min) HNSCC. The cut-off TBF used to differentiate stages I, II from stages III and IV was 148 mL/100 g/min with an area under the curve of 0.701 and accuracy of 69.8%. The TBF was higher in patients with metastatic cervical lymph nodes. The cut-off TBF suspect metastatic node was 147 mL/100 g/min with an area under the curve of 0.671 and accuracy of 67.4%. TBF is a non-invasive imaging parameter that well correlated with pathological degree of tumor differentiation, clinical stage of tumor and nodal metastasis of HNSCC.

  1. Safety and immunogenicity of multi-antigen AMA1-based vaccines formulated with CoVaccine HT™ and Montanide ISA 51 in rhesus macaques

    Directory of Open Access Journals (Sweden)

    Walraven Vanessa

    2011-07-01

    Full Text Available Abstract Background Increasing the breadth of the functional antibody response through immunization with Plasmodium falciparum apical membrane antigen 1 (PfAMA1 multi-allele vaccine formulations has been demonstrated in several rodent and rabbit studies. This study assesses the safety and immunogenicity of three PfAMA1 Diversity-Covering (DiCo vaccine candidates formulated as an equimolar mixture (DiCo mix in CoVaccine HT™ or Montanide ISA 51, as well as that of a PfAMA1-MSP119 fusion protein formulated in Montanide ISA 51. Methods Vaccine safety in rhesus macaques was monitored by animal behaviour observation and assessment of organ and systemic functions through clinical chemistry and haematology measurements. The immunogenicity of vaccine formulations was assessed by enzyme-linked immunosorbent assays and in vitro parasite growth inhibition assays with three culture-adapted P. falciparum strains. Results These data show that both adjuvants were well tolerated with only transient changes in a few of the chemical and haematological parameters measured. DiCo mix formulated in CoVaccine HT™ proved immunologically and functionally superior to the same candidate formulated in Montanide ISA 51. Immunological data from the fusion protein candidate was however difficult to interpret as four out of six immunized animals were non-responsive for unknown reasons. Conclusions The study highlights the safety and immunological benefits of DiCo mix as a potential human vaccine against blood stage malaria, especially when formulated in CoVaccine HT™, and adds to the accumulating data on the specificity broadening effects of DiCo mix.

  2. Safety and High Level Efficacy of the Combination Malaria Vaccine Regimen of RTS,S/AS01B With Chimpanzee Adenovirus 63 and Modified Vaccinia Ankara Vectored Vaccines Expressing ME-TRAP.

    Science.gov (United States)

    Rampling, Tommy; Ewer, Katie J; Bowyer, Georgina; Bliss, Carly M; Edwards, Nick J; Wright, Danny; Payne, Ruth O; Venkatraman, Navin; de Barra, Eoghan; Snudden, Claudia M; Poulton, Ian D; de Graaf, Hans; Sukhtankar, Priya; Roberts, Rachel; Ivinson, Karen; Weltzin, Rich; Rajkumar, Bebi-Yassin; Wille-Reece, Ulrike; Lee, Cynthia K; Ockenhouse, Christian F; Sinden, Robert E; Gerry, Stephen; Lawrie, Alison M; Vekemans, Johan; Morelle, Danielle; Lievens, Marc; Ballou, Ripley W; Cooke, Graham S; Faust, Saul N; Gilbert, Sarah; Hill, Adrian V S

    2016-09-01

    The need for a highly efficacious vaccine against Plasmodium falciparum remains pressing. In this controlled human malaria infection (CHMI) study, we assessed the safety, efficacy and immunogenicity of a schedule combining 2 distinct vaccine types in a staggered immunization regimen: one inducing high-titer antibodies to circumsporozoite protein (RTS,S/AS01B) and the other inducing potent T-cell responses to thrombospondin-related adhesion protein (TRAP) by using a viral vector. Thirty-seven healthy malaria-naive adults were vaccinated with either a chimpanzee adenovirus 63 and modified vaccinia virus Ankara-vectored vaccine expressing a multiepitope string fused to TRAP and 3 doses of RTS,S/AS01B (group 1; n = 20) or 3 doses of RTS,S/AS01B alone (group 2; n = 17). CHMI was delivered by mosquito bites to 33 vaccinated subjects at week 12 after the first vaccination and to 6 unvaccinated controls. No suspected unexpected serious adverse reactions or severe adverse events related to vaccination were reported. Protective vaccine efficacy was observed in 14 of 17 subjects (82.4%) in group 1 and 12 of 16 subjects (75%) in group 2. All control subjects received a diagnosis of blood-stage malaria parasite infection. Both vaccination regimens were immunogenic. Fourteen protected subjects underwent repeat CHMI 6 months after initial CHMI; 7 of 8 (87.5%) in group 1 and 5 of 6 (83.3%) in group 2 remained protected. The high level of sterile efficacy observed in this trial is encouraging for further evaluation of combination approaches using these vaccine types. NCT01883609. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America.

  3. A Controlled Study on Vaginal Blood Flow During Sexual Arousal Among Early-Stage Cervical Cancer Survivors Treated With Conventional Radical or Nerve-Sparing Surgery With or Without Radiotherapy.

    Science.gov (United States)

    Bakker, Rinske Maria; Pieterse, Quirine D; van Lonkhuijzen, Luc R C W; Trimbos, Baptist J B M Z; Creutzberg, Carien L; Kenter, Gemma G; de Kroon, Cor D; Ter Kuile, Moniek M

    2017-06-01

    Sexual problems among cervical cancer survivors may in part be caused by reduced vaginal blood flow due to damaged hypogastric nerves during radical hysterectomy with pelvic lymphadenectomy and/or by radiation-induced vaginal changes after pelvic radiotherapy. A nerve-sparing modification of radical hysterectomy (NSRH) may preserve vaginal blood flow. Vaginal blood flow during sexual arousal was compared between different treatment modalities. We investigated premenopausal women treated for early-stage cervical cancer with radical hysterectomy (n = 29), NSRH (n = 28), NSRH with radiotherapy (n = 14), and controls (n = 31). Genital arousal and subjective sexual arousal in response to sexual stimuli were measured using vaginal photoplethysmography and a questionnaire. Results were compared by using a between-study (treatment groups) by within-study (stimulus) design. Participants were aged 29 to 51 years (mean, 42 years) and at 1 to 14 years (mean, 5 years) after treatment. Measured vaginal blood flow in women treated with NSRH was similar to controls. Women treated with radical hysterectomy had a significantly lower vaginal blood flow compared with controls overall and lower compared with the NSRH group during sexual stimulation. Women treated with radiotherapy had a vaginal blood flow intermediate between the other groups without significant differences. The erotic films were equally effective in enhancing subjective sexual arousal among treatment groups. Cervical cancer treatment with radical hysterectomy disrupts the vaginal blood flow response, and this may be prevented by conducting an NSRH. Treatment with radiotherapy did not significantly impact vaginal blood flow, but further investigation is needed with a larger sample.

  4. [Epidemiological characteristics of children aged 1-4 years without timely birth dose of hepatitis B vaccine vaccination in China, 2014].

    Science.gov (United States)

    Wang, F Z; Zhang, G M; Shen, L P; Liu, J H; Zheng, H; Wang, F; Miao, N; Sun, X J; Liang, X F; Cui, F Q

    2017-01-10

    Objective: To evaluate the epidemiological characteristics of the children aged 1-4 years without timely birth dose of hepatitis B vaccine (HepB(1)) vaccination. Methods: Based on the data from 160 disease surveillance points in 31 provinces of China, two-stage cluster random sampling was used to select the target population aged 1-4 years. A standard questionnaire was used to collect the information about the birth date, gender, ethnic group, place of birth, HepB immunization history of the children selected. A blood sample (3 ml) was taken from each subject for HBsAg testing. SAS software (Version 9.4) was used in our study. We analyzed the age, gender, ethnic group, area specific distributions of the children aged 1-4 years without timely HepB(1) vaccination and the influencing factors, and the relationship between the HepB(1) vaccination time and HBsAg prevalence rate. Results: A total of 12 587 children aged 1-4 years were analyzed and the non-timely HepB(1) vaccination rate was 10.12 % . The place of birth, ethnic group, urban/rural area, eastern/central/western area, age were the main influencing factor of the non-timely HepB(1) vaccination. The non-timely HepB(1) vaccination rate was higher in 3-4 years old children (11.13 % ) than in 1-2 years old children (8.97 % ), in rural area (12.05 % ) than in urban area (8.19 % ), in western area (13.41 % ) than in central area (9.27 % ) and eastern area (7.72 % ), in minority ethnic group (18.06 % ) than in Han ethnic group (8.77 % ) and in children born outside hospital (57.66 % ) than in children born in hospital (9.27 % ). The HBsAg prevalence rate among 1-4 years children was 0.31 % . The HBsAg prevalence rate of the children with timely HepB(1) vaccination (0.25 % ) was lower than that of the children without timely HepB(1) vaccination (0.89 % ). Conclusions: In China, the HBsAg prevalence rate among 1-4 years children with HepB vaccination decreased to vaccination rate reached to 90 % . We should strengthen

  5. Flu Vaccination

    CERN Document Server

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical service

  6. FLU VACCINATION

    CERN Document Server

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service

  7. Flu vaccination

    CERN Multimedia

    CERN Medical Service

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor.CERN Medical Service

  8. Flu Vaccination

    CERN Multimedia

    2006-01-01

    People working on the CERN site who wish to be vaccinated against influenza may go to the Medical Service (ground floor, Bldg. 57) without an appointment (preferably between 14:00 and 16:00), PROVIDED THAT THEY BRING THEIR OWN VACCINE WITH THEM. Ideally, vaccination should take place between 1st October and 30th November 2006. The influenza vaccine is recommended for CERN staff aged 50 and over. Vaccination is particularly important for those suffering from chronic lung, cardio-vascular or kidney problems, for diabetics and for those convalescing from serious medical problems or major surgery. The Medical Service will not administer vaccines to family members or retired staff members, who must contact their family doctor. CERN Medical Service

  9. Towards clinical development of a Pfs48/45-based transmission blocking malaria vaccine.

    Science.gov (United States)

    Theisen, Michael; Jore, Matthijs M; Sauerwein, Robert

    2017-04-01

    Malaria is a devastating vector-borne disease caused by the Plasmodium parasite, resulting in almost 0.5 million casualties per year. The parasite has a complex life-cycle that includes asexual replication in human red blood cells, causing symptomatic malaria, and sexual stages which are essential for the transmission to the mosquito vector. A vaccine targeting the sexual stages of the parasite and thus blocking transmission will be instrumental for the eradication of malaria. One of the leading transmission blocking vaccine candidates is the sexual stage antigen Pfs48/45. Areas covered: PubMed was searched to review the progress and future prospects for clinical development of a Pfs48/45-based subunit vaccine. We will focus on biological function, naturally acquired immunity, functional activity of specific antibodies, sequence diversity, production of recombinant protein and preclinical studies. Expert commentary: Pfs48/45 is one of the lead-candidates for a transmission blocking vaccine and should be further explored in clinical trials.

  10. Leptospirosis vaccines

    OpenAIRE

    Jin Li; Wang Zhijun; Węgrzyn Alicja

    2007-01-01

    Abstract Leptospirosis is a serious infection disease caused by pathogenic strains of the Leptospira spirochetes, which affects not only humans but also animals. It has long been expected to find an effective vaccine to prevent leptospirosis through immunization of high risk humans or animals. Although some leptospirosis vaccines have been obtained, the vaccination is relatively unsuccessful in clinical application despite decades of research and millions of dollars spent. In this review, the...

  11. Combination Vaccines

    OpenAIRE

    Skibinski, David AG; Baudner, Barbara C; Singh, Manmohan; O’Hagan, Derek T

    2011-01-01

    The combination of diphtheria, tetanus, and pertussis vaccines into a single product has been central to the protection of the pediatric population over the past 50 years. The addition of inactivated polio, Haemophilus influenzae, and hepatitis B vaccines into the combination has facilitated the introduction of these vaccines into recommended immunization schedules by reducing the number of injections required and has therefore increased immunization compliance. However, the development of th...

  12. Tumor vaccines:

    OpenAIRE

    Frank, Mojca; Ihan, Alojz

    2006-01-01

    Tumor vaccines have several potential advantages over standard anticancer regirrcents. They represent highly specific anticancer therapy. Inducing tumor-specific memory T-lymphocytes, they have potential for long-lived antitumor effects. However, clinical trials, in which cancer patients were vaccinated with tccmor aaccines, have been so far mainly disappointing. There are many reasons for the inefficiency of tumor vaccines. Most cancer antigens are normal self-molecules to which imrrtune tol...

  13. Issues Related to Recent Dengue Vaccine Development

    OpenAIRE

    Konishi, Eiji

    2011-01-01

    Dengue fever (DF) and dengue hemorrhagic fever (DHF) are mosquito-transmitted diseases of global importance. Despite significant research efforts, no approved vaccines or antiviral drugs against these diseases are currently available. This brief article reviews the status of dengue vaccine development, with particular emphasis on the vaccine strategies in more advanced stages of evaluation; these include traditional attenuation, chimerization and engineered attenuation. Several aspects of the...

  14. Vaccines for Malaria: How Close Are We?

    Science.gov (United States)

    Thera, Mahamadou A.; Plowe, Christopher V.

    2012-01-01

    Vaccines are the most powerful public health tools mankind has created, but malaria parasites are bigger, more complicated, and wilier than the viruses and bacteria that have been conquered or controlled with vaccines. Despite decades of research toward a vaccine for malaria, this goal has remained elusive. Nevertheless, recent advances justify optimism that a licensed malaria vaccine is within reach. A subunit recombinant protein vaccine that affords in the neighborhood of 50% protective efficacy against clinical malaria is in the late stages of clinical evaluation in Africa. Incremental improvements on this successful vaccine are possible and worth pursuing, but the best hope for a highly efficacious malaria vaccine that would improve prospects for malaria eradication may lie with the use of attenuated whole parasites and powerful immune-boosting adjuvants. PMID:22077719

  15. Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

    Directory of Open Access Journals (Sweden)

    Jacqueline M. Miller

    2011-01-01

    Full Text Available Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles.

  16. Rotavirus vaccination in Europe: drivers and barriers.

    Science.gov (United States)

    Parez, N; Giaquinto, C; Du Roure, C; Martinon-Torres, F; Spoulou, V; Van Damme, P; Vesikari, T

    2014-05-01

    Rotavirus gastroenteritis is a vaccine-preventable disease that confers a high medical and economic burden in more developed countries and can be fatal in less developed countries. Two vaccines with high efficacy and good safety profiles were approved and made available in Europe in 2006. We present an overview of the status of rotavirus vaccination in Europe. We discuss the drivers (including high effectiveness and effect of universal rotavirus vaccination) and barriers (including low awareness of disease burden, perception of unfavourable cost-effectiveness, and potential safety concerns) to the implementation of universal rotavirus vaccination in Europe. By February, 2014, national universal rotavirus vaccination had been implemented in Belgium, Luxembourg, Austria, Finland, Greece, Luxembourg, Norway, and the UK. Four other German states have issued recommendations and reimbursement is provided by sickness funds. Other countries were at various stages of recommending or implementing universal rotavirus vaccination. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Conjugate Meningococcal Vaccines Development: GSK Biologicals Experience

    Science.gov (United States)

    Miller, Jacqueline M.; Mesaros, Narcisa; Van Der Wielen, Marie; Baine, Yaela

    2011-01-01

    Meningococcal diseases are serious threats to global health, and new vaccines specifically tailored to meet the age-related needs of various geographical areas are required. This paper focuses on the meningococcal conjugate vaccines developed by GSK Biologicals. Two combined conjugate vaccines were developed to help protect infants and young children in countries where the incidence of meningococcal serogroup C or serogroup C and Y disease is important: Hib-MenC-TT vaccine, which offers protection against Haemophilus influenzae type b and Neisseria meningitidis serogroup C diseases, is approved in several countries; and Hib-MenCY-TT vaccine, which adds N. meningitidis serogroup Y antigen, is currently in the final stages of development. Additionally, a tetravalent conjugate vaccine (MenACWY-TT) designed to help protect against four meningococcal serogroups is presently being evaluated for global use in all age groups. All of these vaccines were shown to be highly immunogenic and to have clinically acceptable safety profiles. PMID:21991444

  18. A flow cytometry-based workflow for detection and quantification of anti-plasmodial antibodies in vaccinated and naturally exposed individuals

    DEFF Research Database (Denmark)

    Ajua, Anthony; Engleitner, Thomas; Esen, Meral

    2012-01-01

    information about natural exposure and vaccine immunogenicity. A novel, cytometry-based workflow for the quantitative detection of anti-plasmodial antibodies in human serum is presented. METHODS: Fixed red blood cells (RBCs), infected with late stages of P. falciparum were utilized to detect malaria......-specific antibodies by flow cytometry with subsequent automated data analysis. Available methods for data-driven analysis of cytometry data were assessed and a new overlap subtraction algorithm (OSA) based on open source software was developed. The complete workflow was evaluated using sera from two GMZ2 malaria...... children vaccinated with 100 mug GMZ2 was present and in vaccinated adults from the same region we measured a baseline-corrected 1.23-fold, vaccine-induced increase in mean fluorescence intensity of positive cells (p=0.03). CONCLUSIONS: The current workflow advances detection and quantification of anti...

  19. An expanding toolkit for preclinical pre-erythrocytic malaria vaccine development: bridging traditional mouse malaria models and human trials.

    Science.gov (United States)

    Steel, Ryan Wj; Kappe, Stefan Hi; Sack, Brandon K

    2016-12-01

    Malaria remains a significant public health burden with 214 million new infections and over 400,000 deaths in 2015. Elucidating relevant Plasmodium parasite biology can lead to the identification of novel ways to control and ultimately eliminate the parasite within geographic areas. Particularly, the development of an effective vaccine that targets the clinically silent pre-erythrocytic stages of infection would significantly augment existing malaria elimination tools by preventing both the onset of blood-stage infection/disease as well as spread of the parasite through mosquito transmission. In this Perspective, we discuss the role of small animal models in pre-erythrocytic stage vaccine development, highlighting how human liver-chimeric and human immune system mice are emerging as valuable components of these efforts.

  20. [The biological reaction of inflammation, methylglyoxal of blood plasma, functional and structural alterations in elastic type arteries at the early stage of hypertension disease].

    Science.gov (United States)

    Titov, V N; Dmitriev, V A; Oshchepkov, E V; Balakhonova, T V; Tripoten', M I; Shiriaeva, Iu K

    2012-08-01

    The article deals with studying of the relationship between biologic reaction of inflammation with glycosylation reaction and content of methylglyoxal in blood serum. The positive correlation between pulse wave velocity and content of methylglyoxal, C-reactive protein in intercellular medium and malleolar brachial index value was established. This data matches the experimental results concerning involvement of biological reaction of inflammation into structural changes of elastic type arteries under hypertension disease, formation of arteries' rigidity and increase of pulse wave velocity. The arterial blood pressure is a biological reaction of hydrodynamic pressure which is used in vivo by several biological functions: biological function of homeostasis, function of endoecology, biological function of adaptation and function of locomotion. The biological reaction of hydrodynamic (hydraulic) pressure is a mode of compensation of derangement of several biological functions which results in the very high rate of hypertension disease in population. As a matter of fact, hypertension disease is a syndrome of lingering pathological compensation by higher arterial blood pressure of the biological functions derangements occurring in the distal section at the level of paracrine cenoses of cells. The arterial blood pressure is a kind of in vivo integral indicator of deranged metabolism. The essential hypertension disease pathogenically is a result of the derangement of three biological functions: biological function of homeostasis, biological function of trophology - nutrition (biological reaction of external feeding - exotrophia) and biological function of endoecology. In case of "littering" of intercellular medium in vivo with nonspecific endogenic flogogens a phylogenetically earlier activation of biological reactions of excretion, inflammation and hydrodynamic arterial blood pressure occur. In case of derangement of biological function of homeostasis, decreasing of

  1. Human Immune Responses to Experimental Vaccinia Vaccines

    National Research Council Canada - National Science Library

    Ennis, Francis

    1996-01-01

    .... During the two years of this contract we have: (1) obtained, separated and cryopreserved peripheral blood mononuclear cells from 92 vaccinees in a clinical study to compare the standard and an experimental small pox vaccine, (2...

  2. Vaccination in food allergic patients | Karabus | South African ...

    African Journals Online (AJOL)

    People with egg allergy may receive influenza vaccination routinely; however, some authorities still perform prior skinprick testing and give two-stage dosing. The purified chick embryo cell culture rabies vaccine contains egg protein, and therefore the human diploid cell and purified verocell rabies vaccines are preferred in ...

  3. Development of a Subunit Vaccine for Contagious Bovine ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    Their work has set the stage for commercial development of a sub-unit vaccine. Field testing and production This scale-up project will ... The research team will conduct a large field trial involving 1,500 commercial cattle to assess the vaccine's safety and efficacy. They will define the regulatory pathway for the vaccine to be ...

  4. Scaling up development, production of CBPP vaccine for cattle in ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    About the vaccine Using a novel genomics-based approach, researchers have identified candidate vaccine proteins and demonstrated their ability to elicit protective immune response in cattle. Their work has set the stage for commercial development of a sub-unit vaccine. Field testing and production This scale-up project ...

  5. Impact of BRICS' investment in vaccine development on the global vaccine market.

    Science.gov (United States)

    Kaddar, Miloud; Milstien, Julie; Schmitt, Sarah

    2014-06-01

    Brazil, the Russian Federation, India, China and South Africa--the countries known as BRICS--have made considerable progress in vaccine production, regulation and development over the past 20 years. In 1993, all five countries were producing vaccines but the processes used were outdated and non-standardized, there was little relevant research and there was negligible international recognition of the products. By 2014, all five countries had strong initiatives for the development of vaccine technology and had greatly improved their national regulatory capacity. South Africa was then the only BRICS country that was not completely producing vaccines. South Africa is now in the process of re-establishing its own vaccine production and passing beyond the stage of simply importing, formulating and filling vaccine bulks. Changes in the public sector's price per dose of selected vaccines, the global market share represented by products from specific manufacturers, and the attractiveness, for multinational companies, of partnership and investment opportunities in BRICS companies have all been analysed. The results indicate that the BRICS countries have had a major impact on vaccine price and availability, with much of that impact attributable to the output of Indian vaccine manufacturers. China is expected to have a greater impact soon, given the anticipated development of Chinese vaccine manufacturers in the near future. BRICS' accomplishments in the field of vaccine development are expected to reshape the global vaccine market and accelerate access to vaccines in the developing world. The challenge is to turn these expectations into strategic actions and practical outcomes.

  6. TUMOUR VACCINE

    NARCIS (Netherlands)

    Wagner, Ernst; Kircheis, Ralf; Crommelin, D.; Van Slooten, Maaike; Storm, Gert

    1999-01-01

    The invention relates to a tumour vaccine with a tumour antigen base. In addition to a source of tumour antigens, the vaccine contains a release system for the delayed release of the active agent IFN- gamma , the active dose of IFN- gamma being 50 ng to 5 mu g. The IFN- gamma is released over a

  7. HPV vaccine

    African Journals Online (AJOL)

    campaign of human papillomavirus (HPV) vaccination of grade 4 girls in South African (SA) public schools, ... This use is of concern in view of the billions of US dollars GSK had to pay for bribery in the USA, and is ... argument used to entice parents to have their daughters vaccinated is to prevent 3 000 women from dying of ...

  8. Flublok Seasonal Influenza (Flu) Vaccination

    Science.gov (United States)

    ... Vaccine Safety and Pregnant Women Febrile Seizures Following Vaccination Flu Vaccine and People with Egg Allergies Guillain- ... Flu Vaccines Quadrivalent Influenza Vaccine Intradermal Influenza (Flu) Vaccination Fluzone High-Dose Seasonal Influenza Vaccine Cell-Based ...

  9. An analysis on the level changing of UET and SET in blood and urine in early stage of kidney disease caused by diabetes

    International Nuclear Information System (INIS)

    Liu Juzhen; Yang Wenying; Cai Tietie

    2001-01-01

    Objective: To study the relationship between UET and SET variation and early changes of diabetic nephropathy. Methods: UET and SET were measured in 24 patients with diabetes, 19 with early stage diabetic nephropathy, 21 with advanced diabetic nephropathy and 30 normal as contrast. Results: Apparent uprise of UET and SET was observed in all patients when compared to normal contrasts (P 2 -macroglobulin was revealed (P<0.05). Conclusion: UET and SET levels uprose as long as diabetic nephropathy deteriorated. As a result, UET and SET may act as sensitive indices in diagnosing early stage diabetic nephropathy

  10. Clonal T cell receptor gamma-chain gene rearrangement by PCR-based GeneScan analysis in the skin and blood of patients with parapsoriasis and early-stage mycosis fungoides.

    Science.gov (United States)

    Klemke, Claus-Detlev; Dippel, Edgar; Dembinski, Antje; Pönitz, Nina; Assaf, Chalid; Hummel, Michael; Stein, Harald; Goerdt, Sergij

    2002-07-01

    Cutaneous T cell lymphoma (CTCL) and reactive T cell skin diseases represent opposite ends of a spectrum of diseases ranging from overtly malignant to persistently benign. Within this spectrum, the parapsoriasis group is not clearly defined regarding malignant potential. In contrast to consistent findings in advanced-stage CTCL, clonality analysis of parapsoriasis has produced conflicting results in previous studies. As T cell receptor gamma-chain polymerase chain reaction GeneScan analysis (TCR-gamma-PCR-GSA) stands out by its sensitivity, its accuracy in size determination of PCR products, its capacity to identify false positives by repeated analysis and its easy applicability, this approach was used to analyse the clonality status of 41 patients with borderline T cell lymphoproliferative skin diseases, including parapsoriasis (n=27) and early-stage mycosis fungoides (MF) (n=14). A monoclonal T cell infiltrate was demonstrated by repeated TCR-gamma-PCR-GSA in lesional skin specimens in 19.2% of parapsoriasis patients and in 66.6% of early-stage MF cases (p=0.013). In peripheral blood, a monoclonal T cell population was found in a similar percentage of parapsoriasis and of early-stage MF patients (26.7% versus 12.5%; p=0.611). A detailed analysis of parapsoriasis subentities, namely small and large plaque parapsoriasis, and parapsoriasis lichenoides, revealed monoclonality in 2(6)/2(5), 3(14)/2(8) and 0(6)/0/(3) of the skin and peripheral blood specimens, respectively. The high detection rate of false positive cases by repeated analysis (20-37.5%) provides a corrected perspective for the high rates of dominant T cell clones found by others in the peripheral blood of such patients. From the results obtained, three major conclusions can be drawn: firstly, CTCL is clearly associated with detection of monoclonality, even in its early stages; secondly, monoclonality is not a prerequisite for potential CTCL precursor entities; and thirdly, recirculating malignant T

  11. Combination vaccines

    Directory of Open Access Journals (Sweden)

    David AG Skibinski

    2011-01-01

    Full Text Available The combination of diphtheria, tetanus, and pertussis vaccines into a single product has been central to the protection of the pediatric population over the past 50 years. The addition of inactivated polio, Haemophilus influenzae, and hepatitis B vaccines into the combination has facilitated the introduction of these vaccines into recommended immunization schedules by reducing the number of injections required and has therefore increased immunization compliance. However, the development of these combinations encountered numerous challenges, including the reduced response to Haemophilus influenzae vaccine when given in combination; the need to consolidate the differences in the immunization schedule (hepatitis B; and the need to improve the safety profile of the diphtheria, tetanus, and pertussis combination. Here, we review these challenges and also discuss future prospects for combination vaccines.

  12. A Plasmodium Promiscuous T Cell Epitope Delivered within the Ad5 Hexon Protein Enhances the Protective Efficacy of a Protein Based Malaria Vaccine.

    Directory of Open Access Journals (Sweden)

    Jairo Andres Fonseca

    Full Text Available A malaria vaccine is a public health priority. In order to produce an effective vaccine, a multistage approach targeting both the blood and the liver stage infection is desirable. The vaccine candidates also need to induce balanced immune responses including antibodies, CD4+ and CD8+ T cells. Protein-based subunit vaccines like RTS,S are able to induce strong antibody response but poor cellular reactivity. Adenoviral vectors have been effective inducing protective CD8+ T cell responses in several models including malaria; nonetheless this vaccine platform exhibits a limited induction of humoral immune responses. Two approaches have been used to improve the humoral immunogenicity of recombinant adenovirus vectors, the use of heterologous prime-boost regimens with recombinant proteins or the genetic modification of the hypervariable regions (HVR of the capsid protein hexon to express B cell epitopes of interest. In this study, we describe the development of capsid modified Ad5 vectors that express a promiscuous Plasmodium yoelii T helper epitope denominated PyT53 within the hexon HVR2 region. Several regimens were tested in mice to determine the relevance of the hexon modification in enhancing protective immune responses induced by the previously described protein-based multi-stage experimental vaccine PyCMP. A heterologous prime-boost immunization regime that combines a hexon modified vector with transgenic expression of PyCMP followed by protein immunizations resulted in the induction of robust antibody and cellular immune responses in comparison to a similar regimen that includes a vector with unmodified hexon. These differences in immunogenicity translated into a better protective efficacy against both the hepatic and red blood cell stages of P. yoelii. To our knowledge, this is the first time that a hexon modification is used to deliver a promiscuous T cell epitope. Our data support the use of such modification to enhance the immunogenicity

  13. A Plasmodium Promiscuous T Cell Epitope Delivered within the Ad5 Hexon Protein Enhances the Protective Efficacy of a Protein Based Malaria Vaccine.

    Science.gov (United States)

    Fonseca, Jairo Andres; Cabrera-Mora, Monica; Kashentseva, Elena A; Villegas, John Paul; Fernandez, Alejandra; Van Pelt, Amelia; Dmitriev, Igor P; Curiel, David T; Moreno, Alberto

    2016-01-01

    A malaria vaccine is a public health priority. In order to produce an effective vaccine, a multistage approach targeting both the blood and the liver stage infection is desirable. The vaccine candidates also need to induce balanced immune responses including antibodies, CD4+ and CD8+ T cells. Protein-based subunit vaccines like RTS,S are able to induce strong antibody response but poor cellular reactivity. Adenoviral vectors have been effective inducing protective CD8+ T cell responses in several models including malaria; nonetheless this vaccine platform exhibits a limited induction of humoral immune responses. Two approaches have been used to improve the humoral immunogenicity of recombinant adenovirus vectors, the use of heterologous prime-boost regimens with recombinant proteins or the genetic modification of the hypervariable regions (HVR) of the capsid protein hexon to express B cell epitopes of interest. In this study, we describe the development of capsid modified Ad5 vectors that express a promiscuous Plasmodium yoelii T helper epitope denominated PyT53 within the hexon HVR2 region. Several regimens were tested in mice to determine the relevance of the hexon modification in enhancing protective immune responses induced by the previously described protein-based multi-stage experimental vaccine PyCMP. A heterologous prime-boost immunization regime that combines a hexon modified vector with transgenic expression of PyCMP followed by protein immunizations resulted in the induction of robust antibody and cellular immune responses in comparison to a similar regimen that includes a vector with unmodified hexon. These differences in immunogenicity translated into a better protective efficacy against both the hepatic and red blood cell stages of P. yoelii. To our knowledge, this is the first time that a hexon modification is used to deliver a promiscuous T cell epitope. Our data support the use of such modification to enhance the immunogenicity and protective

  14. Short communication: amino acid supplementation and stage of lactation alter apparent utilization of nutrients by blood neutrophils from lactating dairy cows in vitro

    Science.gov (United States)

    Glutamine is the preferred AA used by polymorphonuclear leukocytes (PMN) during the inflammatory response. However, the effect of other AA on bovine PMN response during inflammation and how this is altered by stage of lactation has not been fully elucidated. The objective of this study was to dete...

  15. Correlates of protection for enteric vaccines.

    Science.gov (United States)

    Holmgren, Jan; Parashar, Umesh D; Plotkin, Stanley; Louis, Jacques; Ng, Su-Peing; Desauziers, Eric; Picot, Valentina; Saadatian-Elahi, Mitra

    2017-06-08

    An immunological Correlate of Protection (CoP) is an immune response that is statistically interrelated with protection. Identification of CoPs for enteric vaccines would help design studies to improve vaccine performance of licensed vaccines in low income settings, and would facilitate the testing of future vaccines in development that might be more affordable. CoPs are lacking today for most existing and investigational enteric vaccines. In order to share the latest information on CoPs for enteric vaccines and to discuss novel approaches to correlate mucosal immune responses in humans with protection, the Foundation Mérieux organized an international conference of experts where potential CoPs for vaccines were examined using case-studies for both bacterial and viral enteric pathogens. Experts on the panel concluded that to date, all established enteric vaccine CoPs, such as those for hepatitis A, Vi typhoid and poliovirus vaccines, are based on serological immune responses even though these may poorly reflect the relevant gut immune responses or predict protective efficacy. Known CoPs for cholera, norovirus and rotavirus could be considered as acceptable for comparisons of similarly composed vaccines while more work is still needed to establish CoPs for the remaining enteric pathogens and their candidate vaccines. Novel approaches to correlate human mucosal immune responses with protection include the investigation of gut-originating antibody-secreting cells (ASCs), B memory cells and follicular helper T cells from samples of peripheral blood during their recirculation. Copyright © 2017.

  16. [Blood Content of Markers of Inflammation and Cytokines in Patients With Alcoholic Cardiomyopathy and Ischemic Heart Disease at Various Stages of Heart Failure].

    Science.gov (United States)

    Panchenko, L F; Moiseev, V S; Pirozhkov, S V; Terebilina, N N; Naumova, T A; Baronets, V Iu; Goncharov, A S

    2015-01-01

    We conducted a comparative study of content proinflammatory cytokines, biomarkers of inflammatory process, biochemical indicators of congestive heart failure (CHF) and hemodynamic parameters in patients with alcoholic cardiomyopathy (ACMP) and ischemic heart disease (IHD) with various NYHA classes. We examined 62 men with ACMP (n = 45) and IHD (n = 17) and NYHA class III-IV CHF. Patients of both groups had lowered ejection fraction (EF), dilated cardiac chambers, and increased left ventricular (LV) myocardial mass index (MMI). Relative LV wall thickness was within normal limits but in the ACMP group it was significantly lower than in IHD group what corresponded to the eccentric type of myocardial hypertrophy. Higher NYHA class was associated with lower EF and larger end diastolic and end systolic LV dimensions. In ACMP it was also associated with larger dimension of the right ventricle while in IHD--with substantially larger (by 30%) dimension of atria. Substantial amount of endotoxin found in blood plasma of patients with IHD corresponded to the conception of increased intestinal permeability of in CHF. Alcohol abuse was an aggravating factor of endotoxin transmission and its concentration in patients with ACMP was 3 times higher than in patients with IHD. Patients with ACMP had substantially elevated blood concentrations of interleukins (IL) 6, 8, 12, tumor necrosis factor α (TNF-α), and its soluble receptor s-TNF-R; they also had twofold elevation of C-reactive protein concentration. ACMP was associated with manifold rise of blood content of brain natriuretic peptide (BNP). Patients with IHD also had elevated blood concentrations of IL 6, 8 and 12 but their values were 1.5-2 times lower than ACMP group. Blood content of TNF-α and s-TNF-R in IHD group was within normal limits. Higher NYHA class in ACMP patients was associated with higher concentrations of IL 6 and 8, TNF-a, and BNP. In both groups of patients contents of IL-12, s-TNF-R, TGF-1β and factors of

  17. Satisfactory safety and immunogenicity of MSP3 malaria vaccine candidate in Tanzanian children aged 12–24 months

    Directory of Open Access Journals (Sweden)

    Segeja Method D

    2009-07-01

    Full Text Available Abstract Background Development and deployment of an effective malaria vaccine would complement existing malaria control measures. A blood stage malaria vaccine candidate, Merozoite Surface Protein-3 (MSP3, produced as a long synthetic peptide, has been shown to be safe in non-immune and semi-immune adults. A phase Ib dose-escalating study was conducted to assess the vaccine's safety and immunogenicity in children aged 12 to 24 months in Korogwe, Tanzania (ClinicalTrials.gov number: NCT00469651. Methods This was a double-blind, randomized, controlled, dose escalation phase Ib trial, in which children were given one of two different doses of the MSP3 antigen (15 μg or 30 μg or a control vaccine (Engerix B. Children were randomly allocated either to the MSP3 candidate malaria vaccine or the control vaccine administered at a schedule of 0, 1, and 2 months. Immunization with lower and higher doses was staggered for safety reasons starting with the lower dose. The primary endpoint was safety and reactogenicity within 28 days post-vaccination. Blood samples were obtained at different time points to measure immunological responses. Results are presented up to 84 days post-vaccination. Results A total of 45 children were enrolled, 15 in each of the two MSP3 dose groups and 15 in the Engerix B group. There were no important differences in reactogenicity between the two MSP3 groups and Engerix B. Grade 3 adverse events were infrequent; only five were detected throughout the study, all of which were transient and resolved without sequelae. No serious adverse event reported was considered to be related to MSP3 vaccine. Both MSP3 dose regimens elicited strong cytophilic IgG responses (subclasses IgG1 and IgG3, the isotypes involved in the monocyte-dependant mechanism of Plasmodium falciparum parasite-killing. The titers reached are similar to those from African adults having reached a state of premunition. Furthermore, vaccination induced seroconversion in

  18. Plasmodium falciparum field isolates from South America use an atypical red blood cell invasion pathway associated with invasion ligand polymorphisms

    DEFF Research Database (Denmark)

    Lopez-Perez, Mary; Villasis, Elizabeth; Machado, Ricardo L D

    2012-01-01

    members of the PfRh (PfRh1, PfRh2a, PfRh2b, PfRh4, PfRh5) families were determined. We found that most P. falciparum field isolates from Colombia and Peru invade RBCs through an atypical invasion pathway phenotypically characterized as resistant to all enzyme treatments (NrTrCr). Moreover, the invasion...... blood stage vaccine design focused on invasion pathway proteins, suggesting that regional invasion variants and global geographical variation are likely to preclude a simple one size fits all type of vaccine....

  19. 17DD yellow fever vaccine

    Science.gov (United States)

    Martins, Reinaldo M.; Maia, Maria de Lourdes S.; Farias, Roberto Henrique G.; Camacho, Luiz Antonio B.; Freire, Marcos S.; Galler, Ricardo; Yamamura, Anna Maya Yoshida; Almeida, Luiz Fernando C.; Lima, Sheila Maria B.; Nogueira, Rita Maria R.; Sá, Gloria Regina S.; Hokama, Darcy A.; de Carvalho, Ricardo; Freire, Ricardo Aguiar V.; Filho, Edson Pereira; Leal, Maria da Luz Fernandes; Homma, Akira

    2013-01-01

    Objective: To verify if the Bio-Manguinhos 17DD yellow fever vaccine (17DD-YFV) used in lower doses is as immunogenic and safe as the current formulation. Results: Doses from 27,476 IU to 587 IU induced similar seroconversion rates and neutralizing antibodies geometric mean titers (GMTs). Immunity of those who seroconverted to YF was maintained for 10 mo. Reactogenicity was low for all groups. Methods: Young and healthy adult males (n = 900) were recruited and randomized into 6 groups, to receive de-escalating doses of 17DD-YFV, from 27,476 IU to 31 IU. Blood samples were collected before vaccination (for neutralization tests to yellow fever, serology for dengue and clinical chemistry), 3 to 7 d after vaccination (for viremia and clinical chemistry) and 30 d after vaccination (for new yellow fever serology and clinical chemistry). Adverse events diaries were filled out by volunteers during 10 d after vaccination. Volunteers were retested for yellow fever and dengue antibodies 10 mo later. Seropositivity for dengue was found in 87.6% of volunteers before vaccination, but this had no significant influence on conclusions. Conclusion: In young healthy adults Bio-Manguinhos/Fiocruz yellow fever vaccine can be used in much lower doses than usual. International Register ISRCTN 38082350. PMID:23364472

  20. Complex polarimetric and spectral techniques in diagnostics of blood plasma of patients with ovarian cancer as a preliminary stage molecular genetic screening

    Science.gov (United States)

    Grzegorzewski, B.; Peresunko, O. P.; Yermolenko, S. B.

    2018-01-01

    This work is devoted to the substantiation and selection of patients with ovarian cancer (OC) for the purpose of conducting expensive molecular genetic studies on genotyping. As diagnostic methods have been used ultraviolet spectrometry samples of blood plasma in the liquid state, infrared spectroscopy middle range (2,5 - 25 microns) dry residue of plasma polarization and laser diagnostic technique of thin histological sections of biological tissues. Obtained results showed that the use of spectrophotometry in the range of 1000-3000 cm-1 allowed to establish quantitative parameters of the plasma absorption rate of blood of patients in the third group in different ranges, which would allow in the future to conduct an express analysis of the patient's condition (procedure screening) for further molecular-genetic typing on BRCA I and II.

  1. Tumor vaccines

    International Nuclear Information System (INIS)

    Frank, M.; Ihan, A.

    2006-01-01

    Tumor vaccines have several potential advantages over standard anticancer regiments. They represent highly specific anticancer therapy. Inducing tumor-specific memory T-lymphocytes, they have potential for long-lived antitumor effects. However, clinical trials, in which cancer patients were vaccinated with tumor vaccines, have been so far mainly disappointing. There are many reasons for the inefficiency of tumor vaccines. Most cancer antigens are normal self-molecules to which immune tolerance exists. That is why the population of tumor-specific lymphocytes is represented by a small number of low-affinity T-lymphocytes that induce weak antitumor immune response. Simultaneously, tumors evolve many mechanisms to actively evade immune system, what makes them poorly immunogenic or even tolerogenic. Novel immunotherapeutic strategies are directed toward breaking immune tolerance to tumor antigens, enhancing immunogenicity of tumor vaccines and overcoming mechanisms of tumor escape. There are several approaches, unfortunately, all of them still far away from an ideal tumor vaccine that would reject a tumor. Difficulties in the activation of antitumor immune response by tumor vaccines have led to the development of alternative immunotherapeutic strategies that directly focus on effector mechanisms of immune system (adoptive tumor- specific T-lymphocyte transfer and tumor specific monoclonal antibodies). (author)

  2. Serial Determination of bcl-2 Major Breakpoint Region (MBR) Rearrangement, t(14;18) (q32;q21), in the Bone Marrow and Peripheral Blood for Stages I - III Follicular Lymphoma after Central Lymphatic Irradiation (CLI) - A Preliminary Report

    International Nuclear Information System (INIS)

    Ha, C.S.; Cabanillas, F.; Lee, M.; Besa, P.C.; McLaughlin, P.W.; Cox, J.D.

    1995-01-01

    Purpose/Objective: About (2(3)) of all cases of follicular lymphoma have rearrangement of bcl-2 MBR through t(14;18) (q32;q21). This arrangement could serve as a sensitive marker for follicular lymphoma cells. The objectives of this study are two fold: 1) To assess complete molecular response rate of stages I-III follicular lymphoma to CLI by detection of PCR amplifiable bcl-2 MBR rearrangement in the bone marrow and peripheral blood before and after CLI. 2) To assess the significance of the molecular response as a prognostic indicator. Materials and Methods: 13 patients with stages I-III follicular lymphoma were treated with CLI as a part of a prospective randomized protocol comparing CLI with chemotherapy. Bone marrow and peripheral blood samples were obtained from the patients before initiation of CLI. By using the PCR technique, the DNA sequences from the bone marrow and peripheral blood samples that flank the bcl-2 MBR involved in t(14;18) (q32;q21) were amplified. For the patients who had positive PCR result, bone marrow and blood samples were followed at regular intervals during and after CLI. The patients with negative PCR result prior to CLI did not have follow-up PCR analysis. The results of the PCR amplification were correlated with clinical findings. Results: All 13 patients achieved clinical complete response after CLI. No patient has relapsed with a median follow-up period of 11 months (range 5 to 24 months). Pretreatment PCR results are available in 13 patients for peripheral blood and in 9 patients for bone marrow. (7(13)) blood and (5(9)) bone marrow samples were PCR-positive for bcl-2 MBR rearrangement. All 5 patients with positive pretreatment bone marrow also had positive pretreatment peripheral blood. (6(7)) patients with positive pretreatment blood PCR converted to negative within 2,3,5,6,6, and 10 months from the 1st day of CLI. The 7th patient has no follow-up PCR available yet. Follow-up PCR results from the pretreatment bone

  3. EXPERIMENTAL LIPOSOMAL VIRAL VACCINE SAFETY

    Directory of Open Access Journals (Sweden)

    Romanova OA

    2016-12-01

    efficacy should include the definition the content lipid peroxidation products. Conclusion.Thus, experimental samples influenza liposomal vaccine (without modification and with its for liposomal and antigenic components haven`t found increased levels primary products lipid peroxidation – lipid hydro peroxides and protein oxidation products – carbonyl protein and haven`t significant effects inhibition anti-oxidant enzymes in rat`s serum.More results the study stage the safety most effective vaccine samples will be present in the text.

  4. Predictors of seasonal influenza vaccination among older adults in Thailand

    OpenAIRE

    Praphasiri, Prabda; Ditsungnoen, Darunee; Sirilak, Supakit; Rattanayot, Jarawee; Areerat, Peera; Dawood, Fatimah S.; Lindblade, Kim A.

    2017-01-01

    Background In advance of a large influenza vaccine effectiveness (VE) cohort study among older adults in Thailand, we conducted a population-based, cross-sectional survey to measure vaccine coverage and identify factors associated with influenza vaccination among older Thai adults that could bias measures of vaccine effectiveness. Method We selected adults ≥65 years using a two-stage, stratified, cluster sampling design. Functional status was assessed using the 10-point Vulnerable Elders Surv...

  5. Alpha-Mangostin Attenuation of Hyperglycemia-Induced Ocular Hypoperfusion and Blood Retinal Barrier Leakage in the Early Stage of Type 2 Diabetes Rats

    Directory of Open Access Journals (Sweden)

    Amporn Jariyapongskul

    2015-01-01

    Full Text Available The present study examined effects of alpha-mangostin (α-MG supplementation on the retinal microvasculature, including ocular blood flow (OBF and blood-retinal barrier (BRB permeability in a type 2 diabetic animal model. Male Sprague-Dawley rats were divided into four groups: normal control and diabetes with or without α-MG supplementation. Alpha-mangostin (200 mg/Kg/day was administered by gavage feeding for 8 weeks. The effects of α-MG on biochemical and physiological parameters including mean arterial pressure (MAP, OBF, and BRB leakage were investigated. Additionally, levels of retinal malondialdehyde (MDA, advance glycation end products (AGEs, receptor of advance glycation end products (RAGE, tumour necrosis factor alpha (TNF-α, and vascular endothelial growth factor (VEGF were evaluated. The elevated blood glucose, HbA1c, cholesterol, triglyceride, serum insulin, and HOMA-IR were observed in DM2 rats. Moreover, DM2 rats had significantly decreased OBF but statistically increased MAP and leakage of the BRB. The α-MG-treated DM2 rats showed significantly lower levels of retinal MDA, AGEs, RAGE, TNF-α, and VEGF than the untreated group. Interestingly, α-MG supplementation significantly increased OBF while it decreased MAP and leakage of BRB. In conclusion, α-MG supplementation could restore OBF and improve the BRB integrity, indicating its properties closely associated with antihyperglycemic, antioxidant, anti-inflammatory, and antiglycation activities.

  6. Alpha-Mangostin Attenuation of Hyperglycemia-Induced Ocular Hypoperfusion and Blood Retinal Barrier Leakage in the Early Stage of Type 2 Diabetes Rats

    Science.gov (United States)

    Jariyapongskul, Amporn; Areebambud, Chonticha; Suksamrarn, Sunit; Mekseepralard, Chantana

    2015-01-01

    The present study examined effects of alpha-mangostin (α-MG) supplementation on the retinal microvasculature, including ocular blood flow (OBF) and blood-retinal barrier (BRB) permeability in a type 2 diabetic animal model. Male Sprague-Dawley rats were divided into four groups: normal control and diabetes with or without α-MG supplementation. Alpha-mangostin (200 mg/Kg/day) was administered by gavage feeding for 8 weeks. The effects of α-MG on biochemical and physiological parameters including mean arterial pressure (MAP), OBF, and BRB leakage were investigated. Additionally, levels of retinal malondialdehyde (MDA), advance glycation end products (AGEs), receptor of advance glycation end products (RAGE), tumour necrosis factor alpha (TNF-α), and vascular endothelial growth factor (VEGF) were evaluated. The elevated blood glucose, HbA1c, cholesterol, triglyceride, serum insulin, and HOMA-IR were observed in DM2 rats. Moreover, DM2 rats had significantly decreased OBF but statistically increased MAP and leakage of the BRB. The α-MG-treated DM2 rats showed significantly lower levels of retinal MDA, AGEs, RAGE, TNF-α, and VEGF than the untreated group. Interestingly, α-MG supplementation significantly increased OBF while it decreased MAP and leakage of BRB. In conclusion, α-MG supplementation could restore OBF and improve the BRB integrity, indicating its properties closely associated with antihyperglycemic, antioxidant, anti-inflammatory, and antiglycation activities. PMID:25950001

  7. Short report: Echinococcus granulosus from Xinjiang, PR China: cDNAS encoding the EG95 vaccine antigen are expressed in different life cycle stages and are conserved in the oncosphere.

    Science.gov (United States)

    Zhang, Wenbao; Li, Jun; You, Hong; Zhang, Zhuangzhi; Turson, Gulinul; Loukas, Alex; McManus, Donald P

    2003-01-01

    The EG95-based vaccine protects sheep from infection with the dog tapeworm Echinococcus granulosus. The EG95 encoding gene is a member of a multigene family, several members of which are expressed in the oncosphere, believed to be the target of immunity induced by the vaccine. E. granulosus exhibits extensive intraspecific (strain) variation, and variability of the eg95 gene in different isolates of E. granulosus may directly impact the effectiveness of the EG95-based vaccine. We analyzed the eg95 gene from E. granulosus collected in Xinjiang, in northwest China, where hydatid disease is hyperendemic. The gene is expressed in oncospheres, protoscoleces, and immature and mature adult worms, and the eg95 gene family was shown to comprise two basic sequence types. Very limited sequence variation was evident in the EG95 protein from oncospheres. This high degree of sequence conservation predicts that the vaccine will continue to be effective in China and elsewhere.

  8. Targeting nicotine addiction: the possibility of a therapeutic vaccine

    Directory of Open Access Journals (Sweden)

    Escobar-Chávez JJ

    2011-04-01

    Full Text Available José Juan Escobar-Chávez1, Clara Luisa Domínguez-Delgado2, Isabel Marlen Rodríguez-Cruz21Unidad de Investigación Multidisciplinaria, Facultad de Estudios Superiores Cuautitlán-Universidad Nacional Autónoma de México, Cuautitlán Izcalli, Estado de México, México; 2División de Estudios de Posgrado (Tecnología Farmacéutica, Facultad de Estudios Superiores Cuautitlán-Universidad Nacional Autónoma de México, Cuautitlán Izcalli, Estado de México, MéxicoAbstract: Cigarette smoking is the primary cause of lung cancer, cardiovascular diseases, reproductive disorders, and delayed wound healing all over the world. The goals of smoking cessation are both to reduce health risks and to improve quality of life. The development of novel and more effective medications for smoking cessation is crucial in the treatment of nicotine dependence. Currently, first-line smoking cessation therapies include nicotine replacement products and bupropion. The partial nicotinic receptor agonist, varenicline, has recently been approved by the US Food and Drug Administration (FDA for smoking cessation. Clonidine and nortriptyline have demonstrated some efficacy, but side effects may limit their use to second-line treatment products. Other therapeutic drugs that are under development include rimonabant, mecamylamine, monoamine oxidase inhibitors, and dopamine D3 receptor antagonists. Nicotine vaccines are among newer products seeking approval from the FDA. Antidrug vaccines are irreversible, provide protection over years and need booster injections far beyond the critical phase of acute withdrawal symptoms. Interacting with the drug in the blood rather than with a receptor in the brain, the vaccines are free of side effects due to central interaction. For drugs like nicotine, which interacts with different types of receptors in many organs, this is a further advantage. Three anti-nicotine vaccines are today in an advanced stage of clinical evaluation. Results

  9. Whither vaccines?

    Science.gov (United States)

    Rodrigues, Charlene M C; Pinto, Marta V; Sadarangani, Manish; Plotkin, Stanley A

    2017-06-01

    Currently used vaccines have had major effects on eliminating common infections, largely by duplicating the immune responses induced by natural infections. Now vaccinology faces more complex problems, such as waning antibody, immunosenescence, evasion of immunity by the pathogen, deviation of immunity by the microbiome, induction of inhibitory responses, and complexity of the antigens required for protection. Fortunately, vaccine development is now incorporating knowledge from immunology, structural biology, systems biology and synthetic chemistry to meet these challenges. In addition, international organisations are developing new funding and licensing pathways for vaccines aimed at pathogens with epidemic potential that emerge from tropical areas. © 2017 The British Infection Association. Published by Elsevier Ltd. All rights reserved.

  10. Vaccination with Toxoplasma lysate antigen and CpG oligodeoxynucleotides: comparison of immune responses in intranasal versus intramuscular administrations.

    Science.gov (United States)

    EL-Malky, Mohamed A; Al-Harthi, Saeed A; Mohamed, Raafat T; EL Bali, Mohamed A; Saudy, Niveen S

    2014-06-01

    Toxoplasma gondii (T. gondii) is one of the most successful intracellular protozoan parasites on earth and highly prevalent in most warm-blooded vertebrates. There are no drugs that target the chronic cyst stage of this infection; therefore, development of an effective vaccine would be an important advance in disease control. Oligodeoxynucleotides (ODN) which contain immunostimulatory CG motifs (CpG ODN) can promote T-helper 1 (Th1) responses, an adjuvant activity that is desirable for vaccination against intracellular pathogen. In this study, we compare the immune responses of Toxoplasma susceptible C57BL/6 mice following intranasal and intramuscular vaccination with Toxoplasma lysate antigen (TLA) with or without CpG ODN as adjuvant. Immunized and control non-immunized mice were challenged with 85 cyst of the moderately virulent Beverley strain of T. gondii. Intranasal vaccination gave significantly a higher protection compared to other groups as indicated by prolonged survival and significantly reduced brain cyst burden (P intramuscular vaccination enhanced humoral immunity towards a type Th1 pattern characterized by a significant increase of specific IgG and Ig2a. Our results suggest that intranasal administration of CpG/TLA would provide a stable, pronounced, and effective vaccine against toxoplasmosis through stimulation of Th1 cellular immunity and mucosal IgA.

  11. The utility of Plasmodium berghei as a rodent model for anti-merozoite malaria vaccine assessment

    Science.gov (United States)

    Goodman, Anna L.; Forbes, Emily K.; Williams, Andrew R.; Douglas, Alexander D.; de Cassan, Simone C.; Bauza, Karolis; Biswas, Sumi; Dicks, Matthew D. J.; Llewellyn, David; Moore, Anne C.; Janse, Chris J.; Franke-Fayard, Blandine M.; Gilbert, Sarah C.; Hill, Adrian V. S.; Pleass, Richard J.; Draper, Simon J.

    2013-01-01

    Rodent malaria species Plasmodium yoelii and P. chabaudi have been widely used to validate vaccine approaches targeting blood-stage merozoite antigens. However, increasing data suggest the P. berghei rodent malaria may be able to circumvent vaccine-induced anti-merozoite responses. Here we confirm a failure to protect against P. berghei, despite successful antibody induction against leading merozoite antigens using protein-in-adjuvant or viral vectored vaccine delivery. No subunit vaccine approach showed efficacy in mice following immunization and challenge with the wild-type P. berghei strains ANKA or NK65, or against a chimeric parasite line encoding a merozoite antigen from P. falciparum. Protection was not improved in knockout mice lacking the inhibitory Fc receptor CD32b, nor against a Δsmac P. berghei parasite line with a non-sequestering phenotype. An improved understanding of the mechanisms responsible for protection, or failure of protection, against P. berghei merozoites could guide the development of an efficacious vaccine against P. falciparum. PMID:23609325

  12. Microneedle-mediated immunization of an adenovirus-based malaria vaccine enhances antigen-specific antibody immunity and reduces anti-vector responses compared to the intradermal route

    Science.gov (United States)

    Carey, John B.; Vrdoljak, Anto; O'Mahony, Conor; Hill, Adrian V. S.; Draper, Simon J.; Moore, Anne C.

    2014-01-01

    Substantial effort has been placed in developing efficacious recombinant attenuated adenovirus-based vaccines. However induction of immunity to the vector is a significant obstacle to its repeated use. Here we demonstrate that skin-based delivery of an adenovirus-based malaria vaccine, HAdV5-PyMSP142, to mice using silicon microneedles induces equivalent or enhanced antibody responses to the encoded antigen, however it results in decreased anti-vector responses, compared to intradermal delivery. Microneedle-mediated vaccine priming and resultant induction of low anti-vector antibody titres permitted repeated use of the same adenovirus vaccine vector. This resulted in significantly increased antigen-specific antibody responses in these mice compared to ID-treated mice. Boosting with a heterologous vaccine; MVA-PyMSP142 also resulted in significantly greater antibody responses in mice primed with HAdV5-PyMSP142 using MN compared to the ID route. The highest protection against blood-stage malaria challenge was observed when a heterologous route of immunization (MN/ID) was used. Therefore, microneedle-mediated immunization has potential to both overcome some of the logistic obstacles surrounding needle-and-syringe-based immunization as well as to facilitate the repeated use of the same adenovirus vaccine thereby potentially reducing manufacturing costs of multiple vaccines. This could have important benefits in the clinical ease of use of adenovirus-based immunization strategies. PMID:25142082

  13. Humoral immune response to Plasmodium falciparum vaccine candidate GMZ2 and its components in populations naturally exposed to seasonal malaria in Ethiopia

    DEFF Research Database (Denmark)

    Mamo, Hassen; Esen, Meral; Ajua, Anthony

    2013-01-01

    . The significantly higher antibody prevalence and level detected against GMZ2 compared to either of its subunits separately, in naturally exposed populations, suggests the synergistic effect of GLURP-R0 and MSP3 and that GMZ2 could be a more relevant blood-stage malaria vaccine candidate than the individual......ABSTRACT: BACKGROUND: In Ethiopia, the general population is vulnerable to unpredictable epidemics of Plasmodium falciparum malaria. However, there is little information on the anti-malaria immune profile of the population in the endemic regions of the country. METHODS: The study was designed...... for malaria infection microscopically and by the rapid diagnostic test (RDT). Sera were tested by using enzyme-linked immunosorbent assay (ELISA) for total immunoglobulin (Ig) G against P. falciparum blood-stage vaccine candidate GMZ2 and its subunits (Glutamate-rich protein (GLURP-R0), merozoite surface...

  14. Influenza vaccination

    DEFF Research Database (Denmark)

    Østerhus, Sven Frederick

    2015-01-01

    The Cochrane Library was systematically searched for meta-analyses regarding influenza vaccination of various populations, both healthy and sick. An effect in reducing the number of cases of influenza, influenza-like illness or complications to influenza was found in some studies, but, generally......, the quality of the studies was low, and several studies lacked hard clinical endpoints. Data on adverse effects were scarce. More randomised controlled trials investigating the effects of influenza vaccination are warranted....

  15. Ear Infection and Vaccines

    Science.gov (United States)

    ... an ENT Doctor Near You Ear Infection and Vaccines Ear Infection and Vaccines Patient Health Information News ... or may need reinsertion over time. What about vaccines? A vaccine is a preparation administered to stimulate ...

  16. Flu Vaccine Safety Information

    Science.gov (United States)

    ... Types Seasonal Avian Swine Variant Pandemic Other Flu Vaccine Safety Information Questions & Answers Language: English (US) Español ... of flu vaccines monitored? Egg Allergy Are flu vaccines safe? Flu vaccines have good safety record. Hundreds ...

  17. Thimerosal in Flu Vaccine

    Science.gov (United States)

    ... Avian Swine Variant Pandemic Other Thimerosal in Flu Vaccine Questions & Answers Language: English (US) Español Recommend on ... or fungi from contaminating the vaccine. Do flu vaccines contain thimerosal? Flu vaccines in multi-dose vials ...

  18. Vaccinations during Pregnancy

    Science.gov (United States)

    ... community Home > Pregnancy > Prenatal care > Vaccinations and pregnancy Vaccinations and pregnancy E-mail to a friend Please ... date before you get pregnant. What is a vaccination? A vaccination is a shot that contains a ...

  19. DNA Vaccines Against Anthrax

    National Research Council Canada - National Science Library

    Galloway, Darrell R; Baillie, Les

    2004-01-01

    DNA vaccination is vaccination at its simplest. Due to renewed interest in vaccination against anthrax and other biothreat agents, a genetic immunisation approach offers attractive possibilities for rapid, responsive vaccine development...

  20. Progress and challenges in TB vaccine development.

    Science.gov (United States)

    Voss, Gerald; Casimiro, Danilo; Neyrolles, Olivier; Williams, Ann; Kaufmann, Stefan H E; McShane, Helen; Hatherill, Mark; Fletcher, Helen A

    2018-01-01

    The Bacille Calmette Guerin (BCG) vaccine can provide decades of protection against tuberculosis (TB) disease, and although imperfect, BCG is proof that vaccine mediated protection against TB is a possibility. A new TB vaccine is, therefore, an inevitability; the question is how long will it take us to get there? We have made substantial progress in the development of vaccine platforms, in the identification of antigens and of immune correlates of risk of TB disease. We have also standardized animal models to enable head-to-head comparison and selection of candidate TB vaccines for further development.  To extend our understanding of the safety and immunogenicity of TB vaccines we have performed experimental medicine studies to explore route of administration and have begun to develop controlled human infection models. Driven by a desire to reduce the length and cost of human efficacy trials we have applied novel approaches to later stage clinical development, exploring alternative clinical endpoints to prevention of disease outcomes. Here, global leaders in TB vaccine development discuss the progress made and the challenges that remain. What emerges is that, despite scientific progress, few vaccine candidates have entered clinical trials in the last 5 years and few vaccines in clinical trials have progressed to efficacy trials. Crucially, we have undervalued the knowledge gained from our "failed" trials and fostered a culture of risk aversion that has limited new funding for clinical TB vaccine development. The unintended consequence of this abundance of caution is lack of diversity of new TB vaccine candidates and stagnation of the clinical pipeline. We have a variety of new vaccine platform technologies, mycobacterial antigens and animal and human models.  However, we will not encourage progression of vaccine candidates into clinical trials unless we evaluate and embrace risk in pursuit of vaccine development.

  1. Antipneumococcal vaccination

    Directory of Open Access Journals (Sweden)

    Gian Vincenzo Zuccotti

    2013-06-01

    Full Text Available Streptococcus pneumoniae (SP is a gram-positive bacterium with more than 90 known serotypes causing around 11% of all deaths worldwide in children aged 1-59 months. A new era in prevention of SP-related diseases started in at the beginning of 2000s when a 7-valent pneumococcal conjugate vaccine (PCV7 was recommended as the vaccine of choice in pediatric age. PCV7 dramatically reduced invasive pneumococcal diseases (IPD among children with indirect effects noted among other age groups as well. However, thanks to a strict surveillance network, an increase in non-vaccine serotypes (NVTs causing IPD was noted worldwide and in late 2000s a new second generation vaccine (13-valent pneumococcal conjugate vaccine-PCV13 with an expanded serotype coverage was licensed. Due to the lack of solid effectiveness data, up to know it is difficult to predict how the composition of NVTs will change after the large-scale introduction of PCV13 or whether the characteristics of the serotypes will change. Long-term surveillance of both IPD, pneumonia, acute otitis media and carriage will be crucial to ascertain whether these second generation vaccines are having the desired effect of reducing the incidence of diseases in the long term. Proceedings of the 9th International Workshop on Neonatology · Cagliari (Italy · October 23rd-26th, 2013 · Learned lessons, changing practice and cutting-edge research

  2. A randomized trial assessing the safety and immunogenicity of AS01 and AS02 adjuvanted RTS,S malaria vaccine candidates in children in Gabon.

    Directory of Open Access Journals (Sweden)

    Bertrand Lell

    2009-10-01

    Full Text Available The malaria vaccine candidate antigen RTS,S includes parts of the pre-erythrocytic stage circumsporozoite protein fused to the Hepatitis B surface antigen. Two Adjuvant Systems are in development for this vaccine, an oil-in water emulsion--based formulation (AS02 and a formulation based on liposomes (AS01.In this Phase II, double-blind study (NCT00307021, 180 healthy Gabonese children aged 18 months to 4 years were randomized to receive either RTS,S/AS01(E or RTS,S/AS02(D, on a 0-1-2 month vaccination schedule. The children were followed-up daily for six days after each vaccination and monthly for 14 months. Blood samples were collected at 4 time-points. Both vaccines were well tolerated. Safety parameters were distributed similarly between the two groups. Both vaccines elicited a strong specific immune response after Doses 2 and 3 with a ratio of anti-CS GMT titers (AS02(D/AS01(E of 0.88 (95% CI: 0.68-1.15 post-Dose 3. After Doses 2 and 3 of experimental vaccines, anti-CS and anti-HBs antibody GMTs were higher in children who had been previously vaccinated with at least one dose of hepatitis B vaccine compared to those not previously vaccinated.RTS,S/AS01(E proved similarly as well tolerated and immunogenic as RTS,S/AS02(D, completing an essential step in the age de-escalation process within the RTS,S clinical development plan.ClinicalTrials.gov. NCT00307021.

  3. Important advances in malaria vaccine research

    Directory of Open Access Journals (Sweden)

    Priyanka Jadhav

    2012-01-01

    Full Text Available Malaria is one of the most widespread parasitic infection in Asian countries affecting the poor of the poor. In an effort to develop an effective vaccine for the treatment of malaria, various attempts are being made worldwide. If successful, such a vaccine can be effective for treatment of both Plasmodium vivax and Plasmodium falciparum. This would also be able to avoid complications such as drug resistance, resistance to insecticides, nonadherence to the treatment schedule, and eventually high cost of treatment in the resource-limited settings. In the current compilation, the details from the literature were collected by using PubMed and Medline as search engines and searched for terms such as malaria, vaccine, and malaria treatment. This review collates and provides glimpses of the information on the recent malaria vaccine development. The reader will be taken through the historical perspective followed by the approaches to the malaria vaccine development from pre-erythrocytic stage vaccines, asexual stage vaccines, transmission blocking vaccines, etc. Looking at the current scenario of the malaria and treatment strategies, it is an absolute need of an hour that an effective malaria vaccine should be developed. This would bring a revolutionary breakthrough in the treatment modalities especially when there is increasing emergence of resistance to existing drug therapy. It would be of great purpose to serve those living in malaria endemic region and also for travelers which are nonimmune and coming to malaria endemic region. As infection by P. vivax is more prevalent in India and other Asian subcontinent and is often prominent in areas where elimination is being attempted, special consideration is required of the role of vaccines in blocking transmission, regardless of the stages being targeted. Development of vaccines is feasible but with the support of private sector and government organization in terms of regulatory and most importantly

  4. The benefits of combining early aspecific vaccination with later specific vaccination

    NARCIS (Netherlands)

    L.E. Duijzer (Evelot); W.L. van Jaarsveld (Willem); R. Dekker (Rommert)

    2017-01-01

    markdownabstractTiming is of crucial importance for successful vaccination. To avoid a large outbreak, vaccines are administered preferably as quickly as possible. However, in the early stages of an outbreak the information on the disease is limited and waiting with the intervention allows to

  5. Phase II Study of Adjuvant Immunotherapy with the CSF-470 Vaccine Plus Bacillus Calmette–Guerin Plus Recombinant Human Granulocyte Macrophage-Colony Stimulating Factor vs Medium-Dose Interferon Alpha 2B in Stages IIB, IIC, and III Cutaneous Melanoma Patients: A Single Institution, Randomized Study

    Directory of Open Access Journals (Sweden)

    José Mordoh

    2017-05-01

    Full Text Available The irradiated, allogeneic, cellular CSF-470 vaccine plus Bacillus Calmette–Guerin (BCG and recombinant human granulocyte macrophage-colony stimulating factor (rhGM-CSF is being tested against medium-dose IFN-α2b in stages IIB–III cutaneous melanoma (CM patients (pts after surgery in an open, randomized, Phase II/III study. We present the results of the Phase II part of the ongoing CASVAC-0401 study (ClinicalTrials.gov: NCT01729663. Thirty-one pts were randomized to the CSF-470 vaccine (n = 20 or to the IFN-α2b arm (n = 11. During the 2-year treatment, immunized pts should receive 13 vaccinations. On day 1 of each visit, 1.6 × 107 irradiated CSF-470 cells plus 106 colony-forming units BCG plus 100 µg rhGM-CSF were administered intradermally, followed on days 2–4 by 100 µg rhGM-CSF. IFN-α2b pts should receive 10 million units (MU/day/5 days a week for 4 weeks; then 5 MU thrice weekly for 23 months. Toxicity and quality of life (QOL were evaluated at each visit. With a mean and a maximum follow-up of 39.4 and 83 months, respectively, a significant benefit in the distant metastasis-free survival (DMFS for CSF-470 was observed (p = 0.022. Immune monitoring showed an increase in antitumoral cellular and humoral response in vaccinated pts. CSF-470 was well tolerated; 20/20 pts presented grades 1–2 dermic reactions at the vaccination site; 3/20 pts presented grade 3 allergic reactions. Other adverse events (AEs were grade 1. Pts in the IFN-α2b arm presented grades 2–3 hematological (7/11, hepatic (2/11, and cardiac (1/11 toxicity; AEs in 9/11 pts forced treatment interruptions. QOL was significantly superior in the vaccine arm (p < 0.0001. Our results suggest that CSF-470 vaccine plus BCG plus GM-CSF can significantly prolong, with lower toxicity, the DMFS of high-risk CM pts with respect to medium-dose IFN-α2b. The continuation of a Phase III part of the CASVAC-0401 study is encouraged.

  6. Evolution of cerebral blood flow between the acute stage and one month after a global transient amnesia: a study of 18 patients

    International Nuclear Information System (INIS)

    Philippon, B.; Houzard, C.; Cinotti, L.; Croisile, B.

    2001-01-01

    We studied 18 patients within 24 hours of an idiopathic transient global amnesia and one month later using 133 Xe et 99m Tc-HMPAO for CBF measurements. Absolute hemispheric CBF obtained with the 133 Xe were initially: (right) = 46.9 ml/mn/100 g (s.d 6.6) and (left) = 47.9 (s.d 6.8). One month later, a significant increase of the right hemispheric CBF occurred (52.0 ± 6.9). Accordingly, absolute CBF increased bilaterally in the cerebellar and temporal regions. Local relative cerebral blood flow ( 99m Tc-HMPAO) allowed to reinforce these findings with increased resolution. They can also provide quantitative values thanks to the 133 Xe calibration. (authors)

  7. Hepatitis B vaccination: Efficiency of pretesting by RIA-methods

    International Nuclear Information System (INIS)

    Hale, T.I.; Schmid, B.

    1984-01-01

    Vaccination of individuals who possess antibodies against HBs virus from a previous infection is not necessary. Health-care personnel represents a large population of potential vaccine recipients. The risk of developing hepatitis B among these workers is proportional to the degree of their exposure to both blood and blood products as well as to patients with hepatitis B. The decision to screen before vaccination depends on the costs of screening, the costs of vaccination, and the likelihood of vaccination candidates having had hepatitis B. We have demonstrated the cost effective use of screening using RIA-methods in a group of health workers for anti-HBs. If care is taken in the organization of the vaccination program, prevaccination screening of vaccine candidates can save considerable amounts of money. (orig.) [de

  8. A novel genetic technique in Plasmodium berghei allows liver stage analysis of genes required for mosquito stage development and demonstrates that de novo heme synthesis is essential for liver stage development in the malaria parasite.

    Directory of Open Access Journals (Sweden)

    Upeksha L Rathnapala

    2017-06-01

    Full Text Available The combination of drug resistance, lack of an effective vaccine, and ongoing conflict and poverty means that malaria remains a major global health crisis. Understanding metabolic pathways at all parasite life stages is important in prioritising and targeting novel anti-parasitic compounds. The unusual heme synthesis pathway of the rodent malaria parasite, Plasmodium berghei, requires eight enzymes distributed across the mitochondrion, apicoplast and cytoplasm. Deletion of the ferrochelatase (FC gene, the final enzyme in the pathway, confirms that heme synthesis is not essential in the red blood cell stages of the life cycle but is required to complete oocyst development in mosquitoes. The lethality of FC deletions in the mosquito stage makes it difficult to study the impact of these mutations in the subsequent liver stage. To overcome this, we combined locus-specific fluorophore expression with a genetic complementation approach to generate viable, heterozygous oocysts able to produce a mix of FC expressing and FC deficient sporozoites. These sporozoites show normal motility and can invade liver cells, where FC deficient parasites can be distinguished by fluorescence and phenotyped. Parasites lacking FC exhibit a severe growth defect within liver cells, with development failure detectable in the early to mid stages of liver development in vitro. FC deficient parasites could not complete liver stage development in vitro nor infect naïve mice, confirming liver stage arrest. These results validate the heme pathway as a potential target for prophylactic drugs targeting liver stage parasites. In addition, we demonstrate that our simple genetic approach can extend the phenotyping window beyond the insect stages, opening considerable scope for straightforward reverse genetic analysis of genes that are dispensable in blood stages but essential for completing mosquito development.

  9. A novel genetic technique in Plasmodium berghei allows liver stage analysis of genes required for mosquito stage development and demonstrates that de novo heme synthesis is essential for liver stage development in the malaria parasite.

    Science.gov (United States)

    Rathnapala, Upeksha L; Goodman, Christopher D; McFadden, Geoffrey I

    2017-06-01

    The combination of drug resistance, lack of an effective vaccine, and ongoing conflict and poverty means that malaria remains a major global health crisis. Understanding metabolic pathways at all parasite life stages is important in prioritising and targeting novel anti-parasitic compounds. The unusual heme synthesis pathway of the rodent malaria parasite, Plasmodium berghei, requires eight enzymes distributed across the mitochondrion, apicoplast and cytoplasm. Deletion of the ferrochelatase (FC) gene, the final enzyme in the pathway, confirms that heme synthesis is not essential in the red blood cell stages of the life cycle but is required to complete oocyst development in mosquitoes. The lethality of FC deletions in the mosquito stage makes it difficult to study the impact of these mutations in the subsequent liver stage. To overcome this, we combined locus-specific fluorophore expression with a genetic complementation approach to generate viable, heterozygous oocysts able to produce a mix of FC expressing and FC deficient sporozoites. These sporozoites show normal motility and can invade liver cells, where FC deficient parasites can be distinguished by fluorescence and phenotyped. Parasites lacking FC exhibit a severe growth defect within liver cells, with development failure detectable in the early to mid stages of liver development in vitro. FC deficient parasites could not complete liver stage development in vitro nor infect naïve mice, confirming liver stage arrest. These results validate the heme pathway as a potential target for prophylactic drugs targeting liver stage parasites. In addition, we demonstrate that our simple genetic approach can extend the phenotyping window beyond the insect stages, opening considerable scope for straightforward reverse genetic analysis of genes that are dispensable in blood stages but essential for completing mosquito development.

  10. Characterization of germline antibody libraries from human umbilical cord blood and selection of monoclonal antibodies to viral envelope glycoproteins: Implications for mechanisms of immune evasion and design of vaccine immunogens.

    Science.gov (United States)

    Chen, Weizao; Streaker, Emily D; Russ, Daniel E; Feng, Yang; Prabakaran, Ponraj; Dimitrov, Dimiter S

    2012-01-27

    We have previously observed that all known HIV-1 broadly neutralizing antibodies (bnAbs) are highly divergent from germline antibodies in contrast to bnAbs against Hendra virus, Nipah virus and SARS coronavirus (SARS CoV). We have hypothesized that because the germline antibodies are so different from the mature HIV-1-specific bnAbs they may not bind the epitopes of the mature antibodies and provided the first evidence to support this hypothesis by using individual putative germline-like predecessor antibodies. To further validate the hypothesis and understand initial immune responses to different viruses, two phage-displayed human cord blood-derived IgM libraries were constructed which contained mostly germline antibodies or antibodies with very low level of somatic hypermutations. They were panned against different HIV-1 envelope glycoproteins (Envs), SARS CoV protein receptor-binding domain (RBD), and soluble Hendra virus G protein (sG). Despite a high sequence and combinatorial diversity observed in the cord blood-derived IgM antibody repertoire, no enrichment for binders of Envs was observed in contrast to considerable specific enrichments produced with panning against RBD and sG; one of the selected monoclonal antibodies (against the RBD) was of high (nM) affinity with only few somatic mutations. These results further support and expand our initial hypothesis for fundamental differences in immune responses leading to elicitation of bnAbs against HIV-1 compared to SARS CoV and Hendra virus. HIV-1 uses a strategy to minimize or eliminate strong binding of germline antibodies to its Env; in contrast, SARS CoV and Hendra virus, and perhaps other viruses causing acute infections, can bind germline antibody or minimally somatically mutated antibodies with relatively high affinity which could be one of the reasons for the success of sG and RBD as vaccine immunogens. Published by Elsevier Inc.

  11. Status of vaccine research and development of vaccines for leishmaniasis.

    Science.gov (United States)

    Gillespie, Portia M; Beaumier, Coreen M; Strych, Ulrich; Hayward, Tara; Hotez, Peter J; Bottazzi, Maria Elena

    2016-06-03

    A number of leishmaniasis vaccine candidates are at various stages of pre-clinical and clinical development. Leishmaniasis is a vector-borne neglected tropical disease (NTD) caused by a protozoan parasite of the genus Leishmania and transmitted to humans by the bite of a sand fly. Visceral leishmaniasis (VL, kala-azar) is a high mortality NTD found mostly in South Asia and East Africa, while cutaneous leishmaniasis (CL) is a disfiguring NTD highly endemic in the Middle East, Central Asia, North Africa, and the Americas. Estimates attribute 50,000 annual deaths and 3.3 million disability-adjusted life years to leishmaniasis. There are only a few approved drug treatments, no prophylactic drug and no vaccine. Ideally, an effective vaccine against leishmaniasis will elicit long-lasting immunity and protect broadly against VL and CL. Vaccines such as Leish-F1, F2 and F3, developed at IDRI and designed based on selected Leishmania antigen epitopes, have been in clinical trials. Other groups, including the Sabin Vaccine Institute in collaboration with the National Institutes of Health are investigating recombinant Leishmania antigens in combination with selected sand fly salivary gland antigens in order to augment host immunity. To date, both VL and CL vaccines have been shown to be cost-effective in economic modeling studies. Copyright © 2016 World Health Organization. Published by Elsevier Ltd.. All rights reserved.

  12. Transmission blocking malaria vaccines: Assays and candidates in clinical development.

    Science.gov (United States)

    Sauerwein, R W; Bousema, T

    2015-12-22

    Stimulated by recent advances in malaria control and increased funding, the elimination of malaria is now considered to be an attainable goal for an increasing number of malaria-endemic regions. This has boosted the interest in transmission-reducing interventions including vaccines that target sexual, sporogenic, and/or mosquito-stage antigens to interrupt malaria transmission (SSM-VIMT). SSM-VIMT aim to prevent human malaria infection in vaccinated communities by inhibiting parasite development within the mosquito after a blood meal taken from a gametocyte carrier. Only a handful of target antigens are in clinical development and progress has been slow over the years. Major stumbling blocks include (i) the expression of appropriately folded target proteins and their downstream purification, (ii) insufficient induction of sustained functional blocking antibody titers by candidate vaccines in humans, and (iii) validation of a number of (bio)-assays as correlate for blocking activity in the field. Here we discuss clinical manufacturing and testing of current SSM-VIMT candidates and the latest bio-assay development for clinical evaluation. New testing strategies are discussed that may accelerate the evaluation and application of SSM-VIMT. Copyright © 2015. Published by Elsevier Ltd.

  13. Quantitative isolation and in vivo imaging of malaria parasite liver stages.

    Science.gov (United States)

    Tarun, Alice S; Baer, Kerstin; Dumpit, Ronald F; Gray, Sean; Lejarcegui, Nicholas; Frevert, Ute; Kappe, Stefan H I

    2006-10-01

    The liver stages of Plasmodium, the causative agent of malaria, are the least explored forms in the parasite's life cycle despite their recognition as key vaccine and drug targets. In vivo experimental access to liver stages of human malaria parasites is practically prohibited and therefore rodent model malaria parasites have been used for in vivo studies. However, even in rodent models progress in the analysis of liver stages has been limited, mainly due to their low abundance and associated difficulties in visualisation and isolation. Here, we present green fluorescent protein (GFP)-tagged Plasmodium yoelii rodent malaria parasite liver infections in BALB/c mice as an excellent quantitative model for the live visualisation and isolation of the so far elusive liver stages. We believe P. yoelii GFP-tagged liver stages allow, for the first time, the efficient quantitative isolation of intact early and late liver stage-infected hepatocyte units by fluorescence activated cell sorting. GFP-tagged liver stages are also well suited for intravital imaging, allowing us for the first time to visualise them in real time. We identify previously unrecognised features of liver stages including vigorous parasite movement and expulsion of 'extrusomes'. Intravital imaging thus reveals new, important information on the malaria parasite's transition from tissue to blood stage.

  14. Specific Antibody Production by Blood B Cells is Retained in Late Stage Drug-naïve HIV-infected Africans

    Directory of Open Access Journals (Sweden)

    Lydie Béniguel

    2004-01-01

    Full Text Available Unseparated peripheral blood mononuclear cells (PBMCs obtained from drug-naïve African individuals living in a context of multi-infections and presenting with high viral load (VL, were cultured in vitro and tested for their ability to produce antibodies (Abs reacting with HIV-1 antigens. Within these PBMCs, circulating B cells were differentiated in vitro and produced IgG Abs against not only ENV, but also GAG and POL proteins. Under similar experimental conditions, HAART treated patients produced Abs to ENV proteins only. The in vitro antibody production by drug-naïve individuals' PBMCs depended on exogenous cytokines (IL-2 and IL-10 but neither on the re-stimulation of reactive cells in cultures by purified HIV-1-gp 160 antigen nor on the re-engagement of CD40 surface molecules. Further, it was not abrogated by the addition of various monoclonal Abs (mAbs to co-stimulatory molecules. This suggests that the in vitro antibody production by drug-naïve individuals' PBMCs resulted from the maturation of already envelope and core antigen-primed, differentiated B cells, presumably pre-plasma cells, which are not known to circulate at homeostasy. As in vitro produced Abs retained the capacity of binding antigen and forming complexes, this study provides pre-clinical support for functional humoral responses despite major HIV- and other tropical pathogen-induced B cell perturbations.

  15. The effect of viroid infection of citrus trees on the amoebicidal activity of 'Maltese half-blood' (Citrus sinensis) against trophozoite stage of Acanthamoeba castellanii Neff.

    Science.gov (United States)

    Zouaghi, Ghaya; Najar, Asma; Chiboub, Olfa; Sifaoui, Ines; Abderrabba, Manef; Lorenzo Morales, Jacob

    2017-12-01

    In order to promote a local Tunisian product, this study was designed to examine, for the first time, the anti-Acanthamoeba activity (Acanthamoeba castellanii Neff) of the essential oils of Tunisian Citrus sinensis peels (Maltese half-blood) and the effect of viroid plant infection on this activity. To do so, three samples of peels' essential oils were studied: from a healthy plant (Control), a plant inoculated with Citrus exocortis viroid (CEVd) and one inoculated with hot stunt cachexia viroid (HSVd). The samples were extracted by hydrodistillation from dried peels and characterized by GC-MS. Limonene was the major component with a percentage ranging from 90.76 to 93.34% for (CEVd) sample and (Control), respectively. Anti-Acanthamoeba activity of the tested oils was determined by the Alamar Blue ® assay. Primary results showed a strong potential anti-Acanthamoeba activity with an IC 50 ranging from 36.6 to 54.58 μg/ml for (HSVd) and (CEVd) samples, respectively. In terms of the effect of viroid infection, a strong positive correlation was observed between different chemical classes and anti-Acanthamoeba activity. Copyright © 2017 Elsevier Inc. All rights reserved.

  16. Comparative efficacy of an indigenous 'inactivated vaccine' using highly pathogenic field strain of Mycobacterium avium subspecies paratuberculosis 'Bison type' with a commercial vaccine for the control of Capri-paratuberculosis in India.

    Science.gov (United States)

    Singh, S V; Singh, P K; Singh, A V; Sohal, J S; Gupta, V K; Vihan, V S

    2007-10-10

    Johne's disease (JD) is endemic in goatherds located at Central Institute for Research on Goats, Makhdoom, since 1979 and lately it has been reported from farmer's herds in equal frequencies. Despite using test and slaughter method for the control of JD for more than 25 years in these herds, incidence of JD has not been reduced. Efficacy of 'indigenous vaccine' containing native 'Bison type' genotype of Mycobacterium avium subspecies paratuberculosis (MAP) was compared with commercial vaccine using challenge studies with homologous strain of MAP. Goat kids (85) were randomly divided in to three groups. Kids were vaccinated with 1 ml of vaccine subcutaneously and Sham-immunized with 1 ml of sterile PBS. All kids except 3 in each group were challenged twice at 75- and 275-day post-vaccination (DPV). Four goats each from three groups were sacrificed at 200-day post-challenge to evaluate carcass and histopathologically for vaccine and challenge response in kids of different groups. Samples (blood, serum and fecal) were screened for LTT, ELISA and shedding of bacilli and data on live animal traits, mortality and experimental sacrifice were compared. Average body weights gained by goats in three groups at different stages of trials (0, 1-75, 76-275, 276-425 DPV) showed marked improvements in performance of vaccinated groups over 'Sham-immunized' group. Effect of vaccines against challenge became visible in terms of body weights gained at 276-425 DPV ('Bison' group gained significantly higher body weights than 'Sham-immunized'). Mortality was significantly less in two vaccinated as compared to 'Sham-immunized'. Vaccinated groups also had significant stimulation and sero-conversion for cell mediated and humoral immune response, respectively as compared to 'Sham-immunized'. Results of post-challenged fecal culture showed significant reduction in shedding of MAP in both vaccinated groups than in 'Sham-immunized'. There was significant improvement in external and internal

  17. Stage design

    International Nuclear Information System (INIS)

    Shacter, J.

    1975-01-01

    A method is described of cycling gases through a plurality of diffusion stages comprising the steps of admitting the diffused gases from a first diffusion stage into an axial compressor, simultaneously admitting the undiffused gases from a second diffusion stage into an intermediate pressure zone of said compressor corresponding in pressure to the pressure of said undiffused gases, and then admitting the resulting compressed mixture of diffused and undiffused gases into a third diffusion stage

  18. Safety and immunogenicity of an AMA-1 malaria vaccine in Malian adults: results of a phase 1 randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Mahamadou A Thera

    2008-01-01

    Full Text Available The objective was to evaluate the safety, reactogenicity and immunogenicity of the AMA-1-based blood-stage malaria vaccine FMP2.1/AS02A in adults exposed to seasonal malaria.A phase 1 double blind randomized controlled dose escalation trial was conducted in Bandiagara, Mali, West Africa, a rural town with intense seasonal transmission of Plasmodium falciparum malaria. The malaria vaccine FMP2.1/AS02A is a recombinant protein (FMP2.1 based on apical membrane antigen-1 (AMA-1 from the 3D7 clone of P. falciparum, adjuvanted with AS02A. The comparator vaccine was a cell-culture rabies virus vaccine (RabAvert. Sixty healthy, malaria-experienced adults aged 18-55 y were recruited into 2 cohorts and randomized to receive either a half dose or full dose of the malaria vaccine (FMP2.1 25 microg/AS02A 0.25 mL or FMP2.1 50 microg/AS02A 0.5 mL or rabies vaccine given in 3 doses at 0, 1 and 2 mo, and were followed for 1 y. Solicited symptoms were assessed for 7 d and unsolicited symptoms for 30 d after each vaccination. Serious adverse events were assessed throughout the study. Titers of anti-AMA-1 antibodies were measured by ELISA and P. falciparum growth inhibition assays were performed on sera collected at pre- and post-vaccination time points. Transient local pain and swelling were common and more frequent in both malaria vaccine dosage groups than in the comparator group. Anti-AMA-1 antibodies increased significantly in both malaria vaccine groups, peaking at nearly 5-fold and more than 6-fold higher than baseline in the half-dose and full-dose groups, respectively.The FMP2.1/AS02A vaccine had a good safety profile, was well-tolerated, and was highly immunogenic in malaria-exposed adults. This malaria vaccine is being evaluated in Phase 1 and 2 trials in children at this site.

  19. Periodontal Vaccines

    Directory of Open Access Journals (Sweden)

    Daisy Happy

    2013-01-01

    Full Text Available Periodontitis is an infectious disease caused by predominantly gram-negative, anaerobic bacteria like P. gingivalis, A. actinomycetemcomitans T. denticola and T. forsythus etc.. Various immunization approaches both as active and passive immunization, against periodontal pathogens have been explored either using the whole microorganism or their specific virulence factors. Non-human primate and other study models have demonstrated raised production of specific antibody titers against various antigens without any recognizable systemic side-effects. But, the current status of our understanding in the field of vaccines against periodontal disease is incomplete. Ongoing research & collaborative efforts can result in development of functional periodontal vaccine for human use in future.

  20. RNA-seq liver transcriptome analysis reveals an activated MHC-I pathway and an inhibited MHC-II pathway at the early stage of vaccine immunization in zebrafish

    Directory of Open Access Journals (Sweden)

    Yang Dahai

    2012-07-01

    Full Text Available Abstract Background Zebrafish (Danio rerio is a prominent vertebrate model of human development and pathogenic disease and has recently been utilized to study teleost immune responses to infectious agents threatening the aquaculture industry. In this work, to clarify the host immune mechanisms underlying the protective effects of a putative vaccine and improve its immunogenicity in the future efforts, high-throughput RNA sequencing technology was used to investigate the immunization-related gene expression patterns of zebrafish immunized with Edwardsiella tarda live attenuated vaccine. Results Average reads of 18.13 million and 14.27 million were obtained from livers of zebrafish immunized with phosphate buffered saline (mock and E. tarda vaccine (WED, respectively. The reads were annotated with the Ensembl zebrafish database before differential expressed genes sequencing (DESeq comparative analysis, which identified 4565 significantly differentially expressed genes (2186 up-regulated and 2379 down-regulated in WED; p Conclusion These data provided insights into the molecular mechanisms underlying zebrafish immune response to WED immunization and might aid future studies to develop a highly immunogenic vaccine against gram-negative bacteria in teleosts.

  1. Measles vaccination using a microneedle patch☆

    Science.gov (United States)

    Edens, Chris; Collins, Marcus L.; Ayers, Jessica; Rota, Paul A.; Prausnitz, Mark R.

    2013-01-01

    Measles vaccination programs would benefit from delivery methods that decrease cost, simplify logistics, and increase safety. Conventional subcutaneous injection is limited by the need for skilled healthcare professionals to reconstitute and administer injections, and by the need for safe needle handling and disposal to reduce the risk of disease transmission through needle re-use and needlestick injury. Microneedles are micron-scale, solid needles coated with a dry formulation of vaccine that dissolves in the skin within minutes after patch application. By avoiding the use of hypodermic needles, vaccination using a microneedle patch could be carried out by minimally trained personnel with reduced risk of blood-borne disease transmission. The goal of this study was to evaluate measles vaccination using a microneedle patch to address some of the limitations of subcutaneous injection. Viability of vaccine virus dried onto a microneedle patch was stabilized by incorporation of the sugar, trehalose, and loss of viral titer was less than 1 log10(TCID50) after storage for at least 30 days at room temperature. Microneedle patches were then used to immunize cotton rats with the Edmonston-Zagreb measles vaccine strain. Vaccination using microneedles at doses equaling the standard human dose or one-fifth the human dose generated neutralizing antibody levels equivalent to those of a subcutaneous immunization at the same dose. These results show that measles vaccine can be stabilized on microneedles and that vaccine efficiently reconstitutes in vivo to generate a neutralizing antibody response equivalent to that generated by subcutaneous injection. PMID:23044406

  2. Diversity and Vaccine Controversy

    OpenAIRE

    Frempong, Erica

    2010-01-01

    My area of research dealt with many different aspects of the vaccine movement, the main three were: anti-vaccine sentiments over the Internet, global instances of anti-vaccination efforts, and differences in social class and race in vaccine utilization. I have come to realize that there are two distinct issues arising in the organization that encompasses vaccines. The distinctions are the anti-vaccine movement - the spread of anti-vaccine sentiments over the Internet, and global instances ...

  3. Green revolution vaccines, edible vaccines | Tripurani | African ...

    African Journals Online (AJOL)

    Edible vaccines are sub-unit vaccines where the selected genes are introduced into the plants and the transgenic plant is then induced to manufacture the encoded protein. Edible vaccines are mucosal-targeted vaccines where stimulation of both systematic and mucosal immune network takes place. Foods under study ...

  4. Predictors of seasonal influenza vaccination among older adults in Thailand.

    Directory of Open Access Journals (Sweden)

    Prabda Praphasiri

    Full Text Available In advance of a large influenza vaccine effectiveness (VE cohort study among older adults in Thailand, we conducted a population-based, cross-sectional survey to measure vaccine coverage and identify factors associated with influenza vaccination among older Thai adults that could bias measures of vaccine effectiveness.We selected adults ≥65 years using a two-stage, stratified, cluster sampling design. Functional status was assessed using the 10-point Vulnerable Elders Survey (VES; scores ≥3 indicated vulnerability. Questions about attitudes towards vaccination were based on the Health Belief Model. The distance between participants' households and the nearest vaccination clinic was calculated. Vaccination status was determined using national influenza vaccination registry. Prevalence ratios (PR and 95% confidence intervals (CIs were calculated using log-binomial multivariable models accounting for the sampling design.We enrolled 581 participants, of whom 60% were female, median age was 72 years, 41% had at least one chronic underlying illness, 24% met the criteria for vulnerable, and 23% did not leave the house on a daily basis. Influenza vaccination rate was 34%. In multivariable models, no variable related to functional status was associated with vaccination. The strongest predictors of vaccination were distance to the nearest vaccination center (PR 3.0, 95% CI 1.7-5.1 for participants in the closest quartile compared to the furthest, and high levels of a perception of benefits of influenza vaccination (PR 2.8, 95% CI 1.4-5.6 and cues to action (PR 2.7, 95% CI 1.5-5.1.Distance to vaccination clinics should be considered in analyses of influenza VE studies in Thailand. Strategies that emphasize benefits of vaccination and encourage physicians to recommend annual influenza vaccination could improve influenza vaccine uptake among older Thai adults. Outreach to more distant and less mobile older adults may also be required to improve influenza

  5. Influenza and Pneumonia Vaccination Rates and Factors Affecting Vaccination among Patients with Chronic Obstructive Pulmonary Disease

    Directory of Open Access Journals (Sweden)

    Ülkü Aka Aktürk

    2017-06-01

    Full Text Available Background: Influenza and pneumococcal vaccinations are recommended in chronic obstructive pulmonary disease patients to decrease associated risks at all stages. Although the prevalence of chronic obstructive pulmonary disease is high in our country, as previously reported, vaccination rates are low. Aims: To assess the vaccination rates of chronic obstructive pulmonary disease patients and factors that may affect these. Study Design: Multi-centre cross-sectional study. Methods: Patients admitted to the chest diseases clinics of six different centres between 1 February 2013 and 1 January 2014 with a pre-diagnosis of Chronic obstructive pulmonary disease according to the Global initiative for chronic obstructive lung disease criteria, who were in a stable condition were included in the study. The survey, which included demographic characteristics, socio-economic status, severity of disease and vaccination information, was first tested on a small patient population before the study. The survey was completed by the investigators after obtaining written informed consent. Results: The average age of the 296 included patients was 66.3±9.3 years and 91.9% were male. Of these, 36.5% had the influenza vaccination and 14.1% had the pneumococcal vaccination. The most common reason for not being vaccinated was ‘no recommendation by doctors’: 57.2% in the case of influenza vaccinations, and 46.8% in the case of pneumococcal vaccinations. Both vaccination rates were significantly higher in those patients with comorbidities (influenza vaccination p0.05. Vaccination rates were significantly higher in those with a white-collar occupation and higher education level, and who presented to a university hospital (p<0.001. Conclusion: Medical professionals do not request vaccinations as often as the International Guidelines suggest for chronic obstructive pulmonary disease patients. Awareness of the importance of these vaccinations among both doctors and patients

  6. Safety and immunogenicity of a malaria vaccine, Plasmodium falciparum AMA-1/MSP-1 chimeric protein formulated in montanide ISA 720 in healthy adults.

    Directory of Open Access Journals (Sweden)

    Jinhong Hu

    Full Text Available BACKGROUND: The P. falciparum chimeric protein 2.9 (PfCP-2.9 consisting of the sequences of MSP1-19 and AMA-1 (III is a malaria vaccine candidate that was found to induce inhibitory antibodies in rabbits and monkeys. This was a phase I randomized, single-blind, placebo-controlled, dose-escalation study to evaluate the safety and immunogenicity of the PfCP-2.9 formulated with a novel adjuvant Montanide ISA720. Fifty-two subjects were randomly assigned to 4 dose groups of 10 participants, each receiving the test vaccine of 20, 50, 100, or 200 microg respectively, and 1 placebo group of 12 participants receiving the adjuvant only. METHODS AND FINDINGS: The vaccine formulation was shown to be safe and well-tolerated, and none of the participants withdrew. The total incidence of local adverse events (AEs was 75%, distributed among 58% of the placebo group and 80% of those vaccinated. Among the vaccinated, 65% had events that were mild and 15% experienced moderate AEs. Almost all systemic adverse reactions observed in this study were graded as mild and required no therapy. The participants receiving the test vaccine developed detectable antibody responses which were boosted by the repeated vaccinations. Sixty percent of the vaccinated participants had high ELISA titers (>1:10,000 of antigen-specific antibodies which could also recognize native parasite proteins in an immunofluorescence assay (IFA. CONCLUSION: This study is the first clinical trial for this candidate and builds on previous investigations supporting PfCP-2.9/ISA720 as a promising blood-stage malaria vaccine. Results demonstrate safety, tolerability (particularly at the lower doses tested and immunogenicity of the formulation. Further clinical development is ongoing to explore optimizing the dose and schedule of the formulation to decrease reactogenicity without compromising immunogenicity. TRIAL REGISTRATION: Chinese State Food and Drug Administration (SFDA 2002SL0046; Controlled

  7. How advances in immunology provide insight into improving vaccine efficacy

    Science.gov (United States)

    Slifka, Mark K.; Amanna, Ian

    2014-01-01

    Vaccines represent one of the most compelling examples of how biomedical research has improved society by saving lives and dramatically reducing the burden of infectious disease. Despite the importance of vaccinology, we are still in the early stages of understanding how the best vaccines work and how we can achieve better protective efficacy through improved vaccine design. Most successful vaccines have been developed empirically, but recent advances in immunology are beginning to shed new light on the mechanisms of vaccine-mediated protection and development of long-term immunity. Although natural infection will often elicit lifelong immunity, almost all current vaccines require booster vaccination in order to achieve durable protective humoral immune responses, regardless of whether the vaccine is based on infection with replicating live-attenuated vaccine strains of the specific pathogen or whether they are derived from immunization with inactivated, non-replicating vaccines or subunit vaccines. The form of the vaccine antigen (e.g., soluble or particulate/aggregate) appears to play an important role in determining immunogenicity and the interactions between dendritic cells, B cells and T cells in the germinal center are likely to dictate the magnitude and duration of protective immunity. By learning how to optimize these interactions, we may be able to elicit more effective and long-lived immunity with fewer vaccinations. PMID:24709587

  8. DNA Vaccines

    Indian Academy of Sciences (India)

    The year 1996 marked the 200th anniversary of the first vaccine developed against smallpox by Edward Jenner. In the now- famous 1796 experiment, Jenner scratched the arm of eight- year-old James Phipps, infecting the boy with cowpox pus taken from a milkmaid carrying the virus. Two months later, he scratched James ...

  9. Valuing vaccination.

    Science.gov (United States)

    Bärnighausen, Till; Bloom, David E; Cafiero-Fonseca, Elizabeth T; O'Brien, Jennifer Carroll

    2014-08-26

    Vaccination has led to remarkable health gains over the last century. However, large coverage gaps remain, which will require significant financial resources and political will to address. In recent years, a compelling line of inquiry has established the economic benefits of health, at both the individual and aggregate levels. Most existing economic evaluations of particular health interventions fail to account for this new research, leading to potentially sizable undervaluation of those interventions. In line with this new research, we set forth a framework for conceptualizing the full benefits of vaccination, including avoided medical care costs, outcome-related productivity gains, behavior-related productivity gains, community health externalities, community economic externalities, and the value of risk reduction and pure health gains. We also review literature highlighting the magnitude of these sources of benefit for different vaccinations. Finally, we outline the steps that need to be taken to implement a broad-approach economic evaluation and discuss the implications of this work for research, policy, and resource allocation for vaccine development and delivery.

  10. Rotavirus Vaccine

    Science.gov (United States)

    ... rotavirus disease was a common and serious health problem for children in the United States. Almost all children in the U.S. had at least one rotavirus infection before their 5th birthday.Every year before the vaccine was available: more ...

  11. Vexing Vaccines

    Science.gov (United States)

    Bowman, Darcia Harris

    2004-01-01

    Schools play a key role in ensuring that children are being immunized against diseases, but conflicting research is making enforcement difficult. This article discusses a growing trend of vaccine avoidance and the endless supply of conflicting information and research about immunization safety. Despite the controversy, many people appear to accept…

  12. Valuing vaccination

    Science.gov (United States)

    Bärnighausen, Till; Bloom, David E.; Cafiero-Fonseca, Elizabeth T.; O’Brien, Jennifer Carroll

    2014-01-01

    Vaccination has led to remarkable health gains over the last century. However, large coverage gaps remain, which will require significant financial resources and political will to address. In recent years, a compelling line of inquiry has established the economic benefits of health, at both the individual and aggregate levels. Most existing economic evaluations of particular health interventions fail to account for this new research, leading to potentially sizable undervaluation of those interventions. In line with this new research, we set forth a framework for conceptualizing the full benefits of vaccination, including avoided medical care costs, outcome-related productivity gains, behavior-related productivity gains, community health externalities, community economic externalities, and the value of risk reduction and pure health gains. We also review literature highlighting the magnitude of these sources of benefit for different vaccinations. Finally, we outline the steps that need to be taken to implement a broad-approach economic evaluation and discuss the implications of this work for research, policy, and resource allocation for vaccine development and delivery. PMID:25136129

  13. Pertussis vaccination during pregnancy in Vietnam: Results of a randomized controlled trial Pertussis vaccination during pregnancy.

    Science.gov (United States)

    Hoang, Ha Thi Thu; Leuridan, Elke; Maertens, Kirsten; Nguyen, Trung Dac; Hens, Niel; Vu, Ngoc Ha; Caboré, Raissa Nadège; Duong, Hong Thi; Huygen, Kris; Van Damme, Pierre; Dang, Anh Duc

    2016-01-02

    A pertussis vaccination during pregnancy has recently been adopted in several countries to indirectly protect young infants. This study assessed the effect of adding a pertussis component to the tetanus vaccination, in the pregnancy immunization program in Vietnam. A randomized controlled trial was performed. Pregnant women received either a Tdap (tetanus, diphtheria acellular pertussis) vaccine or a tetanus only vaccine between 19 and 35 weeks' gestational age. Immunoglobulin G (IgG) against tetanus (TT), diphtheria (DT), pertussis toxin (PT), filamentous hemaglutinin (FHA) and pertactin (Prn) were measured using commercial ELISA tests, at baseline, 1 month after maternal vaccination, at delivery, and in infants from cord blood and before and after the primary series (EPI: month 2-3-4) of a pertussis containing vaccine. Significantly higher geometric mean concentrations (GMC) were observed for all 3 measured pertussis antigens in the offspring of the Tdap group, up to 2 months of age. One month after completion of the primary infant vaccination schedule, anti-Prn GMC, but not anti-PT and anti-FHA GMCs, was significantly (p=0.006) higher in the control group. Maternal antibodies induced by vaccination during pregnancy close the susceptibility gap for pertussis in young infants. Limited interference with the infant vaccine responses was observed. Whether this interference effect disappears with the administration of a fourth vaccine dose is further studied. Copyright © 2015 Elsevier Ltd. All rights reserved.

  14. Historical clinical and economic consequences of anemia management in patients with end-stage renal disease on dialysis using erythropoietin stimulating agents versus routine blood transfusions: a retrospective cost-effectiveness analysis.

    Science.gov (United States)

    Naci, Huseyin; de Lissovoy, Gregory; Hollenbeak, Christopher; Custer, Brian; Hofmann, Axel; McClellan, William; Gitlin, Matthew

    2012-01-01

    To determine whether Medicare's decision to cover routine administration of erythropoietin stimulating agents (ESAs) to treat anemia of end-stage renal disease (ESRD) has been a cost-effective policy relative to standard of care at the time. The authors used summary statistics from the actual cohort of ESRD patients receiving ESAs between 1995 and 2004 to create a simulated patient cohort, which was compared with a comparable simulated cohort assumed to rely solely on blood transfusions. Outcomes modeled from the Medicare perspective included estimated treatment costs, life-years gained, and quality-adjusted life-years (QALYs). Incremental cost-effectiveness ratio (ICER) was calculated relative to the hypothetical reference case of no ESA use in the transfusion cohort. Sensitivity of the results to model assumptions was tested using one-way and probabilistic sensitivity analyses. Estimated total costs incurred by the ESRD population were $155.47B for the cohort receiving ESAs and $155.22B for the cohort receiving routine blood transfusions. Estimated QALYs were 2.56M and 2.29M, respectively, for the two groups. The ICER of ESAs compared to routine blood transfusions was estimated as $873 per QALY gained. The model was sensitive to a number of parameters according to one-way and probabilistic sensitivity analyses. This model was counter-factual as the actual comparison group, whose anemia was managed via transfusion and iron supplements, rapidly disappeared following introduction of ESAs. In addition, a large number of model parameters were obtained from observational studies due to the lack of randomized trial evidence in the literature. This study indicates that Medicare's coverage of ESAs appears to have been cost effective based on commonly accepted levels of willingness-to-pay. The ESRD population achieved substantial clinical benefit at a reasonable cost to society.

  15. Ensuring the optimal safety of licensed vaccines: a perspective of the vaccine research, development, and manufacturing companies.

    Science.gov (United States)

    Kanesa-thasan, Niranjan; Shaw, Alan; Stoddard, Jeffrey J; Vernon, Thomas M

    2011-05-01

    Vaccine safety is increasingly a focus for the general public, health care providers, and vaccine manufacturers, because the efficacy of licensed vaccines is accepted as a given. Commitment to ensuring safety of all vaccines, including childhood vaccines, is addressed by the federal government, academia, and industry. Safety activities conducted by the vaccine research, development, and manufacturing companies occur at all stages of product development, from selection and formulation of candidate vaccines through postlicensure studies and surveillance of adverse-event reports. The contributions of multiple interacting functional groups are required to execute these tasks through the life cycle of a product. We describe here the safeguards used by vaccine manufacturers, including specific examples drawn from recent experience, and highlight some of the current challenges. Vaccine-risk communication becomes a critical area for partnership of vaccine companies with government, professional associations, and nonprofit advocacy groups to provide information on both benefits and risks of vaccines. The crucial role of the vaccine companies in ensuring the optimal vaccine-safety profile, often overlooked, will continue to grow with this dynamic arena.

  16. Therapeutic vaccination strategies to treat nasopharyngeal carcinoma.

    Science.gov (United States)

    Taylor, Graham S; Steven, Neil M

    2016-04-01

    Epstein-Barr virus (EBV) infects most people worldwide. EBV has oncogenic potential and is strongly associated with several lymphomas and carcinomas, including nasopharyngeal carcinoma (NPC), that together total 200,000 cases of cancer each year. All EBV-associated cancers express viral proteins that allow highly selective immunotherapeutic targeting of the malignant cells. A number of therapeutic EBV vaccines have been tested in clinical trials with evidence of immune boosting and clinical responses in NPC patients. Therapeutic vaccination could be used after adoptive T-cell transfer to increase and sustain the number of infused T-cells or combined with immunotherapies acting at different stages of the cancer immunity cycle to increase efficacy. The therapeutic EBV vaccines tested to date have been well tolerated with minimal off-target toxicity. A safe therapeutic vaccine that was also able to be mass produced could, in principle, be used to vaccinate large numbers of patients after first line therapy to reduce recurrence.

  17. Trading stages

    DEFF Research Database (Denmark)

    Steiner, Uli; Tuljapurkar, Shripad; Coulson, Tim

    2012-01-01

    because they are hard to use and interpret, and tools for age and stage structured populations are missing. We present easily interpretable expressions for the sensitivities and elasticities of life expectancy to vital rates in age-stage models, and illustrate their application with two biological......Interest in stage-and age structured models has recently increased because they can describe quantitative traits such as size that are left out of age-only demography. Available methods for the analysis of effects of vital rates on lifespan in stage-structured models have not been widely applied...... examples. Much of our approach relies on trading of time and mortality risk in one stage for time and risk in others. Our approach contributes to the new framework of the study of age- and stage-structured biodemography....

  18. Limited variation in vaccine candidate Plasmodium falciparum Merozoite Surface Protein-6 over multiple transmission seasons

    Directory of Open Access Journals (Sweden)

    Branch OraLee H

    2010-05-01

    Full Text Available Abstract Background Plasmodium falciparum Merozoite Surface Protein-6 (PfMSP6 is a component of the complex proteinacious coat that surrounds P. falciparum merozoites. This location, and the presence of anti-PfMSP6 antibodies in P. falciparum-exposed individuals, makes PfMSP6 a potential blood stage vaccine target. However, genetic diversity has proven to be a major hurdle for vaccines targeting other blood stage P. falciparum antigens, and few endemic field studies assessing PfMSP6 gene diversity have been conducted. This study follows PfMSP6 diversity in the Peruvian Amazon from 2003 to 2006 and is the first longitudinal assessment of PfMSP6 sequence dynamics. Methods Parasite DNA was extracted from 506 distinct P. falciparum infections spanning the transmission seasons from 2003 to 2006 as part of the Malaria Immunology and Genetics in the Amazon (MIGIA cohort study near Iquitos, Peru. PfMSP6 was amplified from each sample using a nested PCR protocol, genotyped for allele class by agarose gel electrophoresis, and sequenced to detect diversity. Allele frequencies were analysed using JMP v.8.0.1.0 and correlated with clinical and epidemiological data collected as part of the MIGIA project. Results Both PfMSP6 allele classes, K1-like and 3D7-like, were detected at the study site, confirming that both are globally distributed. Allele frequencies varied significantly between transmission seasons, with 3D7-class alleles dominating and K1-class alleles nearly disappearing in 2005 and 2006. There was a significant association between allele class and village location (p-value = 0.0008, but no statistically significant association between allele class and age, sex, or symptom status. No intra-allele class sequence diversity was detected. Conclusions Both PfMSP6 allele classes are globally distributed, and this study shows that allele frequencies can fluctuate significantly between communities separated by only a few kilometres, and over time in the

  19. Levamisole as an adjuvant to hepatitis B vaccination in patients with chronic kidney disease

    Directory of Open Access Journals (Sweden)

    Mohammad-Hossein Somi

    2015-06-01

    Full Text Available Introduction: High risk of blood-borne infections is one of the problems of patients with chronic kidney disease (CKD, above which, there is hepatitis B. One of the ways to prevent this disease is vaccination against hepatitis B besides observing standard precautions. Lack of response to vaccine in uremic patients has been reported up to 33.0%. The aim of this study was to investigate the effect of levamisole as an adjuvant in improving vaccination response in patients suffering from CKD. Methods: In this cohort study, 30 patients suffering from the chronic renal disease who had undergone levamisole plus hepatitis B vaccine were included in the study as exposed group (Group A. Then 30 equivalent patients who had just underwent hepatitis B vaccination were in the study as a unexposed group (Group B. Antibody titer against hepatitis B virus (HBV was compared between two groups monthly, then data was analyzed. Results: Mean age of all investigated patients was 58.1 ± 14.9 years old, and it ranged from 26 to 82. 23 patients (38.3% were female, and 37 patients (61.7% were male. None of the patients in both groups had a history of previous hepatitis B vaccination. Mean antibody titer was higher in group A than that of the group B after the first and second stages of hepatitis B vaccination. However, the difference between two groups was not statistically significant (P = 0.14 and P = 0.46 respectively. Also, the mean antibody titer after the third stage was 98.8 ± 61 u/l in group A and 86.2 ± 49 u/l in group B where the difference between two groups was not statistically significant (P = 0.38. Side effects resulted from levamisole was not observed in any of patients in group A. Conclusion: According to the results it is possible to express that levamisole pill could be used as a proper adjuvant in improving the response of hepatitis B vaccination in patients suffering from CKD. However, further studies in this field are recommended according to the

  20. Blood Types

    Science.gov (United States)

    ... Drive Home Types of Blood Donations Blood Types Blood Types Not all blood is alike. There are eight ... African descent. Learn More About Blood and Diversity Blood Types and Transfusion There are very specific ways in ...

  1. Human Papillomavirus (HPV) Vaccine

    Science.gov (United States)

    Why get vaccinated?HPV vaccine prevents infection with human papillomavirus (HPV) types that are associated with cause ... at http://www.cdc.gov/hpv. HPV Vaccine (Human Papillomavirus) Information Statement. U.S. Department of Health and ...

  2. Vaccines and Pregnancy

    Science.gov (United States)

    ... vaccination. Because it is very unlikely that a live vaccine will cause disease, being in the same household with a healthy child who has received a live vaccine is also not likely to increase the ...

  3. Vaccination in Fish

    DEFF Research Database (Denmark)

    Chettri, Jiwan Kumar

    vaccines have reduced the need for usage of antibiotics with more than 99 % since the 1980s. Fish can be vaccinated by three different administration routes: injection, immersion and oral vaccination. Injection vaccination (intraperitoneal injection of vaccine) is the most time consuming and labor...... intensive method, which however, provides the best protection of the fish. Immersion vaccination is used for immunization of a high number of small fish is cost-efficient and fast (30 sec immersion into vaccine). Oral vaccination (vaccine in feed) is the least efficient. As in higher vertebrates fish...... respond to vaccination by increasing the specific antibody titer and by activating the cellular responses. My talk will cover vaccination methods in fish, immune responses and some adverse effect of oil-adjuvanted vaccines in fish with reference to our work in rainbow trout, Oncorhynchus mykiss....

  4. Vaccines and Thimerosal

    Science.gov (United States)

    ... this? Submit What's this? Submit Button Thimerosal in Vaccines Recommend on Facebook Tweet Share Compartir Thimerosal is ... harm. Thimerosal prevents the growth of bacteria in vaccines. Thimerosal is added to vials of vaccine that ...

  5. Vaccines Stop Illness

    Science.gov (United States)

    Skip Navigation Bar Home Current Issue Past Issues Vaccines Stop Illness Past Issues / Spring 2008 Table of ... meningitis won't infect, cripple, or kill children. Vaccine Safety In light of recent questions about vaccine ...

  6. Childhood Vaccine Schedule

    Science.gov (United States)

    ... Navigation Bar Home Current Issue Past Issues Childhood Vaccine Schedule Past Issues / Spring 2008 Table of Contents ... please turn Javascript on. When to Vaccinate What Vaccine Why Birth (or any age if not previously ...

  7. Vaccines Stop Illness

    Science.gov (United States)

    ... page please turn JavaScript on. Feature: Diseases and Vaccinations Vaccines Stop Illness Past Issues / Spring 2015 Table ... if we take away the protection given by vaccination, more and more people will be infected and ...

  8. Pertussis (Whooping Cough) Vaccination

    Science.gov (United States)

    ... Tetanus-diphtheria-acellular Pertussis vaccine Whooping Cough (Pertussis) Vaccination Pronounced (per-TUS-iss) Recommend on Facebook Tweet ... and adults receive Tdap. CDC recommends whooping cough vaccination for all babies and children, preteens and teens, ...

  9. Vaccine Adverse Events

    Science.gov (United States)

    ... for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More sharing ... in the primary immunization series in infants Report Adverse Event Report a Vaccine Adverse Event Contact FDA ( ...

  10. Implementation research: reactive mass vaccination with single-dose oral cholera vaccine, Zambia.

    Science.gov (United States)

    Poncin, Marc; Zulu, Gideon; Voute, Caroline; Ferreras, Eva; Muleya, Clara Mbwili; Malama, Kennedy; Pezzoli, Lorenzo; Mufunda, Jacob; Robert, Hugues; Uzzeni, Florent; Luquero, Francisco J; Chizema, Elizabeth; Ciglenecki, Iza

    2018-02-01

    To describe the implementation and feasibility of an innovative mass vaccination strategy - based on single-dose oral cholera vaccine - to curb a cholera epidemic in a large urban setting. In April 2016, in the early stages of a cholera outbreak in Lusaka, Zambia, the health ministry collaborated with Médecins Sans Frontières and the World Health Organization in organizing a mass vaccination campaign, based on single-dose oral cholera vaccine. Over a period of 17 days, partners mobilized 1700 health ministry staff and community volunteers for community sensitization, social mobilization and vaccination activities in 10 townships. On each day, doses of vaccine were delivered to vaccination sites and administrative coverage was estimated. Overall, vaccination teams administered 424 100 doses of vaccine to an estimated target population of 578 043, resulting in an estimated administrative coverage of 73.4%. After the campaign, few cholera cases were reported and there was no evidence of the disease spreading within the vaccinated areas. The total cost of the campaign - 2.31 United States dollars (US$) per dose - included the relatively low cost of local delivery - US$ 0.41 per dose. We found that an early and large-scale targeted reactive campaign using a single-dose oral vaccine, organized in response to a cholera epidemic within a large city, to be feasible and appeared effective. While cholera vaccines remain in short supply, the maximization of the number of vaccines in response to a cholera epidemic, by the use of just one dose per member of an at-risk community, should be considered.

  11. Influenza and Pneumonia Vaccination Rates and Factors Affecting Vaccination among Patients with Chronic Obstructive Pulmonary Disease.

    Science.gov (United States)

    Aka Aktürk, Ülkü; Görek Dilektaşlı, Aslı; Şengül, Aysun; Musaffa Salepçi, Banu; Oktay, Nuray; Düger, Mustafa; Arık Taşyıkan, Hale; Durmuş Koçak, Nagihan

    2017-05-05

    Influenza and pneumococcal vaccinations are recommended in chronic obstructive pulmonary disease patients to decrease associated risks at all stages. Although the prevalence of chronic obstructive pulmonary disease is high in our country, as previously reported, vaccination rates are low. To assess the vaccination rates of chronic obstructive pulmonary disease patients and factors that may affect these. Multi-centre cross-sectional study. Patients admitted to the chest diseases clinics of six different centres between 1 February 2013 and 1 January 2014 with a pre-diagnosis of Chronic obstructive pulmonary disease according to the Global initiative for chronic obstructive lung disease criteria, who were in a stable condition were included in the study. The survey, which included demographic characteristics, socio-economic status, severity of disease and vaccination information, was first tested on a small patient population before the study. The survey was completed by the investigators after obtaining written informed consent. The average age of the 296 included patients was 66.3±9.3 years and 91.9% were male. Of these, 36.5% had the influenza vaccination and 14.1% had the pneumococcal vaccination. The most common reason for not being vaccinated was 'no recommendation by doctors': 57.2% in the case of influenza vaccinations, and 46.8% in the case of pneumococcal vaccinations. Both vaccination rates were significantly higher in those patients with comorbidities (influenza vaccination pvaccination p=0.06). There was no significant correlation with age, gender, smoking and severity of disease (p>0.05). Vaccination rates were significantly higher in those with a white-collar occupation and higher education level, and who presented to a university hospital (pvaccinations as often as the International Guidelines suggest for chronic obstructive pulmonary disease patients. Awareness of the importance of these vaccinations among both doctors and patients needs to be

  12. Impact of BRICS’ investment in vaccine development on the global vaccine market

    Science.gov (United States)

    Milstien, Julie; Schmitt, Sarah

    2014-01-01

    Abstract Brazil, the Russian Federation, India, China and South Africa – the countries known as BRICS – have made considerable progress in vaccine production, regulation and development over the past 20 years. In 1993, all five countries were producing vaccines but the processes used were outdated and non-standardized, there was little relevant research and there was negligible international recognition of the products. By 2014, all five countries had strong initiatives for the development of vaccine technology and had greatly improved their national regulatory capacity. South Africa was then the only BRICS country that was not completely producing vaccines. South Africa is now in the process of re-establishing its own vaccine production and passing beyond the stage of simply importing, formulating and filling vaccine bulks. Changes in the public sector’s price per dose of selected vaccines, the global market share represented by products from specific manufacturers, and the attractiveness, for multinational companies, of partnership and investment opportunities in BRICS companies have all been analysed. The results indicate that the BRICS countries have had a major impact on vaccine price and availability, with much of that impact attributable to the output of Indian vaccine manufacturers. China is expected to have a greater impact soon, given the anticipated development of Chinese vaccine manufacturers in the near future. BRICS’ accomplishments in the field of vaccine development are expected to reshape the global vaccine market and accelerate access to vaccines in the developing world. The challenge is to turn these expectations into strategic actions and practical outcomes. PMID:24940018

  13. Relationship Between Tetanus Antitoxin Titration Level and Vaccination History

    OpenAIRE

    Işıkgöz Taşbakan, Meltem; Durusoy, Raika; Tosun, Selma

    2017-01-01

    Objectives: We aimed to determine tetanus antitoxin levels and to evaluate their relationship with history of vaccination among patients applying to the outpatient clinics of a University hospital. Methods: A questionnaire including socio-demographic characteristics and tetanus vaccination status was applied and blood samples taken from 218 subjects between 1 and 30 June 2015. Participants were classified into five groups according to their vaccination timing. Results: The mean age of...

  14. Vaccine refrigeration

    Science.gov (United States)

    McColloster, Patrick J; Martin-de-Nicolas, Andres

    2014-01-01

    This commentary reviews recent changes in Centers for Disease Control (CDC) vaccine storage guidelines that were developed in response to an investigative report by the Office of the Inspector General. The use of temperature data loggers with probes residing in glycol vials is advised along with storing vaccines in pharmaceutical refrigerators. These refrigerators provide good thermal distribution but can warm to 8 °C in less than one hour after the power is discontinued. Consequently, electric grid instability influences appropriate refrigerator selection and the need for power back-up. System Average Interruption Duration Index (SAIDI) values quantify this instability and can be used to formulate region-specific guidelines. A novel aftermarket refrigerator regulator with a battery back-up power supply and microprocessor control system is also described. PMID:24442209

  15. Engineered human vaccines

    Energy Technology Data Exchange (ETDEWEB)

    Sandhu, J.S. (Mount Sinai Hospital, Toronto, Ontario (Canada). Div. of Immunology and Neurobiology)

    1994-01-01

    The limitations of human vaccines in use at present and the design requirements for a new generation of human vaccines are discussed. The progress in engineering of human vaccines for bacteria, viruses, parasites, and cancer is reviewed, and the data from human studies with the engineered vaccines are discussed, especially for cancer and AIDS vaccines. The final section of the review deals with the possible future developments in the field of engineered human vaccines and the requirement for effective new human adjuvants.

  16. Effective Vaccination Policies

    Science.gov (United States)

    2010-03-31

    effective” vaccine can stop the virus spread by causing herd immunity and the disease will die out. Vaccines that have this capability are in the vaccine ...Effective Vaccination Policies L. Shawa, W. Spears∗,b, L. Billingsc, P. Maximd aDepartment of Computer Science, University of Wyoming, Laramie, WY...this study is to develop tools that determine the optimal distribution of a vaccine supply in the model. Using plausible benchmark vaccine allocation

  17. Human Vaccines & Immunotherapeutics

    OpenAIRE

    Riedmann, Eva M

    2014-01-01

    Measles vaccination: Targeted and non-targeted benefits CDC reports: 2-dose regimen of chickenpox vaccine is a success Positive preliminary results from the CAPiTA study Seasonal flu vaccine associate with reduced stroke risk HPV vaccine shown to halve cervical abnormalities Global prize for mobile mast vaccine storage project Developmental pathway of potent HIV-neutralizing antibodies Burkholderia vaccine: US Dep of Defense collaborates with Bavarian Nordic

  18. Primary and booster vaccination with DTPw-HB/Hib pentavalent vaccine in Costa Rican children who had received a birth dose of hepatitis B vaccine

    Directory of Open Access Journals (Sweden)

    Faingezicht Idis

    2002-01-01

    Full Text Available Objective. The DTPw-HB/Hib pentavalent combination vaccine has been developed following recommendations of the World Health Organization for the introduction of hepatitis B (HB and Haemophilus influenzae type b (Hib vaccines into routine childhood vaccination programs. The objectives of this study were to: 1 analyze the immunogenicity and the reactogenicity of the DTPw-HB/Hib pentavalent combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination in a group of children who had received a dose of HB vaccine at birth and 2 in the second year of life to assess the antibody persistence as well as the response to a DTPw-HB/Hib or DTPw/Hib booster. Methods. In the first part of the study (primary-vaccination stage, conducted in 1998-1999, we analyzed the immunogenicity and reactogenicity of the DTPw-HB/Hib combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination at 2, 4, and 6 months of age in 207 Costa Rican children who had received a dose of HB vaccine at birth. Later, in the booster-vaccination stage of the study, in 1999-2000, in a subset of the children (69 toddlers, now 15-18 months old, antibody persistence was measured, and response to a DTPw-HB/Hib or DTPw/Hib booster was also assessed. Results. In both primary-vaccination groups, at least 97.5% of the infants reached protective levels of antibodies (seropositivity against the antigens employed in the vaccines. The DTPw-HB/Hib pentavalent combination vaccine did not result in more local reactions than did the DTPw-HB vaccine alone, and, in terms of general reactions, there was no clinically significant difference between the combination or separate injections, and with the pentavalent vaccine having the benefit of needing one less injection. Nine months after the third dose of the primary-vaccination course, antibody persistence was similar in both groups, with over 93% of children still having

  19. Primary and booster vaccination with DTPw-HB/Hib pentavalent vaccine in Costa Rican children who had received a birth dose of hepatitis B vaccine

    Directory of Open Access Journals (Sweden)

    Idis Faingezicht

    2002-10-01

    Full Text Available Objective. The DTPw-HB/Hib pentavalent combination vaccine has been developed following recommendations of the World Health Organization for the introduction of hepatitis B (HB and Haemophilus influenzae type b (Hib vaccines into routine childhood vaccination programs. The objectives of this study were to: 1 analyze the immunogenicity and the reactogenicity of the DTPw-HB/Hib pentavalent combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination in a group of children who had received a dose of HB vaccine at birth and 2 in the second year of life to assess the antibody persistence as well as the response to a DTPw-HB/Hib or DTPw/Hib booster. Methods. In the first part of the study (primary-vaccination stage, conducted in 1998-1999, we analyzed the immunogenicity and reactogenicity of the DTPw-HB/Hib combination vaccine in comparison to separate injections of DTPw-HB and Hib vaccines as primary vaccination at 2, 4, and 6 months of age in 207 Costa Rican children who had received a dose of HB vaccine at birth. Later, in the booster-vaccination stage of the study, in 1999-2000, in a subset of the children (69 toddlers, now 15-18 months old, antibody persistence was measured, and response to a DTPw-HB/Hib or DTPw/Hib booster was also assessed. Results. In both primary-vaccination groups, at least 97.5% of the infants reached protective levels of antibodies (seropositivity against the antigens employed in the vaccines. The DTPw-HB/Hib pentavalent combination vaccine did not result in more local reactions than did the DTPw-HB vaccine alone, and, in terms of general reactions, there was no clinically significant difference between the combination or separate injections, and with the pentavalent vaccine having the benefit of needing one less injection. Nine months after the third dose of the primary-vaccination course, antibody persistence was similar in both groups, with over 93% of children still having

  20. Schistosomiasis vaccines

    OpenAIRE

    Siddiqui, Afzal A.; Siddiqui, Bilal A.; Ganley-Leal, Lisa

    2011-01-01

    Schistosomiasis is a major neglected tropical disease of public health importance to a billion people. An estimated 200 million people are currently infected; an additional 779 million individuals are at risk to acquire the infection in 74 countries. Despite many years of implementation of mass anti-parasitic drug therapy programs and other control measures, this disease has not been contained and continues to spread to new geographic areas.  The discovery of a protective vaccine still remain...

  1. Psychosocial correlates of HPV vaccine acceptability in college males: A cross-sectional exploratory study.

    Science.gov (United States)

    Tatar, Ovidiu; Perez, Samara; Naz, Anila; Shapiro, Gilla K; Rosberger, Zeev

    2017-12-01

    Most college males are not immunized against the human papillomavirus (HPV) and are at high risk of HPV infection. Most research of correlates of HPV vaccine acceptability in college males has assessed vaccine acceptability as a binary outcome, e.g., vaccinated or not vaccinated, without considering that some students may not even be aware that the HPV vaccine can be given to males. Our objective was to evaluate the psychosocial correlates of HPV acceptability in college males, based on multiple stages of HPV decision-making. We used an online questionnaire to collect data from college men aged 18-26 enrolled at three Canadian universities between September 2013 and April 2014. Vaccine acceptability assessment was informed by the six-stage decision-making Precaution Adoption Process Model (PAPM). We sought information on socio-demographics, health behaviors, HPV vaccine benefits and barriers, worry, susceptibility, severity related to HPV infection and social norms. HPV and HPV vaccine knowledge was measured with validated scales. Psychosocial correlates of HPV vaccine acceptability were assessed with bivariate and multivariate multinomial logistic regression. Actual and perceived HPV and HPV vaccine knowledge scores were calculated. The final sample size was 428. Most male college students were unaware that the HPV vaccine could be given to males, unengaged or undecided about getting the HPV vaccine. Significant correlates of higher HPV vaccine acceptability were: increased HPV knowledge, having discussed the HPV vaccine with a healthcare provider, and social norms. Being in an exclusive sexual relationship was significantly associated with lower HPV vaccine acceptability. Students' actual HPV and HPV vaccine knowledge was low and positively correlated to their perception about their HPV knowledge. We provided a fine-tuned analysis of psychosocial correlates of HPV vaccine acceptability in college males who are in the early stages of HPV vaccine decision

  2. Impact of pre-existing MSP142-allele specific immunity on potency of an erythrocytic Plasmodium falciparum vaccine

    Directory of Open Access Journals (Sweden)

    Bergmann-Leitner Elke S

    2012-09-01

    Full Text Available Abstract Background MSP1 is the major surface protein on merozoites and a prime candidate for a blood stage malaria vaccine. Preclinical and seroepidemiological studies have implicated antibodies to MSP1 in protection against blood stage parasitaemia and/or reduced parasite densities, respectively. Malaria endemic areas have multiple strains of Plasmodium falciparum circulating at any given time, giving rise to complex immune responses, an issue which is generally not addressed in clinical trials conducted in non-endemic areas. A lack of understanding of the effect of pre-existing immunity to heterologous parasite strains may significantly contribute to vaccine failure in the field. The purpose of this study was to model the effect of pre-existing immunity to MSP142 on the immunogenicity of blood-stage malaria vaccines based on alternative MSP1 alleles. Methods Inbred and outbred mice were immunized with various recombinant P. falciparum MSP142 proteins that represent the two major alleles of MSP142, MAD20 (3D7 and Wellcome (K1, FVO. Humoral immune responses were analysed by ELISA and LuminexTM, and functional activity of induced MSP142-specific antibodies was assessed by growth inhibition assays. T-cell responses were characterized using ex vivo ELISpot assays. Results Analysis of the immune responses induced by various immunization regimens demonstrated a strong allele-specific response at the T cell level in both inbred and outbred mice. The success of heterologous regimens depended on the degree of homology of the N-terminal p33 portion of the MSP142, likely due to the fact that most T cell epitopes reside in this part of the molecule. Analysis of humoral immune responses revealed a marked cross-reactivity between the alleles. Functional analyses showed that some of the heterologous regimens induced antibodies with improved growth inhibitory activities. Conclusion The development of a more broadly efficacious MSP1 based vaccine may be

  3. Dengue vaccine development: strategies and challenges.

    Science.gov (United States)

    Ramakrishnan, Lakshmy; Pillai, Madhavan Radhakrishna; Nair, Radhakrishnan R

    2015-03-01

    Infection with dengue virus may result in dengue fever or a more severe outcome, such as dengue hemorrhagic syndrome/shock. Dengue virus infection poses a threat to endemic regions for four reasons: the presence of four serotypes, each with the ability to cause a similar disease outcome, including fatality; difficulties related to vector control; the lack of specific treatment; and the nonavailability of a suitable vaccine. Vaccine development is considered challenging due to the severity of the disease observed in individuals who have acquired dengue-specific immunity, either passively or actively. Therefore, the presence of vaccine-induced immunity against a particular serotype may prime an individual to severe disease on exposure to dengue virus. Vaccine development strategies include live attenuated vaccines, chimeric, DNA-based, subunit, and inactivated vaccines. Each of the candidates is in various stages of preclinical and clinical development. Issues pertaining to selection pressures, viral interaction, and safety still need to be evaluated in order to induce a complete protective immune response against all four serotypes. This review highlights the various strategies that have been employed in vaccine development, and identifies the obstacles to producing a safe and effective vaccine.

  4. Therapeutic Vaccination for HPV Induced Cervical Cancers

    Directory of Open Access Journals (Sweden)

    Joeli A. Brinkman

    2007-01-01

    Full Text Available Cervical Cancer is the second leading cause of cancer–related deaths in women worldwide and is associated with Human Papillomavirus (HPV infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence.

  5. Therapeutic vaccination for HPV induced cervical cancers.

    Science.gov (United States)

    Brinkman, Joeli A; Hughes, Sarah H; Stone, Pamela; Caffrey, Angela S; Muderspach, Laila I; Roman, Lynda D; Weber, Jeffrey S; Kast, W Martin

    2007-01-01

    Cervical Cancer is the second leading cause of cancer-related deaths in women worldwide and is associated with Human Papillomavirus (HPV) infection, creating a unique opportunity to treat cervical cancer through anti-viral vaccination. Although a prophylactic vaccine may be available within a year, millions of women, already infected, will continue to suffer from HPV-related disease, emphasizing the need to develop therapeutic vaccination strategies. A majority of clinical trials examining therapeutic vaccination have shown limited efficacy due to examining patients with more advanced-stage cancer who tend to have decreased immune function. Current trends in clinical trials with therapeutic agents examine patients with pre-invasive lesions in order to prevent invasive cervical cancer. However, longer follow-up is necessary to correlate immune responses to lesion regression. Meanwhile, preclinical studies in this field include further exploration of peptide or protein vaccination, and the delivery of HPV antigens in DNA-based vaccines or in viral vectors. As long as pre-clinical studies continue to advance, the prospect of therapeutic vaccination to treat existing lesions seem good in the near future. Positive consequences of therapeutic vaccination would include less disfiguring treatment options and fewer instances of recurrent or progressive lesions leading to a reduction in cervical cancer incidence.

  6. Cytomegalovirus Vaccines: Current Status and Future Prospects

    Science.gov (United States)

    Anderholm, KM; Bierle, CJ; Schleiss, MR

    2017-01-01

    Congenital human cytomegalovirus (HCMV) infection can result in in severe and permanent neurological injury in newborns, and vaccine development is accordingly a major public health priority. HCMV can also cause disease in solid organ (SOT) and hematopoietic stem cell transplant (HSCT) recipients, and a vaccine would be valuable in prevention of viremia and end-organ disease in these populations. Currently there is no licensed HCMV vaccine, but progress toward this goal has been made in recent clinical trials. A recombinant HCMV glycoprotein B (gB) vaccine has been shown to have some efficacy in prevention of infection in young women and adolescents, and provided benefit to HCMV-seronegative SOT recipients. Similarly, DNA vaccines based on gB and the immunodominant T-cell target, pp65 (ppUL83), have been shown to reduce viremia in HSCT patients. This review provides an overview of HCMV vaccine candidates in various stages of development, as well as an update on the current status of ongoing clinical trials. Protective correlates of vaccine-induced immunity may be different for pregnant woman and transplant patients. As more knowledge emerges about correlates of protection, the ultimate licensure of HCMV vaccines may reflect the uniqueness of the target populations being immunized. PMID:27882457

  7. Nonclinical Development of BCG Replacement Vaccine Candidates

    Directory of Open Access Journals (Sweden)

    Bernd Eisele

    2013-04-01

    Full Text Available The failure of current Mycobacterium bovis bacille Calmette–Guérin (BCG vaccines, given to neonates to protect against adult tuberculosis and the risk of using these live vaccines in HIV-infected infants, has emphasized the need for generating new, more efficacious and safer replacement vaccines. With the availability of genetic techniques for constructing recombinant BCG (rBCG strains containing well-defined gene deletions or insertions, new vaccine candidates are under evaluation at both the preclinical and clinical stages of development. Since most BCG vaccines in use today were evaluated in clinical trials decades ago and are produced by outdated processes, the development of new BCG vaccines offers a number of advantages that include a modern well-defined manufacturing process along with state-of-the-art evaluation of safety and efficacy in target populations. We provide a description of the preclinical development of two novel rBCGs, VPM1002 that was constructed by adding a modified hly gene coding for the protein listeriolysin O (LLO from Listeria monocytogenes and AERAS-422, which carries a modified pfoA gene coding for the protein perfringolysin O (PFO from Clostridium perfringens, and three genes from Mycobacterium tuberculosis. Novel approaches like these should be helpful in generating stable and effective rBCG vaccine candidates that can be better characterized than traditional BCG vaccines.

  8. Immunology Update: New Vaccines.

    Science.gov (United States)

    Starr, S Paul

    2016-11-01

    A new 9-valent human papillomavirus (HPV) vaccine is effective against more cancer-causing HPV types than previous vaccines. HPV vaccine series started with previous vaccines can be completed with the 9-valent vaccine. Two new influenza vaccines are available for adults 65 years and older: a high-dose vaccine and an enhanced adjuvant vaccine. These elicit stronger antibody responses than standard-dose vaccines. Current guidelines specify no preference for the new versus standard-dose vaccines. Two new group B meningococcal vaccines are intended for use during outbreaks and for patients with asplenia, complement deficiencies, frequent occupational meningococcus exposure, or for patients who desire protection from type B meningococcus. These are not substitutes for the quadrivalent vaccine already in use. For pneumococcus, new recommendations state that 13-valent pneumococcal conjugate vaccine (PCV13) should be administered to patients 65 years and older, followed at least 1 year later by the polyvalent pneumococcal polysaccharide vaccine (PPSV23). For patients ages 19 to 64 years with immunocompromise and not previously vaccinated against pneumococcus, administration of these two vaccines should be separated by at least 8 weeks. Rotavirus vaccine is standard for infants at age 2 months. Also, there is a new cholera vaccine approved for use in the United States. Written permission from the American Academy of Family Physicians is required for reproduction of this material in whole or in part in any form or medium.

  9. Hepatitis B Vaccine

    Science.gov (United States)

    Engerix-B® ... as a combination product containing Haemophilus influenzae type b, Hepatitis B Vaccine) ... product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis, Hepatitis B, Polio Vaccine)

  10. Identification of an AP2-family protein that is critical for malaria liver stage development.

    Directory of Open Access Journals (Sweden)

    Shiroh Iwanaga

    Full Text Available Liver-stage malaria parasites are a promising target for drugs and vaccines against malaria infection. However, little is currently known about gene regulation in this stage. In this study, we used the rodent malaria parasite Plasmodium berghei and showed that an AP2-family transcription factor, designated AP2-L, plays a critical role in the liver-stage development of the parasite. AP2-L-depleted parasites proliferated normally in blood and in mosquitoes. However, the ability of these parasites to infect the liver was approximately 10,000 times lower than that of wild-type parasites. In vitro assays showed that the sporozoites of these parasites invaded hepatocytes normally but that their development stopped in the middle of the liver schizont stage. Expression profiling using transgenic P. berghei showed that fluorescent protein-tagged AP2-L increased rapidly during the liver schizont stage but suddenly disappeared with the formation of the mature liver schizont. DNA microarray analysis showed that the expression of several genes, including those of parasitophorous vacuole membrane proteins, was significantly decreased in the early liver stage of AP2-L-depleted parasites. Investigation of the targets of this transcription factor should greatly promote the exploration of liver-stage antigens and the elucidation of the mechanisms of hepatocyte infection by malaria parasites.

  11. Long-term Immunogenicity of Hepatitis B Vaccination in children | El ...

    African Journals Online (AJOL)

    Their data are included. Group `A` included 53 males and 47 females, around 6 years old, all children were vaccinated 5 years ago. Group `B` included 27 males and 73 females, around 11 years old. All children vaccinated 10years ago. HBsAb titre was tested in their blood, booster dose of the vaccine was given to children ...

  12. Field Evaluation of Immunogenicity of Five Commercial Vaccines ...

    African Journals Online (AJOL)

    This study was conducted to evaluate immunogenicity of five commonly used vaccines for prevention of Newcastle disease (ND) in Ibadan, the capital city of Oyo State Nigeria. Two hundred and twenty (220) blood samples were collected from apparently healthy vaccinated chickenin 8 poultry farms in suburbs of the city.

  13. Effects of the DASH-JUMP dietary intervention in Japanese participants with high-normal blood pressure and stage 1 hypertension: an open-label single-arm trial.

    Science.gov (United States)

    Kawamura, Atsuko; Kajiya, Katsuko; Kishi, Hiroko; Inagaki, Junko; Mitarai, Makoto; Oda, Hiroshi; Umemoto, Seiji; Kobayashi, Sei

    2016-11-01

    The Dietary Approaches to Stop Hypertension (DASH) diet is recommended by the American Heart Association to lower blood pressure (BP); however, its effects in Japanese participants have not been rigorously studied. We assessed the effects of the DASH-Japan Ube Modified diet Program (DASH-JUMP), a modified DASH diet, on cardiometabolic and inflammatory biomarkers in Japanese participants with untreated high-normal BP or stage 1 hypertension. Fifty-eight participants (30 men and 28 women; mean age 54.1±8.1 years) with untreated high-normal BP or stage 1 hypertension followed the DASH-JUMP (salt 8.0 g per day) for 2 months. After the intervention period, they resumed their usual diets for 4 months. The DASH-JUMP significantly decreased the participants' body mass index values (24.6±3.5 kg m -2 at baseline23.2±3.3 kg m -2 at 2 months, P=0.000), BP (153±14/91±11 mm Hg at baseline130±16/80±9 mm Hg at 2 months, P=0.000 and 139±16/85±10 mm Hg at 6 months, P=0.000), fasting serum glucose level (100±26 mg dl - 1 94±15 mg dl - 1 at 2 months, P=0.003) and fasting insulin level (6.9±5.9 μIU ml -1 4.4±2.7 μIU ml -1 at 2 months, P=0.000). The mean compliance of the participants for the DASH-JUMP diet was 88.5%. The DASH-JUMP diet reduced cardiovascular risk factors and may be an effective nutritional strategy for preventing cardiovascular events.

  14. [Vaccination in the elderly].

    Science.gov (United States)

    Kwetkat, A; Pletz, M W

    2013-10-01

    The aging immune system, so-called immunosenescence, is well documented as the cause of increased infection rates and severe, often complicated course of infections in the elderly with increased morbidity and mortality rates. Furthermore, it can lead to decreased efficacy of vaccination. The administration of more immunogenic vaccines can be beneficial in the elderly. Implementing vaccination recommendations for the elderly by STIKO can reduce burden of infectious diseases by prevention of infection or reduction of severity of infection. The following vaccinations are recommended by STIKO for all persons aged 60 and above: annual influenza vaccination (additionally all nursing home residents independently of age), once only pneumococcal polysaccharide vaccination, completion of tetanus and diphtheria (Td) vaccination as well as regular revaccination. All adults should be vaccinated against pertussis with Tdap vaccine once. Meanwhile, pneumococcal conjugate vaccine is allowed for administration in adults but is not recommended by STIKO yet. A lifelong course of vaccination may help to attenuate the effect of immunosenescence.

  15. Staging atmospheres

    DEFF Research Database (Denmark)

    Bille, Mikkel; Bjerregaard, Peter; Sørensen, Tim Flohr

    2015-01-01

    The article introduces the special issue on staging atmospheres by surveying the philosophical, political and anthropological literature on atmosphere, and explores the relationship between atmosphere, material culture, subjectivity and affect. Atmosphere seems to occupy one of the classic...