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Sample records for blood stage vaccine

  1. 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.

  2. 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

  3. Evidences of protection against blood-stage infection of Plasmodium falciparum by the novel protein vaccine SE36.

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    Horii, Toshihiro; Shirai, Hiroki; Jie, Li; Ishii, Ken J; Palacpac, Nirianne Q; Tougan, Takahiro; Hato, Mariko; Ohta, Nobuo; Bobogare, Albino; Arakaki, Nana; Matsumoto, Yoshitsugu; Namazue, Junko; Ishikawa, Toyokazu; Ueda, Shigeharu; Takahashi, Michiaki

    2010-09-01

    An effective malaria vaccine is a public health priority. Proteins expressed during the blood-stage of the parasite life cycle have been proposed as good vaccine candidates. No such blood-stage vaccine, however, is available against Plasmodium falciparum, the deadliest Plasmodium species. We show here that P. falciparum serine repeat antigen 5 (SERA5) is a potential vaccine immunogen. We have constructed a new recombinant molecule of SERA5, namely SE36, based on previously reported SE47' molecule by removing the serine repeats. Epidemiological study in the holo-endemic population of Solomon Islands shows highly significant correlation of sero-conversion and malaria protective immunity against this antigen. Animal experiments using non-human primates, and a human phase 1a clinical trial assessed SE36 vaccine immunogenicity. Vaccination of squirrel monkeys with SE36 protein and aluminum hydroxyl gel (SE36/AHG) conferred protection against high parasitemia and boosted serum anti-SE36 IgG after P. falciparum parasite challenge. SE36/AHG was highly immunogenic in chimpanzees, where serum anti-SE36 IgG titers last more than one year. Phase 1a clinical trial (current controlled trials, ISRCTN78679862) demonstrated the safety and immunogenicity of SE36/AHG with 30 healthy adults and 10 placebo controls. Three subcutaneous administrations of 50 and 100microg dose of SE36/AHG were well-tolerated, with no severe adverse events; and resulted in 100% sero-conversion in both dose arms. The current research results for SE36/AHG provide initial clinical validation for future trials and suggest clues/strategies for further vaccine development. PMID:20493274

  4. Vaccination with Plasmodium knowlesi AMA1 formulated in the novel adjuvant co-vaccine HT™ protects against blood-stage challenge in rhesus macaques.

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    Muzamil Mahdi Abdel Hamid

    Full Text Available Plasmodium falciparum apical membrane antigen 1 (PfAMA1 is a leading blood stage vaccine candidate. Plasmodium knowlesi AMA1 (PkAMA1 was produced and purified using similar methodology as for clinical grade PfAMA1 yielding a pure, conformational intact protein. Combined with the adjuvant CoVaccine HT™, PkAMA1 was found to be highly immunogenic in rabbits and the efficacy of the PkAMA1 was subsequently tested in a rhesus macaque blood-stage challenge model. Six rhesus monkeys were vaccinated with PkAMA1 and a control group of 6 were vaccinated with PfAMA1. A total of 50 µg AMA1 was administered intramuscularly three times at 4 week intervals. One of six rhesus monkeys vaccinated with PkAMA1 was able to control parasitaemia, upon blood stage challenge with P. knowlesi H-strain. Four out of the remaining five showed a delay in parasite onset that correlated with functional antibody titres. In the PfAMA1 vaccinated control group, five out of six animals had to be treated with antimalarials 8 days after challenge; one animal did not become patent during the challenge period. Following a rest period, animals were boosted and challenged again. Four of the six rhesus monkeys vaccinated with PkAMA1 were able to control the parasitaemia, one had a delayed onset of parasitaemia and one animal was not protected, while all control animals required treatment. To confirm that the control of parasitaemia was AMA1-related, animals were allowed to recover, boosted and re-challenged with P. knowlesi Nuri strain. All control animals had to be treated with antimalarials by day 8, while five out of six PkAMA1 vaccinated animals were able to control parasitaemia. This study shows that: i Yeast-expressed PkAMA1 can protect against blood stage challenge; ii Functional antibody levels as measured by GIA correlated inversely with the day of onset and iii GIA IC(50 values correlated with estimated in vivo growth rates.

  5. Vaccination with Plasmodium knowlesi AMA1 formulated in the novel adjuvant co-vaccine HT™ protects against blood-stage challenge in rhesus macaques.

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    Mahdi Abdel Hamid, Muzamil; Remarque, Edmond J; van Duivenvoorde, Leonie M; van der Werff, Nicole; Walraven, Vanessa; Faber, Bart W; Kocken, Clemens H M; Thomas, Alan W

    2011-01-01

    Plasmodium falciparum apical membrane antigen 1 (PfAMA1) is a leading blood stage vaccine candidate. Plasmodium knowlesi AMA1 (PkAMA1) was produced and purified using similar methodology as for clinical grade PfAMA1 yielding a pure, conformational intact protein. Combined with the adjuvant CoVaccine HT™, PkAMA1 was found to be highly immunogenic in rabbits and the efficacy of the PkAMA1 was subsequently tested in a rhesus macaque blood-stage challenge model. Six rhesus monkeys were vaccinated with PkAMA1 and a control group of 6 were vaccinated with PfAMA1. A total of 50 µg AMA1 was administered intramuscularly three times at 4 week intervals. One of six rhesus monkeys vaccinated with PkAMA1 was able to control parasitaemia, upon blood stage challenge with P. knowlesi H-strain. Four out of the remaining five showed a delay in parasite onset that correlated with functional antibody titres. In the PfAMA1 vaccinated control group, five out of six animals had to be treated with antimalarials 8 days after challenge; one animal did not become patent during the challenge period. Following a rest period, animals were boosted and challenged again. Four of the six rhesus monkeys vaccinated with PkAMA1 were able to control the parasitaemia, one had a delayed onset of parasitaemia and one animal was not protected, while all control animals required treatment. To confirm that the control of parasitaemia was AMA1-related, animals were allowed to recover, boosted and re-challenged with P. knowlesi Nuri strain. All control animals had to be treated with antimalarials by day 8, while five out of six PkAMA1 vaccinated animals were able to control parasitaemia. This study shows that: i) Yeast-expressed PkAMA1 can protect against blood stage challenge; ii) Functional antibody levels as measured by GIA correlated inversely with the day of onset and iii) GIA IC(50) values correlated with estimated in vivo growth rates. PMID:21655233

  6. 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 BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: Clinical

  7. 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

    (See the article by Greenhouse et al, on pages 19-26.) Background. RTS,S/AS01(E) is the lead candidate malaria vaccine and confers pre-erythrocytic immunity. Vaccination may therefore impact acquired immunity to blood-stage malaria parasites after natural infection. Methods. We measured, by enzyme...... 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...

  8. Combining Viral Vectored and Protein-in-adjuvant Vaccines Against the Blood-stage Malaria Antigen AMA1: Report on a Phase 1a Clinical Trial

    OpenAIRE

    Susanne H. Hodgson; Choudhary, Prateek; Elias, Sean C; Milne, Kathryn H; Thomas W Rampling; Biswas, Sumi; Ian D Poulton; Miura, Kazutoyo; Douglas, Alexander D.; Alanine, Daniel GW; Illingworth, Joseph J.; de Cassan, Simone C.; ZHU, DAMING; Nicosia, Alfredo; Long, Carole A.

    2014-01-01

    The development of effective vaccines against difficult disease targets will require the identification of new subunit vaccination strategies that can induce and maintain effective immune responses in humans. Here we report on a phase 1a clinical trial using the AMA1 antigen from the blood-stage Plasmodium falciparum malaria parasite delivered either as recombinant protein formulated with Alhydrogel adjuvant with and without CPG 7909, or using recombinant vectored vaccines—chimpanzee adenovir...

  9. Phase 1 Trial of AMA1-C1/Alhydrogel plus CPG 7909: An Asexual Blood-Stage Vaccine for Plasmodium falciparum Malaria

    OpenAIRE

    Gregory E D Mullen; Ellis, Ruth D.; Kazutoyo Miura; Elissa Malkin; Caroline Nolan; Mhorag Hay; Fay, Michael P.; Allan Saul; Daming Zhu; Kelly Rausch; Samuel Moretz; Hong Zhou; Long, Carole A.; Miller, Louis H; John Treanor

    2008-01-01

    BACKGROUND: 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. METHODS: 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 enroll...

  10. A PfRH5-Based Vaccine Is Efficacious against Heterologous Strain Blood-Stage Plasmodium falciparum Infection in Aotus Monkeys

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    Douglas, Alexander D.; Baldeviano, G. Christian; Lucas, Carmen M.; Lugo-Roman, Luis A.; Crosnier, Cécile; Bartholdson, S. Josefin; Diouf, Ababacar; Miura, Kazutoyo; Lambert, Lynn E.; Ventocilla, Julio A.; Leiva, Karina P.; Milne, Kathryn H.; Illingworth, Joseph J.; Spencer, Alexandra J.; Hjerrild, Kathryn A.; Alanine, Daniel G.W.; Turner, Alison V.; Moorhead, Jeromy T.; Edgel, Kimberly A.; Wu, Yimin; Long, Carole A.; Wright, Gavin J.; Lescano, Andrés G.; Draper, Simon J.

    2015-01-01

    Summary Antigenic diversity has posed a critical barrier to vaccine development against the pathogenic blood-stage infection of the human malaria parasite Plasmodium falciparum. To date, only strain-specific protection has been reported by trials of such vaccines in nonhuman primates. We recently showed that P. falciparum reticulocyte binding protein homolog 5 (PfRH5), a merozoite adhesin required for erythrocyte invasion, is highly susceptible to vaccine-inducible strain-transcending parasite-neutralizing antibody. In vivo efficacy of PfRH5-based vaccines has not previously been evaluated. Here, we demonstrate that PfRH5-based vaccines can protect Aotus monkeys against a virulent vaccine-heterologous P. falciparum challenge and show that such protection can be achieved by a human-compatible vaccine formulation. Protection was associated with anti-PfRH5 antibody concentration and in vitro parasite-neutralizing activity, supporting the use of this in vitro assay to predict the in vivo efficacy of future vaccine candidates. These data suggest that PfRH5-based vaccines have potential to achieve strain-transcending efficacy in humans. PMID:25590760

  11. Epitope mapping of PfCP-2.9, an asexual blood-stage vaccine candidate of Plasmodium falciparum

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    He Zhicheng

    2010-04-01

    Full Text Available Abstract Background Apical membrane antigen 1 (AMA-1 and merozoite surface protein 1 (MSP1 of Plasmodium falciparum are two leading blood-stage malaria vaccine candidates. A P. falciparum chimeric protein 2.9 (PfCP-2.9 has been constructed as a vaccine candidate, by fusing AMA-1 domain III (AMA-1 (III with a C-terminal 19 kDa fragment of MSP1 (MSP1-19 via a 28-mer peptide hinge. PfCP-2.9 was highly immunogenic in animal studies, and antibodies elicited by the PfCP-2.9 highly inhibited parasite growth in vitro. This study focused on locating the distribution of epitopes on PfCP-2.9. Methods A panel of anti-PfCP-2.9 monoclonal antibodies (mAbs were produced and their properties were examined by Western blot as well as in vitro growth inhibition assay (GIA. In addition, a series of PfCP-2.9 mutants containing single amino acid substitution were produced in Pichia pastoris. Interaction of the mAbs with the PfCP-2.9 mutants was measured by both Western blot and enzyme-linked immunosorbent assay (ELISA. Results Twelve mAbs recognizing PfCP-2.9 chimeric protein were produced. Of them, eight mAbs recognized conformational epitopes and six mAbs showed various levels of inhibitory activities on parasite growth in vitro. In addition, seventeen PfCP-2.9 mutants with single amino acid substitution were produced in Pichia pastoris for interaction with mAbs. Reduced binding of an inhibitory mAb (mAb7G, was observed in three mutants including M62 (Phe491→Ala, M82 (Glu511→Gln and M84 (Arg513→Lys, suggesting that these amino acid substitutions are critical to the epitope corresponding to mAb7G. The binding of two non-inhibitory mAbs (mAbG11.12 and mAbW9.10 was also reduced in the mutants of either M62 or M82. The substitution of Leu31 to Arg resulted in completely abolishing the binding of mAb1E1 (a blocking antibody to M176 mutant, suggesting that the Leu residue at this position plays a crucial role in the formation of the epitope. In addition, the Asn15

  12. Protective Vaccination against Blood-Stage Malaria of Plasmodium chabaudi: Differential Gene Expression in the Liver of Balb/c Mice toward the End of Crisis Phase

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    Al-Quraishy, Saleh A.; Dkhil, Mohamed A.; Abdel-Baki, Abdel-Azeem A.; Delic, Denis; Wunderlich, Frank

    2016-01-01

    Protective vaccination induces self-healing of otherwise fatal blood-stage malaria of Plasmodium chabaudi in female Balb/c mice. To trace processes critically involved in self-healing, the liver, an effector against blood-stage malaria, is analyzed for possible changes of its transcriptome in vaccination-protected in comparison to non-protected mice toward the end of the crisis phase. Gene expression microarray analyses reveal that vaccination does not affect constitutive expression of mRNA and lincRNA. However, malaria induces significant (p 3-fold as compared to the corresponding constitutive expressions. Massive up-regulations, partly by >100-fold, are found for genes as RhD, Add2, Ank1, Ermap, and Slc4a, which encode proteins of erythrocytic surface membranes, and as Gata1 and Gfi1b, which encode transcription factors involved in erythrocytic development. Also, Cldn13 previously predicted to be expressed on erythroblast surfaces is up-regulated by >200-fold, though claudins are known as main constituents of tight junctions acting as paracellular barriers between epithelial cells. Other genes are up-regulated by 10-fold, which can be subgrouped in genes encoding proteins known to be involved in mitosis, in cell cycle regulation, and in DNA repair. Our data suggest that protective vaccination enables the liver to respond to P. chabaudi infections with accelerated regeneration and extramedullary erythropoiesis during crisis, which contributes to survival of otherwise lethal blood-stage malaria. PMID:27471498

  13. Combining viral vectored and protein-in-adjuvant vaccines against the blood-stage malaria antigen AMA1: report on a phase 1a clinical trial.

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    Hodgson, Susanne H; Choudhary, Prateek; Elias, Sean C; Milne, Kathryn H; Rampling, Thomas W; Biswas, Sumi; Poulton, Ian D; Miura, Kazutoyo; Douglas, Alexander D; Alanine, Daniel Gw; Illingworth, Joseph J; de Cassan, Simone C; Zhu, Daming; Nicosia, Alfredo; Long, Carole A; Moyle, Sarah; Berrie, Eleanor; Lawrie, Alison M; Wu, Yimin; Ellis, Ruth D; Hill, Adrian V S; Draper, Simon J

    2014-12-01

    The development of effective vaccines against difficult disease targets will require the identification of new subunit vaccination strategies that can induce and maintain effective immune responses in humans. Here we report on a phase 1a clinical trial using the AMA1 antigen from the blood-stage Plasmodium falciparum malaria parasite delivered either as recombinant protein formulated with Alhydrogel adjuvant with and without CPG 7909, or using recombinant vectored vaccines--chimpanzee adenovirus ChAd63 and the orthopoxvirus MVA. A variety of promising "mixed-modality" regimens were tested. All volunteers were primed with ChAd63, and then subsequently boosted with MVA and/or protein-in-adjuvant using either an 8- or 16-week prime-boost interval. We report on the safety of these regimens, as well as the T cell, B cell, and serum antibody responses. Notably, IgG antibody responses primed by ChAd63 were comparably boosted by AMA1 protein vaccine, irrespective of whether CPG 7909 was included in the Alhydrogel adjuvant. The ability to improve the potency of a relatively weak aluminium-based adjuvant in humans, by previously priming with an adenoviral vaccine vector encoding the same antigen, thus offers a novel vaccination strategy for difficult or neglected disease targets when access to more potent adjuvants is not possible. PMID:25156127

  14. 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

  15. Phase 1 Study in Malaria Naïve Adults of BSAM2/Alhydrogel®+CPG 7909, a Blood Stage Vaccine against P. falciparum Malaria

    OpenAIRE

    Ellis, Ruth D.; Wu, Yimin; Martin, Laura B; Shaffer, Donna; Miura, Kazutoyo; Aebig, Joan; Orcutt, Andrew; Rausch, Kelly; ZHU, DAMING; Mogensen, Anders; Fay, Michael P.; David L. Narum; Long, Carole; Miller, Louis; Durbin, Anna P.

    2012-01-01

    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 MSP142, 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 ...

  16. Phase I Clinical Trial of a Recombinant Blood Stage Vaccine Candidate for Plasmodium falciparum Malaria Based on MSP1 and EBA175.

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    Chetan E Chitnis

    Full Text Available A phase I randomised, controlled, single blind, dose escalation trial was conducted to evaluate safety and immunogenicity of JAIVAC-1, a recombinant blood stage vaccine candidate against Plasmodium falciparum malaria, composed of a physical mixture of two recombinant proteins, PfMSP-1(19, the 19 kD conserved, C-terminal region of PfMSP-1 and PfF2 the receptor-binding F2 domain of EBA175.Healthy malaria naïve Indian male subjects aged 18-45 years were recruited from the volunteer database of study site. Fifteen subjects in each cohort, randomised in a ratio of 2:1 and meeting the protocol specific eligibility criteria, were vaccinated either with three doses (10 μg, 25 μg and 50 μg of each antigen of JAIVAC-1 formulated with adjuvant Montanide ISA 720 or with standard dosage of Hepatitis B vaccine. Each subject received the assigned vaccine in the deltoid muscle of the upper arms on Day 0, Day 28 and Day 180.JAIVAC-1 was well tolerated and no serious adverse event was observed. All JAIVAC-1 subjects sero-converted for PfF2 but elicited poor immune response to PfMSP-1(19. Dose-response relationship was observed between vaccine dose of PfF2 and antibody response. The antibodies against PfF2 were predominantly of IgG1 and IgG3 isotype. Sera from JAIVAC-1 subjects reacted with late schizonts in a punctate pattern in immunofluorescence assays. Purified IgG from JAIVAC-1 sera displayed significant growth inhibitory activity against Plasmodium falciparum CAMP strain.Antigen PfF2 should be retained as a component of a recombinant malaria vaccine but PfMSP-1(19 construct needs to be optimised to improve its immunogenicity.Clinical Trial Registry, India CTRI/2010/091/000301.

  17. 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

    Full Text Available BACKGROUND: 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. METHODS: 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. RESULTS: 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. CONCLUSION/SIGNIFICANCE: 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. TRIAL REGISTRATION: ClinicalTrials.gov NCT00344539.

  18. Phase I Clinical Trial of a Recombinant Blood Stage Vaccine Candidate for Plasmodium falciparum Malaria Based on MSP1 and EBA175

    Science.gov (United States)

    Chitnis, Chetan E.; Mukherjee, Paushali; Mehta, Shantanu; Yazdani, Syed Shams; Dhawan, Shikha; Shakri, Ahmad Rushdi; Bharadwaj, Rukmini; Gupta, Puneet Kumar; Hans, Dhiraj; Mazumdar, Suman; Singh, Bijender; Kumar, Sanjeev; Pandey, Gaurav; Parulekar, Varsha; Imbault, Nathalie; Shivyogi, Preethi; Godbole, Girish; Mohan, Krishna; Leroy, Odile; Singh, Kavita; Chauhan, Virander S.

    2015-01-01

    Background A phase I randomised, controlled, single blind, dose escalation trial was conducted to evaluate safety and immunogenicity of JAIVAC-1, a recombinant blood stage vaccine candidate against Plasmodium falciparum malaria, composed of a physical mixture of two recombinant proteins, PfMSP-119, the 19 kD conserved, C-terminal region of PfMSP-1 and PfF2 the receptor-binding F2 domain of EBA175. Method Healthy malaria naïve Indian male subjects aged 18–45 years were recruited from the volunteer database of study site. Fifteen subjects in each cohort, randomised in a ratio of 2:1 and meeting the protocol specific eligibility criteria, were vaccinated either with three doses (10μg, 25μg and 50μg of each antigen) of JAIVAC-1 formulated with adjuvant Montanide ISA 720 or with standard dosage of Hepatitis B vaccine. Each subject received the assigned vaccine in the deltoid muscle of the upper arms on Day 0, Day 28 and Day 180. Results JAIVAC-1 was well tolerated and no serious adverse event was observed. All JAIVAC-1 subjects sero-converted for PfF2 but elicited poor immune response to PfMSP-119. Dose-response relationship was observed between vaccine dose of PfF2 and antibody response. The antibodies against PfF2 were predominantly of IgG1 and IgG3 isotype. Sera from JAIVAC-1 subjects reacted with late schizonts in a punctate pattern in immunofluorescence assays. Purified IgG from JAIVAC-1 sera displayed significant growth inhibitory activity against Plasmodium falciparum CAMP strain. Conclusion Antigen PfF2 should be retained as a component of a recombinant malaria vaccine but PfMSP-119 construct needs to be optimised to improve its immunogenicity. Trial Registration Clinical Trial Registry, India CTRI/2010/091/000301 PMID:25927360

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

    Directory of Open Access Journals (Sweden)

    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.

  20. Phase 1 trial of the Plasmodium falciparum blood stage vaccine MSP1(42-C1/Alhydrogel with and without CPG 7909 in malaria naive adults.

    Directory of Open Access Journals (Sweden)

    Ruth D Ellis

    Full Text Available BACKGROUND: Merozoite surface protein 1(42 (MSP1(42 is a leading blood stage malaria vaccine candidate. In order to induce immune responses that cover the major antigenic polymorphisms, FVO and 3D7 recombinant proteins of MSP1(42 were mixed (MSP1(42-C1. To improve the level of antibody response, MSP1(42-C1 was formulated with Alhydrogel plus the novel adjuvant CPG 7909. METHODS: A Phase 1 clinical trial was conducted in healthy malaria-naïve adults at the Center for Immunization Research in Washington, D.C., to evaluate the safety and immunogenicity of MSP1(42-C1/Alhydrogel +/- CPG 7909. Sixty volunteers were enrolled in dose escalating cohorts and randomized to receive three vaccinations of either 40 or 160 microg protein adsorbed to Alhydrogel +/- 560 microg CPG 7909 at 0, 1 and 2 months. RESULTS: Vaccinations were well tolerated, with only one related adverse event graded as severe (Grade 3 injection site erythema and all other vaccine related adverse events graded as either mild or moderate. Local adverse events were more frequent and severe in the groups receiving CPG. The addition of CPG enhanced anti-MSP1(42 antibody responses following vaccination by up to 49-fold two weeks after second immunization and 8-fold two weeks after the third immunization when compared to MSP1(42-C1/Alhydrogel alone (p<0.0001. After the third immunization, functionality of the antibody was tested by an in vitro growth inhibition assay. Inhibition was a function of antibody titer, with an average of 3% (range -2 to 10% in the non CPG groups versus 14% (3 to 32% in the CPG groups. CONCLUSION/SIGNIFICANCE: The favorable safety profile and high antibody responses induced with MSP1(42-C1/Alhydrogel + CPG 7909 are encouraging. MSP1(42-C1/Alhydrogel is being combined with other blood stage antigens and will be taken forward in a formulation adjuvanted with CPG 7909. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT00320658.

  1. Towards Developing a Malaria Vaccine Based on CD4 T Cell Mediated Immunity in Blood Stage of Malaria Infection

    Institute of Scientific and Technical Information of China (English)

    徐沪济

    2004-01-01

    Twenty-one years after malaria antigens were first cloned a vaccine still appears to be a long way off. There have been periods of great excitement and in model systems subunit vaccine homologues can induce robust protection. However, significant challenges exist concerning antigenic variation and polymorphism, immunological non-respons-iveness to individual vaccine antigens, parasite-induced apoptosis of immune effector and memory cells and immune deviation as a result of maternal immtmity and alterations of dendritic cell function.

  2. 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

  3. Iron oxide nanoparticles as a clinically acceptable delivery platform for a recombinant blood-stage human malaria vaccine.

    Science.gov (United States)

    Pusic, Kae; Aguilar, Zoraida; McLoughlin, Jaclyn; Kobuch, Sophie; Xu, Hong; Tsang, Mazie; Wang, Andrew; Hui, George

    2013-03-01

    This study explored the novel use of iron oxide (IO) nanoparticles (malaria vaccine antigen, the merozoite surface protein 1 (rMSP1), was conjugated to IO nanoparticles (rMSP1-IO). Immunizations in outbred mice with rMSP1-IO achieved 100% responsiveness with antibody titers comparable to those obtained with rMSP1 formulated with a clinically acceptable adjuvant, Montanide ISA51 (2.7×10 vs. 1.6×10; respectively). Only rMSP1-1O could induce significant levels (80%) of parasite inhibitory antibodies. The rMSP1-IO was highly stable at 4°C and was amenable to lyophilization, maintaining its antigenicity, immunogenicity, and ability to induce inhibitory antibodies. Further testing in nonhuman primates, Aotus monkeys, also elicited 100% immune responsiveness and high levels of parasite inhibitory antibodies (55-100% inhibition). No apparent local or systemic toxicity was associated with IO immunizations. Murine macrophages and dendritic cells efficiently (>90%) internalized IO nanoparticles, but only the latter were significantly activated, with elevated expression/secretion of CD86, cytokines (IL-6, TNF-α, IL1-b, IFN-γ, and IL-12), and chemokines (CXCL1, CXCL2, CCL2, CCL3, CCL4, and CXCL10). Thus, the IO nanoparticles is a novel, safe, and effective vaccine platform, with built-in adjuvancy, that is highly stable and field deployable for cost-effective vaccine delivery.

  4. Immunization of Aotus monkeys with Plasmodium falciparum blood-stage recombinant proteins.

    OpenAIRE

    S Herrera; Herrera, M. A.; Perlaza, B L; Burki, Y; Caspers, P; Döbeli, H; Rotmann, D; Certa, U

    1990-01-01

    The current spread of multidrug-resistant malaria demands rapid vaccine development against the major pathogen Plasmodium falciparum. The high quantities of protein required for a worldwide vaccination campaign select recombinant DNA technology as a practical approach for large-scale antigen production. We describe the vaccination of Aotus monkeys with two recombinant blood-stage antigens (recombinant p41 and 190N) that were considered as vaccine candidates because parasite-derived antigen pr...

  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 BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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

  6. [Immunological characteristics of the 2-stage method of smallpox vaccination].

    Science.gov (United States)

    Marennikova, S S; Matsevich, G R; Sokolova, A F; Shul'ga, L G; Manenkova, G M

    1977-05-01

    As a result of observations carried out on children the authors present immunological characteristics of two-stage smallpox vaccination at different intervals (1 to 60 days) between the injection of inactivated and live vaccine. There proved to be acceleration and intensification of antibody formation after two-stage immunization in comparison with the rutine vaccination. A seven-day interval between the injection of the inactivated and live preparations was recommended on the basis of the data obtained.

  7. IMPULSIVE VACCINATION OF SIRS EPIDEMIC MODEL WITH STAGE-STRUCTURE

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    The period of infection is partitioned into the early and later stages according to the development process of infection. The infected individuals in the different stages have the different ability of transmitting disease. The constant recruitment rate and exponential natural death, as well as the disease-related death and pulse vaccination are incorporated into the model. Through the discrete dynamical system determined by the stroboscopic map, we obtain the exact infection-free periodic solution to the sy...

  8. Autorosette formation of erythrocytes on peripheral blood mononuclear cells in dogs vaccinated with canine distemper live-virus vaccine.

    OpenAIRE

    Chandler, J. P.; Yang, T. J.

    1981-01-01

    A time course study of the peripheral blood leukocytes of dogs vaccinated with canine distemper live virus (a paramyxovirus) vaccines showed that autorosette-forming leukocytes appeared from day 3 to day 10 after vaccination. The number of these cells peaked at day 7 when as many as 35% of mononuclear cells formed rosettes with autologous erythrocytes. In contrast, in nonvaccinated dogs, only 0.6 +/- 0.3% (standard error of the mean) of mononuclear cells formed rosettes throughout the 2-week ...

  9. Protection induced by early stage vaccination with pandemic influenza virus-like particles.

    Science.gov (United States)

    Lee, Gi-Ja; Quan, Fu-Shi

    2016-07-19

    The 2009 worldwide influenza pandemic emphasized the need for new approaches to develop emergency vaccines. In this study, a virus-like particle vaccine comprised of hemagglutinin (HA) and M1 from the pandemic influenza virus A/California/04/09 were used and its ability to induce protective immunity during the early stage of vaccination was assessed in a mouse model. A single intramuscular vaccination with virus-like particles (VLPs) provided protection on days 4 and 7 post-vaccination against lethal virus challenge with only moderate body weight loss. VLP vaccination induced significantly higher IgG antibody responses and high hemagglutinin inhibition (HAI) titers on day 4 post-vaccination. A predominant IgG2a antibody response and viral neutralizing antibodies were induced on day 7. These immune responses were closely correlated with protection. Lung virus titers decreased significantly on day 7 compared to those on day 4 post-vaccination. The lung virus titer on day 4 post-vaccination also decreased significantly compared to that of the naïve control. These results demonstrate that VLP vaccination confers effective protection during the early stage after vaccination in a mouse model. PMID:27317263

  10. Merozoite surface proteins in red blood cell invasion, immunity and vaccines against malaria

    Science.gov (United States)

    Beeson, James G.; Drew, Damien R.; Boyle, Michelle J.; Feng, Gaoqian; Fowkes, Freya J.I.; Richards, Jack S.

    2016-01-01

    Malaria accounts for an enormous burden of disease globally, with Plasmodium falciparum accounting for the majority of malaria, and P. vivax being a second important cause, especially in Asia, the Americas and the Pacific. During infection with Plasmodium spp., the merozoite form of the parasite invades red blood cells and replicates inside them. It is during the blood-stage of infection that malaria disease occurs and, therefore, understanding merozoite invasion, host immune responses to merozoite surface antigens, and targeting merozoite surface proteins and invasion ligands by novel vaccines and therapeutics have been important areas of research. Merozoite invasion involves multiple interactions and events, and substantial processing of merozoite surface proteins occurs before, during and after invasion. The merozoite surface is highly complex, presenting a multitude of antigens to the immune system. This complexity has proved challenging to our efforts to understand merozoite invasion and malaria immunity, and to developing merozoite antigens as malaria vaccines. In recent years, there has been major progress in this field, and several merozoite surface proteins show strong potential as malaria vaccines. Our current knowledge on this topic is reviewed, highlighting recent advances and research priorities. PMID:26833236

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

    DEFF Research Database (Denmark)

    Thakur, Aneesh

    -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...

  12. Human Papillomavirus Vaccine Stages of Change among Male and Female University Students: Ready or Not?

    Science.gov (United States)

    Patel, Divya A.; Grunzweig, Katherine A.; Zochowski, Melissa K.; Dempsey, Amanda F.; Carlos, Ruth C.; Dalton, Vanessa K.

    2013-01-01

    Objective: To examine gender differences in human papillomavirus (HPV) vaccine stages of change following the recommendations for permissive use of HPV vaccine in males. Participants: Students aged 18-26 attending a large, public, Midwest university in April 2010. Methods: Participants completed a self-administered, online questionnaire. HPV…

  13. Presence of mycobacterial L-forms in human blood: Challenge of BCG vaccination

    OpenAIRE

    Markova, Nadya; Slavchev, Georgi; Michailova, Lilia

    2015-01-01

    Possible persistence of bacteria in human blood as cell wall deficient forms (L-forms) represents a top research priority for microbiologists. Application of live BCG vaccine and L-form transformation of vaccine strain may display a new intriguing aspect concerning the opportunity for occurrence of unpredictable colonization inside the human body by unusual microbial life forms. L-form cultures were isolated from 141 blood samples of people previously vaccinated with BCG, none with a history ...

  14. 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

    2011-08-01

    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

  15. 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.

  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. PMID:27238088

  17. Vaccination with recombinant aspartic hemoglobinase reduces parasite load and blood loss after hookworm infection in dogs.

    Directory of Open Access Journals (Sweden)

    Alex Loukas

    2005-10-01

    Full Text Available BACKGROUND: Hookworms infect 730 million people in developing countries where they are a leading cause of intestinal blood loss and iron-deficiency anemia. At the site of attachment to the host, adult hookworms ingest blood and lyse the erythrocytes to release hemoglobin. The parasites subsequently digest hemoglobin in their intestines using a cascade of proteolysis that begins with the Ancylostoma caninum aspartic protease 1, APR-1. METHODS AND FINDINGS: We show that vaccination of dogs with recombinant Ac-APR-1 induced antibody and cellular responses and resulted in significantly reduced hookworm burdens (p = 0.056 and fecal egg counts (p = 0.018 in vaccinated dogs compared to control dogs after challenge with infective larvae of A. caninum. Most importantly, vaccinated dogs were protected against blood loss (p = 0.049 and most did not develop anemia, the major pathologic sequela of hookworm disease. IgG from vaccinated animals decreased the catalytic activity of the recombinant enzyme in vitro and the antibody bound in situ to the intestines of worms recovered from vaccinated dogs, implying that the vaccine interferes with the parasite's ability to digest blood. CONCLUSION: To the best of our knowledge, this is the first report of a recombinant vaccine from a hematophagous parasite that significantly reduces both parasite load and blood loss, and it supports the development of APR-1 as a human hookworm vaccine.

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

    International Nuclear Information System (INIS)

    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

  19. Acquisition of growth-inhibitory antibodies against blood-stage Plasmodium falciparum.

    Directory of Open Access Journals (Sweden)

    Fiona J McCallum

    Full Text Available BACKGROUND: Antibodies that inhibit the growth of blood-stage Plasmodium falciparum may play an important role in acquired and vaccine-induced immunity in humans. However, the acquisition and activity of these antibodies is not well understood. METHODS: We tested dialysed serum and purified immunoglobulins from Kenyan children and adults for inhibition of P. falciparum blood-stage growth in vitro using different parasite lines. Serum antibodies were measured by ELISA to blood-stage parasite antigens, extracted from P. falciparum schizonts, and to recombinant merozoite surface protein 1 (42 kDa C-terminal fragment, MSP1-42. RESULTS: Antibodies to blood-stage antigens present in schizont protein extract and to recombinant MSP1-42 significantly increased with age and were highly correlated. In contrast, growth-inhibitory activity was not strongly associated with age and tended to decline marginally with increasing age and exposure, with young children demonstrating the highest inhibitory activity. Comparison of growth-inhibitory activity among samples collected from the same population at different time points suggested that malaria transmission intensity influenced the level of growth-inhibitory antibodies. Antibodies to recombinant MSP1-42 were not associated with growth inhibition and high immunoglobulin G levels were poorly predictive of inhibitory activity. The level of inhibitory activity against different isolates varied. CONCLUSIONS: Children can acquire growth-inhibitory antibodies at a young age, but once they are acquired they do not appear to be boosted by on-going exposure. Inhibitory antibodies may play a role in protection from early childhood malaria.

  20. Effectiveness of DNA-recombinant anti-hepatitis B vaccines in blood donors: a cohort study

    OpenAIRE

    Petry Andrea; de Souza Denise ER; Kupek Emil

    2007-01-01

    Abstract Background Although various studies have demonstrated efficacy of DNA-recombinant anti-hepatitis B vaccines, their effectiveness in health care settings has not been researched adequately. This gap is particularly visible for blood donors, a group of significant importance in the reduction of transfusion-transmitted hepatitis B. Methods This is a double cohort study of 1411 repeat blood donors during the period 1998–2002, involving a vaccinated and an unvaccinated cohort, with matchi...

  1. Robust Vaccine Responses in Adult and Pediatric Cord Blood Transplantation Recipients Treated for Hematologic Malignancies.

    Science.gov (United States)

    Shah, Gunjan L; Shune, Leyla; Purtill, Duncan; Devlin, Sean; Lauer, Emily; Lubin, Marissa; Bhatt, Valkal; McElrath, Courtney; Kernan, Nancy A; Scaradavou, Andromachi; Giralt, Sergio; Perales, Miguel A; Ponce, Doris M; Young, James W; Shah, Monica; Papanicolaou, Genovefa; Barker, Juliet N

    2015-12-01

    Because cord blood (CB) lacks memory T and B cells and recent decreases in herd immunity to vaccine-preventable diseases in many developed countries have been documented, vaccine responses in CB transplantation (CBT) survivors are of great interest. We analyzed vaccine responses in double-unit CBT recipients transplanted for hematologic malignancies. In 103 vaccine-eligible patients, graft-versus-host disease (GVHD) most commonly precluded vaccination. Sixty-five patients (63%; engrafting units median HLA-allele match 5/8; range, 2 to 7/8) received protein conjugated vaccines, and 63 patients (median age, 34 years; range, .9 to 64) were evaluated for responses. Median vaccination time was 17 months (range, 7 to 45) post-CBT. GVHD (n = 42) and prior rituximab (n = 13) delayed vaccination. Responses to Prevnar 7 and/or 13 vaccines (serotypes 14, 19F, 23F) were seen in children and adults (60% versus 49%, P = .555). Responses to tetanus, diphtheria, pertussis, Haemophilus influenzae, and polio were observed in children (86% to 100%) and adults (53% to 89%) even if patients had prior GVHD or rituximab. CD4(+)CD45RA(+) and CD19(+) cell recovery significantly influenced tetanus and polio responses. In a smaller cohort responses were seen to measles (65%), mumps (50%), and rubella (100%) vaccines. No vaccine side effects were identified, and all vaccinated patients survived (median follow-up, 57 months). Although GVHD and rituximab can delay vaccination, CBT recipients (including adults and those with prior GVHD) have similar vaccine response rates to adult donor allograft recipients supporting vaccination in CBT recipients. PMID:26271191

  2. Effectiveness of DNA-recombinant anti-hepatitis B vaccines in blood donors: a cohort study

    Directory of Open Access Journals (Sweden)

    Petry Andrea

    2007-11-01

    Full Text Available Abstract Background Although various studies have demonstrated efficacy of DNA-recombinant anti-hepatitis B vaccines, their effectiveness in health care settings has not been researched adequately. This gap is particularly visible for blood donors, a group of significant importance in the reduction of transfusion-transmitted hepatitis B. Methods This is a double cohort study of 1411 repeat blood donors during the period 1998–2002, involving a vaccinated and an unvaccinated cohort, with matching of the two in terms of sex, age and residence. Average follow-up was 3.17 person-years. The outcome measure was infection with hepatitis B virus (HBV, defined by testing positive on serologic markers HBsAg or anti-HBC. All blood donors were from the blood bank in Joaçaba, federal state of Santa Catarina, Brazil. Results The cohorts did not differ significantly regarding sex, age and marital status but the vaccinated cohort had higher mean number of blood donations and higher proportion of those residing in the county capital Joaçaba. Hepatitis B incidences per 1000 person-years were zero among vaccinated and 2,33 among non-vaccinated, resulting in 100% vaccine effectiveness with 95% confidence interval from 30,1% to 100%. The number of vaccinated persons necessary to avoid one HBV infection in blood donors was estimated at 429 with 95% confidence interval from 217 to 21422. Conclusion The results showed very high effectiveness of DNA-recombinant anti-HBV vaccines in blood donors. Its considerable variation in this study is likely due to the limited follow-up and the influence of confounding factors normally balanced out in efficacy clinical trials.

  3. 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...... 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...... response to pneumococcal type antigens was similar in healthy adults and in patients with early stage HD before therapy. After treatment, postvaccination antibody response became negligible. Even up to 7 years after cessation of therapy patients were not able to raise a significant antibody response...

  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...... 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...... response to pneumococcal type antigens was similar in healthy adults and in patients with early stage HD before therapy. After treatment, postvaccination antibody response became negligible. Even up to 7 years after cessation of therapy patients were not able to raise a significant antibody response....

  5. P. falciparum and P. vivax Epitope-Focused VLPs Elicit Sterile Immunity to Blood Stage Infections.

    Directory of Open Access Journals (Sweden)

    David C Whitacre

    Full Text Available In order to design P. falciparum preerythrocytic vaccine candidates, a library of circumsporozoite (CS T and B cell epitopes displayed on the woodchuck hepatitis virus core antigen (WHcAg VLP platform was produced. To test the protective efficacy of the WHcAg-CS VLPs, hybrid CS P. berghei/P. falciparum (Pb/Pf sporozoites were used to challenge immunized mice. VLPs carrying 1 or 2 different CS repeat B cell epitopes and 3 VLPs carrying different CS non-repeat B cell epitopes elicited high levels of anti-insert antibodies (Abs. Whereas, VLPs carrying CS repeat B cell epitopes conferred 98% protection of the liver against a 10,000 Pb/Pf sporozoite challenge, VLPs carrying the CS non-repeat B cell eptiopes were minimally-to-non-protective. One-to-three CS-specific CD4/CD8 T cell sites were also fused to VLPs, which primed CS-specific as well as WHcAg-specific T cells. However, a VLP carrying only the 3 T cell domains failed to protect against a sporozoite challenge, indicating a requirement for anti-CS repeat Abs. A VLP carrying 2 CS repeat B cell epitopes and 3 CS T cell sites in alum adjuvant elicited high titer anti-CS Abs (endpoint dilution titer >1x10(6 and provided 80-100% protection against blood stage malaria. Using a similar strategy, VLPs were constructed carrying P. vivax CS repeat B cell epitopes (WHc-Pv-78, which elicited high levels of anti-CS Abs and conferred 99% protection of the liver against a 10,000 Pb/Pv sporozoite challenge and elicited sterile immunity to blood stage infection. These results indicate that immunization with epitope-focused VLPs carrying selected B and T cell epitopes from the P. falciparum and P. vivax CS proteins can elicit sterile immunity against blood stage malaria. Hybrid WHcAg-CS VLPs could provide the basis for a bivalent P. falciparum/P. vivax malaria vaccine.

  6. Blood stage merozoite surface protein conjugated to nanoparticles induce potent parasite inhibitory antibodies.

    Science.gov (United States)

    Pusic, Kae; Xu, Hengyi; Stridiron, Andrew; Aguilar, Zoraida; Wang, Andrew; Hui, George

    2011-11-01

    In this proof-of-concept study we report the use of nanoparticles as a vaccine delivery system for a blood stage malaria vaccine. The recombinant malarial antigen, Merozoite Surface Protein 1 (rMSP1) of Plasmodium falciparum served as the model vaccine. The rMSP1 was covalently conjugated to polymer-coated quantum dot CdSe/ZnS nanoparticles (QDs) via surface carboxyl groups, forming rMSP1-QDs. Anti-MSP1 antibody responses induced by rMSP1-QDs were found to have 2-3 log higher titers than those obtained with rMSP1 administered with the conventional adjuvants, Montanide ISA51 and CFA. Moreover, the immune responsiveness and the induction of parasite inhibitory antibodies were significantly superior in mice injected with rMSP1-QDs. The rMSP1-QDs delivered via intra-peritoneal (i.p.), intra-muscular (i.m.), and subcutaneous (s.c.) routes were equally efficacious. The high level of immunogenicity exhibited by the rMSP1-QDs was achieved without further addition of other adjuvant components. Bone marrow derived dendritic cells were shown to efficiently take up the nanoparticles leading to their activation and the expression/secretion of key cytokines, suggesting that this may be a mode of action for the enhanced immunogenicity. This study provides promising results for the use of water soluble, inorganic nanoparticles (<15 nm) as potent vehicles/platforms to enhance the immunogenicity of polypeptide antigens in adjuvant-free immunizations.

  7. 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

    -specific antibody-secreting cells (AbSC) of the isotypes IgM, IgG, and IgA. The appearance of AbSC in the blood after vaccination of adults with diphtheria toxoid-conjugated Hib polysaccharide was investigated. AbSC were detected from post-vaccination day 5 to day 14. IgA was the predominant isotype among...... these cells. IgM AbSC peaked slightly earlier (median day 7) than IgG and IgA AbSC (both day 8). On post-vaccination day 8 the numbers of AbSC were: IgA, 1217/10(6) mononuclear cells (median); IgG, 211; and IgM, 30 (n = 11). Similar isotype distribution has earlier been found after vaccination with pure...... 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...

  8. Blood biomarkers in the early stage of cerebral ischemia.

    Science.gov (United States)

    Maestrini, I; Ducroquet, A; Moulin, S; Leys, D; Cordonnier, C; Bordet, R

    2016-03-01

    In ischemic stroke patients, blood-based biomarkers may be applied for the diagnosis of ischemic origin and subtype, prediction of outcomes and targeted treatment in selected patients. Knowledge of the pathophysiology of cerebral ischemia has led to the evaluation of proteins, neurotransmitters, nucleic acids and lipids as potential biomarkers. The present report focuses on the role of blood-based biomarkers in the early stage of ischemic stroke-within 72h of its onset-as gleaned from studies published in English in such patients. Despite growing interest in their potential role in clinical practice, the application of biomarkers for the management of cerebral ischemia is not currently recommended by guidelines. However, there are some promising clinical biomarkers, as well as the N-methyl-d-aspartate (NMDA) peptide and NMDA-receptor (R) autoantibodies that appear to identify the ischemic nature of stroke, and the glial fibrillary acidic protein (GFAP) that might be able to discriminate between acute ischemic and hemorrhagic strokes. Moreover, genomics and proteomics allow the characterization of differences in gene expression, and protein and metabolite production, in ischemic stroke patients compared with controls and, thus, may help to identify novel markers with sufficient sensitivity and specificity. Additional studies to validate promising biomarkers and to identify novel biomarkers are needed. PMID:26988891

  9. 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.

  10. Synthetic TLR4 agonists enhance functional antibodies and CD4+ T-cell responses against the Plasmodium falciparum GMZ2.6C multi-stage vaccine antigen.

    Science.gov (United States)

    Baldwin, Susan L; Roeffen, Will; Singh, Susheel K; Tiendrebeogo, Regis W; Christiansen, Michael; Beebe, Elyse; Carter, Darrick; Fox, Christopher B; Howard, Randall F; Reed, Steven G; Sauerwein, Robert; Theisen, Michael

    2016-04-27

    A subunit vaccine targeting both transmission and pathogenic asexual blood stages of Plasmodium falciparum, i.e., a multi-stage vaccine, could be a powerful tool to combat malaria. Here, we report production and characterization of the recombinant protein GMZ2.6C, which contains a fragment of the sexual-stage protein Pfs48/45-6C genetically fused to GMZ2, an asexual vaccine antigen in advanced clinical development. To select the most suitable vaccine formulation for downstream clinical studies, GMZ2.6C was tested with various immune modulators in different adjuvant formulations (stable emulsions, liposomes, and alum) in C57BL/6 mice. Some, but not all, formulations containing either the synthetic TLR4 agonist GLA or SLA elicited the highest parasite-specific antibody titers, the greatest IFN-γ responses in CD4+ TH1 cells, and the highest percentage of multifunctional CD4+ T cells expressing IFN-γ and TNF in response to GMZ2.6C. Both of these agonists have good safety records in humans. PMID:26994314

  11. Major histocompatibility complex class I-associated vaccine protection from simian immunodeficiency virus-infected peripheral blood cells

    OpenAIRE

    1994-01-01

    To evaluate the effectiveness of vaccine protection from infected cells from another individual of the same species, vaccinated rhesus macaques (Macaca mulatta) were challenged with peripheral blood mononuclear cells from another animal diagnosed with acquired immune deficiency syndrome (AIDS). Half of the simian immunodeficiency virus (SIV)- vaccinated animals challenged were protected, whereas unprotected vaccinates progressed as rapidly to AIDS. Protection was unrelated to either total ant...

  12. 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;

    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...... to non-vaccinated calves. All 14 Fet11 vaccinated calves were negative in both single and comparative tuberculin testing. All whole-cell vaccinated calves seroconverted after vaccination, and four and one animal tested positive in the single and comparative tuberculin skin test, respectively...

  13. Presence of mycobacterial L-forms in human blood: Challenge of BCG vaccination.

    Science.gov (United States)

    Markova, Nadya; Slavchev, Georgi; Michailova, Lilia

    2015-01-01

    Possible persistence of bacteria in human blood as cell wall deficient forms (L-forms) represents a top research priority for microbiologists. Application of live BCG vaccine and L-form transformation of vaccine strain may display a new intriguing aspect concerning the opportunity for occurrence of unpredictable colonization inside the human body by unusual microbial life forms. L-form cultures were isolated from 141 blood samples of people previously vaccinated with BCG, none with a history of exposure to tuberculosis. Innovative methodology to access the unusual L-form elements derived from human blood was developed. The methodology outlines the path of transformation of non- cultivable L-form element to cultivable bacteria and their adaptation for growth in vitro. All isolates showed typical L-forms growth features ("fried eggs" colonies and biofilm). Electron microscopy revealed morphology evidencing peculiar characteristics of bacterial L-form population (cell wall deficient polymorphic elements of variable shape and size). Regular detection of acid fast bacteria in smears of isolated blood L-form cultures, led us to start their identification by using specific Mycobactrium spp. genetic tests. Forty five of 97 genetically tested blood cultures provided specific positive signals for mycobacteria, confirmed by at least one of the 3 specific assays (16S rRNA PCR; IS6110 Real Time PCR and spoligotyping). In conclusion, the obtained genetic evidence suggests that these L-forms are of mycobacterial origin. As the investigated people had been vaccinated with BCG, we can assume that the identified mycobacterial L-forms may be produced by persisting live BCG vaccine. PMID:25874947

  14. Vaccinations

    Science.gov (United States)

    ... vaccinated? For many years, a set of annual vaccinations was considered normal and necessary for dogs and ... to protect for a full year. Consequently, one vaccination schedule will not work well for all pets. ...

  15. Protective status of end-stage renal disease children against tetanus and diphtheria vaccination

    Directory of Open Access Journals (Sweden)

    Mohammadreza Modarresi

    2013-01-01

    Methods: This cross-sectional study was carried on 83 participants less than 18 years including 27 patients on hemodialysis or peritoneal dialysis and 56 normal populations from February 2008 until December 2008 at St. Alzahra hospital, Isfahan, Iran. To determine anti-tetanus and anti-diphtheria antibodies level, Tetanus IgG ELISA kit (IBL International, Germany, RE56901 and Diphtheria IgG ELISA kit (IBL International, Germany, RE56191 were used. The participants must not received immunoglobulin, blood products or immunosuppressive medication in the current 6 months. Results: The mean age of case and control group were 12.5 ± 2.7 years and 11.7 ± 3.3 years, respectively, P > 0.05. According to IgG levels, 93% of hemodialysis patients and approximately 87% of peritoneal dialysis children needed booster doses of diphtheria vaccination. The results for IgG titer against tetanus revealed that in 91% of hemodialysis patients and 83% of peritoneal dialysis children booster doses of tetanus were recommended. Conclusions: Booster doses of vaccines may be required in ESRD children. Measuring serum IgG levels against vaccines to define protective levels are recommended.

  16. 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

    Effective control and eventual eradication of malaria drives the imperative need for clinical development of a malaria vaccine. Asexual parasite forms are responsible for clinical disease and death while apathogenic gametocytes are responsible for transmission from man to mosquito. Vaccines...

  17. 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......, PPDj-specific IFN-γ responses or positive PPDa or PPDb skin tests developed in vaccinees. Antibodies and cell-mediated immune responses were developed against FET11 antigens, however. At necropsy 8 or 12 months of age, relative Map burden was determined in a number of gut tissues by quantitative IS900...

  18. 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 ...

  19. Characterization of a multi-component anthrax vaccine designed to target the initial stages of infection as well as toxaemia

    OpenAIRE

    Cote, C. K.; Kaatz, L.; Reinhardt, J.; Bozue, J.; Tobery, S. A.; Bassett, A. D.; Sanz, P; Darnell, S C; Alem, F.; O’Brien, A.D.; Welkos, S. L.

    2012-01-01

    Current vaccine approaches to combat anthrax are effective; however, they target only a single protein [the protective antigen (PA) toxin component] that is produced after spore germination. PA production is subsequently increased during later vegetative cell proliferation. Accordingly, several aspects of the vaccine strategy could be improved. The inclusion of spore-specific antigens with PA could potentially induce protection to initial stages of the disease. Moreover, adding other epitopes...

  20. Decrease in blood pressure and regression of cardiovascular complications by angiotensin II vaccine in mice.

    Directory of Open Access Journals (Sweden)

    Futoshi Nakagami

    Full Text Available Vaccines have been recently developed to treat various diseases such as cancer, rheumatoid arthritis and Alzheimer's disease in addition to infectious diseases. However, before use in the clinical setting, vaccines targeting self-antigens must be demonstrated to be effective and safe, evoking an adequate humoral immune response from B cells while avoiding T cell activation in response to self. Although the vaccine targeting angiotensin II (Ang II is efficient in rodents and humans, little is known regarding the immunological activation and safety of the vaccine. In this study, we evaluated the efficiency and safety of an Ang II peptide vaccine in mice. Immunization with Ang II conjugated to keyhole limpet hemocyanin (KLH successfully induced the production of anti-Ang II antibody, which blocked Ang II signaling in human aortic smooth muscle cells. However, Ang II itself did not activate T cells, as assessed by the proliferation and lymphokine production of T cells in immunized mice, whereas KLH activated T cells. In an Ang II-infused model, the non-immunized mice showed high blood pressure (BP, whereas the immunized mice (Ang II-KLH showed a significant decrease in systolic BP, accompanied by significant reductions in cardiac hypertrophy and fibrosis. Importantly, anti-Ang II antibody titer was not elevated even after the administration of large amounts of Ang II, indicating that Ang II itself boosted antibody production, most likely due to less activation of T cells. In addition, no accumulation of inflammatory cells was observed in immunized mice, because endogenous Ang II would not activate T cells after immunization with Ang II-KLH. Taken together, these data indicate that vaccines targeting Ang II might be effective to decrease high BP and prevent cardiovascular complications without severe side effects.

  1. Brugia malayi: vaccination of jirds with /sup 60/cobalt-attenuated infective stage larvae protects against homologous challenge

    Energy Technology Data Exchange (ETDEWEB)

    Yates, J.A.; Higashi, G.I.

    1985-11-01

    Vaccination of inbred jirds (Meriones unguiculatus) with /sup 60/cobalt radiation-attenuated Brugia malayi infective stage larvae (L3) protected against homologous challenge given either subcutaneously (sc) or by the intraperitoneal (ip) route. Groups of jirds vaccinated once sc with 75, 15 Krad L3 showed from 69% to 91% reduction in recovered worms after ip challenge infection compared to infection in non-vaccinated control jirds, while 75% reduction in mean worm burden was seen in jirds receiving sc challenge infection. A single sc vaccination with 75, 10 or 20 Krad L3 produced no protection (10 Krad) and 64% reduction in recovered worms (20 Krad). Therefore the 15 Krad dose appeared to be best. A marked increase in anti-B. malayi antibody in vaccinated jirds was seen (by ELISA) immediately after challenge infection and an immunofluorescence assay showed that L3 incubated in serum from vaccinated jirds were completely and uniformly covered with specific antibody. Eosinophil-rich granulomas containing dead and moribund L3 were recovered from vaccinated jirds. This model of protective immunity in a Brugia-susceptible small rodent may provide a useful system for identification of molecularly defined filarial-protective immunogens.

  2. Relationship between blood pressure variability and different renal function impairment stages in elderly hypertension patients

    Institute of Scientific and Technical Information of China (English)

    王云

    2014-01-01

    Objective To observe the change of blood pressure variability(BPV)in elderly hypertension patients,and to analyze the correlation between BPV and stages of renal function damage.Methods 127 elderly primary hypertensive patients with chronic kidney disease(CKD)were divided into three groups:stage 2 CKD group(aged 60-

  3. Vital and dispensable roles of Plasmodium multidrug resistance transporters during blood- and mosquito-stage development.

    Science.gov (United States)

    Rijpma, Sanna R; van der Velden, Maarten; Annoura, Takeshi; Matz, Joachim M; Kenthirapalan, Sanketha; Kooij, Taco W A; Matuschewski, Kai; van Gemert, Geert-Jan; van de Vegte-Bolmer, Marga; Siebelink-Stoter, Rianne; Graumans, Wouter; Ramesar, Jai; Klop, Onny; Russel, Frans G M; Sauerwein, Robert W; Janse, Chris J; Franke-Fayard, Blandine M; Koenderink, Jan B

    2016-07-01

    Multidrug resistance (MDR) proteins belong to the B subfamily of the ATP Binding Cassette (ABC) transporters, which export a wide range of compounds including pharmaceuticals. In this study, we used reverse genetics to study the role of all seven Plasmodium MDR proteins during the life cycle of malaria parasites. Four P. berghei genes (encoding MDR1, 4, 6 and 7) were refractory to deletion, indicating a vital role during blood stage multiplication and validating them as potential targets for antimalarial drugs. Mutants lacking expression of MDR2, MDR3 and MDR5 were generated in both P. berghei and P. falciparum, indicating a dispensable role for blood stage development. Whereas P. berghei mutants lacking MDR3 and MDR5 had a reduced blood stage multiplication in vivo, blood stage growth of P. falciparum mutants in vitro was not significantly different. Oocyst maturation and sporozoite formation in Plasmodium mutants lacking MDR2 or MDR5 was reduced. Sporozoites of these P. berghei mutants were capable of infecting mice and life cycle completion, indicating the absence of vital roles during liver stage development. Our results demonstrate vital and dispensable roles of MDR proteins during blood stages and an important function in sporogony for MDR2 and MDR5 in both Plasmodium species. PMID:26991313

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

    Directory of Open Access Journals (Sweden)

    Talwar GP

    2015-01-01

    Full Text Available 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-pregnant women do not make it, the basis on which its detection in serum or urine serves as a reliable test for diagnosis of pregnancy. It plays a critical role in implantation of the embryo & thereby to the onset of pregnancy. The purpose of the vaccine is to generate bioeffective antibodies neutralizing hCG & thereby prevent the onset of pregnancy.br As you can imagine, the making of a workable vaccine, competent to make antibodies against a tolerant molecule to the woman’s immune system (she literally bathes in hCG during pregnancy was not simple. What was also demanded was high immunogenicity of the vaccine to make fairly high titres of antibodies to counteract the large amount of hCG made in early pregnancy. At each stage, it required testing in humans and before that could be done, appropriate toxicology studies & approval of Regulatory and Ethics Committees was needed each taking its time. Eventually the vaccine has to be amenable to industrial production to reach the public, hence a recombinant vaccine had to be developed. Given below is a brief write-up on the evolution of the vaccine against the human chorionic gonadotropin.br Yours, Pran

  5. Tranexamic acid for control of blood loss in bilateral total knee replacement in a single stage

    Directory of Open Access Journals (Sweden)

    Mandeep S Dhillon

    2011-01-01

    Full Text Available Background: Tranexamic acid (TEA reduces blood loss and red cell transfusions in patients undergoing unilateral total knee arthroplasty (TKA. However, there is not much literature regarding the use of TEA in patients undergoing bilateral TKA in a single stage and the protocols for administration of TEA in such patients are ill-defined. Materials and Methods: We carried out a case control study evaluating the effect of TEA on postoperative hemoglobin (Hb, total drain output, and number of blood units transfused in 52 patients undergoing bilateral TKA in a single stage, and compared it with 56 matched controls who did not receive TEA. Two doses of TEA were administered in doses of 10 mg / kg each (slow intravenous (IV infusion, with the first dose given just before tourniquet release of the first knee and the second dose three hours after the first one. Results: A statistically significant reduction in the total drain output and requirement of allogenic blood transfusion in cases who received TEA, as compared to the controls was observed. The postoperative Hb and Hb at the time of discharge were found to be lower in the control group, and this result was found to be statistically significant. Conclusion: TEA administered in patients undergoing single stage bilateral TKA helped reduce total blood loss and decreased allogenic blood transfusion requirements. This might be particularly relevant, where facilities such as autologous reinfusion might not be available.

  6. Action of adrenalin on the circulation of the murine Plasmodium developing stages, in different blood compartments

    Directory of Open Access Journals (Sweden)

    Bertani S.

    2004-12-01

    Full Text Available Adrenalin was used to investigate in vivo the circulation of the different stages of rodent Plasmodium present in the blood. A single dose of adrenalin injected to mice infected with P. yoelii resulted immediately in i a diminution of the parasitaemia of approximately 50 % in the peripheral large vessels (estimated in tail blood films, as well as in the capillaries (estimated in smears of blood collected from a fed Anopheles, and ii an increased parasitaemia in blood collected by cardiac puncture from the right heart. The numbers of young stages of P. yoelii in the peripheral blood were initially somewhat reduced but, unexpectedly, midterm trophozoites were preferentially expelled from the peripheral blood into major organs like the heart. With P. vinckei, parasitaemia decreased only when midterm trophozoites predominated, and with P. chabaudi no effect was observed at any time. We propose that midterm trophozoites, by their increased surface area, as compared to rings, and their flexibility which contrasts with the rigid schizonts, are particularly susceptible to haemodynamic perturbations.

  7. Screening vaccine formulations for biological activity using fresh human whole blood.

    Science.gov (United States)

    Brookes, Roger H; Hakimi, Jalil; Ha, Yukyung; Aboutorabian, Sepideh; Ausar, Salvador F; Hasija, Manvi; Smith, Steven G; Todryk, Stephen M; Dockrell, Hazel M; Rahman, Nausheen

    2014-01-01

    Understanding the relevant biological activity of any pharmaceutical formulation destined for human use is crucial. For vaccine-based formulations, activity must reflect the expected immune response, while for non-vaccine therapeutic agents, such as monoclonal antibodies, a lack of immune response to the formulation is desired. During early formulation development, various biochemical and biophysical characteristics can be monitored in a high-throughput screening (HTS) format. However, it remains impractical and arguably unethical to screen samples in this way for immunological functionality in animal models. Furthermore, data for immunological functionality lag formulation design by months, making it cumbersome to relate back to formulations in real-time. It is also likely that animal testing may not accurately reflect the response in humans. For a more effective formulation screen, a human whole blood (hWB) approach can be used to assess immunological functionality. The functional activity relates directly to the human immune response to a complete formulation (adjuvant/antigen) and includes adjuvant response, antigen response, adjuvant-modulated antigen response, stability, and potentially safety. The following commentary discusses the hWB approach as a valuable new tool to de-risk manufacture, formulation design, and clinical progression. PMID:24401565

  8. Malaria vaccine candidate antigen targeting the pre-erythrocytic stage of Plasmodium falciparum produced at high level in plants.

    Science.gov (United States)

    Voepel, Nadja; Boes, Alexander; Edgue, Güven; Beiss, Veronique; Kapelski, Stephanie; Reimann, Andreas; Schillberg, Stefan; Pradel, Gabriele; Fendel, Rolf; Scheuermayer, Matthias; Spiegel, Holger; Fischer, Rainer

    2014-11-01

    Plants have emerged as low-cost production platforms suitable for vaccines targeting poverty-related diseases. Besides functional efficacy, the stability, yield, and purification process determine the production costs of a vaccine and thereby the feasibility of plant-based production. We describe high-level plant production and functional characterization of a malaria vaccine candidate targeting the pre-erythrocytic stage of Plasmodium falciparum. CCT, a fusion protein composed of three sporozoite antigens (P. falciparum cell traversal protein for ookinetes and sporozoites [PfCelTOS], P. falciparum circumsporozoite protein [PfCSP], and P. falciparum thrombospondin-related adhesive protein [PfTRAP]), was transiently expressed by agroinfiltration in Nicotiana benthamiana leaves, accumulated to levels up to 2 mg/g fresh leaf weight (FLW), was thermostable up to 80°C and could be purified to >95% using a simple two-step procedure. Reactivity of sera from malaria semi-immune donors indicated the immunogenic conformation of the purified fusion protein consisting of PfCelTOS, PfCSP_TSR, PfTRAP_TSR domains (CCT) protein. Total IgG from the CCT-specific mouse immune sera specifically recognized P. falciparum sporozoites in immunofluorescence assays and induced up to 35% inhibition in hepatocyte invasion assays. Featuring domains from three promising sporozoite antigens with different roles (attachment and cell traversal) in the hepatocyte invasion process, CCT has the potential to elicit broader immune responses against the pre-erythrocytic stage of P. falciparum and represents an interesting new candidate, also as a component of multi-stage, multi-subunit malaria vaccine cocktails. PMID:25200253

  9. 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.

  10. In vitro cytokine induction by TLR-activating vaccine adjuvants in human blood varies by age and adjuvant.

    Science.gov (United States)

    van Haren, Simon D; Ganapathi, Lakshmi; Bergelson, Ilana; Dowling, David J; Banks, Michaela; Samuels, Ronald C; Reed, Steven G; Marshall, Jason D; Levy, Ofer

    2016-07-01

    Most infections occur in early life, prompting development of novel adjuvanted vaccines to protect newborns and infants. Several Toll-like receptor (TLR) agonists (TLRAs) are components of licensed vaccine formulations or are in development as candidate adjuvants. However, the type and magnitude of immune responses to TLRAs may vary with the TLR activated as well as age and geographic location. Most notably, in newborns, as compared to adults, the immune response to TLRAs is polarized with lower Th1 cytokine production and robust Th2 and anti-inflammatory cytokine production. The ontogeny of TLR-mediated cytokine responses in international cohorts has been reported, but no study has compared cytokine responses to TLRAs between U.S. neonates and infants at the age of 6months. Both are critical age groups for the currently pediatric vaccine schedule. In this study, we report quantitative differences in the production of a panel of 14 cytokines and chemokines after in vitro stimulation of newborn cord blood and infant and adult peripheral blood with agonists of TLR4, including monophosphoryl lipid A (MPLA) and glucopyranosyl lipid Adjuvant aqueous formulation (GLA-AF), as well as agonists of TLR7/8 (R848) and TLR9 (CpG). Both TLR4 agonists, MPLA and GLA-AF, induced greater concentrations of Th1 cytokines CXCL10, TNF and Interleukin (IL)-12p70 in infant and adult blood compared to newborn blood. All the tested TLRAs induced greater infant IFN-α2 production compared to newborn and adult blood. In contrast, CpG induced greater IFN-γ, IL-1β, IL-4, IL-12p40, IL-10 and CXCL8 in newborn than in infant and adult blood. Overall, to the extent that these in vitro studies mirror responses in vivo, our study demonstrates distinct age-specific effects of TLRAs that may inform their development as candidate adjuvants for early life vaccines. PMID:27081760

  11. 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

  12. Blood Flow and Glucose Metabolism in Stage IV Breast Cancer: Heterogeneity of Response During Chemotherapy

    OpenAIRE

    Krak, Nanda; Hoeven, John; Hoekstra, Otto; Twisk, Jos; Wall, Ernst; Lammertsma, A. A.

    2008-01-01

    textabstractObjective: The purpose of the study was to compare early changes in blood flow (BF) and glucose metabolism (MRglu) in metastatic breast cancer lesions of patients treated with chemotherapy. Methods: Eleven women with stage IV cancer and lesions in breast, lymph nodes, liver, and bone were scanned before treatment and after the first course of chemotherapy. BF, distribution volume of water (Vd), MRglu/BF ratio, MRgluand its corresponding rate constants K1and k3were compared per tum...

  13. Ontology-based Malaria Parasite Stage and Species Identification from Peripheral Blood Smear Images

    OpenAIRE

    Makkapati, V.; Rao, R

    2011-01-01

    The diagnosis and treatment of malaria infection requires detectingthe presence of malaria parasite in the patient as well as identification of the parasite species. We present an image processing-basedapproach to detect parasites in microscope images of blood smear andan ontology-based classification of the stage of the parasite for identifying the species of infection. This approach is patterned after the diagnosis approach adopted by a pathologist for visual examination and hence is expect...

  14. 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.

  15. 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...

  16. The safety and immunogenicity of trivalent inactivated influenza vaccination: a study of maternal-cord blood pairs in Taiwan.

    Directory of Open Access Journals (Sweden)

    Shin-Yu Lin

    Full Text Available BACKGROUND: There are little data about adverse effects and immunogenicity of flu vaccine in Asian pregnant women. METHODS: This prospective trial (NCT01514708 enrolled 46 pregnant women who received a single intramuscular dose of trivalent flu vaccine (AdimFlu-S® containing 15 mcg of hemagglutinin for each strain/0.5 mL from influenza A (H1N1, influenza A (H3N2, and influenza B after the first trimester. Blood samples were collected at day 0 and 28 after vaccination, and at delivery. Cord blood was also collected. Hemagglutination inhibition (HAI assays were performed to determine seroprotection and seroconversion rates and fold increase in the HAI geometric mean titer (GMT. RESULTS: Twenty-eight days after vaccination the seroprotection rate against H1N1, H3N2, and influenza B was 91.3%, 84.8% and 56.5%, respectively. The GMT fold increase was 12.8, 8.4, and 4.6 for H1N1, H3N2, and influenza B, respectively. At delivery, both the seroprotection rate (86.4%, 68.2%, and 47.7% and GMT fold increase (9.4, 5.7 and 3.8 were slightly lower than day 28. The seroprotection rate and GMT fold increase in maternal and cord blood samples were comparable. No significant adverse effects were detected. CONCLUSIONS: Trivalent flu vaccine induces a strong immune response in pregnant women and their infants without adverse effects. TRIAL REGISTRATION: Clinical Trials. gov NCT01514708.

  17. The malaria candidate vaccine liver stage antigen-3 is highly conserved in Plasmodium falciparum isolates from diverse geographical areas

    Directory of Open Access Journals (Sweden)

    Druilhe Pierre

    2009-10-01

    Full Text Available Abstract Background A high level of genetic stability has been formerly identified in segments of the gene coding for the liver stage antigen-3 (LSA-3, a subunit vaccine candidate against Plasmodium falciparum. The exploration of lsa-3 polymorphisms was extended to the whole sequence of this large antigen in 20 clinical isolates from four geographical areas; Senegal, Comoro islands, Brazil and Thailand. Methods The whole 4680 bp genomic sequence of lsa-3 was amplified by polymerase chain reaction and sequenced. The clinical isolate sequences were aligned on the sequence of the laboratory reference P. falciparum strain 3D7. Results The non-repeated sequence of lsa-3 was very well conserved with only a few allelic variations scattered along the sequence. Interestingly, a formerly identified immunodominant region, employed for the majority of pre-clinical vaccine development, was totally conserved at the genetic level. The most significant variations observed were in the number and organization of tetrapeptide repeated units, but not in their composition, resulting in different lengths of these repeated regions. The shorter repeated regions were from Brazilian origin. A correlation between the geographical distribution of the parasites with single nucleotide polymorphisms was not detected. Conclusion The lack of correlation between allelic polymorphisms with a specific transmission pressure suggests that LSA-3 is a structurally constrained molecule. The unusual characteristics of the lsa-3 gene make the molecule an interesting candidate for a subunit vaccine against malaria.

  18. HBV vaccination of HCV-infected patients with occult HBV infection and anti-HBc-positive blood donors

    Directory of Open Access Journals (Sweden)

    J.S.F. Pereira

    2006-04-01

    Full Text Available Anti-HBc positivity is a frequent cause of donation rejection at blood banks. Hepatitis B virus (HBV infection may also occur in HBsAg-negative patients, a situation denoted occult infection. Similarly, very low levels of HBV-DNA have also been found in the sera of patients with chronic hepatitis C virus (HCV infection, even in the absence of serum HBsAg. Initially we searched for HBV-DNA in serum of 100 blood donors and 50 HCV-infected patients who were HBsAg negative/anti-HBc positive by nested-PCR and by an HBV monitor commercial test for HBV-DNA. Anti-HBs seroconversion rates were measured in 100 blood donors and in 22 patients with chronic HCV infection after HBV vaccination to determine if the HBV vaccination could eliminate an occult HBV infection in these individuals. Occult HBV infection was detected in proportionally fewer blood donors (6/100 = 6% than chronic hepatitis C patients (12/50 = 24% (P 0.05. All subjects who were HBV-DNA(+ before the first dose of HBV vaccine (D1, became HBV-DNA(- after D1, D2, and D3. Among 22 HCV-positive patients, 10 HBV-DNA(+ and 12 HBV-DNA(-, seroconversion was observed in 9/10 (90% HBV-DNA(+ and in 9/12 (75% HBV-DNA(- subjects (P > 0.05. The disappearance of HBV-DNA in the majority of vaccinated patients suggests that residual HBV can be eliminated in patients with occult infection.

  19. 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.

  20. Defining antigen-specific plasmablast and memory B cell subsets in human blood after viral infection or vaccination.

    Science.gov (United States)

    Ellebedy, Ali H; Jackson, Katherine J L; Kissick, Haydn T; Nakaya, Helder I; Davis, Carl W; Roskin, Krishna M; McElroy, Anita K; Oshansky, Christine M; Elbein, Rivka; Thomas, Shine; Lyon, George M; Spiropoulou, Christina F; Mehta, Aneesh K; Thomas, Paul G; Boyd, Scott D; Ahmed, Rafi

    2016-10-01

    Antigen-specific B cells bifurcate into antibody-secreting cells (ASCs) and memory B cells (MBCs) after infection or vaccination. ASCs (plasmablasts) have been extensively studied in humans, but less is known about B cells that become activated but do not differentiate into plasmablasts. Here we have defined the phenotype and transcriptional program of a subset of antigen-specific B cells, which we have called 'activated B cells' (ABCs), that were distinct from ASCs and were committed to the MBC lineage. We detected ABCs in humans after infection with Ebola virus or influenza virus and also after vaccination. By simultaneously analyzing antigen-specific ASCs and ABCs in human blood after vaccination against influenza virus, we investigated the clonal overlap and extent of somatic hypermutation (SHM) in the ASC (effector) and ABC (memory) lineages. Longitudinal tracking of vaccination-induced hemagglutinin (HA)-specific clones revealed no overall increase in SHM over time, which suggested that repeated annual immunization might have limitations in enhancing the quality of influenza-virus-specific antibody. PMID:27525369

  1. Secretion of protective antigens by tissue-stage nematode larvae revealed by proteomic analysis and vaccination-induced sterile immunity.

    Science.gov (United States)

    Hewitson, James P; Ivens, Al C; Harcus, Yvonne; Filbey, Kara J; McSorley, Henry J; Murray, Janice; Bridgett, Stephen; Ashford, David; Dowle, Adam A; Maizels, Rick M

    2013-08-01

    Gastrointestinal nematode parasites infect over 1 billion humans, with little evidence for generation of sterilising immunity. These helminths are highly adapted to their mammalian host, following a developmental program through successive niches, while effectively down-modulating host immune responsiveness. Larvae of Heligmosomoides polygyrus, for example, encyst in the intestinal submucosa, before emerging as adult worms into the duodenal lumen. Adults release immunomodulatory excretory-secretory (ES) products, but mice immunised with adult H. polygyrus ES become fully immune to challenge infection. ES products of the intestinal wall 4th stage (L4) larvae are similarly important in host-parasite interactions, as they readily generate sterile immunity against infection, while released material from the egg stage is ineffective. Proteomic analyses of L4 ES identifies protective antigen targets as well as potential tissue-phase immunomodulatory molecules, using as comparators the adult ES proteome and a profile of H. polygyrus egg-released material. While 135 proteins are shared between L4 and adult ES, 72 are L4 ES-specific; L4-specific proteins correspond to those whose transcription is restricted to larval stages, while shared proteins are generally transcribed by all life cycle forms. Two protein families are more heavily represented in the L4 secretome, the Sushi domain, associated with complement regulation, and the ShK/SXC domain related to a toxin interfering with T cell signalling. Both adult and L4 ES contain extensive but distinct arrays of Venom allergen/Ancylostoma secreted protein-Like (VAL) members, with acetylcholinesterases (ACEs) and apyrase APY-3 particularly abundant in L4 ES. Serum antibodies from mice vaccinated with L4 and adult ES react strongly to the VAL-1 protein and to ACE-1, indicating that these two antigens represent major vaccine targets for this intestinal nematode. We have thus defined an extensive and novel repertoire of H

  2. Secretion of protective antigens by tissue-stage nematode larvae revealed by proteomic analysis and vaccination-induced sterile immunity.

    Directory of Open Access Journals (Sweden)

    James P Hewitson

    2013-08-01

    Full Text Available Gastrointestinal nematode parasites infect over 1 billion humans, with little evidence for generation of sterilising immunity. These helminths are highly adapted to their mammalian host, following a developmental program through successive niches, while effectively down-modulating host immune responsiveness. Larvae of Heligmosomoides polygyrus, for example, encyst in the intestinal submucosa, before emerging as adult worms into the duodenal lumen. Adults release immunomodulatory excretory-secretory (ES products, but mice immunised with adult H. polygyrus ES become fully immune to challenge infection. ES products of the intestinal wall 4th stage (L4 larvae are similarly important in host-parasite interactions, as they readily generate sterile immunity against infection, while released material from the egg stage is ineffective. Proteomic analyses of L4 ES identifies protective antigen targets as well as potential tissue-phase immunomodulatory molecules, using as comparators the adult ES proteome and a profile of H. polygyrus egg-released material. While 135 proteins are shared between L4 and adult ES, 72 are L4 ES-specific; L4-specific proteins correspond to those whose transcription is restricted to larval stages, while shared proteins are generally transcribed by all life cycle forms. Two protein families are more heavily represented in the L4 secretome, the Sushi domain, associated with complement regulation, and the ShK/SXC domain related to a toxin interfering with T cell signalling. Both adult and L4 ES contain extensive but distinct arrays of Venom allergen/Ancylostoma secreted protein-Like (VAL members, with acetylcholinesterases (ACEs and apyrase APY-3 particularly abundant in L4 ES. Serum antibodies from mice vaccinated with L4 and adult ES react strongly to the VAL-1 protein and to ACE-1, indicating that these two antigens represent major vaccine targets for this intestinal nematode. We have thus defined an extensive and novel

  3. Secretion of protective antigens by tissue-stage nematode larvae revealed by proteomic analysis and vaccination-induced sterile immunity.

    Science.gov (United States)

    Hewitson, James P; Ivens, Al C; Harcus, Yvonne; Filbey, Kara J; McSorley, Henry J; Murray, Janice; Bridgett, Stephen; Ashford, David; Dowle, Adam A; Maizels, Rick M

    2013-08-01

    Gastrointestinal nematode parasites infect over 1 billion humans, with little evidence for generation of sterilising immunity. These helminths are highly adapted to their mammalian host, following a developmental program through successive niches, while effectively down-modulating host immune responsiveness. Larvae of Heligmosomoides polygyrus, for example, encyst in the intestinal submucosa, before emerging as adult worms into the duodenal lumen. Adults release immunomodulatory excretory-secretory (ES) products, but mice immunised with adult H. polygyrus ES become fully immune to challenge infection. ES products of the intestinal wall 4th stage (L4) larvae are similarly important in host-parasite interactions, as they readily generate sterile immunity against infection, while released material from the egg stage is ineffective. Proteomic analyses of L4 ES identifies protective antigen targets as well as potential tissue-phase immunomodulatory molecules, using as comparators the adult ES proteome and a profile of H. polygyrus egg-released material. While 135 proteins are shared between L4 and adult ES, 72 are L4 ES-specific; L4-specific proteins correspond to those whose transcription is restricted to larval stages, while shared proteins are generally transcribed by all life cycle forms. Two protein families are more heavily represented in the L4 secretome, the Sushi domain, associated with complement regulation, and the ShK/SXC domain related to a toxin interfering with T cell signalling. Both adult and L4 ES contain extensive but distinct arrays of Venom allergen/Ancylostoma secreted protein-Like (VAL) members, with acetylcholinesterases (ACEs) and apyrase APY-3 particularly abundant in L4 ES. Serum antibodies from mice vaccinated with L4 and adult ES react strongly to the VAL-1 protein and to ACE-1, indicating that these two antigens represent major vaccine targets for this intestinal nematode. We have thus defined an extensive and novel repertoire of H

  4. Comparative recognition by human IgG antibodies of recombinant proteins representing three asexual erythrocytic stage vaccine candidates of Plasmodium vivax

    Directory of Open Access Journals (Sweden)

    Mayara B Barbedo

    2007-06-01

    Full Text Available In previous immuno-epidemiological studies of the naturally acquired antibody responses to merozoite surface protein-1 (MSP-1 of Plasmodium vivax, we had evidence that the responses to distinct erythrocytic stage antigens could be differentially regulated. The present study was designed to compare the antibody response to three asexual erythrocytic stage antigens vaccine candidates of P. vivax. Recombinant proteins representing the 19 kDa C-terminal region of MSP-1(PvMSP19, apical membrane antigen n-1 ectodomain (PvAMA-1, and the region II of duffy binding protein (PvDBP-RII were compared in their ability to bind to IgG antibodies of serum samples collected from 220 individuals from the state of Pará, in the North of Brazil. During patent infection with P. vivax, the frequency of individuals with IgG antibodies to PvMSP1(19, PvAMA-1, and PvDBP-RII were 95, 72.7, and 44.5% respectively. Although the frequency of responders to PvDBP-RII was lower, this frequency increased in individuals following multiple malarial infections. Individually, the specific antibody levels did not decline significantly nine months after treatment, except to PvMSP1(19. Our results further confirm a complex regulation of the immune response to distinct blood stage antigens. The reason for that is presently unknown but it may contribute to the high risk of re-infection in individuals living in the endemic areas.

  5. Red blood cell abnormalities and the pathogenesis of anemia in end-stage renal disease.

    Science.gov (United States)

    Georgatzakou, Hara T; Antonelou, Marianna H; Papassideri, Issidora S; Kriebardis, Anastasios G

    2016-08-01

    Anemia is the most common hematologic complication in end-stage renal disease (ESRD). It is ascribed to decreased erythropoietin production, shortened red blood cell (RBC) lifespan, and inflammation. Uremic toxins severely affect RBC lifespan; however, the implicated molecular pathways are poorly understood. Moreover, current management of anemia in ESRD is controversial due to the "anemia paradox" phenomenon, which underlines the need for a more individualized approach to therapy. RBCs imprint the adverse effects of uremic, inflammatory, and oxidative stresses in a context of structural and functional deterioration that is associated with RBC removal signaling and morbidity risk. RBCs circulate in hostile plasma by raising elegant homeostatic defenses. Variability in primary defect, co-morbidity, and therapeutic approaches add complexity to the pathophysiological background of the anemic ESRD patient. Several blood components have been suggested as biomarkers of anemia-related morbidity and mortality risk in ESRD. However, a holistic view of blood cell and plasma modifications through integrated omics approaches and high-throughput studies might assist the development of new diagnostic tests and therapies that will target the underlying pathophysiologic processes of ESRD anemia. PMID:26948278

  6. 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

    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...

  7. Biochemical and Functional Analysis of Two Plasmodium falciparum Blood-Stage 6-Cys Proteins: P12 and P41

    OpenAIRE

    Tana Taechalertpaisarn; Cecile Crosnier; S Josefin Bartholdson; Hodder, Anthony N.; Jenny Thompson; Bustamante, Leyla Y.; Wilson, Danny W.; Sanders, Paul R.; Wright, Gavin J.; Rayner, Julian C.; Cowman, Alan F.; Gilson, Paul R.; Crabb, Brendan S

    2012-01-01

    The genomes of Plasmodium parasites that cause malaria in humans, other primates, birds, and rodents all encode multiple 6-cys proteins. Distinct 6-cys protein family members reside on the surface at each extracellular life cycle stage and those on the surface of liver infective and sexual stages have been shown to play important roles in hepatocyte growth and fertilization respectively. However, 6-cys proteins associated with the blood-stage forms of the parasite have no known function. Here...

  8. Screening vaccine formulations for biological activity using fresh human whole blood

    OpenAIRE

    Brookes, RH; Hakimi, J; Ha, Y; Aboutorabian, S; Ausar, SF; Hasija, M; Smith, SG; Todryk, SM; Dockrell, HM; Rahman, N

    2014-01-01

    Understanding the relevant biological activity of any pharmaceutical formulation destined for human use is crucial. For vaccine-based formulations, activity must reflect the expected immune response, while for non-vaccine therapeutic agents, such as monoclonal antibodies, a lack of immune response to the formulation is desired. During early formulation development, various biochemical and biophysical characteristics can be monitored in a high-throughput screening (HTS) format. However, it rem...

  9. Vaccine Therapy and Cyclophosphamide in Treating Patients With Stage II-III Breast or Stage II-IV Ovarian, Primary Peritoneal, or Fallopian Tube Cancer

    Science.gov (United States)

    2016-01-07

    Recurrent Breast Carcinoma; Recurrent Fallopian Tube Carcinoma; Recurrent Ovarian Carcinoma; Recurrent Primary Peritoneal Carcinoma; Stage IIA Breast Cancer; Stage IIA Fallopian Tube Cancer; Stage IIA Ovarian Cancer; Stage IIB Breast Cancer; Stage IIB Fallopian Tube Cancer; Stage IIB Ovarian Cancer; Stage IIC Fallopian Tube Cancer; Stage IIC Ovarian Cancer; Stage IIIA Breast Cancer; Stage IIIA Fallopian Tube Cancer; Stage IIIA Ovarian Cancer; Stage IIIA Primary Peritoneal Cancer; Stage IIIB Breast Cancer; Stage IIIB Fallopian Tube Cancer; Stage IIIB Ovarian Cancer; Stage IIIB Primary Peritoneal Cancer; Stage IIIC Breast Cancer; Stage IIIC Fallopian Tube Cancer; Stage IIIC Ovarian Cancer; Stage IIIC Primary Peritoneal Cancer; Stage IV Fallopian Tube Cancer; Stage IV Ovarian Cancer; Stage IV Primary Peritoneal Cancer

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

    Directory of Open Access Journals (Sweden)

    FLAVIA BOCHIS

    2013-12-01

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  12. Reversible host cell remodeling underpins deformability changes in malaria parasite sexual blood stages.

    Science.gov (United States)

    Dearnley, Megan; Chu, Trang; Zhang, Yao; Looker, Oliver; Huang, Changjin; Klonis, Nectarios; Yeoman, Jeff; Kenny, Shannon; Arora, Mohit; Osborne, James M; Chandramohanadas, Rajesh; Zhang, Sulin; Dixon, Matthew W A; Tilley, Leann

    2016-04-26

    The sexual blood stage of the human malaria parasite Plasmodium falciparum undergoes remarkable biophysical changes as it prepares for transmission to mosquitoes. During maturation, midstage gametocytes show low deformability and sequester in the bone marrow and spleen cords, thus avoiding clearance during passage through splenic sinuses. Mature gametocytes exhibit increased deformability and reappear in the peripheral circulation, allowing uptake by mosquitoes. Here we define the reversible changes in erythrocyte membrane organization that underpin this biomechanical transformation. Atomic force microscopy reveals that the length of the spectrin cross-members and the size of the skeletal meshwork increase in developing gametocytes, then decrease in mature-stage gametocytes. These changes are accompanied by relocation of actin from the erythrocyte membrane to the Maurer's clefts. Fluorescence recovery after photobleaching reveals reversible changes in the level of coupling between the membrane skeleton and the plasma membrane. Treatment of midstage gametocytes with cytochalasin D decreases the vertical coupling and increases their filterability. A computationally efficient coarse-grained model of the erythrocyte membrane reveals that restructuring and constraining the spectrin meshwork can fully account for the observed changes in deformability. PMID:27071094

  13. [PHENOTYPE OF PERIPHERAL BLOOD NEUTROPHILS IN THE INITIAL STAGE OF ENDOMETRIAL CANCER].

    Science.gov (United States)

    Abakumova, T V; Antoneeva, I I; Gening, T P; Dolgova, D R; Gening, S O

    2016-01-01

    We have examined peripheral blood neutrophils from 123 patients with primary endometrial cancer at stage Ia. Receptor system and the ability of neutrophils to form extracellular traps were assessed by fluorescence microscopy, the spontaneous production of cytokines IL-2, IFN-γ, g-CSF, matrix metalloproteinases-1,9,13 by the method of enzyme-linked immunosorbent assay, phagocytic activity, myeloperoxidase activity, the level of cationic proteis activity in NBT-test were evaluated by cytochemical methods, activity of neutrophils in the spontaneous NBT-test was used to evaluate the oxygen-dependent bactericidal action of neutrophils. The topology and the rigidity of the membrane of neutrophils were assessed by scanning probe microscopy. We have shown that the increase in the relative number of neutrophils lead to a change in their receptor system, aerobic and anaerobic cytotoxicity and ability to phagocytosis are enchanced while reducing NET-activity. We have observed a change in the secretory activity of neutrophils, which is characterized by increased level of MMP-1, possibly initiated by enhanced production of reactive oxygen species, by a reduction in the IL-2 level (inductor of cytotoxic activity) and a sharp increase in the level of the G-CSF. Architectonics of neutrophils in the case of endonetrial cancer at stage Ia is characterized by changing the shape and loss of grit. The rigidity of the cell membrane decreased. Changes in the morphology of neutrophils on the background of the continuing hyperactivity suggests that a state of balance between the immune system and the tumor is already in stage Ia endometrial cancer. PMID:27220248

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

    Directory of Open Access Journals (Sweden)

    Sunil M Kurian

    Full Text Available BACKGROUND: 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. METHODS: 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. FINDINGS: 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. CONCLUSIONS: 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.

  15. Proteomics Reveals that Proteins Expressed During the Early Stage of Bacillus anthracis Infection Are Potential Targets for the Development of Vaccines and Drugs

    Institute of Scientific and Technical Information of China (English)

    Chun-Ming Huang; Craig A. Elmets; De-chu C. Tang; Fuming Li; Nabiha Yusuf

    2004-01-01

    In this review, we advance a new concept in developing vaccines and/or drugs to target specific proteins expressed during the early stage of Bacillus anthracis (an thrax) infection and address existing challenges to this concept. Three proteins (immune inhibitor A, GPR-like spore protease, and alanine racemase) initially identified by proteomics in our laboratory were found to have differential expres sions during anthrax spore germination and early outgrowth. Other studies of different bacillus strains indicate that these three proteins are involved in either germination or cytotoxicity of spores, suggesting that they may serve as potential targets for the design of anti-anthrax vaccines and drugs.

  16. Bad Blood: The Tuskegee Syphilis Study and Legacy Recruitment for Experimental AIDS Vaccines

    Science.gov (United States)

    Hagen, Kimberly Sessions

    2005-01-01

    For African Americans, medical research often connotes exploitation and cruelty, making recruiting African Americans to participate in HIV vaccine trials particularly daunting. But infusing adult education principles into such efforts is both increasing African American participation and helping heal the legacy of the Tuskegee experiment.

  17. 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-a 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-a and IL-2. The regulatory subset of CD4 T cells, characterized by CD25(high) , was...

  18. 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) , was...

  19. Cerebral blood flow distribution and reactivity during the symptom-free stages of transient ischemic attacks

    International Nuclear Information System (INIS)

    Even during the symptom-free stages, patients with transient ischemic attacks (TIA) often show cerebral blood flow (CBF) disturbances. For evaluating the factors which cause these abnormalities, we studied CBF and CBF reactivity to acetazolamide (diamox) using a 99mTc-hexamethylpropyleneamine oxime (HMPAO) SPECT. The results from CBF-SPECT were compared with X-ray computed tomography (CT), cerebral arteriogram, clinical characteristics of TIA and cerebrovascular risk factors. The overall sensitivity rates in detecting the lesion were 68% in CBF-SPECT and 9% in CT. The size of the hypoperfused area tended to be wide in patients who had intracranial, severe stenotic or multiple arterial lesions on the ipsilateral side. No such relations were found between CBF and other examinations. Brain hypoperfusion was located in the subcortical region in eight patients; two patients showed a small hypodense lesion on CT which corresponded to the hypoperfusion on SPECT, and three patients showed no arteriographic abnormality. Hypoperfusion in the cortex was seen in seven patients; all patients showed arteriographic abnormality, but no CT abnormality. The severity rating of the vascular stenosis and hypoperfusion, and the incidence of the intracranial lesions were higher in this group than the group with subcortical hypoperfusion. Seven patients showed fixed normoperfusion before and after diamox injection. Two patients with a subcortical small infarction showed fixed hypoperfusion even after diamox injection. Twelve patients showed focal hypoperfusion before diamox with a new filling-in after diamox. Only one patient showed resting hypoperfusion and decreased CBF reactivity to diamox. The results suggest that most of the patients with a brain hypoperfusion in the symptom-free stages of TIAs have preserved cerebrovascular reactivity although a few patients show hypoperfusion having cerebral infarction or hemodynamically compromised tissue. (author)

  20. Characterization of the Duffy-Binding-Like Domain of Plasmodium falciparum Blood-Stage Antigen 332

    Directory of Open Access Journals (Sweden)

    Sandra Nilsson

    2011-01-01

    Full Text Available Studies on Pf332, a major Plasmodium falciparum blood-stage antigen, have largely been hampered by the cross-reactive nature of antibodies generated against the molecule due to its high content of repeats, which are present in other malaria antigens. We previously reported the identification of a conserved domain in Pf332 with a high degree of similarity to the Duffy-binding-like (DBL domains of the erythrocyte-binding-like (EBL family. We here describe that antibodies towards Pf332-DBL are induced after repeated exposure to P. falciparum and that they are acquired early in life in areas of intense malaria transmission. Furthermore, a homology model of Pf332-DBL was found to be similar to the structure of the EBL-DBLs. Despite their similarities, antibodies towards Pf332-DBL did not display any cross-reactivity with EBL-proteins as demonstrated by immunofluorescence microscopy, Western blotting, and peptide microarray. Thus the DBL domain is an attractive region to use in further studies on the giant Pf332 molecule.

  1. Mechanisms of protective immunity against asexual blood stages of Plasmodium falciparum in the experimental host Saimiri

    Directory of Open Access Journals (Sweden)

    J. Gysin

    1992-01-01

    Full Text Available In the Saimiri monkey, an experimental host for human malaria, acquired protection against Plasmodium falciparum blood stages depends on the IgG antibody populations developed. In vivo protective anti-falciparum activity of IgG antibodies is correlated with the in vivo opsonizing activity promoting phagocytosis of parasited red bloood cells. In contrast, non protective antibodies inhibit this mechanism by competing at the target level. A similar phenomenon can be and human infection. Anti-cytoadherent and anti-rosette antibodies developed by Saimiri and humans prevent the development of physiopathological events like cerebral malaria which can also occur in this experimental host. Furthermore, transfer to protective human anti-falciparum IgG antibodies into infected Saimiri monkeys exerts an anti parasite activity as efficient as that observed when it is transfered into acute falciparum malaria patients, making the Saimiri an even more attractive host. Studies on the role of immunocompetent cells in the protective immune reponse are still in their infancy, however the existance of a restricted polymorphism of MHC II class molecules in the Saimiri confers additional theoretical and practical importance to this model.

  2. 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. PMID:27262417

  3. Biochemical and functional analysis of two Plasmodium falciparum blood-stage 6-cys proteins: P12 and P41.

    Directory of Open Access Journals (Sweden)

    Tana Taechalertpaisarn

    Full Text Available The genomes of Plasmodium parasites that cause malaria in humans, other primates, birds, and rodents all encode multiple 6-cys proteins. Distinct 6-cys protein family members reside on the surface at each extracellular life cycle stage and those on the surface of liver infective and sexual stages have been shown to play important roles in hepatocyte growth and fertilization respectively. However, 6-cys proteins associated with the blood-stage forms of the parasite have no known function. Here we investigate the biochemical nature and function of two blood-stage 6-cys proteins in Plasmodium falciparum, the most pathogenic species to afflict humans. We show that native P12 and P41 form a stable heterodimer on the infective merozoite surface and are secreted following invasion, but could find no evidence that this complex mediates erythrocyte-receptor binding. That P12 and P41 do not appear to have a major role as adhesins to erythrocyte receptors was supported by the observation that antisera to these proteins did not substantially inhibit erythrocyte invasion. To investigate other functional roles for these proteins their genes were successfully disrupted in P. falciparum, however P12 and P41 knockout parasites grew at normal rates in vitro and displayed no other obvious phenotypic changes. It now appears likely that these blood-stage 6-cys proteins operate as a pair and play redundant roles either in erythrocyte invasion or in host-immune interactions.

  4. Factors Associated with Blood Culture Contamination in the Emergency Department: Critical Illness, End-Stage Renal Disease, and Old Age.

    Directory of Open Access Journals (Sweden)

    Chih-Jan Chang

    Full Text Available Blood culture contamination in emergency departments (ED that experience a high volume of patients has negative impacts on optimal patient care. It is therefore important to identify risk factors associated with blood culture contamination in EDs.A prospectively observational study in a university-affiliated hospital were conducted between August 2011 and December 2012. Positive monomicrobial and negative blood cultures drawn from adult patients in the ED were analyzed to evaluate the possible risk factors for contamination. A total of 1,148 positive monomicrobial cases, 391 contamination cases, and 13,689 cases of negative blood culture were identified. Compared to patients with negative blood cultures, patients in triage levels 1 and 2 (Incidence Rate Ratio, IRR = 2.24, patients with end-stage renal disease (ESRD (IRR = 2.05, and older patients (IRR: 1.02 per year were more likely to be associated with ED blood culture contamination.Critical patients (triage levels 1 and 2, ESRD patients, and older patients were more commonly associated with blood culture contamination in the ED. Further studies to evaluate whether the characteristics of skin commensals contribute to blood culture contamination is warranted, especially in hospitals populated with high-risk patients.

  5. Typhoid Vaccine in Testing Response to Immune Stress in Patients With Stage I-IIIA Breast Cancer Who Received Chemotherapy

    Science.gov (United States)

    2016-04-15

    Cognitive Side Effects of Cancer Therapy; Depression; Recurrent Breast Carcinoma; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer

  6. 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) (p<0.001) and 9.25 (5.77-15.72)-fold (p<0.001) in unfed males and unfed females, respectively. Comparing unfed nymphs to unfed adult ticks, the Hd86 expression levels decreased by 13.82 (5.39-24.45) (p=0.035) and 9.93 (2.87-22.08)-fold (p=0.038) in males and females respectively. Lower Hd86 mRNA levels in adult ticks should result in lower protein levels and thus less antibody-antigen interactions necessary for vaccine efficacy in ticks fed on vaccinated animals. Thus, the observed differences in Hd86 expression profile between immature and adult stages might explain, in part, the discrepancy of the Hd86 vaccine efficacy against these two life stages of H. scupense. PMID:24029714

  7. 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 (Ab); 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 DKCV

  8. 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 ......-inflammatory cytokines in serum of patients who achieved stable disease following vaccination suggest the occurrence of vaccine-induced Th1 responses. Since Th1 responses seem to be essential in cancer immunotherapy this may indicate a therapeutic potential of the vaccine....

  9. Can perfusion CT assessment of primary colorectal adenocarcinoma blood flow at staging predict for subsequent metastatic disease? A pilot study

    Energy Technology Data Exchange (ETDEWEB)

    Goh, Vicky [Mount Vernon Hospital, Paul Strickland Scanner Centre, Northwood (United Kingdom); Halligan, Steve [University College Hospital, Department of Academic Radiology, London (United Kingdom); Wellsted, David M. [University of Hertfordshire, Health Research and Development Support Unit, Hatfield (United Kingdom); Bartram, Clive I. [St Mark' s Hospital, Intestinal Imaging Centre, Harrow (United Kingdom)

    2009-01-15

    We aimed to determine whether perfusion CT measurements at colorectal cancer staging may predict for subsequent metastatic relapse. Fifty two prospective patients underwent perfusion CT at staging to estimate tumour blood flow, blood volume, mean transit time, and permeability surface area product. Patients considered metastasis free and suitable for surgery underwent curative resection subsequently. At final analysis, a median of 48.6 months post-surgery, patients were divided into those who remained disease free, and those with subsequent metastases. Vascular parameters for these two groups were compared using t-testing, and receiver operator curve analysis was performed to determine the sensitivity and specificity of these vascular parameters for predicting metastases. Thirty seven (71%) patients underwent curative surgery; data were available for 35: 26 (74%) remained disease free; 9 (26%) recurred (8 metastatic, 1 local). Tumour blood flow differed significantly between disease-free and metastatic patients (76.0 versus 45.7 ml/min/100 g tissue; p=0.008). With blood flow <64 ml/min/100 g tissue, sensitivity and specificity (95% CI) for development of metastases were 100% (60-100%) and 73% (53-87%), respectively. Our preliminary findings suggest that primary tumour blood flow might potentially be a useful predictor warranting further study. (orig.)

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

    OpenAIRE

    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.; Kelly Rausch; Joan Aebig; Kazutoyo Miura; Edwards, Nick J.; Ian D Poulton; Angela Hunt-Cooke; Porter, David W.

    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/II...

  11. Blood Culture (For Parents)

    Science.gov (United States)

    ... KidsHealth in the Classroom What Other Parents Are Reading Upsetting News Reports? What to Say Vaccines: Which ... BMP) Blood Test: Complete Blood Count Basic Blood Chemistry Tests Getting a Blood Test (Video) Blood Test: ...

  12. Bioreactors for high cell density and continuous multi-stage cultivations: options for process intensification in cell culture-based viral vaccine production.

    Science.gov (United States)

    Tapia, Felipe; Vázquez-Ramírez, Daniel; Genzel, Yvonne; Reichl, Udo

    2016-03-01

    With an increasing demand for efficacious, safe, and affordable vaccines for human and animal use, process intensification in cell culture-based viral vaccine production demands advanced process strategies to overcome the limitations of conventional batch cultivations. However, the use of fed-batch, perfusion, or continuous modes to drive processes at high cell density (HCD) and overextended operating times has so far been little explored in large-scale viral vaccine manufacturing. Also, possible reductions in cell-specific virus yields for HCD cultivations have been reported frequently. Taking into account that vaccine production is one of the most heavily regulated industries in the pharmaceutical sector with tough margins to meet, it is understandable that process intensification is being considered by both academia and industry as a next step toward more efficient viral vaccine production processes only recently. Compared to conventional batch processes, fed-batch and perfusion strategies could result in ten to a hundred times higher product yields. Both cultivation strategies can be implemented to achieve cell concentrations exceeding 10(7) cells/mL or even 10(8) cells/mL, while keeping low levels of metabolites that potentially inhibit cell growth and virus replication. The trend towards HCD processes is supported by development of GMP-compliant cultivation platforms, i.e., acoustic settlers, hollow fiber bioreactors, and hollow fiber-based perfusion systems including tangential flow filtration (TFF) or alternating tangential flow (ATF) technologies. In this review, these process modes are discussed in detail and compared with conventional batch processes based on productivity indicators such as space-time yield, cell concentration, and product titers. In addition, options for the production of viral vaccines in continuous multi-stage bioreactors such as two- and three-stage systems are addressed. While such systems have shown similar virus titers compared to

  13. Bioreactors for high cell density and continuous multi-stage cultivations: options for process intensification in cell culture-based viral vaccine production.

    Science.gov (United States)

    Tapia, Felipe; Vázquez-Ramírez, Daniel; Genzel, Yvonne; Reichl, Udo

    2016-03-01

    With an increasing demand for efficacious, safe, and affordable vaccines for human and animal use, process intensification in cell culture-based viral vaccine production demands advanced process strategies to overcome the limitations of conventional batch cultivations. However, the use of fed-batch, perfusion, or continuous modes to drive processes at high cell density (HCD) and overextended operating times has so far been little explored in large-scale viral vaccine manufacturing. Also, possible reductions in cell-specific virus yields for HCD cultivations have been reported frequently. Taking into account that vaccine production is one of the most heavily regulated industries in the pharmaceutical sector with tough margins to meet, it is understandable that process intensification is being considered by both academia and industry as a next step toward more efficient viral vaccine production processes only recently. Compared to conventional batch processes, fed-batch and perfusion strategies could result in ten to a hundred times higher product yields. Both cultivation strategies can be implemented to achieve cell concentrations exceeding 10(7) cells/mL or even 10(8) cells/mL, while keeping low levels of metabolites that potentially inhibit cell growth and virus replication. The trend towards HCD processes is supported by development of GMP-compliant cultivation platforms, i.e., acoustic settlers, hollow fiber bioreactors, and hollow fiber-based perfusion systems including tangential flow filtration (TFF) or alternating tangential flow (ATF) technologies. In this review, these process modes are discussed in detail and compared with conventional batch processes based on productivity indicators such as space-time yield, cell concentration, and product titers. In addition, options for the production of viral vaccines in continuous multi-stage bioreactors such as two- and three-stage systems are addressed. While such systems have shown similar virus titers compared to

  14. Effect of artificial colloids on blood coagulation during shock stage of severe burn injury

    Institute of Scientific and Technical Information of China (English)

    ZHOU Jian-jun; XING Nan; CHEN Jiong; SHI Jian-wu; SU Guo-liang

    2013-01-01

    Background There are controversies about the use of artificial colloids.This research was aimed to determine the effect of various artificial colloids on blood coagulation in the shock stage of severe burn injury.Methods Totally,18 female Ba-Ma mini-pigs were subjected to a 40% total body surface third-degree flame burn under anesthesia.Resuscitation therapy was applied 2 hours after the injury,using the burn shock fluid resuscitation formula commonly accepted in the surgical treatment of burns.The Ba-Ma mini-pigs were randomly assigned to three groups (six pigs in each group):succinylated gelatin group (the artificial colloid used was succinylated gelatin Injection),hydroxyethyl starch group (the artificial colloid used was hydroxyethyl starch (130/0.4)),and allogeneic plasma group (the colloid used was allogeneic plasma).Blood samples were collected from the animals prior to the burn injury and again at intervals of 4,8,24 and 48 hours post-injury.The platelet count (PLT),prothrombin time (PT),international normalized ratio (INR),activated partial thromboplastin time (APTT),and fibrinogen (Fib) were measured,followed by a statistical analysis of all results.Results The PLT of succinylated gelatin group and hydroxyethyl starch group at intervals of 24 and 48 hours were (124.3±52.7),(78.8±16.4)×109/L and (159.0±62.8),(87.3±32.0)×109/L respectively.But in the allogeneic plasma group at intervals of 8,24,and 48 hours were (234.3±52.6),(136.0±47.4),(75.8±31.0)×109/L.The decrease were all statistically significant (P <0.05,P <0.01) when compared to pre-burn ((383.3±77.9),(382.7±65.7),(381.0±49.4)×109/L).The PLT among the three groups,at all the time points,had no statistical difference (P >0.05).Compared to pre-burn ((10.8±0.9),(11.4±0.8),(10.6±0.7) seconds),the PT of succinylated gelatin group and hydroxyethyl starch group at 24 hours were (14.5±1.5) and (16.2±1.3) seconds,whereas in the allogeneic plasma group at 8 and 24 hours the PT were

  15. Recombinant peptide replicates immunogenicity of synthetic linear peptide chimera for use as pre-erythrocytic stage malaria vaccine

    OpenAIRE

    Silva-Flannery, Luciana M.; Cabrera-Mora, Monica; Jiang, Jianlin; Moreno, Alberto

    2008-01-01

    Synthetic linear peptide chimeras (LPCscys+) show promise as delivery platforms for malaria subunit vaccines. Maximal immune response to LPCscys+ in rodent malaria models depends upon formation of cross-linkages to generate homopolymers, presenting challenges for vaccine production. To replicate the immunogenicity of LPCscys+ using a recombinant approach, we designed a recombinant LPC (rLPC) based on Plasmodium yoelii circumsporozoite protein-specific sequences of 208 amino acids consisting o...

  16. Clinical Observation in 45 Cases of Hemorrhagic Apoplexy of the Acute Stage Treated by Promoting Blood Circulation and Removing Blood Stasis

    Institute of Scientific and Technical Information of China (English)

    孙国柱

    2003-01-01

    To explore the therapeutic effects of the method of promoting blood circulation and removing blood stasis on hemorrhagic apoplexy of acute stage, 45 cases were treated by the method and observed for their conscious state and motor function, which were compared with 40 cases treated with regular western drugs. The results showed that the effective rate in the treated group was 82.2% and that in control group 60% with a significant difference (P<0.05) between the two groups. In the treated group, the scores of the conscious state and the motor function after treatment were elevated dramatically (P<0.01), indicating a much better effect in the treated group than in the control group.

  17. Non-invasive assessment of pulmonary blood supply after staged repair of pulmonary atresia.

    OpenAIRE

    Del Torso, S.; Kelly, M J; Kalff, V; Stellin, G; Mee, R B; Venables, A W

    1985-01-01

    Radionuclide studies were performed to determine pulmonary blood flow in six children who had undergone surgery for pulmonary atresia, ventricular septal defect, and hypoplastic pulmonary arteries with or without major aortopulmonary collateral arteries. Lung blood flow was assessed from both particle perfusion lung scans and the pulmonary and systemic phase of a radionuclide dynamic flow study. Five patients had perfusion defects identified on the particle perfusion lung scan. In three of th...

  18. Early Rise of Blood T Follicular Helper Cell Subsets and Baseline Immunity as Predictors of Persisting Late Functional Antibody Responses to Vaccination in Humans

    Science.gov (United States)

    Borgogni, Erica; Zedda, Luisanna; Cantisani, Rocco; Chiappini, Nico; Schiavetti, Francesca; Rosa, Domenico; Castellino, Flora; Montomoli, Emanuele; Bodinham, Caroline L.; Lewis, David J.; Medini, Duccio; Bertholet, Sylvie; Del Giudice, Giuseppe

    2016-01-01

    CD4+ T follicular helper cells (TFH) have been identified as the T-cell subset specialized in providing help to B cells for optimal activation and production of high affinity antibody. We recently demonstrated that the expansion of peripheral blood influenza-specific CD4+IL-21+ICOS1+ T helper (TH) cells, three weeks after vaccination, associated with and predicted the rise of protective neutralizing antibodies to avian H5N1. In this study, healthy adults were vaccinated with plain seasonal trivalent inactivated influenza vaccine (TIIV), MF59®-adjuvanted TIIV (ATIIV), or saline placebo. Frequencies of circulating CD4+ TFH1 ICOS+ TFH cells and H1N1-specific CD4+IL-21+ICOS+ CXCR5+ TFH and CXCR5- TH cell subsets were determined at various time points after vaccination and were then correlated with hemagglutination inhibition (HI) titers. All three CD4+ T cell subsets expanded in response to TIIV and ATIIV, and peaked 7 days after vaccination. To demonstrate that these TFH cell subsets correlated with functional antibody titers, we defined an alternative endpoint metric, decorrelated HI (DHI), which removed any correlation between day 28/day 168 and day 0 HI titers, to control for the effect of preexisting immunity to influenza vaccine strains. The numbers of total circulating CD4+ TFH1 ICOS+ cells and of H1N1-specific CD4+IL-21+ICOS+ CXCR5+, measured at day 7, were significantly associated with day 28, and day 28 and 168 DHI titers, respectively. Altogether, our results show that CD4+ TFH subsets may represent valuable biomarkers of vaccine-induced long-term functional immunity. Trial Registration ClinicalTrials.gov NCT01771367 PMID:27336786

  19. Early Rise of Blood T Follicular Helper Cell Subsets and Baseline Immunity as Predictors of Persisting Late Functional Antibody Responses to Vaccination in Humans.

    Science.gov (United States)

    Spensieri, Fabiana; Siena, Emilio; Borgogni, Erica; Zedda, Luisanna; Cantisani, Rocco; Chiappini, Nico; Schiavetti, Francesca; Rosa, Domenico; Castellino, Flora; Montomoli, Emanuele; Bodinham, Caroline L; Lewis, David J; Medini, Duccio; Bertholet, Sylvie; Del Giudice, Giuseppe

    2016-01-01

    CD4+ T follicular helper cells (T(FH)) have been identified as the T-cell subset specialized in providing help to B cells for optimal activation and production of high affinity antibody. We recently demonstrated that the expansion of peripheral blood influenza-specific CD4(+)IL-21(+)ICOS1(+) T helper (T(H)) cells, three weeks after vaccination, associated with and predicted the rise of protective neutralizing antibodies to avian H5N1. In this study, healthy adults were vaccinated with plain seasonal trivalent inactivated influenza vaccine (TIIV), MF59(®)-adjuvanted TIIV (ATIIV), or saline placebo. Frequencies of circulating CD4(+) T(FH)1 ICOS(+) T(FH) cells and H1N1-specific CD4(+-)IL-21(+)ICOS(+) CXCR5(+) T(FH) and CXCR5(-) T(H) cell subsets were determined at various time points after vaccination and were then correlated with hemagglutination inhibition (HI) titers. All three CD4(+) T cell subsets expanded in response to TIIV and ATIIV, and peaked 7 days after vaccination. To demonstrate that these T(FH) cell subsets correlated with functional antibody titers, we defined an alternative endpoint metric, decorrelated HI (DHI), which removed any correlation between day 28/day 168 and day 0 HI titers, to control for the effect of preexisting immunity to influenza vaccine strains. The numbers of total circulating CD4(+)T(FH)1 ICOS(+) cells and of H1N1-specific CD4(+)IL-21(+)ICOS(+) CXCR5(+), measured at day 7, were significantly associated with day 28, and day 28 and 168 DHI titers, respectively. Altogether, our results show that CD4(+) T(FH) subsets may represent valuable biomarkers of vaccine-induced long-term functional immunity. PMID:27336786

  20. Laser Doppler microscopy of blood flows in fish embryos at different stages of ontogenesis

    Science.gov (United States)

    Savchenko, Natalia B.; Priezzhev, Alexander V.; Levenko, Borislav A.

    1995-02-01

    Laser Doppler microscopy is an efficient method of in vivo measurements of flow velocities in different biological objects. It is based on the registration of frequency shifts in light quasielastically scattered from particles moving in the flows. To study the embryonic development of the cardiac-vascular system in embryos of warm water fishes, embryos of Macropodus opercularis have been used. Doppler spectra from pulsatile blood flows in selected vessels and their changes in the process of ontogenesis have been registered. The recording of the successive spectra and their computer processing yield the varying dynamics of blood flows. Typical age dependencies of velocity patterns in the embryos are presented.

  1. Autologous peripheral blood stem cell transplantation in tumor-stage mycosis fungoides: predictors of disease-free survival.

    Science.gov (United States)

    Russell-Jones, R; Child, F; Olavarria, E; Whittaker, S; Spittle, M; Apperley, J

    2001-09-01

    Nine patients with mycosis fungoides (age range 27-67) underwent autologous peripheral blood stem cell transplantation (PBSCT). All patients had tumor-stage disease, and four had lymph node involvement. Eight patients exhibited a peripheral blood T cell clone using PCR/SSCP analysis of the TCR gamma gene, six prior to harvest and two at the time of harvest. Mobilization of CD34+ stem cells was achieved with etoposide and G-CSF. Harvested cells were positively selected for CD34. After negative selection for CD4 and CD8, only two samples became PCR negative. Conditioning prior to reinfusion of stem cells was achieved with various combinations of total skin electron beam (TSEB), total body irradiation (TBI), and chemotherapy, depending upon the patient's prior exposure to radiotherapy. One patient failed to engraft and died of candidal septicemia 15 days posttransplant. The other eight patients achieved complete remission, but this was short-lived in four (median disease-free survival [DFS] = 2 months) and prolonged in three (median DFS 11 months). Those with a short DFS were distinguished by rapid tumor onset prior to transplant but not by stage at transplant. Loss of a detectable T cell clone after manipulation of the harvest did not discriminate between the two groups, but rapid relapsers had been subjected to a greater degree of T cell depletion, possibly indicating a compromised cytotoxic response post-PBSCT. The median survival of the cohort is four years from tumor onset, 15 months from PBSCT, and 27 months from the date a peripheral blood clone was first detected in the presence of tumor-stage disease. Rapid relapse was associated with poor overall survival. Our data demonstrate the value of PBSCT for inducing remission in tumor-stage mycosis fungoides. Reinfusion of neoplastic cells could be avoided by harvesting stem cells at an earlier stage in the disease process, preferably before a T cell clone is detectable in the peripheral blood. Alternatively T cell

  2. Interruption of the blood-stage cycle of the malaria parasite, Plasmodium chabaudi, by protein tyrosine kinase inhibitors

    Directory of Open Access Journals (Sweden)

    M.L. Gazarini

    2003-11-01

    Full Text Available Malaria is a devastating disease caused by a unicellular protozoan, Plasmodium, which affects 3.7 million people every year. Resistance of the parasite to classical treatments such as chloroquine requires the development of new drugs. To gain insight into the mechanisms that control Plasmodium cell cycle, we have examined the effects of kinase inhibitors on the blood-stage cycle of the rodent malaria parasite, Plasmodium chabaudi. In vitro incubation of red blood cells for 17 h at 37ºC with the inhibitors led to a decrease in the percent of infected cells, compared to control treatment, as follows: genistein (200 µM - 75%, staurosporine (1 µM - 58%, R03 (1 µM - 75%, and tyrphostins B44 (100 µM - 66% and B46 (100 µM - 68%. All these treatments were shown to retard or prevent maturation of the intraerythrocytic parasites. The diverse concentration ranges at which these inhibitors exert their effects give a clue as to the types of signals that initiate the transitions between the different developmental stages of the parasite. The present data support our hypothesis that the maturation of the intraerythrocytic cycle of malaria parasites requires phosphorylation. In this respect, we have recently reported a high Ca2+ microenvironment surrounding the parasite within red blood cells. Several kinase activities are modulated by Ca2+. The molecular identification of the targets of these kinases could provide new strategies against malaria.

  3. In Vitro Activities of Primaquine-Schizonticide Combinations on Asexual Blood Stages and Gametocytes of Plasmodium falciparum.

    Science.gov (United States)

    Cabrera, Mynthia; Cui, Liwang

    2015-12-01

    Currently, the World Health Organization recommends addition of a 0.25-mg base/kg single dose of primaquine (PQ) to artemisinin combination therapies (ACTs) for Plasmodium falciparum malaria as a gametocytocidal agent for reducing transmission. Here, we investigated the potential interactions of PQ with the long-lasting components of the ACT drugs for eliminating the asexual blood stages and gametocytes of in vitro-cultured P. falciparum strains. Using the SYBR green I assay for asexual parasites and a flow cytometry-based assay for gametocytes, we determined the interactions of PQ with the schizonticides chloroquine, mefloquine, piperaquine, lumefantrine, and naphthoquine. With the sums of fractional inhibitory concentrations and isobolograms, we were able to determine mostly synergistic interactions for the various PQ and schizonticide combinations on the blood stages of P. falciparum laboratory strains. The synergism in inhibiting asexual stages and gametocytes was highly evident with PQ-naphthoquine, whereas synergism was moderate for the PQ-piperaquine, PQ-chloroquine, and PQ-mefloquine combinations. We have detected potentially antagonistic interactions between PQ and lumefantrine under certain drug combination ratios, suggesting that precautions might be needed when PQ is added as the gametocytocide to the artemether-lumefantrine ACT (Coartem). PMID:26416869

  4. Ontology-based Malaria Parasite Stage and Species Identification from Peripheral Blood Smear Images

    NARCIS (Netherlands)

    Makkapati, V.; Rao, R.

    2011-01-01

    The diagnosis and treatment of malaria infection requires detectingthe presence of malaria parasite in the patient as well as identification of the parasite species. We present an image processing-basedapproach to detect parasites in microscope images of blood smear andan ontology-based classificati

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

    DEFF Research Database (Denmark)

    Elung-Jensen, Thomas; Strandgaard, Svend; 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...

  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

    /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...

  7. Critical stages of extracting DNA from Aspergillus fumigatus in whole-blood specimens.

    NARCIS (Netherlands)

    White, P.L.; Perry, M.D.; Loeffler, J.; Melchers, W.J.G.; Klingspor, L.; Bretagne, S.; McCulloch, E.; Cuenca-Estrella, M.; Finnstrom, N.; Donnelly, J.P.; Barnes, R.A.

    2010-01-01

    A standardized protocol for extracting DNA from Aspergillus fumigatus has been proposed by the European Aspergillus PCR Initiative (EAPCRI). Using meta-regression analysis, the EAPCRI showed certain stages of the process to be critical to providing a satisfactory analytical sensitivity. The study in

  8. 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

    Rainbow trout fry of average weight 0.5 g were vaccinated against viral haemorrhagic septicaemia (VHS) by intramuscular injection of 1 mug of plasmid DNA encoding the VHS virus glycoprotein gene. Challenge with a lethal dose of virus at two different time points, 9 and 71 days post...

  9. Nitric oxide-mediated vasodilation increases blood flow during the early stages of stress fracture healing.

    Science.gov (United States)

    Tomlinson, Ryan E; Shoghi, Kooresh I; Silva, Matthew J

    2014-02-15

    Despite the strong connection between angiogenesis and osteogenesis in skeletal repair conditions such as fracture and distraction osteogenesis, little is known about the vascular requirements for bone formation after repetitive mechanical loading. Here, established protocols of damaging (stress fracture) and nondamaging (physiological) forelimb loading in the adult rat were used to stimulate either woven or lamellar bone formation, respectively. Positron emission tomography was used to evaluate blood flow and fluoride kinetics at the site of bone formation. In the group that received damaging mechanical loading leading to woven bone formation (WBF), (15)O water (blood) flow rate was significantly increased on day 0 and remained elevated 14 days after loading, whereas (18)F fluoride uptake peaked 7 days after loading. In the group that received nondamaging mechanical loading leading to lamellar bone formation (LBF), (15)O water and (18)F fluoride flow rates in loaded limbs were not significantly different from nonloaded limbs at any time point. The early increase in blood flow rate after WBF loading was associated with local vasodilation. In addition, Nos2 expression in mast cells was increased in WBF-, but not LBF-, loaded limbs. The nitric oxide (NO) synthase inhibitor N(ω)-nitro-l-arginine methyl ester was used to suppress NO generation, resulting in significant decreases in early blood flow rate and bone formation after WBF loading. These results demonstrate that NO-mediated vasodilation is a key feature of the normal response to stress fracture and precedes woven bone formation. Therefore, patients with impaired vascular function may heal stress fractures more slowly than expected. PMID:24356518

  10. Effects of nadolol on blood pressure, sleep efficiency, and sleep stages.

    Science.gov (United States)

    Kales, A; Bixler, E O; Vela-Bueno, A; Cadieux, R J; Manfredi, R L; Bitzer, S; Kantner, T

    1988-06-01

    The effects of nadolol (20 and 80 mg) on blood pressure and sleep parameters were assessed in six patients with mild hypertension. A 32-night experimental protocol in the sleep laboratory was instituted consisting of four placebo-baseline nights followed by 4 weeks of drug administration. Both doses of nadolol had a clear-cut and consistent lowering effect on blood pressure throughout the night and during the day, with a greater reduction noted with the 80 mg dose. In fact, blood pressure values were reduced to normotensive levels. Neither dose had a disrupting effect on sleep, whereas the 80 mg dose improved sleep efficiency and also had a rapid eye movement-enhancing effect. This absence of sleep-disrupting effects is attributed to nadolol's low level of lipophilicity and lack of intrinsic sympathomimetic activity. The clinical significance of the lack of sleep disruption and possible improvement of sleep with nadolol is discussed in light of the well-recognized sleep disturbances produced by other beta-blockers. PMID:3378387

  11. Plasmodium vivax merozoite surface protein-3 (PvMSP3: expression of an 11 member multigene family in blood-stage parasites.

    Directory of Open Access Journals (Sweden)

    Jianlin Jiang

    Full Text Available BACKGROUND: Three members of the Plasmodium vivax merozoite surface protein-3 (PvMSP3 family (PvMSP3-α, PvMSP3-β and PvMSP3-γ were initially characterized and later shown to be part of a larger highly diverse family, encoded by a cluster of genes arranged head-to-tail in chromosome 10. PvMSP3-α and PvMSP3-β have become genetic markers in epidemiological studies, and are being evaluated as vaccine candidates. This research investigates the gene and protein expression of the entire family and pertinent implications. METHODOLOGY/PRINCIPAL FINDINGS: A 60 kb multigene locus from chromosome 10 in P. vivax (Salvador 1 strain was studied to classify the number of pvmsp3 genes present, and compare their transcription, translation and protein localization patterns during blood-stage development. Eleven pvmsp3 paralogs encode an N-terminal NLRNG signature motif, a central domain containing repeated variable heptad sequences, and conserved hydrophilic C-terminal features. One additional ORF in the locus lacks these features and was excluded as a member of the family. Transcripts representing all eleven pvmsp3 genes were detected in trophozoite- and schizont-stage RNA. Quantitative immunoblots using schizont-stage extracts and antibodies specific for each PvMSP3 protein demonstrated that all but PvMSP3.11 could be detected. Homologs were also detected by immunoblot in the closely related simian species, P. cynomolgi and P. knowlesi. Immunofluorescence assays confirmed that eight of the PvMSP3s are present in mature schizonts. Uniquely, PvMSP3.7 was expressed exclusively at the apical end of merozoites. CONCLUSION/SIGNIFICANCE: Specific proteins were detected representing the expression of 10 out of 11 genes confirmed as members of the pvmsp3 family. Eight PvMSP3s were visualized surrounding merozoites. In contrast, PvMSP3.7 was detected at the apical end of the merozoites. Pvmsp3.11 transcripts were present, though no corresponding protein was detected

  12. A Novel Synthetic TLR-4 Agonist Adjuvant Increases the Protective Response to a Clinical-Stage West Nile Virus Vaccine Antigen in Multiple Formulations.

    Science.gov (United States)

    Van Hoeven, Neal; Joshi, Sharvari Waghmare; Nana, Ghislain Ismael; Bosco-Lauth, Angela; Fox, Christopher; Bowen, Richard A; Clements, David E; Martyak, Timothy; Parks, D Elliot; Baldwin, Susan; Reed, Steven G; Coler, Rhea N

    2016-01-01

    West Nile virus (WNV) is a mosquito-transmitted member of the Flaviviridae family that has emerged in recent years to become a serious public health threat. Given the sporadic nature of WNV epidemics both temporally and geographically, there is an urgent need for a vaccine that can rapidly provide effective immunity. Protection from WNV infection is correlated with antibodies to the viral envelope (E) protein, which encodes receptor binding and fusion functions. Despite many promising E-protein vaccine candidates, there are currently none licensed for use in humans. This study investigates the ability to improve the immunogenicity and protective capacity of a promising clinical-stage WNV recombinant E-protein vaccine (WN-80E) by combining it with a novel synthetic TLR-4 agonist adjuvant. Using the murine model of WNV disease, we find that inclusion of a TLR-4 agonist in either a stable oil-in-water emulsion (SE) or aluminum hydroxide (Alum) formulation provides both dose and dosage sparing functions, whereby protection can be induced after a single immunization containing only 100 ng of WN-80E. Additionally, we find that inclusion of adjuvant with a single immunization reduced viral titers in sera to levels undetectable by viral plaque assay. The enhanced protection provided by adjuvanted immunization correlated with induction of a Th1 T-cell response and the resultant shaping of the IgG response. These findings suggest that inclusion of a next generation adjuvant may greatly enhance the protective capacity of WNV recombinant subunit vaccines, and establish a baseline for future development. PMID:26901122

  13. A Novel Synthetic TLR-4 Agonist Adjuvant Increases the Protective Response to a Clinical-Stage West Nile Virus Vaccine Antigen in Multiple Formulations.

    Directory of Open Access Journals (Sweden)

    Neal Van Hoeven

    Full Text Available West Nile virus (WNV is a mosquito-transmitted member of the Flaviviridae family that has emerged in recent years to become a serious public health threat. Given the sporadic nature of WNV epidemics both temporally and geographically, there is an urgent need for a vaccine that can rapidly provide effective immunity. Protection from WNV infection is correlated with antibodies to the viral envelope (E protein, which encodes receptor binding and fusion functions. Despite many promising E-protein vaccine candidates, there are currently none licensed for use in humans. This study investigates the ability to improve the immunogenicity and protective capacity of a promising clinical-stage WNV recombinant E-protein vaccine (WN-80E by combining it with a novel synthetic TLR-4 agonist adjuvant. Using the murine model of WNV disease, we find that inclusion of a TLR-4 agonist in either a stable oil-in-water emulsion (SE or aluminum hydroxide (Alum formulation provides both dose and dosage sparing functions, whereby protection can be induced after a single immunization containing only 100 ng of WN-80E. Additionally, we find that inclusion of adjuvant with a single immunization reduced viral titers in sera to levels undetectable by viral plaque assay. The enhanced protection provided by adjuvanted immunization correlated with induction of a Th1 T-cell response and the resultant shaping of the IgG response. These findings suggest that inclusion of a next generation adjuvant may greatly enhance the protective capacity of WNV recombinant subunit vaccines, and establish a baseline for future development.

  14. A Novel Synthetic TLR-4 Agonist Adjuvant Increases the Protective Response to a Clinical-Stage West Nile Virus Vaccine Antigen in Multiple Formulations.

    Science.gov (United States)

    Van Hoeven, Neal; Joshi, Sharvari Waghmare; Nana, Ghislain Ismael; Bosco-Lauth, Angela; Fox, Christopher; Bowen, Richard A; Clements, David E; Martyak, Timothy; Parks, D Elliot; Baldwin, Susan; Reed, Steven G; Coler, Rhea N

    2016-01-01

    West Nile virus (WNV) is a mosquito-transmitted member of the Flaviviridae family that has emerged in recent years to become a serious public health threat. Given the sporadic nature of WNV epidemics both temporally and geographically, there is an urgent need for a vaccine that can rapidly provide effective immunity. Protection from WNV infection is correlated with antibodies to the viral envelope (E) protein, which encodes receptor binding and fusion functions. Despite many promising E-protein vaccine candidates, there are currently none licensed for use in humans. This study investigates the ability to improve the immunogenicity and protective capacity of a promising clinical-stage WNV recombinant E-protein vaccine (WN-80E) by combining it with a novel synthetic TLR-4 agonist adjuvant. Using the murine model of WNV disease, we find that inclusion of a TLR-4 agonist in either a stable oil-in-water emulsion (SE) or aluminum hydroxide (Alum) formulation provides both dose and dosage sparing functions, whereby protection can be induced after a single immunization containing only 100 ng of WN-80E. Additionally, we find that inclusion of adjuvant with a single immunization reduced viral titers in sera to levels undetectable by viral plaque assay. The enhanced protection provided by adjuvanted immunization correlated with induction of a Th1 T-cell response and the resultant shaping of the IgG response. These findings suggest that inclusion of a next generation adjuvant may greatly enhance the protective capacity of WNV recombinant subunit vaccines, and establish a baseline for future development.

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

    OpenAIRE

    Mariana de Souza Sena; Roberto Carlos Vieira Junior; Cássio Charnoski Rubim; Thiago da Rosa Lima; Joice Cristina dos Santos Trombeta; Alesandro Garcia; Jonato Prestes; Ramires Alsamir Tibana; Fabrício Azevedo Voltarelli

    2015-01-01

    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 performe...

  16. Induction of strain-transcending immunity against Plasmodium chabaudi adami malaria with a multiepitope DNA vaccine.

    Science.gov (United States)

    Scorza, T; Grubb, K; Smooker, P; Rainczuk, A; Proll, D; Spithill, T W

    2005-05-01

    A major goal of current malaria vaccine programs is to develop multivalent vaccines that will protect humans against the many heterologous malaria strains that circulate in endemic areas. We describe a multiepitope DNA vaccine, derived from a genomic Plasmodium chabaudi adami DS DNA expression library of 30,000 plasmids, which induces strain-transcending immunity in mice against challenge with P. c. adami DK. Segregation of this library and DNA sequence analysis identified vaccine subpools encoding open reading frames (ORFs)/peptides of >9 amino acids [aa] (the V9+ pool, 303 plasmids) and >50 aa (V50+ pool, 56 plasmids), respectively. The V9+ and V50+ plasmid vaccine subpools significantly cross-protected mice against heterologous P. c. adami DK challenge, and protection correlated with the induction of both specific gamma interferon production by splenic cells and opsonizing antibodies. Bioinformatic analysis showed that 22 of the V50+ ORFs were polypeptides conserved among three or more Plasmodium spp., 13 of which are predicted hypothetical proteins. Twenty-nine of these ORFs are orthologues of predicted Plasmodium falciparum sequences known to be expressed in the blood stage, suggesting that this vaccine pool encodes multiple blood-stage antigens. The results have implications for malaria vaccine design by providing proof-of-principle that significant strain-transcending immunity can be induced using multiepitope blood-stage DNA vaccines and suggest that both cellular responses and opsonizing antibodies are necessary for optimal protection against P. c. adami.

  17. Effect of mature blood-stage Plasmodium parasite sequestration on pathogen biomass in mathematical and in vivo models of malaria.

    Science.gov (United States)

    Khoury, David S; Cromer, Deborah; Best, Shannon E; James, Kylie R; Kim, Peter S; Engwerda, Christian R; Haque, Ashraful; Davenport, Miles P

    2014-01-01

    Parasite biomass and microvasculature obstruction are strongly associated with disease severity and death in Plasmodium falciparum-infected humans. This is related to sequestration of mature, blood-stage parasites (schizonts) in peripheral tissue. The prevailing view is that schizont sequestration leads to an increase in pathogen biomass, yet direct experimental data to support this are lacking. Here, we first studied parasite population dynamics in inbred wild-type (WT) mice infected with the rodent species of malaria, Plasmodium berghei ANKA. As is commonly reported, these mice became moribund due to large numbers of parasites in multiple tissues. We then studied infection dynamics in a genetically targeted line of mice, which displayed minimal tissue accumulation of parasites. We constructed a mathematical model of parasite biomass dynamics, incorporating schizont-specific host clearance, both with and without schizont sequestration. Combined use of mathematical and in vivo modeling indicated, first, that the slowing of parasite growth in the genetically targeted mice can be attributed to specific clearance of schizonts from the circulation and, second, that persistent parasite growth in WT mice can be explained solely as a result of schizont sequestration. Our work provides evidence that schizont sequestration could be a major biological process driving rapid, early increases in parasite biomass during blood-stage Plasmodium infection. PMID:24144725

  18. Evidence for an amoeba-like infectious stage of ichthyophonus sp. and description of a circulating blood stage: a probable mechanism for dispersal within the fish host

    Science.gov (United States)

    Kocan, Richard; LaPatra, Scott; Hershberger, Paul

    2013-01-01

    Small amoeboid cells, believed to be the infectious stage of Ichthyophonus sp., were observed in the bolus (stomach contents) and tunica propria (stomach wall) of Pacific staghorn sculpins and rainbow trout shortly after they ingested Ichthyophonus sp.–infected tissues. By 24–48 hr post-exposure (PE) the parasite morphed from the classically reported multinucleate thick walled schizonts to 2 distinct cell types, i.e., a larger multinucleate amoeboid cell surrounded by a narrow translucent zone and a smaller spherical cell surrounded by a “halo” and resembling a small schizont. Both cell types also appeared in the tunica propria, indicating that they had recently penetrated the columnar epithelium of the stomach. No Ichthyophonus sp. pseudo-hyphae (“germination tubes”) were observed in the bolus or penetrating the stomach wall. Simultaneously, Ichthyophonus sp. was isolated in vitro from aortic blood, which was consistently positive from 6 to 144 hr PE, then only intermittently for the next 4 wk. Small PAS-positive cells observed in blood cultures grew into colonies consisting of non-septate tubules (pseudo-hyphae) terminating in multinucleated knob-like apices similar to those seen in organ explant cultures. Organ explants were culture positive every day; however, typical Ichthyophonus sp. schizonts were not observed histologically until 20–25 days PE. From 20 to 60 days PE, schizont diameter increased from ≤25 μm to ≥82 μm. Based on the data presented herein, we are confident that we have resolved the life cycle of Ichthyophonus sp. within the piscivorous host.

  19. [The comparison of concentration of endogenous ethanol blood serum in alcoholics and in non-alcoholics at different stages of abstinence].

    Science.gov (United States)

    Lukaszewicz, A; Markowski, T; Pawlak, D

    1997-01-01

    In this report the concentration of endogenous ethanol in blood serum in alcoholics at different stages of abstinence and in non-alcoholics was studied. 36 people--26 alcoholics and 10 non-alcoholics were examined and gas chromatography was used. It was revealed that the longer the period of abstinence in alcoholics, the lower the concentration of endogenous ethanol in blood serum. Moreover, the alcoholics showed a higher concentration of endogenous ethanol in blood serum as compared to non-alcoholics.

  20. 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.

  1. Pf155/RESA protein influences the dynamic microcirculatory behavior of ring-stage Plasmodium falciparum infected red blood cells

    Science.gov (United States)

    Diez-Silva, Monica; Park, Yongkeun; Huang, Sha; Bow, Hansen; Mercereau-Puijalon, Odile; Deplaine, Guillaume; Lavazec, Catherine; Perrot, Sylvie; Bonnefoy, Serge; Feld, Michael S.; Han, Jongyoon; Dao, Ming; Suresh, Subra

    2012-08-01

    Proteins exported by Plasmodium falciparum to the red blood cell (RBC) membrane modify the structural properties of the parasitized RBC (Pf-RBC). Although quasi-static single cell assays show reduced ring-stage Pf-RBCs deformability, the parameters influencing their microcirculatory behavior remain unexplored. Here, we study the dynamic properties of ring-stage Pf-RBCs and the role of the parasite protein Pf155/Ring-Infected Erythrocyte Surface Antigen (RESA). Diffraction phase microscopy revealed RESA-driven decreased Pf-RBCs membrane fluctuations. Microfluidic experiments showed a RESA-dependent reduction in the Pf-RBCs transit velocity, which was potentiated at febrile temperature. In a microspheres filtration system, incubation at febrile temperature impaired traversal of RESA-expressing Pf-RBCs. These results show that RESA influences ring-stage Pf-RBCs microcirculation, an effect that is fever-enhanced. This is the first identification of a parasite factor influencing the dynamic circulation of young asexual Pf-RBCs in physiologically relevant conditions, offering novel possibilities for interventions to reduce parasite survival and pathogenesis in its human host.

  2. The Pf332 gene codes for a megadalton protein of Plasmodium falciparum asexual blood stages

    Directory of Open Access Journals (Sweden)

    Denise Mattei

    1992-01-01

    Full Text Available We characterized the Plasmodium falciparum antigen 332 (Ag332 which is specifically expressed during the asexual intraerythrocytic cycle of the parasite. The corresponding Pf332 gene has been located in the subtelomeric region of chromosome 11. Furthermore, it is present in all strais so far analyzed and shows marked restriction length fragment polymorphism. Partial sequence and restriction endonuclease digestion of cloned fragments revealed that the Pf332 gene is composed of highly degenerated repeats rich is glutamic acid. Mung been nuclease digestion and Northern blot analysis suggested that Pf332 gene codes for a protein of about 700 kDa. These data were further confirmed by Western blot and immunoprecipitation of parasites extracts with an antiserum raised against a recombinant clone expressing part of the Ag332. Confocal immunofluorescence showed that Ag332 is translocated from the parasite to the surface of infected red blood cells within vesicle-like structures. In addition, Ag332 was detected on the surface of monkey erythrocytes infected with Plasmodium falciparum.

  3. 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

  4. 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.

  5. Identification of blood-brain barrier function following subarachnoid hemorrhage in rats at different stages

    Institute of Scientific and Technical Information of China (English)

    Zongyi Xie; Weiwei Shen; Ying Ma; Yuan Cheng

    2008-01-01

    BACKGROUND: Recent studies have indicated that blood-brain barrier (BBB) disruption following subarachnoid hemorrhage (SAH) significantly correlates with the development of brain injury and poor prognosis of patients subjected to SAH. OBJECTIVE: To investigate both functional and structural changes related to BBB in various phases after SAH in rats through quantitative and qualitative methods.DESIGN, TIME AND SETTING: This experiment, a completely randomized design and controlled experiment, was performed at the Department of Neurosurgery, the Second Affiliated Hospital of Chongqing University of Medical Sciences from June 2006 to March 2007.MATERIALS: A total of 128 female, healthy, Sprague-Dawley rats were selected for this study. Main reagents and instruments: Evans Blue dye (Sigma Company, USA), fluorescence spectrophotometer (Shimadzu Company, Japan), and transmission electron microscope (Olympus Company, Japan). MAIN OUTCOME MEASURES: Brain tissue water content was determined by the wet-dry method. BBB permeability in the cerebral cortex was determined by Evans Blue dye and fluorescent spectrophotometer. The ultrastructural changes in BBB were observed with transmission electron microscope.RESULTS: Compared with the sham-operated group, SAH induced a significant increase in brain water content between 24 and 60 hours (F = 888.32, P 0.05). Electron microscopy demonstrated only a mild perivascular edema at 24 hours after SAH. By 36 hours, a notable perivascular edema was associated with a collapse of the capillary. Astrocytic endfeet surrounding the capillary were prominently swollen in the edematous areas. The above-mentioned abnormal ultrastructural changes in the BBB were reversed by 72 hours after SAH. No obvious morphological changes in the BBB were detected in the sham-operated rats.CONCLUSION: These results directly suggest that SAH could induce rapid changes in BBB function and structure during the acute phases of BBB breakdown. Moreover, these dynamic

  6. 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.

  7. Biosynthesis of GDP-fucose and other sugar nucleotides in the blood stages of Plasmodium falciparum.

    Science.gov (United States)

    Sanz, Sílvia; Bandini, Giulia; Ospina, Diego; Bernabeu, Maria; Mariño, Karina; Fernández-Becerra, Carmen; Izquierdo, Luis

    2013-06-01

    Carbohydrate structures play important roles in many biological processes, including cell adhesion, cell-cell communication, and host-pathogen interactions. Sugar nucleotides are activated forms of sugars used by the cell as donors for most glycosylation reactions. Using a liquid chromatography-tandem mass spectrometry-based method, we identified and quantified the pools of UDP-glucose, UDP-galactose, UDP-N-acetylglucosamine, GDP-mannose, and GDP-fucose in Plasmodium falciparum intraerythrocytic life stages. We assembled these data with the in silico functional reconstruction of the parasite metabolic pathways obtained from the P. falciparum annotated genome, exposing new active biosynthetic routes crucial for further glycosylation reactions. Fucose is a sugar present in glycoconjugates often associated with recognition and adhesion events. Thus, the GDP-fucose precursor is essential in a wide variety of organisms. P. falciparum presents homologues of GDP-mannose 4,6-dehydratase and GDP-L-fucose synthase enzymes that are active in vitro, indicating that most GDP-fucose is formed by a de novo pathway that involves the bioconversion of GDP-mannose. Homologues for enzymes involved in a fucose salvage pathway are apparently absent in the P. falciparum genome. This is in agreement with in vivo metabolic labeling experiments showing that fucose is not significantly incorporated by the parasite. Fluorescence microscopy of epitope-tagged versions of P. falciparum GDP-mannose 4,6-dehydratase and GDP-L-fucose synthase expressed in transgenic 3D7 parasites shows that these enzymes localize in the cytoplasm of P. falciparum during the intraerythrocytic developmental cycle. Although the function of fucose in the parasite is not known, the presence of GDP-fucose suggests that the metabolite may be used for further fucosylation reactions.

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

    Directory of Open Access Journals (Sweden)

    Yves Jackson

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSIONS: 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.

  9. Vaccine Safety

    Science.gov (United States)

    ... the safety of Tdap, Meningococcal, and HPV vaccines Human Papillomavirus (HPV) Vaccine is Very Safe Read about the safety of ... Hepatitis A Vaccine Safety Hepatitis B Vaccine Safety Human Papillomavirus (HPV) Vaccine Safety FAQs about HPV Safety Influenza (Flu) Vaccine ...

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

    Science.gov (United States)

    Zuccala, Elizabeth S; Gout, Alexander M; Dekiwadia, Chaitali; Marapana, Danushka S; Angrisano, Fiona; Turnbull, Lynne; Riglar, David T; Rogers, Kelly L; Whitchurch, Cynthia B; Ralph, Stuart A; Speed, Terence P; Baum, Jake

    2012-01-01

    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. PMID:23049965

  12. Combination Chemotherapy and Peripheral Blood Stem Cell Transplant Followed By Aldesleukin and Sargramostim in Treating Patients With Inflammatory Stage IIIB or Metastatic Stage IV Breast Cancer

    Science.gov (United States)

    2011-07-08

    Estrogen Receptor-negative Breast Cancer; Estrogen Receptor-positive Breast Cancer; Inflammatory Breast Cancer; Male Breast Cancer; Progesterone Receptor-negative Breast Cancer; Progesterone Receptor-positive Breast Cancer; Stage IIIB Breast Cancer; Stage IV Breast Cancer

  13. 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......+MSP-1(19), and fused AMA-1/MSP-1(19)). Animals were immunized with equimolar amounts of each antigen, formulated in Montanide ISA720. The specificities and titers of antibodies were compared using immunofluorescence assays and enzyme-linked immunosorbent assay (ELISA). The antiparasite activity...... of immunoglobulin G (IgG) in in vitro cultures was determined by growth inhibition assay, flow cytometry, lactate dehydrogenase assay, and microscopy. Baculovirus MSP-1(19) immunizations produced the highest parasite-specific antibody titers in immunofluorescence assays. In ELISAs, baculovirus-produced MSP-1...

  14. 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

    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...... chain pattern of IgA-secreting cells from individuals vaccinated with pneumococcal polysaccharides and from unvaccinated individuals probably indicates that these cells are being derived from B-cell clones with a limited idiotypic heterogeneity, which have been selected and clonally expanded...

  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

    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...... 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...

  16. Decreased glutathione content and glutathione S-transferase activity in red blood cells of coal miners with early stages of pneumoconiosis.

    OpenAIRE

    Evelo, C T; Bos, R P; Borm, P J

    1993-01-01

    Blood samples of miners heavily exposed to coal dust were examined for changes in glutathione S-transferase (GST) activity. Decreased GST activity was found in red blood cells of subjects with early stages of coal workers' pneumoconiosis (International Labour Office classification 0/1-1/2) when compared with control miners. At further progression of coal workers' pneumoconiosis (> or = 2/1), the activity of GST was not different from controls. In the same group with moderate coal workers' pne...

  17. Clinical development of Ebola vaccines.

    Science.gov (United States)

    Sridhar, Saranya

    2015-09-01

    The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines.

  18. Clinical development of Ebola vaccines.

    Science.gov (United States)

    Sridhar, Saranya

    2015-09-01

    The ongoing outbreak of Ebola virus disease in West Africa highlighted the lack of a licensed drug or vaccine to combat the disease and has renewed the urgency to develop a pipeline of Ebola vaccines. A number of different vaccine platforms are being developed by assessing preclinical efficacy in animal models and expediting clinical development. Over 15 different vaccines are in preclinical development and 8 vaccines are now in different stages of clinical evaluation. These vaccines include DNA vaccines, virus-like particles and viral vectors such as live replicating vesicular stomatitis virus (rVSV), human and chimpanzee adenovirus, and vaccinia virus. Recently, in preliminary results reported from the first phase III trial of an Ebola vaccine, the rVSV-vectored vaccine showed promising efficacy. This review charts this rapidly advancing area of research focusing on vaccines in clinical development and discusses the future opportunities and challenges faced in the licensure and deployment of Ebola vaccines. PMID:26668751

  19. False-positive serologic tests for human T-cell lymphotropic virus type I among blood donors following influenza vaccination, 1992.

    Science.gov (United States)

    1993-03-12

    From October 31 through December 15, 1991, 10 blood donors to the American Red Cross Blood Services, Badger Region (ARCBS), were found to have false-positive screening enzyme-linked immunosorbent assays (ELISAs) for antibodies to two or more of the following viruses: human immunodeficiency virus type 1 (HIV-1), human T-cell lymphotrophic virus type 1 (HTLV-I), and hepatitis C virus (HCV). An investigation by the Division of Health, Wisconsin Department of Health and Social Services (WDOH), and the ARCBS indicated that the risk for false-positive reactivity was associated with antecedent receipt of influenza vaccine formulated for the 1991-92 season. In March 1992, the ARCBS began use of newly available ELISAs for anti-HIV (HIVAB, HIV-1/HIV-2 (rDNA) EIA [Abbott Laboratories, Abbott Park, Illinois]) and anti-HCV (HCV 2.0 ELISA [Ortho Diagnostic Systems, Raritan, New Jersey]), while continuing to test with the ELISA for anti-HTLV-I [HTLV-I ELISA (Abbott Laboratories) used in 1991. From January 1 through October 13, 1992, the ARCBS identified 19 blood donors with repeatedly reactive ELISAs for HTLV-I. However, from October 14 through November 10, 15 false-positive ELISAs for HTLV-I were reported by the ARCBS to the WDOH. As a result of this increase, the ARCBS conducted a case-control study to assess the relation between influenza vaccination and testing positive for HTLV-I. This report summarizes the results of the study. PMID:8446101

  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

    Despite many intervention programmes aimed at curtailing the scourge, malaria remains a formidable problem of human health. Immunity to asexual blood-stage of Plasmodium falciparum malaria is thought to be associated with protective antibodies of certain immunoglobulin classes and subclasses. We ...

  1. EFFECTS OF STRAIN, CAGE DENSITY AND POSITION ON IMMUNE RESPONSE TO VACCINES AND BLOOD PARAMETERS IN LAYER PULLETS

    Directory of Open Access Journals (Sweden)

    Z. BOZKURT

    2013-07-01

    Full Text Available Two thousand 1-day-old layer chicks were used in the study from Lohman Brown, Isa Brown, Lohman White and Bowans White breeds. The chicks were placed in the at 3 cage densities (211.8, 274.5 and 370.6 cm2 per bird and on 3 positions (as top, middle and bottom tiers. All birds were kept under standard management policy and a commercial vaccination program was practiced. Total specific antibody titres to Infectious Brochitis Virus (IBV, Infectious Bursal Desease Virus (IBDV, Newcastle Disease Virus (NDV and Egg Drop Syndrome Virus (EDSV vaccines at the ages of 5, 10 and 20 weeks were serologically determined by ELISA. Cellmediated immune response was also evaluated. In commercial white egg laying strains specific antibody titres to IBV, IBDV, NDV and EDSV vaccines were greater than in Brown egg layer strains. Keeping in cage created more stress in Brown egg laying chicks than those in white egg laying chicks. As cage density increased, the ratio of heterophils to lymphocytes (H/L ratio slightly increased. Cage position had no influence on the titres of antibodies to IBV and IBDV vaccines but the position of cage in pullets where chicks were stocked, from top to bottom, NDV and EDSV antibody titre decreased and percentage of heterophils, H/L ratio and basophil rates were low. These findings suggest that cage-related stress could be decreased, resistance to diseases and finally well-being of hens may be improved if hens are kept under proper position and density within cage systems with respect to their physiological and behavioral characteristics that controlled by genes.

  2. Infection with Plasmodium berghei Boosts Antibody Responses Primed by a DNA Vaccine Encoding Gametocyte Antigen Pbs48/45

    OpenAIRE

    Haddad, Diana; Maciel, Jorge; Kumar, Nirbhay

    2006-01-01

    An important consideration in the development of a malaria vaccine for individuals living in areas of endemicity is whether vaccine-elicited immune responses can be boosted by natural infection. To investigate this question, we used Plasmodium berghei ANKA blood-stage parasites for the infection of mice that were previously immunized with a DNA vaccine encoding the P. berghei sexual-stage antigen Pbs48/45. Intramuscular immunization in mice with one or two doses of DNA-Pbs48/45 or of empty DN...

  3. 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

  4. Life stage-related differences in fatty acid composition of an obligate ectoparasite, the deer ked (Lipoptena cervi)-influence of blood meals and gender.

    Science.gov (United States)

    Mustonen, Anne-Mari; Käkelä, Reijo; Paakkonen, Tommi; Nieminen, Petteri

    2015-01-01

    Metamorphosis and diet often influence fatty acid (FA) signatures (FAS) of insects. We investigated FAS in a hematophagous ectoparasite, the deer ked (Lipoptena cervi). Deer keds shed their wings upon attachment on the host and, thus, the FAS of an individual blood-fed imago/pupa in the fur of its host can be traced back to the blood FA profile of a single moose (Alces alces). Host blood and different life stages of deer keds were investigated for FA by gas chromatography. The FAS of life stages resembled each other more closely than the diet. Blood meals modified the FAS of both sexes but the FAS of the blood-fed females were closer to those of the prepupae/pupae. The parasitizing males had higher proportions of major saturated FA (SFA) and polyunsaturated FA (PUFA) than the females, which contained more monounsaturated FA (MUFA) with higher ratios of n-3/n-6 PUFA and unsaturated FA (UFA)/SFA. The proportions of 16:1n-7 were <1% in the blood but 18% (males) and 29% (females) in the blood-fed keds. Allocation of lipids to offspring by the females and possible accumulation of PUFA in male reproductive organs may have induced these sex-related differences. MUFA percentages and UFA/SFA ratios increased while SFA and many PUFA decreased from the reproducing females to the pupae. The diapausing pupae displayed lowered n-3/n-6 PUFA ratios and could have mobilized 16:0 and 18:3n-3 for the most fundamental metabolic processes. In conclusion, FAS are modified through the life stages of the deer ked possibly due to their different FA requirements. PMID:25223709

  5. Developing a Tablet-Based Self-Persuasion Intervention Promoting Adolescent HPV Vaccination: Protocol for a Three-Stage Mixed-Methods Study

    OpenAIRE

    Tiro, Jasmin A; Lee, Simon Craddock; Marks, Emily G.; Persaud, Donna; Skinner, Celette Sugg; Street, Richard L.; Wiebe, Deborah J.; Farrell, David; Bishop, Wendy Pechero; Fuller, Sobha; Baldwin, Austin S.

    2016-01-01

    Background Human papillomavirus (HPV)-related cancers are a significant burden on the US health care system that can be prevented through adolescent HPV vaccination. Despite guidelines recommending vaccination, coverage among US adolescents is suboptimal particularly among underserved patients (uninsured, low income, racial, and ethnic minorities) seen in safety-net health care settings. Many parents are ambivalent about the vaccine and delay making a decision or talking with a provider about...

  6. Vaccine Therapy With Sargramostim (GM-CSF) in Treating Patients With Her-2 Positive Stage III-IV Breast Cancer or Ovarian Cancer

    Science.gov (United States)

    2016-05-02

    HER2-positive Breast Cancer; Stage III Ovarian Epithelial Cancer; Stage III Ovarian Germ Cell Tumor; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer; Stage IV Breast Cancer; Stage IV Ovarian Epithelial Cancer; Stage IV Ovarian Germ Cell Tumor

  7. Relationship between the Increased Haemostatic Properties of Blood Platelets and Oxidative Stress Level in Multiple Sclerosis Patients with the Secondary Progressive Stage

    Directory of Open Access Journals (Sweden)

    Agnieszka Morel

    2015-01-01

    Full Text Available Multiple sclerosis (MS is the autoimmune disease of the central nervous system with complex pathogenesis, different clinical courses and recurrent neurological relapses and/or progression. Despite various scientific papers that focused on early stage of MS, our study targets selective group of late stage secondary progressive MS patients. The presented work is concerned with the reactivity of blood platelets in primary hemostasis in SP MS patients. 50 SP MS patients and 50 healthy volunteers (never diagnosed with MS or other chronic diseases were examined to evaluate the biological activity of blood platelets (adhesion, aggregation, especially their response to the most important physiological agonists (thrombin, ADP, and collagen and the effect of oxidative stress on platelet activity. We found that the blood platelets from SP MS patients were significantly more sensitive to all used agonists in comparison with control group. Moreover, the platelet hemostatic function was advanced in patients suffering from SP MS and positively correlated with increased production of O2-∙ in these cells, as well as with Expanded Disability Status Scale. We postulate that the increased oxidative stress in blood platelets in SP MS may be primarily responsible for the altered haemostatic properties of blood platelets.

  8. 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).

  9. Safety and immunogenicity of GMZ2 - a MSP3-GLURP fusion protein malaria vaccine candidate

    DEFF Research Database (Denmark)

    Esen, Meral; Kremsner, Peter G; Schleucher, Regina;

    2009-01-01

    Malaria is a major public health problem in Sub-Saharan Africa. In highly endemic regions infants, children and pregnant women are mostly affected. An effective malaria vaccine would complement existing malaria control strategies because it can be integrated in existing immunization programs easily....... Here we present the results of the first phase Ia clinical trial of GMZ2 adjuvanted in aluminium hydroxide. GMZ2 is a malaria vaccine candidate, designed upon the rationale to induce immune responses against asexual blood stages of Plasmodium falciparum similar to those encountered in semi...... is a safe and immunogenic malaria vaccine candidate suitable for further clinical development....

  10. 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.

  11. Efficient monitoring of blood-stage infection in a malaria rodent model by the rotating-crystal magneto-optical method

    CERN Document Server

    Orban, Agnes; Albuquerque, Inês S; Butykai, Adam; Kezsmarki, Istvan; Hänscheid, Thomas

    2015-01-01

    Global research efforts have been focused on the simultaneous improvement of the efficiency and sensitivity of malaria diagnosis in resource-limited settings and for the active case detection of asymptomatic infections. A recently developed magneto-optical (MO) method allows the high-sensitivity detection of malaria pigment (hemozoin) crystals in blood via their magnetically induced rotational motion. The evaluation of the method using synthetic $\\beta$-hematin crystals and P. falciparum in vitro cultures implies its potential for in-field diagnosis. Here, we study the performance of the method in monitoring the in vivo onset and progression of the blood stage infection using a malaria mouse model. We found that the MO method can detect the first generation of intraerythrocytic parasites at the ring stage 61-66 hours after sporozoite injection demonstrating better sensitivity than light microscopy and flow cytometry. MO measurements performed after treatment of severe P. berghei infections show that the clear...

  12. 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.

  13. Research toward Malaria Vaccines

    Science.gov (United States)

    Miller, Louis H.; Howard, Russell J.; Carter, Richard; Good, Michael F.; Nussenzweig, Victor; Nussenzweig, Ruth S.

    1986-12-01

    Malaria exacts a toll of disease to people in the Tropics that seems incomprehensible to those only familiar with medicine and human health in the developed world. The methods of molecular biology, immunology, and cell biology are now being used to develop an antimalarial vaccine. The Plasmodium parasites that cause malaria have many stages in their life cycle. Each stage is antigenically distinct and potentially could be interrupted by different vaccines. However, achieving complete protection by vaccination may require a better understanding of the complexities of B- and T-cell priming in natural infections and the development of an appropriate adjuvant for use in humans.

  14. 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.

  15. 9 CFR 113.317 - Parvovirus Vaccine (Canine).

    Science.gov (United States)

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Parvovirus Vaccine (Canine). 113.317... Virus Vaccines § 113.317 Parvovirus Vaccine (Canine). Parvovirus Vaccine recommended for use in dogs... parvovirus susceptible dogs (20 vaccinates and 5 controls) shall be used as test animals. Blood samples...

  16. Recommendations for using smallpox vaccine in a pre-event vaccination program. Supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC).

    Science.gov (United States)

    Wharton, Melinda; Strikas, Raymond A; Harpaz, Rafael; Rotz, Lisa D; Schwartz, Benjamin; Casey, Christine G; Pearson, Michele L; Anderson, Larry J

    2003-04-01

    This report supplements the 2001 statement by the Advisory Committee on Immunization Practices (ACIP) (CDC. Vaccinia [smallpox] vaccine: recommendations of the Advisory Committee on Immunization Practices [ACIP], 2001. MMWR 2001;50[No. RR-10]:1-25). This supplemental report provides recommendations for using smallpox vaccine in the pre-event vaccination program in the United States. To facilitate preparedness and response, smallpox vaccination is recommended for persons designated by public health authorities to conduct investigation and follow-up of initial smallpox cases that might necessitate direct patient contact. ACIP recommends that each state and territory establish and maintain > or = 1 smallpox response team. ACIP and the Healthcare Infection Control Practices Advisory Committee (HICPAC) recommend that each acute-care hospital identify health-care workers who can be vaccinated and trained to provide direct medical care for the first smallpox patients requiring hospital admission and to evaluate and manage patients who are suspected as having smallpox. When feasible, the first-stage vaccination program should include previously vaccinated health-care personnel to decrease the potential for adverse events. Additionally persons administering smallpox vaccine in this pre-event vaccination program should be vaccinated. Smallpox vaccine is administered by using the multiple-puncture technique with a bifurcated needle, packaged with the vaccine and diluent. According to the product labeling, 2-3 punctures are recommended for primary vaccination and 15 punctures for revaccination. A trace of blood should appear at the vaccination site after 15-20 seconds; if no trace of blood is visible, an additional 3 insertions should be made by using the same bifurcated needle without reinserting the needle into the vaccine vial. If no evidence of vaccine take is apparent after 7 days, the person can be vaccinated again. Optimal infection-control practices and appropriate

  17. 浅析血液生化检测各阶段质控对策%Analysis of the various stages of quality control blood biochemical detection countermeasures

    Institute of Scientific and Technical Information of China (English)

    王光让; 李婷; 刘宁

    2013-01-01

    Objective To investigate the effects of the various stages of quality control sample pass rate of biochemical tests of blood. Methods Patients in February 2013 -2014 February 422 routine blood biochemical examination of the hospital for the study. order by patients admitted to hospital will be divided into a control group (n = 211) and experimental group (n = 211). The control group received routine blood chemistry testing. Experimental group at all stages of biochemical strict quality control testing. Compare two samples of blood biochemical test pass rate case. Results The control group of blood samples biochemical detection rate of 84.36% passing (178/211), the experimental group 98.58% (208/211), blood biochemistry experimental group was significantly higher pass rate specimens (P <0.01). Conclusion The various stages of quality control can significantly improve the pass rate of clinical specimens of blood biochemical tests provide a reliable basis for clinical diagnosis and treatment.%目的:探讨各阶段质控对血液生化检测标本合格率的影响。方法选取我院2013年2月至2013年8月422例行血生化检查的患者作为研究对象。按患者入院顺序,将其分为对照组(n=211)和实验组(n=211)。对照组接受常规血生化检测。实验组对血生化检测的各个阶段进行严格质控。对比两组血生化检测标本合格率情况。结果对照组血生化检测标本合格率84.36%(178/211),实验组98.58%(208/211),实验组血生化检测标本合格率显著高于对照组(P<0.01)。结论各阶段质控可显著提高临床血生化检测标本的合格率,为临床诊断及治疗提供可靠依据。

  18. Complete blood counts, liver function tests, and chest x-rays as routine screening in early-stage breast cancer: value added or just cost?

    Science.gov (United States)

    Louie, Raphael J; Tonneson, Jennifer E; Gowarty, Minda; Goodney, Philip P; Barth, Richard J; Rosenkranz, Kari M

    2015-11-01

    Current National Comprehensive Cancer Network guidelines for breast cancer staging include pre-treatment complete blood count (CBC) and liver function tests (LFT) to screen for occult metastatic disease. To date, the relevance of these tests in detecting metastatic disease in asymptomatic women with early-stage breast cancer (Stage I/II) has not been demonstrated. Although chest x-rays are no longer recommended in the NCCN guidelines, many centers continue to include this imaging as part of their screening process. We aim to determine the clinical and financial impact of these labs and x-rays in the evaluation of early-stage breast cancer patients. A single institution IRB-approved retrospective chart review was conducted of patients with biopsy-proven invasive breast cancer treated from January 1, 2005–December 31, 2009. We collected patient demographics, clinical and pathologic staging, chest x-ray, CBC, and LFT results at the time of referral. Patients were stratified according to radiographic stage at the time of diagnosis. We obtained Medicare reimbursement fees for cost analysis. From 2005 to 2009, 1609 patients with biopsy-proven invasive breast cancer were treated at our institution. Of the 1082 patients with radiographic stage I/II disease, 27.3 % of patients had abnormal CBCs. No additional testing was performed to evaluate these abnormalities. In the early-stage population, 24.7 % of patients had elevated LFTs, resulting in 84 additional imaging studies. No metastatic disease was detected. The cost of CBC, LFTs and chest x-rays was $110.20 per patient, totaling $106,410.99. Additional tests prompted by abnormal results cost $58,143.30 over the five-year period. We found that pre-treatment CBCs, LFTs, and chest x-rays did not improve detection of occult metastatic disease but resulted in additional financial costs. Avoiding routine ordering of these tests would save the US healthcare system $25.7 million annually.

  19. A switch in infected erythrocyte deformability at the maturation and blood circulation of Plasmodium falciparum transmission stages.

    NARCIS (Netherlands)

    Tiburcio, M.; Niang, M.; Deplaine, G.; Perrot, S.; Bischoff, E.; Ndour, P.A.; Silvestrini, F.; Khattab, A.; Milon, G.; David, P.H.; Hardeman, M.; Vernick, K.D.; Sauerwein, R.W.; Preiser, P.R.; Mercereau-Puijalon, O.; Buffet, P.; Alano, P.; Lavazec, C.

    2012-01-01

    Achievement of malaria elimination requires development of novel strategies interfering with parasite transmission, including targeting the parasite sexual stages (gametocytes). The formation of Plasmodium falciparum gametocytes in the human host takes several days during which immature gametocyte-i

  20. Increased P-35, EBI3 Transcripts and Other Treg Markers in Peripheral Blood Mononuclear Cells of Breast Cancer Patients with Different clinical Stages

    Directory of Open Access Journals (Sweden)

    Maryam Hamidinia

    2015-06-01

    Full Text Available Purpose: Currently, cancer as a major problem around the world threatens human health and has a high incidence in developing countries. Many reports have indicated that patients suffering from cancer demonstrate decreased antitumor immune responses as well as a high prevalence of T regulatory population. It has been reported that Foxp3+Tregs exert suppression by cell contact-dependent mechanisms which are mediated by soluble factors such as immunosuppressive cytokines like IL-10, TGF-​B and IL-35. Consequently there is a great need to identify prognostic and diagnostic biomarkers of regulatory T cells for vaccine and drug development. Methods: In this study IL-10, TGF-B, IL-35 and Foxp3 mRNA gene expression has been measured in peripheral blood of 40 breast cancer patients and 40 normal age-matched women using quantitative real-time PCR (qRT-PCR method with Master Mix reaction containing SYBER Green. GAPDH gene was used as housekeeping gene. Results: Our data demonstrated a significant up-regulation of IL-10, TGF-​B, P35, EBI3 and Foxp3 gene expression in patients’ peripheral blood compared to normal healthy controls (p<0.05. Conclusion: The data suggests that the immune system is suppressed in breast cancer patients, which may be due to elevated Treg cells population. These results may be useful for diagnostic or therapeutic purposes. However it may require more investigations

  1. 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......-α were rare. However, CD4+ cells producing IFN-γ or TNF-α after Ag-stimulation were detected in vaccinated pigs, and increased IFN-γ level (iMFI) in cells co-producing IFN-γ and TNF-α was more pronounced in vaccinated pigs compared to placebo pigs in response to M. hyosynoviae challenge (day 15 p...

  2. CFD Simulation of the Two-stage Axial Flow Blood Pump%两级轴流血泵CFD性能仿真

    Institute of Scientific and Technical Information of China (English)

    李涛; 赵慧

    2013-01-01

    In order to reduce rotating speed and improve hemolytic performance of blood pump,the blood pump was designed as two-stage axial structure.The front impeller was designed to helico-axial structure by using one dimension flow theory and the rear impeller was designed to traditional axial structure by using streamline design method.Computational fluid dynamics (CFD) simulation was applied to analyze the blood pump head,flow and distribution status of flow field,stress of blood in the blood pump.The results show that the maximum stress of blood pump appears in the inlet and outlet,besides,maximum stress of rear impeller inlet reduces significantly with the effects of front impeller.In the same conditions,the maximum stress of two-stage blood pump decreases significantly compared with ordinary blood pump.%为了降低血泵转速,提高其溶血性能,将血泵设计为两级轴流式结构,其中前级叶轮采用一元流动理论设计为螺旋轴流结构,后级叶轮采用流线法设计为传统轴流结构.利用计算流体力学(CFD)的方法,对血泵的扬程、流量及其内部血液的流场、应力等分布情况进行了仿真分析.结果表明:血泵最大应力主要出现在其入口和出口处,且后级叶轮在前级叶轮的影响下,其入口处的最大应力明显减小.在相同条件下,两级血泵与普通血泵相比,其最大应力可明显降低.

  3. Plasmodium vivax Pre-Erythrocytic–Stage Antigen Discovery: Exploiting Naturally Acquired Humoral Responses

    Science.gov (United States)

    Molina, Douglas M.; Finney, Olivia C.; Arevalo-Herrera, Myriam; Herrera, Socrates; Felgner, Philip L.; Gardner, Malcolm J.; Liang, Xiaowu; Wang, Ruobing

    2012-01-01

    The development of pre-erythrocytic Plasmodium vivax vaccines is hindered by the lack of in vitro culture systems or experimental rodent models. To help bypass these roadblocks, we exploited the fact that naturally exposed Fy− individuals who lack the Duffy blood antigen (Fy) receptor are less likely to develop blood-stage infections; therefore, they preferentially develop immune responses to pre-erythrocytic–stage parasites, whereas Fy+ individuals experience both liver- and blood-stage infections and develop immune responses to both pre-erythrocytic and erythrocytic parasites. We screened 60 endemic sera from P. vivax-exposed Fy+ or Fy− donors against a protein microarray containing 91 P. vivax proteins with P. falciparum orthologs that were up-regulated in sporozoites. Antibodies against 10 P. vivax antigens were identified in sera from P. vivax-exposed individuals but not unexposed controls. This technology has promising implications in the discovery of potential vaccine candidates against P. vivax malaria. PMID:22826492

  4. The March Toward Malaria Vaccines

    Science.gov (United States)

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

    2016-01-01

    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

  5. 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

  6. Lack of allele-specific efficacy of a bivalent AMA1 malaria vaccine

    Directory of Open Access Journals (Sweden)

    Ellis Ruth D

    2010-06-01

    Full Text Available Abstract Background Extensive genetic diversity in vaccine antigens may contribute to the lack of efficacy of blood stage malaria vaccines. Apical membrane antigen-1 (AMA1 is a leading blood stage malaria vaccine candidate with extreme diversity, potentially limiting its efficacy against infection and disease caused by Plasmodium falciparum parasites with diverse forms of AMA1. Methods Three hundred Malian children participated in a Phase 2 clinical trial of a bivalent malaria vaccine that found no protective efficacy. The vaccine consists of recombinant AMA1 based on the 3D7 and FVO strains of P. falciparum adjuvanted with aluminum hydroxide (AMA1-C1. The gene encoding AMA1 was sequenced from P. falciparum infections experienced before and after immunization with the study vaccine or a control vaccine. Sequences of ama1 from infections in the malaria vaccine and control groups were compared with regard to similarity to the vaccine antigens using several measures of genetic diversity. Time to infection with parasites carrying AMA1 haplotypes similar to the vaccine strains with respect to immunologically important polymorphisms and the risk of infection with vaccine strain haplotypes were compared. Results Based on 62 polymorphic AMA1 residues, 186 unique ama1 haplotypes were identified among 315 ama1 sequences that were included in the analysis. Eight infections had ama1 sequences identical to 3D7 while none were identical to FVO. Several measures of genetic diversity showed that ama1 sequences in the malaria vaccine and control groups were comparable both at baseline and during follow up period. Pre- and post-immunization ama1 sequences in both groups all had a similar degree of genetic distance from FVO and 3D7 ama1. No differences were found in the time of first clinical episode or risk of infection with an AMA1 haplotype similar to 3D7 or FVO with respect to a limited set of immunologically important polymorphisms found in the cluster 1 loop

  7. 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...

  8. T-cell depletion and autologous stem cell transplantation in the management of tumour stage mycosis fungoides with peripheral blood involvement.

    Science.gov (United States)

    Olavarria, E; Child, F; Woolford, A; Whittaker, S J; Davis, J G; McDonald, C; Chilcott, S; Spittle, M; Grieve, R J; Stewart, S; Apperley, J F; Russell-Jones, R

    2001-09-01

    Nine patients with tumour stage mycosis fungoides (MF) have been entered into a pilot study of T-cell depletion and autologous stem cell transplantation (SCT). Eight patients had detectable rearrangements of the T-cell receptor (TCR) gamma-gene demonstrated by polymerase chain reaction (PCR)/single-stranded conformation polymorphism (SSCP) in the peripheral blood. The median age was 47 years and the median duration of disease before SCT was 61 months; Peripheral blood progenitor cells were mobilized using high-dose etoposide (1.6 g/m2) and granulocyte colony-stimulating factor (G-CSF). The apheresis products underwent rigorous T-cell depletion with immunomagnetic methods. Double CD34-positive and CD4/CD8-negative selection achieved a median reduction of 3.89 log of T cells. All nine patients have been transplanted. Conditioning included carmustine (BCNU), etoposide and melphalan (BEM) in seven patients and total body irradiation plus etoposide or melphalan in two. Eight patients engrafted promptly and one patient died of septicaemia. All survivors entered complete remission. Seven patients have relapsed at a median of 7 months (2-14) post SCT. However, most patients have relapsed into a less aggressive stage, which has responded to conventional therapy. Four out of seven evaluable patients had detectable TCR rearrangements in the T-cell depleted graft. A T-cell clone was also detected in the peripheral blood before relapse in four cases. Autologous SCT is feasible, safe and can result in complete remission in a significant proportion of patients with tumour stage mycosis fungoides. Despite a short relapse-free survival, most patients achieved good disease control at the time of relapse.

  9. 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

    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...... 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....

  10. 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...... responses to the GLURP molecule and partly to the Pf155/RESA antigen in this study population were shortlived and dependent on frequent boostering, but whether these antigens play a role in the development of natural clinical immunity remains open. In the experimental group of schoolchildren weekly...

  11. Cancer Vaccines: A Brief Overview.

    Science.gov (United States)

    Thomas, Sunil; Prendergast, George C

    2016-01-01

    Vaccine approaches for cancer differ from traditional vaccine approaches for infectious disease in tending to focus on clearing active disease rather than preventing disease. In this review, we provide a brief overview of different types of vaccines and adjuvants that have been investigated for the purpose of controlling cancer burdens in patients, some of which are approved for clinical use or in late-stage clinical trials, such as the personalized dendritic cell vaccine sipuleucel-T (Provenge) and the recombinant viral prostate cancer vaccine PSA-TRICOM (Prostvac-VF). Vaccines against human viruses implicated in the development and progression of certain cancers, such as human papillomavirus in cervical cancer, are not considered here. Cancers express "altered self" antigens that tend to induce weaker responses than the "foreign" antigens expressed by infectious agents. Thus, immune stimulants and adjuvant approaches have been explored widely. Vaccine types considered include autologous patient-derived immune cell vaccines, tumor antigen-expressing recombinant virus vaccines, peptide vaccines, DNA vaccines, and heterologous whole-cell vaccines derived from established human tumor cell lines. Opportunities to develop effective cancer vaccines may benefit from seminal recent advances in understanding how immunosuppressive barricades are erected by tumors to mediate immune escape. In particular, targeted ablation of these barricades with novel agents, such as the immune checkpoint drug ipilimumab (anti-CTLA-4) approved recently for clinical use, may offer significant leverage to vaccinologists seeking to control and prevent malignancy.

  12. Blood Transfusion

    Science.gov (United States)

    ... to infections including those we develop from our vaccinations (such as poliovirus antibodies, which are made by ... the Transfusion Medicine Unit, Blood Bank, and Stem Cell Storage Facility University of Rochester Medical ... and health educators who are available by phone Monday through Friday, 9 am to 9 pm ( ...

  13. Impact of a Plasmodium falciparum AMA1 vaccine on antibody responses in adult Malians.

    Directory of Open Access Journals (Sweden)

    Alassane Dicko

    Full Text Available BACKGROUND: Apical Membrane Antigen 1 (AMA1 of Plasmodium falciparum merozoites is a leading blood-stage malaria vaccine candidate. Protection of Aotus monkeys after vaccination with AMA1 correlates with antibody responses. STUDY DESIGN/RESULTS: A randomized, controlled, double-blind phase 1 clinical trial was conducted in 54 healthy Malian adults living in an area of intense seasonal malaria transmission to assess the safety and immunogenicity of the AMA1-C1 malaria vaccine. AMA1-C1 contains an equal mixture of yeast-expressed recombinant proteins based on sequences from the FVO and 3D7 clones of P. falciparum, adsorbed on Alhydrogel. The control vaccine was the hepatitis B vaccine (Recombivax. Participants were enrolled into 1 of 3 dose cohorts (n = 18 per cohort and randomized 2:1 to receive either AMA1-C1 or Recombivax. Participants in the first, second, and third cohorts randomized to receive AMA1-C1 were vaccinated with 5, 20 and 80 microg of AMA1-C1, respectively. Vaccinations were administered on days 0, 28, and 360, and participants were followed until 6 months after the final vaccination. AMA1-C1 was well tolerated; no vaccine-related severe or serious adverse events were observed. AMA1 antibody responses to the 80 microg dose increased rapidly from baseline levels by days 14 and 28 after the first vaccination and continued to increase after the second vaccination. After a peak 14 days following the second vaccination, antibody levels decreased to baseline levels one year later at the time of the third vaccination that induced little or no increase in antibody levels. CONCLUSIONS: Although the AMA1-C1 vaccine candidate was well-tolerated and induced antibody responses to both vaccine and non-vaccine alleles, the antibody response after a third dose given at one year was lower than the response to the initial vaccinations. Additionally, post-vaccination increases in anti-AMA1 antibody levels were not associated with significant changes

  14. A novel preclinical method to quantitatively evaluate early-stage metastatic events at the murine blood-brain barrier

    OpenAIRE

    Adkins, Chris E.; Nounou, Mohamed I; Mittapalli, Rajendar K.; Terrell-Hall, Tori B; Mohammad, Afroz S; Jagannathan, Rajaganapathi; Lockman, Paul R.

    2014-01-01

    The observation that approximately 15% of women with disseminated breast cancer will develop symptomatic brain metastases combined with treatment guidelines discouraging single-agent chemotherapeutic strategies facilitates the desire for novel strategies aimed at outright brain metastasis prevention. Effective and robust preclinical methods to evaluate early stage metastatic processes, brain metastases burden, and overall mean survival are lacking. Here, we develop a novel method to quantitat...

  15. Impacts of acupuncture on blood pressure and hematoma in patients of cerebral hemorrhage at the early stage

    Institute of Scientific and Technical Information of China (English)

    陶文强

    2014-01-01

    Objective To explore the therapeutic effect of acupuncture for hypertensive cerebral hemorrhage at the early stage.Methods Fifty-four cases of small-amount cerebral hemorrhage were randomized into an acupuncture group and a conventional treatment group,27 cases in each.In the conventional treatment group,special care,oxygen therapy,nerve nutrition and symptomatic support were applied.If necessary,dehydrant and hypotensive drugs were prescribed for antihypertension,or surgery

  16. 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. PMID:22002157

  17. 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.

  18. Estimated aortic blood pressure based on radial artery tonometry underestimates directly measured aortic blood pressure in patients with advancing chronic kidney disease staging and increasing arterial stiffness

    DEFF Research Database (Denmark)

    Carlsen, Rasmus K; Peters, Christian D; Khatir, Dinah S;

    2016-01-01

    we compared invasive aortic systolic BP (SBP) with estimated central SBP obtained by radial artery tonometry and examined the influence of renal function and arterial stiffness on this relationship. We evaluated 83 patients with stage 3 to 5 CKD (mean estimated glomerular filtration rate [eGFR] 30 ml......% confidence interval -14.9 to -11.4) mm Hg. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cf-PWV) and was significantly increased in CKD patients compared with (versus) control patients (mean 10.7 vs. 9.3 m/s). The difference in BP significantly increased 1.0 mm Hg for every 10 ml....../min decrease in eGFR and by 1.6 mm Hg per 1 m/s increase in cfPWV. Using multivariate regression analysis including both eGFR and cfPWV, the difference between estimated central and invasive aortic SBP was significantly increased by 0.7 mm Hg. For the entire cohort brachial SBP significantly better reflected...

  19. 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.

  20. Pneumococcal vaccine.

    OpenAIRE

    1999-01-01

    Streptococcus pneumoniae is a frequent cause of pneumonia and meningitis. This article looks at the pneumococcal vaccine, its uses, efficacy, and adverse effects and how vaccination may be improved. We also look at the role of the new conjugate vaccines.

  1. Smallpox Vaccination

    Science.gov (United States)

    ... Newsletters Events Also Known As Smallpox = Vaccinia Smallpox Vaccination Recommend on Facebook Tweet Share Compartir The smallpox ... like many other vaccines. For that reason, the vaccination site must be cared for carefully to prevent ...

  2. 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.

  3. Immune response to hepatitis B vaccine among patients onhemodialysis

    Institute of Scientific and Technical Information of China (English)

    Gasim I Gasim; Abdelhaleem Bella; Ishag Adam

    2015-01-01

    Infection with hepatitis B virus (HBV) poses a majorhealth threat worldwide, where the magnitude andoverburden of chronic carrier state approaches 150million chronic carriers. The prevalence of HBV isgreater among dialyzed patients compared to thegeneral population owing to their increased vulnerabilityto blood and its products, along with hazards posedby contaminated hemodialysis tools and devices. Anelectronic systematic search of the published literaturewas carried and data on the immunological riposte tohepatitis B vaccination among hemodialysis patientswas extracted from relevant studies. End stage renaldisease patients on hemodialysis have a lower or anabsolutely negative riposte to HBV vaccine. Severalmeans have been tried to improve this response withsome success, nevertheless none have been universallyadopted. Genetic investigations are foreseen to make abreak through concerning HBV vaccination.

  4. 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...

  5. 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.

  6. 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. PMID:26541249

  7. Correlation between circulating white blood cell counts and level of protective immune response against bovine viral diarrhea virus elicited by a modified live vaccine

    Science.gov (United States)

    Two trials (T1 and T2) were conducted to examine the range of responses elicited against bovine viral diarrhea virus (BVDV) by vaccination with modified live vaccine and to determine the level of response required for prevention of clinical disease. For T1, BVDV neutralizing (BVDV VN) titers were de...

  8. Vaccination Against Tuberculosis With Whole-Cell Mycobacterial Vaccines.

    Science.gov (United States)

    Scriba, Thomas J; Kaufmann, Stefan H E; Henri Lambert, Paul; Sanicas, Melvin; Martin, Carlos; Neyrolles, Olivier

    2016-09-01

    Live attenuated and killed whole-cell vaccines (WCVs) offer promising vaccination strategies against tuberculosis. A number of WCV candidates, based on recombinant bacillus Calmette-Guerin (BCG), attenuated Mycobacterium tuberculosis, or related mycobacterial species are in various stages of preclinical or clinical development. In this review, we discuss the vaccine candidates and key factors shaping the development pathway for live and killed WCVs and provide an update on progress. PMID:27247343

  9. '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

  10. Glycoprotein and Glycan in Tissue and Blood Samples of Patients With Stage IB-IVA Cervical Cancer Undergoing Surgery to Remove Pelvic and Abdominal Lymph Nodes

    Science.gov (United States)

    2016-10-26

    Cervical Adenocarcinoma; Cervical Adenosquamous Carcinoma; Cervical Small Cell Carcinoma; Cervical Squamous Cell Carcinoma, Not Otherwise Specified; Stage IB Cervical Cancer; Stage IIA Cervical Cancer; Stage IIB Cervical Cancer; Stage III Cervical Cancer; Stage IVA Cervical Cancer

  11. Depletion of regulatory T cells augments a vaccine-induced T effector cell response against the liver-stage of malaria but fails to increase memory.

    Directory of Open Access Journals (Sweden)

    Maria del Rosario Espinoza Mora

    Full Text Available Regulatory T cells (T(reg have been shown to restrict vaccine-induced T cell responses in different experimental models. In these studies CD4(+CD25(+ T(reg were depleted using monoclonal antibodies against CD25, which might also interfere with CD25 on non-regulatory T cell populations and would have no effect on Foxp3(+CD25(- T(reg. To obtain more insights in the specific function of T(reg during vaccination we used mice that are transgenic for a bacterial artificial chromosome expressing a diphtheria toxin (DT receptor-eGFP fusion protein under the control of the foxp3 gene locus (depletion of regulatory T cell mice; DEREG. As an experimental vaccine-carrier recombinant Bordetella adenylate cyclase toxoid fused with a MHC-class I-restricted epitope of the circumsporozoite protein (ACT-CSP of Plasmodium berghei (Pb was used. ACT-CSP was shown by us previously to introduce the CD8+ epitope of Pb-CSP into the MHC class I presentation pathway of professional antigen-presenting cells (APC. Using this system we demonstrate here that the number of CSP-specific T cells increases when T(reg are depleted during prime but also during boost immunization. Importantly, despite this increase of T effector cells no difference in the number of antigen-specific memory cells was observed.

  12. Compromised Blood-Brain Barrier Competence in Remote Brain Areas in Ischemic Stroke Rats at Chronic Stage

    Science.gov (United States)

    Garbuzova-Davis, Svitlana; Haller, Edward; Williams, Stephanie N.; Haim, Eithan D.; Tajiri, Naoki; Hernandez-Ontiveros, Diana G.; Frisina-Deyo, Aric; Boffeli, Sean M.; Sanberg, Paul R.; Borlongan, Cesario V.

    2014-01-01

    Stroke is a life threatening disease leading to long-term disability in stroke survivors. Cerebral functional insufficiency in chronic stroke might be due to pathological changes in brain areas remote from initial ischemic lesion, i.e. diaschisis. Previously, we showed that the damaged blood-brain barrier (BBB) was implicated in subacute diaschisis. The present study investigated BBB competence in chronic diaschisis using a transient middle cerebral artery occlusion (tMCAO) rat model. Our results demonstrated significant BBB damage mostly in the ipsilateral striatum and motor cortex in rats at 30 days after tMCAO. The BBB alterations were also determined in the contralateral hemisphere via ultrastructural and immunohistochemical analyses. Major BBB pathological changes in contralateral remote striatum and motor cortex areas included: (1) vacuolated endothelial cells containing large autophagosomes, (2) degenerated pericytes displaying mitochondria with cristae disruption, (3) degenerated astrocytes and perivascular edema, (4) Evans Blue extravasation, and (5) appearance of parenchymal astrogliosis. Importantly, discrete analyses of striatal and motor cortex areas revealed significantly higher autophagosome accumulation in capillaries of ventral striatum and astrogliosis in dorsal striatum in both cerebral hemispheres. These widespread microvascular alterations in ipsilateral and contralateral brain hemispheres suggest persistent and/or continued BBB damage in chronic ischemia. The pathological changes in remote brain areas likely indicate chronic ischemic diaschisis, which should be considered in the development of treatment strategies for stroke. PMID:24610730

  13. Dendritic cell-based vaccines in the setting of peripheral blood stem cell transplantation: CD34+ cell-depleted mobilized peripheral blood can serve as a source of potent dendritic cells.

    Science.gov (United States)

    Choi, D; Perrin, M; Hoffmann, S; Chang, A E; Ratanatharathorn, V; Uberti, J; McDonagh, K T; Mulé, J J

    1998-11-01

    We are investigating the use of tumor-pulsed dendritic cell (DC)-based vaccines in the treatment of patients with advanced cancer. In the current study, we evaluated the feasibility of obtaining both CD34+ hematopoietic stem/ progenitor cells (HSCs) and functional DCs from the same leukapheresis collection in adequate numbers for both peripheral blood stem cell transplantation (PBSCT) and immunization purposes, respectively. Leukapheresis collections of mobilized peripheral blood mononuclear cells (PBMCs) were obtained from normal donors receiving granulocyte colony-stimulating factor (G-CSF) (for allogeneic PBSCT) and from intermediate grade non-Hodgkin's lymphoma or multiple myeloma patients receiving cyclophosphamide plus G-CSF (for autologous PBSCT). High enrichment of CD34+ HSCs was obtained using an immunomagnetic bead cell separation device. After separation, the negative fraction of mobilized PBMCs from normal donors and cancer patients contained undetectable levels of CD34+ HSCs by flow cytometry. This fraction of cells was then subjected to plastic adherence, and the adherent cells were cultured for 7 days in GM-CSF (100 ng/ml) and interleukin 4 (50 ng/ml) followed by an additional 7 days in GM-CSF, interleukin 4, and tumor necrosis factor alpha (10 ng/ml) to generate DCs. Harvested DCs represented yields of 4.1+/-1.4 and 5.8+/-5.4% of the initial cells plated from the CD34+ cell-depleted mobilized PBMCs of normal donors and cancer patients, respectively, and displayed a high level expression of CD80, CD86, HLA-DR, and CD11c but not CD14. This phenotypic profile was similar to that of DCs derived from non-CD34+ cell-depleted mobilized PBMCs. DCs generated from CD34+ cell-depleted mobilized PBMCs elicited potent antitetanus as well as primary allogeneic T-cell proliferative responses in vitro, which were equivalent to DCs derived from non-CD34+ cell-depleted mobilized PBMCs. Collectively, these results demonstrate the feasibility of obtaining both DCs and

  14. 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 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].

  15. A novel preclinical method to quantitatively evaluate early-stage metastatic events at the murine blood-brain barrier.

    Science.gov (United States)

    Adkins, Chris E; Nounou, Mohamed I; Mittapalli, Rajendar K; Terrell-Hall, Tori B; Mohammad, Afroz S; Jagannathan, Rajaganapathi; Lockman, Paul R

    2015-01-01

    The observation that approximately 15% of women with disseminated breast cancer will develop symptomatic brain metastases combined with treatment guidelines discouraging single-agent chemotherapeutic strategies facilitates the desire for novel strategies aimed at outright brain metastasis prevention. Effective and robust preclinical methods to evaluate early-stage metastatic processes, brain metastases burden, and overall mean survival are lacking. Here, we develop a novel method to quantitate early metastatic events (arresting and extravasation) in addition to traditional end time-point parameters such as tumor burden and survival in an experimental mouse model of brain metastases of breast cancer. Using this method, a reduced number of viable brain-seeking metastatic cells (from 3,331 ± 263 cells/brain to 1,079 ± 495 cells/brain) were arrested in brain one week postinjection after TGFβ knockdown. Treatment with a TGFβ receptor inhibitor, galunisertib, reduced the number of arrested cells in brain to 808 ± 82 cells/brain. Furthermore, we observed a reduction in the percentage of extravasated cells (from 63% to 30%) compared with cells remaining intralumenal when TGFβ is knocked down or inhibited with galunisertib (40%). The observed reduction of extravasated metastatic cells in brain translated to smaller and fewer brain metastases and resulted in prolonged mean survival (from 36 days to 62 days). This method opens up potentially new avenues of metastases prevention research by providing critical data important to early brain metastasis of breast cancer events. PMID:25348853

  16. Regional cerebral blood flow in acute stage ischemic cerebrovascular disease by xenon-133 inhalation and single photon emission computerized tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kurokawa, Hiroyuki (Akita Univ. (Japan). School of Medicine)

    1989-03-01

    During the period from February 1984 through June 1985, single photon emission computerized tomography (SPECT) with xenon-133 inhalation method has been performed for the measurement of regional cerebral blood flow (rCBF) during the first 48 hours of onset of cerebral infarction (n=71) and transient ischemic attack (n=21). X-ray CT (CT) and carotid arteriography were concurrently performed in all the patients. In repeated studies performed for 15 normal volunteers, rCBF measurement by SPECT was found reproducible. Mean values of rCBF for the right and left cerebral hemispheres were 60.3{plus minus}6.52 and 61.8{plus minus}6.91 ml/100 g/min, respectively. For cerebral infarction, ischemic foci corresponding to clinical symptoms were detected more frequently on SPECT than on CT (93% vs 63%). In all of the evaluable 35 patients with cerebral infarction, rCBF within the first 8 hours of onset was decreased: 31.0 ml/100 g/min for the internal carotid artery (ICA) occlusion and 36.0 ml/100 g/min for the middle cerebral artery (MCA) occlusion. Crossed cerebellar diaschisis was observed in 50% (9/18) for ICA occlusion and 37% (14/38) for MCA occlusion. For transient ischemic attack, there was no significant difference in the detection of ischemic foci between SPECT and CT (38% vs 43%). In detecting small foci especially in the deep regions such as the basal ganglia, SPECT was inferior to CT. Mean rCBF for transient ischemic attack tended to be lower than the normal rCBF (50.7 ml/100 g/min for the right cerebral hemisphere and 50.6 ml/100 g/min for the left cerebral hemisphere). SPECT may aid in predicting prognosis and chosing treatment strategy, as well as in determining cerebral hemodynamics. (N.K.).

  17. Hepatitis Vaccines

    OpenAIRE

    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 ...

  18. 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.

  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...... 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...... responses to the GLURP molecule and partly to the Pf155/RESA antigen in this study population were shortlived and dependent on frequent boostering, but whether these antigens play a role in the development of natural clinical immunity remains open. In the experimental group of schoolchildren weekly...

  20. Efficient monitoring of the blood-stage infection in a malaria rodent model by the rotating-crystal magneto-optical method

    Science.gov (United States)

    Orbán, Ágnes; Rebelo, Maria; Molnár, Petra; Albuquerque, Inês S.; Butykai, Adam; Kézsmárki, István

    2016-03-01

    Intense research efforts have been focused on the improvement of the efficiency and sensitivity of malaria diagnostics, especially in resource-limited settings for the detection of asymptomatic infections. Our recently developed magneto-optical (MO) method allows the accurate quantification of malaria pigment crystals (hemozoin) in blood by their magnetically induced rotation. First evaluations of the method using β-hematin crystals and in vitro P. falciparum cultures implied its potential for high-sensitivity malaria diagnosis. To further investigate this potential, here we study the performance of the method in monitoring the in vivo onset and progression of the blood-stage infection in a rodent malaria model. Our results show that the MO method can detect the first generation of intraerythrocytic P. berghei parasites 66–76 hours after sporozoite injection, demonstrating similar sensitivity to Giesma-stained light microscopy and exceeding that of flow cytometric techniques. Magneto-optical measurements performed during and after the treatment of P. berghei infections revealed that both the follow up under treatment and the detection of later reinfections are feasible with this new technique. The present study demonstrates that the MO method – besides being label and reagent-free, automated and rapid – has a high in vivo sensitivity and is ready for in-field evaluation.

  1. 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.)

  2. 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)

    To noninvasively assess global cerebral blood flow (CBF), oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO2) 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. CMRO2 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 CMRO2 (199.5 ± 36.4 vs. 193.8 ± 28.6 μmol O2 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 CMRO2. Altered neuropsychological test scores of ESRD patients were associated with OEF and CBF, but not with CMRO2. 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 CMRO2. Despite this compensatory process, however, cognitive function was still impaired and its severity was correlated with their CBF and OEF abnormality. (orig.)

  3. 肺癌患者凝血功能与肺癌分期的关系%The Relationship Between Blood Coagulation Function and Lung Cancer Staging

    Institute of Scientific and Technical Information of China (English)

    何丽钦; 钟可芳

    2012-01-01

    Objective To explore the relationship between the function of blood coagulation in patients with lung cancer and lung cancer staging. Methods EIISA assay for detection of 140 cases of advanced malignant tumor patients and 30 cases of normal human blood coagulation and anticoagulation activity related to laboratory indexes, including plasma fibrinogen ( Fb) , antithrombin III( AT-III) , von Willebrand factor ( Vwf ) , D-D ( D-dimer ). Results The patients with advanced malignant plasma D- dimer, fibrinogen, thrombin antithrombin III and von Willebrand factor antigen levels were significantly elevated and indexes in patients with lung cancer clinical staging with increased. Conclusion The patients with lung cancer usually presence of coagulation, anticoagulation and activation of fibrinolytic system, exists high coagulation state, thus, high coagulation state and clinical staging of lung cancer was positively related to.%目的 探讨肺癌患者凝血功能与肺癌分期的关系.方法 采用ELISA、免疫比浊法检测140例晚期恶性肿瘤患者和30例正常人的凝血、抗凝活性相关的实验室指标,包括血浆纤维蛋白原( Fb),抗凝血酶Ⅲ (AT-Ⅲ),血管性血友病因子 ( vWF),D-二聚体( D-D).结果 晚期恶性肿瘤患者的血浆D-D、Fb、AT-Ⅲ、vWF抗原的水平较正常人显著升高;在肺癌Ⅲ期、Ⅳ期与Ⅰ期相比明显增高(P<0.05),差异有统计学意义;Ⅱ期与Ⅰ期相比增高不明显(P>0.05),差异没有统计学意义.结论 肺癌患者存在凝血、抗凝、纤溶系统的激活,机体呈现高凝状态,并且高凝状态与肺癌临床分期呈正相关.

  4. A model to study the impact of polymorphism driven liver-stage immune evasion by malaria parasites, to help design effective cross-reactive vaccines

    Directory of Open Access Journals (Sweden)

    Kirsty Lee Wilson

    2016-03-01

    Full Text Available Malaria parasites engage a multitude of strategies to evade the immune system of the host, including the generation of polymorphic T cell epitope sequences, termed altered peptide ligands (APLs. Herein we use an animal model to study how single amino acid changes in the sequence of the circumsporozoite protein (CSP, a major target antigen of pre-erythrocytic malaria vaccines, can lead to a reduction of cross reactivity by T cells. For the first time in any APL model, we further compare different inflammatory adjuvants (Montanide, Poly I:C, non-inflammatory adjuvants (nanoparticles, and peptide pulsed dendritic cells (DCs for their potential capacity to induce broadly cross reactive immune responses. Results show that the capacity to induce a cross reactive response is primarily controlled by the T cell epitope sequence and cannot be modified by the use of different adjuvants. Moreover, we identify how specific amino acid changes lead to a one-way cross reactivity: where variant-x induced responses are re-elicited by variant-x and not variant-y, but variant-y induced responses can be re-elicited by variant-y and variant-x. We discuss the consequences of the existence of this one-way cross reactivity phenomenon for parasite immune evasion in the field, as well as the use of variant epitopes as a potential tool for optimized vaccine design.

  5. A Model to Study the Impact of Polymorphism Driven Liver-Stage Immune Evasion by Malaria Parasites, to Help Design Effective Cross-Reactive Vaccines

    Science.gov (United States)

    Wilson, Kirsty L.; Xiang, Sue D.; Plebanski, Magdalena

    2016-01-01

    Malaria parasites engage a multitude of strategies to evade the immune system of the host, including the generation of polymorphic T cell epitope sequences, termed altered peptide ligands (APLs). Herein we use an animal model to study how single amino acid changes in the sequence of the circumsporozoite protein (CSP), a major target antigen of pre-erythrocytic malaria vaccines, can lead to a reduction of cross reactivity by T cells. For the first time in any APL model, we further compare different inflammatory adjuvants (Montanide, Poly I:C), non-inflammatory adjuvants (nanoparticles), and peptide pulsed dendritic cells (DCs) for their potential capacity to induce broadly cross reactive immune responses. Results show that the capacity to induce a cross reactive response is primarily controlled by the T cell epitope sequence and cannot be modified by the use of different adjuvants. Moreover, we identify how specific amino acid changes lead to a one-way cross reactivity: where variant-x induced responses are re-elicited by variant-x and not variant-y, but variant-y induced responses can be re-elicited by variant-y and variant-x. We discuss the consequences of the existence of this one-way cross reactivity phenomenon for parasite immune evasion in the field, as well as the use of variant epitopes as a potential tool for optimized vaccine design. PMID:27014226

  6. 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...

  7. Nucleic Acid Vaccination with Schistosoma mansoni Antioxidant Enzyme Cytosolic Superoxide Dismutase and the Structural Protein Filamin Confers Protection against the Adult Worm Stage

    OpenAIRE

    Cook, Rosemary M.; Carvalho-Queiroz, Claudia; Wilding, Gregory; Philip T. LoVerde

    2004-01-01

    Schistosomiasis remains a worldwide endemic cause of chronic and debilitating illness. There are two paradigms that exist in schistosome immunology. The first is that the schistosomule stages are the most susceptible to immune killing, and the second is that the adult stage, through evolution of defense mechanisms, can survive in the hostile host environment. One mechanism that seems to aid the adult worm in evading immune killing is the expression of antioxidant enzymes to neutralize the eff...

  8. Diphtheria Vaccination

    Science.gov (United States)

    ... children and adults - Tetanus-diphtheria-acellular Pertussis vaccine Diphtheria Vaccination Pronounced (dif-THEER-ee-a) Recommend on Facebook Tweet Share Compartir Diphtheria causes a thick covering in the back of ...

  9. Pneumococcal Vaccines

    OpenAIRE

    Chen-Fang Ho; Tzou-Yien Lin

    2005-01-01

    Streptococcus pneumoniae is the leading bacterial pathogen of infectious diseases inchildren and adolescents. The 23-valent pneumococcal polysaccharide vaccine could preventinvasive pneumococcal infection with broader serotype coverage but still has some limitations.On the other hand, 7-valent pneumococcal conjugate vaccine has been shown todecrease cases of nasopharyngeal acquired S. pneumoniae vaccine serotypes and provedherd immunity. The safety and efficacy against vaccine serotype pneumo...

  10. 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...

  11. Laser Doppler flowmeter study on regional cerebral blood flow in early stage after standard superficial temporal artery-middle cerebral artery bypass surgery for moyamoya disease

    Institute of Scientific and Technical Information of China (English)

    GESANG Dun-zhu; ZHANG Dong; ZHAO Ji-zong; WANG Shuo; ZHAO Yuan-li; WANG Rong; SUN Jian-jun; MENG Ze

    2009-01-01

    Background Standard superficial temporal artery-middle cerebral artery (STA-MCA) bypass surgery is an effective treatment for moyamoya disease, but recent evidence suggests that postoperative cerebral hyperperfusion can occur. In this study, the trendline of changes in regional cerebral blood flow (rCBF) after surgery were continually monitored near the site of anastomosis in order to investigate both the efficacy of the procedure for improving rCBF and the possible riskof hyperperfusion.Methods Standard STA-MCA bypass surgery was performed on 13 patients, rCBF was measured continually using laser Doppler flowmetry (LDF) until the 5th day after the operation with the LDF probe implanted adjacent to the area of the anastomosis. The trendline of rCBF changes postoperatively was recorded for the analysis performed using SPSS 13.0.Results The baseline LDF value of cortical rCBF was (84.68±14.39) perfusion unit (PU), which was linear relative to absolute perfusion volume before anastomosis and (88.90±11.26) PU immediately after anastomosis (P >0.05). The value changed significantly from before to after anastomosis (P 0.05).Conclusions STA-MCA anastomosis improves the cerebral blood supply significantly in the early stage after surgery,however, the risk of symptomatic hyperperfusion may exist, which may possibly occur on the 1st day and 5th day after surgery. A LDF is useful for postoperative monitoring for both the efficacy of bypass and possible risk of neurologic deterioration or bleeding from hyperperfusion.

  12. Frequent detection of CXCR4-using viruses among Brazilian blood donors with HIV-1 long-standing infection and unknown clinical stage: Analysis of massive parallel sequencing data

    Directory of Open Access Journals (Sweden)

    Rodrigo Pessôa

    2016-03-01

    Full Text Available The determination of viral tropism is critically important and highly recommended to guide therapy with the CCR5 antagonist, which does not inhibit the effect of X4-tropic viruses. Here, we report the prevalence of HIV-1×4 HIV strains in 84 proviral DNA massively parallel sequencing “MPS” data from well-defined non-recently infected first-time Brazilian blood donors. The MPS data covering the entire V3 region of the env gene was extracted from our recently generated HIV-1 genomes sequenced by a paired-end protocol (Illumina. Of the 84 MPS data samples, 63 (75% were derived from donors with long-standing infection and 21 (25% were lacking stage information. HIV‐1 tropism was inferred using Geno2pheno (g2p [454] algorithm (FPR=1%, 2.5%, and 3.75%. Among the 84 data samples for which tropism was defined by g2p2.5%, 13 (15.5% participants had detectable CXCR4-using viruses in their MPS reads. Mixed infections with R5 and X4 were observed in 11.9% of the study subjects and minority X4 viruses were detected in 7 (8.3% of participants. Nine of the 63 (14.3% subjects with LS infection were predicted by g2p 2.5% to harbor proviral CXCR4-using viruses. Our findings of a high proportion of blood donors (15.5% harboring CXCR4-using viruses in PBMCs may indicate that this phenomenon is common. These findings may have implications for clinical and therapeutic aspects and may benefit individuals who plan to receive CCR5 antagonists.

  13. Serological response following re-vaccination with Salmonella typhi Vi-capsular polysaccharide vaccines in healthy adult travellers.

    Science.gov (United States)

    Roggelin, Louise; Vinnemeier, Christof D; Fischer-Herr, Johanna; Johnson-Weaver, Brandi T; Rolling, Thierry; Burchard, Gerd D; Staats, Herman F; Cramer, Jakob P

    2015-08-01

    An injectable Vi-capsular polysaccharide vaccine against typhoid fever is available but vaccine-induced immunity tends to wane over time. The phenomenon of immunotolerance or hyporesponsiveness has earlier been described for polysaccharide vaccines such as pneumococcal capsular polysaccharide vaccine and some publications also suggest a possible immunotolerance after revaccination with Vi-capsular polysaccharide vaccines. In this study, post-immunisation antibody concentrations in adult travellers first vaccinated with a Salmonella typhi Vi-capsular polysaccharide vaccine (primary vaccination group) were compared with those having received one or more vaccinations previously (multiple vaccinations group). Vaccines administered were Typherix(®) (GlaxoSmithKline), Typhim Vi(®) (Sanofi Pasteur MSD) or Hepatyrix(®) (GlaxoSmithKline). Blood samples were obtained prior to vaccination (day 0) and on day 28 (-1/+14) after vaccination. Serum Vi-Antigen IgG concentrations were measured by ELISA. Of the 85 subjects included in the per protocol data set, 45 (53%) belonged to the multiple vaccinations group. In both groups, geometric mean antibody concentrations (GMCs) were significantly higher after vaccination than before vaccination. Pre-vaccination GMCs were lower in the primary vaccination group than in the multiple vaccinations group (3.40 μg/ml versus 6.13 μg/ml, P=0.005), while there was no significant difference in the post vaccination GMCs between groups (11.34 μg/ml versus 14.58 μg/ml, P=0.4). In the multiple vaccinations group, vaccination was performed 18 to 57 months after the last vaccination (median 38 months) and there was a negative correlation between time since last vaccination and antibody concentration on day 0. In conclusion, we were not able to demonstrate a relevant immunotolerance after multiple versus primary vaccination with S. typhi Vi-capsular polysaccharide vaccines.

  14. Cerebral blood flow distribution and reactivity during the symptom-free stages of transient ischemic attacks; A [sup 99m]Tc-HMPAO SPECT study

    Energy Technology Data Exchange (ETDEWEB)

    Isaka, Yoshinari; Iiji, Osamu; Imaizumi, Masatoshi; Ashida, Keiichi (Osaka National Hospital (Japan))

    1992-08-01

    Even during the symptom-free stages, patients with transient ischemic attacks (TIA) often show cerebral blood flow (CBF) disturbances. For evaluating the factors which cause these abnormalities, we studied CBF and CBF reactivity to acetazolamide (diamox) using a [sup 99m]Tc-hexamethylpropyleneamine oxime (HMPAO) SPECT. The results from CBF-SPECT were compared with X-ray computed tomography (CT), cerebral arteriogram, clinical characteristics of TIA and cerebrovascular risk factors. The overall sensitivity rates in detecting the lesion were 68% in CBF-SPECT and 9% in CT. The size of the hypoperfused area tended to be wide in patients who had intracranial, severe stenotic or multiple arterial lesions on the ipsilateral side. No such relations were found between CBF and other examinations. Brain hypoperfusion was located in the subcortical region in eight patients; two patients showed a small hypodense lesion on CT which corresponded to the hypoperfusion on SPECT, and three patients showed no arteriographic abnormality. Hypoperfusion in the cortex was seen in seven patients; all patients showed arteriographic abnormality, but no CT abnormality. The severity rating of the vascular stenosis and hypoperfusion, and the incidence of the intracranial lesions were higher in this group than the group with subcortical hypoperfusion. Seven patients showed fixed normoperfusion before and after diamox injection. Two patients with a subcortical small infarction showed fixed hypoperfusion even after diamox injection. Twelve patients showed focal hypoperfusion before diamox with a new filling-in after diamox. Only one patient showed resting hypoperfusion and decreased CBF reactivity to diamox. The results suggest that most of the patients with a brain hypoperfusion in the symptom-free stages of TIAs have preserved cerebrovascular reactivity although a few patients show hypoperfusion having cerebral infarction or hemodynamically compromised tissue. (author).

  15. 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.

  16. Effects of low-fat dairy intake on blood pressure, endothelial function, and lipoprotein lipids in subjects with prehypertension or stage 1 hypertension

    Directory of Open Access Journals (Sweden)

    Maki KC

    2013-07-01

    Full Text Available Kevin C Maki,1 Tia M Rains,1 Arianne L Schild,1 Mary R Dicklin,1 Keigan M Park,2 Andrea L Lawless,1 Kathleen M Kelley1 1Biofortis Clinical Research, Addison, IL, USA; 2Dairy Research Institute/National Dairy Council, Rosemont, IL, USA Objective: This randomized crossover trial assessed the effects of 5 weeks of consuming low-fat dairy (one serving/day each of 1% fluid milk, low-fat cheese, and low-fat yogurt versus nondairy products (one serving/day each of apple juice, pretzels, and cereal bar on systolic and diastolic blood pressures (SBP and DBP, vascular function (reactive hyperemia index [RHI] and augmentation index, and plasma lipids. Methods: Patients were 62 men and women (mean age 54.5 years, body mass index 29.2 kg/m2 with prehypertension or stage 1 hypertension (mean resting SBP/DBP 129.8 mmHg/80.8 mmHg while not receiving antihypertensive medications. A standard breakfast meal challenge including two servings of study products was administered at the end of each treatment period. Results: Dairy and nondairy treatments did not produce significantly different mean SBP or DBP in the resting postprandial state or from premeal to 3.5 hours postmeal (SBP, 126.3 mmHg versus 124.9 mmHg; DBP, 76.5 mmHg versus 75.7 mmHg, premeal (2.35 versus 2.20 or 2 hours postmeal (2.33 versus 2.30 RHI, and premeal (22.5 versus 23.8 or 2 hours postmeal (12.4 versus 13.2 augmentation index. Among subjects with endothelial dysfunction (RHI ≤ 1.67; n = 14 during the control treatment, premeal RHI was significantly higher in the dairy versus nondairy condition (2.32 versus 1.50, P = 0.002. Fasting lipoprotein lipid values were not significantly different between treatments overall, or in subgroup analyses. Conclusion: No significant effects of consuming low-fat dairy products, compared with low-fat nondairy products, were observed for blood pressures, measures of vascular function, or lipid variables in the overall sample, but results from subgroup analyses

  17. DNA vaccines

    Science.gov (United States)

    Gregersen, Jens-Peter

    2001-12-01

    Immunization by genes encoding immunogens, rather than with the immunogen itself, has opened up new possibilities for vaccine research and development and offers chances for new applications and indications for future vaccines. The underlying mechanisms of antigen processing, immune presentation and regulation of immune responses raise high expectations for new and more effective prophylactic or therapeutic vaccines, particularly for vaccines against chronic or persistent infectious diseases and tumors. Our current knowledge and experience of DNA vaccination is summarized and critically reviewed with particular attention to basic immunological mechanisms, the construction of plasmids, screening for protective immunogens to be encoded by these plasmids, modes of application, pharmacokinetics, safety and immunotoxicological aspects. DNA vaccines have the potential to accelerate the research phase of new vaccines and to improve the chances of success, since finding new immunogens with the desired properties is at least technically less demanding than for conventional vaccines. However, on the way to innovative vaccine products, several hurdles have to be overcome. The efficacy of DNA vaccines in humans appears to be much less than indicated by early studies in mice. Open questions remain concerning the persistence and distribution of inoculated plasmid DNA in vivo, its potential to express antigens inappropriately, or the potentially deleterious ability to insert genes into the host cell's genome. Furthermore, the possibility of inducing immunotolerance or autoimmune diseases also needs to be investigated more thoroughly, in order to arrive at a well-founded consensus, which justifies the widespread application of DNA vaccines in a healthy population.

  18. 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

  19. Periodontal vaccine

    Directory of Open Access Journals (Sweden)

    Ranjan Malhotra

    2011-01-01

    Full Text Available Vaccine is the name applied generally to a substance of the nature of dead or attenuated living infectious material introduced into the body with the object of increasing its power to resist or get rid of a disease. Vaccines are generally prophylactic, i.e. they ameliorate the effects of future infection. One such vaccine considered here is the "Periodontal vaccine". Till date, no preventive modality exists for periodontal disease and treatment rendered is palliative. Thus, availability of periodontal vaccine would not only prevent and modulate periodontal disease, but also enhance the quality of life of people for whom periodontal treatment cannot be easily obtained. The aim of the research should be development of a multispecies vaccine targeting the four prime periodontal pathogens, viz. Porphyromonas gingivalis, T. forsythus, T. denticola and A. comitans. Success is still elusive in case of periodontal vaccine due to the complex etiopathogenesis of the disease.

  20. 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

    G 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....

  1. Recommendations for using smallpox vaccine in a pre-event vaccination program. Supplemental recommendations of the Advisory Committee on Immunization Practices (ACIP) and the Healthcare Infection Control Practices Advisory Committee (HICPAC).

    Science.gov (United States)

    Wharton, Melinda; Strikas, Raymond A; Harpaz, Rafael; Rotz, Lisa D; Schwartz, Benjamin; Casey, Christine G; Pearson, Michele L; Anderson, Larry J

    2003-04-01

    This report supplements the 2001 statement by the Advisory Committee on Immunization Practices (ACIP) (CDC. Vaccinia [smallpox] vaccine: recommendations of the Advisory Committee on Immunization Practices [ACIP], 2001. MMWR 2001;50[No. RR-10]:1-25). This supplemental report provides recommendations for using smallpox vaccine in the pre-event vaccination program in the United States. To facilitate preparedness and response, smallpox vaccination is recommended for persons designated by public health authorities to conduct investigation and follow-up of initial smallpox cases that might necessitate direct patient contact. ACIP recommends that each state and territory establish and maintain > or = 1 smallpox response team. ACIP and the Healthcare Infection Control Practices Advisory Committee (HICPAC) recommend that each acute-care hospital identify health-care workers who can be vaccinated and trained to provide direct medical care for the first smallpox patients requiring hospital admission and to evaluate and manage patients who are suspected as having smallpox. When feasible, the first-stage vaccination program should include previously vaccinated health-care personnel to decrease the potential for adverse events. Additionally persons administering smallpox vaccine in this pre-event vaccination program should be vaccinated. Smallpox vaccine is administered by using the multiple-puncture technique with a bifurcated needle, packaged with the vaccine and diluent. According to the product labeling, 2-3 punctures are recommended for primary vaccination and 15 punctures for revaccination. A trace of blood should appear at the vaccination site after 15-20 seconds; if no trace of blood is visible, an additional 3 insertions should be made by using the same bifurcated needle without reinserting the needle into the vaccine vial. If no evidence of vaccine take is apparent after 7 days, the person can be vaccinated again. Optimal infection-control practices and appropriate

  2. ERM immersion vaccination and adjuvants

    DEFF Research Database (Denmark)

    Skov, J.; Chettri, J. K.; Jaafar, R. M.;

    2015-01-01

    Two candidate adjuvants were tested with a commercial ERM dip vaccine (AquaVac™ Relera, MSD Animal Health) for rainbow trout in an experimental design compatible with common vaccination practices at farm level, i.e. immersion of fish in vaccine (±adjuvant) for 30 s. The adjuvants were...... the commercial product Montanide™ IMS 1312 VG PR (SEPPIC), and a soluble and ≥98% pure β-glucan from yeast (Saccharomyces cerevisiae) (Sigma-Aldrich). Hence, five experimental groups in duplicate were established and exposed to vaccine and adjuvants in the following combinations: AquaVac™ Relera (alone); Aqua......Vac™ Relera + Montanide™; AquaVac™ Relera + β-glucan; Montanide™ (alone); and β-glucan (alone). Approximately 450 degree days post-vaccination, the fish were bath-challenged with live Yersinia ruckeri to produce survival curves. Blood, skin and gills were sampled at selected time points during the course...

  3. Efetividade das vacinas anti-VHB (DNA-recombinante em doadores de sangue de uma região endêmica para hepatite B no sul do Brasil Effectiveness of recombinant DNA vaccines against hepatitis B in blood donors in an endemic region of South Brazil

    Directory of Open Access Journals (Sweden)

    Andrea Petry

    2006-10-01

    Full Text Available O objetivo deste estudo foi de estimar a efetividade das vacinas anti-VHB em um estudo longitudinal, retrospectivo composto por 1.012 doadores de sangue que completaram o esquema padrão de vacinação (três doses, incluindo doses de reforço nos doadores com títulos de anti-HBs The objective of this work was to estimate the effectiveness of DNA recombinant anti-HBV vaccines in a retrospective cohort study of 1,012 Brazilian blood donors who completed the vaccination schedule (3 doses + booster of antibody titer <10IU/L during the period 1998-2002. The results showed that seroconversion rates were significantly lower among the donors whose antibody titers was measured six months after completing the vaccination scheme and among older donors, particularly those aged over 50. Overall vaccine effectiveness was 88.7%, ranging from 80.6% in the oldest (50 years or over to 91.4% among the youngest (18-30 years donors. The booster regimen was effective at reducing the percentage of non-responders. We conclude that vaccine effectiveness was significantly better in younger blood donors and that the anti-HBs testing interval influenced the vaccine effectiveness.

  4. 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

  5. Hepatitis Vaccines

    Directory of Open Access Journals (Sweden)

    Sina Ogholikhan

    2016-03-01

    Full Text Available 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.

  6. Relationship between AQP4 expression and structural damage to the blood-brain barrier at early stages of traumatic brain injury in rats

    Institute of Scientific and Technical Information of China (English)

    LU Hong; LEI Xiao-yan; HU Hui; HE Zhan-ping

    2013-01-01

    Background Although some studies have reported that aquaporin-4 (AQP4) plays an important role in the brain edema after traumatic brain injury (TBI),little is known about the AQP4 expression in the early stage of TBI,or about the correlation between the structural damage to the blood-brain barrier (BBB) and angioedema.The aim of this project was to investigate the relationship between AQP4 expression and damage to the BBB at early stages of TBI.Methods One hundred and twenty healthy adult Wistar rats were randomly divided into two greups:sham operation group (SO) and TBI group.The TBI group was divided into five sub-groups according to the different time intervals:1,3,6,12,and 24 hours.The brains of the animals were taken out at different time points after TBI to measure brain water content.The cerebral edema and BBB changes in structure were examined with an optical microscopy (OM) and transmission electron microscopy (TEM),and the IgG content and AQP4 protein expression in traumatic brain tissue were determined by means of immunohistochemistry and Western blotting.The data were analyzed with SPSS 13.0statistical software.Results In the SO greup,tissue was negative for IgG,and there were no abnormalities in brain water content or AQP4 expression.In the TBI group,brain water content significantly increased at 6 hours and peaked at 24 hours following injury.IgG expression significantly increased from 1 to 6 hours following injury,and remained at a high level at 24 hours.Pathological observation revealed BBB damage at 1 hour following injury.Angioedema appeared at 1 hour,was gradually aggravated,and became obvious at 6 hours.Intracellular edema occurred at 3 hours,with the presence of large glial cell bodies and mitochondrial swelling.These phenomena were aggravated with time and became obvious at 12 hours.In addition,microglial proliferation was visible at 24 hours.AQP4 protein expression were reduced at 1 hour,lowest at 6 hours,and began to increase at 12 hours

  7. Rubella Antibody Levels in School-Aged Children in Newfoundland: Implications for a Two-Dose Rubella Vaccination Strategy

    OpenAIRE

    Ratnam, Samuel; West, Roy; Gadag, Veeresh; Williams, Brett; Oates, Elizabeth

    1997-01-01

    OBJECTIVE: To determine the prevailing levels of rubella immunity among school-aged children who received a single dose of measles-mumps-rubella (MMR) vaccine at one year of age.DESIGN: Cross-sectional study with a two stage cluster sampling of randomly picked schools across the province of Newfoundland.STUDY POPULATION AND METHODS: A total of 1053, five to 17-year-old children were enrolled; vaccination history was verified through official records; and a sample of blood was taken. Rubella i...

  8. 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)

    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)

  9. 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)

  10. Nitric oxide synthetic pathway and cGMP levels are altered in red blood cells from end-stage renal disease patients.

    Science.gov (United States)

    Di Pietro, Natalia; Giardinelli, Annalisa; Sirolli, Vittorio; Riganti, Chiara; Di Tomo, Pamela; Gazzano, Elena; Di Silvestre, Sara; Panknin, Christina; Cortese-Krott, Miriam M; Csonka, Csaba; Kelm, Malte; Ferdinandy, Péter; Bonomini, Mario; Pandolfi, Assunta

    2016-06-01

    Red blood cells (RBCs) enzymatically produce nitric oxide (NO) by a functional RBC-nitric oxide synthase (RBC-NOS). NO is a vascular key regulatory molecule. In RBCs its generation is complex and influenced by several factors, including insulin, acetylcholine, and calcium. NO availability is reduced in end-stage renal disease (ESRD) and associated with endothelial dysfunction. We previously demonstrated that, through increased phosphatidylserine membrane exposure, ESRD-RBCs augmented their adhesion to human cultured endothelium, in which NO bioavailability decreased. Since RBC-NOS-dependent NO production in ESRD is unknown, this study aimed to investigate RBC-NOS levels/activation, NO production/bioavailability in RBCs from healthy control subjects (C, N = 18) and ESRD patients (N = 27). Although RBC-NOS expression was lower in ESRD-RBCs, NO, cyclic guanosine monophosphate (cGMP), RBC-NOS Serine1177 phosphorylation level and eNOS/Calmodulin (CaM)/Heat Shock Protein-90 (HSP90) interaction levels were higher in ESRD-RBCs, indicating increased enzyme activation. Conversely, following RBCs stimulation with insulin or ionomycin, NO and cGMP levels were significantly lower in ESRD- than in C-RBCs, suggesting that uremia might reduce the RBC-NOS response to further stimuli. Additionally, the activity of multidrug-resistance-associated protein-4 (MRP4; cGMP-membrane transporter) was significantly lower in ESRD-RBCs, suggesting a possible compromised efflux of cGMP across the ESRD-RBCs membrane. This study for the first time showed highest basal RBC-NOS activation in ESRD-RBCs, possibly to reduce the negative impact of decreased NOS expression. It is further conceivable that high NO production only partially affects cell function of ESRD-RBCs maybe because in vivo they are unable to respond to physiologic stimuli, such as calcium and/or insulin. PMID:27206740

  11. 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

  12. 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

  13. 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

  14. 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

  15. Status of vaccine research and development of vaccines for malaria.

    Science.gov (United States)

    Birkett, Ashley J

    2016-06-01

    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. PMID:26993333

  16. Hepatitis B Vaccine

    Science.gov (United States)

    ... as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... Hepatitis B vaccine: Why get vaccinated?Hepatitis B vaccine can prevent hepatitis B, and the serious consequences of hepatitis ...

  17. [HPV vaccination].

    Science.gov (United States)

    Stronski Huwiler, Susanne; Spaar, Anne

    2016-01-01

    Human Papilloma Viruses are associated with genital carcinoma (of the cervix, anus, vulva, vagina and the penis) as well as with non-genital carcinoma (oropharyngeal carcinoma) and genital warts. In Switzerland two highly efficient and safe vaccines are available. The safety of these vaccines has been repeatedly subject of controversial discussions, however so far post marketing surveillance has always been able to confirm the safety. In Switzerland girls and young women have been offered the HPV vaccination within cantonal programmes since 2008. 2015 the recommendation for the HPV-vaccination for boys and young men was issued, and starting July 1, 2016 they as well will be offered vaccination free of charge within the cantonal programmes. This article discusses the burden of disease, efficacy and safety of the vaccines and presents facts which are important for vaccinating these young people. Specifically, aspects of the decisional capacity of adolescents to consent to the vaccination are presented. Finally, the future perspective with a focus on a new vaccine with an enlarged spectrum of HPV-types is discussed. PMID:27268446

  18. Estimated aortic blood pressure based on radial artery tonometry underestimates directly measured aortic blood pressure in patients with advancing chronic kidney disease staging and increasing arterial stiffness.

    Science.gov (United States)

    Carlsen, Rasmus K; Peters, Christian D; Khatir, Dinah S; Laugesen, Esben; Bøtker, Hans Erik; Winther, Simon; Buus, Niels H

    2016-10-01

    Central blood pressure (BP) can be assessed noninvasively based on radial tonometry and may potentially be a better predictor of clinical outcome than brachial BP. However, the validity of noninvasively obtained estimates has never been examined in patients with chronic kidney disease (CKD). Here we compared invasive aortic systolic BP (SBP) with estimated central SBP obtained by radial artery tonometry and examined the influence of renal function and arterial stiffness on this relationship. We evaluated 83 patients with stage 3 to 5 CKD (mean estimated glomerular filtration rate [eGFR] 30 ml/min/1.73 m(2)) and 41 controls without renal disease undergoing scheduled coronary angiography. BP in the ascending aorta was measured through the angiography catheter and simultaneously estimated using radial tonometry. The mean difference between estimated central and aortic SBP was -13.2 (95% confidence interval -14.9 to -11.4) mm Hg. Arterial stiffness was evaluated by carotid-femoral pulse wave velocity (cf-PWV) and was significantly increased in CKD patients compared with (versus) control patients (mean 10.7 vs. 9.3 m/s). The difference in BP significantly increased 1.0 mm Hg for every 10 ml/min decrease in eGFR and by 1.6 mm Hg per 1 m/s increase in cfPWV. Using multivariate regression analysis including both eGFR and cfPWV, the difference between estimated central and invasive aortic SBP was significantly increased by 0.7 mm Hg. For the entire cohort brachial SBP significantly better reflected invasive SBP than estimated SBP. Thus, tonometry-based estimates of central BP progressively underestimate invasive central SBP with decreasing renal function and increasing arterial stiffness in CKD patients.

  19. 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

  20. Experimental vaccines for sexually transmitted infections

    Directory of Open Access Journals (Sweden)

    Jovanović Marina

    2009-01-01

    Full Text Available Introduction. Sexually transmitted infections (STIs are major global public health problems. Present strategies for prevention have limitations. Vaccines are an attractive addition to the current prevention armamentarium because they provide durable protection and do not require repetitive adherence to be effective. Challenges for vaccination include induction and long-term maintaince of mucosal immune responses in the female genital tract. Vaccines: a realistic goal?. For the time being, US Centers for Disease Control and Prevention have recommended only hepatitis and HPV immunization to be routinely offered. Final, III stage trials are underway on other prophylactic vaccines for human papillomavirus and genital herpes. Though vaccines against Chlamydia trachomatis and Neisseria gonorrhoeae are in early stages of development they do offer the hope of preventing pelvic inflammations. The high incidence of HIV-infection for which a vaccine would not be readily available, 'cries out' for an effective vaccine. Vaccines for HPV infections. According to a recent meta-analysis of worldwide prevalence data, vaccinating with HPV-16/18 VLP against HPV-16 and HPV-18 could prevent over 70% of invasive cervical cancer worldwide. The latest release of data from the phase III trial of a quadrivalent recombinant non-infectious vaccine HPV-6/11/ 16/18 L1 VLP, including HPV types 6,11,16,18 have given complete protection against HPV-16/18-related cervical intraepithelial neoplasias 1, 2/3, and adenocarcinoma in situ and cancer through 2 years of post-vaccination follow up. Conclusion. Despite the fact that the development of vaccines for STI prevention was rather slow in the past, the ideal vaccine would decrease transmission of the infection between partners and would prevent complications of disease. Moreover, in future decades, increasingly successful universal vaccination of newborns and children will substantially reduce the need for vaccination of persons

  1. Development and application of next generation SE36 malaria vaccine formulated with a novel adjuvant: approach to travelers' vaccine.

    Science.gov (United States)

    Tougan, Takahiro; Ishii, Ken J; Horii, Toshihiro

    2013-01-01

    The SE36 antigen, derived from serine repeat antigen 5 (SERA5) of Plasmodium falciparum, is a promising blood stage malaria vaccine candidate. Previous clinical trials indicated the protective efficacy of BK-SE36 malaria vaccine that is constituted of SE36 recombinant protein and aluminum hydroxide gel. In this study, we assessed the safety, immunogenicity and protective efficacy of SE36/AHG formulated with TLR9 ligand adjuvants K3 CpG oligodeoxyribonucleotides (CpG ODNs) (K3 ODN), D3 ODN or synthetic hemozoin, in two non-human primate models. SE36/AHG with or without each adjuvant was administrated to cynomolgus monkeys. A combination of TLR9 ligand adjuvant with SE36/AHG induced higher humoral and cellular immune response compared with SE36/AHG alone. The most effective TLR9 ligand, K3 ODN, was chosen for further vaccine trials in squirrel monkeys, in combination with SE36/AHG. All monkeys immunized SE36/AHG with K3 ODN effectively suppressed parasitemia and symptoms of malaria following challenge infection. Furthermore, no serious adverse events were observed. Our results show that the novel vaccine formulation of K3 ODN with SE36/AHG is safety, potent immunogenicity and efficacy in nonhuman primates. We are conducting the first in human clinical trials with this formulation. PMID:24189556

  2. Rotavirus Vaccine

    Science.gov (United States)

    Why get vaccinated?Rotavirus is a virus that causes diarrhea, mostly in babies and young children. The diarrhea can be severe, and lead ... and fever are also common in babies with rotavirus.Before rotavirus vaccine, rotavirus disease was a common ...

  3. 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.

  4. CLINICAL OBSERVATION ABOUT THE EFFECT OF BLOOD-LETTING OF JING-POINTS ON CEREBRAL BLOOD FLOW IN STROKE PATIENTS AT THE EARLY STAGE AND EXPERIMENTAL STUDY ON ITS MECHANISMS IN THE RABBIT

    Institute of Scientific and Technical Information of China (English)

    WANG Xiuyun; REN Shusheng; GUO Yi; ZHOU Guoping; ZHOU Zhiliang; PAN Rongqing; XU Tangping; LI Qing; WANG Xin; REN Huanzhong

    2002-01-01

    In this paper,the authors sum their research resuits about the effect of blood-letting of Jing(Well)-point on cerebral blood flow both in stroke patients and in experimental cerebral ischemia,cerebral hematoma and hypertension rabbits.In 30cases of stroke (cerebral hemorrhage and cerebral infarction)patients,blood flow state of the anterior cerebral artery(ACA),middle cerebral artery(MCA)and the posterior cerebral artery (PCA), and the blood flow velocity of the bilateral vertebral artery (VA)and the basil artery(BA)are determined before and afterpricking blood of the Twelve Jing-points.In experimental cerebral ischernia (by occlusion of the common carotid ertery) rabbits ,cerebral hematoma model rabbits and intravenous injection of noradrenaline induced hypertension rabbits, rheoencephalogram(REC) is detected before and after blood letting of the twelve"Jing -points.In these 30stroke patients,ultrasound Doppler examination's results show that in 22 cases (73.33%) whose blood flow velocity decreases,after blood-letting of the 12 Jing-points, it ncreases significantly(P< 0.01); in the rest 8 cases (26.67%) whose blood flow velocity speeds up,after treatment,it decreases evidently(P<tly (P< 0.01), showing a good dual-directional regulative effect of blood -letting therapy.In experimental cerebral ischemia rabbits,cerebral hematoma rabbits and hypertension rabbits whose REG lowers in the amplitude apparently ( P < 0.01 ), after blood letting stimulation of the 12 Jing-points, it increases at different degrees.Three patterns of stimulation as blood letting stimulation, pain stimulation and Jing-point stimulation, also the 3factors of blood-letting,may contribute to their effect on improvement of the cerebral blood flow.Somatic affterent nerve,sympathetic nerve of the vasular wall,central cholinergic nerve(M receptors)and adrenergic nerve (α receptors) participate in the effect of blood letting on cerebral blood flow.

  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. Serial transfer of a transplantable tumor: implications for Marek's vaccine mechanisms.

    Science.gov (United States)

    Hunt, Henry D; Dunn, John R

    2011-06-01

    The mechanism of Marek's disease (MD) vaccination to prevent the lymphoproliferative disease in chickens is not well understood. It is generally recognized that vaccination prevents disease, including the induction of T-cell tumors, but it does not prevent the pathogenic virus from infecting and replicating in the vaccinated host, nor does it prevent bird to bird spread of the oncogenic virus. The stage at which the vaccinated immune system intervenes in the process from infection to the induction of tumors remains obscure. Using a transplantable tumor induced by the Md5 strain of MD virus (MDV), we show that CVI988 vaccination does not prevent the induction of transplantable tumors in the 15I(5) x 7(1) chicken line. A monoclonal tumor with a V beta 1 T-cell receptor spectratype of 207 base pairs was used to follow the transplantable tumor in serial passages in vivo. This transplantable tumor could be passed in vaccinated birds. The length of time between vaccination and challenge (5 to 12 days) had little or no influence on the ability to transfer the tumor. There was variability in the manifestation of the disease produced by the transplanted tumor. Some chickens presented as normal but were still capable of transmitting the transplanted tumor to newly vaccinated recipients via their blood. This indicates that some chickens can control, but not eliminate, the tumor. The variables inducing health or disease in the challenged chickens remain obscure, but environmental or other factors likely depress the immune system allowing the tumor to overwhelm the immune system.

  7. Tumor vaccines

    International Nuclear Information System (INIS)

    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)

  8. Absence of detectable measles virus genome sequence in blood of autistic children who have had their MMR vaccination during the routine childhood immunization schedule of UK.

    Science.gov (United States)

    Afzal, M A; Ozoemena, L C; O'Hare, A; Kidger, K A; Bentley, M L; Minor, P D

    2006-05-01

    Leukocyte preparations from children with documented evidence of MMR vaccination and confirmed diagnosis of autism were examined by several assays designed to target multiple regions of the measles virus genome sequence. No sample was found positive by any method. The assays applied were highly sensitive, specific and robust in nature, and were based on the amplification of measles virus RNA transcripts by real-time quantitative RT-PCR (QRT-PCR) as well as by conventional RT-PCR-nested PCR. The assays applied were potentially able to detect measles virus RNA down to single figure copy numbers per reaction. The amount of total nucleic acid extract of leukocytes subjected to various measles virus-specific investigations was several fold higher than minimally required of a sample where measles virus persistence is well documented. This study failed to substantiate reports of the persistence of measles virus in autistic children with development regression.

  9. Find out the Target IOP while Different Blood Pressure in Advanced Stage Glaucoma%晚期青光眼在不同血压段时靶眼压的选择

    Institute of Scientific and Technical Information of China (English)

    晏兴云; 贺平; 刘静

    2016-01-01

    目的:探讨晚期青光眼在不同血压段时病程的进展规律 ,并找出在不同血压段时的治疗靶眼压.方法:长期随访晚期青光眼患者的血压及眼压值 ,并分别做视野检查 ,通过A G IS评分法判断病程的进展.并统计出不同血压时的治疗靶眼压值.结果:随访血压越低 ,视野受损进展越快.当视野无进展时 ,血压越低 ,其随访眼压也越低.血压与目标眼压之间呈近似线性关系.结论:低血压是晚期青光眼病程中的危险因素之一.晚期青光眼患者对靶眼压的选择应根据不同血压段来选择.%Objective:To explore progress rule of advanced stage glaucoma and find out the target intraocular pressure in different blood pressure .Methods:Long term follow-up the intraocular pressure and blood pressure .Judge the course of glaucoma by AGIS .find out the target intraocular pressure in different blood pressure .Results:For the lower blood pressure ,impaired vision progress more quickly .When vision without progress ,the lower blood pressure ,the lower intraocular pressure there has been approximate linear relationship between blood pressure and the target intraocular pressure .Conclusion:Low blood pressure is one of the risk factors of adanced glaucoma progression .The target in-traocular pressure should be selected according to different blood pressure .

  10. Veterinary vaccines against Toxoplasma gondii

    Directory of Open Access Journals (Sweden)

    Elisabeth A Innes

    2009-03-01

    Full Text Available Toxoplasma gondii has a very wide intermediate host range and is thought to be able to infect all warm blooded animals. The parasite causes a spectrum of different diseases and clinical symptoms within the intermediate hosts and following infection most animals develop adaptive humoral and cell-mediated immune responses. The development of protective immunity to T. gondii following natural infection in many host species has led researchers to look at vaccination as a strategy to control disease, parasite multiplication and establishment in animal hosts. A range of different veterinary vaccines are required to help control T. gondii infection which include vaccines to prevent congenital toxoplasmosis, reduce or eliminate tissue cysts in meat producing animals and to prevent oocyst shedding in cats. In this paper we will discuss some of the history, challenges and progress in the development of veterinary vaccines against T. gondii.

  11. Meningococcal Vaccinations.

    Science.gov (United States)

    Crum-Cianflone, Nancy; Sullivan, Eva

    2016-06-01

    Neisseria meningitidis, a gram-negative diplococcal bacterium, is a common asymptomatic nasopharyngeal colonizer that may infrequently lead to invasive disease in the form of meningitis or bacteremia. Six serogroups (A, B, C, W, X and Y) are responsible for the majority of invasive infections. Increased risk of disease occurs in specific population groups including infants, adolescents, those with asplenia or complement deficiencies, and those residing in crowded living conditions such as in college dormitories. The incidence of invasive meningococcal disease varies geographically with some countries (e.g., in the African meningitis belt) having both high endemic disease rates and ongoing epidemics, with annual rates reaching 1000 cases per 100,000 persons. Given the significant morbidity and mortality associated with meningococcal disease, it remains a major global health threat best prevented by vaccination. Several countries have implemented vaccination programs with the selection of specific vaccine(s) based on locally prevalent serogroup(s) of N. meningitidis and targeting population groups at highest risk. Polysaccharide meningococcal vaccines became available over 40 years ago, but are limited by their inability to produce immunologic memory responses, poor immunogenicity in infants/children, hyporesponsiveness after repeated doses, and lack of efficacy against nasopharyngeal carriage. In 1999, the first meningococcal conjugate vaccines were introduced and have been successful in overcoming many of the shortcomings of polysaccharide vaccines. The implementation of meningococcal conjugate vaccination programs in many areas of the world (including the massive campaign in sub-Saharan Africa using a serogroup A conjugate vaccine) has led to dramatic reductions in the incidence of meningococcal disease by both individual and population protection. Progressive advances in vaccinology have led to the recent licensure of two effective vaccines against serogroup B

  12. Duration of serum antibody response to rabies vaccination in horses.

    Science.gov (United States)

    Harvey, Alison M; Watson, Johanna L; Brault, Stephanie A; Edman, Judy M; Moore, Susan M; Kass, Philip H; Wilson, W David

    2016-08-15

    OBJECTIVE To investigate the impact of age and inferred prior vaccination history on the persistence of vaccine-induced antibody against rabies in horses. DESIGN Serologic response evaluation. ANIMALS 48 horses with an undocumented vaccination history. PROCEDURES Horses were vaccinated against rabies once. Blood samples were collected prior to vaccination, 3 to 7 weeks after vaccination, and at 6-month intervals for 2 to 3 years. Serum rabies virus-neutralizing antibody (RVNA) values were measured. An RVNA value of ≥ 0.5 U/mL was used to define a predicted protective immune response on the basis of World Health Organization recommendations for humans. Values were compared between horses vaccinated and those inferred to be immunologically naïve. RESULTS A protective RVNA value (≥ 0.5 U/mL) was maintained for 2 to 3 years in horses inferred to have been previously vaccinated on the basis of prevaccination RVNA values. No significant difference was evident in response to rabies vaccination or duration of protective RVNA values between horses vaccination. Significant differences were identified between horses inferred to have been previously vaccinated and horses inferred to be naïve prior to the study. CONCLUSIONS AND CLINICAL RELEVANCE A rabies vaccination interval > 1 year may be appropriate for previously vaccinated horses but not for horses vaccinated only once. Additional research is required to confirm this finding and characterize the optimal primary dose series for rabies vaccination. PMID:27479286

  13. HPV vaccine

    Science.gov (United States)

    ... EFFECTS The most common side effects are fainting, dizziness, nausea, headache, and skin reactions at the site where the shot was given. WHAT ELSE TO THINK ABOUT The HPV vaccine does not protect against all types of HPV ...

  14. Arthropod vaccines.

    Science.gov (United States)

    Lee, R; Opdebeeck, J P

    1999-03-01

    Antigens located in the midgut of the tick are hidden from the host's immune system. Egg production of ticks can be reduced when ticks are fed on animals vaccinated with midgut antigens of the tick, and a subunit vaccine formulated with the recombinant antigen Bm86 is now available that can reduce the number of ticks infesting cattle grazing on pasture. Midgut antigens used in vaccines against insects that transmit pathogenic organisms to humans have not been as effective in reducing insect fecundity and an alternative approach may be necessary. Transmission-blocking vaccines directed at interfering with the vector-pathogen interaction could result in loss of vector competence and block the spread of disease-causing organisms. PMID:10198800

  15. TLR9 adjuvants enhance immunogenicity and protective efficacy of the SE36/AHG malaria vaccine in nonhuman primate models.

    Science.gov (United States)

    Tougan, Takahiro; Aoshi, Taiki; Coban, Cevayir; Katakai, Yuko; Kai, Chieko; Yasutomi, Yasuhiro; Ishii, Ken J; Horii, Toshihiro

    2013-02-01

    The SE36 antigen, derived from serine repeat antigen 5 (SERA5) of Plasmodium falciparum, is a promising blood stage malaria vaccine candidate. Ongoing clinical trials suggest the efficacy of the SE36 vaccine could be increased by the incorporation of more effective adjuvants into the vaccine formulation. In this study, we assessed the safety, immunogenicity and protective efficacy of SE36/AHG formulated with TLR9 ligand adjuvants K3 CpG oligodeoxyribonucleotides (CpG ODNs) (K3 ODN), D3 ODN or synthetic hemozoin, in two non-human primate models. SE36/AHG with or without each adjuvant was administrated to cynomolgus monkeys. A combination of TLR9 ligand adjuvant with SE36/AHG induced higher humoral and cellular immune response compared with SE36/AHG alone. Administration of a crude extract of P. falciparum parasite resulted in the induction of more SE36-specific IgG antibodies in monkeys vaccinated with a combination of SE36/AHG and adjuvant, as opposed to vaccination with SE36/AHG alone. The most effective TLR9 ligand, K3 ODN, was chosen for further vaccine trials in squirrel monkeys, in combination with SE36/AHG. All monkeys immunized with the combined SE36/AHG and K3 ODN formulation effectively suppressed parasitemia and symptoms of malaria following challenge infections. Furthermore, no serious adverse events were observed. Our results show that the novel vaccine formulation of K3 ODN with SE36/AHG demonstrates safety, potent immunogenicity and efficacy in nonhuman primates, and this vaccine formulation may form the basis of a more effective malaria vaccine. PMID:23291928

  16. 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

  17. Clinical trial in healthy malaria-naïve adults to evaluate the safety, tolerability, immunogenicity and efficacy of MuStDO5, a five-gene, sporozoite/hepatic stage Plasmodium falciparum DNA vaccine combined with escalating dose human GM-CSF DNA

    Science.gov (United States)

    Richie, Thomas L.; Charoenvit, Yupin; Wang, Ruobing; Epstein, Judith E.; Hedstrom, Richard C.; Kumar, Sanjai; Luke, Thomas C.; Freilich, Daniel A.; Aguiar, Joao C.; Sacci, Jr., John B.; Sedegah, Martha; Nosek, Jr., Ronald A.; De La Vega, Patricia; Berzins, Mara P.; Majam, Victoria F.; Abot, Esteban N.; Ganeshan, Harini; Richie, Nancy O.; Banania, Jo Glenna; Baraceros, Maria Fe B.; Geter, Tanya G.; Mere, Robin; Bebris, Lolita; Limbach, Keith; Hickey, Bradley W.; Lanar, David E.; Ng, Jennifer; Shi, Meng; Hobart, Peter M.; Norman, Jon A.; Soisson, Lorraine A.; Hollingdale, Michael R.; Rogers, William O.; Doolan, Denise L.; Hoffman, Stephen L.

    2012-01-01

    When introduced in the 1990s, immunization with DNA plasmids was considered potentially revolutionary for vaccine development, particularly for vaccines intended to induce protective CD8 T cell responses against multiple antigens. We conducted, in 1997−1998, the first clinical trial in healthy humans of a DNA vaccine, a single plasmid encoding Plasmodium falciparum circumsporozoite protein (PfCSP), as an initial step toward developing a multi-antigen malaria vaccine targeting the liver stages of the parasite. As the next step, we conducted in 2000–2001 a clinical trial of a five-plasmid mixture called MuStDO5 encoding pre-erythrocytic antigens PfCSP, PfSSP2/TRAP, PfEXP1, PfLSA1 and PfLSA3. Thirty-two, malaria-naïve, adult volunteers were enrolled sequentially into four cohorts receiving a mixture of 500 μg of each plasmid plus escalating doses (0, 20, 100 or 500 μg) of a sixth plasmid encoding human granulocyte macrophage-colony stimulating factor (hGM-CSF). Three doses of each formulation were administered intramuscularly by needle-less jet injection at 0, 4 and 8 weeks, and each cohort had controlled human malaria infection administered by five mosquito bites 18 d later. The vaccine was safe and well-tolerated, inducing moderate antigen-specific, MHC-restricted T cell interferon-γ responses but no antibodies. Although no volunteers were protected, T cell responses were boosted post malaria challenge. This trial demonstrated the MuStDO5 DNA and hGM-CSF plasmids to be safe and modestly immunogenic for T cell responses. It also laid the foundation for priming with DNA plasmids and boosting with recombinant viruses, an approach known for nearly 15 y to enhance the immunogenicity and protective efficacy of DNA vaccines. PMID:23151451

  18. BCG vaccination: a role for vitamin D?

    Directory of Open Access Journals (Sweden)

    Maeve K Lalor

    Full Text Available BACKGROUND: BCG vaccination is administered in infancy in most countries with the aim of providing protection against tuberculosis. There is increasing interest in the role of vitamin D in immunity to tuberculosis. This study objective was to determine if there was an association between circulating 25(OHD concentrations and BCG vaccination status and cytokine responses following BCG vaccination in infants. METHODS: Blood samples were collected from UK infants who were vaccinated with BCG at 3 (n = 47 and 12 (n = 37 months post BCG vaccination. These two time-points are denoted as time-point 1 and time-point 2. Two blood samples were also collected from age-matched unvaccinated infants (n = 32 and 28 respectively, as a control group. Plasma vitamin D concentrations (25(OHD were measured by radio-immunoassay. The cytokine IFNγ was measured in supernatants from diluted whole blood stimulated with M.tuberculosis (M.tb PPD for 6 days. RESULTS: 58% of infants had some level of hypovitaminosis (25(OHD <30 ng/ml at time-point 1, and this increased to 97% 9 months later. BCG vaccinated infants were almost 6 times (CI: 1.8-18.6 more likely to have sufficient vitamin D concentrations than unvaccinated infants at time-point 1, and the association remained strong after controlling for season of blood collection, ethnic group and sex. Among vaccinees, there was also a strong inverse association between IFNγ response to M.tb PPD and vitamin D concentration, with infants with higher vitamin D concentrations having lower IFNγ responses. CONCLUSIONS: Vitamin D may play an immuno-regulatory role following BCG vaccination. The increased vitamin D concentrations in BCG vaccinated infants could have important implications: vitamin D may play a role in immunity induced by BCG vaccination and may contribute to non-specific effects observed following BCG vaccination.

  19. 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

  20. 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 ...

  1. Vaccines and Thimerosal

    Science.gov (United States)

    ... Preparedness Vaccine Safety Partners About ISO 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 ...

  2. Live Virus Smallpox Vaccine

    Science.gov (United States)

    ... A - Z Index SMALLPOX FACT SHEET The Live Virus Smallpox Vaccine The vaccinia virus is the "live ... it cannot cause smallpox. What is a "live virus" vaccine? A "live virus" vaccine is a vaccine ...

  3. Immune Responses Induced by Gene Gun or Intramuscular Injection of DNA Vaccines That Express Immunogenic Regions of the Serine Repeat Antigen from Plasmodium falciparum

    OpenAIRE

    Belperron, Alexia A.; Feltquate, David; Fox, Barbara A.; Horii, Toshihiro; Bzik, David J.

    1999-01-01

    The liver- and blood-stage-expressed serine repeat antigen (SERA) of Plasmodium falciparum is a candidate protein for a human malaria vaccine. We compared the immune responses induced in mice immunized with SERA-expressing plasmid DNA vaccines delivered by intramuscular (i.m.) injection or delivered intradermally by Gene Gun immunization. Mice were immunized with a pcdna3 plasmid encoding the entire 47-kDa domain of SERA (amino acids 17 to 382) or the N-terminal domain (amino acids 17 to 110)...

  4. Prophylactic vaccines are potent activators of monocyte-derived dendritic cells and drive effective anti-tumor responses in melanoma patients at the cost of toxicity.

    Science.gov (United States)

    Bol, Kalijn F; Aarntzen, Erik H J G; Pots, Jeanette M; Olde Nordkamp, Michel A M; van de Rakt, Mandy W M M; Scharenborg, Nicole M; de Boer, Annemiek J; van Oorschot, Tom G M; Croockewit, Sandra A J; Blokx, Willeke A M; Oyen, Wim J G; Boerman, Otto C; Mus, Roel D M; van Rossum, Michelle M; van der Graaf, Chantal A A; Punt, Cornelis J A; Adema, Gosse J; Figdor, Carl G; de Vries, I Jolanda M; Schreibelt, Gerty

    2016-03-01

    Dendritic cell (DC)-based immunotherapy is explored worldwide in cancer patients, predominantly with DC matured with pro-inflammatory cytokines and prostaglandin E2. We studied the safety and efficacy of vaccination with monocyte-derived DC matured with a cocktail of prophylactic vaccines that contain clinical-grade Toll-like receptor ligands (BCG, Typhim, Act-HIB) and prostaglandin E2 (VAC-DC). Stage III and IV melanoma patients were vaccinated via intranodal injection (12 patients) or combined intradermal/intravenous injection (16 patients) with VAC-DC loaded with keyhole limpet hemocyanin (KLH) and mRNA encoding tumor antigens gp100 and tyrosinase. Tumor antigen-specific T cell responses were monitored in blood and skin-test infiltrating-lymphocyte cultures. Almost all patients mounted prophylactic vaccine- or KLH-specific immune responses. Both after intranodal injection and after intradermal/intravenous injection, tumor antigen-specific immune responses were detected, which coincide with longer overall survival in stage IV melanoma patients. VAC-DC induce local and systemic CTC grade 2 and 3 toxicity, which is most likely caused by BCG in the maturation cocktail. The side effects were self-limiting or resolved upon a short period of systemic steroid therapy. We conclude that VAC-DC can induce functional tumor-specific responses. Unfortunately, toxicity observed after vaccination precludes the general application of VAC-DC, since in DC maturated with prophylactic vaccines BCG appears to be essential in the maturation cocktail.

  5. Research progress on malaria vaccine%疟疾疫苗的研究进展

    Institute of Scientific and Technical Information of China (English)

    杜津; 王东旭; 程莉

    2008-01-01

    疟疾疫苗对控制全球疟疾的流行起着相当重要的作用.当前,全球科学家正在研制3种类型的疟疾疫苗:抗红内期原虫疫苗、抗红前期原虫疫苗和传播阻断疫苗.其中一些候选疫苗已进入临床试验,并产生了有意义的结果.此文就这方面研究的主要进展进行综述.%Malaria vaccine plays an important role in controling malaria epidemic.At present,global scientists are developing three types of malaria vaccine:asexual blood-stage vaccines,pre-erythrocytic vaccines and transmission blocking vaccines,some of which have entered clinical trials and produced meaningful results.In the article,the main progress are reviewed.

  6. Plasmodium falciparum serine repeat antigen 5 (SE36) as a malaria vaccine candidate.

    Science.gov (United States)

    Palacpac, Nirianne Marie Q; Arisue, Nobuko; Tougan, Takahiro; Ishii, Ken J; Horii, Toshihiro

    2011-08-11

    A devastating disease spread by mosquitoes with high-efficiency, malaria imposes an enormous burden for which no licensed vaccine currently exists. Although the genome complexity of the parasite has made vaccine development tenuous, an effective malaria vaccine would be a valuable tool for control, elimination and eventual eradication. The Plasmodium serine repeat antigen 5 (SERA5) is an abundant asexual blood stage antigen that does not show any antigenic variation and exhibits limited polymorphism, making it a suitable vaccine candidate. Identified by comparing the IgG status of people in endemic areas with protective immunity and those with malaria symptoms, the vaccine potential of the N-terminal domain of Plasmodium falciparum SERA5 is also strongly supported by experimental data and immune responses both measured in vitro and in animal challenge models. The current understanding of SERA5 will be presented, particularly in relation to its path towards clinical development. The review highlights lessons learned and sorts out issues upon which further research efforts are needed. PMID:21718740

  7. CRISPR-Cas9-modified pfmdr1 protects Plasmodium falciparum asexual blood stages and gametocytes against a class of piperazine-containing compounds but potentiates artemisinin-based combination therapy partner drugs.

    Science.gov (United States)

    Ng, Caroline L; Siciliano, Giulia; Lee, Marcus C S; de Almeida, Mariana J; Corey, Victoria C; Bopp, Selina E; Bertuccini, Lucia; Wittlin, Sergio; Kasdin, Rachel G; Le Bihan, Amélie; Clozel, Martine; Winzeler, Elizabeth A; Alano, Pietro; Fidock, David A

    2016-08-01

    Emerging resistance to first-line antimalarial combination therapies threatens malaria treatment and the global elimination campaign. Improved therapeutic strategies are required to protect existing drugs and enhance treatment efficacy. We report that the piperazine-containing compound ACT-451840 exhibits single-digit nanomolar inhibition of the Plasmodium falciparum asexual blood stages and transmissible gametocyte forms. Genome sequence analyses of in vitro-derived ACT-451840-resistant parasites revealed single nucleotide polymorphisms in pfmdr1, which encodes a digestive vacuole membrane-bound ATP-binding cassette transporter known to alter P. falciparum susceptibility to multiple first-line antimalarials. CRISPR-Cas9 based gene editing confirmed that PfMDR1 point mutations mediated ACT-451840 resistance. Resistant parasites demonstrated increased susceptibility to the clinical drugs lumefantrine, mefloquine, quinine and amodiaquine. Stage V gametocytes harboring Cas9-introduced pfmdr1 mutations also acquired ACT-451840 resistance. These findings reveal that PfMDR1 mutations can impart resistance to compounds active against asexual blood stages and mature gametocytes. Exploiting PfMDR1 resistance mechanisms provides new opportunities for developing disease-relieving and transmission-blocking antimalarials.

  8. 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

  9. [Vaccination against hepatitis A].

    Science.gov (United States)

    Balli, F; Di Biase, A R; Viola, L

    1996-01-01

    The epidemiology of hepatitis A, a disease endemic in various countries, is in a state of continuous change. Adults are more exposed to infection and considering the frequent absence of immunity, in contrast to children in whom the disease is almost always asymptomatic, the disease is often serious and prolonged with a mortality of up to 2.5%. The mode of transmission of HAV is predominantly the fecal-oral route; the virus is isolated during the prodromic period of the disease from the feces, blood, bile and seminal fluid. The virus can also be found in saliva (OMS '95); in addition it may also be transmitted by the maternal-fetal route. The HAV infects cells in vitro but does not cause a direct cytopathic effect. At the beginning of the acute phase of the disease the production of anti-HAV antibodies is of the IgM type followed later by IgG. Some studies have shown a potential role of cellular immunity in clearance of the virus from the hepatocytes and in the pathogenesis of the infection of HAV. The efficacy of immunoglobulin serum in the prevention of hepatitis A has been demonstrated since 1944. As regards active immunity two types of vaccinations have been prepared. One with live attenuated HAV carried by either bacteria or virus. The other, killed inactivated HAV, HAV capsule, antigenic subunit, synthetic peptides, anti-idiotypes or virosomes. The recent literature describe the vaccine produced by Merck Sharp & Dohme and by Smith Kline Beecham (SKB); both vaccines are made from HAV, grown in vitro, inactivated with formalin and adsorbed to aluminum hydroxide. The protection of the vaccine begins 14 days after administration and lasts from one month to one year. Numerous studies have been conducted which have shown that the vaccine is effective when given in 2 doses and confers protection against HAV for at least one year. The results have shown that the vaccination causes seroconversion in approximately 100% of subjects, and does not cause serious side

  10. 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

    Full Text Available BACKGROUND: 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. METHODS & PRINCIPAL FINDINGS: 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. CONCLUSIONS: 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. TRIAL REGISTRATION: ClinicalTrials.gov. NCT00307021.

  11. Advancing a vaccine to prevent human schistosomiasis.

    Science.gov (United States)

    Merrifield, Maureen; Hotez, Peter J; Beaumier, Coreen M; Gillespie, Portia; Strych, Ulrich; Hayward, Tara; Bottazzi, Maria Elena

    2016-06-01

    Several candidate human schistosomiasis vaccines are in different stages of preclinical and clinical development. The major targets are Schistosoma haematobium (urogenitial schistosomiasis) and Schistosoma mansoni (intestinal schistosomiasis) that account for 99% of the world's 252 million cases, with 90% of these cases in Africa. Two recombinant S. mansoni vaccines - Sm-TSP-2 and Sm-14 are in Phase 1 trials, while Smp80 (calpain) is undergoing testing in non-human primates. Sh28GST, also known as Bilhvax is in advanced clinical development for S. haematobium infection. The possibility remains that some of these vaccines may cross-react to target both schistosome species. These vaccines were selected on the basis of their protective immunity in preclinical challenge models, through human immune-epidemiological studies or both. They are being advanced through a combination of academic research institutions, non-profit vaccine product development partnerships, biotechnology companies, and developing country vaccine manufacturers. In addition, new schistosome candidate vaccines are being identified through bioinformatics, OMICs approaches, and moderate throughput screening, although the full potential of reverse vaccinology for schistosomiasis has not yet been realized. The target product profiles of these vaccines vary but many focus on vaccinating children, in some cases following mass treatment with praziquantel, also known as vaccine-linked chemotherapy. Several regulatory pathways have been proposed, some of which rely on World Health Organization prequalification. PMID:27036511

  12. 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

    2016-06-01

    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. PMID:26973063

  13. 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...

  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.......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...

  15. Phagocytosis and production of reactive oxygen species by peripheral blood phagocytes in patients with different stages of alcohol-induced liver disease: effect of acute exposure to low ethanol concentrations

    DEFF Research Database (Denmark)

    Parlesak, Alexandr; Schäfer, C.; Paulus, S. B.;

    2003-01-01

    BACKGROUND: In rodents, the development of alcoholic liver disease (ALD) after chronic alcohol feeding was shown to depend on the activity of enzymes that are necessary for production of reactive oxygen species (ROS) in phagocytes. The aim of this study was to determine the formation of ROS...... by resting and challenged phagocytes of patients with different stages of ALD in the presence of ethanol concentrations commonly found in the blood of alcohol abusers. PATIENTS AND METHODS: The release of ROS and the phagocytosis of bacteria by neutrophils and monocytes obtained from 60 patients, who were...

  16. Vaccination priorities.

    Science.gov (United States)

    Steffen, Robert; Baños, Ana; deBernardis, Chiara

    2003-02-01

    Selection of immunizations should be based on requirements and on risk of infection. According to the International Health Regulations, many countries require yellow fever vaccination and proof thereof as the International Certificate of vaccination. Additionally selected countries require proof of vaccination against cholera and meningococcal disease. A consultation for travel health advice is always an opportunity to ascertain that routine immunizations have been performed. Recommended immunizations often are more important for traveller's health than the required or routine ones. The most frequent vaccine preventable infection in non-immune travellers to developing countries is hepatitis A with an average incidence rate of 0.3% per month; in high risk backpackers or foreign-aid-volunteers this rate is 2.0%. Many immunizations are recommended for special risk groups only: there is a growing tendency in many countries to immunize all young travellers to developing countries against hepatitis B, as it is uncertain who will voluntarily or involuntarily get exposed. The attack rate of influenza in intercontinental travel is estimated to be 1%. Immunity against poliomyelitis remains essential for travel to Africa and parts of Asia. Many of the 0.2-0.4% who experience an animal bite are at risk of rabies. Typhoid fever is diagnosed with an incidence rate of 0.03% per month among travellers to the Indian subcontinent, North and West Africa (except Tunisia), and Peru, elsewhere this rate is 10-fold lower. Meningococcal disease, Japanese encephalitis, cholera and tuberculosis have been reported in travellers, but these infections are rare in this population. Although no travel health vaccine is cost beneficial, most professionals will offer protection against the frequent risks, while most would find it ridiculous to use all available vaccines in every traveller. It is essentially an arbitrary decision made on the risk level one wishes to recommend protection--but the

  17. Vaccine Vexes

    Institute of Scientific and Technical Information of China (English)

    Maya; Reid

    2011-01-01

    IT’S always nice when expectations are exceeded by half a billion dollars.This was the case for the Global Alliance for Vaccines and Immunization(GAVI) at its fundraising conference in June.A public-private initiative,GAVI,which works to ensure children in developing countries receive crucial vaccinations,had gone into the meeting hoping to net $3.7 billion.They came away with $4.3 billion,"despite the fact that donors everywhere are coping with budget crises," as Bill Gates

  18. Regional cerebral blood flow in acute stage with ischemic cerebrovascular disease by xenon-133 inhalation and single photon emission computerized tomography

    Energy Technology Data Exchange (ETDEWEB)

    Kurokawa, Hiroyuki; Iino, Katsuro; Kojima, Hisashi; Saito, Hitoshi; Suzuki, Mikio; Watanabe, Kazuo; Kato, Toshiro

    1987-05-01

    Single photon emission computed tomography (SPECT) with xenon-133 inhalation method was undertaken within 48 hr after the onset in 68 patients with ischemic cerebrovascular disease. The results for regional cerebral blood flow (rCBF) were compared with concurrently available computed tomography (CT) scans. In patients with cerebral infarction, SPECT detected ischemic lesions earlier than CT, with the detectability being 92 %. The area with a decreased blood flow, as seen on SPECT, was more extensive than the low density area on CT, with a concomitant decrease in blood flow in the contralateral cerebral hemisphere. Crossed cerebellar diaschisis was associated with stenosis of the internal carotid artery in 50 % (7/14), and with stenosis of the middle cerebral artery in 35 % (9/26). Abnormal SPECT findings were seen in 47 % (8/17) of the patients with transient ischemic attack (TIA). Five TIA patients had a decreased rCBF on SPECT, which was not provided by CT scans. On the contrary, small infarct lesions in the cerebral basal ganglia, as observed in 4 patients, was not detected by SPECT, but detected by CT. This may imply the limitations of SPECT in the detection of deep-seated lesions of the cerebrum. The results led to the conclusion that SPECT can be performed safely even in acute, seriously ill patients to know changes in rCBF because it is noninvasive and is capable of being repeated in a short time. (Namekawa, K.).

  19. 不同孕期妊娠妇女凝血四项指标变化及意义%Analysis of the blood coagulation test of pregnant women in different stage and discuss its clinical significance

    Institute of Scientific and Technical Information of China (English)

    魏文迅; 林进考

    2008-01-01

    Objective To study the results of blood coagulation test,including PT,APTT,FG and TT of pregnant women in different stage,and to discuss its clinical significance.Methods Blood coagulation monitor(STA-GO-ArT4,French)was used in this study.The experiment samples were divided into four grroups:group intermediate stage gestation(30 persons),group advanced stage gestation(26 persons),group in labor(30 persons)and group normal of none-gestation(37 persons).The prothrombin time(PT),activated partiat thromboplastin time(APTT).fibrinogen(FG)and thrombin time(TT)of these persons were detected.At last,the data of the test was analysised.Results The PT,FG and TT of the group advanced stage gestation and group in labor were higher compared with the group normal of none-gestation(P<0.05).Conclusion The blood coagulation function of pregnant women in different stage is different from the none-pregnant women,and it is important to know the PT,APTT,FG and TT promptly.%目的 探讨妊娠妇女不同孕期凝血酶原时间(PT)、部分凝血活酶时间(APTT)、纤维蛋白原(FG)和凝血酶时间(TT)四项反映凝血功能指标的变化及其临床意义.方法 采用法国STAGO-ArT4血凝仪检测86例正常中孕、晚孕、临产妇女和37例正常非孕妇女的PT、APTT、FG和TT,并对检测结果进行比较.结果:晚孕组和临产组与健康对照组比较,PT、FG和TT差异有统计学意义(P<0.05).结论 不同孕期妊娠妇女凝血功能发生改变,及时了解这些变化具有重要临床意义.

  20. Replicating vaccines

    Science.gov (United States)

    Early work on fish immunology and disease resistance demonstrated fish (like animals and humans) that survived infection were typically resistant to re-infection with the same pathogen. The concepts of resistance upon reinfection lead to the research and development of replicating (live) vaccines in...

  1. Malaria vaccine.

    Science.gov (United States)

    1994-05-01

    Some have argued that the vaccine against malaria developed by Manuel Pattaroyo, a Colombian scientist, is being tested prematurely in humans and that it is unlikely to be successful. While the Pattaroyo vaccine has been shown to confer protection against the relatively mild malaria found in Colombia, doubts exist over whether it will be effective in Africa. Encouraging first results, however, are emerging from field tests in Tanzania. The vaccine triggered a strong new immune response, even in individuals previously exposed to malaria. Additional steps must be taken to establish its impact upon mortality and morbidity. Five major trials are underway around the world. The creator estimates that the first ever effective malaria vaccine could be available for widespread use within five years and he has no intention of securing a patent for the discovery. In another development, malaria specialists from 35 African countries convened at an international workshop in Zimbabwe to compare notes. Participants disparaged financial outlays for the fight against malaria equivalent to 2% of total AIDS funding as insufficient; noted intercountry differences in prevention, diagnosis, and treatment; and found information exchange between anglophone and francophone doctors to be generally poor. PMID:12287671

  2. 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…

  3. Hepatitis B vaccines: protective efficacy and therapeutic potential.

    Science.gov (United States)

    Michel, M-L; Tiollais, P

    2010-08-01

    Worldwide, two billion people have at some time been infected by hepatitis B virus, 370 millions suffer from chronic infection and around one million die each year from HBV-related liver diseases of which liver cancer is the ultimate stage. Vaccination is the measure that is most effective in reducing the global incidence of hepatitis B and hepatitis B vaccines have now been available for over 20 years. The first hepatitis B vaccine was prepared from inactivated hepatitis B surface antigen particles purified from plasma of asymptomatic carriers of hepatitis B virus. Knowledge of the structure and genomic organization of hepatitis B virus has led to development of the first DNA recombinant vaccine. In preventing hepatocellular carcinoma development, hepatitis B virus vaccines are considered as the first available cancer vaccine. HBV vaccines have recently taken on a new role as therapeutic vaccines as an attempt to cure or to control hepatitis B virus infection in persistently infected individuals. PMID:20382485

  4. 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

    Full Text Available BACKGROUND: 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. METHODOLOGY/PRINCIPAL FINDINGS: 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. CONCLUSION/SIGNIFICANCE: 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.

  5. CONFIRMATION OF HEREDITARY TYROSINEMIA TYPE 1 IN NEONATAL STAGE USING SPECTROPHOTOMETRIC MICROASSAY BASED ON THE DETERMINATION OF SUCCINYLACETONE LEVEL IN DRIED-BLOOD SPOTS

    Directory of Open Access Journals (Sweden)

    Gautam Kumar

    2014-05-01

    Full Text Available Hereditary Tyrosinemia Type 1 (HT1 is a metabolic disorder below to the class of autosomal recessive inheritance caused by the dearth of enzyme fumaryl acetoacetase the last enzyme in the tyrosine catabolic pathway . Affected individuals show increased tyrosine and succinyl acetone concentration (SA in blood. Patients also excrete increased concentration of SA in urine. The disorder is characterized by progressive liver disease and renal tubular defects with accompanying hypophosphatemic rickets. Symptoms of HT1 usually appear in the first few months of life and include failure to gain weight and grow at the expected rate, diarrhea, vomiting, yellowing of the skin and whites of the eyes (jaundice. It may also lead to liver and kidney failure and an increased risk of liver cancer. Liver transplantation is the only effective treatment for hereditary tyrosinemia type 1. In the present study, Succinyl Acetone is measured by using its inhibitory property on d-aminolaevulinate dehydratase enzyme for the diagnosis of HT1 in dried blood spots.

  6. Blood Clots

    Science.gov (United States)

    ... Index A-Z Blood Clots Blood clots are semi-solid masses of blood that can be stationary (thrombosis) ... treated? What are blood clots? Blood clots are semi-solid masses of blood. Normally, blood flows freely through ...

  7. Fish Vaccines in Aquaculture

    Science.gov (United States)

    Vaccination is a proven, cost-effective method to prevent infectious diseases in animals. Current fish vaccines can be categorized as killed fish vaccines or modified live vaccines. The major advantage of live vaccine is their ability to stimulate both cell-mediated and humoral immune responses for ...

  8. Qi and removing blood stasis in treating early stage cirrhosis%益气化瘀法治疗早期肝硬化

    Institute of Scientific and Technical Information of China (English)

    叶思文

    2012-01-01

      目的:就益气化瘀法治疗早期肝硬化进行探讨。方法:选取三个案例进行分析,将益气健脾,活血化瘀辨证治疗肝硬化。结果:案例1:服上方治疗3个月后病愈。随访至今未见再发。案例2诸症悉除,复查肝功能,肝胆脾彩超均属正常范围。后用上方加减研末冲服月余,以巩固疗效,随访1年未见再发。案例3诸症悉除,复查肝功能及肝胆脾彩超,其中彩超示:脾脏肿大,余项均属正常范围。后用上方加减蜜丸服药月余,病告痊愈,随访2年未见再发。结论:臌胀为临床四大疑难重症之一,其病机为肝脾肾三脏功能失调,气、血、水停于腹中,本虚标实,虚实夹杂的病理过程。%  Objective:Yiqi Huayu method treatment early time liver cirrhosis of. Methods:a total of three cases were analyzed, the Qi of the spleen, promoting blood circulation to remove blood stasis syndrome differentiation and treatment of liver cirrhosis. Results:the case of 1: served 3 months after the treatment was over. Up to now no longer hair. 2 cases are in addition to all disease, the liver function, liver spleen ultrasound within the normal range. After using the above addition and subtraction grind end each month, in order to consolidate the curative effect, follow-up of 1 years again. 3 cases are in addition to all disease, the liver function and liver spleen ultrasound, including ultrasonography indicated: enlargement of spleen, the remainder were within normal range. After taking over addition and subtraction pill month, disease to cure, follow-up of 2 years showed no recurrence. Conclusion:swelling for clinical four severe problems, its pathogenesis is spleen kidney three dirty function disorders, gas, blood, water stop in the abdomen, the superficial, inclusion of actual pathological process.

  9. Rotavirus vaccines: targeting the developing world.

    Science.gov (United States)

    Glass, Roger I; Bresee, Joseph S; Turcios, Reina; Fischer, Thea K; Parashar, Umesh D; Steele, A Duncan

    2005-09-01

    For the past 2 decades, rotavirus infection, the most common cause of severe diarrhea in children, has been a priority target for vaccine development. This decision to develop rotavirus vaccines is predicated on the great burden associated with fatal rotavirus disease (i.e., 440,000 deaths/year), the firm scientific basis for developing live oral vaccines, the belief that increased investment in development at this time could speed the introduction of vaccines in developing countries, and the appreciation that implementation of a vaccine program should result in a measurable decrease in the number of hospitalizations and deaths associated with rotavirus disease within 2-3 years. RotaShield (Wyeth-Ayerst), the first rotavirus vaccine licensed in the United States, was withdrawn after 9 months because of a rare association of the vaccine with the development of intussusception. In the developing world, this vaccine could still have had a measurable effect, because the benefits of preventing deaths due to rotavirus disease would have been substantially greater than the rare risk of intussusception. Two live oral vaccines being prepared by GlaxoSmithKline and Merck have completed large-scale clinical trials. The GlaxoSmithKline vaccine has been licensed in Mexico and the Dominican Republic, and the Merck vaccine could be licensed in the United States within 1 year; several other candidate vaccines are in earlier stages of testing. However, many challenges remain before any of these vaccines can be incorporated into childhood immunization programs in the developing world. First, vaccine efficacy, which has already been demonstrated in children in industrialized and middle-income countries, needs to be proven in poor developing countries in Africa and Asia. The safety of vaccines with regard to the associated risk of intussusception must be demonstrated as well. Novel financing strategies will be needed to ensure that new vaccines are affordable and available in the

  10. A randomized controlled Phase Ib trial of the malaria vaccine candidate GMZ2 in African children

    DEFF Research Database (Denmark)

    Bélard, Sabine; Issifou, Saadou; Hounkpatin, Aurore B;

    2011-01-01

    GMZ2 is a fusion protein of Plasmodium falciparum merozoite surface protein 3 (MSP3) and glutamate rich protein (GLURP) that mediates an immune response against the blood stage of the parasite. Two previous phase I clinical trials, one in naïve European adults and one in malaria-exposed Gabonese ...... adults showed that GMZ2 was well tolerated and immunogenic. Here, we present data on safety and immunogenicity of GMZ2 in one to five year old Gabonese children, a target population for future malaria vaccine efficacy trials....

  11. 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

  12. Nanovaccines: recent developments in vaccination

    Indian Academy of Sciences (India)

    Tarala D Nandedkar

    2009-12-01

    In the past 100 years, vaccination has contributed immensely to public health by preventing a number of infectious diseases. Attenuated, killed or part of the microorganism is employed to stimulate the immune system against it. Progress in biotechnology has provided protective immunity through DNA vaccines. In recent years, nanovaccine is a novel approach to the methodology of vaccination. Nanomaterials are delivered in the form of microspheres, nanobeads or micro-nanoprojections. Painless, effective and safe needle-free routes such as the intranasal or the oral route, or patches of microprojections to the skin are some of the approaches which are in the experimental stage at present but may have a great future ahead in nanovaccination.

  13. Quality control of seasonal influenza vaccines.

    Science.gov (United States)

    Mandušić Nazor, Tamara; Pipić Kosanović, Marta; Tomić, Siniša

    2010-12-01

    The purpose of seasonal influenza vaccination is to prevent its spread. The vaccines contain strains of the influenza virus recommended and approved for a particular season. Just like any other medicinal product, all vaccines require marketing approval. Batches of approved vaccines are extensively tested by the manufacturers and additionally controlled by the approving authorities, which issue the quality control certificates. This article not only to describes the legal background of quality control, but also how control test results obtained by a Croatian official control laboratory are compared to manufacturer's results. We have found that testing results can slightly differ depending on methods/analytical procedures used in different laboratories. This investigation has also shown how important it is to test finished medicinal products, independently of testing at intermediate stages, and how retesting by control authorities ensures that marketed vaccines meet quality standards.

  14. 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 ...

  15. 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 ...

  16. Vaccinations and HIV

    Science.gov (United States)

    ... 23, 2014 Select a Language: Fact Sheet 207 Vaccinations and HIV WHAT ARE VACCINATIONS? WHAT’S DIFFERENT FOR ... your viral load within 4 weeks of any vaccination. Flu shots have been studied more than any ...

  17. Vaccinations during Pregnancy

    Science.gov (United States)

    ... you do need any vaccinations, wait 1 month after you get them before you try to get pregnant. ... vaccine during pregnancy, you can get it right after you give birth. Getting the Tdap vaccine soon after ...

  18. Influenza Vaccines

    OpenAIRE

    Ellebedy, A. H.; Webby, R J

    2009-01-01

    Influenza A viruses pose a substantial threat to the human population whether by purposeful manipulation and release or by the natural process of interspecies transmissions from animal reservoirs. The challenge with preparing for these events with vaccination strategies is that the best forms of protective immunity target the most variably of the viral proteins, hemagglutinin. Add to this even just the natural extent of variation in this protein and the challenges to vaccinologists become gre...

  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 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. RESULTS: 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...

  20. 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

  1. Canine distemper virus detection in asymptomatic and non vaccinated dogs

    OpenAIRE

    Del Puerto, Helen L; Vasconcelos, Anilton C.; Luciana Moro; Fabiana Alves; Braz, Gissandra F; Almir S. Martins

    2010-01-01

    A quantitative real time polymerase chain reaction (PCR) revealed canine distemper virus presence in peripheral blood samples from asymptomatic and non vaccinated dogs. Samples from eleven domestic dogs with no signs of canine distemper and not vaccinated at the month of collection were used. Canine distemper virus vaccine samples in VERO cells were used as positive controls. RNA was isolated with Trizol®, and treated with a TURBO DNA-free kit. Primers were designed for canine distemper virus...

  2. 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.

  3. 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

  4. Meningococcal Vaccine (For Parents)

    Science.gov (United States)

    ... Palsy: Shannon's Story" 5 Things to Know About Zika & Pregnancy Your Child's Immunizations: Meningococcal Vaccines KidsHealth > For Parents > Your Child's Immunizations: Meningococcal Vaccines ...

  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. PMID:24940018

  6. Plasmacytoid dendritic cells delineate immunogenicity of influenza vaccine subtypes.

    Science.gov (United States)

    Koyama, Shohei; Aoshi, Taiki; Tanimoto, Takeshi; Kumagai, Yutaro; Kobiyama, Kouji; Tougan, Takahiro; Sakurai, Kazuo; Coban, Cevayir; Horii, Toshihiro; Akira, Shizuo; Ishii, Ken J

    2010-03-31

    A variety of different vaccine types are available for H1N1 influenza A virus infections; however, their immunological mechanisms of action remain unclear. Here, we show that plasmacytoid dendritic cells (pDCs) and type I interferon (IFN)-mediated signaling delineate the immunogenicity of live attenuated virus, inactivated whole-virus (WV), and split-virus vaccines. Although Toll-like receptor 7 acted as the adjuvant receptor for the immunogenicity of both live virus and WV vaccines, the requirement for type I IFN production by pDCs for the immunogenicity of the vaccines was restricted to WV. A split vaccine commonly used in humans failed to immunize naïve mice, but a pDC-activating adjuvant could restore immunogenicity. In blood from human adults, however, split vaccine alone could recall memory T cell responses, underscoring the importance of this adjuvant pathway for primary, but not secondary, vaccination. PMID:20424013

  7. Evaluation of the response to vaccination with hepatitis B vaccine in pediatric patients diagnosed with celiac disease

    OpenAIRE

    Walkiewicz-Jedrzejczak, Dorota; Egberg, Matthew; Nelson, Catherine; Eickoff, Jens

    2014-01-01

    Background: A gap exists in the literature on celiac disease populations and the response to hepatitis B vaccination. Objective: To identify pediatric patients with celiac disease who received the primary hepatitis B vaccination and investigate their response to vaccine. Design/Methods: Patients underwent blood draw for hepatitis B surface antibody titers. Patients with undetectable or non-protective HBsAb titers were contacted. Study outcome measures and patient characteristics variables wer...

  8. Blood Donation and Transfusion (Beyond the Basics)

    Science.gov (United States)

    ... donor, a person who has recently received the hepatitis B vaccine should wait 21 days before donating blood. At ... PARTY WHO HAS BEEN INVOLVED IN THE CREATION, PRODUCTION, PROMOTION OR MARKETING OF THE LICENSED MATERIALS BE ...

  9. Significantly Reduced Genoprevalence of Vaccine-Type HPV-16/18 Infections among Vaccinated Compared to Non-Vaccinated Young Women 5.5 Years after a Bivalent HPV-16/18 Vaccine (Cervarix®) Pilot Project in Uganda

    Science.gov (United States)

    Berggren, Vanja; Wabinga, Henry; Lillsunde-Larsson, Gabriella; Helenius, Gisela; Kaliff, Malin; Karlsson, Mats; Kirimunda, Samuel; Musubika, Caroline; Andersson, Sören

    2016-01-01

    The objective of this study was to determine the prevalence and some predictors for vaccine and non-vaccine types of HPV infections among bivalent HPV vaccinated and non-vaccinated young women in Uganda. This was a comparative cross sectional study 5.5 years after a bivalent HPV 16/18 vaccination (Cervarix®, GlaxoSmithKline, Belgium) pilot project in western Uganda. Cervical swabs were collected between July 2014-August 2014 and analyzed with a HPV genotyping test, CLART® HPV2 assay (Genomica, Madrid Spain) which is based on PCR followed by microarray for determination of genotype. Blood samples were also tested for HIV and syphilis infections as well as CD4 and CD8 lymphocyte levels. The age range of the participants was 15–24 years and mean age was 18.6(SD 1.4). Vaccine-type HPV-16/18 strains were significantly less prevalent among vaccinated women compared to non-vaccinated women (0.5% vs 5.6%, p 0.006, OR 95% CI 0.08(0.01–0.64). At type-specific level, significant difference was observed for HPV16 only. Other STIs (HIV/syphilis) were important risk factors for HPV infections including both vaccine types and non-vaccine types. In addition, for non-vaccine HPV types, living in an urban area, having a low BMI, low CD4 count and having had a high number of life time sexual partners were also significant risk factors. Our data concurs with the existing literature from other parts of the world regarding the effectiveness of bivalent HPV-16/18 vaccine in reducing the prevalence of HPV infections particularly vaccine HPV- 16/18 strains among vaccinated women. This study reinforces the recommendation to vaccinate young girls before sexual debut and integrate other STI particularly HIV and syphilis interventions into HPV vaccination packages. PMID:27482705

  10. Significantly Reduced Genoprevalence of Vaccine-Type HPV-16/18 Infections among Vaccinated Compared to Non-Vaccinated Young Women 5.5 Years after a Bivalent HPV-16/18 Vaccine (Cervarix®) Pilot Project in Uganda.

    Science.gov (United States)

    Kumakech, Edward; Berggren, Vanja; Wabinga, Henry; Lillsunde-Larsson, Gabriella; Helenius, Gisela; Kaliff, Malin; Karlsson, Mats; Kirimunda, Samuel; Musubika, Caroline; Andersson, Sören

    2016-01-01

    The objective of this study was to determine the prevalence and some predictors for vaccine and non-vaccine types of HPV infections among bivalent HPV vaccinated and non-vaccinated young women in Uganda. This was a comparative cross sectional study 5.5 years after a bivalent HPV 16/18 vaccination (Cervarix®, GlaxoSmithKline, Belgium) pilot project in western Uganda. Cervical swabs were collected between July 2014-August 2014 and analyzed with a HPV genotyping test, CLART® HPV2 assay (Genomica, Madrid Spain) which is based on PCR followed by microarray for determination of genotype. Blood samples were also tested for HIV and syphilis infections as well as CD4 and CD8 lymphocyte levels. The age range of the participants was 15-24 years and mean age was 18.6(SD 1.4). Vaccine-type HPV-16/18 strains were significantly less prevalent among vaccinated women compared to non-vaccinated women (0.5% vs 5.6%, p 0.006, OR 95% CI 0.08(0.01-0.64). At type-specific level, significant difference was observed for HPV16 only. Other STIs (HIV/syphilis) were important risk factors for HPV infections including both vaccine types and non-vaccine types. In addition, for non-vaccine HPV types, living in an urban area, having a low BMI, low CD4 count and having had a high number of life time sexual partners were also significant risk factors. Our data concurs with the existing literature from other parts of the world regarding the effectiveness of bivalent HPV-16/18 vaccine in reducing the prevalence of HPV infections particularly vaccine HPV- 16/18 strains among vaccinated women. This study reinforces the recommendation to vaccinate young girls before sexual debut and integrate other STI particularly HIV and syphilis interventions into HPV vaccination packages.

  11. 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.

  12. 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.

  13. Nonclinical Development of BCG Replacement Vaccine Candidates.

    Science.gov (United States)

    Velmurugan, Kamalakannan; Grode, Leander; Chang, Rosemary; Fitzpatrick, Megan; Laddy, Dominick; Hokey, David; Derrick, Steven; Morris, Sheldon; McCown, David; Kidd, Reginald; Gengenbacher, Martin; Eisele, Bernd; Kaufmann, Stefan H E; Fulkerson, John; Brennan, Michael J

    2013-01-01

    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. PMID:26343962

  14. Yellow Fever Vaccine: What You Need to Know

    Science.gov (United States)

    ... a risk of transmitting the vaccine virus through blood products during that period. 4 Wfevheorsvhaocuclidnen?ot get yellow • Anyone with a severe (life-threatening) allergy to any component of the vaccine, including eggs, chicken proteins, or gelatin, or who has had a ...

  15. Child mortality related to seroconversion or lack of seroconversion after measles vaccination

    DEFF Research Database (Denmark)

    Aaby, Peter; Pedersen, I R; Knudsen, K;

    1989-01-01

    When blood samples were analyzed for seroconversion after measles vaccination, it was discovered that the vaccine had been ineffective for a certain period. During the 2 years between vaccination and the time of seroanalysis, nonseroconverters had a significantly higher mortality than seroconvert...

  16. Influence of Tricaine Methanesulfonate on Streptococcus agalactiae vaccination of Nile tilapia (Oreochromis niloticus)

    Science.gov (United States)

    Experiments were conducted to study the influence of tricaine methanesulfonate (MS-222) on blood glucose levels and percent cumulative survival of Nile tilapia (Oreochromis niloticus) challenged with Streptococcus agalactiae 30 days post-vaccination with S. agalactiae vaccine or sham-vaccination wit...

  17. Amino acid efflux by asexual blood-stage Plasmodium falciparum and its utility in interrogating the kinetics of hemoglobin endocytosis and catabolism in vivo.

    Science.gov (United States)

    Dalal, Seema; Klemba, Michael

    2015-06-01

    The endocytosis and catabolism of large quantities of host cell hemoglobin is a hallmark of the intraerythrocytic asexual stage of the human malaria parasite Plasmodium falciparum. It is known that the parasite's production of amino acids from hemoglobin far exceeds its metabolic needs. Here, we show that P. falciparum effluxes large quantities of certain non-polar (Ala, Leu, Val, Pro, Phe, Gly) and polar (Ser, Thr, His) amino acids to the external medium. That these amino acids originate from hemoglobin catabolism is indicated by the strong correlation between individual amino acid efflux rates and their abundances in hemoglobin, and the ability of the food vacuole falcipain inhibitor E-64d to greatly suppress efflux rates. We then developed a rapid, sensitive and precise method for quantifying flux through the hemoglobin endocytic-catabolic pathway that is based on leucine efflux. Optimization of the method involved the generation of a novel amino acid-restricted RPMI formulation as well as the validation of D-norvaline as an internal standard. The utility of this method was demonstrated by characterizing the effects of the phosphatidylinositol-3-kinase inhibitors wortmannin and dihydroartemisinin on the kinetics of Leu efflux. Both compounds rapidly inhibited Leu efflux, which is consistent with a role for phosphtidylinositol-3-phosphate production in the delivery of hemoglobin to the food vacuole; however, wortmannin inhibition was transient, which was likely due to the instability of this compound in culture medium. The simplicity, convenience and non-invasive nature of the Leu efflux assay described here makes it ideal for characterizing the in vivo kinetics of hemoglobin endocytosis and catabolism, for inhibitor target validation studies, and for medium-throughput screens to identify novel inhibitors of cytostomal endocytosis.

  18. Pancreatic Cancer Stage 4

    Science.gov (United States)

    ... lung, liver, and peritoneal cavity. An inset shows cancer cells spreading from the pancreas, through the blood and lymph system, to another ... abdomen that contains the intestines, stomach, and liver). Cancer may also have spread to ... pancreas or to lymph nodes. Stage IV pancreatic cancer. ...

  19. 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

  20. Nine μg intradermal influenza vaccine and 15 μg intramuscular influenza vaccine induce similar cellular and humoral immune responses in adults

    Science.gov (United States)

    Nougarede, Nolwenn; Bisceglia, Hélène; Rozières, Aurore; Goujon, Catherine; Boudet, Florence; Laurent, Philippe; Vanbervliet, Beatrice; Rodet, Karen; Hennino, Ana; Nicolas, Jean-François

    2014-01-01

    Intanza® 9 μg (Sanofi Pasteur), a trivalent split-virion vaccine administered by intradermal (ID) injection, was approved in Europe in 2009 for the prevention of seasonal influenza in adults 18 to 59 years. Here, we examined the immune responses induced in adults by the ID 9 μg vaccine and the standard trivalent intramuscular (IM) vaccine (Vaxigrip® 15 μg, Sanofi Pasteur). This trial was a randomized, controlled, single-center, open-label study in healthy adults 18 to 40 years of age during the 2007/8 influenza season. Subjects received a single vaccination with the ID 9 μg (n = 38) or IM 15 μg (n = 42) vaccine. Serum, saliva, and peripheral blood mononuclear cells were collected up to 180 days post-vaccination. Geometric mean hemagglutination inhibition titers, seroprotection rates, seroconversion rates, and pre-vaccination-to-post-vaccination ratios of geometric mean hemagglutination inhibition titers did not differ between the two vaccines. Compared with pre-vaccination, the vaccines induced similar increases in vaccine-specific circulating B cells at day 7 but did not induce significant increases in vaccine-specific memory B cells at day 180. Cell-mediated immunity to all three vaccine strains, measured in peripheral blood mononuclear cells, was high at baseline and not increased by either vaccine. Neither vaccine induced a mucosal immune response. These results show that the humoral and cellular immune responses to the ID 9 μg vaccine are similar to those to the standard IM 15 μg vaccine. PMID:25483667

  1. Female contraceptive vaccine possible, but not for years.

    Science.gov (United States)

    1989-10-01

    Researchers are presently testing 2 types of contraceptive vaccines in animal models. One of these is the sperm antigen vaccine which would cause immunity to sperm within the female reproductive tract. The other works against the zona pellucida (the extracellular membrane surrounding the ovum) which the sperm must bind to and penetrate for fertilization to take place. At this time, researchers do not yet know what vaccine is the best route. The sperm antigen vaccine would inhibit capacitation--that stage where they become capable of fertilizing the ovum. The researchers foresee certain problems with this vaccine, however. For example, it will be difficult to get a vaccine to work properly within just the reproductive tract since most antigen vaccines work within the entire immune system. Further, all the areas of the reproductive tract are biologically different. In addition, researchers must find a vaccine potent enough to affect the millions of sperm that enter the uterus. A potential problem with the zona pellucida vaccine is that it could create ovarian dysfunction permanently. Therefore, researchers realize the importance of finding a zona pellucida vaccine that will induce fertilization but not destroy the ovaries. WHO is in the early stages of working on a vaccine against human chorionic gonadotropin to prevent implantation, but this and any postfertilization vaccine will probably not be produced for the US market because of the present antiabortion sentiment. Additional barriers to production of a contraceptive vaccine is that pharmaceutical companies fear liability in marketing a new contraceptive and their profit margin will be low. Nevertheless, the earliest a contraceptive vaccine would become available in 1999.

  2. Mucosal vaccination of fish

    NARCIS (Netherlands)

    Rombout, J.H.W.M.; Kiron, V.

    2014-01-01

    Among the novel vaccination methods, mucosal vaccination seems to possess all the desired criteria. The chapter reviews the state-of-the-art knowledge regarding this type of vaccination with a focus on their uptake, immune stimulation, and where possible, discusses their potential as future vaccines

  3. History of vaccination

    OpenAIRE

    Plotkin, Stanley

    2014-01-01

    Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before.

  4. Correlates of Protection Following Vaccination with Inactivated Porcine Circovirus 2 Vaccines.

    Science.gov (United States)

    Zanotti, Cinzia; Martinelli, Nicola; Lelli, Davide; Amadori, Massimo

    2015-12-01

    Porcine circovirus type 2 (PCV2) is associated with a number of diseases and syndromes, collectively referred to as porcine circovirus-associated disease. The main objective of this study was to define some in vitro correlates of protection after injection of inactivated PCV2 vaccines with a defined antigen mass. Twelve pigs were vaccinated with three different doses of inactivated, whole-virus antigen (211-844 ng), while four animals were injected with a commercial vaccine (positive control) and four other pigs were mock-vaccinated with phosphate-buffered saline (PBS) in the same oil emulsion. Four weeks later, they were intranasally challenged with 2 × 10(5) TCID50 of a PCV2a strain. Antibody was measured in blood and oral fluids by enzyme-linked immunosorbent assay (ELISA) and a neutralization assay. PCV2 was quantified in serum by real-time polymerase chain reaction for ORF2 gene. PCV2-specific cell-mediated responses were investigated by an IFN-γ release assay in whole blood, IFN-γ ELISPOT, and lymphocyte proliferation (Ki-67 and BrDU assays). All the vaccines under study but mock provided complete or incomplete protection from PCV2 infection in terms of post-challenge viremia. Serum antibody titers (ELISA and neutralizing) after vaccination were not correlated with protection, as opposed to the early neutralizing antibody levels of vaccinated pigs at day 7 after infection. Cell-mediated immune parameters showed a good correlation with vaccine efficacy. In particular, the IFN-γ release assay at 3 weeks after vaccination was an effective marker for predicting protection. All control pigs always tested negative in assays of cell-mediated immunity. Our results outline in vitro testing procedures toward reduced animal usage in the control of PCV2 vaccine batches. PMID:26401584

  5. Vaccine adverse events.

    Science.gov (United States)

    Follows, Jill

    2012-01-01

    Millions of adults are vaccinated annually against the seasonal influenza virus. An undetermined number of individuals will develop adverse events to the influenza vaccination. Those who suffer substantiated vaccine injuries, disabilities, and aggravated conditions may file a timely, no-fault and no-cost petition for financial compensation under the National Vaccine Act in the Vaccine Court. The elements of a successful vaccine injury claim are described in the context of a claim showing the seasonal influenza vaccination was the cause of Guillain-Barré syndrome.

  6. Nucleic Acid Vaccines

    Institute of Scientific and Technical Information of China (English)

    LU Shan

    2004-01-01

    @@ Anew method of immunization was discovered in the early 1990s. Several research groups independently demonstrated that direct inoculation of DNA plasmids coding for a specific protein antigen could elicit immune responses against that antigen[1-4].Since in theory the mRNA molecules also have the potential to be translated into the protein antigen, this vaccination approach was officially named by WHO as the nucleic acid vaccination even though the term DNA vaccine has been used more commonly in the literature. This novel approach is considered the fourth generation of vaccines after live attenuated vaccines, killed or inactivated vaccines and recombinant protein based subunit vaccines.

  7. [Childhood vaccines and autism--much ado about nothing?].

    Science.gov (United States)

    Solt, Ido; Bornstein, Jacob

    2010-04-01

    The increased diagnoses of autism and developmental disorders in recent decades, together with the childhood vaccination program, has led to the hypothesis that vaccination in general, and the measles, mumps, and rubella virus live vaccine, and vaccines that contain mercury, in particular, cause autism. It has been hypothesized that intestinal infection caused by live virus vaccines change the permeability of the intestinal wall, and subsequently, the passage of peptides through the intestinal wall to the blood, and from there to the brain. It has been suggested that the accumulation of these peptides in the central nervous system causes autism. Studies that investigated this theory did not find an association between vaccine administration and between digestive system symptoms and autism. According to a second hypothesis, an organomercury compound (Thimerosal), used as a preservative in vaccines that do not include live viruses, is a cause of autism. Like the former, this hypothesis has been well researched, and refuted. Some studies have in fact found an increase in autism diagnosis among children who were vaccinated after Thimerosal was removed from the vaccine preparation. Recent studies have refuted the theory that the consecutive administration of vaccines weakens the young immune system in children, and leads to an autoimmune process that causes autism. The etiology of autism is still unknown, with research continuing from different directions. The extensive research conducted so far indicates that childhood vaccination is not a cause of the sharp increase in autism diagnoses in recent decades.

  8. Staging Mobilities

    DEFF Research Database (Denmark)

    Jensen, Ole B.

    and lived as people are “staging themselves” (from below). Staging mobilities is a dynamic process between “being staged” (for example, being stopped at traffic lights) and the “mobile staging” of interacting individuals (negotiating a passage on the pavement). Staging Mobilities is about the fact...

  9. OBSERVATION ON VACCINATING Newcastle Disease Virus Vaccine with Inhalation and Preventing Recurrence of Nasopharyngeal cancer after Radiotherapy

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    Objective: To understand whether the Newcastle disease virus(NDV) vaccine can successfully vaccinate the rabbits and volunteers of cancer patients by inhalation and to observe the effects of NDV vaccine on nasopharyngeal carcinoma (NRC) patients after radiotherapy. Methods: The live NDV vaccine was vaccinated through nasal cavities of rabbits, NPC patients and other cancer patients who were treated by surgery or chemotherapy with larynx spray. The blood specimens of vein from the tested rabbits and volunteers of patients with cancer were collected before and after vaccination. The anti-NDV-antibody in serum was detected by conventional blood coagulation inhibiting method. The white blood cell (WBC) amount in blood samples was counted. In addition, the NPC patients after radiotherapy were divided into both test group and control group with random match. The both were followed-up by multiple kinds of way in order to understand effects of NDV immunotherapy for NPC. Results: The anti-NDV-antibody level of the rabbits and the patients with NPC rose significantly after vaccination. The WBC amount of cancer patients treated by surgery or chemotherapy also rose significantly after vaccination. The recurrence rate (3.23%) of NRC patients in test group who received immunotherapy of NDV vaccine for 4 to 10 treatment courses within 3 years after end of radiotherapy were significantly lower than that (25.81%) of the control group (P<0.025). Conclusion: The NDV vaccine La Sota strain can vaccinate the rabbits and the cancer patients in success by inhalation. And it has remarkable effect to decrease 3 year recurrence rate of NRC patients after radiotherapy.

  10. Human anti-anthrax protective antigen neutralizing monoclonal antibodies derived from donors vaccinated with anthrax vaccine adsorbed

    OpenAIRE

    Sawada-Hirai, Ritsuko; Jiang, Ivy; Wang, Fei; Sun, Shu Man; Nedellec, Rebecca; Ruther, Paul; Alvarez, Alejandro; Millis, Diane; Morrow, Phillip R.; Kang, Angray S

    2004-01-01

    Background Potent anthrax toxin neutralizing human monoclonal antibodies were generated from peripheral blood lymphocytes obtained from Anthrax Vaccine Adsorbed (AVA) immune donors. The anti-anthrax toxin human monoclonal antibodies were evaluated for neutralization of anthrax lethal toxin in vivo in the Fisher 344 rat bolus toxin challenge model. Methods Human peripheral blood lymphocytes from AVA immunized donors were engrafted into severe combined immunodeficient (SCID) mice. Vaccination w...

  11. The Complexity of a Dengue Vaccine : A Review of the Human Antibody Response

    NARCIS (Netherlands)

    Flipse, Jacky; Smit, Jolanda M.

    2015-01-01

    Dengue is the most prevalent mosquito-borne viral disease worldwide. Yet, there are no vaccines or specific antivirals available to prevent or treat the disease. Several dengue vaccines are currently in clinical or preclinical stages. The most advanced vaccine is the chimeric tetravalent CYD-TDV vac

  12. Induced HBs antigenemia in healthy adults after immunization with two different hepatitis B recombinant vaccines

    OpenAIRE

    Masoud ZIAEE; Saádatjoo, Alireza; Mohamadpour, Malihe; Namaei, Mohammad Hasan

    2010-01-01

    Background and Aims Currently, vaccination is the most effective protective tool against hepatitis B virus infection. Some studies have shown that positive results for a hepatitis B virus surface antigen (HBsAg) test may be seen after vaccination. Materials and Methods In this clinical trial study, 62 healthy adult volunteers were randomly assigned to receive either the Engerix-B or the Hepavax-Gene hepatitis B recombinant vaccine. Blood samples were drawn 1, 3, and 5 days after vaccination a...

  13. Oral vaccination of fish

    OpenAIRE

    Embregts, Carmen W.E.; Forlenza, Maria

    2016-01-01

    The limited number of oral vaccines currently approved for use in humans and veterinary species clearly illustrates that development of efficacious and safe oral vaccines has been a challenge not only for fish immunologists. The insufficient efficacy of oral vaccines is partly due to antigen breakdown in the harsh gastric environment, but also to the high tolerogenic gut environment and to inadequate vaccine design. In this review we discuss current approaches used to develop oral vaccines fo...

  14. Towards universal influenza vaccines?

    OpenAIRE

    Osterhaus, Ab; Fouchier, Ron; Rimmelzwaan, Guus

    2011-01-01

    Vaccination is the most cost-effective way to reduce the considerable disease burden of seasonal influenza. Although seasonal influenza vaccines are effective, their performance in the elderly and immunocompromised individuals would benefit from improvement. Major problems related to the development and production of pandemic influenza vaccines are response time and production capacity as well as vaccine efficacy and safety. Several improvements can be envisaged. Vaccine production technologi...

  15. Vaccines against poverty

    OpenAIRE

    MacLennan, Calman A.; Saul, Allan

    2014-01-01

    With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vacc...

  16. Dental caries vaccine

    Directory of Open Access Journals (Sweden)

    Shivakumar K

    2009-01-01

    Full Text Available Dental caries is one of the most common diseases in humans. In modern times, it has reached epidemic proportions. Dental caries is an infectious microbiologic disease of the teeth that results in localized dissolution and destruction of the calcified tissue. Dental caries is a mulitifactorial disease, which is caused by host, agent, and environmental factors. The time factor is important for the development and progression of dental caries. A wide group of microorganisms are identified from carious lesions of which S. mutans , Lactobacillus acidophilus , and Actinomyces viscosus are the main pathogenic species involved in the initiation and development of dental caries. In India, surveys done on school children showed caries prevalence of approximately 58%. Surveys among the U.S. population showed an incidence of 45.3% in children and 93.8% in adults with either past or present coronal caries. Huge amounts of money and time are spent in treating dental caries. Hence, the prevention and control of dental caries is the main aim of public health, eventually the ultimate objective of public health is the elimination of the disease itself. Recently, dental caries vaccines have been developed for the prevention of dental caries. These dental caries vaccines are still in the early stages.

  17. Staging of moyamoya disease by perfusion SPECT

    Energy Technology Data Exchange (ETDEWEB)

    Kuwabara, Yasuo [Kyushu Univ., Fukuoka (Japan). Hospital; Matsushima, Toshio; Fukui, Masashi

    2001-04-01

    Staging of moyamoya disease, based on angiography and PET have already been established. The authors have established staging of moyamoya disease based on perfusion SPECT, that can be summarized as follows: Stage I, no abnormality is seen at rest or after acetazolamide loading; Stage II, no abnormality is seen at rest, however, a decreased response (blood flow increase rate: <15%) is seen to acetazolamide loading (a, a decreased response is seen only in the frontal lobe; b, a decreased response is seen in regions other than the frontal lobe; and c, a decreased response is seen throughout the cerebrum); Stage III, localized decrease in blood flow (blood flow decrease compared with peripheral tissue: {>=}15%) and marked decrease in response to acetazolamide (blood flow increase rate: <5%) are seen at rest. In Stage III, CT and MRI show no abnormal findings or only mild lesions of the white matter; and Stage IV, multiple decreases in blood flow are seen at rest, and CT and MRI reveal infarctions and severe atrophy at the same sites. The above staging does not require determination of cerebral blood flow, and thus it can be used in children, in whom cerebral blood flow determination is difficult. The authors performed 99m-Tc ECD perfusion SPECT in 25 patients with moyamoya disease for the staging, and compared staging based on angiography with staging based on perfusion SPECT. The results did not show a correlation between the 2 staging methods. A problem inherent in the staging of moyamoya disease based on perfusion SPECT is that the relationship between cerebral blood flow and cerebral radioactivity concentrations may differ depending on the drug used to determine cerebral blood flow. Thus, although the present staging system does not depend on any specific radioactive drug to determine cerebral blood flow, further investigation is necessary to identify a more appropriate drug than those in current use. (K.H.)

  18. Blood transfusions

    Science.gov (United States)

    ... called homologous blood donation. Many communities have a blood bank at which any healthy person can donate blood. ... need to arrange with your hospital or local blood bank before your surgery to have directed donor blood. ...

  19. Large animal models for vaccine development and testing.

    Science.gov (United States)

    Gerdts, Volker; Wilson, Heather L; Meurens, Francois; van Drunen Littel-van den Hurk, Sylvia; Wilson, Don; Walker, Stewart; Wheler, Colette; Townsend, Hugh; Potter, Andrew A

    2015-01-01

    The development of human vaccines continues to rely on the use of animals for research. Regulatory authorities require novel vaccine candidates to undergo preclinical assessment in animal models before being permitted to enter the clinical phase in human subjects. Substantial progress has been made in recent years in reducing and replacing the number of animals used for preclinical vaccine research through the use of bioinformatics and computational biology to design new vaccine candidates. However, the ultimate goal of a new vaccine is to instruct the immune system to elicit an effective immune response against the pathogen of interest, and no alternatives to live animal use currently exist for evaluation of this response. Studies identifying the mechanisms of immune protection; determining the optimal route and formulation of vaccines; establishing the duration and onset of immunity, as well as the safety and efficacy of new vaccines, must be performed in a living system. Importantly, no single animal model provides all the information required for advancing a new vaccine through the preclinical stage, and research over the last two decades has highlighted that large animals more accurately predict vaccine outcome in humans than do other models. Here we review the advantages and disadvantages of large animal models for human vaccine development and demonstrate that much of the success in bringing a new vaccine to market depends on choosing the most appropriate animal model for preclinical testing.

  20. Large animal models for vaccine development and testing.

    Science.gov (United States)

    Gerdts, Volker; Wilson, Heather L; Meurens, Francois; van Drunen Littel-van den Hurk, Sylvia; Wilson, Don; Walker, Stewart; Wheler, Colette; Townsend, Hugh; Potter, Andrew A

    2015-01-01

    The development of human vaccines continues to rely on the use of animals for research. Regulatory authorities require novel vaccine candidates to undergo preclinical assessment in animal models before being permitted to enter the clinical phase in human subjects. Substantial progress has been made in recent years in reducing and replacing the number of animals used for preclinical vaccine research through the use of bioinformatics and computational biology to design new vaccine candidates. However, the ultimate goal of a new vaccine is to instruct the immune system to elicit an effective immune response against the pathogen of interest, and no alternatives to live animal use currently exist for evaluation of this response. Studies identifying the mechanisms of immune protection; determining the optimal route and formulation of vaccines; establishing the duration and onset of immunity, as well as the safety and efficacy of new vaccines, must be performed in a living system. Importantly, no single animal model provides all the information required for advancing a new vaccine through the preclinical stage, and research over the last two decades has highlighted that large animals more accurately predict vaccine outcome in humans than do other models. Here we review the advantages and disadvantages of large animal models for human vaccine development and demonstrate that much of the success in bringing a new vaccine to market depends on choosing the most appropriate animal model for preclinical testing. PMID:25991698

  1. Association of IDDM and attenuated response of 2',5'-oligoadenylate synthetase to yellow fever vaccine

    DEFF Research Database (Denmark)

    Bonnevie-Nielsen, V; Larsen, M L; Frifelt, J J;

    1989-01-01

    Basal and yellow fever vaccination-induced 2',5'-oligoadenylate synthetase (2',5'A) activity was determined in blood mononuclear cells (peripheral blood lymphocytes [PBLs]) from insulin-dependent diabetes mellitus (IDDM) and matched control subjects. The live attenuated yellow fever vaccine repre...

  2. IMMUNE RESPONSES OF GOATS (SHAMI BREED TO VACCINATION WITH A FULL, REDUCED AND CONJUNCTIVAL DOSE OF BRUCEVAC (BRUCELLA MELITENSIS REV.1 VACCINE

    Directory of Open Access Journals (Sweden)

    F. ALDOMY, M. ALKHAWALDEH1 AND I. B. YOUNIS

    2009-10-01

    Full Text Available Three groups of Shami goats were randomly vaccinated with Brucevac (Rev. 1 vaccine. Group 1 was vaccinated subcutaneously with a full dose (1.54 x 109 organisms. Group 2 was vaccinated conjunctively with one eye drop (5.2 x 108 organisms, while Group 3 was injected subcutaneously with a reduced dose (7.1 x 105 organisms of vaccine. Blood samples were collected before vaccination, two, four, eight, 15 and 24 weeks post vaccination. All samples were tested through CFT, ELISA, SAT and Rose Bengal plate test. All serological tests used detected a higher percentage of vaccinated female kids with a full dose than they did in other groups vaccinated with a reduced dose or with a conjunctival dose of Rev.1 vaccine. The overall results suggested that 100% of animals vaccinated with a conjunctival dose became positive to CFT at two, four, eight and 15 weeks post vaccination, and then the percentage of seropositive animals declined and became 20% at 24 weeks post inoculation. The conjunctival route of vaccination significantly reduced the intensity and duration of the post vaccination serological response, which makes the use of this vaccine compatible with brucellosis programmes, even when these are based on a test-and–slaughter policy. The overall results showed that Shami goats responded to Rev.1 vaccine in the expected way. The majority of animals were seropositive to the CFT by two weeks after vaccination with higher numbers of seropositive animals in the kids group vaccinated with a full dose of Rev.1 vaccine.

  3. Typhoid fever vaccination strategies.

    Science.gov (United States)

    Date, Kashmira A; Bentsi-Enchill, Adwoa; Marks, Florian; Fox, Kimberley

    2015-06-19

    Typhoid vaccination is an important component of typhoid fever prevention and control, and is recommended for public health programmatic use in both endemic and outbreak settings. We reviewed experiences with various vaccination strategies using the currently available typhoid vaccines (injectable Vi polysaccharide vaccine [ViPS], oral Ty21a vaccine, and injectable typhoid conjugate vaccine [TCV]). We assessed the rationale, acceptability, effectiveness, impact and implementation lessons of these strategies to inform effective typhoid vaccination strategies for the future. Vaccination strategies were categorized by vaccine disease control strategy (preemptive use for endemic disease or to prevent an outbreak, and reactive use for outbreak control) and vaccine delivery strategy (community-based routine, community-based campaign and school-based). Almost all public health typhoid vaccination programs used ViPS vaccine and have been in countries of Asia, with one example in the Pacific and one experience using the Ty21a vaccine in South America. All vaccination strategies were found to be acceptable, feasible and effective in the settings evaluated; evidence of impact, where available, was strongest in endemic settings and in the short- to medium-term. Vaccination was cost-effective in high-incidence but not low-incidence settings. Experience in disaster and outbreak settings remains limited. TCVs have recently become available and none are WHO-prequalified yet; no program experience with TCVs was found in published literature. Despite the demonstrated success of several typhoid vaccination strategies, typhoid vaccines remain underused. Implementation lessons should be applied to design optimal vaccination strategies using TCVs which have several anticipated advantages, such as potential for use in infant immunization programs and longer duration of protection, over the ViPS and Ty21a vaccines for typhoid prevention and control.

  4. Who Should Not Get Vaccinated with These Vaccines?

    Science.gov (United States)

    ... be updated.) Top of Page HPV-Cervarix (Human Papillomavirus) vaccine Some people should not get HPV vaccine or ... updated.) Top of Page HPV-Gardasil-9 (Human Papillomavirus) vaccine Some people should not get HPV vaccine. Anyone ...

  5. Rotavirus vaccine: a review.

    Science.gov (United States)

    Kumar, Goel Manish; Arun, Kumar; Bilas, Jain Ram; Ruchi, Jain; Pardeep, Khanna; Pradeep, Siwach

    2012-12-01

    Worldwide, large proportion i.e., 37% of deaths due to diarrhea in young children is attributed to rotavirus. A monovalent P1A[8] G1 vaccine and a pentavalent bovine-human reassortant vaccine human rotavirus vaccine had shown good clinical efficacy without any increase in intussusception among vaccine recipients. WHO recommends that the first dose of rotavirus vaccine should be administered to infants up to age of 6-15 weeks irrespective of the prior history of rotavirus infection and the maximum age for administering the last dose of the vaccine should be 32 weeks. Booster doses are not recommended. The current update reviews the issues related to rotavirus vaccines and their usages like milestones in the development of rotavirus vaccines, concerns regarding their efficacy and cost-effectiveness, immunity after natural infection, potential for changes in virus strains, current recommendations, post marketing surveillance, and future challenges and scope for further research regarding rotavirus vaccines. PMID:25145068

  6. Commercialisation of a recombinant vaccine against Boophilus microplus.

    Science.gov (United States)

    Willadsen, P; Bird, P; Cobon, G S; Hungerford, J

    1995-01-01

    Increasingly, there is need for methods to control cattle tick (Boophilus microplus) infestations by the use of non-chemical technology. This need is brought about by a mixture of market forces and the failure or inadequacy of existing technology. A recombinant vaccine has now been developed against the tick. This vaccine relies on the uptake with the blood meal of antibody directed against a critical protein in the tick gut. The isolation of the vaccine antigen, Bm86, and its production as a recombinant protein is briefly described. The vaccine has been tested in the field, has been taken through the full registration process and is now in commercial use in Australia. A related development has occurred in Cuba. The potential for improvement of the current vaccine and for the development of similar vaccines against other haematophagous parasites is discussed. PMID:7784128

  7. Influenza virus vaccination and kidney graft rejection: causality or coincidence.

    Science.gov (United States)

    Fischer, Anne Sophie Lind; Møller, Bjarne Kuno; Krag, Søren; Jespersen, Bente

    2015-06-01

    Influenza can cause significant morbidity and mortality in renal transplant recipients especially with a high rate of lower respiratory disease. Annual influenza vaccination is therefore recommended to renal transplant recipients. We report the first three cases of acute kidney injury in renal transplant recipients following influenza vaccination that all led to graft loss. They all had different native diseases and were all vaccinated in the same season of 2009-10. The time span from vaccination to decline of kidney function is shorter than the time to diagnosis since the three patients only had blood tests every 3 months or when symptoms became severe. These reports do not justify a change of current recommendations regarding influenza vaccination in renal transplant recipients, but they support the continued attention and registration of vaccinations to monitor side effects. PMID:26034595

  8. Application of autologous tumor cell vaccine and NDV vaccine in treatment of tumors of digestive tract

    Institute of Scientific and Technical Information of China (English)

    Wei Liang; Hui Wang; Tie-Mie Sun; Wen-Qing Yao; Li-Li Chen; Yu Jin; Chun-Ling Li; Fan-Juan Meng

    2003-01-01

    AIM: To treat patients with stage Ⅰ-Ⅳ malignant tumors of digestive tract using autologous tumor cell vaccine and NDV (Newcastle disease virus) vaccine, and observe the survival period and curative effect.METHODS: 335 patients with malignant tumors of digestive tract were treated with autologous tumor cell vaccine and NDV vaccine. The autologous tumor cell vaccine were assigned for long-term survival observation. While these failed to obtain the autologous tumor tissue were given with NDV vaccine for a short-term observation on curative effect.RESULTS: The colorectal cancer patients treated with autologous tumor cell vaccine were divided into two groups:the controlled group (subjected to resection alone) (n=257),the vaccine group (subjected to both resection and immunotherapy) (n=310). 25 patients treated with NDV immunotherapy were all at stage Ⅳ without having resection.In postoperation adjuvant therapy patients, the 5, 6 and 7-year survival rates were 66.51%, 60.52 %, 56.50 %respectively; whereas in patients with resection alone, only 45.57 %, 44.76 % and 43.42 % respectively. The average survival period was 5.13 years (resection alone group 4.15years), the median survival period was over 7 years (resection alone group 4.46 years). There were significant differences between the two groups. The patients treated with resection plus vaccine were measured delayed-type hypersensitivity (DTH) reactions after vaccination, (indurative scope >5 mm).The magnitude of DTH was related to the prognosis. The 5-year survival rate was 80 % for those with indurations greater than 5 mm, compared with 30 % for those with indurations less than 5 mm. The 1-year survival rate was 96 % for 25patients treated with NDV immunotherapy. The total effective rate (CR+PR) was 24.00 % in NDV immunotherapy; complete remission (CR) in 1 case (4.00 %), partial remission (PR) in 5 cases (20.00 %), stabilizedin in 16 cases (64.00 %),progression (PD) in 1 case (4.00 %). After NDV vaccine

  9. Well staged

    Energy Technology Data Exchange (ETDEWEB)

    Budd, Godfrey

    2011-06-15

    Packers Plus Energy Services Inc. has commercially launched QuickFRAC, a multi-stage completition system which can fracture four to five isolated stages in one treatment and set up a record of 23-stage slickwater frac in less than 10 hours. It could take up to 40 days to do 100 fracture treatments with other systems. This technology makes it possible to distribute fluid at each port thanks to the limited entry system. In order to make multiple isolated stages within one treatment zone, each zone includes multiple QuickPORT sleeves with packers on either side. The other technology which made this possible is the repeater port system, it allows them to perform more frac stages. This technology could be useful in the future since the need for stages will be doubling soon with microdarcy shale oil extraction which is more difficult than gas.

  10. Vaccination of adult animals with a reduced dose of Brucella abortus S19 vaccine to control brucellosis on dairy farms in endemic areas of India.

    Science.gov (United States)

    Chand, Puran; Chhabra, Rajesh; Nagra, Juhi

    2015-01-01

    Bovine brucellosis is an economically important disease which seriously affects dairy farming by causing colossal losses. It can be controlled by practicing vaccination of animals with Brucella abortus S19 vaccine (S19 vaccine). In the present study, adult bovines were vaccinated on seven dairy farms with a reduced dose of S19 vaccine to control brucellosis. Serological screening of adult animals (N = 1,082) by Rose Bengal test (RBT) and ELISA prior to vaccination revealed the presence and absence of brucellosis on five and two farms, respectively. The positive animals (N = 171) were segregated and those which tested negative (N = 911) were vaccinated by conjunctival route with a booster after 4 months. The conjunctival vaccination induced weak antibody response in animals, which vanished within a period of 9 to 12 weeks. Abortion in 12 animals at various stages of pregnancy and post-vaccination was recorded, but none was attributed to S19 vaccine. However, virulent B. abortus was incriminated in six heifers, and the cause of abortion could not be established in six animals. The six aborted heifers perhaps acquired infection through in utero transmission or from the environment which remained undetected until abortion. These findings suggested that vaccination of adult animals with a reduced dose of S19 vaccine by conjunctival route did not produce adverse effects like abortion in pregnant animals and persistent vaccinal antibody titers, which are the major disadvantages of subcutaneous vaccination of adult animals. PMID:25274621

  11. Diphtheria Vaccination: Who Needs It?

    Science.gov (United States)

    ... and adults - Tetanus-diphtheria-acellular Pertussis vaccine Diphtheria Vaccination: Who Needs It? Recommend on Facebook Tweet Share ... Vaccine Information Statement (VIS) See also: Healthcare Personnel Vaccination Recommendations [1 page] July 2008 Top of Page ...

  12. 75 FR 48712 - Proposed Vaccine Information Materials for Influenza Vaccine

    Science.gov (United States)

    2010-08-11

    ..., rotavirus, hepatitis A, meningococcal, human papillomavirus (HPV), and trivalent influenza vaccines.... People who got the 2009 H1N1 vaccine still need to get vaccinated with the 2010-2011 influenza vaccine... always changing. Because of this, influenza vaccines are updated every year, and an annual vaccination...

  13. The relationship between RTS,S vaccine-induced antibodies, CD4⁺ T cell responses and protection against Plasmodium falciparum infection.

    Directory of Open Access Journals (Sweden)

    Michael T White

    Full Text Available Vaccination with the pre-erythrocytic malaria vaccine RTS,S induces high levels of antibodies and CD4(+ T cells specific for the circumsporozoite protein (CSP. Using a biologically-motivated mathematical model of sporozoite infection fitted to data from malaria-naive adults vaccinated with RTS,S and subjected to experimental P. falciparum challenge, we characterised the relationship between antibodies, CD4(+ T cell responses and protection from infection. Both anti-CSP antibody titres and CSP-specific CD4(+ T cells were identified as immunological surrogates of protection, with RTS,S induced anti-CSP antibodies estimated to prevent 32% (95% confidence interval (CI 24%-41% of infections. The addition of RTS,S-induced CSP-specific CD4(+ T cells was estimated to increase vaccine efficacy against infection to 40% (95% CI, 34%-48%. This protective efficacy is estimated to result from a 96.1% (95% CI, 93.4%-97.8% reduction in the liver-to-blood parasite inoculum, indicating that in volunteers who developed P. falciparum infection, a small number of parasites (often the progeny of a single surviving sporozoite are responsible for breakthrough blood-stage infections.

  14. The Use of a New CellCollector to Isolate Circulating Tumor Cells from the Blood of Patients with Different Stages of Prostate Cancer and Clinical Outcomes - A Proof-of-Concept Study

    Science.gov (United States)

    Theil, Gerit; Fischer, Kersten; Weber, Ekkehard; Medek, Rita; Hoda, Raschid; Lücke, Klaus; Fornara, Paolo

    2016-01-01

    Background and Methods Circulating tumor cells (CTCs) constitute a useful approach for personalized medicine. Nevertheless, the isolation of these cells remains very challenging because they rarely circulate in the blood. Another current problem is the cancer-specific characterization of these cells, which requires a method that allows for the molecular and immunocytochemical profiling of all captured cells. The purpose of our proof of concept study was to investigate the use of a medical wire (CellCollector, GILUPI) to isolate CTCs in the blood of prostate cancer (PCa) patients, which allowed CTCs to be counted and molecularly characterized. Forty-three PCa patients in different stages and 11 control subjects were studied. Some randomized samples were used to detect tumor-associated transcripts, such as prostate-specific membrane antigen (PSMA), prostate-specific antigen (PSA) and epidermal growth factor receptor (EGFR), in the isolated CTCs. Results The mean CTC counts were 4.6 CTCs [range, 0–8] in patients with localized PCa, 16.8 CTCs [range, 10–25] in patients with locally advanced PCa, and 26.8 CTCs [range, 0–98] in patients with metastatic PCa. The median follow-up time was 24 months, and there was a significant difference in the cancer-specific survival rates. Patients with CTC counts under 5 CTCs lived significantly longer (p = 0.035) than patients with more than 5 CTCs. We also demonstrated that the captured CTCs could be molecularly characterized. We detected tumor-associated transcripts of EGFR and PSMA in patients with metastatic PCa in 42.8% and 14.3% of the analyzed samples, respectively. Conclusion Our results indicate that the sensitive isolation and molecular characterization of CTCs can be achieved ex vivo using the wire. Patients with more than 5 CTCs had a mortality risk that was 7.0 times greater that of those with fewer than 5 CTCs (hazard ratio 7.0 95%, CI 1.1–29.39). This proof of concept was required for the approval of the use of

  15. Comparison of Plasmodium berghei challenge models for the evaluation of pre-erythrocytic malaria vaccines and their effect on perceived vaccine efficacy

    Directory of Open Access Journals (Sweden)

    Bergmann-Leitner Elke S

    2010-05-01

    Full Text Available Abstract Background The immunological mechanisms responsible for protection against malaria infection vary among Plasmodium species, host species and the developmental stage of parasite, and are poorly understood. A challenge with live parasites is the most relevant approach to testing the efficacy of experimental malaria vaccines. Nevertheless, in the mouse models of Plasmodium berghei and Plasmodium yoelii, parasites are usually delivered by intravenous injection. This route is highly artificial and particularly in the P. berghei model produces inconsistent challenge results. The initial objective of this study was to compare an optimized intravenous (IV delivery challenge model with an optimized single infectious mosquito bite challenge model. Finding shortcomings of both approaches, an alternative approach was explored, i.e., the subcutaneous challenge. Methods Mice were infected with P. berghei sporozoites by intravenous (tail vein injection, single mosquito bite, or subcutaneous injection of isolated parasites into the subcutaneous pouch at the base of the hind leg. Infection was determined in blood smears 7 and 14 days later. To determine the usefulness of challenge models for vaccine testing, mice were immunized with circumsporozoite-based DNA vaccines by gene gun. Results Despite modifications that allowed infection with a much smaller than reported number of parasites, the IV challenge remained insufficiently reliable and reproducible. Variations in the virulence of the inoculum, if not properly monitored by the rigorous inclusion of sporozoite titration curves in each experiment, can lead to unacceptable variations in reported vaccine efficacies. In contrast, mice with different genetic backgrounds were consistently infected by a single mosquito bite, without overwhelming vaccine-induced protective immune responses. Because of the logistical challenges associated with the mosquito bite model, the subcutaneous challenge route was

  16. Blood groups systems

    Directory of Open Access Journals (Sweden)

    Ranadhir Mitra

    2014-01-01

    Full Text Available International Society of Blood Transfusion has recently recognized 33 blood group systems. Apart from ABO and Rhesus system, many other types of antigens have been noticed on the red cell membranes. Blood grouping and cross-matching is one of the few important tests that the anaesthesiologist orders during perioperative period. Hence, a proper understanding of the blood group system, their clinical significance, typing and cross-matching tests, and current perspective are of paramount importance to prevent transfusion-related complications. Nonetheless, the knowledge on blood group system is necessary to approach blood group-linked diseases which are still at the stage of research. This review addresses all these aspects of the blood groups system.

  17. Blood groups systems.

    Science.gov (United States)

    Mitra, Ranadhir; Mishra, Nitasha; Rath, Girija Prasad

    2014-09-01

    International Society of Blood Transfusion has recently recognized 33 blood group systems. Apart from ABO and Rhesus system, many other types of antigens have been noticed on the red cell membranes. Blood grouping and cross-matching is one of the few important tests that the anaesthesiologist orders during perioperative period. Hence, a proper understanding of the blood group system, their clinical significance, typing and cross-matching tests, and current perspective are of paramount importance to prevent transfusion-related complications. Nonetheless, the knowledge on blood group system is necessary to approach blood group-linked diseases which are still at the stage of research. This review addresses all these aspects of the blood groups system. PMID:25535412

  18. Malaria vaccines:looking back and lessons learnt

    Institute of Scientific and Technical Information of China (English)

    Veronique; Lorenz; Panagiotis; Karanis

    2011-01-01

    The current status of malaria vaccine approaches has the background of a long and arduous path of malaria disease control and vaccine development.Here,we critically review with regard to unilateral interventional approaches and highlight the impact of socioeconomic elements of malaria endemicity. The necessity of re-energizing basic research of malaria life-cycle and Plasmodium developmental biology to provide the basis for promising and cost-effective vaccine approaches and to reach eradication goals is more urgent than previously believed.We closely analyse the flaws of various vaccine approaches,outline future directions and challenges that still face us and conclude that the focus of the field must be shifted to the basic research efforts including findings on the skin stage of infection.We also reflect on economic factors of vaccine development and the impact of public perception when it comes to vaccine uptake.

  19. 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...

  20. A single vaccination with an improved nonspreading Rift Valley fever virus vaccine provides sterile immunity in lambs.

    Directory of Open Access Journals (Sweden)

    Nadia Oreshkova

    Full Text Available Rift Valley fever virus (RVFV is an important pathogen that affects ruminants and humans. Recently we developed a vaccine based on nonspreading RVFV (NSR and showed that a single vaccination with this vaccine protects lambs from viremia and clinical signs. However, low levels of viral RNA were detected in the blood of vaccinated lambs shortly after challenge infection. These low levels of virus, when present in a pregnant ewe, could potentially infect the highly susceptible fetus. We therefore aimed to further improve the efficacy of the NSR vaccine. Here we report the expression of Gn, the major immunogenic protein of the virus, from the NSR genome. The resulting NSR-Gn vaccine was shown to elicit superior CD8 and CD4-restricted memory responses and improved virus neutralization titers in mice. A dose titration study in lambs revealed that the highest vaccination dose of 10(6.3 TCID50/ml protected all lambs from clinical signs and viremia. The lambs developed neutralizing antibodies within three weeks after vaccination and no anamnestic responses were observed following challenge. The combined results suggest that sterile immunity was achieved by a single vaccination with the NSR-Gn vaccine.

  1. A single vaccination with an improved nonspreading Rift Valley fever virus vaccine provides sterile immunity in lambs.

    Science.gov (United States)

    Oreshkova, Nadia; van Keulen, Lucien; Kant, Jet; Moormann, Rob J M; Kortekaas, Jeroen

    2013-01-01

    Rift Valley fever virus (RVFV) is an important pathogen that affects ruminants and humans. Recently we developed a vaccine based on nonspreading RVFV (NSR) and showed that a single vaccination with this vaccine protects lambs from viremia and clinical signs. However, low levels of viral RNA were detected in the blood of vaccinated lambs shortly after challenge infection. These low levels of virus, when present in a pregnant ewe, could potentially infect the highly susceptible fetus. We therefore aimed to further improve the efficacy of the NSR vaccine. Here we report the expression of Gn, the major immunogenic protein of the virus, from the NSR genome. The resulting NSR-Gn vaccine was shown to elicit superior CD8 and CD4-restricted memory responses and improved virus neutralization titers in mice. A dose titration study in lambs revealed that the highest vaccination dose of 10(6.3) TCID50/ml protected all lambs from clinical signs and viremia. The lambs developed neutralizing antibodies within three weeks after vaccination and no anamnestic responses were observed following challenge. The combined results suggest that sterile immunity was achieved by a single vaccination with the NSR-Gn vaccine.

  2. 9 CFR 113.327 - Bronchitis Vaccine.

    Science.gov (United States)

    2010-01-01

    ... respiratory signs or death shall be counted as failures. Two-stage sequential testing may be conducted if the.... Final container samples of completed product shall be tested for virus titer using the procedure... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Bronchitis Vaccine. 113.327...

  3. 2株间日疟原虫18S rDNA的克隆及其同源性分析%Cloning and homology analysis of blood stage 18S rDNA of two Plasmodium vivax isolates

    Institute of Scientific and Technical Information of China (English)

    高世同; 李晓恒; 耿艺介; 黄达娜; 谢旭; 梅树江; 张仁利

    2013-01-01

    目的 克隆间日疟原虫河南分离株与湖北分离株红内期18S rDNA,并进行同源性分析.方法 采用PCR方法从间日疟患者血样DNA中扩增间日疟原虫18S rDNA,纯化后与pGEM-Teasy质粒连接,转化大肠埃希氏菌JM109;阳性克隆质粒经双酶切鉴定后,进行序列测定,采用BLAST和MEGA4生物软件分析同源性. 结果 间日疟原虫18S rDNA扩增片段大小为998 bp;阳性克隆重组质粒经双酶切鉴定,与预期结果相符;序列测定结果显示,河南、湖北2分离株间日疟原虫18S rDNA序列完全相同,与GenBank中报道的12株间日疟原虫相同序列进行比对,其同源性均大于99%;用邻位连接法(neigh-bor-joining,NJ)和非加权组平均法(UPGMA)2种方法构建系统发生树发现,河南分离株、湖北分离株与间日疟原虫X13926.1株遗传距离小,同属一个分支.结论 克隆了间日疟原虫河南与湖北分离株红内期18S rDNA,该基因序列在不同地理株间遗传稳定.%Objective To clone and homology analyze the sequences of blood stage 18S rRNA-encoding gene fragment of two P.vivax isolates from Henan and Hubei provinces in China.Methods The 18S rDNA fragments were amplified by PCR from the DNA extracted from two P.vivax infection blood samples.After purification,the gene fragments were ligated with plasmid pGEM-Teasy to construct recombinant plasmids,and transformed into E.coli JM109.Positive clones were identified by double enzymes digestion methods.The sequences of inserted 18S rDNA fragments were finally determined and analyzed with BLAST and MEGA4 biological software.Results The amplified 18S rDNA fragments of two isolates were about 998 bp in length,and the 18S rDNA sequence of Henan isolate was same as that of Hubei isolate.As aligned with the corresponding sequences of twelve P.vivax strains deposited in the GenBank database,the indentity of nucleotides was more than 99% respectively.Based on the 18S rDNA sequence,phylogenetic analysis with

  4. Key Facts about Seasonal Flu Vaccine

    Science.gov (United States)

    ... flu is to get vaccinated each year. Flu Vaccination Why should people get vaccinated against the flu? ... Vaccine Benefits What are the benefits of flu vaccination? While how well the flu vaccine works can ...

  5. Pertussis (Whooping Cough) Vaccination

    Science.gov (United States)

    ... Tdap= Tetanus-diphtheria-acellular Pertussis vaccine Pertussis (Whooping Cough) Vaccination Pronounced (per-TUS-iss) Recommend on Facebook Tweet Share Compartir Whooping cough — known medically as pertussis — is a ...

  6. Screening Tests and Vaccines

    Science.gov (United States)

    ... Contact Us Text size | Print | Screening Tests and Vaccines This information in Spanish ( en español ) Getting important screening tests and vaccines can save your life. Check this section of ...

  7. Vaccine Safety Datalink

    Science.gov (United States)

    The Vaccine Safety Datalink is part of the National Immunization Program within the Centers for Disease Control and Prevention and was started in recognition of gaps in the scientific knowledge of rare vaccine side effects.

  8. The HPV Vaccination Crisis

    Science.gov (United States)

    Following the release of a consensus statement from the NCI-Designated Cancer Centers urging HPV vaccination in the United States, Dr. Noel Brewer discusses the country’s low vaccination rates and how clinicians can help to improve them.

  9. Blood culture

    Science.gov (United States)

    Culture - blood ... A blood sample is needed . The site where blood will be drawn is first cleaned with an antiseptic such ... organism from the skin getting into (contaminating) the blood sample and causing a false-positive result (see ...

  10. Blood Thinners

    Science.gov (United States)

    If you have some kinds of heart or blood vessel disease, or if you have poor blood flow to your brain, your doctor may recommend that you take a blood thinner. Blood thinners reduce the risk of heart ...

  11. Blood Basics

    Science.gov (United States)

    ... Patient Group Links Advocacy Toolkit Home For Patients Blood Basics Blood is a specialized body fluid. It ... about 9 pints. Jump To: The Components of Blood and Their Importance Many people have undergone blood ...

  12. Blood pressure

    Science.gov (United States)

    ... the walls of the arteries is called blood pressure. Blood pressure is measured both as the heart contracts, which ... as it relaxes, which is called diastole. Normal blood pressure is considered to be a systolic blood pressure ...

  13. Vaccines for viral and bacterial pathogens causing acute gastroenteritis: Part I: Overview, vaccines for enteric viruses and Vibrio cholerae.

    Science.gov (United States)

    O'Ryan, Miguel; Vidal, Roberto; del Canto, Felipe; Salazar, Juan Carlos; Montero, David

    2015-01-01

    Efforts to develop vaccines for prevention of acute diarrhea have been going on for more than 40 y with partial success. The myriad of pathogens, more than 20, that have been identified as a cause of acute diarrhea throughout the years pose a significant challenge for selecting and further developing the most relevant vaccine candidates. Based on pathogen distribution as identified in epidemiological studies performed mostly in low-resource countries, rotavirus, Cryptosporidium, Shigella, diarrheogenic E. coli and V. cholerae are predominant, and thus the main targets for vaccine development and implementation. Vaccination against norovirus is most relevant in middle/high-income countries and possibly in resource-deprived countries, pending a more precise characterization of disease impact. Only a few licensed vaccines are currently available, of which rotavirus vaccines have been the most outstanding in demonstrating a significant impact in a short time period. This is a comprehensive review, divided into 2 articles, of nearly 50 vaccine candidates against the most relevant viral and bacterial pathogens that cause acute gastroenteritis. In order to facilitate reading, sections for each pathogen are organized as follows: i) a discussion of the main epidemiological and pathogenic features; and ii) a discussion of vaccines based on their stage of development, moving from current licensed vaccines to vaccines in advanced stage of development (in phase IIb or III trials) to vaccines in early stages of clinical development (in phase I/II) or preclinical development in animal models. In this first article we discuss rotavirus, norovirus and Vibrio cholerae. In the following article we will discuss Shigella, Salmonella (non-typhoidal), diarrheogenic E. coli (enterotoxigenic and enterohemorragic), and Campylobacter jejuni. PMID:25715048

  14. RECOMBINANT INFLUENZA VACCINES

    OpenAIRE

    Sedova, E.; Shcherbinin, D.; Migunov, A.; Smirnov, Iu; Logunov, D.; Shmarov, M.; Tsybalova, L.; Naroditskiĭ, B.; O. Kiselev; Gintsburg, A.

    2012-01-01

    This review covers the problems encountered in the construction and production of new recombinant influenza vaccines. New approaches to the development of influenza vaccines are investigated; they include reverse genetics methods, production of virus-like particles, and DNA- and viral vector-based vaccines. Such approaches as the delivery of foreign genes by DNA- and viral vector-based vaccines can preserve the native structure of antigens. Adenoviral vectors are a promising gene-delivery pla...

  15. Clinical vaccine development

    OpenAIRE

    Han, Seunghoon

    2015-01-01

    Vaccination is regarded as one of the biggest triumphs in the history of medicine. We are living in the most successful period of vaccine development. The accumulation of multidisciplinary knowledge and the investment of massive funding have enabled the development of vaccines against many infectious diseases as well as other diseases including malignant tumors. The paradigm of clinical vaccine evaluation and licensure has also been modernized based on scientific improvements and historical e...

  16. Immune responses induced by gene gun or intramuscular injection of DNA vaccines that express immunogenic regions of the serine repeat antigen from Plasmodium falciparum.

    Science.gov (United States)

    Belperron, A A; Feltquate, D; Fox, B A; Horii, T; Bzik, D J

    1999-10-01

    The liver- and blood-stage-expressed serine repeat antigen (SERA) of Plasmodium falciparum is a candidate protein for a human malaria vaccine. We compared the immune responses induced in mice immunized with SERA-expressing plasmid DNA vaccines delivered by intramuscular (i.m.) injection or delivered intradermally by Gene Gun immunization. Mice were immunized with a pcdna3 plasmid encoding the entire 47-kDa domain of SERA (amino acids 17 to 382) or the N-terminal domain (amino acids 17 to 110) of SERA. Minimal antibody responses were detected following DNA vaccination with the N-terminal domain of SERA, suggesting that the N-terminal domain alone is not highly immunogenic by this route of vaccine delivery. Immunization of mice by Gene Gun delivery of the 47-kDa domain of SERA elicited a significantly higher serum antibody titer to the antigen than immunization of mice by i.m. injection with the same plasmid did. The predominant isotype subclass of the antibodies elicited to the SERA protein following i.m. and Gene Gun immunizations with SERA plasmid DNA was immunoglobulin G1. Coimmunization of mice with SERA plasmid DNA and a plasmid expressing the hepatitis B surface antigen (pCMV-s) by the i.m. route resulted in higher anti-SERA titers than those generated in mice immunized with the SERA DNA plasmid alone. Vaccination with DNA may provide a viable alternative or may be used in conjunction with protein-based subunit vaccines to maximize the efficacy of a human malaria vaccine that includes immunogenic regions of the SERA protein. PMID:10496891

  17. Immune Response to Hepatitis B Vaccine among Dental Students

    Directory of Open Access Journals (Sweden)

    HR Abdolsamadi

    2009-06-01

    Full Text Available "nBackground: Hepatitis B infection is a major public health problem worldwide. Dental students who are frequently in contact with body fluids like blood and saliva are still at high risk for HBV exposure. The aim of this study was to evaluate the effectiveness of HBV vaccine and personal factors associated with serologic evidence of the immune response."nMethods: A descriptive-cross sectional study was carried out using data from Hamadan dental school students that received just three doses of HBV vaccine. The serum sample of 86 dental clinical students were examined in order to determine hepatitis B surface antigen and the level of anti-HBs using IEMA method. Logistic regression models were used to assess the relationship of vaccine response to the variables Sex, age weight, smoking status and the time lasting from the third dose of vaccine injection."nResults: Ninety-three percent had positive anti-HBs response and 7% were non-responders. No one showed HBsAg. Vaccine response was most strongly associated with age, smoking status, sex and weight. The time lasting from the third dose was unrelated to vaccine response."nConclusion: Clinical dental students had desirable immune response to the HBV vaccine nevertheless recommended num­ber of doses, standard protocol and early vaccination are critical to adequate protection against hepatitis infection among all health care workers, in particular dental students and dentists who are often exposed to blood and other body fluids.

  18. Vaccines in dermatology

    Directory of Open Access Journals (Sweden)

    Mitali M Shah

    2015-01-01

    Full Text Available A vaccine is a biological preparation that improves immunity to a specific disease. More than two centuries have passed since the first successful vaccine for smallpox was developed. We′ve come a long way since. Today′s vaccines are among the 21 st century′s most successful and cost-effective public health tools for preventing diseases.

  19. Vaccination: problems and perspectives.

    OpenAIRE

    S. M. Kharit

    2014-01-01

    Massive vaccination had proved its effective morbidity reduction. Today it is necessary to extend vaccination schedule, creation of selective, regional schedules based on epidemiological, clinical, economical substantiation. Development of vaccination needs the profound scientific research, modernization of adverse reaction observing system, betterment training system and awareness of population.

  20. A Dengue Vaccine.

    Science.gov (United States)

    Durbin, Anna P

    2016-06-30

    Denvaxia is the first licensed vaccine for the prevention of dengue. It is a live vaccine developed using recombinant DNA technology. The vaccine is given as three doses over the course of a year and has the potential to prevent hundreds of thousands of hospitalizations each year. PMID:27368091

  1. Drying drops of blood

    Science.gov (United States)

    Brutin, David; Sobac, Benjamin; Loquet, Boris; Sampol, José.

    2010-11-01

    The drying of a drop of human blood is fascinating by the complexity of the physical mechanisms that occur as well as the beauty of the phenomenon which has never been previously evidenced in the literature. The final stage of full blood evaporation reveals for a healthy person the same regular pattern with a good reproducibility. Other tests on anemia and hyperlipidemic persons were performed and presented different patterns. By means of digital camera, the influence of the motion of red blood cells (RBCs) which represent about 50% of the blood volume, is revealed as well as its consequences on the final stages of drying. The mechanisms which lead to the final pattern of dried blood drops are presented and explained on the basis of fluid and solid mechanics in conjunction with the principles of hematology. Our group is the first to evidence that the specific regular patterns characteristic of a healthy individual do not appear in a dried drop of blood from a person with blood disease. Blood is a complex colloidal suspension for which the flow motion is clearly non-Newtonian. When drops of blood evaporate, all the colloids are carried by the flow motion inside the drop and interact.

  2. Vaccination Against Dengue: Challenges and Current Developments.

    Science.gov (United States)

    Guy, Bruno; Lang, Jean; Saville, Melanie; Jackson, Nicholas

    2016-01-01

    Dengue is a growing threat worldwide, and the development of a vaccine is a public health priority. The completion of the active phase of two pivotal efficacy studies conducted in Asia and Latin America by Sanofi Pasteur has constituted an important step. Several other approaches are under development, and whichever technology is used, vaccine developers face several challenges linked to the particular nature and etiology of dengue disease. We start our review by defining questions and potential issues linked to dengue pathology and presenting the main types of vaccine approaches that have explored these questions; some of these candidates are in a late stage of clinical development. In the second part of the review, we focus on the Sanofi Pasteur dengue vaccine candidate, describing the steps from research to phase III efficacy studies. Finally, we discuss what could be the next steps, before and after vaccine introduction, to ensure that the vaccine will provide the best benefit with an acceptable safety profile to the identified target populations.

  3. Formalin-inactivated whole virus and recombinant subunit flavivirus vaccines.

    Science.gov (United States)

    Eckels, Kenneth H; Putnak, Robert

    2003-01-01

    The Flaviviridae is a family of arthropod-borne, enveloped, RNA viruses that contain important human pathogens such as yellow fever (YF), Japanese encephalitis (JE), tick-borne encephalitis (TBE), West Nile (WN), and the dengue (DEN) viruses. Vaccination is the most effective means of disease prevention for these viral infections. A live-attenuated vaccine for YF, and inactivated vaccines for JE and TBE have significantly reduced the incidence of disease for these viruses, while licensed vaccines for DEN and WN are still lacking despite a significant disease burden associated with these infections. This review focuses on inactivated and recombinant subunit vaccines (non-replicating protein vaccines) in various stages of laboratory development and human testing. A purified, inactivated vaccine (PIV) candidate for DEN will soon be evaluated in a phase 1 clinical trial, and a second-generation JE PIV produced using similar technology has advanced to phase 2/3 trials. The inactivated TBE vaccine used successfully in Europe for almost 30 years continues to be improved by additional purification, new stabilizers, an adjuvant, and better immunization schedules. The recent development of an inactivated WN vaccine for domestic animals demonstrates the possibility of producing a similar vaccine for human use. Advances in flavivirus gene expression technology have led to the production of several recombinant subunit antigen vaccine candidates in a variety of expression systems. Some of these vaccines have shown sufficient promise in animal models to be considered as candidates for evaluation in clinical trials. Feasibility of non-replicating flavivirus vaccines has been clearly demonstrated and further development is now warranted. PMID:14714438

  4. Hamsters vaccinated with Ace-mep-7 DNA vaccine produced protective immunity against Ancylostoma ceylanicum infection.

    Science.gov (United States)

    Wiśniewski, Marcin; Jaros, Sławomir; Bąska, Piotr; Cappello, Michael; Długosz, Ewa; Wędrychowicz, Halina

    2016-04-01

    Hookworms are intestinal nematodes that infect up to 740 million people, mostly in tropical and subtropical regions. Adult worms suck blood from damaged vessels in the gut mucosa, digesting hemoglobin using aspartic-, cysteine- and metalloproteases. Targeting aspartic hemoglobinases using drugs or vaccines is therefore a promising approach to ancylostomiasis control. Based on homology to metalloproteases from other hookworm species, we cloned the Ancylostoma ceylanicum metalloprotease 7 cDNA (Ace-mep-7). The corresponding Ace-MEP-7 protein has a predicted molecular mass of 98.8 kDa. The homology to metallopeptidases from other hookworm species and its predicted transmembrane region support the hypothesis that Ace-MEP-7 may be involved in hemoglobin digestion in the hookworm gastrointestinal tract, especially that our analyses show expression of Ace-mep-7 in the adult stage of the parasite. Immunization of Syrian golden hamsters with Ace-mep-7 cDNA resulted in 50% (p < 0.01) intestinal worm burden reduction. Additionally 78% (p < 0.05) egg count reduction in both sexes was observed. These results suggest that immunization with Ace-mep-7 may contribute to reduction in egg count released into the environment during the A. ceylanicum infection. PMID:26795262

  5. Vaccination in Fish

    DEFF Research Database (Denmark)

    Chettri, Jiwan Kumar

    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...... significant losses in aquacultural enterprises but vaccination methods implemented since the 1990s have demonstrated their role as one of the most efficient disease control strategies. These have been particularly successful with regard to bacterial diseases in Norwegian salmon farming where multivalent...

  6. Vaccination for Disease

    Science.gov (United States)

    Oehen, Stephan; Hengartner, Hans; Zinkernagel, Rolf M.

    1991-01-01

    Recombinant virus vaccines that express a limited number of epitopes are currently being developed to prevent disease by changing the relative balance between viral spread and the immune response. Some circumstances, however, were found in infections with a noncytopathic virus in which vaccination caused disease; sensitive parameters included the genetic background of the host, the time or dose of infection, and the constituents of the vaccine. Thus, immunopathologic damage by T cells may be an unwanted consequence of vaccination with the new types of peptide or recombinant vaccines that are being investigated for the human immunodeficiency viruses and other pathogens.

  7. Advances in FIV vaccine technology

    OpenAIRE

    Uhl, Elizabeth W.; Martin, Marcus; Coleman, James K.; Yamamoto, Janet K

    2008-01-01

    Advances in vaccine technology are occurring in the molecular techniques used to develop vaccines and in the assessment of vaccine efficacy, allowing more complete characterization of vaccine-induced immunity correlating to protection. FIV vaccine development has closely mirrored and occasionally surpassed the development of HIV-1 vaccine, leading to first licensed technology. This review will discuss technological advances in vaccine designs, challenge infection assessment, and characterizat...

  8. Protective activity of Vi capsular polysaccharide vaccine against typhoid fever.

    Science.gov (United States)

    Klugman, K P; Gilbertson, I T; Koornhof, H J; Robbins, J B; Schneerson, R; Schulz, D; Cadoz, M; Armand, J

    1987-11-21

    The protective efficacy against typhoid fever of a single intramuscular injection of 25 micrograms of the Vi capsular polysaccharide (CPS) was assessed in a randomised double-blind controlled trial. Vaccination of 11,384 children was followed by 21 months' surveillance. 47 blood-culture-proven cases of typhoid occurred in children who received meningococcal A + C CPS vaccine and 19 cases in those vaccinated with Vi CPS. Protective efficacy was 60% calculated from the day of vaccination and 64% from 6 weeks after vaccination. Surveillance also included 11,691 unvaccinated children; 173 cases occurred in this group. Protective efficacy in relation to the unvaccinated group was 77.4% and 81.0% after 21 months, calculated immediately and 6 weeks after vaccination, respectively. Vaccination was associated with minimum local side-effects, and an increase in anti-Vi antibodies occurred, as measured by radioimmunoassay and enzyme-linked immunosorbent assay. Antibody levels remained significantly raised at 6 and 12 months post vaccination. Vi CPS is thus a safe and effective means of typhoid vaccination.

  9. Biodegradable Microspheres as Hepatitis B Vaccine Delivery Systems

    Institute of Scientific and Technical Information of China (English)

    杨春; 贾文祥; 陈恬; 曾蔚; 杨远; 杨发龙; 谢轶; 杨维清; 周绍兵; 李孝红

    2003-01-01

    In order to investigate the immtmogenicity of the controlled-release microencapsulated hepatitis B vaccine in mice, polyethylene glycol-poly-dl-lactide (PELA) microspheres with entrapped HSsAg were prepared by double emulsion W/O/W based on solvent extraction methods. BALB/c mice were immunized with the encapsulated vaccine by oral feeding or injection. Blood samples were collected at 8th, 10th, 14th and 24th weeks, respectively, and the levels of antibody response were detected by EI.ISA. It was found that the scanning electron microscopy showed the prepared microspheres had smoothand spherical surface, suitable for vaccine delivery. Two groups of mice orally fed with the encapsulated or conventional recombinant vaccines, respectively, there sere showed no obvious difference in the IgG levels. At 14th week, the group injected with a single dose of encapsulated vaccine had a similar level of IgG response to the group injected with two doses of the recombination vaccine. At 24th week, the IgG levels of the group injected with two doses of encapsulated vaccine were higher than those of the group injected with two doses of the recombination vaccine. It concludes that Controlled-release microencapsulated hepatitis B vaccine possesses the feature of slowly releasing in v/vo and long times immtmogenicity.

  10. Bacterial otitis media: current vaccine development strategies.

    Science.gov (United States)

    Cripps, Allan W; Kyd, Jennelle

    2003-02-01

    Otitis media is the most common reason for children less than 5 years of age to visit a medical practitioner. Whilst the disease rarely results in death, there is significant associated morbidity. The most common complication is loss of hearing at a critical stage of the development of speech, language and cognitive abilities in children. The cause and pathogenesis of otitis media is multifactorial. Among the contributing factors, the single most important are viral and bacterial infections. Infection with respiratory syncytial virus, influenza viruses, para-influenza viruses, enteroviruses and adenovirus are most commonly associated with acute and chronic otitis media. Streptococcus pneumoniae, non-typeable Haemophilus influenzae and Moraxella catarrhalis are the most commonly isolated bacteria from the middle ears of children with otitis media. Treatment of otitis media has largely relied on the administration of antimicrobials and surgical intervention. However, attention has recently focused on the development of a vaccine. For a vaccine to be effective against bacterial otitis media, it must, at the very least, contain antigens that induce a protective immune response in the middle ear against the three most common infecting bacteria. Whilst over the past decade there has been significant progress in the development of vaccines against invasive S. pneumoniae disease, these vaccines are less efficacious for otitis media. The search for candidate vaccine antigens for non-typeable H. influenzae are well advanced whilst less progress has been made for M. catarrhalis. No human studies have been conducted for non-typeable H. influenzae or M. catarrhalis and the concept of a tribacterial vaccine remains to be tested in animal models. Only when vaccine antigens are determined and an understanding of the immune responses induced in the middle ear by infection and immunization is gained will the formulation of a tribacterial vaccine against otitis media be possible.

  11. Emerging Vaccine Informatics

    Directory of Open Access Journals (Sweden)

    Yongqun He

    2010-01-01

    Full Text Available Vaccine informatics is an emerging research area that focuses on development and applications of bioinformatics methods that can be used to facilitate every aspect of the preclinical, clinical, and postlicensure vaccine enterprises. Many immunoinformatics algorithms and resources have been developed to predict T- and B-cell immune epitopes for epitope vaccine development and protective immunity analysis. Vaccine protein candidates are predictable in silico from genome sequences using reverse vaccinology. Systematic transcriptomics and proteomics gene expression analyses facilitate rational vaccine design and identification of gene responses that are correlates of protection in vivo. Mathematical simulations have been used to model host-pathogen interactions and improve vaccine production and vaccination protocols. Computational methods have also been used for development of immunization registries or immunization information systems, assessment of vaccine safety and efficacy, and immunization modeling. Computational literature mining and databases effectively process, mine, and store large amounts of vaccine literature and data. Vaccine Ontology (VO has been initiated to integrate various vaccine data and support automated reasoning.

  12. Vaccines for allergy.

    Science.gov (United States)

    Linhart, Birgit; Valenta, Rudolf

    2012-06-01

    Vaccines aim to establish or strengthen immune responses but are also effective for the treatment of allergy. The latter is surprising because allergy represents a hyper-immune response based on immunoglobulin E production against harmless environmental antigens, i.e., allergens. Nevertheless, vaccination with allergens, termed allergen-specific immunotherapy is the only disease-modifying therapy of allergy with long-lasting effects. New forms of allergy diagnosis and allergy vaccines based on recombinant allergen-derivatives, peptides and allergen genes have emerged through molecular allergen characterization. The molecular allergy vaccines allow sophisticated targeting of the immune system and may eliminate side effects which so far have limited the use of traditional allergen extract-based vaccines. Successful clinical trials performed with the new vaccines indicate that broad allergy vaccination is on the horizon and may help to control the allergy pandemic.

  13. Vaccine epidemiology: A review.

    Science.gov (United States)

    Lahariya, Chandrakant

    2016-01-01

    This review article outlines the key concepts in vaccine epidemiology, such as basic reproductive numbers, force of infection, vaccine efficacy and effectiveness, vaccine failure, herd immunity, herd effect, epidemiological shift, disease modeling, and describes the application of this knowledge both at program levels and in the practice by family physicians, epidemiologists, and pediatricians. A case has been made for increased knowledge and understanding of vaccine epidemiology among key stakeholders including policy makers, immunization program managers, public health experts, pediatricians, family physicians, and other experts/individuals involved in immunization service delivery. It has been argued that knowledge of vaccine epidemiology which is likely to benefit the society through contributions to the informed decision-making and improving vaccination coverage in the low and middle income countries (LMICs). The article ends with suggestions for the provision of systematic training and learning platforms in vaccine epidemiology to save millions of preventable deaths and improve health outcomes through life-course. PMID:27453836

  14. Alterations in p53-specific T cells and other lymphocyte subsets in breast cancer patients during vaccination with p53-peptide loaded dendritic cells and low-dose interleukin-2

    DEFF Research Database (Denmark)

    Svane, Inge Marie; Pedersen, Anders E; Nikolajsen, Kirsten;

    2008-01-01

    We have previously established a cancer vaccine using autologous DCs, generated by in vitro stimulation with IL-4 and GM-CSF, and pulsed with six HLA-A*0201 binding wild-type p53 derived peptides. This vaccine was used in combination with low-dose interleukin-2 in a recently published clinical...... Phase II trial where 26 HLA-A2+ patients with progressive late-stage metastatic breast cancer (BC) were included. Almost 1/3rd of the patients obtained stable disease or minor regression during treatment with a positive correlation to tumour over-expression of p53. In the present study, we performed...... a comprehensive analysis of the effector stage of the p53-specific CD8+ T cells by the use of Dextramer Technology and multicolour FACS. Pre- and post-treatment blood samples from eight BC patients were analysed. Independent of clinical outcome p53-specific T cells were phenotypic distinctly antigen experienced...

  15. New tuberculosis vaccines.

    Science.gov (United States)

    Martín Montañés, Carlos; Gicquel, Brigitte

    2011-03-01

    The current tuberculosis (TB) vaccine, bacille Calmette-Guerin (BCG), is a live vaccine used worldwide, as it protects against severe forms of the disease, saving thousands of lives every year, but its efficacy against pulmonary forms of TB, responsible for transmission of the diseases, is variable. For more than 80 years now no new TB vaccines have been successfully developed. Over the last decade the effort of the scientific community has resulted in the design and construction of promising vaccine candidates. The goal is to develop a new generation of vaccines effective against respiratory forms of the disease. We will focus this review on new prophylactic vaccine candidates that aim to prevent TB diseases. Two are the main strategies used to improve the immunity conferred by the current BCG vaccine, by boosting it with new subunit vaccines, and a second strategy is focused on the construction of new more effective live vaccines, capable to replace the current BCG and to be used as prime vaccines. After rigorous preclinical studies in different animal models new TB vaccine candidates enter in clinical trials in humans. First, a small Phase I for safety followed by immunological evaluation in Phase II trials and finally evaluated in large population Phase III efficacy trials in endemic countries. At present BCG prime and boost with different subunit vaccine candidates are the more advanced assessed in Phase II. Two prime vaccines (based on recombinant BCG) have been successfully evaluated for safety in Phase I trials. A short number of live attenuated vaccines are in advance preclinical studies and the candidates ready to enter Phase I safety trials are produced under current good manufacturing practices. PMID:21420568

  16. Proteins involved in invasion of human red blood cells by malaria parasites

    Directory of Open Access Journals (Sweden)

    Ewa Jaśkiewicz

    2010-11-01

    Full Text Available Malaria is a disease caused by parasites of Plasmodium species. It is responsible for around 1-2 million deaths annually, mainly children under the age of 5. It occurs mainly in tropical and subtropical areas.Malaria is caused by five Plasmodium species:[i] P. falciparum, P. malariae, P. vivax, P. knowlesi[/i] and [i]P. ovale[/i]. Mosquitoes spread the disease by biting humans. The malaria parasite has two stages of development: the human stage and the mosquito stage. The first stage occurs in the human body and is divided into two phases: the liver phase and the blood phase.The invasion of erythrocytes by [i]Plasmodium[/i] merozoites is a multistep process of specific protein interactions between the parasite and red blood cell. The first step is the reversible merozoite attachment to the erythrocyte followed by its apical reorientation, then formation of an irreversible “tight” junction and finally entry into the red cell in a parasitophorous vacuole.The blood phase is supported by a number of proteins produced by the parasite. The merozoite surface GPI-anchored proteins (MSP-1, 2, 4, 5, 8 and 10 assist in the process of recognition of susceptible erythrocytes, apical membrane antigen (AMA-1 may be directly responsible for apical reorientation of the merozoite and apical proteins which function in tight junction formation. These ligands are members of two families: Duffy binding-like (DBL and reticulocyte binding-like (RBL proteins. In [i]Plasmodium[/i] [i]falciparum[/i] the DBL family includes: EBA-175, EBA-140 (BAEBL, EBA-181 (JESEBL, EBA-165 (PEBL and EBL-1 ligands.To date, no effective antimalarial vaccine has been developed, but there are several studies for this purpose. Therefore, it is crucial to understand the molecular basis of host cells invasion by parasites. Major efforts are focused on developing a multiantigenic and multiepitope vaccine preventing all steps of [i]Plasmodium[/i] invasion.

  17. Results from tandem Phase 1 studies evaluating the safety, reactogenicity and immunogenicity of the vaccine candidate antigen Plasmodium falciparum FVO merozoite surface protein-1 (MSP142 administered intramuscularly with adjuvant system AS01

    Directory of Open Access Journals (Sweden)

    Otsyula Nekoye

    2013-01-01

    Full Text Available Abstract Background The development of an asexual blood stage vaccine against Plasmodium falciparum malaria based on the major merozoite surface protein-1 (MSP1 antigen is founded on the protective efficacy observed in preclinical studies and induction of invasion and growth inhibitory antibody responses. The 42 kDa C-terminus of MSP1 has been developed as the recombinant protein vaccine antigen, and the 3D7 allotype, formulated with the Adjuvant System AS02A, has been evaluated extensively in human clinical trials. In preclinical rabbit studies, the FVO allele of MSP142 has been shown to have improved immunogenicity over the 3D7 allele, in terms of antibody titres as well as growth inhibitory activity of antibodies against both the heterologous 3D7 and homologous FVO parasites. Methods Two Phase 1 clinical studies were conducted to examine the safety, reactogenicity and immunogenicity of the FVO allele of MSP142 in the adjuvant system AS01 administered intramuscularly at 0-, 1-, and 2-months: one in the USA and, after evaluation of safety data results, one in Western Kenya. The US study was an open-label, dose escalation study of 10 and 50 μg doses of MSP142 in 26 adults, while the Kenya study, evaluating 30 volunteers, was a double-blind, randomized study of only the 50 μg dose with a rabies vaccine comparator. Results In these studies it was demonstrated that this vaccine formulation has an acceptable safety profile and is immunogenic in malaria-naïve and malaria-experienced populations. High titres of anti-MSP1 antibodies were induced in both study populations, although there was a limited number of volunteers whose serum demonstrated significant inhibition of blood-stage parasites as measured by growth inhibition assay. In the US volunteers, the antibodies generated exhibited better cross-reactivity to heterologous MSP1 alleles than a MSP1-based vaccine (3D7 allele previously tested at both study sites. Conclusions Given that the primary

  18. 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...... localities of tensions between matter and the immaterial, the practical and the ideal, and subject and object. In the colloquial language there can, moreover, often seem to be something authentic or genuine about atmosphere, juxtaposing it to staging, which is implied to be something simulated or artificial....... This introduction seeks to outline how a number of scholars have addressed the relationship between staged atmospheres and experience, and thus highlight both the philosophical, social and political aspects of atmospheres...

  19. Immunity to viruses: learning from successful human vaccines.

    Science.gov (United States)

    Pulendran, Bali; Oh, Jason Z; Nakaya, Helder I; Ravindran, Rajesh; Kazmin, Dmitri A

    2013-09-01

    For more than a century, immunologists and vaccinologists have existed in parallel universes. Immunologists have for long reveled in using 'model antigens', such as chicken egg ovalbumin or nitrophenyl haptens, to study immune responses in model organisms such as mice. Such studies have yielded many seminal insights about the mechanisms of immune regulation, but their relevance to humans has been questioned. In another universe, vaccinologists have relied on human clinical trials to assess vaccine efficacy, but have done little to take advantage of such trials for studying the nature of immune responses to vaccination. The human model provides a nexus between these two universes, and recent studies have begun to use this model to study the molecular profile of innate and adaptive responses to vaccination. Such 'systems vaccinology' studies are beginning to provide mechanistic insights about innate and adaptive immunity in humans. Here, we present an overview of such studies, with particular examples from studies with the yellow fever and the seasonal influenza vaccines. Vaccination with the yellow fever vaccine causes a systemic acute viral infection and thus provides an attractive model to study innate and adaptive responses to a primary viral challenge. Vaccination with the live attenuated influenza vaccine causes a localized acute viral infection in mucosal tissues and induces a recall response, since most vaccinees have had prior exposure to influenza, and thus provides a unique opportunity to study innate and antigen-specific memory responses in mucosal tissues and in the blood. Vaccination with the inactivated influenza vaccine offers a model to study immune responses to an inactivated immunogen. Studies with these and other vaccines are beginning to reunite the estranged fields of immunology and vaccinology, yielding unexpected insights about mechanisms of viral immunity. Vaccines that have been proven to be of immense benefit in saving lives offer us a new

  20. The Efficacy of Administration of a Single Booster dose of Hepatitis B Vaccine in 5-7 Year Old Children in Kogiloyeh and Boyerahmad Province- Iran

    Directory of Open Access Journals (Sweden)

    B Yazdanpanah

    2009-07-01

    Full Text Available ABESTRACT: Introduction & Objective: The efficacy of hepatitis B vaccine and duration of protection after vaccination of infants reported to be different in various studies. The necessity of booster dose after primary vaccination is controversial. The Iranian Immunization Committee has approved 0, 1 and 6 months hepatitis vaccination schedule for children. Considering the high prevalence and serious outcome of hepatitis B infection, the aim of the present study was to evaluate the immunity level of school age children against HBV in order to determine the necessity of single booster dose in these ages. Materials & Methods: In this clinical trial study, the population was all of the children at 5-7 years of age in Kohgiloyeh & Boyerahmad province who had been vaccinated starting at birth with hepatitis B vaccine. Among them 800 children were selected by multiple stage sampling method. Data gathering tool was questionnaire. After obtaining informed consent from parents of each subject, 3ml blood sample was taken from each individual and hepatitis B surface antibody (HBS-Ab and hepatitis B surface antigen (HBS-Ag were determined by ELISA method. Subjects with non protective titers (<10mIU/ml received a booster does of DNA recombinant vaccine. Four weeks after the administration of booster dose, the anti- HBS titers were measured. Collected data were analyzed using SPSS software and x2 and T tests. Results: In all subjects the HBS- Ag were negative. 84.4% of subjects were immune against HBV (had protective anti body titer. The mean antibody titer was 230.5 ±308.9 IU/ml with range 10.6 – 1175 IU/ml. 15.6% of subjects had non protective antibody titer and mean antibody titer was 4.97 ±3.5 IU/ml. Following booster dose 78.1% of them had protective titer and significantly increased titers from 4.97 ±3.5 to 332.1 ± 402 IU/ml (p<0.001. No statistically significant differences were found between sexes in term of antibody level. The level of immunity

  1. Influenza virus neuraminidase (NA): a target for antivirals and vaccines.

    Science.gov (United States)

    Jagadesh, Anitha; Salam, Abdul Ajees Abdul; Mudgal, Piya Paul; Arunkumar, Govindakarnavar

    2016-08-01

    Influenza, the most common infectious disease, poses a great threat to human health because of its highly contagious nature and fast transmissibility, often leading to high morbidity and mortality. Effective vaccination strategies may aid in the prevention and control of recurring epidemics and pandemics associated with this infectious disease. However, antigenic shifts and drifts are major concerns with influenza virus, requiring effective global monitoring and updating of vaccines. Current vaccines are standardized primarily based on the amount of hemagglutinin, a major surface antigen, which chiefly constitutes these preparations along with the varying amounts of neuraminidase (NA). Anti-influenza drugs targeting the active site of NA have been in use for more than a decade now. However, NA has not been approved as an effective antigenic component of the influenza vaccine because of standardization issues. Although some studies have suggested that NA antibodies are able to reduce the severity of the disease and induce a long-term and cross-protective immunity, a few major scientific issues need to be addressed prior to launching NA-based vaccines. Interestingly, an increasing number of studies have shown NA to be a promising target for future influenza vaccines. This review is an attempt to consolidate studies that reflect the strength of NA as a suitable vaccine target. The studies discussed in this article highlight NA as a potential influenza vaccine candidate and support taking the process of developing NA vaccines to the next stage. PMID:27255748

  2. Effect of feeding whole compared with cell-free colostrum on calf immune status: Vaccination response.

    Science.gov (United States)

    Langel, S N; Wark, W A; Garst, S N; James, R E; McGilliard, M L; Petersson-Wolfe, C S; Kanevsky-Mullarky, I

    2016-05-01

    Vaccination contributes to improved herd health and production. Boosting immune development at a young age may have long-term effects by enhancing vaccine immune response and efficacy. In the bovine, colostrum is the sole source of maternal immunity, having a substantial effect on health status in the neonate. To date, colostral antibody concentration is used to evaluate colostrum quality. However, colostrum also contains proteins and cells, which may affect immune development and future responses to vaccines. To determine the effect of maternal colostral cells on immune development, 37 female Holstein and Jersey dairy calves were bottle-fed 4 quarts total of whole colostrum (WC) or cell-free colostrum (CFC) at birth. Calves were vaccinated with 2 series of multivalent vaccines. Series A consisted of vaccines given between 1 and 4mo of life. Series B consisted of vaccines given between 5 and 10mo of life. Calf peripheral blood samples were obtained before each vaccination series and monthly for 3mo after each vaccination series. Cellular blood parameters were determined by flow cytometry. Quantitative real-time PCR was used to determine cytokine gene expression in peripheral blood mononuclear cells before vaccination series B and once a month for 2mo after vaccination series B. Calves fed CFC had fewer numbers of B cells in mo 2 after vaccination series A when compared with WC-fed calves. Calves fed CFC had decreased gene expression levels of IL-2 in mo 1 and numbers of CD4(+)CD62L(+)CD45RO(-) and CD4(+)CD62L(+)CD45RO(+) T cells in mo 0 and 1 after vaccination series B as compared with WC-fed calves. Our findings indicate a greater response to vaccines up to 6 to 10mo post-WC feeding when compared with CFC. These data suggest that adoptive transfer of maternal colostral cells at birth has a long-term effect on development of the neonatal immune system. PMID:26923041

  3. Effect of feeding whole compared with cell-free colostrum on calf immune status: Vaccination response.

    Science.gov (United States)

    Langel, S N; Wark, W A; Garst, S N; James, R E; McGilliard, M L; Petersson-Wolfe, C S; Kanevsky-Mullarky, I

    2016-05-01

    Vaccination contributes to improved herd health and production. Boosting immune development at a young age may have long-term effects by enhancing vaccine immune response and efficacy. In the bovine, colostrum is the sole source of maternal immunity, having a substantial effect on health status in the neonate. To date, colostral antibody concentration is used to evaluate colostrum quality. However, colostrum also contains proteins and cells, which may affect immune development and future responses to vaccines. To determine the effect of maternal colostral cells on immune development, 37 female Holstein and Jersey dairy calves were bottle-fed 4 quarts total of whole colostrum (WC) or cell-free colostrum (CFC) at birth. Calves were vaccinated with 2 series of multivalent vaccines. Series A consisted of vaccines given between 1 and 4mo of life. Series B consisted of vaccines given between 5 and 10mo of life. Calf peripheral blood samples were obtained before each vaccination series and monthly for 3mo after each vaccination series. Cellular blood parameters were determined by flow cytometry. Quantitative real-time PCR was used to determine cytokine gene expression in peripheral blood mononuclear cells before vaccination series B and once a month for 2mo after vaccination series B. Calves fed CFC had fewer numbers of B cells in mo 2 after vaccination series A when compared with WC-fed calves. Calves fed CFC had decreased gene expression levels of IL-2 in mo 1 and numbers of CD4(+)CD62L(+)CD45RO(-) and CD4(+)CD62L(+)CD45RO(+) T cells in mo 0 and 1 after vaccination series B as compared with WC-fed calves. Our findings indicate a greater response to vaccines up to 6 to 10mo post-WC feeding when compared with CFC. These data suggest that adoptive transfer of maternal colostral cells at birth has a long-term effect on development of the neonatal immune system.

  4. Vaccine strategies against schistosomiasis

    Directory of Open Access Journals (Sweden)

    A. Capron

    1992-01-01

    Full Text Available In this review the authors analyze the effector and regulatory mechanisms in the immune response to schistosomiasis. To study these mechanisms two animal models were used, mouse and rat. The mouse totaly permissive host like human, show prominent-T cell control in the acquisition of resistance. But other mechanisms like antibody mediated cytotoxity (ADCC involving eosinophils and IgG antibodies described in humans, are observed in rats. Also in this animal, it is observed specific IgE antibody high production and blood and tisssue eosinophilia. Using the rat model and schistosomula as target, some ADCC features have emerged: the cellular population involved are bone marrow derived inflammatory cell (mononuclear phagocytes, eosinophils and platelets, interacting with IgE through IgE Fc receptors. Immunization has been attempted using the recombinant protein Sm28/GST. Protection has been observed in rodents with significant decrease of parasite fecundity and egg viability affecting the number, size and volume of liver egg granulomas. The association of praziquantel and immunization with with Sm28/GST increases the resistance to infection and decreases egg viability. The authors suggest the possibility of the stablishment of a future vaccine against Schistosoma mansoni.

  5. Estimation of Nationwide Vaccination Coverage and Comparison of Interview and Telephone Survey Methodology for Estimating Vaccination Status

    Science.gov (United States)

    Park, Boyoung; Lee, Yeon-Kyeng; Cho, Lisa Y.; Go, Un Yeong; Yang, Jae Jeong; Ma, Seung Hyun; Choi, Bo-Youl; Lee, Moo-Sik; Lee, Jin-Seok; Choi, Eun Hwa; Lee, Hoan Jong

    2011-01-01

    This study compared interview and telephone surveys to select the better method for regularly estimating nationwide vaccination coverage rates in Korea. Interview surveys using multi-stage cluster sampling and telephone surveys using stratified random sampling were conducted. Nationwide coverage rates were estimated in subjects with vaccination cards in the interview survey. The interview survey relative to the telephone survey showed a higher response rate, lower missing rate, higher validity and a less difference in vaccination coverage rates between card owners and non-owners. Primary vaccination coverage rate was greater than 90% except for the fourth dose of DTaP (diphtheria/tetanus/pertussis), the third dose of polio, and the third dose of Japanese B encephalitis (JBE). The DTaP4: Polio3: MMR1 fully vaccination rate was 62.0% and BCG1:HepB3:DTaP4:Polio3:MMR1 was 59.5%. For age-appropriate vaccination, the coverage rate was 50%-80%. We concluded that the interview survey was better than the telephone survey. These results can be applied to countries with incomplete registry and decreasing rates of landline telephone coverage due to increased cell phone usage and countries. Among mandatory vaccines, efforts to increase vaccination rate for the fourth dose of DTaP, the third dose of polio, JBE and regular vaccinations at recommended periods should be conducted in Korea. PMID:21655054

  6. Estimation of nationwide vaccination coverage and comparison of interview and telephone survey methodology for estimating vaccination status.

    Science.gov (United States)

    Park, Boyoung; Lee, Yeon-Kyeng; Cho, Lisa Y; Go, Un Yeong; Yang, Jae Jeong; Ma, Seung Hyun; Choi, Bo-Youl; Lee, Moo-Sik; Lee, Jin-Seok; Choi, Eun Hwa; Lee, Hoan Jong; Park, Sue K

    2011-06-01

    This study compared interview and telephone surveys to select the better method for regularly estimating nationwide vaccination coverage rates in Korea. Interview surveys using multi-stage cluster sampling and telephone surveys using stratified random sampling were conducted. Nationwide coverage rates were estimated in subjects with vaccination cards in the interview survey. The interview survey relative to the telephone survey showed a higher response rate, lower missing rate, higher validity and a less difference in vaccination coverage rates between card owners and non-owners. Primary vaccination coverage rate was greater than 90% except for the fourth dose of DTaP (diphtheria/tetanus/pertussis), the third dose of polio, and the third dose of Japanese B encephalitis (JBE). The DTaP4: Polio3: MMR1 fully vaccination rate was 62.0% and BCG1:HepB3:DTaP4:Polio3:MMR1 was 59.5%. For age-appropriate vaccination, the coverage rate was 50%-80%. We concluded that the interview survey was better than the telephone survey. These results can be applied to countries with incomplete registry and decreasing rates of landline telephone coverage due to increased cell phone usage and countries. Among mandatory vaccines, efforts to increase vaccination rate for the fourth dose of DTaP, the third dose of polio, JBE and regular vaccinations at recommended periods should be conducted in Korea. PMID:21655054

  7. A prospective study of hepatitis B vaccination - a comparison of responders versus nonresponders.

    LENUS (Irish Health Repository)

    Brown, Catherine M

    2012-02-01

    Herein we present one of the largest single-center reports of the response of hemodialysis patients to a two-vaccine hepatitis B virus vaccination protocol in a European dialysis population. A hepatitis B recombinant DNA vaccine, HBvaxPRO, was given at a dose of 40 microg intramuscularly using a four-dose schedule at 0, 1, 2, and 12 months. Responses were (1) a titer >100 mIU\\/mL = patient immune, (2) a titer level 10-99 mIU\\/mL = give a booster dose and recheck level 2 months later, and (3) 0 <\\/= 10 mIU\\/mL = repeat vaccination course using a different vaccine, Engerix-B. We compared responder groups in terms of titer levels for each vaccine and variables including age, gender, serum albumin, parathyroid hormone (PTH), calcium, phosphate, hemoglobin, years on dialysis, and type of dialysis access. Of the 176 patients who received the first vaccine course, 71 patients achieved immunity, that is, 40% uptake for the first vaccine. Of the 105 who failed, 72 received the second vaccine with 46 responders, that is, 64% uptake for the second vaccine. Overall, 143 of the 176 patients who entered the vaccination program completed the protocol with 117 achieving immunity, representing an 82% success rate. The only variable overall to show significance in achieving seroconversion was serum albumin (p = 0.03). Using a two-vaccine protocol, hepatitis B vaccination response was high in our population of end-stage renal disease patients.

  8. A prospective study of hepatitis B vaccination - a comparison of responders versus nonresponders.

    LENUS (Irish Health Repository)

    Brown, Catherine M

    2011-01-01

    Herein we present one of the largest single-center reports of the response of hemodialysis patients to a two-vaccine hepatitis B virus vaccination protocol in a European dialysis population. A hepatitis B recombinant DNA vaccine, HBvaxPRO, was given at a dose of 40 µg intramuscularly using a four-dose schedule at 0, 1, 2, and 12 months. Responses were (1) a titer >100 mIU\\/mL = patient immune, (2) a titer level 10-99 mIU\\/mL = give a booster dose and recheck level 2 months later, and (3) 0 ≤ 10 mIU\\/mL = repeat vaccination course using a different vaccine, Engerix-B. We compared responder groups in terms of titer levels for each vaccine and variables including age, gender, serum albumin, parathyroid hormone (PTH), calcium, phosphate, hemoglobin, years on dialysis, and type of dialysis access. Of the 176 patients who received the first vaccine course, 71 patients achieved immunity, that is, 40% uptake for the first vaccine. Of the 105 who failed, 72 received the second vaccine with 46 responders, that is, 64% uptake for the second vaccine. Overall, 143 of the 176 patients who entered the vaccination program completed the protocol with 117 achieving immunity, representing an 82% success rate. The only variable overall to show significance in achieving seroconversion was serum albumin (p = 0.03). Using a two-vaccine protocol, hepatitis B vaccination response was high in our population of end-stage renal disease patients.

  9. Blood Types

    Science.gov (United States)

    ... How Can I Help a Friend Who Cuts? Blood Types KidsHealth > For Teens > Blood Types Print A A ... or straight hair instead of curly. ...Make Eight Blood Types The different markers that can be found in ...

  10. Leukocyte transcript alterations in West-African girls following a booster vaccination with diphtheria-tetanus-pertussis vaccine

    DEFF Research Database (Denmark)

    Orntoft, Nikolaj W; Thorsen, Kasper; Benn, Christine S;

    2013-01-01

    Background. Observational studies from low-income countries have shown that the vaccination against diphtheria, tetanus and pertussis (DTP) is associated with excess female mortality due to infectious diseases. Methods. To investigate possible changes in gene expression after DTP vaccination, we...... identified a group of nine comparable West African girls, from a biobank of 356 children, who were due to receive DTP booster vaccine at age 18 months. As a pilot experiment we extracted RNA from blood samples before, and 6 weeks after, vaccination to analyze the coding transcriptome in leukocytes using...... expression microarrays, and ended up with information from eight girls. The data was further analyzed using dedicated array pathway and network software. We aimed to study whether DTP vaccination introduced a systematic alteration in the immune system in girls. Results. We found very few transcripts to alter...

  11. 75 FR 48706 - Proposed Vaccine Information Materials for Rotavirus Vaccine

    Science.gov (United States)

    2010-08-11

    ..., rotavirus, hepatitis A, meningococcal, human papillomavirus (HPV), and trivalent influenza vaccines... HUMAN SERVICES Centers for Disease Control and Prevention Proposed Vaccine Information Materials for Rotavirus Vaccine AGENCY: Centers for Disease Control and Prevention (CDC), Department of Health and...

  12. Vaccine Effectiveness - How Well Does the Seasonal Flu Vaccine Work?

    Science.gov (United States)

    ... flu viruses. What are the benefits of flu vaccination? While how well the flu vaccine works can ... of age and older). How are benefits of vaccination measured? Public health researchers measure how well flu ...

  13. Blocking Babesia bovis vaccine reactions of dairy cattle in milk

    Directory of Open Access Journals (Sweden)

    Michael P. Combrink

    2012-12-01

    Full Text Available The use of 1.16 mg/kg (one third of the recommended dose of diminazene aceturate, administered indiscriminately to cattle on day seven of the unfrozen Babesia bovis and Babesia bigemina bivalent live blood vaccine reaction, was an infection and block treatment method of immunisation used successfully with no known adverse effect on the parasites or the development of protective immunity. Continuing with this practice after replacement of the unfrozen vaccine with deep-frozen monovalent B. bovis and B. bigemina live blood vaccines resulted in reports of vaccine failure. Laboratory investigation indicated the harmful effect of block treatment in preventing the development of durable immunity against B. bigemina as opposed to the much lesser effect it had on B. bovis. Consequently the practice was no longer recommended. A B. bovis vaccination attempt aimed at controlling the disease of dairy cows in milk (n = 30 resulted in 20% fatalities during the expected vaccine reaction period. The practice of block treating B. bovis was therefore reinvestigated, this time in a field trial using dairy cattle in milk (n = 11. Using 0.88 mg/kg (one quarter of the recommended dose of diminazene administered on day 12 of the B. bovis vaccine reaction resulted in only two animals (n = 5 testing ≥ 1/80 positive with the indirect fluorescent antibody test (IFAT although parasites could be demonstrated in three. In the untreated control group, by contrast, five of the vaccinated animals (n = 6 tested ≥ 1/80 positive with IFAT and parasites could be demonstrated in all. The unsatisfactory outcome obtained in this study, combined with that of the earlier investigation, indicated that there are more factors that influence successful vaccination than previously considered. It is therefore concluded that block treatment of the live frozen South African cattle babesiosis vaccines reactions is not recommended.

  14. Immunoelectrophoresis - blood

    Science.gov (United States)

    IEP - serum; Immunoglobulin electrophoresis - blood; Gamma globulin electrophoresis; Serum immunoglobulin electrophoresis ... A blood sample is needed. For information on how this is done, see: Venipuncture

  15. Antigen-Specific CD4+ T Cells Recognize Epitopes of Protective Antigen following Vaccination with an Anthrax Vaccine

    OpenAIRE

    Laughlin, Elsa M.; Miller, Joseph D.; James, Eddie; Fillos, Dimitri; Ibegbu, Chris C.; Mittler, Robert S.; Akondy, Rama; Kwok, William; Ahmed, Rafi; Nepom, Gerald,

    2007-01-01

    Detection of antigen-specific CD4+ T cells is facilitated by the use of fluorescently labeled soluble peptide-major histocompatibility complex (MHC) multimers which mirror the antigen specificity of T-cell receptor recognition. We have used soluble peptide-MHC class II tetramers containing peptides from the protective antigen (PA) of Bacillus anthracis to detect circulating T cells in peripheral blood of subjects vaccinated with an anthrax vaccine. PA-specific HLA class II-restricted T lympho...

  16. Developments of Subunit and VLP Vaccines Against Influenza A Virus

    Institute of Scientific and Technical Information of China (English)

    Ma-ping Deng; Zhi-hong Hu; Hua-lin Wang; Fei Deng

    2012-01-01

    Influenza virus is a continuous and severe global threat to mankind.The continuously re-emerging disease gives rise to thousands of deaths and enormous economic losses each year,which emphasizes the urgency and necessity to develop high-quality influenza vaccines in a safer,more efficient and economic way.The influenza subunit and VLP vaccines,taking the advantage of recombinant DNA technologies and expression system platforms,can be produced in such an ideal way.This review summarized the recent advancements in the research and development of influenza subunit and VLP vaccines based on the recombinant expression of hemagglutinin antigen (HA),neuraminidase antigen (NA),Matrix 2 protein (M2) and nucleocapsid protein (NP).It would help to get insight into the current stage of influenza vaccines,and suggest the future design and development of novel influenza vaccines.

  17. Cytokine responses in camels (Camelus bactrianus) vaccinated with Brucella abortus strain 19 vaccine.

    Science.gov (United States)

    Odbileg, Raadan; Purevtseren, Byambaa; Gantsetseg, Dorj; Boldbaatar, Bazartseren; Buyannemekh, Tumurjav; Galmandakh, Zagd; Erdenebaatar, Janchivdorj; Konnai, Satoru; Onuma, Misao; Ohashi, Kazuhiko

    2008-02-01

    In the present study, we determined the levels of cytokines produced by camel (Camelus bactrianus) peripheral blood mononuclear cells (PBMCs) in response to live attenuated Brucella abortus (B. abortus) S19 vaccine. Seven camels were vaccinated with commercial B. abortus S19 vaccine, and their cytokine responses were determined using a real-time PCR assay. Cytokine responses to B. abortus S19 were examined at 6 hr, 48 hr and 1, 2 and 3 weeks post-vaccination. Serological tests were performed to further confirm these immune responses. The results revealed that IFN-gamma and IL-6 were upregulated during the first week post-vaccination. Low level expressions of IL-1alpha, IL-1beta, TNFalpha and IL-10 and no expression of IL-2 and IL-4 were observed compared with the control camels. The findings showed that B. abortus stimulates cell-mediated immunity by directly activating camel Th1 cells to secrete IFN-gamma. This quantification of cytokine expression in camels is essential for understanding of Camelidae disease development and protective immune responses. This is the first report of in vivo camel cytokine quantification after vaccination. PMID:18319583

  18. Vaccination and neurological disorders

    Directory of Open Access Journals (Sweden)

    Anastasia Gkampeta

    2015-12-01

    Full Text Available Active immunization of children has been proven very effective in elimination of life threatening complications of many infectious diseases in developed countries. However, as vaccination-preventable infectious diseases and their complications have become rare, the interest focuses on immunization-related adverse reactions. Unfortunately, fear of vaccination-related adverse effects can led to decreased vaccination coverage and subsequent epidemics of infectious diseases. This review includes reports about possible side effects following vaccinations in children with neurological disorders and also published recommendations about vaccinating children with neurological disorders. From all international published data anyone can conclude that vaccines are safer than ever before, but the challenge remains to convey this message to society.

  19. Vaccination against seasonal flu

    CERN Multimedia

    2015-01-01

    The Medical Service once again recommends you to get your annual flu vaccination for the year.   Vaccination is the most effective way of avoiding the illness and any serious consequences and protecting those around you. The flu can have especially serious consequences for people with chronic conditions (diabetes, cardio-vascular disease, etc.), pregnant women, infants, and people over 65 years of age. Remember, anyone working on the CERN site who wishes to be vaccinated against seasonal flu should go to the Infirmary (Building 57, ground floor) with their vaccine. The Medical Service will issue a prescription on the day of the vaccination for the purposes of reimbursement by UNIQA. NB: The Medical Service cannot provide this vaccination service for family members or retired members of the personnel. For more information: • The "Seasonal flu" flyer by the Medical Service • Recommendations of the Swiss Federal Office of Public...

  20. [Vaccination for international travelers].

    Science.gov (United States)

    Arrazola, M Pilar; Serrano, Almudena; López-Vélez, Rogelio

    2016-05-01

    Traveler's vaccination is one of the key strategies for the prevention of infectious diseases during international travel. The risk of acquiring an infectious disease is determined in each case by the characteristics of the traveler and the travel, so the pre-departure medical advice of the traveler must be individualized. The World Health Organization classifies travelerś vaccines into three groups. - Vaccines for routine use in national immunization programs: Haemophilus influenzae type b, hepatitis B, polio, measles-mumps-rubella, tetanus-diphtheria-whooping a cough, and chickenpox. - Vaccinations required by law in certain countries before to enter them: yellow fever, meningococcal disease and poliomyelitis. - Vaccines recommended depending on the circumstances: cholera, japanese encephalitis, tick-borne encephalitis, meningococcal disease, typhoid fever, influenza, hepatitis A, hepatitis B, rabies and BCG. This review is intended to introduce the reader to the field of international vaccination. PMID:26920587

  1. Vaccine herd effect.

    Science.gov (United States)

    Kim, Tae Hyong; Johnstone, Jennie; Loeb, Mark

    2011-09-01

    Vaccination ideally protects susceptible populations at high risk for complications of the infection. However, vaccines for these subgroups do not always provide sufficient effectiveness. The herd effect or herd immunity is an attractive way to extend vaccine benefits beyond the directly targeted population. It refers to the indirect protection of unvaccinated persons, whereby an increase in the prevalence of immunity by the vaccine prevents circulation of infectious agents in susceptible populations. The herd effect has had a major impact in the eradication of smallpox, has reduced transmission of pertussis, and protects against influenza and pneumococcal disease. A high uptake of vaccines is generally needed for success. In this paper we aim to provide an update review on the herd effect, focusing on the clinical benefit, by reviewing data for specific vaccines.

  2. Evaluation of Serum Anti-Hbs Concentration in Children Vaccinated with Recombinant Hepatitis B Vaccine at Birth

    OpenAIRE

    M Nejad-Ghaderi; Mozafari, A.; J Montazerifar; GH Hassanshahi; HR Rashidi-Nejad; A Jafarzadeh

    2006-01-01

    Introduction: Vaccination with the major surface antigen of hepatitis B virus (HBsAg) induces anti-HBs antibody production and level of 10 IU/L is considered protective. It has been shown that the level of anti-HBs antibody does wane after vaccination. The aim of this study was to evaluate the persistence of anti-HBs antibodies in healthy Iranian children 10 years after primary vaccination. Methods: Blood samples were collected from 146 children, 10 years after completion of primary hepatitis...

  3. TH1 and TH2 responses are influenced by HLA antigens in healthy neonates vaccinated with recombinant hepatitis B vaccine.

    OpenAIRE

    Abdollah Jafarzadeh; Fazel Shokri

    2012-01-01

    The immune response to hepatitis B surface antigen (HBsAg) is influenced by several factors, of which HLA antigens and balanced secretion of Th1/Th2 cytokines play important roles. The aim of this study was to evaluate the influence of HLA antigens on cytokine secretion by HBsAg-stimulated peripheral blood mononuclear cells (PBMC) from healthy neonates vaccinated with recombinant HBsAg. PBMCs were isolated from 48 Iranian neonates vaccinated with a recombinant HBV vaccine. The cells were stim...

  4. Anthrax vaccination strategies

    OpenAIRE

    Cybulski, Robert J.; Sanz, Patrick; O'Brien, Alison D.

    2009-01-01

    The biological attack conducted through the U.S. postal system in 2001 broadened the threat posed by anthrax from one pertinent mainly to soldiers on the battlefield to one understood to exist throughout our society. The expansion of the threatened population placed greater emphasis on the reexamination of how we vaccinate against Bacillus anthracis. The currently-licensed Anthrax Vaccine, Adsorbed (AVA) and Anthrax Vaccine, Precipitated (AVP) are capable of generating a protective immune res...

  5. Immunobiology of Influenza Vaccines

    OpenAIRE

    Gomez Lorenzo, Margarita M.; Fenton, Matthew J.

    2013-01-01

    Vaccination is the primary strategy for prevention and control of influenza. The surface hemagglutinin (HA) protein of the influenza virus contains two structural elements (head and stalk) that differ in their potential utility as vaccine targets. The head of the HA protein is the primary target of antibodies that confer protective immunity to influenza viruses. The underlying health status, age, and gene polymorphisms of vaccine recipients and, just as importantly, the extent of the antigeni...

  6. Influenza vaccination during pregnancy.

    OpenAIRE

    Goldman, Ran D.; Koren, Gideon

    2002-01-01

    QUESTION: A 27-year-old patient of mine recently learned she is pregnant. She took the influenza vaccine offered at work when she was 7 weeks pregnant. Is her fetus at risk of malformations? ANSWER: No evidence indicates that killed influenza vaccine is teratogenic, even if given during the first trimester. Since 1996, Health Canada's Centre for Disease Control and Prevention has recommended that pregnant women in their second and third trimesters be vaccinated. This should not be interpreted...

  7. Vaccines for Drug Abuse

    Science.gov (United States)

    Shen, Xiaoyun; Orson, Frank M.; Kosten, Thomas R.

    2012-01-01

    Current medications for drug abuse have had only limited success. Anti-addiction vaccines to elicit antibodies that block the pharmacological effects of drugs have great potential for treating drug abuse. We review the status for two vaccines that are undergoing clinical trials (cocaine and nicotine) and two that are still in pre-clinical development (methamphetamine and heroin). We also outline the challenges and ethical concerns for anti-addiction vaccine development and their use as future therapeutics. PMID:22130115

  8. Vaccination against RSV

    OpenAIRE

    Kaaijk, Patricia; Luytjes, Willem; Rots, Nynke Y.

    2013-01-01

    The respiratory syncytial virus (RSV) is the major cause of lower respiratory tract illness (LRI) in infants worldwide. Also persons with heart/lung disease or an immunodeficiency disorder, and the elderly are at increased risk for severe LRI upon RSV infection. Although there is at present no licensed RSV vaccine available, it is a priority target for several vaccine developers. For the implementation of a future RSV vaccination within national immunization schemes, various strategies can be...

  9. 自体树突细胞与混合T淋巴细胞疫苗治疗慢性乙型肝炎的护理%Nursing effect on blood collection and doping for cbronic hepatitis B patients treated with self dendritic cells and mixed T lymphocytes vaccine

    Institute of Scientific and Technical Information of China (English)

    王选琴; 李玲香

    2012-01-01

    Objective To explore the clinical blood collection and doping nursing care for hepatitis B patients who use self dendritic cells (DC)and mixed T lymphocytes vaccine (resistant HBV-DC-MTL for short ) for treatment.Methods Thirty-eight chronic hepatitis B virus (HBV) infection patients including 33 chronic hepatitis B and 5 chronic HBV carriers undergone clinical trial during December 2010 to July 2011.Fifty millilitre heparin anticoagulation peripheral venous blood was taken for cultivating mature DC and mixed T lymphocytes vaccine with laboratory biological immune technology,the DC obtained on the seventh day and resistant HBV-MTL obtained on the fourteenth day intravenously injected to the patients and we observed the cell collection and doping nursing effect.Results No case was recollected blood for blood coagulation,the obtained cells after cultivated were returned to the patient without adverse effects and showed a distinct effect in 38 patients.Conclusions It is more successful in blood collection by using the heparin 50 ml syringe and anticoagulant 9 infusion scalp needle in the great vessels; it is the key in obtaining cell vaccine that the specimen is cold preservation in 4 ℃,and separated and cultured in 2 h; doping method is of high safety and Iess complications.%目的 探讨乙肝患者使用自体树突细胞和混合T淋巴细胞疫苗(简称抗HBV-DC-MTL)治疗慢性乙型肝炎的临床采血与回输的护理.方法 取乙肝患者的肝素抗凝外周静脉血50 ml,通过实验室生物免疫技术培养获得成熟的树突细胞和混合T淋巴细胞疫苗,培养第7天将收获的DC、第14天收获的抗HBV-MTL分别回输给患者.并对38例乙肝患者采集细胞与回输的护理进行观察.结果 38例患者好转36例,无效1例,治愈1例.结论 采用肝素抗凝的50 ml注射器加9号输液头皮针在大血管处采血,采血成功率高;标本4℃左右冷藏保存,2h内分离培养,是收获细胞疫苗成功的关键;回

  10. Monitoring the immune response to vaccination with an inactivated vaccine associated to bovine neonatal pancytopenia by deep sequencing transcriptome analysis in cattle.

    Science.gov (United States)

    Demasius, Wiebke; Weikard, Rosemarie; Hadlich, Frieder; Müller, Kerstin Elisabeth; Kühn, Christa

    2013-01-01

    Bovine neonatal pancytopenia (BNP) is a new fatal, alloimmune/alloantibody mediated disease of new-born calves induced by ingestion of colostrum from cows, which had been vaccinated with a specific vaccine against the Bovine Virus Diarrhoea Virus (BVDV). The hypothesis of pathogenic MHC class I molecules in the vaccine had been put up, but no formal proof of specific causal MHC class I alleles has been provided yet. However, the unique features of the vaccine obviously result in extremely high specific antibody titres in the vaccinated animals, but apparently also in further molecules inducing BNP. Thus, a comprehensive picture of the immune response to the vaccine is essential. Applying the novel approach of next generation RNA sequencing (RNAseq), our study provides a new holistic, comprehensive analysis of the blood transcriptome regulation after vaccination with the specific BVDV vaccine. Our RNAseq approach identified a novel cytokine-like gene in the bovine genome that is highly upregulated after vaccination. This gene has never been described before in any other species and might be specific to ruminant immune response. Furthermore, our data revealed a very coordinated immune response to double-stranded (ds) RNA or a dsRNA analogue after vaccination with the inactivated single-stranded (ss) RNA vaccine. This would suggest either a substantial contamination of the vaccine with dsRNA from host cells after virus culture or a dsRNA analogue applied to the vaccine. The first option would highlight the potential risks associated with virus culture on homologous cells during vaccine production; the latter option would emphasise the potential risks associated with immune stimulating adjuvants used in vaccine production. PMID:24099437

  11. Immunological effects of a 10-μg dose of domestic hepatitis B vaccine in adults*

    OpenAIRE

    Ren, Jing-jing; Dai, Xue-wei; Jiang, Zheng-gang; Shen, Ling-zhi; Chen, Yong-di; Li, Qian; Ren, Wen; Liu, Ying; Yao, Jun; Li, Lan-Juan

    2012-01-01

    Objective: To evaluate the immunological effects of three types of domestic 10-μg/dose hepatitis B vaccines in adults compared with a foreign vaccine, and to provide scientific evidence in support of adult hepatitis B vaccination. Methods: Adults from five counties (Deqing, Changxing, Nanxun, Wuxing, Anji) in Huzhou City, Shaoxing County and Tongxiang County, Zhejiang Province, China were selected. Blood samples were taken to assess serum HBsAg, anti-HBs, and anti-HBc using a chemiluminescenc...

  12. Vaccines for metabolic diseases: current perspectives

    Directory of Open Access Journals (Sweden)

    Morais T

    2014-09-01

    Full Text Available Tiago Morais, Sara Andrade, Sofia S Pereira, Mariana P MonteiroDepartment of Anatomy, Unit for Multidisciplinary Biomedical Research, Institute for Biomedical Sciences Abel Salazar, University of Porto, Porto, PortugalAbstract: Several metabolic disorders, such as diabetes, hypertension, dyslipidemia, and obesity, represent significant risk factors for cardiovascular disease, which is the leading cause of morbidity and mortality among adult populations in western societies. Understandably, these chronic disorders have now replaced infectious diseases as the most important public health problem and economic burden to society in most countries. Treatment of metabolic risk factors in order to prevent cardiovascular disease requires an enduring approach with multiple drugs, which can be associated with considerable costs, side effects, and a low rate of therapeutic compliance due to lack of symptoms until later stages of the disease. Since vaccines have proven to be a powerful and effective approach to preventing infectious diseases, attempts to expand the therapeutic use of vaccines into the context of highly prevalent diseases has been attracting increased research interest. Vaccination strategies for chronic diseases in particular are an exciting area of research, with new treatment targets and strategies on the horizon. This review discusses the development of innovative therapeutic agents, focusing on the use of molecular vaccines for the treatment of common and highly prevalent chronic metabolic disorders, ie, diabetes, hypertension, dyslipidemia, and obesity.Keywords: vaccines, diabetes, hypertension, dyslipidemia, obesity

  13. Identification of 11 potential malaria vaccine candidates using Bioinformatics

    OpenAIRE

    Isea, Raul

    2010-01-01

    In this paper, we suggested eleven protein targets to be used as possible vaccines against Plasmodium falciparum causative agent of almost two to three million deaths per year. A comprehensive analysis of protein target have been selected from the small experimental fragment of antigen in the P. falciparum genome, all of them common to the four stages of the parasite life cycle (i.e., sporozoites, merozoites, trophozoites and gametocytes). The potential vaccine candidates should be analyzed i...

  14. Concerns regarding hepatitis B vaccination and post-vaccination test among Brazilian dentists

    Directory of Open Access Journals (Sweden)

    Teixeira Rosângela

    2010-07-01

    Full Text Available Abstract Background Hepatitis B infection is the major cause of acute and chronic liver disease, cirrhosis and hepatocellular carcinoma worldwide and has long been recognized as an occupational hazard among dentists. The aim of the present study was to examine factors associated to the self-reporting of hepatitis B vaccination and immunization status among dentists working in the city of Belo Horizonte, Brazil. Methods A cross-sectional survey was carried out with 1302 dentists in Belo Horizonte, Brazil. After signing a term of informed consent, the participants answered a structured questionnaire on their knowledge regarding their vaccination and immunization status against hepatitis B. Data on demographic, behavioural and occupational exposure aspects were also collected through questionnaires. Results The results revealed that 73.8% of the dentists reported having received three doses of the vaccine. Multivariate analysis revealed that gender (p = 0.006, use of individual protective equipment (p = 0.021, history of blood transfusion (p = 0.024 and history of illicit drug use (p = 0.013 were independently associated with vaccination against hepatitis B. Only 14.8% had performed a post-vaccination test. The use of individual protective equipment (p = 0.038, dentists who asked patients about hepatitis during dental treatment (p Conclusions Although there were a large number of vaccinated dentists in Belo Horizonte, the percentage was less than what was expected, as Brazil offers the National Program of Viral Hepatitis Vaccination, which provides free hepatitis B vaccinations to all healthcare workers. Despite being part of a high risk group for contamination, most of the dentists did not know their immunization status.

  15. Tetanus, Diphtheria, Pertussis (Tdap) Vaccine

    Science.gov (United States)

    Adacel® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine) ... Boostrix® (as a combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis Vaccine)

  16. Typhim Vi vaccine against typhoid fever: a clinical trial in Kenya.

    Science.gov (United States)

    Mirza, N B; Wamola, I A; Estambale, B A; Mbithi, E; Poillet, M

    1995-03-01

    Safety, tolerance and immunogenicity of the purified Vi polysaccharide vaccine (Typhim Vi) against typhoid fever was evaluated in primary school children aged 5-15 years. A total of 435 children were vaccinated, each with a single intramuscular injection in the left deltoid muscle. One hundred and ten children were randomly selected for blood samples on day 0 (pre vaccination) and day 30 (post vaccination). Vi antibodies studied by Radio immuno assay (RIA) on 97(88%) paired sera showed a seroconversion rate of 76.2% and seroprotection rate after vaccination was 74.2%, while 6.2% of children already had protective immunity before vaccination. The vaccine was well tolerated. Most commonly reported reactions were mild pain at site of injection (83%), and a few complained of mild swelling (4.6%), induration (1.1%), itching (1.1%) and headaches (1.4%). All reactions were of mild severity and disappeared within 24 to 48 hours.

  17. Adjuvant therapeutic vaccination in patients with non-small cell lung cancer made lymphopenic and reconstituted with autologous PBMC: first clinical experience and evidence of an immune response

    Directory of Open Access Journals (Sweden)

    Schendel Dolores J

    2007-09-01

    Full Text Available Abstract Background Given the considerable toxicity and modest benefit of adjuvant chemotherapy for non-small cell lung cancer (NSCLC, there is clearly a need for new treatment modalities in the adjuvant setting. Active specific immunotherapy may represent such an option. However, clinical responses have been rare so far. Manipulating the host by inducing lymphopenia before vaccination resulted in a magnification of the immune response in the preclinical setting. To evaluate feasibility and safety of an irradiated, autologous tumor cell vaccine given following induction of lymphopenia by chemotherapy and reinfusion of autologous peripheral blood mononuclear cells (PBMC, we are currently conducting a pilot-phase I clinical trial in patients with NSCLC following surgical resection. This paper reports on the first clinical experience and evidence of an immune response in patients suffering from NSCLC. Methods NSCLC patients stages I-IIIA are recruited. Vaccines are generated from their resected lung specimens. Patients undergo leukapheresis to harvest their PBMC prior to or following the surgical procedure. Furthermore, patients receive preparative chemotherapy (cyclophosphamide 350 mg/m2 and fludarabine 20 mg/m2 on 3 consecutive days for induction of lymphopenia followed by reconstitution with their autologous PBMC. Vaccines are administered intradermally on day 1 following reconstitution and every two weeks for a total of up to five vaccinations. Granulocyte-macrophage-colony-stimulating-factor (GM-CSF is given continuously (at a rate of 50 μg/24 h at the site of vaccination via minipump for six consecutive days after each vaccination. Results To date, vaccines were successfully manufactured for 4 of 4 patients. The most common toxicities were local injection-site reactions and mild constitutional symptoms. Immune responses to chemotherapy, reconstitution and vaccination are measured by vaccine site and delayed type hypersensitivity (DTH skin

  18. Immunogenicity and protection from malaria infection in BK-SE36 vaccinated volunteers in Uganda is not influenced by HLA-DRB1 alleles.

    Science.gov (United States)

    Tougan, Takahiro; Ito, Kazuya; Palacpac, Nirianne Marie Q; Egwang, Thomas G; Horii, Toshihiro

    2016-10-01

    SE36 antigen, derived from serine repeat antigen 5 (SERA5) of Plasmodium falciparum, is a promising blood stage malaria vaccine candidate. Designated as BK-SE36, the SE36 antigen was formulated with aluminum hydroxyl gel (AHG) and produced under Good Manufacturing Practice (GMP) constraints. In a Phase Ib clinical trial and follow-up study in Uganda, the risk for malaria symptoms was reduced by 72% compared with the control group. Although promising, the number of responders to the vaccine in 6-20years-olds was approximately 30% with the majority in the younger cohort. This is in contrast to the phase Ia clinical trial where response to the vaccine was 100% in Japanese malaria naive adults. A consideration that can be of importance is the involvement of host genetic factors that may influence the ability to mount an effective immune response to vaccination as well as susceptibility to malaria infection. We, therefore, analyzed allelic polymorphism of human leukocyte antigen (HLA)-DRB1 alleles using sequence-based typing (SBT). In this study, DRB1 alleles did not influence antibody response to BK-SE36 and the vaccinees susceptibility to clinical malaria. PMID:27343834

  19. Approaches to improve development methods for therapeutic cancer vaccines.

    Science.gov (United States)

    Ogi, Chizuru; Aruga, Atsushi

    2015-04-01

    Therapeutic cancer vaccines are an immunotherapy that amplify or induce an active immune response against tumors. Notably, limitations in the methodology for existing anti-cancer drugs may subsist while applying them to cancer vaccine therapy. A retrospective analysis was performed using information obtained from ClinicalTrials.gov, PubMed, and published articles. Our research evaluated the optimal methodologies for therapeutic cancer vaccines based on (1) patient populations, (2) immune monitoring, (3) tumor response evaluation, and (4) supplementary therapies. Failure to optimize these methodologies at an early phase may impact development at later stages; thus, we have proposed some points to be considered during the early phase. Moreover, we compared our proposal with the guidance for industry issued by the US Food and Drug Administration in October 2011 entitled "Clinical Considerations for Therapeutic Cancer Vaccines". Consequently, while our research was aligned with the guidance, we hope it provides further insights in order to predict the risks and benefits and facilitate decisions for a new technology. We identified the following points for consideration: (1) include in the selection criteria the immunological stage with a prognostic value, which is as important as the tumor stage; (2) select immunological assays such as phenotype analysis of lymphocytes, based on their features and standardize assay methods; (3) utilize optimal response criteria for immunotherapy in therapeutic cancer vaccine trials; and (4) consider supplementary therapies, including immune checkpoint inhibitors, for future therapeutic cancer vaccines. PMID:25746315

  20. The level of plasma lipid in different blood glucose control stages of type 2 diabetics%血糖控制不同阶段2型糖尿病患者的血脂水平

    Institute of Scientific and Technical Information of China (English)

    季方圆; 逄曙光; 田玉玲

    2015-01-01

    目的:探讨2型糖尿病(T2DM)患者血糖控制不同阶段的血脂水平特点。方法对361例T2DM住院患者(根据既往病史及血糖水平分为血糖控制达标组、血糖控制较差组)及239例健康体检对照组分别测糖化血红蛋白(HbA1c)、血清甘油三酯(TG)、总胆固醇(TCH)、高密度脂蛋白(HDL-C)及低密度脂蛋白(LDL-C)水平,比较血糖控制达标组、血糖控制较差组及对照组间血脂水平。结果与正常对照组比较,T2DM组TG、TCH、LDL-C水平明显升高,HDL-C水平降低;血糖控制达标组TCH、HDL-C和 LDL-C水平无显著差异( P>0.05);而血糖控制较差组 TCH和 LDL-C水平与正常对照组比较显著升高,HDL-C 水平降低(P<0.05);所有 DM 组的 TG 水平均与正常对照组有显著差异(P<0.05);TG、TCH、HDL-C 和LDL-C均与HbA1c具有平行关系(P<0.05),TG、TCH和LDL-C随HbA1c升高而升高,HDL-C则相反。结论 T2DM 血糖控制情况与血脂水平具有一定的关联性,血糖控制达标有助于TCH和LDL-C的降低及HDL-C的提高,对TG异常亦有所改善。%Objective To investigate the characteristic of plasma lipid in different blood glucose control stages of type 2 diabetics (T2DM).Methods 390T2DMpatientsweredividedintowell-controlledandpoorly-controlledgroupsintermsofmedicalhistoryandblood glucose level,and 210 healthy samples were examined the levels of Hemoglobin A1C(HbA1c),serum triglyceride(TG),total cholesterol (TCH),high density lipoprotein cholesterol (HDL-C) and low density lipoprotein cholesterol (LDL-C),respectively.Results After elimi-nating other factors on their influence of plasma lipid ,compared with those of normal control group ,the levels of TCH ,HDL-C and LDL-C had no significant differences in the well-controlled group ( P>0.05 ) ;while the levels of TCH and LDL-C were significantly higher and the level of HDL-C was

  1. The haematological profile of female bronze turkeys (Meleagris gallopavo vaccinated with various commercial strains of Newcastle disease

    Directory of Open Access Journals (Sweden)

    Elizabeth M.d.S. Schmidt

    2014-02-01

    Full Text Available The effects of vaccination on avian blood parameters are poorly understood. The present study was designed to evaluate whether different strains (Ulster 2C, B1, live LaSota and inactivated LaSota of Newcastle disease vaccines had an effect on the haematological profile of female turkeys. Seventy-five female turkeys were allocated to treatment groups according to vaccination strain. All the birds, except those in the control group, were vaccinated at 32 weeks of age and revaccinated at 40 and 48 weeks of age. Blood samples were obtained for haematological analyses and serum samples for the haemagglutination inhibition test. Haemoglobin concentration was significantly lower (p < 0.05 in vaccinated female turkeys than in the control birds 28 days after vaccination. Monocytes were significantly higher (p < 0.05 in 44-week-old female turkeys vaccinated with inactivated LaSota strain compared with the other groups. Turkeys vaccinated with the B1 strain showed significantly higher (p < 0.05 total white blood cell counts compared with the other groups vaccinated with various commercial strains of the Newcastle disease virus. In conclusion, female turkeys showed significant differences in haemoglobin concentrations, monocytes and white blood cell counts when vaccinated against Newcastle disease.

  2. The haematological profile of female bronze turkeys (Meleagris gallopavo) vaccinated with various commercial strains of Newcastle disease.

    Science.gov (United States)

    Schmidt, Elizabeth M d S; Santos, Ivan F C; Paulillo, António C; Martins, Gislaine R V; Denadai, Janine; Lapela, Ivan M

    2014-08-25

    The effects of vaccination on avian blood parameters are poorly understood. The present study was designed to evaluate whether different strains (Ulster 2C, B1, live LaSota and inactivated LaSota) of Newcastle disease vaccines had an effect on the haematological profile of female turkeys. Seventy-five female turkeys were allocated to treatment groups according to vaccination strain. All the birds, except those in the control group, were vaccinated at 32 weeks of age and revaccinated at 40 and 48 weeks of age. Blood samples were obtained for haematological analyses and serum samples for the haemagglutination inhibition test. Haemoglobin concentration was significantly lower (p < 0.05) in vaccinated female turkeys than in the control birds 28 days after vaccination. Monocytes were significantly higher (p < 0.05) in 44-week-old female turkeys vaccinated with inactivated LaSota strain compared with the other groups. Turkeys vaccinated with the B1 strain showed significantly higher (p < 0.05) total white blood cell counts compared with the other groups vaccinated with various commercial strains of the Newcastle disease virus. In conclusion, female turkeys showed significant differences in haemoglobin concentrations, monocytes and white blood cell counts when vaccinated against Newcastle disease.

  3. 具有阶段结构、时滞和接种的幼年染病单种群模型的稳定性%Stability of a delayed stage-structured single-species model with disease in infancy and vaccination

    Institute of Scientific and Technical Information of China (English)

    王烈; 陈斯养

    2013-01-01

    A delayed stage-structured single-species model with disease in infancy and vaccination is investigated. Using limit system theorem and constructing Liapunov function, the sufficient conditions for the global asymptotically stability of the positive equilibrium point and the infection-free equilibrium point are obtained. The results show that in the certain immunization coverage rate, the disease will eventually become extinct when the birth rate of the species is located in an interval,and when the birth rate is large than a threshold, the disease will eventually become an endemic.%研究了一类具有阶段结构、时滞和接种的幼年染病单种群模型的稳定性.应用极限系统理论和构造Liapunov函数,得到系统各类平衡点全局渐近稳定的充分条件.结果表明:在一定的接种率下,且整个种群的生育率位于某一区间时,最终疾病将趋于灭绝;当种群的生育率高于某一阈值时,疾病将最终成为地方病.

  4. Intratracheal infection as an efficient route for testing vaccines against Chlamydia abortus in sheep.

    Science.gov (United States)

    Álvarez, D; Salinas, J; Buendía, A J; Ortega, N; del Río, L; Sánchez, J; Navarro, J A; Gallego, M C; Murcia-Belmonte, A; Cuello, F; Caro, M R

    2015-09-01

    Pregnant ewes have been widely used to test vaccines against Chlamydia abortus. However, this model entails many disadvantages such as high economic costs and long periods of pregnancy. The murine model is very useful for specific studies but cannot replace the natural host for the later stages of vaccine evaluation. Therefore, a non-pregnant model of the natural host might be useful for a vaccine trial to select the best vaccine candidates prior to use of the pregnant model. With this aim, two routes of infection were assessed in young non-pregnant sheep, namely, intranasal (IN) and intratracheal (IT). In addition, groups of non-vaccinated sheep and sheep immunised with an inactivated vaccine were established to investigate the suitability of the model for testing vaccines. After the experimental infection, isolation of the microorganism in several organs, with pathological and immunohistochemical analyses, antibody production assessment and investigation by PCR of the presence of chlamydia in the vagina or rectum were carried out. Experimental IT inoculation of C. abortus induced pneumonia in sheep during the first few days post-infection, confirming the suitability of the IT route for testing vaccines in the natural host. The course of infection and the resulting pathological signs were less severe in vaccinated sheep compared with non-vaccinated animals, demonstrating the success of vaccination. IN infection did not produce evident lesions or demonstrate the presence of chlamydial antigen in the lungs and cannot be considered an appropriate model for testing vaccines. PMID:26095034

  5. Cochlear-Meningitis Vaccination

    Science.gov (United States)

    ... Prevnar 13®) 23-valent pneumococcal polysaccharide (PPSV) (Pneumovax®) Haemophilus influenzae type b conjugate (Hib) Tetravalent (A, C, Y, W-135) ... CDC immunization guidelines for routine meningococcal vaccination. The Haemophilus influenzae type b (Hib) vaccine is not routinely recommended for those ...

  6. Vaccines and autoimmunity.

    Science.gov (United States)

    Agmon-Levin, Nancy; Paz, Ziv; Israeli, Eitan; Shoenfeld, Yehuda

    2009-11-01

    Vaccines have been used for over 200 years and are the most effective way of preventing the morbidity and mortality associated with infections. Like other drugs, vaccines can cause adverse events, but unlike conventional medicines, which are prescribed to people who are ill, vaccines are administered to healthy individuals, thus increasing the concern over adverse reactions. Most side effects attributed to vaccines are mild, acute and transient; however, rare reactions such as hypersensitivity, induction of infection, and autoimmunity do occur and can be severe and even fatal. The rarity and subacute presentation of post-vaccination autoimmune phenomena means that ascertaining causality between these events can be difficult. Moreover, the latency period between vaccination and autoimmunity ranges from days to years. In this article, on the basis of published evidence and our own experience, we discuss the various aspects of the causal and temporal interactions between vaccines and autoimmune phenomena, as well as the possible mechanisms by which different components of vaccines might induce autoimmunity.

  7. Vaccines and autoimmunity.

    Science.gov (United States)

    De Martino, M; Chiappini, E; Galli, L

    2013-01-01

    Vaccines have eradicated or controlled many infectious diseases, saving each year millions of lives and quality of life of many other millions of people. In spite of the success of vaccines over the last two centuries, parents (and also some health care workers) gloss over the devastating consequences of diseases, which are now avoided thanks to vaccines, and direct their attention to possible negative effects of immunization. Three immunological objections are raised: vaccines cause antigenic overload, natural immunity is safer and better than vaccine-induced immunity, and vaccines induce autoimmunity. The last point is examined in this review. Theoretically, vaccines could trigger autoimmunity by means of cytokine production, anti-idiotypic network, expression of human histocompatibility leukocyte antigens, modification of surface antigens and induction of novel antigens, molecular mimicry, bystander activation, epitope spreading, and polyclonal activation of B cells. There is strong evidence that none of these mechanisms is really effective in causing autoimmune diseases. Vaccines are not a source of autoimmune diseases. By contrast, absolute evidence exists that infectious agents can trigger autoimmune mechanisms and that they do cause autoimmune diseases.

  8. Chimeric Pestivirus Experimental Vaccines.

    Science.gov (United States)

    Reimann, Ilona; Blome, Sandra; Beer, Martin

    2016-01-01

    Chimeric pestiviruses have shown great potential as marker vaccine candidates against pestiviral infections. Exemplarily, we describe here the construction and testing of the most promising classical swine fever vaccine candidate "CP7_E2alf" in detail. The description is focused on classical cloning technologies in combination with reverse genetics. PMID:26458840

  9. The Complexity of a Dengue Vaccine: A Review of the Human Antibody Response.

    Directory of Open Access Journals (Sweden)

    Jacky Flipse

    Full Text Available Dengue is the most prevalent mosquito-borne viral disease worldwide. Yet, there are no vaccines or specific antivirals available to prevent or treat the disease. Several dengue vaccines are currently in clinical or preclinical stages. The most advanced vaccine is the chimeric tetravalent CYD-TDV vaccine of Sanofi Pasteur. This vaccine has recently cleared Phase III, and efficacy results have been published. Excellent tetravalent seroconversion was seen, yet the protective efficacy against infection was surprisingly low. Here, we will describe the complicating factors involved in the generation of a safe and efficacious dengue vaccine. Furthermore, we will discuss the human antibody responses during infection, including the epitopes targeted in humans. Also, we will discuss the current understanding of the assays used to evaluate antibody response. We hope this review will aid future dengue vaccine development as well as fundamental research related to the phenomenon of antibody-dependent enhancement of dengue virus infection.

  10. Vaccination and Clinical Severity: Is the Effectiveness of Contact Tracing and Case Isolation Hampered by Past Vaccination?

    Directory of Open Access Journals (Sweden)

    Hiroshi Nishiura

    2013-02-01

    Full Text Available While contact tracing and case isolation are considered as the first choice of interventions against a smallpox bioterrorist event, their effectiveness under vaccination is questioned, because not only susceptibility of host and infectiousness of case but also the risk of severe clinical manifestations among cases is known to be reduced by vaccine-induced immunity, thereby potentially delaying the diagnosis and increasing mobility among vaccinated cases. We employed a multi-type stochastic epidemic model, aiming to assess the feasibility of contact tracing and case isolation in a partially vaccinated population and identify data gaps. We computed four epidemiological outcome measures, i.e., (i the threshold of a major epidemic under the interventions; (ii the expected total number of cases; (iii the probability of extinction, and (iv the expected duration of an outbreak, demonstrating that all of these outcomes critically depend on the clinical impact of past vaccination on the diagnosis and movement of vaccinated cases. We discuss that, even in the absence of smallpox in the present day, one should consider the way to empirically quantify the delay in case detection and an increase in the frequency of contacts among previously vaccinated cases compared to unvaccinated during the early stage of an epidemic so that the feasibility of contact tracing and case isolation in a vaccinated population can be explicitly assessed.

  11. Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production.

    Science.gov (United States)

    Oyarzún, Patricio; Kobe, Bostjan

    2016-03-01

    Novel vaccination approaches based on rational design of B- and T-cell epitopes - epitope-based vaccines - are making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B- and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process. PMID:26430814

  12. Recombinant and epitope-based vaccines on the road to the market and implications for vaccine design and production.

    Science.gov (United States)

    Oyarzún, Patricio; Kobe, Bostjan

    2016-03-01

    Novel vaccination approaches based on rational design of B- and T-cell epitopes - epitope-based vaccines - are making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B- and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process.

  13. Endorsement of compulsory HIV vaccination policy among populations at high risk of HIV exposure (LA VOICES).

    Science.gov (United States)

    Newman, Peter A; Lee, Sung-Jae; Rudy, Ellen T; Diamant, Allison; Duan, Naihua; Nakazono, Terry; Nakazano, Terry; Cunningham, William E

    2014-06-01

    Compulsory vaccination is a frequently implemented policy option for ensuring comprehensive vaccine coverage. Ongoing controversies around human papillomavirus vaccine dissemination, and suboptimal coverage, suggest the value of assessing acceptability of compulsory vaccinations-particularly among likely target populations-in advance of their public availability to support evidence-informed interventions. With the first HIV vaccine to demonstrate partial efficacy in a large-scale clinical trial, we examined individual characteristics and attitudes associated with support for compulsory HIV vaccination policy among a diverse, representative sample of adults attending probable HIV vaccine dissemination venues in a large urban county. Participants were recruited using three-stage probability sampling from likely venues for future HIV vaccine dissemination. We used Audio-CASI to administer a 60-min structured questionnaire. Items included endorsement of compulsory HIV vaccination policy, sociodemographic characteristics, injecting drug use, vaccine attitudes and perceived HIV risk. Among 1,225 participants (mean age = 36.8 years; 55.6 % males, 37.6 % non-English speaking Hispanic, 78.8 % heterosexual, 25.7 % injection drug users), almost half (48.2 %) endorsed a compulsory HIV vaccination policy. Non-English speaking Hispanics compared to whites, participants with less than high school education, higher positive vaccine attitude scores and higher perceived HIV risk were significantly more likely, and people who inject drugs significantly less likely to endorse compulsory HIV vaccination. Public health interventions to promote positive vaccine attitudes and accurate perceptions of HIV risk among vulnerable populations, and strategies tailored for people who inject drugs, may build support for compulsory HIV vaccination policy and promote broad HIV vaccine coverage.

  14. Artificial blood

    Directory of Open Access Journals (Sweden)

    Sarkar Suman

    2008-01-01

    Full Text Available Artificial blood is a product made to act as a substitute for red blood cells. While true blood serves many different functions, artificial blood is designed for the sole purpose of transporting oxygen and carbon dioxide throughout the body. Depending on the type of artificial blood, it can be produced in different ways using synthetic production, chemical isolation, or recombinant biochemical technology. Development of the first blood substitutes dates back to the early 1600s, and the search for the ideal blood substitute continues. Various manufacturers have products in clinical trials; however, no truly safe and effective artificial blood product is currently marketed. It is anticipated that when an artificial blood product is available, it will have annual sales of over $7.6 billion in the United States alone.

  15. Therapeutic HIV Peptide Vaccine

    DEFF Research Database (Denmark)

    Fomsgaard, Anders

    2015-01-01

    infection directed to subdominant conserved HIV-1 epitopes restricted to frequent HLA supertypes. The rationale for selecting HIV peptides and adjuvants are provided. Peptide subunit vaccines are regarded as safe due to the simplicity, quality, purity, and low toxicity. The caveat is reduced immunogenicity......Therapeutic vaccines aim to control chronic HIV infection and eliminate the need for lifelong antiretroviral therapy (ART). Therapeutic HIV vaccine is being pursued as part of a functional cure for HIV/AIDS. We have outlined a basic protocol for inducing new T cell immunity during chronic HIV-1...... and hence adjuvants are included to enhance and direct the immune response. Although the vaccine has been tested in ART naïve individuals, we recommend future testing of the vaccine during (early started) ART that improves immune function and to select individuals likely to benefit. Peptides representing...

  16. Neisseria meningitidis B vaccines.

    Science.gov (United States)

    Panatto, Donatella; Amicizia, Daniela; Lai, Piero Luigi; Gasparini, Roberto

    2011-09-01

    Invasive infections caused by Neisseria meningitidis are a serious public health problem worldwide and have a heavy economic impact. The incidence of invasive disease due to Neisseria meningitidis is highly variable according to geographical area and serogroup distribution. Since the introduction of vaccination programs with conjugated vaccine C in children and adolescents, most cases of invasive meningococcal disease in developed countries have been caused by meningococcus B. It is important to underline that invasive meningococcal disease will not be controlled until safe and effective vaccines for meningococcal B are available and widely used. The aims of this article are to describe the most recent developments in meningococcal B vaccines and to discuss how these vaccines can contribute to containing meningococcal disease.

  17. DNA fusion gene vaccines

    DEFF Research Database (Denmark)

    Holst, Peter Johannes; Bassi, Maria Rosaria; Thomsen, Allan Randrup;

    2010-01-01

    DNA vaccines are versatile and safe, but limited immunogenicity has prevented their use in the clinical setting. Experimentally, immunogenicity may be enhanced by the use of new delivery technologies, by coadministration of cytokines and pathogen-associated molecular patterns, or by fusion...... of antigens into molecular domains that enhance antigen presentation. More specifically, the immunogenicity of DNA vaccines may benefit from increased protein synthesis, increased T-cell help and MHC class I presentation, and the addition of a range of specific cytokines and pathogen-associated molecular...... with viral-vectored vaccines, various synergistic components may need to be incorporated into DNA vaccines. From the perspective of the future clinical use of DNA vaccines, it has been suggested that antigen presentation should be improved and cytokine coadministration attempted. However, even...

  18. Immune memory responses to HBV vaccine 13-18 years after primary vaccination.

    Science.gov (United States)

    Hou, L; Li, W; Wei, X; Zhou, Y; Zhuo, Y; Wu, H; Shen, B

    2015-01-01

    The aim of this study was to evaluate the immune memory response 13-18 years after an hepatitis B virus (HBV) vaccine by performing a specific in vitro stimulation experiment. Thirty healthy volunteers who had been inoculated 13-18 years ago with the HBV vaccine were collected from the physical examination center. Peripheral blood mononuclear cells were stimulated with 50 ng/mL recombinant HBsAg. An ELISA kit was used for the detection of antibodies that were produced by these cells in vitro. It was found that even 13-18 years after inoculation with the HBV vaccine, an anamnestic antibody response still existed, and was not correlated with the serum antibody levels (r = -0.177, P = 0.377). In conclusion, our data showed that the individuals after inoculation, including those with anti-HBs B cells. PMID:26345774

  19. Vaccine safety--vaccine benefits: science and the public's perception.

    Science.gov (United States)

    Wilson, C B; Marcuse, E K

    2001-11-01

    The development of cowpox vaccination by Jenner led to the development of immunology as a scientific discipline. The subsequent eradication of smallpox and the remarkable effects of other vaccines are among the most important contributions of biomedical science to human health. Today, the need for new vaccines has never been greater. However, in developed countries, the public's fear of vaccine-preventable diseases has waned, and awareness of potential adverse effects has increased, which is threatening vaccine acceptance. To further the control of disease by vaccination, we must develop safe and effective new vaccines to combat infectious diseases, and address the public's concerns.

  20. Detection of Francisella tularensis in blood by polymerase chain reaction.

    OpenAIRE

    Long, G W; Oprandy, J J; Narayanan, R. B.; Fortier, A H; Porter, K R; Nacy, C.A.

    1993-01-01

    We developed a polymerase chain reaction-based assay for Francisella tularensis which we evaluated by using spiked blood samples and experimentally infected mice. The assay detected both type A and type B F. tularensis at levels equivalent to one CFU/microliter of spiked blood. Results from polymerase chain reaction-based assay of limiting dilutions of blood from mice infected with the live vaccine strain agreed closely with results from blood culture.

  1. Vaccines for canine leishmaniasis

    Directory of Open Access Journals (Sweden)

    Clarisa B. Palatnik-De-Sousa

    2012-04-01

    Full Text Available Leishmaniasis is the third most important vector-borne disease worldwide. Visceral leishmaniasis (VL is a severe and frequently lethal protozoan disease of increasing incidence and severity due to infected human and dog migration, new geographical distribution of the insect due to global-warming, co-infection with immunosuppressive diseases and poverty. The disease is an anthroponosis in India and Central Africa and a canid zoonosis (ZVL in the Americas, the Middle East, Central Asia, China and the Mediterranean. The ZVL epidemic has been controlled by one or more measures including the culling of infected dogs, treatment of human cases and insecticidal treatment of homes and dogs. However, the use of vaccines is considered the most cost-effective control tool for human and canine disease. Since the severity of the disease is related to the generation of T-cell immunosuppression, effective vaccines should be capable of sustaining or enhancing the T-cell immunity. In this review we summarize the clinical and parasitological characteristics of ZVL with special focus on the cellular and humoral canine immune response and review state-of-the-art vaccine development against human and canine visceral leishmaniasis. Experimental vaccination against leishmaniasis has evolved from the practice of leishmanization with living parasites to vaccination with crude lysates, native parasite extracts to recombinant and DNA vaccination. Although more than 30 defined vaccines have been studied in laboratory models no human formulation has been licensed so far; however three second-generation canine vaccines have already been registered. As expected for a zoonotic disease, the recent preventive vaccination of dogs in Brazil has led to a reduction in the incidence of canine and human disease. The recent identification of several Leishmania proteins with T-cell epitopes anticipates development of a multiprotein vaccine that will be capable of protecting both humans

  2. Lassa fever vaccine.

    Science.gov (United States)

    Fisher-Hoch, Susan P; McCormick, Joseph B

    2004-04-01

    Lassa fever remains a serious challenge to public health in West Africa threatening both local residents in rural areas and those who serve them, particularly medical care providers. Given the ecology of the rodent host and conditions in the endemic area, a vaccine is mandatory for control. The challenge is to overcome the scientific, political and economic obstacles to producing a human use vaccine candidate. There are some scientific issues to resolve. It is known that the G-protein confers protection but we do not know its duration. If the N-protein is also included there may be a better duration of protection but it is unclear whether the N-protein as a vaccine may possibly enhance the infection. The original vaccinia vector must be replaced by new vectors, chimeras or by delivering DNA in some format. A live vaccine is attractive because it can confer protection in a single shot. A killed vaccine is more stable, particularly for distribution in the tropics but usually requires repeated shots. For practical reasons a live vaccine format should probably be pursued, which could then be combined with a yellow fever vaccine, using the same cold chains, since this disease occupies the same endemic areas in West Africa. Lassa vaccine initiatives have suffered from a lack of funding in the past but bioterrorism has brought new resources to Lassa virus science. Adequate funding and applications of new vaccine technologies give hope that we may soon see a vaccine in clinical trials. However, the difficulty of conducting trials in endemic areas and lack of political stability remain serious problems. PMID:15056044

  3. The Vaccine Safety Datalink: successes and challenges monitoring vaccine safety.

    Science.gov (United States)

    McNeil, Michael M; Gee, Julianne; Weintraub, Eric S; Belongia, Edward A; Lee, Grace M; Glanz, Jason M; Nordin, James D; Klein, Nicola P; Baxter, Roger; Naleway, Allison L; Jackson, Lisa A; Omer, Saad B; Jacobsen, Steven J; DeStefano, Frank

    2014-09-22

    The Vaccine Safety Datalink (VSD) is a collaborative project between the Centers for Disease Control and Prevention (CDC) and 9 health care organizations. Established in 1990, VSD is a vital resource informing policy makers and the public about the safety of vaccines used in the United States. Large linked databases are used to identify and evaluate adverse events in over 9 million individuals annually. VSD generates rapid, important safety assessments for both routine vaccinations and emergency vaccination campaigns. VSD monitors safety of seasonal influenza vaccines in near-real time, and provided essential information on the safety of influenza A (H1N1) 2009 monovalent vaccine during the recent pandemic. VSD investigators have published important studies demonstrating that childhood vaccines are not associated with autism or other developmental disabilities. VSD prioritizes evaluation of new vaccines; searches for possible unusual health events after vaccination; monitors vaccine safety in pregnant women; and has pioneered development of biostatistical research methods.

  4. Human peripheral blood lymphocytes from recently vaccinated individuals produce both type-specific and intertypic cross-reacting neutralizing antibody on in vitro stimulation with one type of poliovirus.

    NARCIS (Netherlands)

    F.G.C.M. Uytdehaag (Fons); H.G. Loggen; T. Logtenberg (Ton); R.A. Lichtveld; G. van Steenis (Bert); J.A.A.M. van Asten (Jack); A.D.M.E. Osterhaus (Ab)

    1985-01-01

    textabstractAn in vitro system of poliovirus-specific antibody production by peripheral blood B cells on stimulation by the virus has been developed. Virus-neutralizing antibodies in culture supernatant fluids, or virus-specific antibody-secreting cells (ASC) were detected by microneutralization ass

  5. Oral DNA Vaccine in Chickens

    Directory of Open Access Journals (Sweden)

    Seyed Davoud Jazayeri

    2012-01-01

    Full Text Available Attenuated Salmonella has been used as a carrier for DNA vaccine. However, in vitro and in vivo studies on the bacteria following transfection of plasmid DNA were poorly studied. In this paper, eukaryotic expression plasmids encoding avian influenza virus (AIV subtype H5N1 genes, pcDNA3.1/HA, NA, and NP, were transfected into an attenuated Salmonella enteric typhimurium SV4089. In vitro stability of the transfected plasmids into Salmonella were over 90% after 100 generations. The attenuated Salmonella were able to invade MCF-7 (1.2% and MCF-10A (0.5% human breast cancer cells. Newly hatched specific-pathogen-free (SPF chicks were inoculated once by oral gavage with 109 colony-forming unit (CFU of the attenuated Salmonella. No abnormal clinical signs or deaths were recorded after inoculation. Viable bacteria were detected 3 days after inoculation by plating from spleen, liver, and cecum. Fluorescent in situ hybridization (FISH and polymerase chain reaction (PCR were carried out for confirmation. Salmonella was not detected in blood cultures although serum antibody immune responses to Salmonella O antiserum group D1 factor 1, 9, and 12 antigens were observed in all the inoculated chickens after 7 days up to 35 days. Our results showed that live attenuated S. typhimurium SV4089 harboring pcDNA3.1/HA, NA, and NP may provide a unique alternative as a carrier for DNA oral vaccine in chickens.

  6. H. influenzae type b (Hib) vaccine--controversies.

    Science.gov (United States)

    Shah, Nitin K

    2003-06-01

    Hib vaccine is the 8th vaccine knocking at the door to be included in the EPI the world over. However there are some controversies that need to be addressed, especially when it comes to use of this vaccine in India. It is difficult to culture Hib unless one uses sheep blood enriched media for culture. There is a lack of good community based data on Hib burden in India. This makes many feel that Hib is rare in India. However this is not true. There are many studies that have looked at this closely. Hib is a common cause of meningitis and pneumonitis in children less than 5 years old in India. There is wide spread problem of multi-drug resistance by Hib in India. Mortality of meningitis is as high as 100% if third generation cephalosporins are not used in time. Of the survivors of meningitis, 60% develop long-term sequelae. Hib vaccine is very effective and can lead to 99% reduction with mass vaccination in just 2-3 years. It is also a very safe vaccine. Of the conjugated vaccines available in India all are equally effective and safe and there is nothing to choose one over the other. There is a need to give a booster dose at 15-18 months of age. Even UK, which never gave the booster dose, is seriously thinking of changing their practice and give a booster dose. Lastly the combination vaccines of Hib with IPV, DPwT/DPaT, and Hepatitis B are safe and effective and should be encouraged to improve the compliance. The use of Hib vaccine is recommended in India, for those who can afford the vaccine. PMID:12921318

  7. [Current events in vaccination].

    Science.gov (United States)

    Aubert, M; Aumaître, H; Beytout, J; Bloch, K; Bouhour, D; Callamand, P; Chave, C; Cheymol, J; Combadière, B; Dahlab, A; Denis, F; De Pontual, L; Dodet, B; Dommergues, M-A; Dufour, V; Gagneur, A; Gaillat, J; Gaudelus, J; Gavazzi, G; Gillet, Y; Gras-le-Guen, C; Haas, H; Hanslik, T; Hau-Rainsard, I; Larnaudie, S; Launay, O; Lorrot, M; Loulergue, P; Malvy, D; Marchand, S; Picherot, G; Pinquier, D; Pulcini, C; Rabaud, C; Regnier, F; Reinert, P; Sana, C; Savagner, C; Soubeyrand, B; Stephan, J-L; Strady, C

    2011-11-01

    The annual meeting of the Infectious Disease Society of America (IDSA) ; which brought together nearly 5000 participants from over 80 countries in Vancouver, Canada, October 21 to 24, 2010 ; provided a review of the influenza (H1N1) 2009 pandemic, evaluated vaccination programmes and presented new vaccines under development. With 12,500 deaths in the United States in 2009-2010, the influenza (H1N1) 2009 pandemic was actually less deadly than the seasonal flu. But it essentially hit the young, and the toll calculated in years of life lost is high. The monovalent vaccines, whether live attenuated or inactivated with or without adjuvants, were well tolerated in toddlers, children, adults and pregnant women. In order to protect infants against pertussis, family members are urged to get their booster shots. The introduction of the 13-valent Pneumococcal conjugated vaccine in the beginning of 2010 may solve - but for how long ? - the problem of serotype replacement, responsible for the re-increasing incidence of invasive Pneumococcal infections observed in countries that had introduced the 7-valent vaccine. The efficacy of a rotavirus vaccine has been confirmed, with a reduction in hospitalization in the United States and a reduction in gastroenteritis-related deaths in Mexico. In the United States, vaccination of pre-adolescents against human papillomavirus (HPV) has not resulted in any specific undesirable effects. Routine vaccination against chicken pox, recommended since 1995, has not had an impact on the evolution of the incidence of shingles. Vaccination against shingles, recommended in the United States for subjects 60 years and over, shows an effectiveness of 55 %, according to a cohort study (Kaiser Permanente, Southern California). Although some propose the development of personalized vaccines according to individual genetic characteristics, the priority remains with increasing vaccine coverage, not only in infants but also in adults and the elderly. Vaccine

  8. [Present status of vaccines in 1989].

    Science.gov (United States)

    Roussey, M; Dabadie, A

    1989-01-01

    The authors describe 2 new vaccines now available in France: one is the GenHevac, an hepatitis B vaccine, the first virus recombinant vaccine; the other one is the Typhim Vi, a polysaccharide typhoid vaccine. Three other vaccines are currently used in foreign countries and will be soon available: the Hemophilus influenzae vaccine, the acellular pertussis vaccine and the varicella vaccine. Rotavirus and Cytomegalovirus vaccines are studied for their clinical efficacy.

  9. Development of fowl cholera vaccine: I. Protection of Pasteurella multocida local isolate vaccine against challenge of homologous and heterologous strains.

    Directory of Open Access Journals (Sweden)

    Supar

    2001-03-01

    Full Text Available Pasteurella multocida locally isolated from chicken and ducks (BCC 299, BCC 2331, DY1, DY2, 12TG, 15TG andimported strains (BCC 1359, 1362; HEDDLESTON group 1 and 6 respectively had been tested for its pathogenicity in theprevious study. The aims of this experiment were to study the preparation of local isolate pasteurellosis vaccines and to determine the protective effect of that vaccines in chicken against the highly pathogenic local isolates of P. multocida. Killed monovalent, bivalent and polyvalent pasteurellosis vaccines were prepared and each was adjunvanted with aluminum hydroxide gel at a final concentration of 1.5% and the cell concentration was equal to the No 10 of MacFarland tube standard. Each of the vaccine prepared was used to vaccinated on a group of six week old of layer chicken (8 per group. Each chicken was subcutaneously injected with 0.2 ml of vaccine, four weeks later each was boostered with similar vaccine with the same dose. Two weeks after giving the boostered vaccine each group of chicken were challenged, half with life bacterium of P. Multocida BCC 2331 and other with DY2. Any chick which survive after challenge was designated as protected by vaccination. Before vaccination 1 ml of blood was drawn from each of chicken and then two weeks apart up to challenge. Serum from each sample was separated and kept in deep freeze until tested by enzyme-linked immunosorbent assay (ELISA. Chicken vaccinated with killed whole cell P. multocida vaccines of monovalent (BCC 2331 or DY2 and bivalent (BCC 2331 + DY2 were protected against challenge with live bacterium of either BCC 2331 or DY2 at rate 67-100%. There was no protection in chicken vaccinated with either BCC 299, DY1, 12TG, 15TG, BCC 1359, or 1362 killed vaccine. Similarly no protection of chicken vaccinated with either DY1 + BCC299, 12TG + 15TG or BCC 1359 + BCC 1362 bivalent vaccines. The protection rate of the polyvalent local isolate vaccine was at average 50-75%. All

  10. Immunogenicity of a combined DTPa-HB vaccine co-administered with Haemophilus influenzae type B conjugate vaccine (PRP-T for primary and booster vaccinations

    Directory of Open Access Journals (Sweden)

    Humberto Bracco Neto

    2005-10-01

    Full Text Available OBJECTIVE: To evaluate the immunogenicity of a combined DTPa-HB vaccine co-administered with Haemophilus influenzae type b conjugate vaccine (PRP-T in Brazilian infants. MATERIAL AND METHODS: A prospective and open clinical study, in which 110 infants were immunized with a three-dose primary vaccination regime at two, four and six months of age and with a single booster vaccination. Blood samples were drawn immediately before the first dose, one month after the third dose, at the time of the booster dose and one month after the booster to assess seropositivity and antibody geometric mean titers (GMTs of antibodies for diphtheria, tetanus, hepatitis B, Haemophilus influenzae type b and for the three pertussis antigens: Pertussis Toxin (PT, Filamentous Hemagglutinin (FHA and Pertactin (PRN. RESULTS: Among the original 110 infants, 93 completed the study. Seropositivity was 100% for all seven involved antibodies, after the primary vaccination course. At the time of the booster dose, all antibodies (except diphtheria 33.7% and anti-PT 59% were seropositive for more than 94% of subjects. After the booster, seropositivity increased to 100% for all antibodies. The GMT of these antibodies followed a similar pattern, with a strong increase after the primary course, followed by a second increase after the booster dose. At this time, GMT was2- to 7-fold higher than after the primary course, for all vaccine components. CONCLUSIONS: Concomitant administration of DTPa-HB and Hib vaccines elicited strong seroprotection for all the antigenic components. No interference with antibody response was evident. The vaccines provided high immunogenicity, following both the primary vaccinations and the booster dose.

  11. Blood smear

    Science.gov (United States)

    ... osmotic fragility ) Deficiency of an enzyme called lecithin cholesterol acyl transferase Abnormalities of hemoglobin , the protein in ... sickle and Pappenheimer Red blood cells, target cells Formed elements of blood References Bain BJ. The peripheral ...

  12. Safety, tolerability, and immunogenicity of a recombinant, genetically engineered, live-attenuated vaccine against canine blastomycosis.

    Science.gov (United States)

    Wüthrich, Marcel; Krajaejun, Theerapong; Shearn-Bochsler, Valerie; Bass, Chris; Filutowicz, Hanna I; Legendre, Alfred M; Klein, Bruce S

    2011-05-01

    Blastomycosis is a severe, commonly fatal infection caused by the dimorphic fungus Blastomyces dermatitidis in dogs that live in the United States, Canada, and parts of Africa. The cost of treating an infection can be expensive, and no vaccine against this infection is commercially available. A genetically engineered live-attenuated strain of B. dermatitidis lacking the major virulence factor BAD-1 successfully vaccinates against lethal experimental infection in mice. Here we studied the safety, toxicity, and immunogenicity of this strain as a vaccine in dogs, using 25 beagles at a teaching laboratory and 78 foxhounds in a field trial. In the beagles, escalating doses of live vaccine ranging from 2 × 10⁴ to 2 × 10⁷ yeast cells given subcutaneously were safe and did not disseminate to the lung or induce systemic illness, but a dose of vaccine dose of 10⁵ yeast cells was also well tolerated in vaccinated foxhounds who had never had blastomycosis; however, vaccinated dogs with prior infection had more local reactions at the vaccine site. The draining lymph node cells and peripheral blood lymphocytes from vaccinated dogs demonstrated gamma interferon (IFN-γ), tumor necrosis factor alpha (TNF-α), and granulocyte-macrophage colony-stimulating factor (GM-CSF) specifically in response to stimulation with Blastomyces antigens. Thus, the live-attenuated vaccine against blastomycosis studied here proved safe, well tolerated, and immunogenic in dogs and merits further studies of vaccine efficacy.

  13. Protection of inactive intranasal ántrax vaccine to Bacillus anthracis infection

    Directory of Open Access Journals (Sweden)

    Adin Priadi

    2010-06-01

    Full Text Available Ánthrax is an endemic zoonotic disease distributed in many parts of Indonesia. Although vaccination program has been implemented in many areas, cases are still frequently reported. Farmers are reluctant to vaccinate their livestock since spore vaccine used in the field often cause side effects and death of the animals. To overcome this problem, an inactive vaccine composes of Bacillus anthracis toxins, cell wall and capsule subunits was developed. B. anthracis Sterne strain (34F2 was selected to produce toxins and cell walls. Local Bacillus anthracis isolated from Citaringgul was used to produce capsule as the Polymerase Chain Reaction (PCR revealed that this isolate poses cap gene encoding for capsule. Two vaccines compose of 15 μg toxoid, 30 μg of capsule, 15 μg of cell wall and 30 μg toxoid, 60 μg of capsule, 15 μg of cell walls were designated as vaccine I and vaccine II respectively. For each experiment, 10 mice were nasally immunized by placing 5 μl of vaccine into each nare 3 times at 2-week intervals. A group of 10 mice were unvaccinated and used as control. Blood was collected fortnightly to monitor antibody responses. All mice were challenged with 2 x 105 B. anthracis Sterne spores injected subcutaneously two weeks after the last vaccination. Two weeks after vaccination of antibodies to B. anthracis toxin, capsule and cell wall were detected in dot-blot assay. Mice that were immunised intranasally with chitosan adjuvanted vaccine developed high IgG responses in sera as detected by ELISA, and the response was dose dependent. Vaccine II gave better response than vaccine I. Vaccine I and II protected mice from challenge at a rate of 60 and 80% respectively. This results showed that intranasal B. anthracis vaccine composes of toxin, capsule and cell wall with chitosan as an adjuvant gave a good protection against B. anthracis Sterne spores challenge in mice.

  14. Efficacy of two canine distemper vaccines in wild Nearctic river otters (Lontra canadensis).

    Science.gov (United States)

    Peper, Steven T; Peper, Randall L; Kollias, George V; Brooks, Robert P; Stevens, Sadie S; Serfass, Thomas L

    2014-09-01

    Canine distemper virus (CDV), a contagious morbillivirus, infects families in the order Carnivora, including Nearctic river otters (Lontra canadensis). As a preventative measure, vaccinations against CDV are frequently given to mustelids in captive environments. The Pennsylvania River Otter Reintroduction Project (PRORP) used wild-caught river otters to evaluate the efficacy and need for vaccinations against CDV as part of any reintroduction project. The objectives of this study were to: 1) evaluate the prevalence of exposure to CDV in wild river otters, 2) determine the immunologic response of river otters (i.e., seroconversion) after vaccination with a single (primary) vaccine dose compared to a second (booster) dose of Galaxy-D, a modified live-virus canine distemper (CD) vaccine (MLV CDV), and 3) determine the immunologic response after being vaccinated with a primary vaccination compared to a booster dose of Fervac-D, an MLV CDV. River otters were injected subcutaneously in the nape of the neck with their designated vaccine. Timeframes for collection of blood samples and/or injection of booster vaccines varied depending on the parameters of PRORP. Ten of the 22 river otters had positive prevaccination titer levels to CD. Both vaccines, Galaxy-D and Fervac-D, produced sufficient seroconversion or rise of titer levels (86% and 57%, respectively) to recommend the use of vaccines in wild river otters. Future studies are recommended to evaluate currently produced CD vaccines. Future research should also focus on the number of days required between administration of primary and booster vaccines to achieve sufficient immune response. If only a primary dose is required, then hard-release reintroduction projects for river otters could be recommended. If primary and booster vaccines are required then soft-release reintroduction projects should be recommended. Soft-release projects should include captive management periods that allow for appropriate vaccination intervals

  15. DNA vaccine: the miniature miracle

    Directory of Open Access Journals (Sweden)

    Karthik Kaliaperumal

    2013-08-01

    Full Text Available DNA, the essential part of the life is making way in to new vaccine technology. Plasmid vectors from the bacteria have revolutionized the world of vaccine design by its new technology – DNA vaccines. Small portion of the nucleotides from the pathogen held under the control of promoter in a plasmid vector can be used as a vaccine. DNA vaccines alleviate the odds of the other vaccines by having good hold on both the faces of the immunity. The key to the success of DNA vaccine lies in the route of administration of the vaccine which can be done in many ways. Prime boost strategy is an approach used to boost the action of DNA vaccine. To date there are only four DNA vaccine available in the market. [Vet World 2013; 6(4.000: 228-232

  16. Vaccine delivery in the 21st century

    International Nuclear Information System (INIS)

    A major problem in many vaccination programmes aimed at the effective immunization of human and agricultural animal populations is the logistics of sustained vaccine delivery. These problems stem from the formulation of the vaccine antigen, the selection of adjuvants, the cost of production, quality control, the shelf-life of the vaccine itself, delivery to the target population and ensuring an appropriate programme of injections so that full immunity develops. The authors wish to explore the idea of an essentially passive system for the delivery of vaccines. Over a number of years, they have focused their attention on the development of transgenic technology in insect vectors of animal and human disease. One essential stage in the life cycle of these insects, and the reason why they act as vectors of disease causing agents, is the necessity for a bloodmeal. The authors have been exploring the concept of using these haematophagous insects as a vehicle to deliver antigens directly to human and animal populations as one part of an overall immunization programme. The concept essentially involves creating transgenic haematophagous insects which are capable of expressing the desired antigens in their saliva, so that when they take a bloodmeal a small amount of antigen is delivered to the host. Current data strongly suggest that over a prolonged period of time this repeated low level exposure to the vaccine antigen could potentially lead to immunity in the human or animal host. The progress which has been made in developing this approach, together with its potential advantages and disadvantages, is discussed. (author)

  17. Human anthelminthic vaccines: Rationale and challenges.

    Science.gov (United States)

    Hotez, Peter J; Strych, Ulrich; Lustigman, Sara; Bottazzi, Maria Elena

    2016-06-24

    Helminth infections are the most common afflictions of humankind, affecting almost every single person living in profound poverty. Through mass drug administration (MDA) we have seen sharp declines in the global prevalence of some helminth infections, including lymphatic filariasis, onchocerciasis, and ascariasis. However, since 1990, there has been no appreciable decrease in the global prevalence of hookworm infection, schistosomiasis, or food-borne trematodiases. Through the activities of a non-profit product development partnerships and two research institutes, a total of five human anthelmintic vaccines for hookworm infection (two) and schistosomiasis (three) have advanced from discovery through manufacture and are now in Phase 1 clinical testing. At least three additional antigens, including two for onchocerciasis and one for schistosomiasis, are also advancing through preclinical development with the intention of moving into the clinic soon. These preventive human anthelmintic vaccines could be used as stand-alone technologies administered to infants as part of the Expanded Program on Immunization (EPI), or together with anthelmintic drugs in programs linked to MDA. Significant hurdles though could hinder the advancement of these vaccines into later-stage clinical and product development and licensure. They include the absence of a major pharma partner (and the resultant access to adjuvants and industrial scale manufacturing expertise), an uncharted roadmap for how to introduce anthelmintic vaccines into appropriate health systems, uncertain global access and regulatory strategies that might need to rely on developing country vaccine manufacturers and national regulatory authorities, and the lack of innovative financing schemes. However, the public health and economic benefits of introducing these vaccines could be massive and therefore deserve international attention and support. PMID:27171753

  18. [Vaccinations in respiratory medicine].

    Science.gov (United States)

    Lode, H M; Stahlmann, R

    2015-09-01

    Vaccinations are the most successful and cost-effective measures for prevention of infections. Important pathogens of respiratory tract infections (e.g. influenza viruses and pneumococci) can be effectively treated by vaccinations. The seasonal trivalent and recently now quadrivalent influenza vaccines include antigens from influenza A and B type viruses, which have to be modified annually oriented to the circulating strains. The effective protection by influenza vaccination varies considerably (too short protection time, mismatch); therefore, administration late in the year is the best approach (November/December). Two pneumococcal vaccines are recommended for adults: the over 30-year-old 23-valent polysaccharide vaccine (PPV23) and the 4-year-old 13-valent conjugate vaccine (PCV13). The immunological and clinical efficacy of PPV23 is controversially discussed; however, a moderate reduction of invasive pneumococcal infections is widely accepted. The PCV13 stimulates a T-cell response and has currently demonstrated its clinical efficacy in an impressive study (CAPiTA). The problem of PCV13 is the relatively limited coverage of only 47% of the currently circulating invasive pneumococcal serotypes. PMID:26330051

  19. Flu vaccination in pregnancy

    Directory of Open Access Journals (Sweden)

    Maria Siettou

    2012-04-01

    Full Text Available In periods of seasonal influenza, during pandemic flu in the past and from recent experience that we have the emergence of influenza A (H1N1, pregnant compared with non-pregnant women are at increased risk to get sick and to develop serious complications up to mortality. Purpose: This paper examines the risks that arise for pregnant from contamination with the flu virus and the safety of influenza vaccination in pregnancy. Method: The method involves searching review and research studies in Pubmed data base mainly of the 2000 until 2009 and the words were used is pregnancy, flu vaccination, complications of the flu vaccination at the period of pregnancy. Results: Morbidity during periods of seasonal influenza in pregnant women is increased, while in times of pandemic are recorded fatalities. Based on this, specific recommendations have been made for a flu vaccination in pregnant women, both from the CDC, the American College of Obstetricians and Gynecologists in the U.S. and other official bodies like the World Health Organization, according to that the constitution of influenza vaccine in the pregnancy is necessary, given that the probability of morbidity in this period is increased at 10%. Conclusions: The studies so far to influenza vaccination in pregnancy, do not record serious complications for pregnant women and infants. However more research needs to be done on the safety of influenza vaccination in pregnancy.

  20. Vaccine acceptance: The UK perspective

    OpenAIRE

    Ford, John A; Mahgoub, Hamid; Shankar, Ananda Giri

    2013-01-01

    The United Kingdom has had a long history with vaccine acceptability dating back to Edward Jenner’s theory of small pox vaccination. More recently, the discredited, Wakefield study published in 1998 continues to cause MMR skepticism. In pregnant women pertussis vaccination has been considerably more successful than influenza vaccination. Influenza vaccine uptake in healthcare workers remains poor. The media, politicians, and health reforms have contributed to the mixed coverage for these vacc...