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Sample records for attenuated pertussis vaccine

  1. Live Attenuated Pertussis Vaccine BPZE1 Protects Baboons Against Bordetella pertussis Disease and Infection

    Science.gov (United States)

    Papin, James F.; Lecher, Sophie; Debrie, Anne-Sophie; Thalen, Marcel; Solovay, Ken; Rubin, Keith; Mielcarek, Nathalie

    2017-01-01

    Abstract Evidence suggests that the resurgence of pertussis in many industrialized countries may result from the failure of current vaccines to prevent nasopharyngeal colonization by Bordetella pertussis, the principal causative agent of whooping cough. Here, we used a baboon model to test the protective potential of the novel, live attenuated pertussis vaccine candidate BPZE1. A single intranasal/intratracheal inoculation of juvenile baboons with BPZE1 resulted in transient nasopharyngeal colonization and induction of immunoglobulin G and immunoglobulin A to all antigens tested, while causing no adverse symptoms or leukocytosis. When BPZE1-vaccinated baboons were challenged with a high dose of a highly virulent B. pertussis isolate, they were fully protected against disease, whereas naive baboons developed illness (with 1 death) and leukocytosis. Total postchallenge nasopharyngeal virulent bacterial burden of vaccinated animals was substantially reduced (0.002%) compared to naive controls, providing promising evidence in nonhuman primates that BPZE1 protects against both pertussis disease and B. pertussis infection. PMID:28535276

  2. 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)

  3. Construction and evaluation of Bordetella pertussis live attenuated vaccine strain BPZE1 producing Fim3.

    NARCIS (Netherlands)

    Debrie, Anne-Sophie; Coutte, Loïc; Raze, Dominique; Mooi, Frits; Alexander, Frances; Gorringe, Andrew; Mielcarek, Nathalie; Locht, Camille

    2018-01-01

    Pertussis or whooping cough is currently the most prevalent vaccine-preventable childhood disease despite >85% global vaccination coverage. In recent years incidence has greatly increased in several high-income countries that have switched from the first-generation, whole-cell vaccine to the newer

  4. Development of improved pertussis vaccine.

    Science.gov (United States)

    Rumbo, Martin; Hozbor, Daniela

    2014-01-01

    Rates of infection with Bordetella pertussis, the gram-negative bacterium that causes the respiratory disease called whooping cough or pertussis, have not abated and 16 million cases with almost 200,000 deaths are estimated by the WHO to have occurred worldwide in 2008. Despite relatively high vaccination rates, the disease has come back in recent years to afflict people in numbers not seen since the pre-vaccine days. Indeed, pertussis is now recognized as a frequent infection not only in newborn and infants but also in adults. The disease symptoms also can be induced by the non-vaccine-preventable infection with the close species B. parapertussis for which an increasing number of cases have been reported. The epidemiologic situation and current knowledge of the limitations of pertussis vaccine point out the need to design improved vaccines. Several alternative approaches and their challenges are summarized.

  5. Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine

    Science.gov (United States)

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

  6. Maternal vaccination to prevent pertussis in infants

    African Journals Online (AJOL)

    2016-09-09

    Sep 9, 2016 ... that maternal immunisation with the Tdap (tetanus, diphtheria and acellular pertussis) vaccine is safe. Indeed, maternal vaccination is now recommended to prevent pertussis infection in vulnerable young infants. In the USA and UK, the immunisation of pregnant women with a Tdap or dTaP/IPV (diphtheria, ...

  7. Bordetella Pertussis virulence factors in the continuing evolution of whooping cough vaccines for improved performance.

    Science.gov (United States)

    Dorji, Dorji; Mooi, Frits; Yantorno, Osvaldo; Deora, Rajendar; Graham, Ross M; Mukkur, Trilochan K

    2018-02-01

    Despite high vaccine coverage, whooping cough caused by Bordetella pertussis remains one of the most common vaccine-preventable diseases worldwide. Introduction of whole-cell pertussis (wP) vaccines in the 1940s and acellular pertussis (aP) vaccines in 1990s reduced the mortality due to pertussis. Despite induction of both antibody and cell-mediated immune (CMI) responses by aP and wP vaccines, there has been resurgence of pertussis in many countries in recent years. Possible reasons hypothesised for resurgence have ranged from incompliance with the recommended vaccination programmes with the currently used aP vaccine to infection with a resurged clinical isolates characterised by mutations in the virulence factors, resulting in antigenic divergence with vaccine strain, and increased production of pertussis toxin, resulting in dampening of immune responses. While use of these vaccines provide varying degrees of protection against whooping cough, protection against infection and transmission appears to be less effective, warranting continuation of efforts in the development of an improved pertussis vaccine formulations capable of achieving this objective. Major approaches currently under evaluation for the development of an improved pertussis vaccine include identification of novel biofilm-associated antigens for incorporation in current aP vaccine formulations, development of live attenuated vaccines and discovery of novel non-toxic adjuvants capable of inducing both antibody and CMI. In this review, the potential roles of different accredited virulence factors, including novel biofilm-associated antigens, of B. pertussis in the evolution, formulation and delivery of improved pertussis vaccines, with potential to block the transmission of whooping cough in the community, are discussed.

  8. Pertussis epidemic despite high levels of vaccination coverage with acellular pertussis vaccine.

    Science.gov (United States)

    Sala-Farré, Maria-Rosa; Arias-Varela, César; Recasens-Recasens, Assumpta; Simó-Sanahuja, Maria; Muñoz-Almagro, Carmen; Pérez-Jové, Josefa

    2015-01-01

    We describe the pertussis epidemic, based only on confirmed whooping cough cases. We have analyzed data on the diagnosis, epidemiology and vaccine history in order to understand the factors that might explain the trends of the disease. A descriptive study of the confirmed pertussis cases reported during 2011 in the Vallès region (population 1,283,000). Laboratory criteria for confirmed pertussis cases include isolation of Bordetella pertussis from a clinical specimen or detection of B. pertussis by PCR in nasopharyngeal swabs. A total of 421 pertussis confirmed cases were reported, which was the highest incidence reported in the last decade (33 cases/100,000 people/year in 2011). The highest incidence rate was among infants less than 1 year old (448/100,000), followed by children 5-9 years old (154/100,000). Pertussis cases aged 2 months-1 year were 90% vaccinated following the current DTaP schedule for their age group in Catalonia, and cases of 5-9 years were 87% fully vaccinated with 5 doses of DTaP vaccine. There were no deaths, although 8% of cases were hospitalized. Pertussis was more severe in infants, 30% required hospitalization despite having received the vaccine doses corresponding to their age. Children of 5-9 years were most often identified as primary cases in households or school clusters. Despite high levels of vaccination coverage, pertussis circulation cannot be controlled at all. The results question the efficacy of the present immunization programmes. Copyright © 2013 Elsevier España, S.L.U. y Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  9. Purification of heat labile toxin from Bordetella pertussis vaccine ...

    African Journals Online (AJOL)

    . pertussis vaccine strain 134 by employing indigenous technology and examining the immuno-biochemical aspects of the purified protein. Materials and methods: Shaker cultivation of B. pertussis strain 134, sterility, opacity confirmation, TCA ...

  10. Cellular and humoral immunity after infection with B. pertussis : the role of age, antigen and vaccination history

    NARCIS (Netherlands)

    van Twillert, I

    2017-01-01

    Pertussis (whooping cough), is a bacterial disease of the respiratory tract, caused by the human pathogen Bordetella pertussis. Vaccination against pertussis has dramatically lowered pertussis incidence and mortality rates; however pertussis still occurs. The duration of immunity to B. pertussis

  11. Tetanus–diphtheria–acellular pertussis vaccination for adults: an update

    Science.gov (United States)

    2017-01-01

    Although tetanus and diphtheria have become rare in developed countries, pertussis is still endemic in some developed countries. These are vaccine-preventable diseases and vaccination for adults is important to prevent the outbreak of disease. Strategies for tetanus, diphtheria, and pertussis vaccines vary from country to country. Each country needs to monitor consistently epidemiology of the diseases and changes vaccination policies accordingly. Recent studies showed that tetanus–diphtheria–acellular pertussis vaccine for adults is effective and safe to prevent pertussis disease in infants. However, vaccine coverage still remains low than expected and seroprevalence of protective antibodies levels for tetanus, diphtheria, and pertussis decline with aging. The importance of tetanus–diphtheria–acellular pertussis vaccine administration should be emphasized for the protection of young adult and elderly people also, not limited to children. PMID:28168170

  12. Pertussis: herd immunity and vaccination coverage in St Lucia.

    Science.gov (United States)

    Cooper, E; Fitch, L

    1983-11-12

    In a single complete epidemic in St Lucia, an island too small to support constant clinical pertussis, the pertussis case rates in small communities (villages and small towns) with differing levels of vaccination coverage of young children were compared. The association between greater vaccination coverage and greater herd immunity was clear, despite the imperfect protection given to individuals. An analysis in terms of population dynamics is evidence against the theory that endemic subclinical pertussis maintains transmission in a highly vaccinated population. We suggest that with a homogeneous vaccination coverage of 80% of 2-year-old children pertussis might be eradicated from the island, and that this is a practicable experiment.

  13. Pertussis vaccination and whooping cough: and now what?

    Science.gov (United States)

    Guiso, Nicole

    2014-10-01

    Pertussis or whooping cough is a respiratory disease caused by Bordetella pertussis or Bordetella parapertussis that are only known to infect humans. This severe and acute respiratory disease presents epidemic cycles and became a vaccine-preventable disease in the 1940s/1950s when developed countries introduced vaccination. The first type of vaccine developed against this disease was a whole-cell pertussis (wP) vaccine containing inactivated B. pertussis bacteria. Most developed countries produced their own vaccine and given the pediatric nature of the disease at the time of licensure, infants and toddlers were the primary targets and were thus massively vaccinated. The characterization of few virulence factors produced by B. pertussis enabled the development of second-generation pertussis vaccines called the acellular pertussis (aP) vaccines. These only contain 1-5 purified, detoxified B. pertussis proteins and were first introduced in Japan around 30 years ago. Australia, Europe and North America introduced aP vaccines approximately 15 years later, which replaced wP vaccines since then.

  14. Pertussis vaccinations in Dutch children: memory immune responses

    NARCIS (Netherlands)

    Hendrikx, L.H.

    2011-01-01

    Despite high pertussis vaccination coverage, pertussis is reemerging in the Netherlands since 1996. In attempt to improve protection against whooping cough, two major changes in the national immunization program have been made; the introduction of a preschool booster vaccination in children 4 years

  15. Bordetella Pertussis virulence factors in the continuing evolution of whooping cough vaccines for improved performance.

    NARCIS (Netherlands)

    Dorji, Dorji; Mooi, Frits; Yantorno, Osvaldo; Deora, Rajendar; Graham, Ross M; Mukkur, Trilochan K

    Despite high vaccine coverage, whooping cough caused by Bordetella pertussis remains one of the most common vaccine-preventable diseases worldwide. Introduction of whole-cell pertussis (wP) vaccines in the 1940s and acellular pertussis (aP) vaccines in 1990s reduced the mortality due to pertussis.

  16. Tdap Vaccine (Tetanus, Diphtheria and Pertussis): What You Need to Know

    Science.gov (United States)

    ... Tdap Vaccine What You Need to Know (Tetanus, Diphtheria and Pertussis) Many Vaccine Information Statements are available ... immunize. org/ vis 1 Why get vaccinated? Tetanus, diphtheria and pertussis are very serious diseases. Tdap vaccine ...

  17. Complement evasion by Bordetella pertussis: implications for improving current vaccines.

    Science.gov (United States)

    Jongerius, Ilse; Schuijt, Tim J; Mooi, Frits R; Pinelli, Elena

    2015-04-01

    Bordetella pertussis causes whooping cough or pertussis, a highly contagious disease of the respiratory tract. Despite high vaccination coverage, reported cases of pertussis are rising worldwide and it has become clear that the current vaccines must be improved. In addition to the well-known protective role of antibodies and T cells during B. pertussis infection, innate immune responses such as the complement system play an essential role in B. pertussis killing. In order to evade this complement activation and colonize the human host, B. pertussis expresses several molecules that inhibit complement activation. Interestingly, one of the known complement evasion proteins, autotransporter Vag8, is highly expressed in the recently emerged B. pertussis isolates. Here, we describe the current knowledge on how B. pertussis evades complement-mediated killing. In addition, we compare this to complement evasion strategies used by other bacterial species. Finally, we discuss the consequences of complement evasion by B. pertussis on adaptive immunity and how identification of the bacterial molecules and the mechanisms involved in complement evasion might help improve pertussis vaccines.

  18. DTaP Vaccine (Diphtheria, Tetanus, and Pertussis): What You Need to Know

    Science.gov (United States)

    ... STATEMENT DTaP Vaccine What You Need to Know (Diphtheria, Tetanus and Pertussis) Many Vaccine Information Statements are ... www. immunize. org/ vis 1 Why get vaccinated? Diphtheria, tetanus, and pertussis are serious diseases caused by ...

  19. Incompatibility of lyophilized inactivated polio vaccine with liquid pentavalent whole-cell-pertussis-containing vaccine

    NARCIS (Netherlands)

    Kraan, H.; Have, Ten R.; Maas, van der L.; Kersten, G.F.A.; Amorij, J.P.

    2016-01-01

    A hexavalent vaccine containing diphtheria toxoid, tetanus toxoid, whole cell pertussis, Haemophilius influenza type B, hepatitis B and inactivated polio vaccine (IPV) may: (i) increase the efficiency of vaccination campaigns, (ii) reduce the number of injections thereby reducing needlestick

  20. Licensed pertussis vaccines in the United States. History and current state.

    Science.gov (United States)

    Klein, Nicola P

    2014-01-01

    The United States switched from whole cell to acellular pertussis vaccines in the 1990s following global concerns with the safety of the whole cell vaccines. Despite high levels of acellular pertussis vaccine coverage, the United States and other countries are experiencing large pertussis outbreaks. The aim of this article is to describe the historical context which led to acellular pertussis vaccine development, focusing on vaccines currently licensed in the US, and to review evidence that waning protection following licensed acellular pertussis vaccines have been significant factors in the widespread reappearance of pertussis.

  1. [Optimization of the pertussis vaccine production process].

    Science.gov (United States)

    Germán Santiago, J; Zamora, N; de la Rosa, E; Alba Carrión, C; Padrón, P; Hernández, M; Betancourt, M; Moretti, N

    1995-01-01

    The production of Pertussis Vaccine was reevaluated at the Instituto Nacional de Higiene "Rafael Rangel" in order to optimise it in terms of vaccine yield, potency, specific toxicity and efficiency (cost per doses). Four different processes, using two culture media (Cohen-Wheeler and Fermentación Glutamato Prolina-1) and two types of bioreactors (25 L Fermentador Caracas and a 450 L industrial fermentor) were compared. Runs were started from freeze-dried strains (134 or 509) and continued until the obtention of the maximal yield. It was found that the combination Fermentación Glutamato Prolina-1/industrial fermentor, shortened the process to 40 hours while consistently yielding a vaccine of higher potency (7.91 +/- 2.56 IU/human dose) and lower specific toxicity in a mice bioassay. In addition, the physical aspect of the preparation was rather homogeneous and free of dark aggregates. Most importantly, the biomass yield more than doubled those of the Fermentador Caracas using the two different media and that in the industrial fermentor with the Cohen-Wheeler medium. Therefore, the cost per doses was substantially decreased.

  2. Licensed pertussis vaccines in the United States: History and current state

    OpenAIRE

    Klein, Nicola P

    2014-01-01

    The United States switched from whole cell to acellular pertussis vaccines in the 1990s following global concerns with the safety of the whole cell vaccines. Despite high levels of acellular pertussis vaccine coverage, the United States and other countries are experiencing large pertussis outbreaks. The aim of this article is to describe the historical context which led to acellular pertussis vaccine development, focusing on vaccines currently licensed in the US, and to review evidence that w...

  3. Acellular pertussis vaccines--a question of efficacy.

    Science.gov (United States)

    Olin, P

    1995-06-01

    Whole cell pertussis vaccine is considered to offer at least 80% protection against typical whooping cough. The quest for an equally effective but less reactogenic vaccine is now drawing to a close. During the forthcoming year a number of efficacy trials of acellular pertussis vaccines will be terminated. A variety of vaccines containing one, two, three or five purified pertussis antigens are being tested in Germany, Italy, Senegal and Sweden. About 30,000 infants have been enrolled in placebo-controlled studies and more than 100,000 in whole cell vaccine-controlled trials. The final plans for analysis of a Swedish placebo-controlled trial of whole cell and acellular vaccines is presented. Due to the unexpected high incidence of pertussis in Sweden during 1993-1994, relative risk comparisons between vaccines will be attempted in that trial, in addition to estimating absolute efficacy. A crucial issue is to what extent data may be compared between trials, given differences in design, vaccination schedules, and chosen endpoints. A primary case definition of laboratory-confirmed pertussis with at least 21 days of paroxysmal cough have been adopted in most trials. Pre-planned meta-analysis using this single endpoint will facilitate comparisons between vaccines. Serological correlates to protection in individuals will be sought in the ongoing placebo-controlled trials. The concept of a serological correlate valid for a vaccinated population but not necessarily for the vaccinated individual, as is the case with Hib vaccines, may turn out to be the only alternative to performing large efficacy trials in the future.

  4. Pertussis-associated persistent cough in previously vaccinated children.

    Science.gov (United States)

    Principi, Nicola; Litt, David; Terranova, Leonardo; Picca, Marina; Malvaso, Concetta; Vitale, Cettina; Fry, Norman K; Esposito, Susanna

    2017-11-01

    To evaluate the role of Bordetella pertussis infection, 96 otherwise healthy 7- to 17-year-old subjects who were suffering from a cough lasting from 2 to 8 weeks were prospectively recruited. At enrolment, a nasopharyngeal swab and an oral fluid sample were obtained to search for pertussis infection by the detection of B. pertussis DNA and/or an elevated titre of anti-pertussis toxin IgG. Evidence of pertussis infection was found in 18 (18.7 %; 95 % confidence interval, 11.5-28.0) cases. In 15 cases, the disease occurred despite booster administration. In two cases, pertussis was diagnosed less than 2 years after the booster injection, whereas in the other cases it was diagnosed between 2 and 9 years after the booster dose. This study used non-invasive testing to show that pertussis is one of the most important causes of long-lasting cough in school-age subjects. Moreover, the protection offered by acellular pertussis vaccines currently wanes more rapidly than previously thought.

  5. New Data on Vaccine Antigen Deficient Bordetella pertussis Isolates

    Directory of Open Access Journals (Sweden)

    Valérie Bouchez

    2015-09-01

    Full Text Available Evolution of Bordetella pertussis is driven by natural and vaccine pressures. Isolates circulating in regions with high vaccination coverage present multiple allelic and antigenic variations as compared to isolates collected before introduction of vaccination. Furthermore, during the last epidemics reported in regions using pertussis acellular vaccines, isolates deficient for vaccine antigens, such as pertactin (PRN, were reported to reach high proportions of circulating isolates. More sporadic filamentous hemagglutinin (FHA or pertussis toxin (PT deficient isolates were also collected. The whole genome of some recent French isolates, deficient or non-deficient in vaccine antigens, were analyzed. Transcription profiles of the expression of the main virulence factors were also compared. The invasive phenotype in an in vitro human tracheal epithelial (HTE cell model of infection was evaluated. Our genomic analysis focused on SNPs related to virulence genes known to be more likely to present allelic polymorphism. Transcriptomic data indicated that isolates circulating since the introduction of pertussis vaccines present lower transcription levels of the main virulence genes than the isolates of the pre-vaccine era. Furthermore, isolates not producing FHA present significantly higher expression levels of the entire set of genes tested. Finally, we observed that recent isolates are more invasive in HTE cells when compared to the reference strain, but no multiplication occurs within cells.

  6. Identifying long-term memory B-cells in vaccinated children despite waning antibody levels specific for Bordetella pertussis proteins

    NARCIS (Netherlands)

    Hendrikx, Lotte H.; Ozturk, Kemal; de Rond, Lia G. H.; Veenhoven, Reinier H.; Sanders, Elisabeth A. M.; Berbers, Guy A. M.; Buisman, Anne-Marie

    2011-01-01

    Whooping cough is a respiratory disease caused by Bordetella pertussis. Since the 1950s in developed countries pertussis vaccinations are included in the national immunization program. However, antibody levels rapidly wane after both whole cell and acellular pertussis vaccination. Therefore

  7. Dynamic models for health economic assessments of pertussis vaccines : what goes around comes around ...

    NARCIS (Netherlands)

    Rozenbaum, M.H.; De Cao, E.; Westra, T.A.; Postma, M.J.

    2012-01-01

    Despite childhood vaccination programs, pertussis remains endemic. To reduce the burden of pertussis, various extended pertussis vaccination strategies have been suggested. The aim of this article is to evaluate dynamic models used to assess the cost-effectiveness of vaccination. In total, 16

  8. Reduction of Direct Health Costs Associated with Pertussis Vaccination with Acellular Vaccines in Children Aged 0-9 Years with Pertussis in Catalonia (Spain).

    Science.gov (United States)

    Plans-Rubió, Pedro; Navas, Encarna; Godoy, Pere; Carmona, Gloria; Domínguez, Angela; Jané, Mireia; Muñoz-Almagro, Carmen; Brotons, Pedro

    2018-05-14

    The aim of this study was to assess direct health costs in children with pertussis aged 0-9 years who were vaccinated, partially vaccinated, and unvaccinated during childhood, and to assess the association between pertussis costs and pertussis vaccination in Catalonia (Spain) in 2012-2013. Direct healthcare costs included pertussis treatment, pertussis detection, and preventive chemotherapy of contacts. Pertussis patients were considered vaccinated when they had received 4-5 doses, and unvaccinated or partially vaccinated when they had received 0-3 doses of vaccine. The Chi square test and the odds ratios were used to compare percentages and the t test was used to compare mean pertussis costs in different groups, considering a p case after taking into account the effect of other study variables, and €200 per case after taking into account pertussis severity. Direct healthcare costs were lower in children with pertussis aged 0-9 years vaccinated with 4-5 doses of acellular vaccines than in unvaccinated or partially vaccinated children with pertussis of the same age.

  9. Community awareness and predictors of uptake of pertussis booster vaccine in South Australian adults.

    Science.gov (United States)

    Clarke, Michelle; Thomas, Natalie; Giles, Lynne; Marshall, Helen

    2015-12-16

    Pertussis is a highly virulent vaccine preventable disease that remains a global challenge. This study aimed to assess community knowledge of pertussis infection as well as awareness and uptake of adult pertussis booster vaccine. A cross-sectional survey was conducted of randomly selected households in South Australia by Computer Assisted Telephone Interviews in 2011. Survey data were weighted to the age, gender and geographical area profile of the population. From 3124 randomly sampled contactable households, 1967 interviews were conducted (participation rate 63%) with individuals aged 18-93 years, including 608 parents of children aged pertussis (whooping cough) and 18% reported that a household member had previously contracted whooping cough infection. Most respondents considered whooping cough to be highly contagious (73%) and severe for infants (89%). Over half (51%) of those surveyed were aware that family members commonly transmit pertussis to infants. Despite high knowledge, pertussis vaccine uptake was low, with only 10% of respondents reporting pertussis vaccination in the previous five years. Whilst 61% of respondents were aware of the availability of an adult pertussis booster vaccine, only 8% (n=154) reported their Family Physician had discussed it with them. If provided free, 77% agreed that they would be more likely to accept a booster pertussis vaccination. Independent predictors of recent pertussis vaccination included higher education, larger household size, perception of greater disease severity for infants and discussion with a Family Physician about pertussis vaccination. Whilst knowledge regarding transmission and severity of Bordetella pertussis was high, uptake of pertussis vaccination for adults is remarkably low amongst the South Australian community. Improved awareness regarding the availability of a booster pertussis vaccine through Family Physicians and/or provision of funded pertussis vaccination for adults has the potential to improve

  10. Your Child's Immunizations: Diphtheria, Tetanus & Pertussis Vaccine (DTaP)

    Science.gov (United States)

    ... Safe Videos for Educators Search English Español Your Child's Immunizations: Diphtheria, Tetanus & Pertussis Vaccine (DTaP) KidsHealth / For ... child outweigh the potential risks. Caring for Your Child After DTaP Immunization Your child may have a ...

  11. Diphtheria, tetanus, and pertussis (DTaP) vaccines - what you need to know

    Science.gov (United States)

    ... is taken in its entirety from the CDC Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine Information Statement (VIS): ... vis-statements/dtap.html CDC review information for Diphtheria, Tetanus, and Pertussis (DTaP) VIS: Page last reviewed: ...

  12. Bordetella pertussis, B. parapertussis, vaccines and cycles of whooping cough.

    Science.gov (United States)

    Bouchez, Valérie; Guiso, Nicole

    2015-10-01

    Whooping cough is a vaccine-preventable disease due to Bordetella pertussis and B. parapertussis. This highly contagious respiratory disease occurs through epidemic cycles every 3-5 years and vaccination did not change this frequency. Models suggest that the cyclic increase of susceptibles is linked to demographic differences and different vaccine coverage. However, differences in surveillance of the disease as well as adaptation of the agents of the disease to their human hosts and to vaccine pressure might also play an important role. These parameters are discussed in this review. © FEMS 2015. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. Tdap (tetanus, diphtheria, pertussis) Vaccine and Pregnancy

    Science.gov (United States)

    ... Can I receive the Tdap vaccine while breastfeeding? Yes. Noninfectious vaccines like Tdap are compatible with breastfeeding. If you get the vaccine while breastfeeding, it can help prevent you from getting sick and passing the illness to your baby. ...

  14. Assessing determinants of the intention to accept a pertussis cocooning vaccination: A survey among Dutch parents.

    Science.gov (United States)

    Visser, Olga; Kraan, Janneke; Akkermans, Reinier; Ruiter, Robert A C; van der Velden, Koos; Hautvast, Jeannine L A; Hulscher, Marlies E J L

    2016-09-07

    Pertussis cocooning is one of the strategies aiming to prevent the potential harm of pertussis in infants by vaccinating (among others) their parents. Several countries adopted this strategy, but uptake is a problem. Determinants of parental uptake are important in the design of an effective vaccination programme. Therefore, this study aims to assess parents' intention to accept a pertussis cocooning vaccination and its determinants. A 98 item questionnaire was developed based on a theoretical framework, assessing parents' intention to accept a pertussis cocooning vaccination and its personal and psychosocial determinants. In addition, beliefs underlying parents' attitude towards pertussis cocooning vaccination were assessed. Both logistic and linear regression analysis were used to assess univariate and multivariate associations amongst study variables. Parents returned 282 questionnaires. The majority of the parents (78%) reported a positive intention to accept a pertussis cocooning vaccination. Attitude (OR 6.6, pexpectations (β 0.15, p.011) were significant correlates of attitude towards pertussis cocooning vaccination. The parental intention to accept a pertussis cocooning vaccination in this study is rather high. Targeting the identified determinants of parents' acceptance in a pertussis cocooning vaccination programme is crucial to secure that intention is translated into actual vaccination uptake. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Persistence of pertussis immunity in children and adults : Influence of priming vaccination

    NARCIS (Netherlands)

    Lee, Saskia van der

    2018-01-01

    Pertussis, or whooping cough, is a highly contagious infection of the upper respiratory tract and may cause severe clinical disease, particularly in young unvaccinated infants. Despite a consistent high pertussis vaccination coverage, pertussis re-emerged in the late 1990s, with cyclic outbreaks

  16. Attitudes, knowledge and perceptions towards whooping cough and pertussis vaccine in hospitalized adults.

    Science.gov (United States)

    Ridda, Iman; Gao, Zhanhai; Macintyre, C Raina

    2014-02-19

    Whooping cough or pertussis is a major cause of morbidity and mortality for adults and children around the world. There has been a rise in pertussis-related deaths in the elderly; pertussis vaccination is not currently routinely recommended in adults, excepting new parents and other adults household members including grandparents and care-givers of young children. Currently, there is lack of clear vaccine recommendations after the age of 50 years. Given the increase in adult pertussis, adult vaccine recommendations are a policy consideration. The study surveyed a convenience sample of patients previously recruited in a case control study designed to examine the burden of influenza with and without AMI in adults aged ≥ 40 years. Our findings showed that only 9.6% had received the pertussis vaccination within the past five years and 79.4% of participants had no knowledge of the pertussis adult booster vaccine, and 30.7% of participants who had regular contact with children under the age of two years in the past 12 months. The results showed that even though there is general acceptance of prevention by vaccines, there is low awareness about pertussis vaccination. This lack of knowledge presents a barrier against pertussis vaccination thus it is imperative that any future adult immunisation policy recommendations around pertussis vaccine include awareness programs in the target population. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Intention to Accept Pertussis Vaccination for Cocooning: A Qualitative Study of the Determinants.

    Directory of Open Access Journals (Sweden)

    Olga Visser

    Full Text Available Several countries have reported a resurgence of pertussis in the last decades. This puts infants (especially <6 months at risk of severe complications, because they are too young to be fully protected by vaccination. The global pertussis initiative has proposed pertussis vaccination of young infants' close contacts, in order to reduce pertussis transmission and the burden of the disease on infants. Our aim is to explore the perceived determinants (barriers and facilitators of intention to accept vaccination among the possible target groups of pertussis vaccination for cocooning. Consideration of these determinants is necessary to optimise the uptake of the vaccination.We conducted 13 focus groups and six individual semi-structured interviews with members of possible target groups for pertussis cocooning (i.e. parents, maternity assistants, midwives, and paediatric nurses in the Netherlands. Here, both maternal pertussis vaccination as well as pertussis cocooning has not been implemented. The topic list was based on a literature review and a barrier framework. All interviews were transcribed verbatim and two researchers performed thematic content analysis.The participants' risk perception, outcome expectations, general vaccination beliefs, moral norms, opinion of others, perceived autonomy, anticipated regret, decisional uncertainty, and perceived organisational barriers were all factors that influenced the intention to accept pertussis vaccination for cocooning.This study has identified nine perceived determinants that influence the intention to accept pertussis cocooning vaccination. We add the following determinants to the literature: perceived cost-effectiveness (as a concept of outcome expectations, justice (as a concept of moral norms, anticipated regret, and decisional uncertainty. We recommend considering these determinants in vaccination programmes for pertussis cocooning vaccination. Experience, information and trust emerged as

  18. Maternal Vaccination With a Monocomponent Pertussis Toxoid Vaccine Is Sufficient to Protect Infants in a Baboon Model of Whooping Cough.

    Science.gov (United States)

    Kapil, Parul; Papin, James F; Wolf, Roman F; Zimmerman, Lindsey I; Wagner, Leslie D; Merkel, Tod J

    2018-03-28

    Bordetella pertussis is a human pathogen responsible for serious respiratory illness. The disease is most severe in infants too young to be vaccinated with most hospitalizations and deaths occurring within this age group. The Advisory Committee on Immunization Practices recommended immunization of pregnant women to protect infants from birth until their first vaccination at 6-8 weeks of age. We previously demonstrated that maternal vaccination with licensed acellular pertussis vaccines protected newborn baboons from disease. We hypothesized that protection was due to toxin-neutralizing, maternal anti-pertussis toxin antibodies and predicted that maternal vaccination with a pertussis toxoid (PTx)-only vaccine would protect newborns from disease. Infant baboons born to unvaccinated mothers or mothers vaccinated with a PTx-only vaccine were challenged with B. pertussis at 5 weeks of age and followed for infection and signs of disease. Although all challenged infants were heavily colonized, the infant baboons born to mothers vaccinated with PTx-only vaccine were free from clinical disease following exposure to B. pertussis. In contrast, disease was observed in infants born to unvaccinated mothers. Our results demonstrated that maternal vaccination with a PTx-only vaccine is sufficient to protect newborn baboons from disease following exposure to pertussis.

  19. Subclinical pertussis in incompletely vaccinated and unvaccinated ...

    African Journals Online (AJOL)

    subclinical whooping cough) does in fact occur. Recent studies have shown subclinical disease in vaccinated infants ... through home visits by a community health nurse with ..... The current study extends the knowledge of contagious spread of ...

  20. Pertussis.

    NARCIS (Netherlands)

    Maas, N.A.T. van der; Kemmeren, J.M.; Lugner, A.K.; Suijkerbuijk, A.W.M.; Donker, G.A.; Buisman, A.; Berbers, G.A.M.; Els, C.A.C.M. van; Melker, H.E. de; Mooi, F.R.

    2014-01-01

    In 2012, a large pertussis epidemic occurred with the highest number of notified cases since the introduction of notifications in 1976. Data on GP consultations and hospitalisations from 2012 also showed an increase. In the first six months of 2013 the incidence of pertussis notifications was found

  1. Evidence of Bordetella pertussis infection in vaccinated 1-year-old Danish children

    DEFF Research Database (Denmark)

    von Linstow, Marie-Louise; Pontoppidan, Peter Lotko; von König, Carl-Heinz Wirsing

    2010-01-01

    We measured IgA and IgG antibodies to pertussis toxin (PT) and filamentous hemagglutinin (FHA) in sera from 203 1-year-old children who had received one to three doses of a monocomponent PT toxoid vaccine. Ten children (5%) had IgA antibody to PT indicating recent infection; seven of these children......%. The apparent high Bordetella pertussis infection rate in Danish infants suggests that the monocomponent PT toxoid vaccine used in Denmark has limited efficacy against B. pertussis infection. A prospective immunization study comparing a multi-component vaccine with the present monocomponent PT toxoid vaccine...

  2. Does whole-cell pertussis vaccine protect black South African infants?

    African Journals Online (AJOL)

    The whole-cell pertussis vaccine currently used in South Africa has not been adequately evaluated for post-vaccination events and immunogenicity. A trial of this vaccine combined with diphtheria and tetanus toxoids (DTP) was undertaken in 115 black babies who received primary vaccination at 2, 4 and 6 months of age.

  3. Intention to Accept Pertussis Vaccination for Cocooning: A Qualitative Study of the Determinants.

    Science.gov (United States)

    Visser, Olga; Hautvast, Jeannine L A; van der Velden, Koos; Hulscher, Marlies E J L

    2016-01-01

    Several countries have reported a resurgence of pertussis in the last decades. This puts infants (especially organisational barriers were all factors that influenced the intention to accept pertussis vaccination for cocooning. This study has identified nine perceived determinants that influence the intention to accept pertussis cocooning vaccination. We add the following determinants to the literature: perceived cost-effectiveness (as a concept of outcome expectations), justice (as a concept of moral norms), anticipated regret, and decisional uncertainty. We recommend considering these determinants in vaccination programmes for pertussis cocooning vaccination. Experience, information and trust emerged as predominant themes within these determinants. These themes require particular attention in future research on vaccination acceptance, especially with regard to their role in use and implementation in policy and practice.

  4. Assessing determinants of the intention to accept a pertussis cocooning vaccination: A survey among Dutch parents

    NARCIS (Netherlands)

    Visser, O.; Kraan, J.; Akkermans, R.P.; Ruiter, R.A.; Velden, K. van der; Hautvast, J.L.A.; Hulscher, M.E.J.L.

    2016-01-01

    INTRODUCTION: Pertussis cocooning is one of the strategies aiming to prevent the potential harm of pertussis in infants by vaccinating (among others) their parents. Several countries adopted this strategy, but uptake is a problem. Determinants of parental uptake are important in the design of an

  5. Whole-cell or acellular pertussis vaccination in infancy determines IgG subclass profiles to DTaP booster vaccination.

    NARCIS (Netherlands)

    van der Lee, Saskia; Sanders, Elisabeth A M; Berbers, Guy A M; Buisman, Anne-Marie

    2018-01-01

    Duration of protection against pertussis is shorter in adolescents who have been immunized with acellular pertussis (aP) in infancy compared with adolescents who received whole-cell pertussis (wP) vaccines in infancy, which is related to immune responses elicited by these priming vaccines. To better

  6. Risk of Brain Damage Following Pertussis Immunization with Whole-Cell cf Acellular Vaccines

    Directory of Open Access Journals (Sweden)

    J Gordon Millichap

    2004-06-01

    Full Text Available Serious neurological disorders reported following whole-cell (WC in comparison to acellular (AC pertussis vaccines (PV were evaluated by the Genetic Centers of America, Silver Spring, MD.

  7. Genotypic characterization by multi locus variable number of tandem repeats analysis international Bordetella pertussis vaccine strains

    Directory of Open Access Journals (Sweden)

    M. Fatah Moghadam

    2017-10-01

    Full Text Available Background: In 1930's first whole cell pertussis vaccines became available to the public heralding a dramatic success in overcoming the global burden of the disease. To date only a handful of B. pertussis strains have been used by international/local pertussis vaccine manufacturers. Inevitable well-documented genetic changes in the world population of this pathogen have prompted serious questions on suitability of traditional vaccine strains protect human against currently circulating wild isolates of Bordetella pertussis. Objective: Analyzing the genetic diversity within the most frequently-used vaccine strains of B. pertussis in the world Methods: A recently developed multi locus variable number of tandem repeats analysis (MLVA genotyping system along with a bioinforamtic piece of analysis was conducted on 11 strain / substrains of B137, B203 (10536, C393, Cs, E476, Tohama I, J445 (134, B202 and J446 (509 plus 2 sub-strains of 134 and 509 that are used at Razi institute for preparation of pertussis vaccine. In this study have used 6 individual loci of VNTR1, VNTR3a, VNTR3b, VNTR4, VNTR5 and VNTR6. Findings: Six distinct genotypes were recognized among the examined strains by comparing our data with the Dutch MLVA databank. These were all new and not reported before in the database. Conclusion: This observation reiterates on necessity for detection of predominant native strains to include in vaccine preparations suitable for different countries.

  8. Cost-Effectiveness Analysis of Various Pertussis Vaccination Strategies Primarily Aimed at Protecting Infants in the Netherlands

    NARCIS (Netherlands)

    Westra, Tjalke A.; de Vries, Robin; Tamminga, Johannes J.; Sauboin, Christophe J.; Postma, Maarten J.

    Background: Pertussis is a highly contagious respiratory disease. Despite a high rate of vaccine coverage through the Dutch national immunization program, the incidence of pertussis remains high in the Netherlands and the risk of infection continues. Because pertussis is most severe in unimmunized

  9. Different IgG-subclass distributions after whole-cell and acellular pertussis infant primary vaccinations in healthy and pertussis infected children

    NARCIS (Netherlands)

    Hendrikx, Lotte H.; Schure, Rose-Minke; Ozturk, Kemal; de Rond, Lia G. H.; de Greeff, S. C.; Sanders, Elisabeth A. M.; Berbers, Guy A. M.; Buisman, Anne-Marie

    2011-01-01

    The distribution of IgG-subclasses provides insight in the immunological mechanisms of protection against whooping cough. We investigated the effect of Dutch whole-cell pertussis and acellular pertussis vaccines administered in infancy on the IgG-subclass distributions in healthy children aged 12

  10. Evidence of Bordetella pertussis infection in vaccinated 1-year-old Danish children

    DEFF Research Database (Denmark)

    von Linstow, Marie-Louise; Pontoppidan, Peter Lotko; von König, Carl-Heinz Wirsing

    2010-01-01

    We measured IgA and IgG antibodies to pertussis toxin (PT) and filamentous hemagglutinin (FHA) in sera from 203 1-year-old children who had received one to three doses of a monocomponent PT toxoid vaccine. Ten children (5%) had IgA antibody to PT indicating recent infection; seven of these children...... had received three doses of vaccine. PT IgA responders did not have significantly longer coughing episodes than PT IgA non-responders. Since an IgA antibody response occurs in only approximately 50% of infected children, the actual infection rate in our cohort is estimated to approximately 10......%. The apparent high Bordetella pertussis infection rate in Danish infants suggests that the monocomponent PT toxoid vaccine used in Denmark has limited efficacy against B. pertussis infection. A prospective immunization study comparing a multi-component vaccine with the present monocomponent PT toxoid vaccine...

  11. Whole-cell or acellular pertussis vaccination in infancy determines IgG subclass profiles to DTaP booster vaccination

    NARCIS (Netherlands)

    van der Lee, Saskia; Sanders, Elisabeth A.M.; Berbers, Guy A M; Buisman, Anne-Marie

    2018-01-01

    Introduction Duration of protection against pertussis is shorter in adolescents who have been immunized with acellular pertussis (aP) in infancy compared with adolescents who received whole-cell pertussis (wP) vaccines in infancy, which is related to immune responses elicited by these priming

  12. Examining the role of different age groups, and of vaccination during the 2012 Minnesota pertussis outbreak

    Science.gov (United States)

    Worby, Colin J.; Kenyon, Cynthia; Lynfield, Ruth; Lipsitch, Marc; Goldstein, Edward

    2015-01-01

    There is limited information on the roles of different age groups during pertussis outbreaks. Little is known about vaccine effectiveness against pertussis infection (both clinically apparent and subclinical), which is different from effectiveness against reportable pertussis disease, with the former influencing the impact of vaccination on pertussis transmission in the community. For the 2012 pertussis outbreak in Minnesota, we estimated odds ratios for case counts in pairs of population groups before vs. after the epidemic’s peak. We found children aged 11–12y, 13–14y and 8–10y experienced the greatest rates of depletion of susceptible individuals during the outbreak’s ascent, with all ORs for each of those age groups vs. groups outside this age range significantly above 1, with the highest ORs for ages 11–12y. Receipt of the fifth dose of DTaP was associated with a decreased relative role during the outbreak’s ascent compared to non-receipt [OR 0.16 (0.01, 0.84) for children aged 5, 0.13 (0.003, 0.82) for ages 8–10y, indicating a protective effect of DTaP against pertussis infection. No analogous effect of Tdap was detected. Our results suggest that children aged 8–14y played a key role in propagating this outbreak. The impact of immunization with Tdap on pertussis infection requires further investigation. PMID:26278132

  13. [Pertussis vaccination in pregnancy: Security and effectiveness in the protection of the infant].

    Science.gov (United States)

    Villena, Rodolfo; Vidal, Pamela; Carrillo, Felipe; Salinas, Mónica

    2017-06-01

    Whooping cough is an immune preventable disease that can be life threatening. Despite infant immunization starting at 2 month of age, there are many cases and outbreaks in our country and also around the world, with a high risk of mortality specially in infants under 6 month of age. It has been proposed that antenatal vaccination with acellular pertussis component (Tdap) would be useful, safe and effective since it transfers a high antibody rate to the child, reducing the incidence of pertussis in this group by 85%. No higher incidence of adverse effects has been found in pregnant women with this vaccine. This strategy has been implemented in several developed and Latin American countries. The purpose of this manuscript is to review and discuss the benefits of antenatal vaccination with Tdap. It was concluded that maternal immunization with Tdap vaccine should be promoted to prevent infection and associated mortality in the less than 6 months of age by Bordetella pertussis.

  14. Global Population Structure and Evolution of Bordetella pertussis and Their Relationship with Vaccination

    Science.gov (United States)

    Bart, Marieke J.; Harris, Simon R.; Advani, Abdolreza; Arakawa, Yoshichika; Bottero, Daniela; Bouchez, Valérie; Cassiday, Pamela K.; Chiang, Chuen-Sheue; Dalby, Tine; Fry, Norman K.; Gaillard, María Emilia; van Gent, Marjolein; Guiso, Nicole; Hallander, Hans O.; Harvill, Eric T.; He, Qiushui; van der Heide, Han G. J.; Heuvelman, Kees; Hozbor, Daniela F.; Kamachi, Kazunari; Karataev, Gennady I.; Lan, Ruiting; Lutyńska, Anna; Maharjan, Ram P.; Mertsola, Jussi; Miyamura, Tatsuo; Octavia, Sophie; Preston, Andrew; Quail, Michael A.; Sintchenko, Vitali; Stefanelli, Paola; Tondella, M. Lucia; Tsang, Raymond S. W.; Xu, Yinghua; Yao, Shu-Man; Zhang, Shumin; Mooi, Frits R.

    2014-01-01

    ABSTRACT Bordetella pertussis causes pertussis, a respiratory disease that is most severe for infants. Vaccination was introduced in the 1950s, and in recent years, a resurgence of disease was observed worldwide, with significant mortality in infants. Possible causes for this include the switch from whole-cell vaccines (WCVs) to less effective acellular vaccines (ACVs), waning immunity, and pathogen adaptation. Pathogen adaptation is suggested by antigenic divergence between vaccine strains and circulating strains and by the emergence of strains with increased pertussis toxin production. We applied comparative genomics to a worldwide collection of 343 B. pertussis strains isolated between 1920 and 2010. The global phylogeny showed two deep branches; the largest of these contained 98% of all strains, and its expansion correlated temporally with the first descriptions of pertussis outbreaks in Europe in the 16th century. We found little evidence of recent geographical clustering of the strains within this lineage, suggesting rapid strain flow between countries. We observed that changes in genes encoding proteins implicated in protective immunity that are included in ACVs occurred after the introduction of WCVs but before the switch to ACVs. Furthermore, our analyses consistently suggested that virulence-associated genes and genes coding for surface-exposed proteins were involved in adaptation. However, many of the putative adaptive loci identified have a physiological role, and further studies of these loci may reveal less obvious ways in which B. pertussis and the host interact. This work provides insight into ways in which pathogens may adapt to vaccination and suggests ways to improve pertussis vaccines. PMID:24757216

  15. Pharmacists’ Attitudes and Practices Regarding Tetanus, Diphtheria and Pertussis (Tdap Vaccination in Pregnancy and Surrounding Newborns

    Directory of Open Access Journals (Sweden)

    Christine A Echtenkamp

    2018-04-01

    Full Text Available Background: Bordetella pertussis or whooping cough is a serious and vaccine-preventable illness. Despite widespread vaccination in the pediatric population, pertussis still infects approximately 100,000 infants each year in the United States. The purpose of this study was to determine gaps in pharmacists’ understanding, attitudes, practices, and barriers surrounding the tetanus, diphtheria, and pertussis (Tdap vaccination recommendation for patients who are pregnant or planning to come in close contact with infants. Methods: This study was a descriptive, exploratory electronic survey. The survey assessed three major areas; the role of the pharmacist in Tdap vaccination, perceived barriers to vaccination, and understanding the recommendations. Results: A total of 225 pharmacists responded to the survey. Pharmacists who responded to this survey agreed that pharmacists should have a role vaccinating the public and individuals expecting to come into contact with a newborn, (88.5% and 86.9% respectively, but fewer agreed that pharmacists should have a role vaccinating pregnant women against tetanus, diphtheria, and pertussis (77%, p < 0.001. Based on the responses to case scenarios, only 22.5% and 30.6% of respondents understood the recommendations. Numerous barriers to vaccinating pregnant women were identified. Conclusion: While most pharmacists surveyed felt they should have a role in vaccinating pregnant women and those expecting to come in contact with a newborn, there are barriers to implementing this practice. Future efforts should focus on further evaluating identified gaps and developing programs for pharmacists that emphasize the significance of vaccinating these patients to reduce the burden of pertussis in infants.

  16. Influence of maternal vaccination against diphtheria, tetanus, and pertussis on the avidity of infant antibody responses to a pertussis containing vaccine in Belgium.

    Science.gov (United States)

    Caboré, Raïssa Nadège; Maertens, Kirsten; Dobly, Alexandre; Leuridan, Elke; Van Damme, Pierre; Huygen, Kris

    2017-10-03

    Maternal antibodies induced by vaccination during pregnancy cross the placental barrier and can close the susceptibility gap to pertussis in young infants up to the start of primary immunization. As not only the quantity but also the quality of circulating antibodies is important for protection, we assessed whether maternal immunization affects the avidity of infant vaccine-induced IgG antibodies, in the frame of a prospective clinical trial on pregnancy vaccination in Belgium. Infants born from Tdap (Boostrix®) vaccinated (N = 55) and unvaccinated (N = 26) mothers were immunized with a hexavalent pertussis containing vaccine (Infanrix Hexa®) at 8, 12 and 16 weeks, followed by a fourth dose at 15 months of age. Right before and one month after this fourth vaccine dose, the avidity of IgG antibodies against diphtheria toxin (DT), tetanus toxin (TT), pertussis toxin (PT), filamentous hemagglutinin (FHA) and pertactin (Prn) was determined using 1.5 M ammonium thiocyanate as dissociating agent. In both groups, antibody avidity was moderate for TT, PT, FHA and Prn and low for DT after priming. After a fourth dose, antibody avidity increased significantly to high avidity for TT and PT, whereas it remained moderate for FHA and Prn and low for DT. The avidity correlated positively with antibody level in both study groups, yet not significantly for PT. When comparing both study groups, only PT-specific antibodies showed significantly lower avidity in infants born from vaccinated than from unvaccinated mothers after the fourth vaccine dose. The clinical significance of lower avidity of vaccine induced infant antibodies after maternal vaccination, if any, needs further investigation.

  17. Resurgence of pertussis at the age of vaccination: clinical, epidemiological, and molecular aspects

    Directory of Open Access Journals (Sweden)

    Rosângela S.L.A. Torres

    2015-08-01

    Full Text Available OBJECTIVE: Report the incidence, epidemiology, clinical features, death, and vaccination status of patients with whooping cough and perform genotypic characterization of isolates of B. pertussis identified in the state of Paraná, during January 2007 to December 2013.METHODS: Cross-sectional study including 1,209 patients with pertussis. Data were obtained through the Notifiable Diseases Information System (Sistema de Informação de Agravos de Notificação - SINAN and molecular epidemiology was performed by repetitive sequence-based polymerase chain reaction (rep-PCR; DiversiLab(r, bioMerieux, France.RESULTS: The incidence of pertussis in the state of Paraná increased sharply from 0.15-0.76 per 100,000 habitants between 2007-2010 to 1.7-4.28 per 100,000 between 2011-2013. Patients with less than 1 year of age were more stricken (67.5%. Fifty-nine children (5% developed pertussis even after receiving three doses and two diphtheria-tetanus-pertussis (DTP boosters vaccine. The most common complications were pneumonia (14.5%, otitis (0.9%, and encephalopathy (0.7%. Isolates of B. pertussis were grouped into two groups (G1 and G2 and eight distinct patterns (G1: P1-P5 and G2: P6-P8.CONCLUSION: The resurgence of pertussis should stimulate new research to develop vaccines with greater capacity of protection against current clones and also encourage implementation of new strategies for vaccination in order to reduce the risk of disease in infants.

  18. Effect of different forms of adenylate cyclase toxin of Bordetella pertussis on protection afforded by an acellular pertussis vaccine in a murine model.

    Science.gov (United States)

    Cheung, Gordon Y C; Xing, Dorothy; Prior, Sandra; Corbel, Michael J; Parton, Roger; Coote, John G

    2006-12-01

    Four recombinant forms of the cell-invasive adenylate cyclase toxin (CyaA) of Bordetella pertussis were compared for the ability to enhance protection against B. pertussis in mice when coadministered with an acellular pertussis vaccine (ACV). The four forms were as follows: fully functional CyaA, a CyaA form lacking adenylate cyclase enzymatic activity (CyaA*), and the nonacylated forms of these toxins, i.e., proCyaA and proCyaA*, respectively. None of these forms alone conferred significant (P > 0.05) protection against B. pertussis in a murine intranasal challenge model. Mice immunized with ACV alone showed significant (P protection was only significant (P protection provided by CyaA* was due to an augmentation of both Th1 and Th2 immune responses to B. pertussis antigens.

  19. Pertussis infections and vaccinations in Bolivia, Brazil and Mexico from 1980 to 2009.

    Science.gov (United States)

    McCormick, Colleen M; Czachor, John S

    2013-01-01

    Global coverage with three doses of the diphtheria, tetanus and pertussis vaccine (DTP3) increased from less than 5% in 1974 to 82% in 2009 due to worldwide focus on universal vaccination. Nonetheless, pertussis remains the fifth-leading cause of vaccine-preventable deaths. This study examines DTP3 vaccination from 1980 through 2009 in three countries within Latin America, Bolivia, Brazil and Mexico, selected for their distinct health care systems and vaccination strategies. Similar to global trends, these nations have achieved dramatic improvements in pertussis immunization. In Bolivia, immunization rates increased from 11% to 85%; in Brazil, rates increased from 37% to 97%; and in Mexico, the immunization rates increased from 44% to 72%. Pertussis infections have concomitantly decreased from 1980 to 2009. In Bolivia, cases decreased from 44.4 per 100,000 people to zero reported cases. In Brazil, the incidence decreased from 37.6 to 0.5 cases per 100,000. The incidence in Mexico decreased from 8.2 to 0.5 cases per 100,000. In order to increase vaccination rates further, health systems must continue to raise awareness about disease prevention, expand health surveillance systems, and improve access to health services. Copyright © 2013 Elsevier Ltd. All rights reserved.

  20. A randomised, double-blind, non-inferiority clinical trial on the safety and immunogenicity of a tetanus, diphtheria and monocomponent acellular pertussis (TdaP) vaccine in comparison to a tetanus and diphtheria (Td) vaccine when given as booster vaccinations to healthy adults

    DEFF Research Database (Denmark)

    Thierry-Carstensen, Birgit; Jordan, Karina; Uhlving, Hilde Hylland

    2012-01-01

    Increasing incidence of pertussis in adolescents and adults has stimulated the development of safe and immunogenic acellular pertussis vaccines for booster vaccination of adolescents and adults.......Increasing incidence of pertussis in adolescents and adults has stimulated the development of safe and immunogenic acellular pertussis vaccines for booster vaccination of adolescents and adults....

  1. Low seroprevalence of diphtheria, tetanus and pertussis in ambulatory adult patients: the need for lifelong vaccination.

    Science.gov (United States)

    Tanriover, Mine Durusu; Soyler, Canan; Ascioglu, Sibel; Cankurtaran, Mustafa; Unal, Serhat

    2014-07-01

    Tetanus, diphtheria, pertussis and measles are vaccine preventable diseases that have been reported to cause morbidity and mortality in adult population in the recent years. We aimed to document the seropositivity rates and vaccination indication for these four vaccine preventable diseases among adult and elderly patients who were seen as outpatients in a university hospital. Blood samples for tetanus, diphtheria, pertussis and measles antibodies were obtained. Results were evaluated with regards to protection levels and booster vaccine indications according to the cut-off values. A total of 1367 patients consented for the study and 1303 blood samples were available for analysis at the end of the study. The antibody levels against measles conferred protection in 98% of patients. However, 65% of the patients had no protection for diphtheria, 69% had no protection for tetanus and 90% of the patients had no protection for pertussis. Only 1.3% of the study population had seropositivity against three of the diseases-Tdap booster was indicated in 98.7%. Multivariable logistic regression showed that tetanus protection decreased with increasing age. Having a chronic disease was associated with a lower rate of protective antibodies for pertussis. We demonstrated very low rates of protection against three of the vaccine preventable diseases of childhood-diphtheria, pertussis and tetanus. Booster vaccinations are required in adult life in accordance with national and international adult vaccination guidelines. The concept of "lifelong vaccination" should be implemented and every encounter with the patient should be regarded as a chance for catch-up. Copyright © 2014 European Federation of Internal Medicine. Published by Elsevier B.V. All rights reserved.

  2. Primary vaccination of adults with reduced antigen-content diphtheria-tetanus-acellular pertussis or dTpa-inactivated poliovirus vaccines compared to diphtheria-tetanus-toxoid vaccines.

    NARCIS (Netherlands)

    Theeten, H.; Rumke, H.C.; Hoppener, F.J.; Vilatimo, R.; Narejos, S.; Damme, P. van; Hoet, B.

    2007-01-01

    OBJECTIVE: To evaluate immunogenicity and reactogenicity of primary vaccination with reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) or dTpa-inactivated poliovirus (dTpa-IPV) vaccine compared to diphtheria-tetanus-toxoid vaccines (Td) in adults > or = 40 years of age without

  3. Genomic content of Bordetella pertussis clinical isolates circulating in areas of intensive children vaccination.

    Directory of Open Access Journals (Sweden)

    Valérie Bouchez

    Full Text Available BACKGROUND: The objective of the study was to analyse the evolution of Bordetella pertussis population and the influence of herd immunity in different areas of the world where newborns and infants are highly vaccinated. METHODOLOGY: The analysis was performed using DNA microarray on 15 isolates, PCR on 111 isolates as well as GS-FLX sequencing technology on 3 isolates and the B. pertussis reference strain, Tohama I. PRINCIPAL FINDINGS: Our analyses demonstrate that the current circulating isolates are continuing to lose genetic material as compared to isolates circulating during the pre-vaccine era whatever the area of the world considered. The lost genetic material does not seem to be important for virulence. Our study confirms that the use of whole cell vaccines has led to the control of isolates that were similar to vaccine strains. GS-FLX sequencing technology shows that current isolates did not acquire any additional material when compared with vaccine strains or with isolates of the pre-vaccine era and that the sequenced strain Tohama I is not representative of the isolates. Furthermore, this technology allowed us to observe that the number of Insertion Sequence elements contained in the genome of the isolates is temporally increasing or varying between isolates. CONCLUSIONS: B. pertussis adaptation to humans is still in progress by losing genetic material via Insertion Sequence elements. Furthermore, recent isolates did not acquire any additional material when compared with vaccine strains or with isolates of the pre-vaccine era. Herd immunity, following intensive vaccination of infants and children with whole cell vaccines, has controlled isolates similar to the vaccine strains without modifying significantly the virulence of the isolates. With the replacement of whole cell vaccines by subunit vaccines, containing only few bacterial antigens targeting the virulence of the bacterium, one could hypothesize the circulation of isolates

  4. Tetanus, diphtheria, and acellular pertussis vaccination during pregnancy and reduced risk of infant acute respiratory infections.

    Science.gov (United States)

    Khodr, Zeina G; Bukowinski, Anna T; Gumbs, Gia R; Conlin, Ava Marie S

    2017-10-09

    To protect infants from pertussis infection, the Advisory Committee on Immunization Practices (ACIP) recommends women receive the tetanus toxoid, reduced diphtheria toxoid, acellular pertussis (Tdap) vaccine between 27 and 36weeks of pregnancy. Here, we assessed the association between timing of maternal Tdap vaccination during pregnancy and acute respiratory infection (ARI) in infants risks (RRs) and 95% confidence intervals (CIs) for the association between maternal Tdap vaccination during pregnancy and infant ARI at vaccination during pregnancy vs those who did not were 9% less likely to be diagnosed with an ARI at risk was 17% lower if vaccination was received between 27 and 36weeks of pregnancy (RR, 0.83; 95% CI, 0.74-0.93). Similar results were observed when comparing mothers who received Tdap vaccination prior to pregnancy in addition to Tdap vaccination between 27 and 36weeks of pregnancy versus mothers who only received vaccination prior to pregnancy (RR, 0.85; 95% CI, 0.74-0.98). Maternal Tdap vaccination between 27 and 36weeks of pregnancy was consistently protective against infant ARI in the first 2months of life vs no vaccination during pregnancy, regardless of Tdap vaccination prior to pregnancy. Our findings strongly support current ACIP guidelines recommending Tdap vaccination in late pregnancy for every pregnancy. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Update on pertussis and pertussis immunization

    Directory of Open Access Journals (Sweden)

    Jung Yun Hong

    2010-05-01

    Full Text Available Pertussis is a highly contagious respiratory tract disease caused by Bordetella pertussis infection. The clinical manifestation of this infection can be severe enough to cause death. Although pertussis has been supposed to be a vaccine-preventable disease ever since the widespread vaccination of children against pertussis was started, since the 1990s, cases of pertussis and related fatalities are on the rise, especially in countries with high vaccination coverage. In Korea, there have been no deaths due to pertussis since 1990, and the vaccination rate continues to be approximately 94%. However, the number of pertussis cases reported to the Korea Center for Disease Control and Prevention has tended to increase in the 2000s, and in 2009, there was an obvious increase in the number of pertussis cases reported. This review aims to present the latest information about the pathogenesis, diagnosis, treatment, and prevention of pertussis.

  6. Transferability study of CHO cell clustering assays for monitoring of pertussis toxin activity in acellular pertussis vaccines.

    Science.gov (United States)

    Isbrucker, R; Daas, A; Wagner, L; Costanzo, A

    2016-01-01

    Current regulations for acellular pertussis (aP) vaccines require that they are tested for the presence of residual or reversion-derived pertussis toxin (PTx) activity using the mouse histamine sensitisation test (HIST). Although a CHO cell clustering assay can be used by manufacturers to verify if sufficient inactivation of the substance has occurred in-process, this assay cannot be used at present for the final product due to the presence of aluminium adjuvants which interfere with mammalian cell cultures. Recently, 2 modified CHO cell clustering assays which accommodate for the adjuvant effects have been proposed as alternatives to the HIST. These modified assays eliminate the adjuvant-induced cytotoxicity either through dilution of the vaccine (called the Direct Method) or by introducing a porous barrier between the adjuvant and the cells (the Indirect Method). Transferability and suitability of these methods for testing of products present on the European market were investigated during a collaborative study organised by the European Directorate for the Quality of Medicines & HealthCare (EDQM). Thirteen laboratories participated in this study which included 4 aP-containing vaccines spiked by addition of PTx. This study also assessed the transferability of a standardised CHO cell clustering assay protocol for use with non-adjuvanted PTx preparations. Results showed that the majority of laboratories were able to detect the PTx spike in all 4 vaccines at concentrations of 4 IU/mL or lower using the Indirect Method. This sensitivity is in the range of the theoretical sensitivity of the HIST. The Direct Method however did not show the expected results and would need additional development work.

  7. The WHO Review of the Possible Nonspecific Effects of Diphtheria-Tetanus-Pertussis Vaccine

    DEFF Research Database (Denmark)

    Aaby, Peter; Ravn, Henrik; Benn, Christine S

    2016-01-01

    BACKGROUND: World Health Organization recently reviewed the possible nonspecific effects of diphtheria-tetanus-pertussis (DTP) vaccine. The results were considered inconsistent though most studies suggested deleterious effects. We examined whether inconsistencies in results reflected differences...... in effect of DTP or differences in the methodology used in different studies. METHODS: If children remain unvaccinated because they are frail or if children (including dead ones) with no information on vaccination status are classified as "unvaccinated," the mortality rate becomes unnaturally high among...

  8. Estimates of Pertussis Vaccine Effectiveness in United States Air Force Pediatric Dependents

    Science.gov (United States)

    2015-06-22

    SAS 9.3 (SAS Institute Inc., Cary, NC). Chi- square and Fisher’s exact tests were used to examine demographic and vaccination status differences...members were sig- nificantly (95% CI: 1.70, 9.37; p < 0.001) protected from pertussis, having 74.9% reduced odds of disease (OR = 0.25). Latino ...children had higher odds of pertussis than non- Latinos (OR = 1.98, 95% CI: 0.66, 5.94; p = 0.22), a non-significant finding. No significant trends were

  9. Adult vaccination strategies for the control of pertussis in the United States: an economic evaluation including the dynamic population effects.

    Directory of Open Access Journals (Sweden)

    Laurent Coudeville

    Full Text Available BACKGROUND: Prior economic evaluations of adult and adolescent vaccination strategies against pertussis have reached disparate conclusions. Using static approaches only, previous studies failed to analytically include the indirect benefits derived from herd immunity as well as the impact of vaccination on the evolution of disease incidence over time. METHODS: We assessed the impact of different pertussis vaccination strategies using a dynamic compartmental model able to consider pertussis transmission. We then combined the results with economic data to estimate the relative cost-effectiveness of pertussis immunization strategies for adolescents and adults in the US. The analysis compares combinations of programs targeting adolescents, parents of newborns (i.e. cocoon strategy, or adults of various ages. RESULTS: In the absence of adolescent or adult vaccination, pertussis incidence among adults is predicted to more than double in 20 years. Implementing an adult program in addition to childhood and adolescent vaccination either based on 1 a cocoon strategy and a single booster dose or 2 a decennial routine vaccination would maintain a low level of pertussis incidence in the long run for all age groups (respectively 30 and 20 cases per 100,000 person years. These strategies would also result in significant reductions of pertussis costs (between -77% and -80% including additional vaccination costs. The cocoon strategy complemented by a single booster dose is the most cost-effective one, whereas the decennial adult vaccination is slightly more effective in the long run. CONCLUSIONS: By providing a high level of disease control, the implementation of an adult vaccination program against pertussis appears to be highly cost-effective and often cost-saving.

  10. Malaria chemoprophylaxis and the serologic response to measles and diphtheria-tetanus-whole-cell pertussis vaccines

    Directory of Open Access Journals (Sweden)

    Saliou Pierre

    2005-11-01

    Full Text Available Abstract Background Acute malaria has been associated with a decreased antibody response to tetanus and diphtheria toxoids, meningococcal, salmonella, and Hib vaccines. Interest in giving malaria drug therapy and prevention at the time of childhood immunizations has increased greatly following recent trials of intermittent preventive therapy during infancy (IPTi, stimulating this re-analysis of unpublished data. The effect of malaria chemoprophylaxis on vaccine response was studied following administration of measles vaccines and diphtheria-tetanus-whole cell pertussis (DTP vaccines. Methods In 1975, six villages divided into two groups of children ≤74 months of age from Burkina Faso, were assigned to receive amodiaquine hydrochloride chemoprophylaxis (CH+ every two weeks for seven months or no chemoprophylaxis (CH-. After five months, children in each group received either one dose of measles or two doses of DTP vaccines. Results For recipients of the measles vaccine, the seroconversion rates in CH+ and CH- children, respectively, were 93% and 96% (P > 0.05. The seroresponse rates in CH+ and CH- children respectively, were 73% and 86% for diphtheria (P > 0.05 and 77% and 91% for tetanus toxoid (P > 0.05. In a subset analysis, in which only children who strictly adhered to chemoprophylaxis criteria were included, there were, likewise, no significant differences in seroconversion or seroresponse for measles, diphtheria, or tetanus vaccines (P > 0.05. While analysis for pertussis showed a 43% (CH+ and 67% (CH- response (P Conclusion Malaria chemoprophylaxis prior to vaccination in malaria endemic settings did not improve or impair immunogenicity of DTP and measles vaccines. This is the first human study to look at the association between malaria chemoprophylaxis and the serologic response to whole-cell pertussis vaccine.

  11. Radiation-attenuated vaccine for lungworm disease

    International Nuclear Information System (INIS)

    Singh, C.M.

    1977-01-01

    The work done at the Indian Veternary Research Institute, Izatnagar, on the development of a vaccine for lungworm diseases is reported. Research work done includes: (1) studies on the epidemiology and the incidence of the lungworm infections, (ii) studies on the radiation-attenuated lungworm Dictyocaulus filaria vaccine, (iii) studies on other parasites using ionizing radiation, (iv) incidence of lungworm infection in sheep in Jammu and Kashmir State, (v) suitable dose of gamma radiation for attenuation, (vi) laboratory studies with radiation-attenuated D. filaria vaccine, (vii) serology of D. filaria infection, (viii) field trials with the radiation-attenuated vaccine, (ix) immune response of previously exposed lambs to vaccination, (x) comparative susceptibility of sheep and goats to infection with D. filaria, (xi) quantitative studies of D. filaria in lambs and (xii) production and supply of lungworm vaccine. (A.K.)

  12. Identifying long-term memory B-cells in vaccinated children despite waning antibody levels specific for Bordetella pertussis proteins.

    Science.gov (United States)

    Hendrikx, Lotte H; Oztürk, Kemal; de Rond, Lia G H; Veenhoven, Reinier H; Sanders, Elisabeth A M; Berbers, Guy A M; Buisman, Anne-Marie

    2011-02-04

    Whooping cough is a respiratory disease caused by Bordetella pertussis. Since the 1950s in developed countries pertussis vaccinations are included in the national immunization program. However, antibody levels rapidly wane after both whole cell and acellular pertussis vaccination. Therefore protection against pertussis may depend largely on long-term B- and T-cell immunities. We investigated long-term pertussis-specific memory B-cell responses in children who were primed at infant age with the Dutch wP-vaccine (ISRCTN65428640). Purified B-cells were characterized by FACS-analysis and after polyclonal stimulation memory B-cells were detected by ELISPOT-assays specific for pertussis toxin, filamentous haemagglutinin, pertactin and tetanus. In addition, plasma IgG levels directed to the same antigens were measured by a fluorescent bead-based multiplex immunoassay. Two and 3 years after wP priming as well as 2 and 5 years after the aP booster at the age of 4, low plasma IgG levels to the pertussis proteins were found. At the same time, however pertussis protein-specific memory B-cells could be detected and their number increased with age. The number of tetanus-specific memory B-cells was similar in all age groups, whereas IgG-tetanus levels were high 2 years after tetanus booster compared to pre- and 5 years post-booster levels. This study shows the presence of long-term pertussis protein-specific memory B-cells in children despite waning antibody levels after vaccination, which suggests that memory B-cells in addition to antibodies may contribute to protection against pertussis. Copyright © 2010 Elsevier Ltd. All rights reserved.

  13. Adenylate cyclase toxin-hemolysin relevance for pertussis vaccines

    Czech Academy of Sciences Publication Activity Database

    Šebo, Peter; Osička, Radim; Mašín, Jiří

    2014-01-01

    Roč. 13, č. 10 (2014), s. 1215-1227 ISSN 1476-0584 R&D Projects: GA ČR GA13-14547S; GA ČR(CZ) GAP302/11/0580; GA ČR GAP302/12/0460 Institutional support: RVO:61388971 Keywords : adenylate cyclase toxin * antigen delivery * Bordetella pertussis Subject RIV: EE - Microbiology, Virology Impact factor: 4.210, year: 2014

  14. Seroprevalence of pertussis in the Gambia : evidence for continued circulation of bordetella pertussis despite high vaccination rates

    NARCIS (Netherlands)

    Scott, Susana; van der Sande, Marianne; Faye-Joof, Tisbeh; Mendy, Maimuna; Sanneh, Bakary; Barry Jallow, Fatou; de Melker, Hester; van der Klis, Fiona; van Gageldonk, Pieter; Mooi, Frits; Kampmann, Beate

    BACKGROUND: Bordetella pertussis can cause severe respiratory disease and death in children. In recent years, large outbreaks have occurred in high-income countries; however, little is known about pertussis incidence in sub-Saharan Africa. METHODS: We evaluated antibody responses to pertussis toxin

  15. Pertussis Maternal Immunization: Narrowing the Knowledge Gaps on the Duration of Transferred Protective Immunity and on Vaccination Frequency

    Directory of Open Access Journals (Sweden)

    María Emilia Gaillard

    2017-09-01

    Full Text Available Maternal safety through pertussis vaccination and subsequent maternal–fetal-antibody transfer are well documented, but information on infant protection from pertussis by such antibodies and by subsequent vaccinations is scarce. Since mice are used extensively for maternal-vaccination studies, we adopted that model to narrow those gaps in our understanding of maternal pertussis immunization. Accordingly, we vaccinated female mice with commercial acellular pertussis (aP vaccine and measured offspring protection against Bordetella pertussis challenge and specific-antibody levels with or without revaccination. Maternal immunization protected the offspring against pertussis, with that immune protection transferred to the offspring lasting for several weeks, as evidenced by a reduction (4–5 logs, p < 0.001 in the colony-forming-units recovered from the lungs of 16-week-old offspring. Moreover, maternal-vaccination-acquired immunity from the first pregnancy still conferred protection to offspring up to the fourth pregnancy. Under the conditions of our experimental protocol, protection to offspring from the aP-induced immunity is transferred both transplacentally and through breastfeeding. Adoptive-transfer experiments demonstrated that transferred antibodies were more responsible for the protection detected in offspring than transferred whole spleen cells. In contrast to reported findings, the protection transferred was not lost after the vaccination of infant mice with the same or other vaccine preparations, and conversely, the immunity transferred from mothers did not interfere with the protection conferred by infant vaccination with the same or different vaccines. These results indicated that aP-vaccine immunization of pregnant female mice conferred protective immunity that is transferred both transplacentally and via offspring breastfeeding without compromising the protection boostered by subsequent infant vaccination. These results

  16. Cost-effectiveness analysis of universal maternal immunization with tetanus-diphtheria-acellular pertussis (Tdap) vaccine in Brazil.

    Science.gov (United States)

    Sartori, Ana Marli Christovam; de Soárez, Patrícia Coelho; Fernandes, Eder Gatti; Gryninger, Ligia Castellon Figueiredo; Viscondi, Juliana Yukari Kodaira; Novaes, Hillegonda Maria Dutilh

    2016-03-18

    Pertussis incidence has increased significantly in Brazil since 2011, despite high coverage of whole-cell pertussis containing vaccines in childhood. Infants cost-effectiveness of introducing universal maternal vaccination with tetanus-diphtheria-acellular pertussis vaccine (Tdap) into the National Immunization Program in Brazil. Economic evaluation using a decision tree model comparing two strategies: (1) universal vaccination with one dose of Tdap in the third trimester of pregnancy and (2) current practice (no pertussis maternal vaccination), from the perspective of the health system and society. An annual cohort of newborns representing the number of vaccinated pregnant women were followed for one year. Vaccine efficacy were based on literature review. Epidemiological, healthcare resource utilization and cost estimates were based on local data retrieved from Brazilian Health Information Systems. Costs of epidemiological investigation and treatment of contacts of cases were included in the analysis. No discount rate was applied to costs and benefits, as the temporal horizon was one year. Primary outcome was cost per life year saved (LYS). Univariate and best- and worst-case scenarios sensitivity analysis were performed. Maternal vaccination of one annual cohort, with vaccine effectiveness of 78%, and vaccine cost of USD$12.39 per dose, would avoid 661 cases and 24 infant deaths of pertussis, save 1800 years of life and cost USD$28,942,808 and USD$29,002,947, respectively, from the health system and societal perspective. The universal immunization would result in ICERs of USD$15,608 and USD$15,590 per LYS, from the health system and societal perspective, respectively. In sensitivity analysis, the ICER was most sensitive to discounting of life years saved, variation in case-fatality, disease incidence, vaccine cost, and vaccine effectiveness. The results indicate that universal maternal immunization with Tdap is a cost-effective intervention for preventing

  17. Control selection and confounding factors: A lesson from a Japanese case-control study to examine acellular pertussis vaccine effectiveness.

    Science.gov (United States)

    Ohfuji, Satoko; Okada, Kenji; Nakano, Takashi; Ito, Hiroaki; Hara, Megumi; Kuroki, Haruo; Hirota, Yoshio

    2017-08-24

    When using a case-control study design to examine vaccine effectiveness, both the selection of control subjects and the consideration of potential confounders must be the important issues to ensure accurate results. In this report, we described our experience from a case-control study conducted to evaluate the effectiveness of acellular pertussis vaccine combined with diphtheria-tetanus toxoids (DTaP vaccine). Newly diagnosed pertussis cases and age- and sex-matched friend-controls were enrolled, and the history of DTaP vaccination was compared between groups. Logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) of vaccination for development of pertussis. After adjustment for potential confounders, four doses of DTaP vaccination showed a lower OR for pediatrician-diagnosed pertussis (OR=0.11, 95% CI, 0.01-0.99). In addition, the decreasing OR of four doses vaccination was more pronounced for laboratory-confirmed pertussis (OR=0.07, 95%CI, 0.01-0.82). Besides, positive association with pertussis was observed in subjects with a history of steroid treatment (OR=5.67) and those with a recent contact with a lasting cough (OR=4.12). When using a case-control study to evaluate the effectiveness of vaccines, particularly those for uncommon infectious diseases such as pertussis, the use of friend-controls may be optimal due to the fact that they shared a similar experience for exposure to the pathogen as the cases. In addition, to assess vaccine effectiveness as accurately as possible, the effects of confounding should be adequately controlled with a matching or analysis technique. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  18. LIVE ATTENUATED VACCINES FOR THE IMMUNOPROPHYLAXIS

    Directory of Open Access Journals (Sweden)

    O. A. Shamsutdinova

    2017-01-01

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

  19. Seroprevalence of Bordetella pertussis among vaccinated and unvaccinated pregnant women and newborn infants in a university hospital of Buenos Aires.

    Science.gov (United States)

    Bosch, Juan J; Fernández, Hilaria; Polak, Fernando P; Musante, Gabriel; Libster, Romina; Rocca Rivarola, Manuel

    2017-08-01

    Pertussis is a highly contagious disease caused by Bordetella pertussis. It poses a high morbidity and mortality rate, especially among infants younger than 6 months old. In Argentina, pertussis incidence and mortality have increased over the past three decades. To establish Bordetella pertussisantibody titers among pregnant women in their third trimester and among newborn infants, as measured in cord blood. This was an observational, cross-sectional study. The study started in 2011; at that time, pertussis vaccination was not mandatory for pregnant women as per the national immunization schedule, only optional. Maternal antibodies were measured in the last trimester of pregnancy for women and in cord blood for newborn infants. Antibody titers were determined using Abcam's anti-Bordetella pertussis toxin (PT) IgG in vitro ELISA kit. The χ² test was used to compare prevalence rates. The study included 111 mother-newborn infant dyads; 35 infants from unvaccinated mothers (before the introduction of the vaccine) and 76 from vaccinated mothers. Positive IgG antibodies were found in 92% (70/76) of infants born from vaccinated mothers whereas 100% (35/35) of infants born from unvaccinated mothers had negative results for antibodies; p < 0.001. In the vaccinated population of this study, 92% of infants had positive IgG antibodies. This study supports the need for maternal immunization against Bordetella pertussis to provide protection to newborn infants. Sociedad Argentina de Pediatría

  20. Pertussis Maternal Immunization: Narrowing the Knowledge Gaps on the Duration of Transferred Protective Immunity and on Vaccination Frequency

    Science.gov (United States)

    Gaillard, María Emilia; Bottero, Daniela; Zurita, María Eugenia; Carriquiriborde, Francisco; Martin Aispuro, Pablo; Bartel, Erika; Sabater-Martínez, David; Bravo, María Sol; Castuma, Celina; Hozbor, Daniela Flavia

    2017-01-01

    Maternal safety through pertussis vaccination and subsequent maternal–fetal-antibody transfer are well documented, but information on infant protection from pertussis by such antibodies and by subsequent vaccinations is scarce. Since mice are used extensively for maternal-vaccination studies, we adopted that model to narrow those gaps in our understanding of maternal pertussis immunization. Accordingly, we vaccinated female mice with commercial acellular pertussis (aP) vaccine and measured offspring protection against Bordetella pertussis challenge and specific-antibody levels with or without revaccination. Maternal immunization protected the offspring against pertussis, with that immune protection transferred to the offspring lasting for several weeks, as evidenced by a reduction (4–5 logs, p protection to offspring up to the fourth pregnancy. Under the conditions of our experimental protocol, protection to offspring from the aP-induced immunity is transferred both transplacentally and through breastfeeding. Adoptive-transfer experiments demonstrated that transferred antibodies were more responsible for the protection detected in offspring than transferred whole spleen cells. In contrast to reported findings, the protection transferred was not lost after the vaccination of infant mice with the same or other vaccine preparations, and conversely, the immunity transferred from mothers did not interfere with the protection conferred by infant vaccination with the same or different vaccines. These results indicated that aP-vaccine immunization of pregnant female mice conferred protective immunity that is transferred both transplacentally and via offspring breastfeeding without compromising the protection boostered by subsequent infant vaccination. These results—though admittedly not necessarily immediately extrapolatable to humans—nevertheless enabled us to test hypotheses under controlled conditions through detailed sampling and data collection. These

  1. Experimental Study of Interference Between Pertussis Antigens and Salk Poliomyelitis Vaccine

    Directory of Open Access Journals (Sweden)

    H. Mirehamsy

    1962-01-01

    Full Text Available An interference is observed between whooping-cough antigens and Salk polioc vaccine even if the two components are mixed immediately before use. The phenomenon is more evident when flUlid antigens are injected. Pertussis soluble antigen, which gives a good serological response in rabbits, when used alone or combined with DT, is inactivated in the presence of Salk polio vacc:ne

  2. Whooping cough in school age children presenting with persistent cough in UK primary care after introduction of the preschool pertussis booster vaccination: prospective cohort study.

    Science.gov (United States)

    Wang, Kay; Fry, Norman K; Campbell, Helen; Amirthalingam, Gayatri; Harrison, Timothy G; Mant, David; Harnden, Anthony

    2014-06-24

    To estimate the prevalence and clinical severity of whooping cough (pertussis) in school age children presenting with persistent cough in primary care since the introduction and implementation of the preschool pertussis booster vaccination. Prospective cohort study (November 2010 to December 2012). General practices in Thames Valley, UK. 279 children aged 5 to 15 years who presented in primary care with a persistent cough of two to eight weeks' duration. Exclusion criteria were cough likely to be caused by a serious underlying medical condition, known immunodeficiency or immunocompromise, participation in another clinical research study, and preschool pertussis booster vaccination received less than one year previously. Evidence of recent pertussis infection based on an oral fluid anti-pertussis toxin IgG titre of at least 70 arbitrary units. Cough frequency was measured in six children with laboratory confirmed pertussis. 56 (20%, 95% confidence interval 16% to 25%) children had evidence of recent pertussis infection, including 39 (18%, 13% to 24%) of 215 children who had been fully vaccinated. The risk of pertussis was more than three times higher (21/53; 40%, 26% to 54%) in children who had received the preschool pertussis booster vaccination seven years or more previously than in those who had received it less than seven years previously (20/171; 12%, 7% to 17%). The risk of pertussis was similar between children who received five and three component preschool pertussis booster vaccines (risk ratio for five component vaccine 1.14, 0.64 to 2.03). Four of six children in whom cough frequency was measured coughed more than 400 times in 24 hours. Pertussis can still be found in a fifth of school age children who present in primary care with persistent cough and can cause clinically significant cough in fully vaccinated children. These findings will help to inform consideration of the need for an adolescent pertussis booster vaccination in the United Kingdom. UK

  3. Pertussis toxin treatment attenuates some effects of insulin in BC3H-1 murine myocytes

    International Nuclear Information System (INIS)

    Luttrell, L.M.; Hewlett, E.L.; Romero, G.; Rogol, A.D.

    1988-01-01

    The effects of pertussis toxin (PT) treatment on insulin-stimulated myristoyl-diacylglycerol (DAG) generation, hexose transport, and thymidine incorporation were studied in differentiated BC3H-1 mycocytes. Insulin treatment caused a biphasic increase in myristoyl-DAG production which was abolished in myocytes treated with PT. There was no effect of PT treatment on basal (nonstimulated) myristoyl-DAG production. Insulin-stimulated hydrolysis of a membrane phosphatidylinositol glycan was blocked by PT treatment. ADP-ribosylation of BC3H-1 plasma membranes with [ 32 P]NAD revealed a 40-kDa protein as the major PT substrate in vivo and in vitro. The time course and dose dependence of the effects of PT on diacylglycerol generation correlated with the in vivo ADP-ribosylation of the 40-kDa substrate. Pertussis toxin treatment resulted in a 71% attenuation of insulin-stimulated hexose uptake without effect on either basal or phorbol ester-stimulated uptake. The stimulatory effects of insulin and fetal calf serum on [ 3 H]thymidine incorporation into quiescent myocytes were attenuated by 61 and 59%, respectively, when PT was added coincidently with the growth factors. Nonstimulated and EGF-stimulated [ 3 H]thymidine incorporation was unaffected by PT treatment. These data suggest that a PT-sensitive G protein is involved in the cellular signaling mechanisms of insulin

  4. Tetanus, diphtheria, and acellular pertussis vaccination among women of childbearing age-United States, 2013.

    Science.gov (United States)

    O'Halloran, Alissa C; Lu, Peng-Jun; Williams, Walter W; Ding, Helen; Meyer, Sarah A

    2016-07-01

    The incidence of pertussis in the United States has increased since the 1990s. Tetanus, diphtheria, and acellular pertussis (Tdap) vaccination of pregnant women provides passive protection to infants. Tdap vaccination is currently recommended for pregnant women during each pregnancy, but coverage among pregnant women and women of childbearing age has been suboptimal. Data from the 2013 Behavioral Risk Factor Surveillance System (BRFSS) and 2013 National Health Interview Survey (NHIS) were used to determine national and state-specific Tdap vaccination coverage among women of childbearing age by self-reported pregnancy status at the time of the survey. Although this study could not assess coverage of Tdap vaccination received during pregnancy because questions on whether Tdap vaccination was received during pregnancy were not asked in BRFSS and NHIS, demographic and access-to-care factors associated with Tdap vaccination coverage in this population were assessed. Tdap vaccination coverage among all women 18-44 years old was 38.4% based on the BRFSS and 23.3% based on the NHIS. Overall, coverage did not differ by pregnancy status at the time of the survey. Coverage among all women 18-44 years old varied widely by state. Age, race and ethnicity, education, number of children in the household, and access-to-care characteristics were independently associated with Tdap vaccination in both surveys. We identified associations of demographic and access-to-care characteristics with Tdap vaccination that can guide strategies to improve vaccination rates in women during pregnancy. Copyright © 2016 Association for Professionals in Infection Control and Epidemiology, Inc. All rights reserved.

  5. 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

    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......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...... 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...

  6. Impact of infant and preschool pertussis vaccinations on memory B-cell responses in children at 4 years of age.

    Science.gov (United States)

    Hendrikx, Lotte H; de Rond, Lia G H; Oztürk, Kemal; Veenhoven, Reinier H; Sanders, Elisabeth A M; Berbers, Guy A M; Buisman, Anne-Marie

    2011-08-05

    Whooping cough, caused by Bordetella pertussis, is reemerging in the vaccinated population. Antibody levels to pertussis antigens wane rapidly after both whole-cell (wP) and acellular pertussis (aP) vaccination and protection may largely depend on long-term B- and T-cell immunity. We studied the effect of wP and aP infant priming at 2, 3, 4 and 11 months according to the Dutch immunization program on pertussis-specific memory B-cell responses before and after a booster vaccination with either a high- or low-pertussis dose vaccine at 4 years of age. Purified B-cells were characterized by FACS-analysis and after polyclonal stimulation, memory B-cells were detected by ELISPOT-assays specific for pertussis toxin, filamentous haemagglutinin and pertactin. Before and after the booster, higher memory B-cell responses were measured in aP primed children compared with wP primed children. In contrast with antibody levels, no dose-effect was observed on the numbers of memory B-cell responses. In aP primed children a fifth high-dose aP vaccination tended to induce even lower memory B-cell responses than a low-dose aP booster. In both wP and aP primed children, the number of memory B-cells increased after the booster and correlated with the pertussis-specific antibody concentrations and observed affinity maturation. This study indicates that aP vaccinations in the first year of life induce higher pertussis-specific memory B-cell responses in children 4 years of age compared with Dutch wP primary vaccinations. Since infant aP vaccinations have improved protection against whooping cough in children despite waning antibody levels, this suggests that an enhanced memory B-cell pool induction may have an important role in protection. However, the pertussis-dose of the preschool booster needs to be considered depending on the vaccine used for priming to optimize long-term protection against whooping cough. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. Serum reactome induced by Bordetella pertussis infection and Pertussis vaccines: qualitative differences in serum antibody recognition patterns revealed by peptide microarray analysis.

    Science.gov (United States)

    Valentini, Davide; Ferrara, Giovanni; Advani, Reza; Hallander, Hans O; Maeurer, Markus J

    2015-07-01

    Pertussis (whooping cough) remains a public health problem despite extensive vaccination strategies. Better understanding of the host-pathogen interaction and the detailed B. pertussis (Bp) target recognition pattern will help in guided vaccine design. We characterized the specific epitope antigen recognition profiles of serum antibodies ('the reactome') induced by whooping cough and B. pertussis (Bp) vaccines from a case-control study conducted in 1996 in infants enrolled in a Bp vaccine trial in Sweden (Gustafsson, NEJM, 1996, 334, 349-355). Sera from children with whooping cough, vaccinated with Diphtheria Tetanus Pertussis (DTP) whole-cell (wc), acellular 5 (DPTa5), or with the 2 component (a2) vaccines and from infants receiving only DT (n=10 for each group) were tested with high-content peptide microarrays containing 17 Bp proteins displayed as linear (n=3175) peptide stretches. Slides were incubated with serum and peptide-IgG complexes detected with Cy5-labeled goat anti-human IgG and analyzed using a GenePix 4000B microarray scanner, followed by statistical analysis, using PAM (Prediction Analysis for Microarrays) and the identification of uniquely recognized peptide epitopes. 367/3,085 (11.9%) peptides were recognized in 10/10 sera from children with whooping cough, 239 (7.7%) in DTPwc, 259 (8.4%) in DTPa5, 105 (3.4%) DTPa2, 179 (5.8%) in the DT groups. Recognition of strongly recognized peptides was similar between whooping cough and DPTwc, but statistically different between whooping cough vs. DTPa5 (p<0.05), DTPa2 and DT (p<0.001 vs. both) vaccines. 6/3,085 and 2/3,085 peptides were exclusively recognized in (10/10) sera from children with whooping cough and DTPa2 vaccination, respectively. DTPwc resembles more closely the whooping cough reactome as compared to acellular vaccines. We could identify a unique recognition signature common for each vaccination group (10/10 children). Peptide microarray technology allows detection of subtle differences in

  8. Comparisons of the effect of naturally acquired maternal pertussis antibodies and antenatal vaccination induced maternal tetanus antibodies on infant's antibody secreting lymphocyte responses and circulating plasma antibody

    Science.gov (United States)

    The goal of this study was to explore the effects of trans-placental tetanus toxoid (TT) and pertussis (PT) antibodies on an infant's response to vaccination in the context of antenatal immunization with tetanus but not with pertussis. 38 mothers received a single dose of TT vaccine during pregnancy...

  9. Elevated Immune Response Among Children 4 Years of Age With Pronounced Local Adverse Events After the Fifth Diphtheria, Tetanus, Acellular Pertussis Vaccination.

    NARCIS (Netherlands)

    van der Lee, Saskia; Kemmeren, Jeanet M; de Rond, Lia G H; Öztürk, Kemal; Westerhof, Anneke; de Melker, Hester E; Sanders, Elisabeth A M; Berbers, Guy A M; van der Maas, Nicoline A T; Rümke, Hans C; Buisman, Anne-Marie

    In the Netherlands, acellular pertussis vaccines replaced the more reactogenic whole-cell pertussis vaccines. This replacement in the primary immunization schedule of infants coincided with a significant increase in pronounced local adverse events (AEs) in 4 years old children shortly after the

  10. Lichen planus following tetanus-diphtheria-acellular pertussis vaccination: A case report and review of the literature.

    Science.gov (United States)

    Rosengard, Heather C; Wheat, Chikoti M; Tilson, Matthew P; Cuda, Jonathan D

    2018-01-01

    Lichen planus is an inflammatory dermatosis with a prevalence of approximately 1%. Recent meta-analyses show that patients with hepatitis C virus have a 2.5- to 4.5-fold increased risk of developing lichen planus. Lichen planus has also followed vaccinations and has specifically been attributed to the hepatitis B vaccine, the influenza vaccine, and the tetanus-diphtheria-acellular pertussis vaccine. We describe a case of lichen planus in a hepatitis C virus-infected African American male occurring in temporal association with the administration of the tetanus-diphtheria-acellular pertussis vaccine. The patient's presentation was clinically consistent with lichen planus and confirmed by biopsy. It is likely that many cases of vaccine-induced lichen planus have gone unpublished or unrecognized. In areas with high prevalence of hepatitis C virus infection, we may expect to see more cases of vaccine-induced lichen planus especially in light of the updated Centers for Disease Control and Prevention tetanus-diphtheria-acellular pertussis vaccination recommendations. This case serves to educate healthcare providers about vaccine-induced lichen planus and, in particular, the need to counsel hepatitis C virus-infected patients about a potential risk of developing lichen planus following vaccination. We also reflect on current theories suggesting the T-cell-mediated pathogenesis of lichen planus and the role that hepatitis C virus and toxoid or protein vaccines may play in initiating the disease.

  11. Finding the 'who' in whooping cough: vaccinated siblings are important pertussis sources in infants 6 months of age and under.

    Science.gov (United States)

    Bertilone, Christina; Wallace, Tania; Selvey, Linda A

    2014-09-30

    To describe the epidemiology of pertussis, and to identify changes in the source of pertussis in infants 6 months of age and under, during the 2008-2012 epidemic in south metropolitan Perth. Analysis of all pertussis cases notified to the South Metropolitan Population Health Unit and recorded on the Western Australian Notifiable Infectious Disease Database over the study period. Information on the source of pertussis was obtained from enhanced surveillance data. Notification rates were highest in the 5-9 years age group, followed by the 0-4 years and 10-14 years age groups. There was a significant increase in the proportion of known sources who were siblings from the early epidemic period of 2008-2010, compared with the peak epidemic period of 2011-2012 (14.3% versus 51.4%, p = 0.002). The majority of sibling sources were fully vaccinated children aged 2 and 3 years. The incidence of pertussis was highest in children aged 12 years and under in this epidemic. At its peak, siblings were the most important sources of pertussis in infants 6 months and younger, particularly fully vaccinated children aged 2 and 3 years. Waning immunity before the booster at 4 years may leave this age group susceptible to infection. Even if cocooning programs could achieve full vaccination coverage of parents and ensure all siblings were fully vaccinated according to national schedules, waning immunity in siblings could provide a means for ongoing transmission to infants. Recent evidence suggests that maternal antenatal vaccination would significantly reduce the risk of pertussis in infants 3 months of age and under.

  12. Low tetanus, diphtheria and acellular pertussis (Tdap) vaccination coverage among HIV infected individuals in Austria.

    Science.gov (United States)

    Grabmeier-Pfistershammer, K; Herkner, H; Touzeau-Roemer, V; Rieger, A; Burgmann, H; Poeppl, W

    2015-07-31

    Current management guidelines of HIV infected adults include recommendation to immunization against common vaccine preventable diseases. This effort is hindered by the scarce knowledge regarding the immunization status of this especially vulnerable patient group. This study analyzed the serostatus for pertussis, diphtheria and tetanus of more than 700 HIV infected individuals residing in Austria. These individuals were representative for the Austrian HIV cohort regarding sex, age, transmission risk and HIV progression markers. Overall, 73.6% were on suppressive HAART, mean CD4 cell count was 603c/μl. Seropositivity was 84% for diphtheria, 51% for tetanus and 1% for pertussis. Migrants had a lower chance of tetanus seropositivity (OR 0.30 (CI 0.21 to 0.43)). Increase in CDC classification were associated with increased diphtheria seropositivity (OR 1.42 (CI 1.02 to 1.98)) and a CD4 nadir200c/μl, 95% lacked seroprotection to at least one of the antigens included in the triple vaccine Tdap and could be vaccinated. Thus, a proactive approach would largely reduce the number of patients at risk for these vaccine-preventable diseases. Copyright © 2015 Elsevier Ltd. All rights reserved.

  13. Influenza Vaccination Strategies: Comparing Inactivated and Live Attenuated Influenza Vaccines

    Directory of Open Access Journals (Sweden)

    Saranya Sridhar

    2015-04-01

    Full Text Available Influenza is a major respiratory pathogen causing annual outbreaks and occasional pandemics. Influenza vaccination is the major method of prophylaxis. Currently annual influenza vaccination is recommended for groups at high risk of complications from influenza infection such as pregnant women, young children, people with underlying disease and the elderly, along with occupational groups such a healthcare workers and farm workers. There are two main types of vaccines available: the parenteral inactivated influenza vaccine and the intranasal live attenuated influenza vaccine. The inactivated vaccines are licensed from 6 months of age and have been used for more than 50 years with a good safety profile. Inactivated vaccines are standardized according to the presence of the viral major surface glycoprotein hemagglutinin and protection is mediated by the induction of vaccine strain specific antibody responses. In contrast, the live attenuated vaccines are licensed in Europe for children from 2–17 years of age and provide a multifaceted immune response with local and systemic antibody and T cell responses but with no clear correlate of protection. Here we discuss the immunological immune responses elicited by the two vaccines and discuss future work to better define correlates of protection.

  14. Influenza and Pertussis Vaccination Among Pregnant Women and Their Infants' Close Contacts: Reported Practices and Attitudes.

    Science.gov (United States)

    O'Leary, Sean T; Pyrzanowski, Jennifer; Brewer, Sarah E; Barnard, Juliana; Beaty, Brenda; Donnelly, Meghan; Mazzoni, Sara; Dempsey, Amanda F

    2015-11-01

    Our objectives were to describe the receipt of influenza and tetanus-diphtheria-acellular pertussis (Tdap) vaccines among postpartum women and their close contacts and the factors associated with cocooning. A survey between February 2013 and April 2013 of 613 postpartum women from 9 obstetrics practices assessed vaccine receipt among respondents and close contacts, demographics and 5 domains of health beliefs (benefits, barriers, susceptibility, severity and social norms). Multivariable models assessed the association of these factors with Tdap or influenza "cocooning," defined as the mother plus at least 1 close contact of her newborn receiving the vaccine. The response rate was 45%; 61% of mothers reported that they and at least 1 close contact of their newborn had received influenza vaccine, and 67% reported this for Tdap. Infants whose mothers received influenza vaccine had a mean of 2.8 close contacts who also received influenza vaccine versus a mean of 0.9 contacts for infants whose mothers did not receive influenza vaccine (P referent to White). Maternal vaccination and obstetrician recommendation are associated with infant cocooning. Interventions to increase cocooning of infants should focus on encouraging strong provider recommendations, increasing maternal knowledge of disease risk and addressing identified barriers. Reasons for possible racial/ethnic differences should be further explored.

  15. Relative Contribution of Th1 and Th17 Cells in Adaptive Immunity to Bordetella pertussis: Towards the Rational Design of an Improved Acellular Pertussis Vaccine

    Science.gov (United States)

    Ross, Pádraig J.; Allen, Aideen C.; Walsh, Kevin; Misiak, Alicja; Lavelle, Ed C.; McLoughlin, Rachel M.; Mills, Kingston H. G.

    2013-01-01

    Whooping cough caused by Bordetella pertussis is a re-emerging infectious disease despite the introduction of safer acellular pertussis vaccines (Pa). One explanation for this is that Pa are less protective than the more reactogenic whole cell pertussis vaccines (Pw) that they replaced. Although Pa induce potent antibody responses, and protection has been found to be associated with high concentrations of circulating IgG against vaccine antigens, it has not been firmly established that host protection induced with this vaccine is mediated solely by humoral immunity. The aim of this study was to examine the relative contribution of Th1 and Th17 cells in host immunity to infection with B. pertussis and in immunity induced by immunization with Pw and Pa and to use this information to help rationally design a more effective Pa. Our findings demonstrate that Th1 and Th17 both function in protective immunity induced by infection with B. pertussis or immunization with Pw. In contrast, a current licensed Pa, administered with alum as the adjuvant, induced Th2 and Th17 cells, but weak Th1 responses. We found that IL-1 signalling played a central role in protective immunity induced with alum-adsorbed Pa and this was associated with the induction of Th17 cells. Pa generated strong antibody and Th2 responses, but was fully protective in IL-4-defective mice, suggesting that Th2 cells were dispensable. In contrast, Pa failed to confer protective immunity in IL-17A-defective mice. Bacterial clearance mediated by Pa-induced Th17 cells was associated with cell recruitment to the lungs after challenge. Finally, protective immunity induced by an experimental Pa could be enhanced by substituting alum with a TLR agonist that induces Th1 cells. Our findings demonstrate that alum promotes protective immunity through IL-1β-induced IL-17A production, but also reveal that optimum protection against B. pertussis requires induction of Th1, but not Th2 cells. PMID:23592988

  16. Differences in female-male mortality after high-titre measles vaccine and association with subsequent vaccination with diphtheria-tetanus-pertussis and inactivated poliovirus

    DEFF Research Database (Denmark)

    Aaby, Peter; Jensen, Henrik; Samb, Badara

    2003-01-01

    Females given high-titre measles vaccine (HTMV) have high mortality; diphtheria-tetanus-pertussis (DTP) vaccination might be associated with increased female mortality. We aimed to assess whether DTP or inactivated poliovirus (IPV) administered after HTMV was associated with increased female...

  17. Study of Serologic Response Rate to Pertussis after Administration of the Third Dose of Pentavalent Vaccine in Children 12 Months Old in Karaj City, Iran

    Directory of Open Access Journals (Sweden)

    Reza Arjmand

    2018-02-01

    Full Text Available Background: After substitution of Pentavalent vaccine with diphtheria, tetanus, pertussis (DTP in the Iranian National Vaccination program with 3 Pentavalent (three times vaccination with Pentavalent vaccine at months 2, 4, and 6 in 2014 and the lack of published research in the field of immunogenicity of pertussis component of this vaccine, the efficacy of pertussis vaccine was studied 6 months after the last dose of Pentavalent vaccine in Iranian infants.  Materials and Methods: Five hundred blood samples were collected from healthy one-year-old children who attended 18 health care centers of Karaj, Iran for routine vaccination selected by cluster sampling (2016. Sampling checklists contained demographic information and risk factors. The blood samples were sent to the laboratory for determination of Immunoglobulin G (IgG and IgA anti-pertussis antibody titer by ELISA method. Data were analyzed by STATA software (version 14.0. Results: 82.7% (n=413 of children (95% confidence interval [CI]: 79.49-86.11 had IgG titer less than 16 IU/ml against pertussis (no immune response, and 17.3% (n=87 had equal or greater than 16 IU/ml IgG titer against pertussis (95% CI: 13.89-20.51. IgA titer against pertussis was less than 8U/ml in all cases. Anti-pertussis IgG geometric mean titer (GMT was 15.80 U/ml (95% CI: 15.26-16.36, and IgA GMT was 6.26 U/ml (95% CI: 6.22-6.30. There was not a significant correlation between titer of pertussis antibody and demographic factors. Conclusion: Based on low IgG titer in vaccinated children, immunogenicity of pentavalent vaccine in Iranian children needs more investigation. In this study, 100 % of children had negative serologic response (IgA

  18. Evaluation of two vaccine education interventions to improve pertussis vaccination among pregnant African American women: A randomized controlled trial.

    Science.gov (United States)

    Kriss, Jennifer L; Frew, Paula M; Cortes, Marielysse; Malik, Fauzia A; Chamberlain, Allison T; Seib, Katherine; Flowers, Lisa; Ault, Kevin A; Howards, Penelope P; Orenstein, Walter A; Omer, Saad B

    2017-03-13

    Vaccination coverage with tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine in pregnancy or immediately postpartum has been low. Limited data exist on rigorously evaluated interventions to increase maternal vaccination, including Tdap. Tailored messaging based on the Elaboration Likelihood Model (ELM) framework has been successful in improving uptake of some public health interventions. We evaluated the effect of two ELM-based vaccine educational interventions on Tdap vaccination among pregnant African American women, a group of women who tend to have lower vaccine uptake compared with other groups. We conducted a prospective randomized controlled trial to pilot test two interventions - an affective messaging video and a cognitive messaging iBook - among pregnant African American women recruited during routine prenatal care visits. We measured Tdap vaccination during the perinatal period (during pregnancy and immediately postpartum), reasons for non-vaccination, and intention to receive Tdap in the next pregnancy. Among the enrolled women (n=106), 90% completed follow-up. Tdap vaccination in the perinatal period was 18% in the control group; 50% in the iBook group (Risk Ratio [vs. control group]: 2.83; 95% CI, 1.26-6.37), and 29% in the video group (RR: 1.65; 95% CI, 0.66-4.09). From baseline to follow-up, women's reported intention to receive Tdap during the next pregnancy improved in all three groups. Among unvaccinated women, the most common reason reported for non-vaccination was lack of a recommendation for Tdap by the woman's physician. Education interventions that provide targeted information for pregnant women in an interactive manner may be useful to improve Tdap vaccination during the perinatal period. However, larger studies including multiple racial and ethnic groups are needed to evaluate robustness of our findings. clinicaltrials.gov Identifier: NCT01740310. Copyright © 2017 Elsevier Ltd. All rights reserved.

  19. Uptake of a government-funded pertussis-containing booster vaccination program for parents of new babies in Victoria, Australia.

    Science.gov (United States)

    Rowe, Stacey L; Cunningham, Helen M; Franklin, Lucinda J; Lester, Rosemary A

    2015-04-08

    An epidemic of Bordetella pertussis in Victoria, Australia, led to the implementation of a Government-funded vaccination program for parents of new babies. The rationale was to protect unimmunised infants from infection by vaccinating parents with a pertussis-containing vaccine. This is known as cocooning. To estimate uptake of the vaccine among parents of new babies, two-and-a-half years after the program was implemented. A state-wide cross-sectional survey of parents was conducted to ascertain vaccine uptake, and to identify where and when the vaccination took place. Surveys were administered between 15 February and 14 March 2012, inclusive. Of 6308 surveys distributed, 2510 completed surveys were returned (response rate 40%). Ninety-five surveys completed outside the study period were excluded, leaving 2415 available for analysis. Overall, 1937 (80%) mothers and 1385 (70%) fathers were vaccinated in relation to the birth of their most recent child. A majority of mothers were vaccinated in hospital (62%). Most fathers were vaccinated by a general practitioner (72%). The most common point at which mothers were vaccinated was before their child turned two weeks of age (65%). Fathers' vaccination time-point varied more widely: during pregnancy (25%); before their child turned two weeks of age (29%); and when their child was between two and eight weeks of age (28%). Results of this survey indicated excellent uptake of the vaccine among both mothers and fathers under the Government-funded cocooning program. The findings are suggestive of an effective communications program designed to raise awareness of the risks of pertussis, and to promote availability of the funded vaccination program. The results may contribute to policy implementation of adult immunisation programs such as cocooning. Copyright © 2015 Elsevier Ltd. All rights reserved.

  20. Communication and mass vaccination strategies after pertussis outbreak in rural Amish communities-Illinois, 2009-2010.

    Science.gov (United States)

    Medina-Marino, Andrew; Reynolds, Debra; Finley, Carol; Hays, Susan; Jones, Jane; Soyemi, Kenneth

    2013-01-01

    During January 2010, 2 infants from an Amish community in east-central Illinois were hospitalized with pertussis. The local health department (LDH) intervened to control disease transmission, identify contributing factors, and determine best communications methods to improve vaccination coverage. A retrospective cohort study was conducted using public health surveillance data to determine the extent of the outbreak; the standard Centers for Disease Control and Prevention and Council of State and Territorial Epidemiologists case definition for pertussis was used. The standardized Illinois Department of Public Health pertussis patient interview form was used to collect demographic, symptom, vaccination history, and treatment history information. To control disease transmission, LDH staff worked with the Amish community to promote a vaccination campaign during February 6-April 30, 2010. Forty-seven cases were identified, with onsets during December 2009-March 2010. Median age was 7 (interquartile range 1-12) years. Nineteen (40%) patients were male; 39 (83%) were aged communication and outreach resulted in a successful vaccine campaign and long-running monthly vaccination clinic. Amish do not universally reject vaccines, and their practices regarding vaccination are not static. No claim to original US government works.

  1. Laboratory Diagnosis of Pertussis

    Science.gov (United States)

    Schellekens, Joop F. P.; Mooi, Frits R.

    2015-01-01

    SUMMARY The introduction of vaccination in the 1950s significantly reduced the morbidity and mortality of pertussis. However, since the 1990s, a resurgence of pertussis has been observed in vaccinated populations, and a number of causes have been proposed for this phenomenon, including improved diagnostics, increased awareness, waning immunity, and pathogen adaptation. The resurgence of pertussis highlights the importance of standardized, sensitive, and specific laboratory diagnoses, the lack of which is responsible for the large differences in pertussis notifications between countries. Accurate laboratory diagnosis is also important for distinguishing between the several etiologic agents of pertussis-like diseases, which involve both viruses and bacteria. If pertussis is diagnosed in a timely manner, antibiotic treatment of the patient can mitigate the symptoms and prevent transmission. During an outbreak, timely diagnosis of pertussis allows prophylactic treatment of infants too young to be (fully) vaccinated, for whom pertussis is a severe, sometimes fatal disease. Finally, reliable diagnosis of pertussis is required to reveal trends in the (age-specific) disease incidence, which may point to changes in vaccine efficacy, waning immunity, and the emergence of vaccine-adapted strains. Here we review current approaches to the diagnosis of pertussis and discuss their limitations and strengths. In particular, we emphasize that the optimal diagnostic procedure depends on the stage of the disease, the age of the patient, and the vaccination status of the patient. PMID:26354823

  2. The Introduction of Diphtheria-Tetanus-Pertussis and Oral Polio Vaccine Among Young Infants in an Urban African Community

    DEFF Research Database (Denmark)

    Mogensen, Søren Wengel; Andersen, Andreas; Rodrigues, Amabelia

    2017-01-01

    Background We examined the introduction of diphtheria-tetanus-pertussis (DTP) and oral polio vaccine (OPV) in an urban community in Guinea-Bissau in the early 1980s. Methods The child population had been followed with 3-monthly nutritional weighing sessions since 1978. From June 1981 DTP and OPV...

  3. The effect of vitamin A supplementation and diphtheria-tetanus-pertussis vaccination on parasitaemia in an experimental murine malaria model

    DEFF Research Database (Denmark)

    Jørgensen, Mathias Jul; Hein-Kristensen, Line; Hempel, Casper

    2011-01-01

    infectious diseases when given with the diphtheria-tetanus-pertussis (DTP) vaccine. The immunological effects of combining the 2 treatments are unknown. Methods: We studied the effect of treating C57BL/6 mice with VAS and DTP, 1 week prior to infection with Plasmodium berghei ANKA. The progression of disease...

  4. Substantial gaps in knowledge of Bordetella pertussis antibody and T cell epitopes relevant for natural immunity and vaccine efficacy

    Science.gov (United States)

    Vaughan, Kerrie; Seymour, Emily; Peters, Bjoern; Sette, Alessandro

    2016-01-01

    The recent increase in whooping cough in vaccinated populations has been attributed to waning immunity associated with the acellular vaccine. The Immune Epitope Database (IEDB) is a repository of immune epitope data from the published literature and includes T cell and antibody epitopes for human pathogens. The IEDB conducted a review of the epitope literature, which revealed 300 Bordetella pertussis-related epitopes from 39 references. Epitope data are currently available for six virulence factors of B. pertussis: pertussis toxin, pertactin, fimbrial 2, fimbrial 3, adenylate cyclase and filamentous hemagglutinin. The majority of epitopes were defined for antibody reactivity; fewer T cell determinants were reported. Analysis of available protective correlates data revealed a number of candidate epitopes; however few are defined in humans and few have been shown to be protective. Moreover, there are a limited number of studies defining epitopes from natural infection versus whole cell or acellular/subunit vaccines. The relationship between epitope location and structural features, as well as antigenic drift (SNP analysis) was also investigated. We conclude that the cumulative data is yet insufficient to address many fundamental questions related to vaccine failure and this underscores the need for further investigation of B. pertussis immunity at the molecular level. PMID:24530743

  5. Clinical presentation of infants hospitalised with pertussis

    African Journals Online (AJOL)

    [7] In SA, whole-cell pertussis vaccine (administered as a trivalent vaccine to include tetanus and diphtheria) was replaced by acellular pertussis vaccine in 2009. The pentavalent vaccine (diphtheria, tetanus, acellular pertussis, inactivated polio vaccine and haemophilus influenza type b (DTaP-. IPV/Hib) was also introduced ...

  6. Vaccine independence, local competences and globalisation: lessons from the history of pertussis vaccines

    NARCIS (Netherlands)

    Blume, S.; Zanders, M.

    2006-01-01

    In the context of global vaccine politics ‘vaccine independence’ has been defined as the assumption of financial responsibility for vaccine procurement. This paper suggests ‘the possibility of vaccine choice’ as an alternative meaning for the term. How far does local competence in vaccine

  7. Gulf war syndrome: could it be triggered by biological warfare-vaccines using pertussis as an adjuvant?

    Science.gov (United States)

    Tournier, J-N; Jouan, A; Mathieu, J; Drouet, E

    2002-04-01

    Several recent epidemiological studies have shown that vaccinations against biological warfare using pertussis as an adjuvant were associated with the Gulf war syndrome. If such epidemiological findings are confirmed, we propose that the use of pertussis as an adjuvant could trigger neurodegeneration through induction of interleukin-1beta secretion in the brain. In turn, neuronal lesions may be sustained by stress or neurotoxic chemical combinations. Particular susceptibility for IL-1beta secretion and potential distant neuronal damage could provide an explanation for the diversity of the symptoms observed on veterans. Copyright 2002 Elsevier Science Ltd. All rights reserved.

  8. Dose response and efficacy of a live, attenuated human rotavirus vaccine in Mexican infants.

    Science.gov (United States)

    Ruiz-Palacios, Guillermo M; Guerrero, M Lourdes; Bautista-Márquez, Aurora; Ortega-Gallegos, Hilda; Tuz-Dzib, Fernando; Reyes-González, Leticia; Rosales-Pedraza, Gustavo; Martínez-López, Julia; Castañón-Acosta, Erika; Cervantes, Yolanda; Costa-Clemens, SueAnn; DeVos, Beatrice

    2007-08-01

    Immunization against rotavirus has been proposed as the most cost-effective intervention to reduce the disease burden associated with this infection worldwide. The objective of this study was to determine the dose response, immunogenicity, and efficacy of 2 doses of an oral, attenuated monovalent G1[P8] human rotavirus vaccine in children from the same setting in Mexico, where the natural protection against rotavirus infection was studied. From June 2001 through May 2003, 405 healthy infants were randomly assigned to 1 of 3 vaccine groups (virus concentrations 10(4.7), 10(5.2), and 10(5.8) infectious units) and to a placebo group and were monitored to the age of 2 years. The vaccine/placebo was administered concurrently with diphtheria-tetanus toxoid-pertussis/hepatitis B/Haemophilus influenzae type b vaccine at 2 and 4 months of age. After the administration of the first vaccine/placebo dose, weekly home visits to collect information regarding infant health were conducted. Stool samples were collected during each gastroenteritis episode and tested for rotavirus antigen and serotype. The vaccine was well tolerated and induced a greater rate of seroconversion than observed in infants who received placebo. For the pooled vaccine groups, efficacy after 2 oral doses was 80% and 95% against any and severe rotavirus gastroenteritis, respectively. Efficacy was 100% against severe rotavirus gastroenteritis and 70% against severe gastroenteritis of any cause with the vaccine at the highest virus concentration (10(5.8) infectious units). The predominant infecting rotavirus serotype in this cohort was wild-type G1 (85%). Adverse events, including fever, irritability, loss of appetite, cough, diarrhea, and vomiting, were similar among vaccinees and placebo recipients. This new oral, live, attenuated human rotavirus vaccine was safe, immunogenic, and highly efficacious in preventing any and, more importantly, severe rotavirus gastroenteritis in healthy infants. This vaccine

  9. Prior DNA vaccination does not interfere with the live-attenuated measles vaccine.

    Science.gov (United States)

    Premenko-Lanier, Mary; Rota, Paul; Rhodes, Gary; Bellini, William; McChesney, Michael

    2004-01-26

    The currently used live-attenuated measles vaccine is very effective although maternal antibody prevents its administration prior to 6 months of age. We are investigating the ability of a DNA vaccine encoding the measles viral hemagglutinin, fusion and nucleoprotein to protect newborn infants from measles. Here, we show that a measles DNA vaccine protects juvenile macaques from pathogenic measles virus challenge and that macaques primed and boosted with this DNA vaccine have anemnestic antibody and cell-mediated responses after vaccination with a live-attenuated canine distemper-measles vaccine. Therefore, this DNA vaccine administered to newborn infants may not hinder the subsequent use of live-attenuated measles vaccine.

  10. Experience with monocomponent acellular pertussis combination vaccines for infants, children, adolescents and adults--a review of safety, immunogenicity, efficacy and effectiveness studies and 15 years of field experience.

    Science.gov (United States)

    Thierry-Carstensen, Birgit; Dalby, Tine; Stevner, Michael A; Robbins, John B; Schneerson, Rachel; Trollfors, Birger

    2013-10-25

    Combination vaccines containing a monocomponent acellular pertussis (aP) vaccine, manufactured at Statens Serum Institut (SSI), Denmark, have successfully controlled Bordetella pertussis infections in Denmark since 1997. The efficacy of this aP vaccine was 71% in a double-blind, randomised and controlled clinical trial. Its safety and immunogenicity have been demonstrated in infants, children, adolescents and adults. In approximately 500,000 children it was effective against pertussis requiring hospitalisation (VE: 93% after 3 doses) and against pertussis not requiring hospitalisation (VE: 78% after 3 doses). IgG antibodies against pertussis toxin (IgG anti-PT) response rates after booster vaccination of adults with tetanus, diphtheria and aP combination vaccine (TdaP) were considerably higher for this monocomponent aP vaccine containing 20μg pertussis toxoid, inactivated by hydrogen peroxide (92.0%), than for two multicomponent aP vaccines inactivated by formaldehyde and/or glutaraldehyde: 3-component aP with 8μg pertussis toxoid (77.2%) and 5-component aP with 2.5μg pertussis toxoid (47.1%), without compromising the safety profile. In Denmark where this monocomponent aP vaccine has been the only pertussis vaccine in use for 15 years, there has been no pertussis epidemic since 2002 (population incidence 36 per 100,000), in contrast to neighbouring countries, where epidemics have occurred. This monocomponent aP vaccine can be used in combination vaccines for primary and booster vaccination against pertussis in all age groups and is an important tool for successful pertussis control. Copyright © 2013 The Authors. Published by Elsevier Ltd.. All rights reserved.

  11. [Local reactions after diphtheria-tetanus-acellular pertussis vaccines in mice; changes in histopathology at the injection site].

    Science.gov (United States)

    Nagaoka, Chiharu; Katsuta, Tomohiro; Honjo, Ayako; Tateyama, Satoshi; Tokutake, Tadaomi; Arimoto, Yutaka; Nakajima, Natsuki; Goshima, Toshiro; Kato, Tatsuo

    2006-03-01

    Diphtheria-tetanus-acellular pertussis vaccine (DTaP) developed in Japan is now widely used worldwide. DTaP is safer than the diphtheria-tetanus-whole-cell pertussis vaccine (DTwP) and has fewer severe side effects, but local reactions such as redness, swelling, and induration are still reported. The pathophysiological mechanism of these reactions is controversial. To clarify the cause of local reactions, we conducted studies using the mouse model. After administering either one or two abdominal subcutaneous DTaP inoculations, we observed changes in histopathology at the injection site at 24h, 48h, and 7 days. The control group, inoculated with physiologic saline, showed no significant changes either pathologically or with the naked eye. All mice after DTaP vaccination showed indurations at the injection site. Pathologically, we watched leukocyte invasion into or around the site, especially neutrophils and eosinophils. After the first vaccination, the extent of the invasion was strong 24h and 7 days later. At 24h following the second vaccination, a dramatic leukocyte invasion seen persisted at 7days. At 7 days after the first vaccination, peripheral fibrosis had begun, and when a second vaccination was administered, it began even earlier at the second site. These histopathological changes show that local reactions are caused by both inflammatory and allergic responses. Because this mouse study resulted in the same pattern of reactions observed in humans, this method will be useful for studies focusing on local reactions.

  12. Safety and immunogenicity of tetanus-diphtheria-acellular pertussis vaccine administered to children 10 or 11 years of age.

    Science.gov (United States)

    Marshall, Gary S; Pool, Vitali; Greenberg, David P; Johnson, David R; Sheng, Xiaohua; Decker, Michael D

    2014-11-01

    Boosting immunity to tetanus, diphtheria, and pertussis through the use of Tdap vaccines is routinely recommended at 11 to 12 years of age; some states, however, require Tdap for entry into middle school, which may begin at 10 years of age. This study was conducted to determine whether Tdap5 (Adacel), which is licensed for use in children beginning at 11 years of age, is as safe and immunogenic in 10-year-olds as it is in 11-year-olds. Children who had received 5 previous doses of any diphtheria-tetanus-acellular pertussis (DTaP) vaccine were enrolled in a phase IV clinical trial; 646 10-year-olds and 645 11-year-olds completed the study, which involved a single intramuscular dose of Tdap5 along with pre- and postvaccination serologies. Postvaccination geometric mean concentrations (GMCs) of antibody to pertussis antigens (pertussis toxoid, filamentous hemagglutinin, pertactin, and fimbria types 2 and 3) of 10-year-olds were noninferior to those of 11-year-olds, as were booster response rates for all pertussis antibodies, except for those to fimbrial antigens (94% and 97%, respectively). Seroprotection rates among 10-year-olds for tetanus and diphtheria were noninferior to those in 11-year-olds. Rates of injection site reactions, solicited systemic reactions, and unsolicited adverse events, adverse reactions, and serious adverse events were similar in the two groups. These data support the conclusion that Tdap5 is safe and immunogenic in 10-year-olds. (This study has been registered at ClinicalTrials.gov under registration no. NCT01311557.). Copyright © 2014, American Society for Microbiology. All Rights Reserved.

  13. Safety and immunogenicity of a combined Tetanus, Diphtheria, recombinant acellular Pertussis vaccine (TdaP) in healthy Thai adults.

    Science.gov (United States)

    Sirivichayakul, Chukiat; Chanthavanich, Pornthep; Limkittikul, Kriengsak; Siegrist, Claire-Anne; Wijagkanalan, Wassana; Chinwangso, Pailinrut; Petre, Jean; Hong Thai, Pham; Chauhan, Mukesh; Viviani, Simonetta

    2017-01-02

    An acellular Pertussis (aP) vaccine containing recombinant genetically detoxified Pertussis Toxin (PTgen), Filamentous Hemagglutinin (FHA) and Pertactin (PRN) has been developed by BioNet-Asia (BioNet). We present here the results of the first clinical study of this recombinant aP vaccine formulated alone or in combination with tetanus and diphtheria toxoids (TdaP). A phase I/II, observer-blind, randomized controlled trial was conducted at Mahidol University in Bangkok, Thailand in healthy adult volunteers aged 18-35 y. The eligible volunteers were randomized to receive one dose of either BioNet's aP or Tetanus toxoid-reduced Diphtheria toxoid-acellular Pertussis (TdaP) vaccine, or the Tdap Adacel® vaccine in a 1:1:1 ratio. Safety follow-up was performed for one month. Immunogenicity was assessed at baseline, at 7 and 28 d after vaccination. Anti-PT, anti-FHA, anti-PRN, anti-tetanus and anti-diphtheria IgG antibodies were assessed by ELISA. Anti-PT neutralizing antibodies were assessed also by CHO cell assay. A total of 60 subjects (20 per each vaccine group) were enrolled and included in the safety analysis. Safety laboratory parameters, incidence of local and systemic post-immunization reactions during 7 d after vaccination and incidence of adverse events during one month after vaccination were similar in the 3 vaccine groups. One month after vaccination, seroresponse rates of anti-PT, anti-FHA and anti-PRN IgG antibodies exceeded 78% in all vaccine groups. The anti-PT IgG, anti-FHA IgG, and anti-PT neutralizing antibody geometric mean titers (GMTs) were significantly higher following immunization with BioNet's aP and BioNet's TdaP than Adacel® (Pdiphtheria GMTs at one month after immunization were comparable in all vaccine groups. All subjects had seroprotective titers of anti-tetanus and anti-diphtheria antibodies at baseline. In this first clinical study, PTgen-based BioNet's aP and TdaP vaccines showed a similar tolerability and safety profile to Adacel

  14. Risk of febrile seizures and epilepsy after vaccination with diphtheria, tetanus, acellular pertussis, inactivated poliovirus, and Haemophilus influenzae type B.

    Science.gov (United States)

    Sun, Yuelian; Christensen, Jakob; Hviid, Anders; Li, Jiong; Vedsted, Peter; Olsen, Jørn; Vestergaard, Mogens

    2012-02-22

    Vaccination with whole-cell pertussis vaccine carries an increased risk of febrile seizures, but whether this risk applies to the acellular pertussis vaccine is not known. In Denmark, acellular pertussis vaccine has been included in the combined diphtheria-tetanus toxoids-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine since September 2002. To estimate the risk of febrile seizures and epilepsy after DTaP-IPV-Hib vaccination given at 3, 5, and 12 months. A population-based cohort study of 378,834 children who were born in Denmark between January 1, 2003, and December 31, 2008, and followed up through December 31, 2009; and a self-controlled case series (SCCS) study based on children with febrile seizures during follow-up of the cohort. Hazard ratio (HR) of febrile seizures within 0 to 7 days (0, 1-3, and 4-7 days) after each vaccination and HR of epilepsy after first vaccination in the cohort study. Relative incidence of febrile seizures within 0 to 7 days (0, 1-3, and 4-7 days) after each vaccination in the SCCS study. A total of 7811 children were diagnosed with febrile seizures before 18 months, of whom 17 were diagnosed within 0 to 7 days after the first (incidence rate, 0.8 per 100,000 person-days), 32 children after the second (1.3 per 100,000 person-days), and 201 children after the third (8.5 per 100,000 person-days) vaccinations. Overall, children did not have higher risks of febrile seizures during the 0 to 7 days after the 3 vaccinations vs a reference cohort of children who were not within 0 to 7 days of vaccination. However, a higher risk of febrile seizures was found on the day of the first (HR, 6.02; 95% CI, 2.86-12.65) and on the day of the second (HR, 3.94; 95% CI, 2.18-7.10), but not on the day of the third vaccination (HR, 1.07; 95% CI, 0.73-1.57) vs the reference cohort. On the day of vaccination, 9 children were diagnosed with febrile seizures after the first (5.5 per 100,000 person-days), 12

  15. Safety and reactogenicity of the combined diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae type b (DTPa-IPV/Hib) vaccine in healthy Vietnamese toddlers: An open-label, phase III study.

    Science.gov (United States)

    Anh, Dang Duc; Van Der Meeren, Olivier; Karkada, Naveen; Assudani, Deepak; Yu, Ta-Wen; Han, Htay Htay

    2016-03-03

    The introduction of combination vaccines plays a significant role in increasing vaccine acceptance and widening vaccine coverage. Primary vaccination against diphtheria, tetanus, pertussis, poliomyelitis and Haemophilus influenza type b (Hib) diseases has been implemented in Vietnam. In this study we evaluated the safety and reactogenicity of combined diphtheria-tetanus-pertussis-inactivated polio (DTPa-IPV)/Hib vaccine when administered as a booster dose in 300 healthy Vietnamese children Vietnamese children aged <2 years.

  16. [Modification of pertussis vaccination schedule in Chile, immunization of special groups and control strategies: Commentary from the Consultive Committee of Immunizations of The Chilean Society of Infectious Diseases].

    Science.gov (United States)

    Potin, Marcela; Cerda, Jaime; Contreras, Lily; Muñoz, Alma; Ripoll, Erna; Vergara, Rodrigo

    2012-06-01

    In Chile, an increased number of notifications of cases of whooping cough was detected at the beginning of October 2010, and maintained through 2012. Accumulated cases during 2011 were 2,581 (15.0 per 100,000), which is greater than the number of cases registered during the period 2008-2010 (2,460 cases). On the other hand, the local sanitary authority introduced a modification of pertussis vaccination schedule (starting 2012), which consists in the replacement of the second booster of pertussis vaccine (DTwP, administered to 4-year-old children) as well as diphtheria-tetanus toxoid (dT, administered to second grade scholars) for an acellular pertussis vaccine with reduced antigenic content (dTpa), which will be administrated to first grade scholars. The Consultive Committee of Immunizations considers that the modification is adequate, since it extends the age of protection, reducing at least in theory the infection in older scholars and adolescents -who are significant sources of transmission of Bordetella pertussis to infants- using an adequate vaccine formulation (acellular pertussis vaccine). The available evidence regarding vaccination in special groups (adolescents and adults, health-care workers and pregnant women) and cocooning strategy are commented.

  17. Immunogenicity, reactogenicity and consistency of production of a Brazilian combined vaccine against diphtheria, tetanus, pertussis and Haemophilus influenzae type b

    Directory of Open Access Journals (Sweden)

    Reinaldo de Menezes Martins

    2008-11-01

    Full Text Available A randomized, double-blinded study evaluating the immunogenicity, safety and consistency of production of a combined diphtheria-tetanus-pertussis-Haemophilus influenzae type b vaccine entirely produced in Brazil by Bio-Manguinhos and Instituto Butantan (DTP/Hib-BM was undertaken. The reference vaccine had the same DTP vaccine but the Hib component was produced using purified materials supplied by GlaxoSmithKline (DTP/Hib-GSK, which is registered and has supplied the Brazilian National Immunization Program for over more than five years. One thousand infants were recruited for the study and received vaccinations at two, four and six months of age. With respect to immunogenicity, the vaccination protocol was followed in 95.6% and 98.4% of infants in the DTP/Hib-BM and DTP/Hib-GSK groups, respectively. For the Hib component of the study, there was 100% seroprotection (>0.15 µg/mL with all three lots of DTP/Hib-BM and DTP/Hib-GSK. The geometric mean titer (GMT was 9.3 µg/mL, 10.3 µg/mL and 10.3 µg/mL for lots 1, 2 and 3 of DTP/Hib-BM, respectively, and the GMT was 11.3 g/mL for DTP/Hib-GSK. For diphtheria, tetanus and pertussis, seroprotection was 99.7%, 100% and 99.9%, respectively, for DTP/Hib-BM, three lots altogether and 99.2%, 100% and 100% for DTP/Hib-GSK. GMTs were similar across all lots and vaccines. Adverse events rates were comparable among the vaccine groups. The Brazilian DTP/Hib vaccine demonstrated an immunogenicity and reactogenicity profile similar to that of the reference vaccine.

  18. Risk factors of delay proportional probability in diphtheria-tetanus-pertussis vaccination of Iranian children; Life table approach analysis

    Directory of Open Access Journals (Sweden)

    Mohsen Mokhtari

    2015-01-01

    Full Text Available Despite success in expanded program immunization for an increase in vaccination coverage in the children of world, timeliness and schedule of vaccination remains as one of the challenges in public health. This study purposed to demonstrate the related factors of delayed diphtheria-tetanus-pertussis (DTP vaccination using life table approach. A historical cohort study conducted in the poor areas of five large Iran cities. Totally, 3610 children with 24-47 months old age who had documented vaccination card were enrolled. Time of vaccination for the third dose of DTP vaccine was calculated. Life table survival was used to calculate the proportional probability of vaccination in each time. Wilcoxon test was used for the comparison proportional probability of delayed vaccination based on studies factors. The overall median delayed time for DTP3 was 38.52 days. The Wilcoxon test showed that city, nationality, education level of parents, birth order and being in rural areas are related to the high probability of delay time for DTP3 vaccination (P 0.05. Being away from the capital, a high concentration of immigrants in the city borders with a low socioeconomic class leads to prolonged delay in DTP vaccination time. Special attention to these areas is needed to increase the levels of parental knowledge and to facilitate access to the health services care.

  19. RE-VACCINATION OF CHILDREN OVER 1,5 YEARS OLD AGAINST DIPHTHERIA, PERTUSSIS, TETANUS, POLIOMYELITIS AND HEMOPHILIC INFECTION

    Directory of Open Access Journals (Sweden)

    S.M. Kharit

    2009-01-01

    Full Text Available The article presents the results of the observation of 200 children under the age 18–42 months (64 healthy children and 136 patients with allergic symptoms, residual lesions of CNS, frequently ailing children, and having reactions of previous vaccination in medical history who were re-vaccinated with vaccine Pentaxim. It was shown that 77% of children had asymptomatic post-vaccinal period. Only 1,5% of patients showed severe reactions with fever > 38,6_С. Local reactions (not over 3–5 cm developed in 25,5% of children with allergy, lesions of CNS and frequently ailing children, their rate was significantly higher than in healthy children (7,8%. No one had post-vaccinal complications. An estimation of reactogenicity of vaccine proved its safety and suitability of administration as first re-vaccination against pertussis, diphtheria, tetanus, poliomyelitis and one-time vaccination against Haemophilus influenzae type b in children after 1 year old in different state of health.Key words: children, vaccinations, Pentaxim, post-vaccinal period, safety.(Voprosy sovremennoi pediatrii — Current Pediatrics. 2009;8(6:20-25

  20. [SAFETY AND IMMUNOGENICITY OF A NATIONAL COMBINED VACCINE AGAINST PERTUSSIS, DIPHTHERIA, TETANUS, HEPATITIS B AND Hib-INFECTION, CONTAINING ACELLULAR PERTUSSIS COMPONENT, DURING IMMUNIZATION OF ADULTS].

    Science.gov (United States)

    Feldblyum, I V; Nikolaeva, A M; Pavroz, K A; Danilina, T V; Sosnina, O Yu; Vyaznikova, T V; Ershov, A E; Trofimov, D M; Polushkina, A V

    2016-01-01

    Study safety, reactogenicity and immunologic effectiveness of a national combined vaccine against diphtheria, pertussis (acellular component), tetanus, hepatitis B and Hib-infection during immunization of volunteers aged 18-60 years. The study was carried out in accordance with ethical standards and requirements, regulated by Helsinki declaration and Good clinical practice (ICHGCP). In a simple non-randomized clinical trial 20 adult volunteers took part, the mean age of those was 46.9 years. Registered: post-vaccination reactions (both local and systemic) were mild and of moderate degree of severity, stopped independently after 2-3 days without administration of drug treatment. Postvaccinal complications were not noted. Parameters of general and biochemical analysis of blood, urine, IgE content in dynamics of immunization were within normal limits. A single administration of aAPDT--HepB+Hib to individuals aged 18-60 years resulted in development of antibodies against all the components of the preparation. Seroconversion factor fluctuated from 6.9 to 53.5: The results obtained allow to recommend the vaccine for evaluation of its safety, reactogenicity, immunologic and prophylaxis effectiveness in randomized clinical observation trials in children.

  1. Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products

    International Nuclear Information System (INIS)

    May, J.C.; Rey, L.; Lee, C.-J.; Arciniega, Juan

    2004-01-01

    Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine

  2. Evaluation of components of X-ray irradiated 7-valent pneumococcal conjugate vaccine and pneumococcal vaccine polyvalent and X-ray and gamma-ray irradiated acellular pertussis component of DTaP vaccine products

    Energy Technology Data Exchange (ETDEWEB)

    May, J.C. E-mail: may@cber.fda.gov; Rey, L. E-mail: louis.rey@bluewin.ch; Lee, C.-J.; Arciniega, Juan

    2004-10-01

    Samples of pneumococcal vaccine polyvalent, 7-valent pneumococcal conjugate vaccine, and two different diphtheria and tetanus toxoids and acellular pertussis vaccines adsorbed were irradiated with X-rays and/or gamma-rays (Co-60). Mouse IgG and IgM antibody responses (ELISA) for types 9V, 14, 18C, and 19F pneumococcal polysaccharides and conjugates indicated that the polysaccharides were more tolerant of the radiation than the conjugates. The mouse antibody response for the detoxified pertussis toxin (PT) antigen, filamentous hemagglutinin antigen (FHA), pertactin (PRN), and fimbriae types 2 and 3 (FIM) antigens for the appropriate vaccine type indicated that the antibody response was not significantly changed in the 25 kGy X-ray irradiated vaccines frozen in liquid nitrogen compared to the control vaccine.

  3. Early diphtheria-tetanus-pertussis vaccination associated with higher female mortality and no difference in male mortality in a cohort of low birthweight children

    DEFF Research Database (Denmark)

    Aaby, Peter; Ravn, Henrik; Roth, Adam Anders Edvin

    2012-01-01

    Studies from low-income countries have suggested that diphtheria-tetanus-pertussis (DTP) vaccine provided after Bacille Calmette-Guerin (BCG) vaccination may have a negative effect on female survival. The authors examined the effect of DTP in a cohort of low birthweight (LBW) infants....

  4. The safety and reactogenicity of a reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) booster vaccine in healthy Vietnamese children.

    Science.gov (United States)

    Anh, Dang Duc; Jayadeva, Girish; Kuriyakose, Sherine; Han, Htay Htay

    2016-08-17

    Despite effective infant immunization against pertussis, the disease continues to circulate due to waning immunity. Booster vaccinations against pertussis beyond infancy are widely recommended. In Vietnam, however, no recommendations for pertussis boosters beyond the second year of life exist. This open-label, single-centre study was designed to assess the safety of a single booster dose of reduced-antigen-content-diphtheria-tetanus-acellular-pertussis vaccine (dTpa) in 300 healthy Vietnamese children (mean age 7.9years), who had completed primary vaccination against diphtheria, tetanus and pertussis. Solicited symptoms were recorded for 4days and unsolicited and serious adverse events (SAEs) for 31days post-vaccination. Pain and fatigue were the most common solicited local and general symptoms in 35.0% and 14.0% of children, respectively. Grade 3 swelling occurred in 3 children; no large injection site reactions or SAEs were reported. The dTpa booster vaccine was well tolerated and this study supports its administration in school age Vietnamese children. Copyright © 2016 GSK group of companies. Published by Elsevier Ltd.. All rights reserved.

  5. Safety of a tetanus-diphtheria-acellular pertussis vaccine when used off-label in an elderly population.

    Science.gov (United States)

    Tseng, Hung Fu; Sy, Lina S; Qian, Lei; Marcy, S Michael; Jackson, Lisa A; Glanz, Jason; Nordin, Jim; Baxter, Roger; Naleway, Allison; Donahue, James; Weintraub, Eric; Jacobsen, Steven J

    2013-02-01

    Published data on the safety of tetanus-diphtheria-acellular pertussis vaccine (Tdap) in persons aged ≥65 years are limited. This study aims to examine a large cohort of Tdap users ≥65 years for evidence of increased risk of adverse events following vaccination. A matched cohort study design and a self-controlled case series (SCCS) design were used. The study population was adults aged ≥65 years who received the Tdap or tetanus and diphtheria (Td) vaccine during 1 January 2006-31 December 2010 at 7 health maintenance organizations in the United States. Seven major groups of prespecified events were identified electronically by diagnostic codes. The study included 119 573 Tdap vaccinees and the same number of Td vaccinees. The results indicated that the risk of the prespecified events following Tdap was comparable to that following Td vaccination in this elderly population. There was a small increased rate of codes suggesting medically attended inflammatory or allergic events in 1-6 days following Tdap in the SCCS analysis (incidence rate ratio, 1.59 [95% confidence interval, 1.40-1.81]). Although there is a small increased risk of medically attended inflammatory or allergic events in 1-6 days following Tdap compared to other time periods, it is no more common than that following Td. This study provides empirical safety data suggesting that immunizing adults aged ≥65 years with Tdap to reduce the risk of pertussis in the elderly and their contacts should not have untoward safety consequences.

  6. Pertussis circulation has increased T-cell immunity during childhood more than a second acellular booster vaccination in Dutch children 9 years of age.

    Directory of Open Access Journals (Sweden)

    Rose-Minke Schure

    Full Text Available UNLABELLED: Here we report the first evaluation of T-cell responses upon a second acellular pertussis booster vaccination in Dutch children at 9 years of age, 5 years after a preschool booster vaccination. Blood samples of children 9 years of age were studied longitudinally until 1 year after the second aP booster and compared with those after the first aP booster in children 4 and 6 years of age from a cross-sectional study. After stimulation with pertussis-vaccine antigens, Th1, Th2 and Th17 cytokine responses were measured and effector memory cells (CCR7-CD45RA- were characterized by 8-colour FACS analysis. The second aP booster vaccination at pre-adolescent age in wP primed individuals did increase pertussis-specific Th1 and Th2 cytokine responses. Noticeably, almost all T-cell responses had increased with age and were already high before the booster vaccination at 9 years of age. The enhancement of T-cell immunity during the 5 year following the booster at 4 years of age is probably caused by natural boosting due to the a high circulation of pertussis. However, the incidence of pertussis is high in adolescents and adults who have only received the Dutch wP vaccine during infancy and no booster at 4 years of age. Therefore, an aP booster vaccination at adolescence or later in these populations might improve long-term immunity against pertussis and reduce the transmission to the vulnerable newborns. TRIAL REGISTRATION: Controlled-Trials.com ISRCTN64117538.

  7. [Immunogenicity of sabin inactivated poliovirus vaccine induced by diphtheria-tetanus-acellular pertussis and Sabin inactivated poliovirus combined vaccine].

    Science.gov (United States)

    Ma, Yan; Qin, Min; Hu, Hui-Qiong; Ji, Guang; Feng, Ling; Gao, Na; Gu, Jie; Xie, Bing-Feng; He, Ji-Hong; Sun, Ming-Bo

    2011-06-01

    In order to search the preparation process and optimazing dosage ratio of adsorbed diphtheria-tetanus-acellular pertussis and sabin inactivated poliovirus combined vaccine (DTaP-sIPV), the neutralizing antibody titers of IPV induced by different concentration of DTaP-sIPV were investigated on rats. Two batches of DTaP-sLPV were produced using different concentration of sIPV and the quality control was carried. Together with sabin-IPV and DTaP-wIPV ( boostrix-polio, GSK, Belgium) as control group, the DTaP-sIPV were administrated on three-dose schedule at 0, 1, 2 month on rats. Serum sample were collected 30 days after each dose and neutralizing antibody titers against three types poliovirus were determined using micro-neutralization test. Two batches of prepared DTaP-sIPV and control sLPV were according to the requirement of Chinese Pharmacopoeia (Volume III, 2005 edition) and showed good stability. The seropositivity rates were 100% for sabin inactivated poliovirus antigen in all groups. The GMTs (Geometric mean titers) of neutralizing antibodies against three types poliovirus increased. The prepared DTaP-sIPV was safe, stable and effective and could induced high level neutralizing antibody against poliovirus on rats.

  8. A case-control study to assess the effectiveness of pertussis vaccination during pregnancy on newborns, Valencian community, Spain, 1 March 2015 to 29 February 2016.

    Science.gov (United States)

    Bellido-Blasco, Juan; Guiral-Rodrigo, Silvia; Míguez-Santiyán, Ana; Salazar-Cifre, Antonio; González-Morán, Francisco

    2017-06-01

    In the Valencian Community (Spain), the programme of maternal pertussis vaccination during pregnancy started in January 2015. The objective of this study was to estimate in this region the vaccine effectiveness (VE) in protecting newborns against laboratory-confirmed pertussis infection. A matched case-control study was undertaken in the period between 1 March 2015 and 29 February 2016. Twenty-two cases and 66 controls (+/- 15 days of age difference) were included in the study. Cases were non-vaccinated infants case three unvaccinated controls were selected. Odds ratios (OR) were calculated by multiple conditional logistic regression for association between maternal vaccination and infant pertussis. Other children in the household, as well as mother- and environmental covariates were taken into account. The VE was calculated as 1 - OR. Mothers of five cases (23%) and of 41 controls (62%) were vaccinated during pregnancy. The adjusted VE was 90.9% (95% confidence interval (CI): 56.6 to 98.1). The only covariate in the final model was breastfeeding (protective effect). Our study provides evidence in favour of pertussis vaccination programmes for pregnant women in order to prevent whooping cough in infants aged less than 3 months. This article is copyright of The Authors, 2017.

  9. Influence of vaccination with Bordetella pertussis cells on haemopoiesis in sublethally irradiated mice and their radiation lethality

    International Nuclear Information System (INIS)

    Kwiek, S.; Bitny-Szlachto, S.

    1978-01-01

    Post-irradiation lethality of CFW mice has turned out to be enhanced by vaccination with Bordetella pertussis cells 10 min., 48 hrs. prior or 48 hrs. after the exposure to X-rays. The sensitization factor was found to be 1.23, as it revealed by decrease of radiation LD 50 . Granulopoiesis and erythropoiesis proved to be stimulated by vaccination, in mice irradiated with 200 or 400 R but not in those after 600 R. Direct radiosensitivity of CFU was not altered by vaccination, but the subsequent loss of bone marrow stem cells was enhanced in vaccinated mice. On the other hand, endocolonization of spleens with bone marrow stem cells has turned out to be highly enhanced by the vaccine, resulting in confluent growth of colonies. This effect of the vaccine was not abolished by hydroxyurea given 15 min. or 1 hr. after vaccination. Enhanced post-irradiation lethality is considered to result from fall of the bone marrow stem cell pool below the level indispensable to ensure the post-irradiation recovery of the haemopoietic system. (author)

  10. Non-specific effects of diphtheria-tetanus-pertussis and measles vaccinations? An analysis of surveillance data from Navrongo, Ghana.

    Science.gov (United States)

    Welaga, Paul; Nielsen, Jens; Adjuik, Martin; Debpuur, Cornelius; Ross, David A; Ravn, Henrik; Benn, Christine S; Aaby, Peter

    2012-12-01

    Studies from low-income countries have suggested that routine vaccinations may have non-specific effects on child mortality; measles vaccine (MV) is associated with lower mortality and diphtheria-tetanus-pertussis (DTP) with relatively higher mortality. We used data from Navrongo, Ghana, to examine the impact of vaccinations on child mortality. Vaccination status was assessed at the initiation of a trial of vitamin A supplementation and after 12 and 24 months of follow-up. Within the placebo group, we compared the mortality over the first 4 months and the full 2 years of follow-up for different vaccination status groups with different likelihoods of additional vaccinations during follow-up. The frequency of additional vaccinations was assessed among children whose vaccination card was seen at 12 and 24 months of follow-up. Among children with a vaccination card, more than 75% received missing DTP or MV during the first 12 months of follow-up, whereas only 25% received these vaccines among children with no vaccination card at enrollment. Children without a card at enrollment had a significant threefold higher mortality over the 2-year follow-up period than those fully vaccinated. The small group of children with DTP3-4 but no MV at enrollment had lower mortality than children without a card and had the same mortality as fully vaccinated children. In contrast, children with 1-2 DTP doses but no MV had a higher mortality during the first 4 months than children without a card [MRR = 1.65 (0.95, 2.87)]; compared with the fully vaccinated children, they had significantly higher mortality after 4 months [MRR = 2.38 (1.07, 5.30)] and after 2 years [MRR = 2.41 (1.41, 4.15)]. Children with 0-2 DTP doses at enrollment had higher mortality after 4 months (MRR = 1.67 (0.82, 3.43) and after 2 years [MRR = 1.85 (1.16, 2.95)] than children who had all three doses of DTP at enrollment. As hypothesised, DTP vaccination was associated with higher child mortality than measles

  11. Using the 4 Pillars™ Practice Transformation Program to increase adolescent human papillomavirus, meningococcal, tetanus-diphtheria-pertussis and influenza vaccination.

    Science.gov (United States)

    Zimmerman, Richard K; Raviotta, Jonathan M; Nowalk, Mary Patricia; Moehling, Krissy K; Reis, Evelyn Cohen; Humiston, Sharon G; Lin, Chyongchiou Jeng

    2017-10-27

    To report the results of an intervention using the 4 Pillars™ Practice Transformation Program (4 Pillars™ Program) to increase adolescent vaccinations including human papillomavirus vaccine (HPV) and influenza vaccines, which remain underutilized in this population. Eleven pediatric and family medicine practices, previously control sites from a randomized controlled cluster trial, with ≥50 adolescent patients participated. The 4 Pillars™ Program was the foundation of the intervention. De-identified demographic, office visit and vaccination data were derived from electronic medical record extractions for patients whose date of birth was 4/1/1997 to 4/1/2004 (ages 11-17years at baseline). Vaccination rates for HPV, influenza, tetanus-pertussis-diphtheria (Tdap) and meningococcal (MenACWY) vaccines were determined for all eligible patients pre- and post intervention (i.e., vaccination rates on 4/1/2015 and 4/30/2016). Among 9473 patients ages 11-17years at baseline (4/1/2015), mean pre-intervention vaccination rates for HPV initiation and completion, meningococcal, Tdap and influenza vaccines were below national levels. Rates increased significantly post intervention (P<0.001) for HPV initiation which increased 17.1 percentage points (PP) from 51.4%; HPV completion increased 14.8PP from 30.7%, meningococcal vaccine uptake increased 16.6PP from 79.1%, Tdap vaccine uptake increased 14.6PP from 76.9%. Influenza vaccine uptake did not increase significantly (2.3PP from 40.1%). In the regression using generalized estimating equations, odds of vaccination were higher for younger, non-white adolescents for all vaccines; being in a smaller practice decreased the odds of Tdap vaccination but increased the odds of influenza vaccination. Clinically and statistically significant improvements in HPV series initiation and completion, and meningococcal and Tdap vaccinations were observed in primary care practices implementing the 4 Pillars™ Practice Transformation Program

  12. Vaccination coverage against pertussis in pregnant women of Catalonia in the first year of implementation of the immunisation program.

    Science.gov (United States)

    Fernández-Cano, María Isabel; Espada-Trespalacios, Xavier; Reyes-Lacalle, Azahara; Manresa Domínguez, Josep Maria; Armadans-Gil, Lluís; Campins-Martí, Magda; Falguera-Puig, Gemma; Toran Monserrat, Pere

    2017-11-01

    The re-emergence of pertussis and the severity of its complications in infants younger than 3 months, were determining factors for starting a vaccination program for pregnant women in the third trimester of gestation in Catalonia in February 2014. This was the first autonomous community to introduce it in Spain. The aim of the study was to estimate the coverage of the program in its first year of implementation. A retrospective analysis was performed on the data from the Primary Care Centre computerised medical records of pregnant women attending Sexual and Reproductive Health Care centres of the Metropolitan Nord area of the province of Barcelona, part of the Catalan Institute of Health. The overall coverage was estimated, as well as the sociodemographic variables of Tdap vaccination of women who had registered a delivery of a live birth between August 2014 and August 2015. A total of 6,697 deliveries of live births were recorded, and 1,713 pregnant women were vaccinated, which represented an overall coverage of 25.6% (95% CI; 24.1-26.1). Vaccination coverage was higher in pregnant women under 18 years and Spanish women (P=.018 and P=.036, respectively). The estimation of vaccine coverage against pertussis in pregnant women in the third trimester of pregnancy, after the first year of implementation of the program in a health area of Catalonia was lower than the objective set. Strategies need to be designed in order to improve program coverage. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Enfermedades Infecciosas y Microbiología Clínica. All rights reserved.

  13. An Open-Label, Randomized Study of a 9-Valent Human Papillomavirus Vaccine Given Concomitantly with Diphtheria, Tetanus, Pertussis, and Poliomyelitis Vaccines to Healthy Adolescents 11 to 15 Years of Age

    DEFF Research Database (Denmark)

    Kosalaraksa, Pope; Mehlsen, Jesper; Vesikari, Timo

    2015-01-01

    .8% in both groups at month 7. For REPEVAX, noninferiority of immune response was established for diphtheria, tetanus, and all polio and pertussis antigens for both groups. There were no vaccine-related serious AEs. CONCLUSION: Overall, concomitant administration of 9vHPV vaccine and REPEVAX was generally...

  14. A Meningococcal Outer Membrane Vesicle Vaccine Incorporating Genetically Attenuated Endotoxin Dissociates Inflammation From Immunogenicity

    Directory of Open Access Journals (Sweden)

    David J. Dowling

    2016-12-01

    Full Text Available Background. Group B Neisseria meningitidis, an endotoxin-producing gram-negative bacterium, causes the highest incidence of group B meningococcus (MenB disease in the first year of life. The Bexsero vaccine is indicated in Europe from 8 weeks of age. Endotoxin components of outer membrane vesicles (OMVs or soluble lipopolysaccharide (LPS represent a potential source of inflammation and residual reactogenicity. The purpose of this study was to compare novel candidate MenB vaccine formulations with licensed vaccines, including Bexsero, using age-specific in vitro culture systems.Methods. OMVs from wild type and inactivated lpxL1 gene mutant N. meningitidis strains were characterized in human neonatal and adult in vitro whole blood assays and dendritic cell arrays. OMVs were benchmarked against licensed vaccines, including Bexsero and whole cell pertussis formulations, with respect to Th-polarizing cytokine and PGE2 production, as well as cell surface activation markers (HLA-DR, CD86, CCR7. OMV immunogenicity was assessed in mice.Results. ΔlpxLI native OMVs demonstrated significantly less cytokine induction in human blood and DCs than Bexsero and most of the other pediatric vaccines (e.g., PedvaxHib, EasyFive, Bacillus Calmette–Guérin (BCG tested. Despite a much lower inflammatory profile in vitro than Bexsero, ΔlpxLI native OMVs still had moderate DC maturing ability and induced robust anti-N. meningitidis antibody responses after murine immunization.Conclusions. A meningococcal vaccine comprised of attenuated LPS-based OMVs with a limited inflammatory profile in vitro induces robust antigen-specific immunogenicity in vivo.

  15. Immunogenicity and safety after booster vaccination of diphtheria, tetanus, and acellular pertussis in young adults: an open randomized controlled trial in Japan.

    Science.gov (United States)

    Hara, Megumi; Okada, Kenji; Yamaguchi, Yuko; Uno, Shingo; Otsuka, Yasuko; Shimanoe, Chisato; Nanri, Hinako; Horita, Mikako; Ozaki, Iwata; Nishida, Yuichiro; Tanaka, Keitaro

    2013-12-01

    The recent increase of pertussis in young adults in Japan is hypothesized to be due in part to waning protection from the acellular pertussis vaccine. While a booster immunization may prevent an epidemic of pertussis among these young adults, little is known about the safety and immunogenicity of such a booster with the diphtheria, tetanus, and acellular pertussis vaccine (DTaP), which is currently available in Japan. One hundred and eleven medical students with a mean age of 19.4 years were randomly divided into 2 groups of 55 and 56 subjects and received, respectively, 0.2 or 0.5 ml of DTaP. Immunogenicity was assessed by performing the immunoassay using serum, and the geometric mean concentration (GMC), GMC ratio (GMCR), seropositive rate, and booster response rate were calculated. Adverse reactions and adverse events were monitored for 7 days after vaccination. After booster vaccination in the two groups, significant increases were found in the antibodies against pertussis toxin, filamentous hemagglutinin, diphtheria toxoid, and tetanus toxoid, and the booster response rates for all subjects reached 100%. The GMCs and GMCRs against all antigens were significantly higher in the 0.5-ml group than in the 0.2-ml group. No serious adverse events were observed. Frequencies of local reactions were similar in the 2 groups, although the frequency of severe local swelling was significantly higher in the 0.5-ml group. These data support the acceptability of booster immunization using both 0.2 and 0.5 ml of DTaP for young adults for controlling pertussis. (This study was registered at UMIN-CTR under registration number UMIN000010672.).

  16. Vaccines.gov

    Science.gov (United States)

    ... Vaccine Safety Vaccines Work Vaccine Types Vaccine Ingredients Vaccines by Disease Chickenpox ... Typhoid Fever Whooping Cough (Pertussis) Yellow Fever Who and When Infants, Children, and Teens ...

  17. Acute necrotizing encephalopathy secondary to diphtheria, tetanus toxoid and whole-cell pertussis vaccination: diffusion-weighted imaging and proton MR spectroscopy findings

    International Nuclear Information System (INIS)

    Aydin, Hale; Ozgul, Esra; Agildere, Ahmet Muhtesem

    2010-01-01

    We present a previously healthy 6-month-old boy who was admitted to our hospital with lethargy, hypotonia and focal clonic seizures 6 days following diptheria, tetanus toxoid and whole-cell pertussis vaccination. A diagnosis of acute necrotising encephalopathy was made with the aid of MRI, including diffusion-weighted imaging and proton MR spectroscopy. (orig.)

  18. Acute necrotizing encephalopathy secondary to diphtheria, tetanus toxoid and whole-cell pertussis vaccination: diffusion-weighted imaging and proton MR spectroscopy findings

    Energy Technology Data Exchange (ETDEWEB)

    Aydin, Hale; Ozgul, Esra; Agildere, Ahmet Muhtesem [Baskent University Hospital, Department of Radiology, Ankara (Turkey)

    2010-07-15

    We present a previously healthy 6-month-old boy who was admitted to our hospital with lethargy, hypotonia and focal clonic seizures 6 days following diptheria, tetanus toxoid and whole-cell pertussis vaccination. A diagnosis of acute necrotising encephalopathy was made with the aid of MRI, including diffusion-weighted imaging and proton MR spectroscopy. (orig.)

  19. Concomitant administration of diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine derived from Sabin strains (DTaP-sIPV) with pentavalent rotavirus vaccine in Japanese infants.

    Science.gov (United States)

    Tanaka, Yoshiyuki; Yokokawa, Ruriko; Rong, Han Shi; Kishino, Hiroyuki; Stek, Jon E; Nelson, Margaret; Lawrence, Jody

    2017-06-03

    Rotavirus is the leading cause of severe acute gastroenteritis in infants and young children. Most children are infected with rotavirus, and the health and economic burdens of rotavirus gastroenteritis on healthcare systems and families are considerable. In 2012 pentavalent rotavirus vaccine (RV5) and diphtheria, tetanus, acellular pertussis and inactivated poliovirus vaccine derived from Sabin strains (DTaP-sIPV) were licensed in Japan. We examined the immunogenicity and safety of DTaP-sIPV when administrated concomitantly with RV5 in Japanese infants. A total of 192 infants 6 to 11 weeks of age randomized to Group 1 (N = 96) received DTaP-sIPV and RV5 concomitantly, and Group 2 (N = 96) received DTaP-sIPV and RV5 separately. Antibody titer to diphtheria toxin, pertussis antigens (PT and FHA), tetanus toxin, and poliovirus type 1, 2, and 3 were measured at 4 to 6 weeks following 3-doses of DTaP-sIPV. Seroprotection rates for all components of DTaP-sIPV were 100% in both groups, and the geometric mean titers for DTaP-sIPV in Group 1 were comparable to Group 2. Incidence of systemic AEs (including diarrhea, vomiting, fever, and nasopharyngitis) were lower in Group 1 than in Group 2. All vaccine-related AEs were mild or moderate in intensity. There were no vaccine-related serious AEs, no deaths, and no cases of intussusception during the study. Concomitant administration of DTaP-sIPV and RV5 induced satisfactory immune responses to DTaP-sIPV and acceptable safety profile. The administration of DTaP-sIPV given concomitantly with RV5 is expected to facilitate compliance with the vaccination schedule and improve vaccine coverage in Japanese infants.

  20. [A case of orchitis following vaccination with freeze-dried live attenuated mumps vaccine].

    Science.gov (United States)

    Suzuki, Masayasu; Takizawa, Akitoshi; Furuta, Akira; Yanada, Shuichi; Iwamuro, Shinya; Tashiro, Kazuya

    2002-05-01

    In Japan, freeze-dried live attenuated mumps vaccine has been used optionally since 1981. The effectiveness of mumps vaccination has been established by worldwide research since 1971. On the other hand, because of it's live activity several untoward effects have been reported. Vaccination-related mumps orchitis is a rare adverse effect of mumps vaccine. Only 9 cases of vaccination-related mumps orchitis have been reported in Japan. We describe a case of orchitis following mumps vaccination in adolescence. A 16 years-old male has admitted because of acute orchitis with high fever and painful swelling of right testis. The patient had received vaccination with freeze-dried live attenuated mumps vaccine 16 days before admission. After admission, the bed-rest had completely relieved the symptoms on 6th hospital day. The impaired testis has maintained normal size and consistency 6 months after discharge.

  1. A novel live-attenuated vaccine candidate for mayaro Fever.

    Directory of Open Access Journals (Sweden)

    William J Weise

    2014-08-01

    Full Text Available Mayaro virus (MAYV is an emerging, mosquito-borne alphavirus that causes a dengue-like illness in many regions of South America, and which has the potential to urbanize. Because no specific treatment or vaccine is available for MAYV infection, we capitalized on an IRES-based approach to develop a live-attenuated MAYV vaccine candidate. Testing in infant, immunocompetent as well as interferon receptor-deficient mice demonstrated a high degree of attenuation, strong induction of neutralizing antibodies, and efficacy against lethal challenge. This vaccine strain was also unable to infect mosquito cells, a major safety feature for a live vaccine derived from a mosquito-borne virus. Further preclinical development of this vaccine candidate is warranted to protect against this important emerging disease.

  2. SPECIFIC PERTUSSIS PREVENTION: PROBLEMS AND PERSPECTIVES

    Directory of Open Access Journals (Sweden)

    S.M. Kharit

    2007-01-01

    Full Text Available The lecture shows the modern state of the pertussis issue among the children. Based on the analysis of the presented data, the authors conclude that vaccination with the full cellular vaccine is rather safe; moreover, it protects the infants from the severe forms of the disease and lethal outcomes. However, the fact that there are children with constant contraindications to immunization with the full cellular vaccine, the change of the circulating B. pertussis serotypes, morbidity of the older children due to the loss of the postcvaccinal immunity define the necessity to introduce revaccination, as well as they are indications to the wider implementation of the non-cellular pertussis vaccine.Key words: pertussis, children, vaccination, full cellular pertussis vaccine, non-cellular pertussis vaccine.

  3. Contribution of pertussis toxin to the pathogenesis of pertussis disease

    Science.gov (United States)

    Carbonetti, Nicholas H.

    2015-01-01

    Pertussis toxin (PT) is a multisubunit protein toxin secreted by Bordetella pertussis, the bacterial agent of the disease pertussis or whooping cough. PT in detoxified form is a component of all licensed acellular pertussis vaccines, since it is considered to be an important virulence factor for this pathogen. PT inhibits G protein-coupled receptor signaling through Gi proteins in mammalian cells, an activity that has led to its widespread use as a cell biology tool. But how does this activity of PT contribute to pertussis, including the severe respiratory symptoms of this disease? In this minireview, the contribution of PT to the pathogenesis of pertussis disease will be considered based on evidence from both human infections and animal model studies. Although definitive proof of the role of PT in humans is lacking, substantial evidence supports the idea that PT is a major contributor to pertussis pathology, including the severe respiratory symptoms associated with this disease. PMID:26394801

  4. Principles underlying rational design of live attenuated influenza vaccines

    Science.gov (United States)

    Jang, Yo Han

    2012-01-01

    Despite recent innovative advances in molecular virology and the developments of vaccines, influenza virus remains a serious burden for human health. Vaccination has been considered a primary countermeasure for prevention of influenza infection. Live attenuated influenza vaccines (LAIVs) are particularly attracting attention as an effective strategy due to several advantages over inactivated vaccines. Cold-adaptation, as a classical means for attenuating viral virulence, has been successfully used for generating safe and effective donor strains of LAIVs against seasonal epidemics and occasional pandemics. Recently, the advent of reverse genetics technique expedited a variety of rational strategies to broaden the pool of LAIVs. Considering the breadth of antigenic diversity of influenza virus, the pool of LAIVs is likely to equip us with better options for controlling influenza pandemics. With a brief reflection on classical attenuating strategies used at the initial stage of development of LAIVs, especially on the principles underlying the development of cold-adapted LAIVs, we further discuss and outline other attenuation strategies especially with respect to the rationales for attenuation, and their practicality for mass production. Finally, we propose important considerations for a rational vaccine design, which will provide us with practical guidelines for improving the safety and effectiveness of LAIVs. PMID:23596576

  5. Phase II and III Clinical Studies of Diphtheria-Tetanus-Acellular Pertussis Vaccine Containing Inactivated Polio Vaccine Derived from Sabin Strains (DTaP-sIPV).

    Science.gov (United States)

    Okada, Kenji; Miyazaki, Chiaki; Kino, Yoichiro; Ozaki, Takao; Hirose, Mizuo; Ueda, Kohji

    2013-07-15

    Phase II and III clinical studies were conducted to evaluate immunogenicity and safety of a novel DTaP-IPV vaccine consisting of Sabin inactivated poliovirus vaccine (sIPV) and diphtheria-tetanus-acellular pertussis vaccine (DTaP). A Phase II study was conducted in 104 healthy infants using Formulation H of the DTaP-sIPV vaccine containing high-dose sIPV (3, 100, and 100 D-antigen units for types 1, 2, and 3, respectively), and Formulations M and L, containing half and one-fourth of the sIPV in Formulation H, respectively. Each formulation was administered 3 times for primary immunization and once for booster immunization. A Phase III study was conducted in 342 healthy infants who received either Formulation M + oral polio vaccine (OPV) placebo or DTaP + OPV. The OPV or OPV placebo was orally administered twice between primary and booster immunizations. Formulation M was selected as the optimum dose. In the Phase III study, the seropositive rate was 100% for all Sabin strains after primary immunization, and the neutralizing antibody titer after booster immunization was higher than in the control group (DTaP + OPV). All adverse reactions were clinically acceptable. DTaP-sIPV was shown to be a safe and immunogenic vaccine. JapicCTI-121902 for Phase II study, JapicCTI-101075 for Phase III study (http://www.clinicaltrials.jp/user/cte_main.jsp).

  6. Evolution of Live-Attenuated HIV Vaccines

    NARCIS (Netherlands)

    Berkhout, Ben

    2011-01-01

    Despite intensive research since the viral pathogen was discovered some 25 years ago, not much progress has been reported on the development of a safe vaccine that protects against human immunodeficiency virus type 1. A vaccine approach that has been abandoned because its safety cannot be guaranteed

  7. Development and validation of an attenuated Mycoplasma hyopneumoniae aerosol vaccine.

    Science.gov (United States)

    Feng, Zhi-Xin; Wei, Yan-Na; Li, Gui-Lan; Lu, Xiao-Ming; Wan, Xiu-Feng; Pharr, G Todd; Wang, Zhan-Wei; Kong, Meng; Gan, Yuan; Bai, Fang-Fang; Liu, Mao-Jun; Xiong, Qi-Yan; Wu, Xu-Su; Shao, Guo-Qing

    2013-12-27

    Mycoplasma hyopneumoniae (M. hyopneumoniae) causes a chronic respiratory disease with high morbidity and low mortality in swine, and has been presented as a major cause of growth retardation in the swine industry. Aerosol vaccination presents a needle free, high throughput, and efficient platform for vaccine delivery, and has been widely applied in poultry vaccination. However, aerosol vaccines have rarely been used in swine vaccination primarily because the long and curving respiratory track of swine presents a barrier for vaccine particle delivery. To develop an effective M. hyopneumoniae aerosol vaccine, three major barriers need to be overcome: to optimize particle size for aerosol delivery, to maintain the viability of mycoplasma cells in the vaccine, and to optimize the environmental conditions for vaccine delivery. In this study, an aerosol mycoplasma vaccine was successfully developed based on a conventional live attenuated M. hyopneumoniae vaccine. Specifically, the Pari LCD nebulizer was used to produce an aerosol vaccine particle size less than 5 μm; and a buffer with 5% glycerol was developed and optimized to prevent inactivation of M. hyopneumoniae caused by aerosolization and evaporation. Before nebulization, the room temperature and relative humidity were control to 20-25 °C and 70-75%, respectively, which helped maintain the viability of aerosol vaccine. Animal experiments demonstrated that this newly developed aerosol vaccine was effectively delivered to swine low respiratory track, being confirmed by nested-PCR, in situ hybridization and scanning electron microscope. Moreover, M. hyopneumoniae specific sIgA secretion was detected in the nasal swab samples at 14 days post-immunization. To our knowledge, this is the first report on a live M. hyopneumoniae aerosol vaccine. Copyright © 2013 Elsevier B.V. All rights reserved.

  8. Brunenders: a partially attenuated historic poliovirus type I vaccine strain.

    Science.gov (United States)

    Sanders, Barbara P; Liu, Ying; Brandjes, Alies; van Hoek, Vladimir; de Los Rios Oakes, Isabel; Lewis, John; Wimmer, Eckard; Custers, Jerome H H V; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

    2015-09-01

    Brunenders, a type I poliovirus (PV) strain, was developed in 1952 by J. F. Enders and colleagues through serial in vitro passaging of the parental Brunhilde strain, and was reported to display partial neuroattenuation in monkeys. This phenotype of attenuation encouraged two vaccine manufacturers to adopt Brunenders as the type I component for their inactivated poliovirus vaccines (IPVs) in the 1950s, although today no licensed IPV vaccine contains Brunenders. Here we confirmed, in a transgenic mouse model, the report of Enders on the reduced neurovirulence of Brunenders. Although dramatically neuroattenuated relative to WT PV strains, Brunenders remains more virulent than the attenuated oral vaccine strain, Sabin 1. Importantly, the neuroattenuation of Brunenders does not affect in vitro growth kinetics and in vitro antigenicity, which were similar to those of Mahoney, the conventional type I IPV vaccine strain. We showed, by full nucleotide sequencing, that Brunhilde and Brunenders differ at 31 nucleotides, eight of which lead to amino acid changes, all located in the capsid. Upon exchanging the Brunenders capsid sequence with that of the Mahoney capsid, WT neurovirulence was regained in vivo, suggesting a role for the capsid mutations in Brunenders attenuation. To date, as polio eradication draws closer, the switch to using attenuated strains for IPV is actively being pursued. Brunenders preceded this novel strategy as a partially attenuated IPV strain, accompanied by decades of successful use in the field. Providing data on the attenuation of Brunenders may be of value in the further construction of attenuated PV strains to support the grand pursuit of the global eradication of poliomyelitis.

  9. Yellow fever live attenuated vaccine: A very successful live attenuated vaccine but still we have problems controlling the disease.

    Science.gov (United States)

    Barrett, Alan D T

    2017-10-20

    Yellow fever (YF) is regarded as the original hemorrhagic fever and has been a major public health problem for at least 250years. A very effective live attenuated vaccine, strain 17D, was developed in the 1930s and this has proved critical in the control of the disease. There is little doubt that without the vaccine, YF virus would be considered a biosafety level 4 pathogen. Significantly, YF is currently the only disease where an international vaccination certificate is required under the International Health Regulations. Despite having a very successful vaccine, there are occasional issues of supply and demand, such as that which occurred in Angola and Democratic Republic of Congo in 2016 when there was insufficient vaccine available. For the first time fractional dosing of the vaccine was approved on an emergency basis. Thus, continued vigilance and improvements in supply and demand are needed in the future. Copyright © 2017. Published by Elsevier Ltd.

  10. Encephalopathy after whole-cell pertussis or measles vaccination: lack of evidence for a causal association in a retrospective case-control study.

    Science.gov (United States)

    Ray, Paula; Hayward, Jean; Michelson, David; Lewis, Edwin; Schwalbe, Joan; Black, Steve; Shinefield, Henry; Marcy, Michael; Huff, Ken; Ward, Joel; Mullooly, John; Chen, Robert; Davis, Robert

    2006-09-01

    Whole-cell pertussis (wP) and measles vaccines are effective in preventing disease but have also been suspected of increasing the risk of encephalopathy or encephalitis. Although many countries now use acellular pertussis vaccines, wP vaccine is still widely used in the developing world. It is therefore important to evaluate whether wP vaccine increases the risk of neurologic disorders. A retrospective case-control study was performed at 4 health maintenance organizations. Records from January 1, 1981, through December 31, 1995, were examined to identify children aged 0 to 6 years old hospitalized with encephalopathy or related conditions. The cause of the encephalopathy was categorized as known, unknown or suspected but unconfirmed. Up to 3 controls were matched to each case. Conditional logistic regression was used to analyze the relative risk of encephalopathy after vaccination with diphtheria-tetanus-pertussis (DTP) or measles-mumps-rubella (MMR) vaccines in the 90 days before disease onset as defined by chart review compared with an equivalent period among controls indexed by matching on case onset date. Four-hundred fifty-two cases were identified. Cases were no more likely than controls to have received either vaccine during the 90 days before disease onset. When encephalopathies of known etiology were excluded, the odds ratio for case children having received DTP within 7 days before onset of disease was 1.22 (95% confidence interval [CI] = 0.45-3.31, P = 0.693) compared with control children. For MMR in the 90 days before onset of encephalopathy, the odds ratio was 1.23 (95% confidence interval = 0.51-2.98, P = 0.647). In this study of more than 2 million children, DTP and MMR vaccines were not associated with an increased risk of encephalopathy after vaccination.

  11. Live Attenuated Yellow Fever 17D Vaccine: A Legacy Vaccine Still Controlling Outbreaks In Modern Day.

    Science.gov (United States)

    Collins, Natalie D; Barrett, Alan D T

    2017-03-01

    Live attenuated 17D vaccine is considered one of the safest and efficacious vaccines developed to date. This review highlights what is known and the gaps in knowledge of vaccine-induced protective immunity. Recently, the World Health Organization modifying its guidance from 10-year booster doses to one dose gives lifelong protection in most populations. Nonetheless, there are some data suggesting immunity, though protective, may wane over time in certain populations and more research is needed to address this question. Despite having an effective vaccine to control yellow fever, vaccine shortages were identified during outbreaks in 2016, eventuating the use of a fractional-dosing campaign in the Democratic Republic of the Congo. Limited studies hinder identification of the underlying mechanism(s) of vaccine longevity; however, concurrent outbreaks during 2016 provide an opportunity to evaluate vaccine immunity following fractional dosing and insights into vaccine longevity in populations where there is limited information.

  12. Impact of age and vaccination history on long-term serological responses after symptomatic B. pertussis infection, a high dimensional data analysis

    Science.gov (United States)

    van Twillert, Inonge; Bonačić Marinović, Axel A.; Kuipers, Betsy; van Gaans-van den Brink, Jacqueline A. M.; Sanders, Elisabeth A. M.; van Els, Cécile A. C. M.

    2017-01-01

    Capturing the complexity and waning patterns of co-occurring immunoglobulin (Ig) responses after clinical B. pertussis infection may help understand how the human host gradually loses protection against whooping cough. We applied bi-exponential modelling to characterise and compare B. pertussis specific serological dynamics in a comprehensive database of IgG, IgG subclass and IgA responses to Ptx, FHA, Prn, Fim2/3 and OMV antigens of (ex-) symptomatic pertussis cases across all age groups. The decay model revealed that antigen type and age group were major factors determining differences in levels and kinetics of Ig (sub) classes. IgG-Ptx waned fastest in all age groups, while IgA to Ptx, FHA, Prn and Fim2/3 decreased fast in the younger but remained high in older (ex-) cases, indicating an age-effect. While IgG1 was the main IgG subclass in response to most antigens, IgG2 and IgG3 dominated the anti-OMV response. Moreover, vaccination history plays an important role in post-infection Ig responses, demonstrated by low responsiveness to Fim2/3 in unvaccinated elderly and by elevated IgG4 responses to multiple antigens only in children primed with acellular pertussis vaccine (aP). This work highlights the complexity of the immune response to this re-emerging pathogen and factors determining its Ig quantity and quality. PMID:28091579

  13. Live attenuated hepatitis A vaccines developed in China

    Science.gov (United States)

    Xu, Zhi-Yi; Wang, Xuan-Yi

    2014-01-01

    Two live, attenuated hepatitis A vaccines, H2 and LA-1 virus strains, were developed through serial passages of the viruses in cell cultures at 32 °C and 35 °C respectively. Both vaccines were safe and immunogenic, providing protection against clinical hepatitis A in 95% of the vaccinees, with a single dose by subcutaneous injection. The vaccine recipients were not protected from asymptomatic, subclinical hepatitis A virus (HAV) infection, which induced a similar antibody response as for unvaccinated subjects. A second dose caused anamnestic response and can be used for boosting. Oral immunization of human with H2 vaccine or of marmoset with LA-1 vaccine failed, and no evidence was found for person-to-person transmission of H2 strain or for marmoset-to-marmoset transmission of LA-1 strain by close contact. H2 strain was genetically stable when passaged in marmosets, humans or cell cultures at 37 °C; 3 consecutive passages of the virus in marmosets did not cause virulence mutation. The live vaccines offer the benefits of low cost, single dose injection, long- term protection, and increased duration of immunity through subclinical infection. Improved sanitation and administration of 150 million doses of the live vaccines to children had led to a 90% reduction in the annual national incidence rate of hepatitis A in China during the 16-year period, from 1991 to 2006. Hepatitis A (HA) immunization with both live and inactivated HA vaccines was implemented in the national routine childhood immunization program in 2008 and around 92% of the 16 million annual births received the affordable live, attenuated vaccines at 18 months of age. Near elimination of the disease was achieved in a county of China for 14 years following introduction of the H2 live vaccine into the Expanded Immunization Program (EPI) in 1992. PMID:24280971

  14. Enhanced surveillance of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccines in pregnancy in the Vaccine Adverse Event Reporting System (VAERS), 2011-2015.

    Science.gov (United States)

    Moro, Pedro L; Cragan, Janet; Tepper, Naomi; Zheteyeva, Yenlik; Museru, Oidda; Lewis, Paige; Broder, Karen

    2016-04-29

    In October 2011, the Advisory Committee on Immunization Practices (ACIP) issued updated recommendations that all pregnant women routinely receive a dose of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine. We characterized reports to the Vaccine Adverse Event Reporting System (VAERS) in pregnant women who received Tdap after this updated recommendation (2011-2015) and compared the pattern of adverse events (AEs) with the period before the updated recommendation (2005-2010). We searched the VAERS database for reports of AEs in pregnant women who received Tdap vaccine after the routine recommendation (11/01/2011-6/30/2015) and compared it to published data before the routine Tdap recommendation (01/01/2005-06/30/2010). We conducted clinical review of reports and available medical records. The clinical pattern of reports in the post-recommendation period was compared with the pattern before the routine Tdap recommendation. We found 392 reports of Tdap vaccination after the routine recommendation. One neonatal death but no maternal deaths were reported. No maternal or neonatal deaths were reported before the recommendation. We observed an increase in proportion of reports for stillbirths (1.5-2.8%) and injection site reactions/arm pain (4.5-11.9%) after the recommendation compared to the period before the routine recommendation for Tdap during pregnancy. We noted a decrease in reports of spontaneous abortion (16.7-1%). After the 2011 Tdap recommendation, in most reports, vaccination (79%) occurred during the third trimester compared to 4% before the 2011 Tdap recommendation. Twenty-six reports of repeat Tdap were received in VAERS; 13 did not report an AE. One medical facility accounted for 27% of all submitted reports. No new or unexpected vaccine AEs were noted among pregnant women who received Tdap after routine recommendations for maternal Tdap vaccination. Changes in reporting patterns would be expected, given the broader use of

  15. Oral vaccination with attenuated Salmonella choleraesuis C500 ...

    African Journals Online (AJOL)

    user

    Marshall, 1983), and well known as the major gastro- duodenal ... The CagA is encoded in a pathogenicity island known as 'Cag PAI' and is .... HindIII to release the CagA fragment. The purified .... vaccine strain attenuated by chemical methods, which is .... pylori antigens is achieved using a non-toxic mutant of E. coli heat-.

  16. Effects of a Diphtheria-Tetanus-Acellular Pertussis Vaccine on Immune Responses in Murine Local Lymph Node and Lung Allergy Models▿

    Science.gov (United States)

    Vandebriel, Rob J.; Gremmer, Eric R.; van Hartskamp, Michiel; Dormans, Jan A. M. A.; Mooi, Frits R.

    2007-01-01

    We have previously shown that in mice, diphtheria-tetanus-acellular pertussis (DTaP) vaccination before Bordetella pertussis infection resulted in, besides effective clearance, immediate hypersensitivity (lung eosinophilia, increased total serum immunoglobulin E [IgE], and increased ex vivo Th2 cytokine production by cells from the bronchial lymph nodes). To better appreciate the extent of these findings, we measured DTaP vaccination effects in the local lymph node assay (LLNA) and an ovalbumin (OVA) lung allergy model. In the LLNA, mice were vaccinated or adjuvant treated before being sensitized with trimellitic anhydride (TMA; inducing a Th2-directed response) and dinitrochlorobenzene (DNCB; inducing a Th1-directed response). Compared to the adjuvant-treated controls, the vaccinated mice showed a decreased response to TMA and (to a much lesser extent) an increased response to DNCB. The decreased response to TMA coincided with increased transforming growth factor β levels. With the exception of filamentous hemagglutinin, all vaccine constituents contributed to the decreased response to TMA. In the lung allergy model, sensitization induced OVA-specific IgE, lung pathology (peribronchiolitis, perivasculitis, and hypertrophy of the bronchiolar mucus cells) and increased the number of eosinophils, lymphocytes, and neutrophils in the bronchoalveolar lavage fluid. Vaccination failed to modulate these parameters. In conclusion, although DTaP vaccination may affect the LLNA response, we found no evidence of an effect on lung allergy. PMID:17202304

  17. A CpG-containing oligodeoxynucleotide as an efficient adjuvant counterbalancing the Th1/Th2 immune response in diphtheria-tetanus-pertussis vaccine.

    Science.gov (United States)

    Sugai, Toshiyuki; Mori, Masaaki; Nakazawa, Masatoshi; Ichino, Motohide; Naruto, Takuya; Kobayashi, Naoki; Kobayashi, Yoshinori; Minami, Mutsuhiko; Yokota, Shumpei

    2005-11-16

    Adjuvants in vaccines are immune stimulants that play an important role in the induction of effective and appropriate immune responses to vaccine component(s). Diphtheria-tetanus-pertussis (DPT) vaccine contains not only aluminum hydrate (alum) to enhance the immune response to the vaccine ingredients, but also, both for that purpose and as a principal ingredient, pertussis toxin (PT). However, both adjuvants strongly promote T helper (Th) 2 type immune responses. Th1 and Th2 type immune responses are counterbalanced in vivo, and a Th2-prone immune response is not effective against intracellular infections but promotes IgE production, which is related to allergic disease. In this study, we used the CpG motif contained in oligodeoxynucleotide (CpG-ODN), which has an adjuvant effect and also induces the Th1 response, as an adjuvant to this vaccine, and we investigated its adjuvanticity and its potential to modulate immune responses to DPT vaccine. Administration of DPT vaccine with CpG-ODN (DPT-alum/ODN) to mice significantly reduced the total IgE levels and increased the anti-PT specific IgG2a titer in serum, in comparison with ordinary DPT vaccine (DPT-alum). Moreover, we investigated the antibody response to orally administrated ovalbumin (OVA) after vaccine administration. In the DPT-alum/ODN-administered group, the OVA specific IgE production in serum greatly decreased in comparison with that in the DPT-alum-administered group. These data indicate that CpG-ODN was not useful only as an efficient vaccine adjuvant but also shifted the immune responses substantially toward Th1 and modulated the Th1/Th2 immune response in DPT vaccine. These data suggested new applications of CpG-ODN as adjuvants in DPT vaccine.

  18. Herpes Simplex Vaccines: Prospects of Live-attenuated HSV Vaccines to Combat Genital and Ocular infections

    Science.gov (United States)

    Stanfield, Brent; Kousoulas, Konstantin Gus

    2015-01-01

    Herpes simplex virus type-1 (HSV-1) and its closely related type-2 (HSV-2) viruses cause important clinical manifestations in humans including acute ocular disease and genital infections. These viruses establish latency in the trigeminal ganglionic and dorsal root neurons, respectively. Both viruses are widespread among humans and can frequently reactivate from latency causing disease. Currently, there are no vaccines available against herpes simplex viral infections. However, a number of promising vaccine approaches are being explored in pre-clinical investigations with few progressing to early phase clinical trials. Consensus research findings suggest that robust humoral and cellular immune responses may partially control the frequency of reactivation episodes and reduce clinical symptoms. Live-attenuated viral vaccines have long been considered as a viable option for generating robust and protective immune responses against viral pathogens. Varicella zoster virus (VZV) belongs to the same alphaherpesvirus subfamily with herpes simplex viruses. A live-attenuated VZV vaccine has been extensively used in a prophylactic and therapeutic approach to combat primary and recurrent VZV infection indicating that a similar vaccine approach may be feasible for HSVs. In this review, we summarize pre-clinical approaches to HSV vaccine development and current efforts to test certain vaccine approaches in human clinical trials. Also, we discuss the potential advantages of using a safe, live-attenuated HSV-1 vaccine strain to protect against both HSV-1 and HSV-2 infections. PMID:27114893

  19. In vitro characterization of pertussis vaccines : Functional analysis as part of the Consistency Approach

    NARCIS (Netherlands)

    Hoonakker, M.E.

    2017-01-01

    The current paradigm in vaccine lot release testing is that each final lot of vaccine produced is unique, due to the considerable inherent variation in the preceding biological production process. Consequently, each individual vaccine lot needs to be tested for safety and potency, frequently

  20. Pertussis Tests

    Science.gov (United States)

    ... of Conditions Not Listed? Not Listed? Acidosis and Alkalosis Adrenal Insufficiency and Addison Disease Alcoholism Allergies Alzheimer ... tested? Pertussis, commonly called whooping cough, is a respiratory infection caused by the bacteria Bordetella pertussis . These ...

  1. Sex-differential effects of diphtheria-tetanus-pertussis vaccine for the outcome of paediatric admissions? A hospital based observational study from Guinea-Bissau

    DEFF Research Database (Denmark)

    Andersen, Annemette; Bjerregaard-Andersen, Morten; Rodrigues, Amabelia

    2017-01-01

    study using data from Bandim Health Project's continuous registration of all admissions to the paediatric ward at the National Hospital Simão Mendes in Bissau, we investigated whether DTP was associated with higher female than male in-hospital mortality (female/male case fatality ratio (F/M CFR......Background: In spite of protection against the targeted infections, a large volume of observational data indicates that diphtheria-tetanus-pertussis (DTP) vaccine may have a negative impact on overall childhood mortality in low-income countries, especially in girls. Methods: In an observational......-vaccinated children was 1.23 (1.03-1.46); while it was 0.95 (0.66-1.38) among the 506 children who had not received DTP. DTP-vaccinated children were older and had better socioeconomic status. Adjusted for age, BCG-vaccination, residence, and maternal education the CFR comparing DTP-vaccinated boys with DTP...

  2. Bordetella pertussis strains with increased toxin production associated with pertussis resurgence.

    NARCIS (Netherlands)

    Mooi, F.R.; Loo, I.H. van; Gent, M. van; He, Q.; Bart, M.J.; Heuvelman, K.J.; Greeff, S.C. de; Diavatopoulos, D.A.; Teunis, P.; Nagelkerke, N.; Mertsola, J.

    2009-01-01

    Before childhood vaccination was introduced in the 1940s, pertussis was a major cause of infant death worldwide. Widespread vaccination of children succeeded in reducing illness and death. In the 1990s, a resurgence of pertussis was observed in a number of countries with highly vaccinated

  3. Bordetella pertussis pathogenesis: current and future challenges

    Science.gov (United States)

    Melvin, Jeffrey A.; Scheller, Erich V.; Miller, Jeff F.; Cotter, Peggy A.

    2014-01-01

    Pertussis, or whooping cough, has recently reemerged as a major public health threat despite high levels of vaccination against the etiological agent, Bordetella pertussis. In this Review, we describe the pathogenesis of this disease, with a focus on recent mechanistic insights into virulence factor function. We also discuss the changing epidemiology of pertussis and the challenges of vaccine development. Despite decades of research, many aspects of B. pertussis physiology and pathogenesis remain poorly understood. We highlight knowledge gaps that must be addressed to develop improved vaccines and therapeutic strategies. PMID:24608338

  4. Safety and immunogenicity of a live attenuated mumps vaccine

    Science.gov (United States)

    Liang, Yan; Ma, Jingchen; Li, Changgui; Chen, Yuguo; Liu, Longding; Liao, Yun; Zhang, Ying; Jiang, Li; Wang, Xuan-Yi; Che, Yanchun; Deng, Wei; Li, Hong; Cui, Xiaoyu; Ma, Na; Ding, Dong; Xie, Zhongping; Cui, Pingfang; Ji, Qiuyan; Wang, Jingjing; Zhao, Yuliang; Wang, Junzhi; Li, Qihan

    2014-01-01

    Background: Mumps, a communicable, acute and previously well-controlled disease, has had recent and occasional resurgences in some areas. Methods: A randomized, double-blind, controlled and multistep phase I study of an F-genotype attenuated mumps vaccine produced in human diploid cells was conducted. A total of 300 subjects were enrolled and divided into 4 age groups: 16–60 years, 5–16 years, 2–5 years and 8–24 months. The groups were immunized with one injection per subject. Three different doses of the F-genotype attenuated mumps vaccine, A (3.5 ± 0.25 logCCID50), B (4.25 ± 0.25 logCCID50) and C (5.0 ± 0.25 logCCID50), as well as a placebo control and a positive control of a licensed A-genotype vaccine (S79 strain) were used. The safety and immunogenicity of this vaccine were compared with those of the controls. Results: The safety evaluation suggested that mild adverse reactions were observed in all groups. No serious adverse event (SAE) was reported throughout the trial. The immunogenicity test showed a similar seroconversion rate of the neutralizing and ELISA antibody in the 2- to 5-year-old and 8- to 24-month-old groups compared with the seroconversion rate in the positive control. The GMT of the neutralizing anti-F-genotype virus antibodies in the vaccine groups was slightly higher than that in the positive control group. Conclusions: The F-genotype attenuated mumps vaccine evaluated in this clinical trial was demonstrated to be safe and have effective immunogenicity vs. control. PMID:24614759

  5. Combination of pneumococcal surface protein A (PspA with whole cell pertussis vaccine increases protection against pneumococcal challenge in mice.

    Directory of Open Access Journals (Sweden)

    Maria Leonor S Oliveira

    Full Text Available Streptococcus pneumoniae is the leading cause of respiratory acute infections around the world. In Latin America, approximately 20,000 children under 5 years of age die of pneumococcal diseases annually. Pneumococcal surface protein A (PspA is among the best-characterized pneumococcal antigens that confer protection in animal models of pneumococcal infections and, as such, is a good alternative for the currently available conjugated vaccines. Efficient immune responses directed to PspA in animal models have already been described. Nevertheless, few low cost adjuvants for a subunit pneumococcal vaccine have been proposed to date. Here, we have tested the adjuvant properties of the whole cell Bordetella pertussis vaccine (wP that is currently part of the DTP (diphtheria-tetanus-pertussis vaccine administrated to children in several countries, as an adjuvant to PspA. Nasal immunization of BALB/c mice with a combination of PspA5 and wP or wP(low--a new generation vaccine that contains low levels of B. pertussis LPS--conferred protection against a respiratory lethal challenge with S. pneumoniae. Both PspA5-wP and PspA5-wP(low vaccines induced high levels of systemic and mucosal antibodies against PspA5, with similar profile, indicating no essential requirement for B. pertussis LPS in the adjuvant properties of wP. Accordingly, nasal immunization of C3H/HeJ mice with PspA5-wP conferred protection against the pneumococcal challenge, thus ruling out a role for TLR4 responses in the adjuvant activity and the protection mechanisms triggered by the vaccines. The high levels of anti-PspA5 antibodies correlated with increased cross-reactivity against PspAs from different clades and also reflected in cross-protection. In addition, passive immunization experiments indicated that antibodies played an important role in protection in this model. Finally, subcutaneous immunization with a combination of PspA5 with DTP(low protected mice against challenge with two

  6. Monospecific antibody against Bordetella pertussis Adenylate Cyclase protects from Pertussis

    Directory of Open Access Journals (Sweden)

    Yasmeen Faiz Kazi

    2012-06-01

    Full Text Available Objectives: Acellular pertussis vaccines has been largely accepted world-wide however, there are reports about limitedantibody response against these vaccines suggesting that multiple antigens should be included in acellular vaccinesto attain full protection. The aim of present study was to evaluate the role of Bordetella pertussis adenylate cyclase as aprotective antigen.Materials and methods: Highly mono-specific antibody against adenylate cyclase (AC was raised in rabbits usingnitrocellulose bound adenylate cyclase and the specificity was assessed by immuoblotting. B.pertussis 18-323, wasincubated with the mono-specific serum and without serum as a control. Mice were challenged intra-nasally and pathophysiolgicalresponses were recorded.Results: The production of B.pertussis adenylate cyclase monospecific antibody that successfully recognized on immunoblotand gave protection against fatality (p< 0.01 and lung consolidation (p <0.01. Mouse weight gain showedsignificant difference (p< 0.05.Conclusion: These preliminary results highlight the role of the B.pertussis adenylate cyclase as a potential pertussisvaccine candidate. B.pertussis AC exhibited significant protection against pertussis in murine model. J Microbiol InfectDis 2012; 2(2: 36-43Key words: Pertussis; monospecific; antibody; passive-protection

  7. Demonstration of 1-year duration of immunity for attenuated Bordetella bronchiseptica vaccines in dogs.

    Science.gov (United States)

    Lehar, Craig; Jayappa, Huchappa; Erskine, Jason; Brown, Alicia; Sweeney, Diane; Wassmoen, Terri

    2008-01-01

    Three groups of healthy dogs with low antibody titers to Bordetella bronchiseptica (Bb), canine parainfluenza virus (CPI), and canine adenovirus type 2 (CAV-2) were used in this study. One group was vaccinated with a single dose of monovalent attenuated Bb vaccine and one group with a trivalent vaccine containing attenuated Bb, CPI, and CAV-2; dogs were vaccinated intranasally with a single dose of the respective vaccines. The third group served as unvaccinated controls. All vaccinated dogs subsequently developed serum antibody titers to Bb that persisted for at least 1 year. Following Bb challenge 1 year after vaccination, all vaccinated dogs, regardless of group, showed significantly fewer clinical signs and shed significantly fewer challenge organisms than unvaccinated controls. These results demonstrate that intranasal administration of a single dose of monovalent attenuated Bb vaccine or trivalent vaccine containing attenuated Bb, CPI, and CAV-2 provides 1 year of protection against Bb.

  8. Whole-cell pertussis vaccine induces low antibody levels in human immunodeficiency virus-infected children living in sub-Saharan Africa.

    Science.gov (United States)

    Tejiokem, Mathurin C; Njamkepo, Elisabeth; Gouandjika, Ionela; Rousset, Dominique; Béniguel, Lydie; Bilong, Catherine; Tene, Gilbert; Penda, Ida; Ngongueu, Carine; Gody, Jean C; Guiso, Nicole; Baril, Laurence

    2009-04-01

    The WHO recommendations for the immunization of children infected with human immunodeficiency virus (HIV) differ slightly from the guidelines for uninfected children. The introduction of antiretroviral therapy for HIV-infected infants should considerably prolong their life expectancy. The question of the response to the whole-cell pertussis (wP) vaccine should now be addressed, particularly in countries in which pertussis remains endemic. To evaluate the persistence of antibodies to the wP vaccine in HIV-infected and uninfected children who had previously received this vaccine in routine clinical practice, we conducted a cross-sectional study of children aged 18 to 36 months, born to HIV-infected mothers and living in Cameroon or the Central African Republic. We tested blood samples for antibodies to the wP vaccine and for antibodies to diphtheria and tetanus toxoids (D and T, respectively) in the context of the use of a combined DTwP vaccine. We enrolled 50 HIV-infected children and 78 uninfected, HIV-exposed children in the study. A lower proportion of HIV-infected children than uninfected children had antibodies against the antigens tested for all valences of the DTwP vaccine. Agglutinin levels were substantially lower in HIV-infected than in HIV-exposed but uninfected children (30.0% versus 55.1%, respectively; P = 0.005). We also observed a high risk of low antibody levels in response to the DTwP vaccine in HIV-infected children with severe immunodeficiency (CD4 T-cell level, <25%). The concentrations of antibodies induced by the DTwP vaccine were lower in HIV-infected children than in uninfected children. This study supports the need for a booster dose of the DTwP vaccine in order to maintain high antibody levels in HIV-infected children.

  9. Cost Effectiveness of Influenza Vaccine for U.S. Children: Live Attenuated and Inactivated Influenza Vaccine.

    Science.gov (United States)

    Shim, Eunha; Brown, Shawn T; DePasse, Jay; Nowalk, Mary Patricia; Raviotta, Jonathan M; Smith, Kenneth J; Zimmerman, Richard K

    2016-09-01

    Prior studies showed that live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in children aged 2-8 years, supporting the Centers for Disease Control and Prevention (CDC) recommendations in 2014 for preferential LAIV use in this age group. However, 2014-2015 U.S. effectiveness data indicated relatively poor effectiveness of both vaccines, leading CDC in 2015 to no longer prefer LAIV. An age-structured model of influenza transmission and vaccination was developed, which incorporated both direct and indirect protection induced by vaccination. Based on this model, the cost effectiveness of influenza vaccination strategies in children aged 2-8 years in the U.S. was estimated. The base case assumed a mixed vaccination strategy where 33.3% and 66.7% of vaccinated children aged 2-8 years receive LAIV and IIV, respectively. Analyses were performed in 2014-2015. Using published meta-analysis vaccine effectiveness data (83% LAIV and 64% IIV), exclusive LAIV use would be a cost-effective strategy when vaccinating children aged 2-8 years, whereas IIV would not be preferred. However, when 2014-2015 U.S. effectiveness data (0% LAIV and 15% IIV) were used, IIV was likely to be preferred. The cost effectiveness of influenza vaccination in children aged 2-8 years is highly dependent on vaccine effectiveness; the vaccine type with higher effectiveness is preferred. In general, exclusive IIV use is preferred over LAIV use, as long as vaccine effectiveness is higher for IIV than for LAIV. Copyright © 2016 American Journal of Preventive Medicine. Published by Elsevier Inc. All rights reserved.

  10. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... immunizations current news Flu's Gonna Lose hepatitis a & b vaccines im/sq how to do kids infect ... vaccine safety q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus shingles ...

  11. Attenuate Eimeria Tenella parasite by gamma radiation in chicken vaccination

    International Nuclear Information System (INIS)

    El-atar, M.A.

    1998-01-01

    Mature occysts of eimeria tenella were attenuated by different doses of gamma radiation. The vitality, pathogenicity and immunogenicity of these occysts were examined by infecting one day old broiler chicks. The study revealed that the irradiated occysts lost pathogenicity by increasing radiation dose. To examine the immunogenicity of irradiated occysts, chickens were challenged 28 days post immunogenic infection. It was shown that the irradiated occycts kept their immunogenicity but this ability decreased when the irradiation dose was increased. Also, the number of vaccination doses as well as the level of irradiation were studied. Occysts irradiated with 15, 18, 20 Krad were used to vaccinate one-day old broiler chicks for one or two times, and seven-day old chicks for three times. High level of protection was observed as shown by disappeaeance of clinical signs or mortality in most vaccinated groups

  12. Live attenuated vaccines: Historical successes and current challenges.

    Science.gov (United States)

    Minor, Philip D

    2015-05-01

    Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed. Copyright © 2015 The Author. Published by Elsevier Inc. All rights reserved.

  13. Humoral immunity 10 years after booster immunization with an adolescent and adult formulation combined tetanus, diphtheria, and 5-component acellular pertussis vaccine.

    Science.gov (United States)

    Tomovici, A; Barreto, L; Zickler, P; Meekison, W; Noya, F; Voloshen, T; Lavigne, P

    2012-03-30

    Persistence of antibodies after a single dose of Tdap vaccine (tetanus, diphtheria, and 5-component acellular pertussis vaccine) was evaluated in a follow-up study of adolescents (N=324) and adults (N=644) who had received Tdap in earlier clinical trials. Outcome measures were seroprotection (tetanus and diphtheria) or seropositivity (pertussis) and geometric mean concentrations. Humoral immune responses to all antigens were robust 1 month after initial immunization, decreased at subsequent measurements, but continued to exceed pre-immunization levels 1, 3, 5, and 10 years later. Protective levels of diphtheria and tetanus antitoxin persisted in 99.3% of adolescents 10 years after a booster dose of Tdap. Seropositivity to 1 or more pertussis antigens also persisted in most adolescents for 10 years. Although tetanus antitoxin responses were similar in adults to those observed in adolescents, diphtheria antitoxin titers were lower, reflecting the fact that a smaller proportion of adults had received diphtheria toxoid in the previous 10 years compared to adolescents. These data will contribute to the selection of the optimal interval for repeat doses of Tdap. Copyright © 2012 Elsevier Ltd. All rights reserved.

  14. Studies of parvovirus vaccination in the dog: the performance of live attenuated feline parvovirus vaccines.

    Science.gov (United States)

    Thompson, H; McCandlish, I A; Cornwell, H J; Macartney, L; Maxwell, N S; Weipers, A F; Wills, I R; Black, J A; Mackenzie, A C

    1988-04-16

    The performance of three live attenuated feline parvovirus vaccines licensed for use in the dog was studied. At the end of the primary vaccination course 67 per cent of dogs had inadequate antibody levels (less than or equal to 32) as measured by a haemagglutination inhibition test. Interference by maternal antibody accounted for some of the failures but the fact that there was no significant difference in performance between dogs vaccinated at 12 weeks or 16 weeks of age indicated that maternal antibody was not the only factor.

  15. Pertussis toxins, other antigens become likely targets for genetic engineering

    Energy Technology Data Exchange (ETDEWEB)

    Marwick, C.

    1990-11-14

    Genetically engineered pertussis vaccines have yet to be fully tested clinically. But early human, animal, and in vitro studies indicate effectiveness in reducing toxic effects due to Bordetella pertussis. The licensed pertussis vaccines consists of inactivated whole cells of the organism. Although highly effective, they have been associated with neurologic complications. While the evidence continues to mount that these complications are extremely rare, if they occur at all, it has affected the public's acceptance of pertussis immunization.

  16. Immunogenicity and safety of an inactivated hepatitis A vaccine when coadministered with Diphtheria-tetanus-acellular pertussis and haemophilus influenzae type B vaccines in children 15 months of age.

    Science.gov (United States)

    Trofa, Andrew F; Klein, Nicola P; Paul, Ian M; Michaels, Marian G; Goessler, Mary; Chandrasekaran, Vijayalakshmi; Blatter, Mark

    2011-09-01

    This study (NCT00197236) evaluated the safety and immunogenicity of a hepatitis A virus (HAV) vaccine when coadministered with diphtheria-tetanus-acellular pertussis (DTaP) and Haemophilus influenzae type b (Hib) vaccines in children 15 months of age. This was an open-labeled, multicenter study with healthy subjects enrolled and randomized (1:1:1) into 3 treatment groups. A total of 394 subjects received the first study vaccinations at 15 months of age. Group HAV (N = 135) received 2 doses of HAV vaccine 6 to 9 months apart. Group HAV+DTaP+Hib (N = 127) received HAV vaccine coadministered with DTaP and Hib vaccines and the second dose of HAV vaccine, 6 to 9 months later. Group DTaP+Hib→HAV (N = 132) received the DTaP and Hib vaccines at 15 months of age, followed by HAV vaccine 30 days later and the second dose of HAV vaccine 7 to 10 months after the DTaP+Hib vaccines. Immune responses were evaluated before the first study vaccination and 30 days after each vaccine dose. Solicited, unsolicited, and serious adverse events were collected. After 2 doses of the HAV vaccine, all subjects in the 3 groups were seropositive. The geometric mean concentration of anti-HAV antibodies ranged between 1625.1 and 1904.4 mIU/mL. Coadministration of the 3 vaccines did not impact immunogenicity of the HAV, DTaP, or Hib vaccines. Vaccines were well tolerated in all groups. A 2-dose schedule of HAV vaccine was well tolerated and immunogenic when administered to children starting at 15 months of age. Immune responses to the DTaP or Hib vaccines were similar whether they were administered alone or were coadministered with the HAV vaccine.

  17. Randomized trial on the safety, tolerability, and immunogenicity of MenACWY-CRM, an investigational quadrivalent meningococcal glycoconjugate vaccine, administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis vaccine in adolescents and young adults.

    Science.gov (United States)

    Gasparini, Roberto; Conversano, Michele; Bona, Gianni; Gabutti, Giovanni; Anemona, Alessandra; Dull, Peter M; Ceddia, Francesca

    2010-04-01

    This study evaluated the safety, tolerability, and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine, MenACWY-CRM, when administered concomitantly with a combined tetanus, reduced diphtheria, and acellular pertussis (Tdap) vaccine, in subjects aged 11 to 25 years. Subjects received either MenACWY-CRM and Tdap, MenACWY-CRM and saline placebo, or Tdap and saline placebo. No significant increase in reactogenicity and no clinically significant vaccine-related adverse events (AEs) occurred when MenACWY-CRM and Tdap were administered concomitantly. Similar immunogenic responses to diphtheria, tetanus, and meningococcal (serogroups A, C, W-135, and Y) antigens were observed, regardless of concomitant vaccine administration. Antipertussis antibody responses were comparable between vaccine groups for filamentous hemagglutinin and were slightly lower, although not clinically significantly, for pertussis toxoid and pertactin when the two vaccines were administered concomitantly. These results indicate that the investigational MenACWY-CRM vaccine is well tolerated and immunogenic and that it can be coadministered with Tdap to adolescents and young adults.

  18. The intention of Dutch general practitioners to offer vaccination against pneumococcal disease, herpes zoster and pertussis to people aged 60 years and older.

    Science.gov (United States)

    Lehmann, Birthe A; Eilers, Renske; Mollema, Liesbeth; Ferreira, José; de Melker, Hester E

    2017-06-07

    Increasing life expectancy results in a larger proportion of older people susceptible to vaccine preventable diseases (VPDs). In the Netherlands, influenza vaccination is routinely offered to people aged 60 years and older. Vaccination against pneumococcal disease, herpes zoster and pertussis is rarely used. These vaccines will be evaluated by the Dutch Health Council and might be routinely offered to older people in the near future. Possible expansion of the program depends partly on the willingness of general practitioners (GPs) to endorse additional vaccinations. In this study, we assessed predictors of GPs' attitude and intention to vaccinate people aged 60 years and older. GPs (N = 12.194) were invited to fill in an online questionnaire consisting of questions about social cognitive factors that can influence the willingness of GPs to vaccinate people aged 60 years and older, including underlying beliefs, practical considerations of adding more vaccines to the national program, demographics, and GPs' patient population characteristics. The questionnaire was filled in by 732 GPs. GPs were positive both about vaccination as a preventive tool and the influenza vaccination program, but somewhat less positive about expanding the current program. Prediction analysis showed that the intention of GPs to offer additional vaccination was predicted by their attitude towards offering additional vaccination, towards vaccination as a preventive tool, towards offering vaccination during an outbreak and on GPs opinion regarding suitability to offer additional vaccination (R 2  = 0.60). The attitude of GPs towards offering additional vaccination was predicted by the perceived severity of herpes zoster and pneumonia, as well as the perceived incidence of herpes zoster. Severity of diseases was ranked as important argument to recommend vaccination, followed by effectiveness and health benefits of vaccines. Providing GPs with evidence-based information about the severity

  19. Decennial administration in young adults of a reduced-antigen content diphtheria, tetanus, acellular pertussis vaccine containing two different concentrations of aluminium.

    Science.gov (United States)

    Vandermeulen, Corinne; Theeten, Heidi; Rathi, Niraj; Kuriyakose, Sherine; Han, Htay Htay; Sokal, Etienne; Hoppenbrouwers, Karel; Van Damme, Pierre

    2015-06-12

    Regular booster vaccination might be necessary throughout life to protect against pertussis infection. Nevertheless the duration of protection after booster vaccination remains unclear. In this study, antibody persistence up to 10 years after previous vaccination of adolescents (N=478) with combined reduced-antigen-content diphtheria-tetanus-acellular pertussis vaccine (dTpa, Boostrix™, GlaxoSmithKline Belgium) containing 0.5mg, 0.3mg or 0.133mg of aluminium was assessed. The immunogenicity, reactogenicity and safety of a decennial booster dTpa dose were also investigated. Young adults vaccinated as adolescents in the initial booster study were invited to participate in an assessment of antibody persistence at years 8.5 and 10, and to receive a dTpa booster dose at year 10 with immunogenicity assessment one month later. Those who originally received the 0.5mg or 0.3mg formulations received the same vaccine at year 10. Those in the 0.133mg group received the 0.5mg formulation. Reactogenicity and safety endpoints were captured until 30 days after booster vaccination. Prior to the decennial booster at year 8.5 and year 10, all participants had seroprotective antibodies for diphtheria (ELISA or neutralisation assay) and tetanus. At least 77.8% were seropositive for anti-pertussis toxin (PT) antibodies at year 8.5 and 82.8% at year 10. All participants were seropositive for antibodies for filamentous haemagglutinin and pertactin at both time points. The decennial booster dose induced robust increases in antibody GMCs to all antigens. The post-booster anti-PT geometric mean concentration was 82.5EL.U/ml (95%CI 67.0-101.6) and 124.0 (103.5-148.5) in the 0.3mg and 0.5mg groups, respectively. The reactogenicity and safety profile of the decennial booster dose was consistent with the known safety profile of dTpa. No serious adverse events were reported. Decennial booster vaccination with either of the two licensed formulations of dTpa was highly immunogenic and well

  20. Pertussis: Microbiology, Disease, Treatment, and Prevention

    Science.gov (United States)

    Salim, Abdulbaset M.; Zervos, Marcus J.; Schmitt, Heinz-Josef

    2016-01-01

    SUMMARY Pertussis is a severe respiratory infection caused by Bordetella pertussis, and in 2008, pertussis was associated with an estimated 16 million cases and 195,000 deaths globally. Sizeable outbreaks of pertussis have been reported over the past 5 years, and disease reemergence has been the focus of international attention to develop a deeper understanding of pathogen virulence and genetic evolution of B. pertussis strains. During the past 20 years, the scientific community has recognized pertussis among adults as well as infants and children. Increased recognition that older children and adolescents are at risk for disease and may transmit B. pertussis to younger siblings has underscored the need to better understand the role of innate, humoral, and cell-mediated immunity, including the role of waning immunity. Although recognition of adult pertussis has increased in tandem with a better understanding of B. pertussis pathogenesis, pertussis in neonates and adults can manifest with atypical clinical presentations. Such disease patterns make pertussis recognition difficult and lead to delays in treatment. Ongoing research using newer tools for molecular analysis holds promise for improved understanding of pertussis epidemiology, bacterial pathogenesis, bioinformatics, and immunology. Together, these advances provide a foundation for the development of new-generation diagnostics, therapeutics, and vaccines. PMID:27029594

  1. [Pertussis (Whooping cough)--an update].

    Science.gov (United States)

    Stock, Ingo

    2015-12-01

    Whooping cough is a highly contagious respiratory disease which is caused predominantly by the gram-negative bacterium Bordetella pertussis. Further Bordetella species such as B. parapertussis and the recently discovered species B. holmesii are also involved in whooping cough-like diseases. Depending on age, vaccination status and distance to pre-infection with B. pertussis, whooping cough shows a wide range of symptoms. The disease occurs at any age, leaving only short time immunity. During the last 15 years, in industrialized countries the number of reported pertussis cases has been increased markedly. The reason for this observation is still unclear Macrolides such as azithromycin and clarithromycin are regarded as antibiotics of first choice. In Germany, combination vaccines containing acellular pertussis vaccines is the most important strategy of prevention. To ensure the best possible protection against pertussis, booster doses at determined times should be given after primary vaccination in infancy.

  2. IMMUNOGENICITY AND SAFETY OF QUINVAXEM® (DIPHTHERIA, TETANUS, WHOLE-CELL PERTUSSIS, HEPATITIS B AND HAEMOPHILUS INFLUENZAE TYPE B VACCINE) GIVEN TO VIETNAMESE INFANTS AT 2 TO 4 MONTHS OF AGE.

    Science.gov (United States)

    Huu, Tran Ngoc; Phuong, Nguyen Thi Minh; Toan, Nguyen Trong; Thang, Ho Vinh

    2015-07-01

    Vietnam plans to replace the routine childhood diphtheria, pertussis and tetanus combination (DPT) vaccine with a pentavalent vaccine. The present study was performed to assess the immunogenicity and safety of the combined diphtheria, tetanus, whole-cell pertussis, hepatitis B (HepB), and Haemophilus influenzae type b (Hib) (DTwP-HepB-Hib) Quinvaxem® vaccine in children. A total of 131 infants received the Quinvaxem® vaccine at 2, 3 and 4 months. Antibody levels were measured at baseline, at one month after the third injection and one year after the first injection. Seroprotection rates were high for each vaccine antigen at one month after the third dose: 93.1% for diphtheria, 98.5% for tetanus, 99.2% for pertussis (seroconversion rate), 93.1% for HepB, and 100% for Hib (anti-PRP ≥ 0.15 µg/ml). The rate of children with protective antibodies persisting at one year after the first dose was 88.4% for diphtheria, 49.6% for pertussis, 82.2% for tetanus, 76.7% for HepB and 97.7% for Hib (anti-PRP ≥ 0.15 µg/ml). The Quinvaxem® vaccine was well tolerated and has a low rate of adverse events. Quinvaxem® given at 2, 3 and 4 months of age was immunogenic and safe for primary immunization among infants in Vietnam.

  3. Report of the Task Force on Pertussis and Pertussis Immunization--1988.

    Science.gov (United States)

    American Academy of Pediatrics, Elk Grove Village, IL.

    Pertussis is a severe epidemic and endemic disease with significant morbidity and mortality. The use of whole-cell pertussis vaccines in the United States has been effective in controlling the disease but not in decreasing the circulation of the organism. Whole-cell vaccines commonly cause reactions in children, and in addition, they are often…

  4. Live Attenuated Recombinant Vaccine Protects Nonhuman Primates Against Ebola and Marburg Viruses

    National Research Council Canada - National Science Library

    Jones, Steven M; Feldmann, Heinz; Stroher, Ute; Geisbert, Joan B; Fernando, Lisa; Grolla, Allen; Klenk, Hans-Dieter; Sullivan, Nancy J; Volchkov, Viktor E; Fritz, Elizabeth A; Daddario, Kathleen M; Hensley, Lisa E; Jahrling, Peter B; Geisbert, Thomas W

    2005-01-01

    ...). Here, we developed replication-competent vaccines against EBOV and MARV based on attenuated recombinant vesicular stomatitis virus vectors expressing either the EBOV glycoprotein or MARV glycoprotein...

  5. Live attenuated vaccines: Historical successes and current challenges

    Energy Technology Data Exchange (ETDEWEB)

    Minor, Philip D., E-mail: Philip.Minor@nibsc.org

    2015-05-15

    Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed. - Highlights: • Live vaccines against human diseases caused by viruses have been very successful. • They have been developed by empirical clinical studies and problems identified in later use. • It can be difficult to balance ability to cause disease and ability to immunise for a strain. • There is currently no reliable basis for predicting success from pure virological studies. • Vaccinia, which eradicated smallpox, is the paradigm for all successes and issues.

  6. Live attenuated vaccines: Historical successes and current challenges

    International Nuclear Information System (INIS)

    Minor, Philip D.

    2015-01-01

    Live attenuated vaccines against human viral diseases have been amongst the most successful cost effective interventions in medical history. Smallpox was declared eradicated in 1980; poliomyelitis is nearing global eradication and measles has been controlled in most parts of the world. Vaccines function well for acute diseases such as these but chronic infections such as HIV are more challenging for reasons of both likely safety and probable efficacy. The derivation of the vaccines used has in general not been purely rational except in the sense that it has involved careful clinical trials of candidates and subsequent careful follow up in clinical use; the identification of the candidates is reviewed. - Highlights: • Live vaccines against human diseases caused by viruses have been very successful. • They have been developed by empirical clinical studies and problems identified in later use. • It can be difficult to balance ability to cause disease and ability to immunise for a strain. • There is currently no reliable basis for predicting success from pure virological studies. • Vaccinia, which eradicated smallpox, is the paradigm for all successes and issues

  7. Comparative analysis of the intracerebral mouse protection test and serological method for potency assays of pertussis component in DTP vaccine

    Directory of Open Access Journals (Sweden)

    Denise Cristina Souza Matos

    2012-06-01

    Full Text Available The aim of this study was to compare the PSPT standardized in-house as an alternative to MPT for potency assays of pertussis component. Statistical analyses have showed similar pertussis potency values when PSPT was compared to MPT. Significant correlation between the potency results obtained by in vivo and in vitro assays was also been observed. Results by PSPT have demonstrated reproducibility and accuracy for potency pertussis control and this approach has been considered promising for use at least during the steps of production.

  8. Tetanus-diphtheria-pertussis vaccine may suppress the immune response to subsequent immunization with pneumococcal CRM197-conjugate vaccine (coadministered with quadrivalent meningococcal TT-conjugate vaccine): a randomized, controlled trial⋆.

    Science.gov (United States)

    Tashani, Mohamed; Heron, Leon; Wong, Melanie; Rashid, Harunor; Booy, Robert

    2017-07-01

    : Due to their antigenic similarities, there is a potential for immunological interaction between tetanus/diphtheria-containing vaccines and carrier proteins presented on conjugate vaccines. The interaction could, unpredictably, result in either enhancement or suppression of the immune response to conjugate vaccines if they are injected soon after or concurrently with diphtheria or tetanus toxoid. We examined this interaction among adult Australian travellers before attending the Hajj pilgrimage of 2015. We randomly assigned each participant to one of three vaccination schedules. Group A received tetanus, diphtheria and acellular pertussis vaccine (Tdap) 3-4 weeks before receiving CRM197-conjugated 13-valent pneumococcal vaccine (PCV13) coadministered with TT-conjugated quadrivalent meningococcal vaccine (MCV4). Group B received all three vaccines concurrently. Group C received PCV13 and MCV4 3-4 weeks before Tdap. Blood samples collected at baseline, at each vaccination visit and 3-4 weeks after vaccination were tested for the pneumococcal opsonophagocytic assay (OPA). A total of 166 participants aged 18-64 (median 42) years were recruited, 159 completed the study. Compared with the other groups, Group A had significantly ( P  vaccination in seven serotypes of PCV13 (1, 3, 4, 5, 14, 18C and 9V). Additionally, Group A had lower frequency of serorises (≥ 4-fold rise in OPA titres) in serotype5 (79%, p = 0.01) and 18C (73.5%, p = 0.06); whereas Groups B and C had significantly lower frequencies of serorises in Serotype 4 (82%) and 6A (73.5%), respectively. No statistically significant difference was detected across the three groups in frequencies achieving OPA titre ≥ 1:8 post-vaccination. Tdap vaccination 3-4 weeks before administration of PCV13 and MCV4 significantly reduced the GMTs to seven of the 13 pneumococcal serotypes in adults. If multiple vaccination is required before travel, deferring tetanus/diphtheria until after administering the

  9. Negative Correlation between Circulating CD4+FOXP3+CD127− Regulatory T Cells and Subsequent Antibody Responses to Infant Measles Vaccine but Not Diphtheria–Tetanus–Pertussis Vaccine Implies a Regulatory Role

    Directory of Open Access Journals (Sweden)

    Jorjoh Ndure

    2017-08-01

    Full Text Available Regulatory T cells (Tregs play a key homeostatic role by suppressing immune responses. They have been targeted in mouse and human cancer studies to improve vaccine immunogenicity and tumor clearance. A number of commercially available drugs and experimental vaccine adjuvants have been shown to target Tregs. Infants have high numbers of Tregs and often have poor responses to vaccination, yet the role Tregs play in controlling vaccine immunogenicity has not been explored in this age group. Herein, we explore the role of CD4+FOXP3+CD127− Tregs in controlling immunity in infant males and females to vaccination with diphtheria–tetanus–whole cell pertussis (DTP and/or measles vaccine (MV. We find correlative evidence that circulating Tregs at the time of vaccination suppress antibody responses to MV but not DTP; and Tregs 4 weeks after DTP vaccination may suppress vaccine-specific cellular immunity. This opens the exciting possibility that Tregs may provide a future target for improved vaccine responses in early life, including reducing the number of doses of vaccine required. Such an approach would need to be safe and the benefits outweigh the risks, thus further research in this area is required.

  10. Combined DTP-HBV-HIB vaccine versus separately administered DTP-HBV and HIB vaccines for primary prevention of diphtheria, tetanus, pertussis, hepatitis B and Haemophilus influenzae B (HIB).

    Science.gov (United States)

    Bar-On, Edna S; Goldberg, Elad; Hellmann, Sarah; Leibovici, Leonard

    2012-04-18

    Advantages to combining childhood vaccines include reducing the number of visits, injections and patient discomfort, increasing compliance and optimising prevention. The World Health Organization (WHO) recommends that routine infant immunisation programmes include a vaccination against Haemophilus influenzae (H. influenzae) type B (HIB) in the combined diphtheria-tetanus-pertussis (DTP)-hepatitis B virus (HBV) vaccination. The effectiveness and safety of the combined vaccine should be carefully and systematically assessed to ensure its acceptability by the community. To compare the effectiveness of combined DTP-HBV-HIB vaccines versus combined DTP-HBV and separate HIB vaccinations. We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 4), which contains the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (January 1966 to week 1, November 2011), EMBASE (January 1990 to November 2011) and www.clinicaltrials.gov (up to April 2011). Randomised controlled trials (RCTs) or quasi-RCTs comparing vaccination with any combined DTP-HBV-HIB vaccine, with or without three types of inactivated polio virus (IPV) or concomitant oral polio vaccine (OPV) in any dose, preparation or time schedule, compared with separate vaccines or placebo, administered to infants up to two years old. Two review authors independently inspected references identified by the searches and evaluated them against the inclusion criteria, extracted data and assessed the methodological quality of included trials. Data for the primary outcome (prevention of disease) were lacking. We performed a meta-analysis to pool the results of 20 studies with 5874 participants in an immunogenicity analysis and 5232 participants in the reactogenicity analysis. There were no data on clinical outcomes for the primary outcome (prevention of disease) and all studies used immunogenicity and reactogenicity (adverse events). The number of vaccine

  11. Live attenuated S. Typhimurium vaccine with improved safety in immuno-compromised mice.

    Directory of Open Access Journals (Sweden)

    Balamurugan Periaswamy

    Full Text Available Live attenuated vaccines are of great value for preventing infectious diseases. They represent a delicate compromise between sufficient colonization-mediated adaptive immunity and minimizing the risk for infection by the vaccine strain itself. Immune defects can predispose to vaccine strain infections. It has remained unclear whether vaccine safety could be improved via mutations attenuating a vaccine in immune-deficient individuals without compromising the vaccine's performance in the normal host. We have addressed this hypothesis using a mouse model for Salmonella diarrhea and a live attenuated Salmonella Typhimurium strain (ssaV. Vaccination with this strain elicited protective immunity in wild type mice, but a fatal systemic infection in immune-deficient cybb(-/-nos2(-/- animals lacking NADPH oxidase and inducible NO synthase. In cybb(-/-nos2(-/- mice, we analyzed the attenuation of 35 ssaV strains carrying one additional mutation each. One strain, Z234 (ssaV SL1344_3093, was >1000-fold attenuated in cybb(-/-nos2(-/- mice and ≈100 fold attenuated in tnfr1(-/- animals. However, in wt mice, Z234 was as efficient as ssaV with respect to host colonization and the elicitation of a protective, O-antigen specific mucosal secretory IgA (sIgA response. These data suggest that it is possible to engineer live attenuated vaccines which are specifically attenuated in immuno-compromised hosts. This might help to improve vaccine safety.

  12. Development of a human live attenuated West Nile infectious DNA vaccine: Suitability of attenuating mutations found in SA14-14-2 for WN vaccine design

    Energy Technology Data Exchange (ETDEWEB)

    Yamshchikov, Vladimir, E-mail: yaximik@gmail.com; Manuvakhova, Marina; Rodriguez, Efrain

    2016-01-15

    Direct attenuation of West Nile (WN) virus strain NY99 for the purpose of vaccine development is not feasible due to its high virulence and pathogenicity. Instead, we created highly attenuated chimeric virus W1806 with the serological identity of NY99. To further attenuate W1806, we investigated effects of mutations found in Japanese encephalitis virus vaccine SA14-14-2. WN viruses carrying all attenuating mutations lost infectivity in mammalian, but not in mosquito cells. No single reversion restored infectivity in mammalian cells, although increased infectivity in mosquito cells was observed. To identify a subset of mutations suitable for further attenuation of W1806, we analyzed effects of E{sub 138}K and K{sub 279}M changes on virulence, growth properties, and immunogenicity of derivatized W956, from which chimeric W1806 inherited its biological properties and attenuation profile. Despite strong dominant attenuating effect, introduction of only two mutations was not sufficient for attenuating W1806 to the safety level acceptable for human use. - Highlights: • Further attenuation of a WN vaccine precursor is outlined. • Effect of SA14-14-2 attenuating mutations is tested. • Mechanism of attenuation is proposed and illustrated. • The need for additional attenuating mutations is justified.

  13. Vaccinating high-risk children with the intranasal live-attenuated influenza vaccine: the Quebec experience.

    Science.gov (United States)

    Quach, Caroline

    2014-12-01

    Given the burden of illness associated with influenza, vaccination is recommended for individuals at high risk of complications. The live-attenuated influenza vaccine (LAIV) is administered by intranasal spray, thus directly stimulating mucosal immunity. In this review, we aimed to provide evidence for its efficacy and safety in different paediatric populations. We also share the Quebec experience of LAIV use through a publicly funded vaccination program for children with chronic, high-risk conditions. from randomized controlled trials in healthy children and in asthmatics have demonstrated superior efficacy of LAIV over the injectable vaccine (IIV). LAIV is well tolerated: its administration is associated with runny nose and nasal congestion, but not with asthma exacerbations and is well tolerated in children with cystic fibrosis, when compared to IIV. The vaccine is well accepted by children and parents and can easily be part of vaccination clinics in paediatric tertiary care centres targeting children with chronic, high-risk conditions, not leading to immunosuppression. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Induction and maintenance of Bordetella pertussis specific immune responses

    NARCIS (Netherlands)

    Stenger, R.M.

    2010-01-01

    Pertussis, also referred to as whooping cough, is a serious respiratory disease mainly caused by the gram-negative bacterium Bordetella pertussis. The disease is most severe in neonates and children under the age of 1. Before childhood vaccination was introduced in the 1950s, pertussis was an

  15. Clinical presentation of infants hospitalised with pertussis | Kahl ...

    African Journals Online (AJOL)

    Background. Despite the widespread use of pertussis vaccine, there has been a resurgence of pertussis cases in developed and developing countries. South Africa lacks data regarding clinical presentation and healthcare impact of pertussis. Objectives. To describe the clinical presentation and healthcare impact in ...

  16. Development of a chimeric Zika vaccine using a licensed live-attenuated flavivirus vaccine as backbone.

    Science.gov (United States)

    Li, Xiao-Feng; Dong, Hao-Long; Wang, Hong-Jiang; Huang, Xing-Yao; Qiu, Ye-Feng; Ji, Xue; Ye, Qing; Li, Chunfeng; Liu, Yang; Deng, Yong-Qiang; Jiang, Tao; Cheng, Gong; Zhang, Fu-Chun; Davidson, Andrew D; Song, Ya-Jun; Shi, Pei-Yong; Qin, Cheng-Feng

    2018-02-14

    The global spread of Zika virus (ZIKV) and its unexpected association with congenital defects necessitates the rapid development of a safe and effective vaccine. Here we report the development and characterization of a recombinant chimeric ZIKV vaccine candidate (termed ChinZIKV) that expresses the prM-E proteins of ZIKV using the licensed Japanese encephalitis live-attenuated vaccine SA14-14-2 as the genetic backbone. ChinZIKV retains its replication activity and genetic stability in vitro, while exhibiting an attenuation phenotype in multiple animal models. Remarkably, immunization of mice and rhesus macaques with a single dose of ChinZIKV elicits robust and long-lasting immune responses, and confers complete protection against ZIKV challenge. Significantly, female mice immunized with ChinZIKV are protected against placental and fetal damage upon ZIKV challenge during pregnancy. Overall, our study provides an alternative vaccine platform in response to the ZIKV emergency, and the safety, immunogenicity, and protection profiles of ChinZIKV warrant further clinical development.

  17. RESULTS OF ADMINISTRATION OF COMBINED VACCINE AGAINST DIPHTHERIA, PERTUSSIS, TETANUS, POLIOMYELITIS AND HAEMOPHILIC INFECTION TYPE B IN CHILDREN WITH CONCOMITANT DISEASES

    Directory of Open Access Journals (Sweden)

    N. F. Snegova

    2011-01-01

    Full Text Available The article summarizes data on methods and opportunities of frequently ailing children rehabilitation. Authors mark a leading role of vaccination against pneumotropic infections. Questions of successful interaction between doctor and frequently ailing child’s parents are highlighted. The observation of 94 children 3 months — 3 years old (patients had different types of initial immune insuffiiency, neurological pathology, recurrent obstructive bronchitis, or were included in group of frequently ailing children vaccinated with Pentaxim was performed. 94% of children showed asymptomatic postvaccinal period. Fever up to 39°C occurred in 2.3% of patients. Local reactions (diameter was not over 3–5 cm developed in 1.7% of children. There was no any case of postvaccinal complication. Evaluation of vaccine’s reactogenity proves its safety and reasonability in immunization against pertussis, diphtheria, tetanus, poliomyelitis, Haemophilis influenzae type b in children of different health state including those with concomitant diseases.

  18. Conditional live virus as a novel approach towards a safe live attenuated HIV vaccine

    NARCIS (Netherlands)

    Das, Atze T.; Zhou, Xue; Vink, Monique; Klaver, Bep; Berkhout, Ben

    2002-01-01

    To control the worldwide spread of HIV, a safe and effective prophylactic vaccine is urgently needed. Studies with the simian immunodeficiency virus demonstrated that a live attenuated virus can be effective as a vaccine, but serious concerns about the safety of such a vaccine virus have arisen. We

  19. In vitro pyrogenicity of the diphtheria, tetanus and acellular pertussis components of a trivalent vaccine.

    Science.gov (United States)

    Carlin, Gunnar; Viitanen, Eila

    2005-05-25

    We have earlier found that a trivalent vaccine, containing antigenic components from both Gram-positive and Gram-negative bacteria, induced secretion of the endogenous pyrogen interleukin 6 (IL-6) when added to fresh human blood in vitro. The results of the present study showed that the IL-6 secretion was induced by toxoids derived from the Gram-positive bacterium Corynebacterium diphtheriae. However, fresh whole blood from different donors reacted differently to the stimulation. The blood from some donors induced secretion of large concentrations of IL-6, while the blood from other donors induced essentially no IL-6 secretion as a response to stimulation with diphtheria toxoid or a mixture of diphtheria and tetanus toxoids. Repeated testing over several years using blood from the same donor confirmed a donor-dependency of the reaction. This donor-dependency was only found for the toxoid, since blood from all donors reacted with approximately similar IL-6 production to stimulation by endotoxin from the Gram-negative bacterium Escherichia coli, known to be mediated via the toll-like receptor (TLR) 4. Also, no donor-dependecy was found to highly purified lipoteichoic acid from the Gram-positive bacteria Bacillus subtilis and Staphylococcus aureus, known to be mediated via TLR-2 and TLR-6. The receptors involved in stimulation by diphtheria toxoid are not known, but may differ from those used by endotoxin and lipoteichoic acid.

  20. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... hiv/aids overview current news labs links & resources hpv overview why vaccinate posters buttons and banners videos ... q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus shingles media room ...

  1. Whooping Cough (Pertussis) - Fact Sheet for Parents

    Science.gov (United States)

    ... months 4 through 6 years Fact Sheet for Parents Color [2 pages] Español: Tosferina (pertussis) The best ... according to the recommended schedule. Fact Sheets for Parents Diseases and the Vaccines that Prevent Them Chickenpox ...

  2. Live-attenuated tetravalent dengue vaccines: The needs and challenges of post-licensure evaluation of vaccine safety and effectiveness.

    Science.gov (United States)

    Wichmann, Ole; Vannice, Kirsten; Asturias, Edwin J; de Albuquerque Luna, Expedito José; Longini, Ira; Lopez, Anna Lena; Smith, Peter G; Tissera, Hasitha; Yoon, In-Kyu; Hombach, Joachim

    2017-10-09

    Since December 2015, the first dengue vaccine has been licensed in several Asian and Latin American countries for protection against disease from all four dengue virus serotypes. While the vaccine demonstrated an overall good safety and efficacy profile in clinical trials, some key research questions remain which make risk-benefit-assessment for some populations difficult. As for any new vaccine, several questions, such as very rare adverse events following immunization, duration of vaccine-induced protection and effectiveness when used in public health programs, will be addressed by post-licensure studies and by data from national surveillance systems after the vaccine has been introduced. However, the complexity of dengue epidemiology, pathogenesis and population immunity, as well as some characteristics of the currently licensed vaccine, and potentially also future, live-attenuated dengue vaccines, poses a challenge for evaluation through existing monitoring systems, especially in low and middle-income countries. Most notable are the different efficacies of the currently licensed vaccine by dengue serostatus at time of first vaccination and by dengue virus serotype, as well as the increased risk of dengue hospitalization among young vaccinated children observed three years after the start of vaccination in one of the trials. Currently, it is unknown if the last phenomenon is restricted to younger ages or could affect also seronegative individuals aged 9years and older, who are included in the group for whom the vaccine has been licensed. In this paper, we summarize scientific and methodological considerations for public health surveillance and targeted post-licensure studies to address some key research questions related to live-attenuated dengue vaccines. Countries intending to introduce a dengue vaccine should assess their capacities to monitor and evaluate the vaccine's effectiveness and safety and, where appropriate and possible, enhance their surveillance

  3. Epidemiology of whooping cough & typing of Bordetella pertussis.

    Science.gov (United States)

    Hegerle, Nicolas; Guiso, Nicole

    2013-11-01

    Bordetella pertussis is a Gram-negative human-restricted bacterium that evolved from the broad-range mammalian pathogen, Bordetella bronchiseptica. It causes whooping cough or pertussis in humans, which is the most prevalent vaccine-preventable disease worldwide. The introduction of the pertussis whole-cell vaccination for young children, followed by the introduction of the pertussis acellular vaccination (along with booster vaccination) for older age groups, has affected the bacterial population and epidemiology of the disease. B. pertussis is relatively monomorphic worldwide, but nevertheless, different countries are facing different epidemiological evolutions of the disease. Although it is tempting to link vaccine-driven phenotypic and genotypic evolution of the bacterium to epidemiology, many other factors should be considered and surveillance needs to continue, in addition to studies investigating the impact of current clinical isolates on vaccine efficacy.

  4. Hepatitis B Vaccine

    Science.gov (United States)

    ... a combination product containing Haemophilus influenzae type b, Hepatitis B Vaccine) ... combination product containing Diphtheria, Tetanus Toxoids, Acellular Pertussis, Hepatitis B, Polio Vaccine)

  5. Immunogenicity, Safety, and Tolerability of Bivalent rLP2086 Meningococcal Group B Vaccine Administered Concomitantly With Diphtheria, Tetanus, and Acellular Pertussis and Inactivated Poliomyelitis Vaccines to Healthy Adolescents.

    Science.gov (United States)

    Vesikari, Timo; Wysocki, Jacek; Beeslaar, Johannes; Eiden, Joseph; Jiang, Qin; Jansen, Kathrin U; Jones, Thomas R; Harris, Shannon L; O'Neill, Robert E; York, Laura J; Perez, John L

    2016-06-01

    Concomitant administration of bivalent rLP2086 (Trumenba [Pfizer, Inc] and diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine (DTaP/IPV) was immunologically noninferior to DTaP/IPV and saline and was safe and well tolerated. Bivalent rLP2086 elicited robust and broad bactericidal antibody responses to diverse Neisseria meningitidis serogroup B strains expressing antigens heterologous to vaccine antigens after 2 and 3 vaccinations. Bivalent rLP2086, a Neisseria meningitidis serogroup B (MnB) vaccine (Trumenba [Pfizer, Inc]) recently approved in the United States to prevent invasive MnB disease in individuals aged 10-25 years, contains recombinant subfamily A and B factor H binding proteins (fHBPs). This study evaluated the coadministration of Repevax (diphtheria, tetanus, and acellular pertussis and inactivated poliovirus vaccine [DTaP/IPV]) (Sanofi Pasteur MSD, Ltd) and bivalent rLP2086. Healthy adolescents aged ≥11 to B proteins different from the vaccine antigens. Participants were randomly assigned to receive bivalent rLP2086 + DTaP/IPV (n = 373) or saline + DTaP/IPV (n = 376). Immune responses to DTaP/IPV in participants who received bivalent rLP2086 + DTaP/IPV were noninferior to those in participants who received saline + DTaP/IPV.The proportions of bivalent rLP2086 + DTaP/IPV recipients with prespecified seroprotective hSBA titers to the 4 MnB test strains were 55.5%-97.3% after vaccination 2 and 81.5%-100% after vaccination 3. The administration of bivalent rLP2086 was well tolerated and resulted in few serious adverse events. Immune responses to DTaP/IPV administered with bivalent rLP2086 to adolescents were noninferior to DTaP/IPV administered alone. Bivalent rLP2086 was well tolerated and elicited substantial and broad bactericidal responses to diverse MnB strains in a high proportion of recipients after 2 vaccinations, and these responses were further enhanced after 3 vaccinations.ClinicalTrials.gov identifier NCT01323270

  6. Testing the hypothesis that diphtheria-tetanus-pertussis vaccine has negative non-specific and sex-differential effects on child survival in high-mortality countries.

    Science.gov (United States)

    Aaby, Peter; Benn, Christine; Nielsen, Jens; Lisse, Ida Maria; Rodrigues, Amabelia; Ravn, Henrik

    2012-01-01

    Measles vaccines (MV) have sex-differential effects on mortality not explained by protection against measles infection. The authors examined whether whole-cell diphtheria-tetanus-pertussis (DTP) vaccine has sex-differential and non-specific effects. Following previous reviews and a new search, the effect of DTP on mortality up to the next vaccination was assessed in all studies where DTP was given after BCG or DTP was given after MV and there was prospective follow-up after ascertainment of vaccination status. High-mortality countries in Africa and Asia. The initial observation of negative effect of DTP generated six hypotheses, which were examined in all available studies and two randomised trials reducing the time of exposure to DTP. Consistency between studies. In the first study, DTP had negative effects on survival in contrast to the beneficial effects of BCG and MV. This pattern was repeated in the six other studies available. Second, the two 'natural experiments' found significantly higher mortality for DTP-vaccinated compared with DTP-unvaccinated children. Third, the female-male mortality ratio was increased after DTP in all nine studies; in contrast, the ratio was decreased after BCG and MV in all studies. Fourth, the increased female mortality associated with high-titre measles vaccine was found only among children who had received DTP after high-titre measles vaccine. Fifth, in six randomised trials of early MV, female but not male mortality was increased if DTP was likely to be given after MV. Sixth, the mortality rate declined markedly for girls but not for boys when DTP-vaccinated children received MV. The authors reduced exposure to DTP as most recent vaccination by administering a live vaccine (MV and BCG) shortly after DTP. Both trials reduced child mortality. These observations are incompatible with DTP merely protecting against the targeted diseases. With herd immunity to whooping cough, DTP is associated with higher mortality for girls

  7. Potency Studies of live- Attenuated Viral Vaccines Administered in ...

    African Journals Online (AJOL)

    We critically carried out a potency study in 1992 and 1997 on measles and poliovirus vaccines administered at five different vaccination centers in the metropolitan Lagos, Nigeria. using WHO guidelines on titration of live- viral vaccines, our results revealed that only 6 (16.7%) of 36 measles vaccine (MV) vials and 11 ...

  8. Cross-Protection against Marburg Virus Strains by Using a Live, Attenuated Recombinant Vaccine

    National Research Council Canada - National Science Library

    Daddario-DiCaprio, Kathleen M; Geisbert, Thomas W; Geisbert, Joan B; Stroeher, Ute; Hensley, Lisa E; Grolla, Allen; Fritz, Elizabeth A; Feldmann, Friederike; Feldmann, Heinz; Jones, Steven M

    2006-01-01

    .... MARV is also considered to have potential as a biological weapon. Recently, we reported the development of a promising attenuated, replication-competent vaccine against MARV based on recombinant vesicular stomatitis virus (VSV...

  9. A retrospective study of acute pertussis in Hasan Sadikin Hospital–Indonesia

    Directory of Open Access Journals (Sweden)

    Heda Melinda Nataprawira

    2015-06-01

    Conclusions: Mostly patients were admitted on paroxysmal phase when no more active B. pertussis could be found from nasopharyngeal secret. A rigorous history taking particularly excessive cough, posttussive vomitting, and pertussis vaccination status need to be taken into account.

  10. Determinants of attenuation and temperature sensitivity in the type 1 poliovirus Sabin vaccine.

    OpenAIRE

    Bouchard, M J; Lam, D H; Racaniello, V R

    1995-01-01

    To identify determinants of attenuation in the poliovirus type 1 Sabin vaccine strain, a series of recombinant viruses were constructed by using infectious cDNA clones of the virulent type 1 poliovirus P1/Mahoney and the attenuated type 1 vaccine strain P1/Sabin. Intracerebral inoculation of these viruses into transgenic mice which express the human receptor for poliovirus identified regions of the genome that conferred reduced neurovirulence. Exchange of smaller restriction fragments and sit...

  11. Development of a human live attenuated West Nile infectious DNA vaccine: Identification of a minimal mutation set conferring the attenuation level acceptable for a human vaccine

    Energy Technology Data Exchange (ETDEWEB)

    Yamshchikov, Vladimir, E-mail: yaximik@gmail.com; Manuvakhova, Marina; Rodriguez, Efrain; Hébert, Charles

    2017-01-15

    ABSTRACT: For the development of a human West Nile (WN) infectious DNA (iDNA) vaccine, we created highly attenuated chimeric virus W1806 with the serological identity of highly virulent WN-NY99. Earlier, we attempted to utilize mutations found in the E protein of the SA14-14-2 vaccine to bring safety of W1806 to the level acceptable for human use (). Here, we analyzed effects of the SA14-14-2 changes on growth properties and neurovirulence of W1806. A set including the E138K, K279M, K439R and G447D changes was identified as the perspective subset for satisfying the target safety profile without compromising immunogenicity of the vaccine candidate. The genetic stability of the attenuated phenotype was found to be unsatisfactory being dependent on a subset of attenuating changes incorporated in W1806. Elucidation of underlying mechanisms influencing selection of pathways for restoration of the envelope protein functionality will facilitate resolution of the emerged genetic stability issue. - Highlights: •Effect of mutations in E on properties of WN1806 is determined. •A subset of attenuating mutations suitable for a human vaccine is defined. •Mechanism of attenuation is proposed and illustrated. •Underlying mechanisms of neurovirulence reversion are suggested.

  12. A review of immunogenicity and tolerability of live attenuated Hepatitis A vaccine in children

    Science.gov (United States)

    Rao, Sameer; Mao, J. S.; Motlekar, Salman; Fangcheng, Zhuang; Kadhe, Ganesh

    2016-01-01

    ABSTRACT Changing epidemiology of Hepatitis A virus (HAV) has led to an increased susceptibility of adolescents and adults to the infection. Vaccination can remarkably reduce the incidence and associated morbidity of HAV infection. This review is focused on the safety and efficacy of H2 strain derived live attenuated Hepatitis A vaccine. We found the vaccine to be highly immunogenic with minimal or negligible safety issues. Moreover, a single dose of live attenuated vaccine persists a long term immune response and can be a preferred option for developing countries. In 2014, Indian Academy of Paediatrics (IAP) also updated their recommendations for H2 vaccine as a single dose as against the previous 2 dose schedule. A focused approach to include the vaccine in national immunization program should be explored. PMID:27532370

  13. Neurologic manifestations of diphtheria and pertussis.

    Science.gov (United States)

    Sanghi, Viraj

    2014-01-01

    Historically, diphtheria was a major cause of morbidity and mortality in the prevaccine era. However, in recent times there has been a resurgence of diphtheria, especially in the newly independent states of the former USSR. Diphtheritic polyneuropathy can be a serious complication in patients who have a severe infection. In patients with pertussis, seizures and encephalopathy can occur as a complication of asphyxia. Vaccination against diphtheria and pertussis in children and booster vaccination in adults is recommended. DTP (diphtheria, tetanus, pertussis) vaccination has been shown to increase the risk of febrile seizures in children. Currently, it appears that the risk of vaccine-induced encephalopathy and/or epilepsy following DTP vaccination, if any, is extremely low. © 2014 Elsevier B.V. All rights reserved.

  14. Pertussis (Whooping Cough) Outbreaks

    Science.gov (United States)

    ... of Search Controls Search Form Controls Cancel Submit Pertussis (Whooping Cough) Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Pertussis Home About Pertussis Causes & Transmission Signs & Symptoms Complications ...

  15. Pertussis (Whooping Cough) Complications

    Science.gov (United States)

    ... of Search Controls Search Form Controls Cancel Submit Pertussis (Whooping Cough) Note: Javascript is disabled or is not supported ... message, please visit this page: About CDC.gov . Pertussis Home About Pertussis Causes & Transmission Signs & Symptoms Complications ...

  16. Co-administration of live measles and yellow fever vaccines and inactivated pentavalent vaccines is associated with increased mortality compared with measles and yellow fever vaccines only. An observational study from Guinea-Bissau

    DEFF Research Database (Denmark)

    Fisker, Ane Bærent; Ravn, Henrik Bylling; Rodrigues, Amabelia

    2014-01-01

    is replacing DTP in many low-income countries and yellow fever vaccine (YF) has been introduced to be given together with MV. Pentavalent and YF vaccines were introduced in Guinea-Bissau in 2008. We investigated whether co-administration of pentavalent vaccine with MV and yellow fever vaccine has similar......Studies from low-income countries indicate that co-administration of inactivated diphtheria-tetanus-pertussis (DTP) vaccine and live attenuated measles vaccine (MV) is associated with increased mortality compared with receiving MV only. Pentavalent (DTP-H. Influenza type B-Hepatitis B) vaccine...

  17. Immunogenicity and safety of a live attenuated varicella vaccine in ...

    African Journals Online (AJOL)

    children were vaccinated, of whom 189 (44,5%) completed the study. ... varicella vaccination.. Results. The vaccine was safe and well tolerated. No local symptoms were ... of varicella (e.g. encephalitis, pneumonia, scars); inhibition of the spread of the .... intestinal disorders, respiratory infections, measles and conjunctivitis) ...

  18. Clinical and economic assessment of different general population strategies of pertussis vaccine booster regarding number of doses and age of application for reducing whooping cough disease burden: a systematic review.

    Science.gov (United States)

    Rodríguez-Cobo, Iria; Chen, Yen-Fu; Olowokure, Babatunde; Litchfield, Ian

    2008-12-09

    Pertussis continues to be an important cause of morbidity and mortality in children too young to be fully protected despite high vaccination coverage. This has been attributed to waning immunity in older people, leading to the development of strategies to increase levels of immunity. A systematic review was conducted to assess the clinical and cost effectiveness of four population-based strategies for pertussis booster vaccination: single booster at 12-24 months old, single pre-school booster, single adolescent booster and multiple boosters in adulthood every 10 years. Electronic databases and Internet resources were searched to June 2006. Nine observational studies, four mathematical models and eight economic evaluations were included, evaluating four different strategies. Strong evidence to recommend any of these strategies was not found.

  19. Titration of individual strains in trivalent live-attenuated influenza vaccine without neutralization.

    Science.gov (United States)

    Sirinonthanawech, Naraporn; Surichan, Somchaiya; Namsai, Aphinya; Puthavathana, Pilaipan; Auewarakul, Prasert; Kongchanagul, Alita

    2016-11-01

    Formulation and quality control of trivalent live-attenuated influenza vaccine requires titration of infectivity of individual strains in the trivalent mix. This is usually performed by selective neutralization of two of the three strains and titration of the un-neutralized strain in cell culture or embryonated eggs. This procedure requires standard sera with high neutralizing titer against each of the three strains. Obtaining standard sera, which can specifically neutralize only the corresponding strain of influenza viruses and is able to completely neutralize high concentration of virus in the vaccine samples, can be a problem for many vaccine manufacturers as vaccine stocks usually have very high viral titers and complete neutralization may not be obtained. Here an alternative approach for titration of individual strain in trivalent vaccine without the selective neutralization is presented. This was done by detecting individual strains with specific antibodies in an end-point titration of a trivalent vaccine in cell culture. Similar titers were observed in monovalent and trivalent vaccines for influenza A H3N2 and influenza B strains, whereas the influenza A H1N1 strain did not grow well in cell culture. Viral interference among the vaccine strains was not observed. Therefore, providing that vaccine strains grow well in cell culture, this assay can reliably determine the potency of individual strains in trivalent live-attenuated influenza vaccines. Copyright © 2016 Elsevier B.V. All rights reserved.

  20. Bordetella pertussis evolution in the (functional) genomics era

    Science.gov (United States)

    Belcher, Thomas; Preston, Andrew

    2015-01-01

    The incidence of whooping cough caused by Bordetella pertussis in many developed countries has risen dramatically in recent years. This has been linked to the use of an acellular pertussis vaccine. In addition, it is thought that B. pertussis is adapting under acellular vaccine mediated immune selection pressure, towards vaccine escape. Genomics-based approaches have revolutionized the ability to resolve the fine structure of the global B. pertussis population and its evolution during the era of vaccination. Here, we discuss the current picture of B. pertussis evolution and diversity in the light of the current resurgence, highlight import questions raised by recent studies in this area and discuss the role that functional genomics can play in addressing current knowledge gaps. PMID:26297914

  1. A phase III, open-label, randomised multicentre study to evaluate the immunogenicity and safety of a booster dose of two different reduced antigen diphtheria-tetanus-acellular pertussis-polio vaccines, when co-administered with measles-mumps-rubella vaccine in 3 and 4-year-old healthy children in the UK.

    Science.gov (United States)

    Marlow, Robin; Kuriyakose, Sherine; Mesaros, Narcisa; Han, Htay Htay; Tomlinson, Richard; Faust, Saul N; Snape, Matthew D; Pollard, Andrew J; Finn, Adam

    2018-04-19

    To evaluate the immunogenicity and safety of a reduced antigen diphtheria-tetanus-acellular pertussis-inactivated poliovirus (dTap-IPV B ) vaccine (Boostrix-IPV, GSK) as a pre-school booster in 3-4 year old children as compared to dTap-IPV R (Repevax, Sanofi Pasteur), when co-administered with mumps-measles-rubella vaccine (MMRV). This phase III, open label, randomised study was conducted in the UK between April 2011 and April 2012. Children due their pre-school dTap-IPV booster vaccination were randomised 2:1 to receive one of two different dTap-IPV vaccines (dTap-IPV B or dTap-IPV R ) with blood sample for immunogenicity assessment just prior and one month after vaccination. Immune responses to diphtheria, tetanus and polio antigens were compared between the study vaccines (inferential comparison). In the absence of an accepted pertussis correlate of protection, the immunogenicity of dTap-IPV B vaccine against pertussis was compared with historical pertussis efficacy data (inferential comparison). Safety and reactogenicity of both study vaccines were evaluated. 387 children were randomised and 385 vaccinated: 255 in the dTap-IPV B group and 130 in the dTap-IPV R group. Prior to vaccination, ≥76.8% of children had anti-diphtheria and ≥65.5% had anti-tetanus titres above the protection threshold; for pertussis, the pre-vaccination seropositivity rate ranged between 18.1 and 70.6%. Both vaccines were immunogenic with 99.2-100% of children achieving titres above the pre-specified seroprotection/seropositivity thresholds. One serious adverse event not considered as causally related to the study vaccination by the study investigator was reported in the dTap-IPV B group. Non-inferiority of dTap-IPV B to dTap-IPV R was demonstrated. Both vaccines had a clinically acceptable safety and reactogenicity profile when co-administered with MMRV to children 3-4 years old. NCT01245049 (ClinicalTrials.gov). Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All

  2. Clinical development of a novel inactivated poliomyelitis vaccine based on attenuated Sabin poliovirus strains.

    Science.gov (United States)

    Verdijk, Pauline; Rots, Nynke Y; Bakker, Wilfried A M

    2011-05-01

    Following achievement of polio eradication, the routine use of all live-attenuated oral poliovirus vaccines should be discontinued. However, the costs per vaccine dose for the alternative inactivated poliovirus vaccine (IPV) are significantly higher and the current production capacity is not sufficient for worldwide distribution of the vaccine. In order to achieve cost-prize reduction and improve affordability, IPV production processes and dose-sparing strategies should be developed to facilitate local manufacture at a relatively lower cost. The use of attenuated Sabin instead of wild-type polio strains will provide additional safety during vaccine production and permits production in low-cost settings. Sabin-IPV is under development by several manufacturers. This article gives an overview of results from clinical trials with Sabin-IPV and discusses the requirements and challenges in the clinical development of this novel IPV.

  3. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... immunizations about immunizations current news Flu's Gonna Lose hepatitis a & b vaccines im/sq how to do kids ... abcs of mmr & dtp thimerosal vaccine safety q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus ...

  4. Oral vaccination with attenuated Salmonella choleraesuis C500 ...

    African Journals Online (AJOL)

    Helicobacter pylori are well known as the major gastro-duodenal pathogen of peptic ulcer disease and gastric cancer. Recombinant H. pylori vaccine comprising a single subunit antigen can only induce immune response with limited protection efficiency. Development of oral vaccine would be a new effective strategy for the ...

  5. High frequency of pertussis in older children and adolescents with prolonged cough in Turkey.

    Science.gov (United States)

    Aslan, Aslı; Kurugöl, Zafer; Aydemir, Şöhret; Gürsel, Derya; Koturoğlu, Güldane

    2016-01-01

    This study aimed to determine the frequency of B. pertussis infection among Turkish children with prolonged cough. Nasopharyngeal specimens were collected from 7-18 year old children, presenting with prolonged cough of two to four weeks' duration. Specimens were examined for B. pertussis by PCR. Of 101 children with prolonged cough, 20 (19.8%) had a positive PCR testing for B. pertussis. Children who were vaccinated ≥5 years previously had a 6.13-fold higher risk of PCR-confirmed pertussis than those who were vaccinated pertussis (paroxysmal cough, whooping and post-tussive vomiting) were seen in 30%, 15% and 25% of the patients with positive PCR, respectively; 55% of them had only a prolonged cough without any classic symptoms. Pertussis is common among Turkish children with prolonged cough, even after implementation of a fifth dose of pertussis vaccination and despite high vaccination coverage.

  6. The importance of Bordetella pertussis strains which do not produce virulence factors in the epidemiology of pertussis

    Directory of Open Access Journals (Sweden)

    Maciej Polak

    2017-05-01

    Full Text Available Bordetella pertussis strains, which have lost the ability to produce antigens, such as pertactin - Prn, pertussis toxin - Ptx, filamentous haemagglutinin - FHA, fimbriae type 2 and 3 - Fim 2 and 3, tracheal colonization factor - TcfA, have recently been isolated in countries with a high vaccination coverage. The emergence of such isolates might have resulted from B. pertussis natural evolution course or adaptive mechanisms, allowing increased circulation of the pathogen in vaccinated populations. So far, the majority of described mutants were deficient in the Prn production. Prn deficient isolates were found in countries which use acellular pertussis vaccines (aP in routine immunization programmes. The increase of frequency of Prn¯ strains isolation was correlated with the period of routine vaccination with aP vaccines. In most countries, the spread of these isolates has resulted from independent mutations rather than from the expansion of a single clone. Prn¯ isolates were collected from patients showing typical clinical symptoms of pertussis found for Prn+ strains. Results of in vitro and in vivo studies have shown that Prn¯, Ptx¯ and FHA¯ isolates retain cytotoxic properties, and besides Ptx¯ isolates, were lethal in intranasally infected mice. Further explanation of the impact of antigen deficiencies on virulence and transmission of B. pertussis in the context of the continuous increase of pertussis incidence is necessary to develop a new, optimized strategy of pertussis prevention.

  7. Risk of Febrile Seizures and Epilepsy After Vaccination With Diphtheria, Tetanus, Acellular Pertussis, Inactivated Poliovirus, and Haemophilus Influenzae Type b

    DEFF Research Database (Denmark)

    Sun, Yuelian; Christensen, Jakob Christensen; Hviid, Anders

    2012-01-01

    -acellular pertussis–inactivated poliovirus– Haemophilus influenzae type b (DTaP-IPV-Hib) vaccine since September 2002. Objective To estimate the risk of febrile seizures and epilepsy after DTaP-IPV-Hib vaccination given at 3, 5, and 12 months. Design, Setting, and Participants A population-based cohort study of 378...

  8. Comparison of the nucleotide sequence of wild-type hepatitis - A virus and its attenuated candidate vaccine derivative

    International Nuclear Information System (INIS)

    Cohen, J.I.; Rosenblum, B.; Ticehurst, J.R.; Daemer, R.; Feinstone, S.; Purcell, R.H.

    1987-01-01

    Development of attenuated mutants for use as vaccines is in progress for other viruses, including influenza, rotavirus, varicella-zoster, cytomegalovirus, and hepatitis-A virus (HAV). Attenuated viruses may be derived from naturally occurring mutants that infect human or nonhuman hosts. Alternatively, attenuated mutants may be generated by passage of wild-type virus in cell culture. Production of attenuated viruses in cell culture is a laborious and empiric process. Despite previous empiric successes, understanding the molecular basis for attenuation of vaccine viruses could facilitate future development and use of live-virus vaccines. Comparison of the complete nucleotide sequences of wild-type (virulent) and vaccine (attenuated) viruses has been reported for polioviruses and yellow fever virus. Here, the authors compare the nucleotide sequence of wild-type HAV HM-175 with that of a candidate vaccine derivative

  9. Live Attenuated Tularemia Vaccines for Protection Against Respiratory Challenge With Virulent F. tularensis subsp. tularensis

    Science.gov (United States)

    Jia, Qingmei; Horwitz, Marcus A.

    2018-01-01

    Francisella tularensis is the causative agent of tularemia and a Tier I bioterrorism agent. In the 1900s, several vaccines were developed against tularemia including the killed “Foshay” vaccine, subunit vaccines comprising F. tularensis protein(s) or lipoproteins(s) in an adjuvant formulation, and the F. tularensis Live Vaccine Strain (LVS); none were licensed in the U.S.A. or European Union. The LVS vaccine retains toxicity in humans and animals—especially mice—but has demonstrated efficacy in humans, and thus serves as the current gold standard for vaccine efficacy studies. The U.S.A. 2001 anthrax bioterrorism attack spawned renewed interest in vaccines against potential biowarfare agents including F. tularensis. Since live attenuated—but not killed or subunit—vaccines have shown promising efficacy and since vaccine efficacy against respiratory challenge with less virulent subspecies holarctica or F. novicida, or against non-respiratory challenge with virulent subsp. tularensis (Type A) does not reliably predict vaccine efficacy against respiratory challenge with virulent subsp. tularensis, the route of transmission and species of greatest concern in a bioterrorist attack, in this review, we focus on live attenuated tularemia vaccine candidates tested against respiratory challenge with virulent Type A strains, including homologous vaccines derived from mutants of subsp. holarctica, F. novicida, and subsp. tularensis, and heterologous vaccines developed using viral or bacterial vectors to express F. tularensis immunoprotective antigens. We compare the virulence and efficacy of these vaccine candidates with that of LVS and discuss factors that can significantly impact the development and evaluation of live attenuated tularemia vaccines. Several vaccines meet what we would consider the minimum criteria for vaccines to go forward into clinical development—safety greater than LVS and efficacy at least as great as LVS, and of these, several meet the

  10. A meta-analysis of experimental studies of attenuated Schistosoma mansoni vaccines in the mouse model

    Directory of Open Access Journals (Sweden)

    Mizuho eFukushige

    2015-02-01

    Full Text Available Schistosomiasis is a water-borne, parasitic disease of major public health importance. There has been considerable effort for several decades towards the development of a vaccine against the disease. Numerous mouse experimental studies using attenuated Schistosoma mansoni parasites for vaccination have been published since the 1960s. However, to date, there has been no systematic review or meta-analysis of these data. The aim of this study is to identify measurable experimental conditions that affect the level of protection against re-infection with S. mansoni in mice vaccinated with radiation attenuated cercariae. Following a systematic review, a total of 755 observations were extracted from 105 articles (published 1963-2007 meeting the searching criteria. Random effects meta-regression models were used to identify the influential predictors.Three predictors were found to have statistically significant effects on the level of protection from vaccination: increasing numbers of immunizing parasites had a positive effect on fraction of protection whereas increasing radiation dose and time to challenge infection had negative effects. Models showed that the irradiated cercariae vaccine has the potential to achieve protection as high as 78% with a single dose vaccination. This declines slowly over time but remains high for at least 8 months after the last immunization. These findings provide insights into the optimal delivery of attenuated parasite vaccination and into the nature and development of protective vaccine induced immunity against schistosomiasis which may inform the formulation of human vaccines and the predicted duration of protection and thus frequency of booster vaccines.

  11. Pertussis resurgence: waning immunity and pathogen adaptation - two sides of the same coin

    NARCIS (Netherlands)

    Mooi, F.R.; Maas, N. van der; Melker, H.E. de

    2014-01-01

    SUMMARY Pertussis or whooping cough has persisted and resurged in the face of vaccination and has become one of the most prevalent vaccine-preventable diseases in Western countries. The high circulation rate of Bordetella pertussis poses a threat to infants that have not been (completely) vaccinated

  12. Immunogenicity and safety of one dose of diphtheria, tetanus, acellular pertussis and poliomyelitis vaccine (Repevax®) followed by two doses of diphtheria, tetanus and poliomyelitis vaccine (Revaxis®) in adults aged ≥ 40 years not receiving a diphtheria- and tetanus-containing vaccination in the last 20 years.

    Science.gov (United States)

    Dominicus, Rolf; Galtier, Florence; Richard, Patrick; Baudin, Martine

    2014-06-30

    The immunogenicity and safety of one dose of Tdap-IPV (tetanus, diphtheria, acellular pertussis and inactivated poliomyelitis vaccine) and two doses of Td-IPV (tetanus, diphtheria and inactivated poliomyelitis vaccine) were assessed in adults who had not received a diphtheria- and tetanus-containing vaccine in the last 20 years. This open-label, multicentre study was conducted in adults aged ≥ 40 years with no diphtheria- and tetanus-containing vaccine in the last 20 years. Participants received one dose of Tdap-IPV followed by two doses of Td-IPV (0, 1, 6 month schedule). Primary immunogenicity objectives: to demonstrate acceptable seroprotection rates (percentage of participants with antibody titre above threshold) post-dose 3 for diphtheria (≥ 0.1IU/mL by seroneutralization assay [SNA]); tetanus (≥ 0.1IU/mL by enzyme-linked immunosorbent assay [ELISA]); and poliomyelitis (≥ 8 1/dil by SNA); and to evaluate the percentage of participants with an antibody concentration ≥ 5EU/mL (by ELISA) for pertussis antigens post-dose 1. Seroprotection rates were acceptable if the lower limit of the 95% confidence interval (CI) was >95%. Percentage of participants with basic clinical immunity against diphtheria (≥ 0.01IU/mL) was also assessed. Safety (adverse events [AEs] and serious AEs) was assessed after each dose. Overall, 336 participants were included (mean age: 60.2 years). Post-dose 3 seroprotection rates were: diphtheria, 94.6% (CI 91.5-96.8); tetanus and poliomyelitis, 100% (CI: 98.8-100). Percentage of participants with an antibody titre ≥ 5EU/mL against pertussis antigens was ≥ 95.8% for all five pertussis components. Basic clinical immunity against diphtheria was achieved in 100% (CI: 98.8-100) of participants. AEs were reported more frequently following vaccination with Tdap-IPV (post-dose 1: 65.3%) than with Td-IPV (post-dose 2: 48.3%; post-dose 3: 50.3%). This study highlights the benefits of using Tdap-IPV followed by two doses of Td-IPV in an

  13. Bordetella pertussis pertactin knock-out strains reveal immunomodulatory properties of this virulence factor.

    NARCIS (Netherlands)

    Hovingh, Elise Sofie; Mariman, Rob; Solans, Luis; Hijdra, Daniëlle; Hamstra, Hendrik-Jan; Jongerius, Ilse; van Gent, Marjolein; Mooi, Frits; Locht, Camille; Pinelli, Elena

    2018-01-01

    Whooping cough, caused by Bordetella pertussis, has resurged and presents a global health burden worldwide. B. pertussis strains unable to produce the acellular pertussis vaccine component pertactin (Prn), have been emerging and in some countries represent up to 95% of recent clinical isolates.

  14. The new health legacy: when pertussis becomes a heritage transmitted from mothers to infants.

    Science.gov (United States)

    Zouari, Asma; Smaoui, Hanen; Bousnina, Souad; Menif, Khaled; Ben Jaballah, Najla; Kechrid, Amel

    2011-10-01

    Despite high vaccination coverage rates, there has been a gradual increase in reported pertussis cases. Although whooping cough affects all ages, young infants continue to suffer the greatest pertussis disease burden. Adolescents and adults are the primary source of infection for young babies. In this paper, we report two cases involving the likely transmission of pertussis from mothers to infants in Tunisia.

  15. Rotavirus specific plasma secretory immunoglobulin in children with acute gastroenteritis and children vaccinated with an attenuated human rotavirus vaccine

    Science.gov (United States)

    Herrera, Daniel; Vásquez, Camilo; Corthésy, Blaise; Franco, Manuel A; Angel, Juana

    2013-01-01

    Rotavirus (RV)–specific secretory immunoglobulin (RV-SIg) has been previously detected in serum of naturally RV infected children and shown to reflect the intestinal Ig immune response. Total plasma SIgA and plasma RV-SIg were evaluated by ELISA in children with gastroenteritis due or not due to RV infection and in 50 children vaccinated with the attenuated RIX4414 human RV vaccine and 62 placebo recipients. RV-SIg was only detected in children with evidence of previous RV infection or with acute RV gastroenteritis. Vaccinees had higher RV-SIg titers than placebo recipients and RV-SIg titers increased after the second vaccine dose. RV-SIg measured after the second dose correlated with protection when vaccinees and placebo recipients were analyzed jointly. RV-SIg may serve as a valuable correlate of protection for RV vaccines. PMID:23839157

  16. Development of an attenuated live heartwater vaccine for use in ...

    International Development Research Centre (IDRC) Digital Library (Canada)

    ... it requires ultra-cold storage (-196° C), intravenous administration by veterinary health professionals, ... It is expected that by the end of the project, the production process of the new heartwater vaccine will ... Agricultural Research Council.

  17. A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence

    International Nuclear Information System (INIS)

    Papaneri, Amy B.; Wirblich, Christoph; Cann, Jennifer A.; Cooper, Kurt; Jahrling, Peter B.; Schnell, Matthias J.; Blaney, Joseph E.

    2012-01-01

    We are developing inactivated and live-attenuated rabies virus (RABV) vaccines expressing Ebola virus (EBOV) glycoprotein for use in humans and endangered wildlife, respectively. Here, we further characterize the pathogenesis of the live-attenuated RABV/EBOV vaccine candidates in mice in an effort to define their growth properties and potential for safety. RABV vaccines expressing GP (RV-GP) or a replication-deficient derivative with a deletion of the RABV G gene (RVΔG-GP) are both avirulent after intracerebral inoculation of adult mice. Furthermore, RVΔG-GP is completely avirulent upon intracerebral inoculation of suckling mice unlike parental RABV vaccine or RV-GP. Analysis of RVΔG-GP in the brain by quantitative PCR, determination of virus titer, and immunohistochemistry indicated greatly restricted virus replication. In summary, our findings indicate that RV-GP retains the attenuation phenotype of the live-attenuated RABV vaccine, and RVΔG-GP would appear to be an even safer alternative for use in wildlife or consideration for human use.

  18. A replication-deficient rabies virus vaccine expressing Ebola virus glycoprotein is highly attenuated for neurovirulence

    Energy Technology Data Exchange (ETDEWEB)

    Papaneri, Amy B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States); Wirblich, Christoph [Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Cann, Jennifer A.; Cooper, Kurt [Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick MD, 21702 (United States); Jahrling, Peter B. [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States); Integrated Research Facility, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick MD, 21702 (United States); Schnell, Matthias J., E-mail: matthias.schnell@jefferson.edu [Department of Microbiology and Immunology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Jefferson Vaccine Center, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107 (United States); Blaney, Joseph E., E-mail: jblaney@niaid.nih.gov [Emerging Viral Pathogens Section, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Fort Detrick, MD 21702 (United States)

    2012-12-05

    We are developing inactivated and live-attenuated rabies virus (RABV) vaccines expressing Ebola virus (EBOV) glycoprotein for use in humans and endangered wildlife, respectively. Here, we further characterize the pathogenesis of the live-attenuated RABV/EBOV vaccine candidates in mice in an effort to define their growth properties and potential for safety. RABV vaccines expressing GP (RV-GP) or a replication-deficient derivative with a deletion of the RABV G gene (RV{Delta}G-GP) are both avirulent after intracerebral inoculation of adult mice. Furthermore, RV{Delta}G-GP is completely avirulent upon intracerebral inoculation of suckling mice unlike parental RABV vaccine or RV-GP. Analysis of RV{Delta}G-GP in the brain by quantitative PCR, determination of virus titer, and immunohistochemistry indicated greatly restricted virus replication. In summary, our findings indicate that RV-GP retains the attenuation phenotype of the live-attenuated RABV vaccine, and RV{Delta}G-GP would appear to be an even safer alternative for use in wildlife or consideration for human use.

  19. Comparison of the Effectiveness of Trivalent Inactivated Influenza Vaccine and Live, Attenuated Influenza Vaccine in Preventing Influenza-Like Illness among US Service Members, 2006-2009

    Science.gov (United States)

    2012-11-26

    controlled studies. Vaccine 2012; 30:886–92. 11. Piedra PA, Gaglani MJ, Kozinetz CA, et al. Trivalent live attenuated intranasal influenza vaccine...120:e553–64. 12. Halloran ME, Piedra PA, Longini IM Jr, et al. Efficacy of trivalent, cold-adapted, influenza virus vaccine against influenza A (Fujian

  20. Live Attenuated Influenza Vaccine Enhances Colonization of Streptococcus pneumoniae and Staphylococcus aureus in Mice

    Science.gov (United States)

    Mina, Michael J.; McCullers, Jonathan A.; Klugman, Keith P.

    2014-01-01

    ABSTRACT Community interactions at mucosal surfaces between viruses, like influenza virus, and respiratory bacterial pathogens are important contributors toward pathogenesis of bacterial disease. What has not been considered is the natural extension of these interactions to live attenuated immunizations, and in particular, live attenuated influenza vaccines (LAIVs). Using a mouse-adapted LAIV against influenza A (H3N2) virus carrying the same mutations as the human FluMist vaccine, we find that LAIV vaccination reverses normal bacterial clearance from the nasopharynx and significantly increases bacterial carriage densities of the clinically important bacterial pathogens Streptococcus pneumoniae (serotypes 19F and 7F) and Staphylococcus aureus (strains Newman and Wright) within the upper respiratory tract of mice. Vaccination with LAIV also resulted in 2- to 5-fold increases in mean durations of bacterial carriage. Furthermore, we show that the increases in carriage density and duration were nearly identical in all aspects to changes in bacterial colonizing dynamics following infection with wild-type (WT) influenza virus. Importantly, LAIV, unlike WT influenza viruses, had no effect on severe bacterial disease or mortality within the lower respiratory tract. Our findings are, to the best of our knowledge, the first to demonstrate that vaccination with a live attenuated viral vaccine can directly modulate colonizing dynamics of important and unrelated human bacterial pathogens, and does so in a manner highly analogous to that seen following wild-type virus infection. PMID:24549845

  1. Crucial role of antibodies to pertactin in Bordetella pertussis immunity

    NARCIS (Netherlands)

    Hellwig, SMM; Rodriguez, ME; Berbers, GAM; de Winkel, JGJV; Mooi, FR

    2003-01-01

    Pertussis, a serious infectious disease of the respiratory tract caused by Bordetella pertussis, is reemerging in vaccinated populations. Efforts to curtail this disease are hampered by limited insight into the basis of protective immunity. Opsonophagocytosis was recently found to play a central

  2. No evidence of murine leukemia virus-related viruses in live attenuated human vaccines.

    Directory of Open Access Journals (Sweden)

    William M Switzer

    Full Text Available The association of xenotropic murine leukemia virus (MLV-related virus (XMRV in prostate cancer and chronic fatigue syndrome reported in previous studies remains controversial as these results have been questioned by recent data. Nonetheless, concerns have been raised regarding contamination of human vaccines as a possible source of introduction of XMRV and MLV into human populations. To address this possibility, we tested eight live attenuated human vaccines using generic PCR for XMRV and MLV sequences. Viral metagenomics using deep sequencing was also done to identify the possibility of other adventitious agents.All eight live attenuated vaccines, including Japanese encephalitis virus (JEV (SA-14-14-2, varicella (Varivax, measles, mumps, and rubella (MMR-II, measles (Attenuvax, rubella (Meruvax-II, rotavirus (Rotateq and Rotarix, and yellow fever virus were negative for XMRV and highly related MLV sequences. However, residual hamster DNA, but not RNA, containing novel endogenous gammaretrovirus sequences was detected in the JEV vaccine using PCR. Metagenomics analysis did not detect any adventitious viral sequences of public health concern. Intracisternal A particle sequences closest to those present in Syrian hamsters and not mice were also detected in the JEV SA-14-14-2 vaccine. Combined, these results are consistent with the production of the JEV vaccine in Syrian hamster cells.We found no evidence of XMRV and MLV in eight live attenuated human vaccines further supporting the safety of these vaccines. Our findings suggest that vaccines are an unlikely source of XMRV and MLV exposure in humans and are consistent with the mounting evidence on the absence of these viruses in humans.

  3. Development and efficacy of an attenuated Vibrio harveyi vaccine candidate with cross protectivity against Vibrio alginolyticus.

    Science.gov (United States)

    Hu, Yong-hua; Deng, Tian; Sun, Bo-guang; Sun, Li

    2012-06-01

    Vibrio harveyi is a Gram-negative bacterial pathogen that can infect a wide range of marine animals. In previous studies, we have reported a virulent V. harveyi strain, T4D. In the present study, an attenuated mutant of T4D, T4DM, was obtained by selection of rifampicin resistance. Compared to the wild type, T4DM was different in whole-cell protein profile and much slower in growth rate when cultured in stress conditions caused by iron depletion. Virulence analysis showed that compared to T4D, T4DM exhibited a dramatically increased median lethal dose, impaired tissue dissemination capacity, defective hemolytic activity, and significantly reduced resistance against the killing effect of host serum. To examine the potential of T4DM as a live attenuated vaccine, Japanese flounder (Paralichthys olivaceus) were vaccinated with T4DM via intraperitoneal injection or immersion. The results showed that at one and two months post-vaccination, fish administered with T4DM via both approaches, in particular that of immersion, were effectively protected against not only V. harveyi but also Vibrio alginolyticus, another important fish pathogen. Microbiological analysis showed that following immersion vaccination, T4DM was recovered from the internal organs of the vaccinated fish in a time-dependent manner within the first 6 days post-vaccination. Serum antibodies against V. harveyi and V. alginolyticus were detected in T4DM-vaccinated fish, and, compared to serum from control fish, serum from T4DM-vaccinated fish was significantly enhanced in bactericidal activity. These results indicate that T4DM is an attenuated strain with residual infectivity and that T4DM can induce effective cross-species protection against both V. harveyi and V. alginolyticus when used as a live immersion vaccine. Copyright © 2012 Elsevier Ltd. All rights reserved.

  4. 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...... represented a primary stimulus in all subjects. First, basal 2',5'A activity increased severalfold in response to yellow fever vaccination. In IDDM subjects, this increase was significantly lower (P = .025). Second, the 2',5'A activity increased proportionately to the higher basal 2',5'A activity in IDDM...

  5. Schistosoma japonicum: An ultraviolet-attenuated cercarial vaccine applicable in the field for water buffaloes

    International Nuclear Information System (INIS)

    Shi, Y.E.; Jiang, C.F.; Han, J.J.; Li, Y.L.; Ruppel, A.

    1990-01-01

    Water buffaloes were vaccinated three times with 10,000 Schistosoma japonicum cercariae irradiated with ultraviolet (uv) light at a dose of 400 microW x min/cm2. The irradiation was performed with cheap, simple, and portable equipment in a rural area of Hubei Province (People's Republic of China). A challenge infection of 1000 untreated cercariae was given to six vaccinated and six naive control buffaloes, while two vaccinated animals were not challenged. The experiment was terminated 6 weeks after the challenge. Control animals had lost body weight and harbored a mean of 110 worms and 37 eggs per gram of liver. The vaccinated animals gained weight after the challenge and developed 89% resistance to infection with S. japonicum. Since schistosomiasis japonica is nowadays transmitted in China predominantly by domestic livestock, a uv-attenuated cercarial vaccine for bovines may contribute to the control of this disease

  6. Envelope exchange for the generation of live-attenuated arenavirus vaccines.

    Directory of Open Access Journals (Sweden)

    Andreas Bergthaler

    2006-06-01

    Full Text Available Arenaviruses such as Lassa fever virus cause significant mortality in endemic areas and represent potential bioterrorist weapons. The occurrence of arenaviral hemorrhagic fevers is largely confined to Third World countries with a limited medical infrastructure, and therefore live-attenuated vaccines have long been sought as a method of choice for prevention. Yet their rational design and engineering have been thwarted by technical limitations. In addition, viral genes had not been identified that are needed to cause disease but can be deleted or substituted to generate live-attenuated vaccine strains. Lymphocytic choriomeningitis virus, the prototype arenavirus, induces cell-mediated immunity against Lassa fever virus, but its safety for humans is unclear and untested. Using this virus model, we have developed the necessary methodology to efficiently modify arenavirus genomes and have exploited these techniques to identify an arenaviral Achilles' heel suitable for targeting in vaccine design. Reverse genetic exchange of the viral glycoprotein for foreign glycoproteins created attenuated vaccine strains that remained viable although unable to cause disease in infected mice. This phenotype remained stable even after extensive propagation in immunodeficient hosts. Nevertheless, the engineered viruses induced T cell-mediated immunity protecting against overwhelming systemic infection and severe liver disease upon wild-type virus challenge. Protection was established within 3 to 7 d after immunization and lasted for approximately 300 d. The identification of an arenaviral Achilles' heel demonstrates that the reverse genetic engineering of live-attenuated arenavirus vaccines is feasible. Moreover, our findings offer lymphocytic choriomeningitis virus or other arenaviruses expressing foreign glycoproteins as promising live-attenuated arenavirus vaccine candidates.

  7. Envelope Exchange for the Generation of Live-Attenuated Arenavirus Vaccines.

    Directory of Open Access Journals (Sweden)

    2006-06-01

    Full Text Available Arenaviruses such as Lassa fever virus cause significant mortality in endemic areas and represent potential bioterrorist weapons. The occurrence of arenaviral hemorrhagic fevers is largely confined to Third World countries with a limited medical infrastructure, and therefore live-attenuated vaccines have long been sought as a method of choice for prevention. Yet their rational design and engineering have been thwarted by technical limitations. In addition, viral genes had not been identified that are needed to cause disease but can be deleted or substituted to generate live-attenuated vaccine strains. Lymphocytic choriomeningitis virus, the prototype arenavirus, induces cell-mediated immunity against Lassa fever virus, but its safety for humans is unclear and untested. Using this virus model, we have developed the necessary methodology to efficiently modify arenavirus genomes and have exploited these techniques to identify an arenaviral Achilles' heel suitable for targeting in vaccine design. Reverse genetic exchange of the viral glycoprotein for foreign glycoproteins created attenuated vaccine strains that remained viable although unable to cause disease in infected mice. This phenotype remained stable even after extensive propagation in immunodeficient hosts. Nevertheless, the engineered viruses induced T cell-mediated immunity protecting against overwhelming systemic infection and severe liver disease upon wild-type virus challenge. Protection was established within 3 to 7 d after immunization and lasted for approximately 300 d. The identification of an arenaviral Achilles' heel demonstrates that the reverse genetic engineering of live-attenuated arenavirus vaccines is feasible. Moreover, our findings offer lymphocytic choriomeningitis virus or other arenaviruses expressing foreign glycoproteins as promising live-attenuated arenavirus vaccine candidates.

  8. Immunogenicity and protective efficacy of a live attenuated H5N1 vaccine in nonhuman primates.

    Directory of Open Access Journals (Sweden)

    Shufang Fan

    2009-05-01

    Full Text Available The continued spread of highly pathogenic H5N1 influenza viruses among poultry and wild birds, together with the emergence of drug-resistant variants and the possibility of human-to-human transmission, has spurred attempts to develop an effective vaccine. Inactivated subvirion or whole-virion H5N1 vaccines have shown promising immunogenicity in clinical trials, but their ability to elicit protective immunity in unprimed human populations remains unknown. A cold-adapted, live attenuated vaccine with the hemagglutinin (HA and neuraminidase (NA genes of an H5N1 virus A/VN/1203/2004 (clade 1 was protective against the pulmonary replication of homologous and heterologous wild-type H5N1 viruses in mice and ferrets. In this study, we used reverse genetics to produce a cold-adapted, live attenuated H5N1 vaccine (AH/AAca that contains HA and NA genes from a recent H5N1 isolate, A/Anhui/2/05 virus (AH/05 (clade 2.3, and the backbone of the cold-adapted influenza H2N2 A/AnnArbor/6/60 virus (AAca. AH/AAca was attenuated in chickens, mice, and monkeys, and it induced robust neutralizing antibody responses as well as HA-specific CD4+ T cell immune responses in rhesus macaques immunized twice intranasally. Importantly, the vaccinated macaques were fully protected from challenge with either the homologous AH/05 virus or a heterologous H5N1 virus, A/bar-headed goose/Qinghai/3/05 (BHG/05; clade 2.2. These results demonstrate for the first time that a cold-adapted H5N1 vaccine can elicit protective immunity against highly pathogenic H5N1 virus infection in a nonhuman primate model and provide a compelling argument for further testing of double immunization with live attenuated H5N1 vaccines in human trials.

  9. Field Efficacy of an Attenuated Infectious Bronchitis Variant 2 Virus Vaccine in Commercial Broiler Chickens

    Directory of Open Access Journals (Sweden)

    Mohamed A. Elhady

    2018-05-01

    Full Text Available Egyptian poultry suffer from frequent respiratory disease outbreaks associated with Infectious Bronchitis Virus (IBV variant 2 strains (Egy/VarII. Different vaccination programs using imported vaccines have failed to protect the flocks from field challenge. Recent studies confirmed a successful protection using homologous strains as live attenuated vaccines. In this study, a newly developed live attenuated IB-VAR2 vaccine representing the GI-23 Middle East IBV lineage was evaluated in day-old commercial broilers in an IBV-endemic area. A commercial broiler flock was vaccinated with the IB-VAR2 vaccine at day-old age followed by IB-H120 at day 16. The vaccinated flock was monitored on a weekly basis till the slaughter age. The health status and growth performance were monitored, and selected viral pathogen real-time RT-PCR (rRT-PCR detection was conducted on a weekly basis. Finally, the flock was compared to a nearby farm with only the classical IB-H120 vaccination program. Results showed that the IB-VAR2 vaccine was tolerable in day-old broiler chicks. The IBV virus rRT-PCR detection was limited to the trachea as compared to its nephropathogenic parent virus. Respiratory disease problems and high mortalities were reported in the IB-H120-only vaccinated flock. An exposure to a wild-type Egy/VarII strain was confirmed in both flocks as indicated by partial IBV S1 gene sequence. Even though the IB-VAR2-vaccinated flock performance was better than the flock that received only IB-H120, the IBV ELISA (enzyme-linked immunosorbent assay and log2 Haemagglutination inhibition (HI antibody mean titers remained high (3128 ± 2713 and ≥9 log2, respectively until the 28th day of age. The current study demonstrates the safety and effectiveness of IB-VAR2 as a live attenuated vaccine in day-old commercial broilers. Also, the combination of IB-VAR2 and classical IBV vaccines confers a broader protective immune response against IBV in endemic areas.

  10. New Approaches to Attenuated Hepatitis a Vaccine Development: Cloning and Sequencing of Cell-Culture Adapted Viral cDNA.

    Science.gov (United States)

    1987-10-13

    after multiple passages in vivo and in vitro. J. Gen. Virol. 67, 1741- 1744. Sabin , A.B. (1985). Oral poliovirus vaccine : history of its development...IN (N NEW APPROACHES TO ATTENUATED HEPATITIS A VACCINE DEVELOPMENT: Q) CLONING AND SEQUENCING OF CELL-CULTURE ADAPTED VIRAL cDNA I ANNUAL REPORT...6ll02Bsl0 A 055 11. TITLE (Include Security Classification) New Approaches to Attenuated Hepatitis A Vaccine Development: Cloning and Sequencing of Cell

  11. CANINE DISTEMPER VIRUS ANTIBODY TITERS IN DOMESTIC CATS AFTER DELIVERY OF A LIVE ATTENUATED VIRUS VACCINE.

    Science.gov (United States)

    Ramsay, Edward; Sadler, Ryan; Rush, Robert; Seimon, Tracie; Tomaszewicz, Ania; Fleetwood, Ellen A; McAloose, Denise; Wilkes, Rebecca P

    2016-06-01

    Three methods for delivering a live attenuated canine distemper virus (CDV) vaccine to domestic cats ( Felis catus ) were investigated, as models for developing vaccination protocols for tigers (Panthera tigris). Twenty domestic cats were randomly divided into four treatment groups: saline injection (negative controls); and oral, intranasal, and subcutaneous vaccinates. Cats were injected with saline or a CDV vaccine (Nobivac DP, Merck) at wk 0 and 4. Blood and nasal swabs were collected at wk 0 (prior to the initial vaccination) and weekly thereafter for 9 wk. Urine samples were collected on wk 1 to 9 after initial vaccination. Forty-nine weeks following the initial vaccination series, three cats from the subcutaneous group and three cats from the intranasal group were revaccinated. Blood was collected immediately prior, and 7 and 21 days subsequent to revaccination. Nasal swabs and urine samples were collected from each cat prior to wk 49 revaccination and daily for 7 days thereafter. Nasal swabs and urine were analyzed by quantitative PCR for vaccine virus presence. Sera were tested for CDV antibodies by virus neutralization. All cats were sero-negative for CDV antibodies at the beginning of the study, and saline-injected cats remained sero-negative throughout the study. A dramatic anamnestic response was seen following wk 4 subcutaneous vaccinations, with titers peaking at wk 6 (geometric mean = 2,435.5). Following wk 49 revaccination, subcutaneous vaccinates again mounted impressive titers (wk 52 geometric mean = 2,048). Revaccination of the intranasal group cats at wk 49 produced a small increase in titers (wk 52 geometric mean = 203). CDV viral RNA was detected in six nasal swabs but no urine samples, demonstrating low viral shedding postvaccination. The strong antibody response to subcutaneous vaccination and the lack of adverse effects suggest this vaccine is safe and potentially protective against CDV infection in domestic cats.

  12. 78 FR 43219 - Prospective Grant of Exclusive License: Live Attenuated Dengue Tetravalent Vaccine Containing a...

    Science.gov (United States)

    2013-07-19

    ...) E-120-2001/0, Whitehead et al., ``Development of Mutations Useful for Attenuating Dengue Viruses and..., and (3) E-139-2006/0, Whitehead et al., ``Development of Dengue Vaccine Components'', Australian... August 15, 2007, Chinese Patent Application Number 200780031489.4, filed August 15, 2007, European Patent...

  13. Development of live attenuated sparfloxacin-resistant Streptococcus agalactiae polyvalent vaccines to protect Nile tilapia

    Science.gov (United States)

    To develop attenuated bacteria as potential live vaccines, sparfloxacin was used in this study to modify 40 isolates of Streptococcus agalactiae. Majority of S. agalactiae used in this study were able to develop at least 80-fold resistance to sparfloxacin. When the virulence of the sparfloxacin-resi...

  14. Suppression of immune-mediated liver injury after vaccination with attenuated pathogenic cells.

    Science.gov (United States)

    Mei, Yunhua; Wang, Ying; Xu, Lingyun

    2007-05-15

    Cell vaccination via immunization with attenuated pathogenic cells is an effective preventive method that has been successfully applied in several animal models of inflammatory or autoimmune diseases. Concanavalin A (Con A)-induced hepatitis (CIH) is a commonly used experimental model to study immune-mediated liver injury. Multiple cell types including T lymphocytes, macrophages and neutrophils have been found to be involved in the pathogenesis of CIH. In this study, we used attenuated spleen lymphocytes or peripheral blood lymphocytes as vaccines to investigate whether they could induce protective immune responses to prevent mice from developing CIH. We found that mice receiving such vaccination before CIH induction developed much milder diseases, exhibited a lower level of alanine aminotransferase (ALT) released into their plasma and had less inflammatory lesions in their livers. Such CIH-suppression is dose- and frequency-dependent. The suppressive effect was associated with inhibition of several major inflammatory mediators, pro-inflammatory cytokines and chemokines.

  15. A randomized study to evaluate the immunogenicity and safety of a heptavalent diphtheria, tetanus, pertussis, hepatitis B, poliomyelitis, haemophilus influenzae b, and meningococcal serogroup C combination vaccine administered to infants at 2, 4 and 12 months of age.

    Science.gov (United States)

    Thollot, Franck; Scheifele, David; Pankow-Culot, Heidemarie; Cheuvart, Brigitte; Leyssen, Maarten; Ulianov, Liliana; Miller, Jacqueline M

    2014-12-01

    The immunogenicity and safety of the investigational diphtheria, tetanus, acellular pertussis, hepatitis B, poliomyelitis, Haemophilus influenzae type b (Hib) and meningococcal serogroup C (MenC) heptavalent combination vaccine were compared with those of licensed control vaccines. In this open, phase II, randomized study (NCT01090453), 480 infants from Germany, France and Canada received the heptavalent vaccine (Hepta group) or hexavalent and monovalent MenC control vaccines (HexaMenC group) co-administered with a 13-valent pneumococcal conjugate vaccine at 2, 4 and 12 months of age. Immunogenicity was measured 1 month after the second primary dose, and before and 1 month after the booster dose. Safety and reactogenicity were also evaluated. Non-inferiority of immune responses to MenC and Hib induced by 2-dose primary vaccination with the heptavalent vaccine versus control vaccines was demonstrated. In exploratory analyses, postprimary and postbooster functional antibody geometric mean titers against MenC tended to be lower (1119.5 vs. 3200.5; 2653.8 vs. 6028.4) and antibody geometric mean concentrations against Hib higher (1.594 vs. 0.671 μg/mL; 17.678 vs. 13.737 μg/mL) in the Hepta versus the HexaMenC group. The heptavalent and control vaccines were immunogenic to all other antigens, although immune responses to poliovirus were lower than expected in both groups. No differences in safety and reactogenicity profiles were detected between groups. The heptavalent vaccine induced non-inferior MenC and Hib responses compared with control vaccines. Both vaccination regimens, when administered at 2, 4 and 12 months of age, had comparable safety profiles and were immunogenic to all antigens, with lower-than-expected responses to poliomyelitis.

  16. Updated recommendations for use of tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine in adults aged 65 years and older - Advisory Committee on Immunization Practices (ACIP), 2012.

    Science.gov (United States)

    2012-06-29

    Since 2005, the Advisory Committee on Immunization Practices (ACIP) has recommended a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine booster dose for all adolescents aged 11 through 18 years (preferred at 11 through 12 years) and for those adults aged 19 through 64 years who have not yet received a dose. In October 2010, despite the lack of an approved Tdap vaccine for adults aged 65 years and older, ACIP recommended that unvaccinated adults aged 65 years and older be vaccinated with Tdap if in close contact with an infant, and that other adults aged 65 years and older may receive Tdap. In July 2011, the Food and Drug Administration (FDA) approved expanding the age indication for Boostrix (GlaxoSmithKline Biologicals, Rixensart, Belgium) to aged 65 years and older. In February 2012, ACIP recommended Tdap for all adults aged 65 years and older. This recommendation supersedes previous Tdap recommendations regarding adults aged 65 years and older.

  17. Sex-differential effects on mortality of BCG and diphtheria-tetanus-pertussis vaccines in a rural area with high vaccination coverage

    DEFF Research Database (Denmark)

    Aaby, Peter; Nielsen, Jens; Benn, Christine S

    2016-01-01

    and inactivated polio vaccine (DTP-IPV) with BCG. Subsequent doses of DTP-IPV were administered alone. We analysed mortality according to sex and number of doses of DTP-IPV vaccine. RESULTS: BCG and DTP-IPV1 simultaneously reduced mortality from 60/1000 person-years in unvaccinated girls to 35/1000 person...

  18. Attenuation of the goose parvovirus strain B. Laboratory and field trials of the attenuated mutant for vaccination against Derzsy's disease.

    Science.gov (United States)

    Kisary, J; Derzsy, D; Meszaros, J

    1978-07-01

    Serial transfer of the goose parvovirus strain B, causal agent of Derzsy's gosling disease, in cultured goose-embryo fibroblast (GEF) resulted in a mutant (designated as Bav) apathogenic for both goose embryos and susceptible goslings. Goose embryos inoculated with the 38th or higher passages of strain B survived the infection, although the virus replicated in their organs. Susceptible goslings survived challenge with the Bav strain without showing symptoms, and developed normally. Only 4.2% of gosling progeny of parents vaccinated twice with strain Bav died after challenge with the virulent strain B goose parvovirus compared with 95% of gosling progeny of unvaccinated parents. Progeny of vaccinated and unvaccinated geese were placed on a farm on which Derzsy's disease was present. During the first month of life mortality was 7.7% in the progeny of vaccinated geese compared with 59.8% in the progeny of the unvaccinated geese. At 8 weeks of age the mean weight of the vaccinated goslings was 20% greater than for the unvaccinated goslings. These results indicate that the attenuated apathogenic Bav mutant is suitable for the immunisation of layers to protect their progeny by passive immunisation against Derzsy's disease.

  19. Preliminary development of a live attenuated canine parvovirus vaccine from an isolate of British origin.

    Science.gov (United States)

    Churchill, A E

    1987-04-04

    Canine parvovirus isolated from a case of haemorrhagic enteritis in a breeding kennel in England was passaged and cloned in cultured feline and canine cells. No significant evidence of pathogenicity was found during six serial passages of the modified virus back through young dogs. The attenuated virus was excreted by inoculated animals and spread rapidly to uninoculated animals held in contact. When high titre attenuated virus was given to the six-week-old offspring of a seropositive dam a prompt seroconversion was observed. When the attenuated virus was used as an experimental vaccine in 108 pups in an infected breeding colony a highly significant improvement was obtained in the accumulated morbidity and mortality compared with a parallel group vaccinated with modified live feline panleucopenia virus.

  20. Clinical development and regulatory points for consideration for second-generation live attenuated dengue vaccines.

    Science.gov (United States)

    Vannice, Kirsten S; Wilder-Smith, Annelies; Barrett, Alan D T; Carrijo, Kalinka; Cavaleri, Marco; de Silva, Aravinda; Durbin, Anna P; Endy, Tim; Harris, Eva; Innis, Bruce L; Katzelnick, Leah C; Smith, Peter G; Sun, Wellington; Thomas, Stephen J; Hombach, Joachim

    2018-03-07

    Licensing and decisions on public health use of a vaccine rely on a robust clinical development program that permits a risk-benefit assessment of the product in the target population. Studies undertaken early in clinical development, as well as well-designed pivotal trials, allow for this robust characterization. In 2012, WHO published guidelines on the quality, safety and efficacy of live attenuated dengue tetravalent vaccines. Subsequently, efficacy and longer-term follow-up data have become available from two Phase 3 trials of a dengue vaccine, conducted in parallel, and the vaccine was licensed in December 2015. The findings and interpretation of the results from these trials released both before and after licensure have highlighted key complexities for tetravalent dengue vaccines, including concerns vaccination could increase the incidence of dengue disease in certain subpopulations. This report summarizes clinical and regulatory points for consideration that may guide vaccine developers on some aspects of trial design and facilitate regulatory review to enable broader public health recommendations for second-generation dengue vaccines. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. A single-dose live-attenuated vaccine prevents Zika virus pregnancy transmission and testis damage.

    Science.gov (United States)

    Shan, Chao; Muruato, Antonio E; Jagger, Brett W; Richner, Justin; Nunes, Bruno T D; Medeiros, Daniele B A; Xie, Xuping; Nunes, Jannyce G C; Morabito, Kaitlyn M; Kong, Wing-Pui; Pierson, Theodore C; Barrett, Alan D; Weaver, Scott C; Rossi, Shannan L; Vasconcelos, Pedro F C; Graham, Barney S; Diamond, Michael S; Shi, Pei-Yong

    2017-09-22

    Zika virus infection during pregnancy can cause congenital abnormities or fetal demise. The persistence of Zika virus in the male reproductive system poses a risk of sexual transmission. Here we demonstrate that live-attenuated Zika virus vaccine candidates containing deletions in the 3' untranslated region of the Zika virus genome (ZIKV-3'UTR-LAV) prevent viral transmission during pregnancy and testis damage in mice, as well as infection of nonhuman primates. After a single-dose vaccination, pregnant mice challenged with Zika virus at embryonic day 6 and evaluated at embryonic day 13 show markedly diminished levels of viral RNA in maternal, placental, and fetal tissues. Vaccinated male mice challenged with Zika virus were protected against testis infection, injury, and oligospermia. A single immunization of rhesus macaques elicited a rapid and robust antibody response, conferring complete protection upon challenge. Furthermore, the ZIKV-3'UTR-LAV vaccine candidates have a desirable safety profile. These results suggest that further development of ZIKV-3'UTR-LAV is warranted for humans.Zika virus infection can result in congenital disorders and cause disease in adults, and there is currently no approved vaccine. Here Shan et al. show that a single dose of a live-attenuated Zika vaccine prevents infection, testis damage and transmission to the fetus during pregnancy in different animal models.

  2. Estimated incidence of pertussis in people aged <50 years in the United States

    Science.gov (United States)

    Chen, Chi-Chang; Balderston McGuiness, Catherine; Krishnarajah, Girishanthy; Blanchette, Christopher M.; Wang, Yuanyuan; Sun, Kainan; Buck, Philip O.

    2016-01-01

    ABSTRACT The introduction of pertussis vaccination in the United States (US) in the 1940s has greatly reduced its burden. However, the incidence of pertussis is difficult to quantify, as many cases are not laboratory-confirmed or reported, particularly in adults. This study estimated pertussis incidence in a commercially insured US population aged pertussis or cough illness using International Classification of Diseases (ICD-9) codes, a commercial outpatient laboratory database for patients with a pertussis laboratory test, and the Centers for Disease Control influenza surveillance database. US national pertussis incidence was projected using 3 methods: (1) diagnosed pertussis, defined as a claim for pertussis (ICD-9 033.0, 033.9, 484.3) during 2008–2013; (2) based on proxy pertussis predictive logistic regression models; (3) using the fraction of cough illness (ICD-9 033.0, 033.9, 484.3, 786.2, 466.0, 466.1, 487.1) attributed to laboratory-confirmed pertussis, estimated by time series linear regression models. Method 1 gave a projected annual incidence of diagnosed pertussis of 9/100,000, which was highest in those aged pertussis of 649/100,000, approximately 58–93 times higher than method 1 depending on the year. These estimations, which are consistent with considerable underreporting of pertussis in people aged pertussis burden. PMID:27246119

  3. Pertussis Diagnosis & Treatment

    Science.gov (United States)

    ... in Other Countries Latin American Pertussis Project Countries Argentina Brazil Chile Colombia Mexico Panama Surveillance & Epidemiology Materials ... been exposed to pertussis and by doing a: History of typical signs and symptoms Physical examination Laboratory ...

  4. Photos of Pertussis

    Science.gov (United States)

    ... Prophylaxis Pertussis in Other Countries Latin American Pertussis Project Countries Argentina Brazil Chile Colombia Mexico Panama Surveillance & ... PPT, MPEG) on this site? Adobe PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel file ...

  5. Pertussis Signs & Symptoms

    Science.gov (United States)

    ... Prophylaxis Pertussis in Other Countries Latin American Pertussis Project Countries Argentina Brazil Chile Colombia Mexico Panama Surveillance & ... PPT, MPEG) on this site? Adobe PDF file Microsoft PowerPoint file Microsoft Word file Microsoft Excel file ...

  6. Whooping Cough (Pertussis)

    Science.gov (United States)

    ... Staying Safe Videos for Educators Search English Español Whooping Cough (Pertussis) KidsHealth / For Parents / Whooping Cough (Pertussis) What's in this article? Signs & Symptoms Contagiousness ...

  7. Extended Preclinical Safety, Efficacy and Stability Testing of a Live-attenuated Chikungunya Vaccine Candidate.

    Directory of Open Access Journals (Sweden)

    Kenneth S Plante

    Full Text Available We recently described a new, live-attenuated vaccine candidate for chikungunya (CHIK fever, CHIKV/IRES. This vaccine was shown to be well attenuated, immunogenic and efficacious in protecting against CHIK virus (CHIKV challenge of mice and nonhuman primates. To further evaluate its preclinical safety, we compared CHIKV/IRES distribution and viral loads in interferon-α/β receptor-incompetent A129 mice to another CHIK vaccine candidate, 181/clone25, which proved highly immunogenic but mildly reactive in human Phase I/II clinical trials. Compared to wild-type CHIK virus, (wt-CHIKV, both vaccines generated lower viral loads in a wide variety of tissues and organs, including the brain and leg muscle, but CHIKV/IRES exhibited marked restrictions in dissemination and viral loads compared to 181/clone25, and was never found outside the blood, spleen and muscle. Unlike wt-CHIKV, which caused disrupted splenic architecture and hepatic lesions, histopathological lesions were not observed in animals infected with either vaccine strain. To examine the stability of attenuation, both vaccines were passaged 5 times intracranially in infant A129 mice, then assessed for changes in virulence by comparing parental and passaged viruses for footpad swelling, weight stability and survival after subcutaneous infection. Whereas strain 181/clone25 p5 underwent a significant increase in virulence as measured by weight loss (from 30% and mortality (from 0 to 100%, CHIKV/IRES underwent no detectible change in any measure of virulence (no significant weight loss and no mortality. These data indicate greater nonclinical safety of the CHIKV/IRES vaccine candidate compared to 181/clone25, further supporting its eligibility for human testing.

  8. Safety and immunogenicity of a live attenuated Japanese encephalitis chimeric virus vaccine (IMOJEV®) in children.

    Science.gov (United States)

    Chokephaibulkit, K; Houillon, G; Feroldi, E; Bouckenooghe, A

    2016-01-01

    JE-CV (IMOJEV®, Sanofi Pasteur, France) is a live attenuated virus vaccine constructed by inserting coding sequences of the prM and E structural proteins of the Japanese encephalitis SA14-14-2 virus into the genome of yellow fever 17D virus. Primary immunization with JE-CV requires a single dose of the vaccine. This article reviews clinical trials of JE-CV in children aged up to 6 years conducted in countries across South-East Asia. Strong and persistent antibody responses were observed after single primary and booster doses, with 97% of children seroprotected up to five years after booster vaccination. Models of long-term antibody persistence predict a median duration of protection of approximately 30 years after a booster dose. The safety and reactogenicity profiles of JE-CV primary and booster doses are comparable to other widely used childhood vaccines.

  9. Bordetella pertussis transmission

    Science.gov (United States)

    Bordetella pertussis and Bordetella bronchiseptica are Gram negative bacterial respiratory pathogens. B. pertussis is the causative agent of whooping cough and is considered a human-adapted variant of B. bronchiseptica. B. pertussis and B. bronchiseptica share mechanisms of pathogenesis and are gene...

  10. Low Dose Vaccination with Attenuated Francisella tularensis Strain SchuS4 Mutants Protects against Tularemia Independent of the Route of Vaccination

    Science.gov (United States)

    Rockx-Brouwer, Dedeke; Chong, Audrey; Wehrly, Tara D.; Child, Robert; Crane, Deborah D.

    2012-01-01

    Tularemia, caused by the Gram-negative bacterium Francisella tularensis, is a severe, sometimes fatal disease. Interest in tularemia has increased over the last decade due to its history as a biological weapon. In particular, development of novel vaccines directed at protecting against pneumonic tularemia has been an important goal. Previous work has demonstrated that, when delivered at very high inoculums, administration of live, highly attenuated strains of virulent F. tularensis can protect against tularemia. However, lower vaccinating inoculums did not offer similar immunity. One concern of using live vaccines is that the host may develop mild tularemia in response to infection and use of high inoculums may contribute to this issue. Thus, generation of a live vaccine that can efficiently protect against tularemia when delivered in low numbers, e.g. tularemia when delivered at concentrations of approximately 50 or fewer bacteria. Attenuated strains for use as vaccines were selected by their inability to efficiently replicate in macrophages in vitro and impaired replication and dissemination in vivo. Although all strains were defective for replication in vitro within macrophages, protective efficacy of each attenuated mutant was correlated with their ability to modestly replicate and disseminate in the host. Finally, we demonstrate the parenteral vaccination with these strains offered superior protection against pneumonic tularemia than intranasal vaccination. Together our data provides proof of principle that low dose attenuated vaccines may be a viable goal in development of novel vaccines directed against tularemia. PMID:22662210

  11. Genotyping assay for differentiation of wild-type and vaccine viruses in subjects immunized with live attenuated influenza vaccine.

    Directory of Open Access Journals (Sweden)

    Victoria Matyushenko

    Full Text Available Live attenuated influenza vaccines (LAIVs are considered as safe and effective tool to control influenza in different age groups, especially in young children. An important part of the LAIV safety evaluation is the detection of vaccine virus replication in the nasopharynx of the vaccinees, with special attention to a potential virus transmission to the unvaccinated close contacts. Conducting LAIV clinical trials in some geographical regions with year-round circulation of influenza viruses warrants the development of robust and reliable tools for differentiating vaccine viruses from wild-type influenza viruses in nasal pharyngeal wash (NPW specimens of vaccinated subjects. Here we report the development of genotyping assay for the detection of wild-type and vaccine-type influenza virus genes in NPW specimens of young children immunized with Russian-backbone seasonal trivalent LAIV using Sanger sequencing from newly designed universal primers. The new primer set allowed amplification and sequencing of short fragments of viral genes in NPW specimens and appeared to be more sensitive than conventional real-time RT-PCR protocols routinely used for the detection and typing/subtyping of influenza virus in humans. Furthermore, the new assay is capable of defining the origin of wild-type influenza virus through BLAST search with the generated sequences of viral genes fragments.

  12. Safety and immunogenicity of a live attenuated mumps vaccine: a phase I clinical trial.

    Science.gov (United States)

    Liang, Yan; Ma, Jingchen; Li, Changgui; Chen, Yuguo; Liu, Longding; Liao, Yun; Zhang, Ying; Jiang, Li; Wang, Xuan-Yi; Che, Yanchun; Deng, Wei; Li, Hong; Cui, Xiaoyu; Ma, Na; Ding, Dong; Xie, Zhongping; Cui, Pingfang; Ji, Qiuyan; Wang, JingJing; Zhao, Yuliang; Wang, Junzhi; Li, Qihan

    2014-01-01

    Mumps, a communicable, acute and previously well-controlled disease, has had recent and occasional resurgences in some areas. A randomized, double-blind, controlled and multistep phase I study of an F-genotype attenuated mumps vaccine produced in human diploid cells was conducted. A total of 300 subjects were enrolled and divided into 4 age groups: 16-60 years, 5-16 years, 2-5 years and 8-24 months. The groups were immunized with one injection per subject. Three different doses of the F-genotype attenuated mumps vaccine, A (3.5 ± 0.25 logCCID50), B (4.25 ± 0.25 logCCID50) and C (5.0 ± 0.25 logCCID50), as well as a placebo control and a positive control of a licensed A-genotype vaccine (S79 strain) were used. The safety and immunogenicity of this vaccine were compared with those of the controls. The safety evaluation suggested that mild adverse reactions were observed in all groups. No serious adverse event (SAE) was reported throughout the trial. The immunogenicity test showed a similar seroconversion rate of the neutralizing and ELISA antibody in the 2- to 5-year-old and 8- to 24-month-old groups compared with the seroconversion rate in the positive control. The GMT of the neutralizing anti-F-genotype virus antibodies in the vaccine groups was slightly higher than that in the positive control group. The F-genotype attenuated mumps vaccine evaluated in this clinical trial was demonstrated to be safe and have effective immunogenicity vs. control.

  13. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... thimerosal vaccine safety q & a videos chickenpox (varicella) hepatitis b hib hpv pertussis (whooping cough) pneumococcal rotavirus shingles media room Flu's Gonna Lose M.O.V.E. newsfeeds PSAs publications infectious disease workshop pediatric hepatitis report someone you know has hbv/hcv standard ...

  14. Recognizing and Preventing Whooping Cough 2 (Pertussis)

    Centers for Disease Control (CDC) Podcasts

    2010-09-16

    This podcast encourages everyone to get vaccinated against whooping cough (pertussis), especially those who will have close contact with an infant.  Created: 9/16/2010 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 9/16/2010.

  15. Enhancement of the safety of live influenza vaccine by attenuating mutations from cold-adapted hemagglutinin

    International Nuclear Information System (INIS)

    Lee, Yoon Jae; Jang, Yo Han; Kim, Paul; Lee, Yun Ha; Lee, Young Jae; Byun, Young Ho; Lee, Kwang-Hee; Kim, Kyusik; Seong, Baik Lin

    2016-01-01

    In our previous study, X-31ca-based H5N1 LAIVs, in particular, became more virulent in mice than the X-31ca MDV, possibly by the introduction of the surface antigens of highly pathogenic H5N1 influenza virus, implying that additional attenuation is needed in this cases to increase the safety level of the vaccine. In this report we suggest an approach to further increase the safety of LAIV through additional cold-adapted mutations in the hemagglutinin. The cold-adaptation of X-31 virus resulted in four amino acid mutations in the HA. We generated a panel of 7:1 reassortant viruses each carrying the hemagglutinins with individual single amino acid mutations. We examined their phenotypes and found a major attenuating mutation, N81K. This attenuation marker conferred additional temperature-sensitive and attenuation phenotype to the LAIV. Our data indicate that the cold-adapted mutation in the HA confers additional attenuation to the LAIV strain, without compromising its productivity and immune response. - Highlights: • Cold-adaptation process induced four amino acid mutations in the HA of X-31 virus. • The four mutations in the HA also contributed to attenuation of the X-31ca virus • N81K mutation was the most significant marker for the attenuation of X-31ca virus. • Introduction of N81K mutation into H3N2 LAIV further attenuated the vaccine. • This approach provides a useful guideline for enhancing the safety of the LAIVs.

  16. Enhancement of the safety of live influenza vaccine by attenuating mutations from cold-adapted hemagglutinin

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Yoon Jae [Graduate Program in Biomaterials Science and Engineering, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of); Jang, Yo Han [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Kim, Paul; Lee, Yun Ha; Lee, Young Jae [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of); Byun, Young Ho; Lee, Kwang-Hee; Kim, Kyusik [Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Seong, Baik Lin, E-mail: blseong@yonsei.ac.kr [Graduate Program in Biomaterials Science and Engineering, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Laboratory of Molecular Medicine, Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul (Korea, Republic of); Vaccine Translational Research Center, Yonsei University, Seoul (Korea, Republic of)

    2016-04-15

    In our previous study, X-31ca-based H5N1 LAIVs, in particular, became more virulent in mice than the X-31ca MDV, possibly by the introduction of the surface antigens of highly pathogenic H5N1 influenza virus, implying that additional attenuation is needed in this cases to increase the safety level of the vaccine. In this report we suggest an approach to further increase the safety of LAIV through additional cold-adapted mutations in the hemagglutinin. The cold-adaptation of X-31 virus resulted in four amino acid mutations in the HA. We generated a panel of 7:1 reassortant viruses each carrying the hemagglutinins with individual single amino acid mutations. We examined their phenotypes and found a major attenuating mutation, N81K. This attenuation marker conferred additional temperature-sensitive and attenuation phenotype to the LAIV. Our data indicate that the cold-adapted mutation in the HA confers additional attenuation to the LAIV strain, without compromising its productivity and immune response. - Highlights: • Cold-adaptation process induced four amino acid mutations in the HA of X-31 virus. • The four mutations in the HA also contributed to attenuation of the X-31ca virus • N81K mutation was the most significant marker for the attenuation of X-31ca virus. • Introduction of N81K mutation into H3N2 LAIV further attenuated the vaccine. • This approach provides a useful guideline for enhancing the safety of the LAIVs.

  17. Vaccination against Canine Distemper Virus Infection in Infant Ferrets with and without Maternal Antibody Protection, Using Recombinant Attenuated Poxvirus Vaccines

    Science.gov (United States)

    Welter, Janet; Taylor, Jill; Tartaglia, James; Paoletti, Enzo; Stephensen, Charles B.

    2000-01-01

    Canine distemper virus (CDV) infection of ferrets is clinically and immunologically similar to measles, making this a useful model for the human disease. The model was used to determine if parenteral or mucosal immunization of infant ferrets at 3 and 6 weeks of age with attenuated vaccinia virus (NYVAC) or canarypox virus (ALVAC) vaccine strains expressing the CDV hemagglutinin (H) and fusion (F) protein genes (NYVAC-HF and ALVAC-HF) would induce serum neutralizing antibody and protect against challenge infection at 12 weeks of age. Ferrets without maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 5) or ALVAC-HF (n = 4) developed significant neutralizing titers (log10 inverse mean titer ± standard deviation of 2.30 ± 0.12 and 2.20 ± 0.34, respectively) by the day of challenge, and all survived with no clinical or virologic evidence of infection. Ferrets without maternal antibody that were vaccinated intranasally (i.n.) developed lower neutralizing titers, with NYVAC-HF producing higher titers at challenge (1.11 ± 0.57 versus 0.40 ± 0.37, P = 0.02) and a better survival rate (6/7 versus 0/5, P = 0.008) than ALVAC-HF. Ferrets with maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 7) and ALVAC-HF (n = 7) developed significantly higher antibody titers (1.64 ± 0.54 and 1.28 ± 0.40, respectively) than did ferrets immunized with an attenuated CDV vaccine (0.46 ± 0.59; n = 7) or the recombinant vectors expressing rabies glycoprotein (RG) (0.19 ± 0.32; n = 8, P = 7 × 10−6). The NYVAC vaccine also protected against weight loss, and both the NYVAC and attenuated CDV vaccines protected against the development of some clinical signs of infection, although survival in each of the three vaccine groups was low (one of seven) and not significantly different from the RG controls (none of eight). Combined i.n.-parenteral immunization of ferrets with maternal antibody using NYVAC-HF (n = 9) produced higher titers (1.63 ± 0

  18. Vaccination against canine distemper virus infection in infant ferrets with and without maternal antibody protection, using recombinant attenuated poxvirus vaccines.

    Science.gov (United States)

    Welter, J; Taylor, J; Tartaglia, J; Paoletti, E; Stephensen, C B

    2000-07-01

    Canine distemper virus (CDV) infection of ferrets is clinically and immunologically similar to measles, making this a useful model for the human disease. The model was used to determine if parenteral or mucosal immunization of infant ferrets at 3 and 6 weeks of age with attenuated vaccinia virus (NYVAC) or canarypox virus (ALVAC) vaccine strains expressing the CDV hemagglutinin (H) and fusion (F) protein genes (NYVAC-HF and ALVAC-HF) would induce serum neutralizing antibody and protect against challenge infection at 12 weeks of age. Ferrets without maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 5) or ALVAC-HF (n = 4) developed significant neutralizing titers (log(10) inverse mean titer +/- standard deviation of 2.30 +/- 0.12 and 2.20 +/- 0.34, respectively) by the day of challenge, and all survived with no clinical or virologic evidence of infection. Ferrets without maternal antibody that were vaccinated intranasally (i.n.) developed lower neutralizing titers, with NYVAC-HF producing higher titers at challenge (1.11 +/- 0.57 versus 0.40 +/- 0.37, P = 0.02) and a better survival rate (6/7 versus 0/5, P = 0.008) than ALVAC-HF. Ferrets with maternal antibody that were vaccinated parenterally with NYVAC-HF (n = 7) and ALVAC-HF (n = 7) developed significantly higher antibody titers (1.64 +/- 0. 54 and 1.28 +/- 0.40, respectively) than did ferrets immunized with an attenuated CDV vaccine (0.46 +/- 0.59; n = 7) or the recombinant vectors expressing rabies glycoprotein (RG) (0.19 +/- 0.32; n = 8, P = 7 x 10(-6)). The NYVAC vaccine also protected against weight loss, and both the NYVAC and attenuated CDV vaccines protected against the development of some clinical signs of infection, although survival in each of the three vaccine groups was low (one of seven) and not significantly different from the RG controls (none of eight). Combined i.n.-parenteral immunization of ferrets with maternal antibody using NYVAC-HF (n = 9) produced higher titers (1

  19. Stability of live attenuated rotavirus vaccine with selected preservatives and primary containers.

    Science.gov (United States)

    Lal, Manjari; Jarrahian, Courtney; Zhu, Changcheng; Hosken, Nancy A; McClurkan, Chris L; Koelle, David M; Saxon, Eugene; Roehrig, Andrew; Zehrung, Darin; Chen, Dexiang

    2016-05-11

    Rotavirus infection, which can be prevented by vaccination, is responsible for a high burden of acute gastroenteritis disease in children, especially in low-income countries. An appropriate formulation, packaging, and delivery device for oral rotavirus vaccine has the potential to reduce the manufacturing cost of the vaccine and the logistical impact associated with introduction of a new vaccine, simplify the vaccination procedure, and ensure that the vaccine is safely and accurately delivered to children. Single-dose prefilled presentations can be easy to use; however, they are typically more expensive, can be a bottleneck during production, and occupy a greater volume per dose vis-à-vis supply chain storage and medical waste disposal, which is a challenge in low-resource settings. Multi-dose presentations used thus far have other issues, including increased wastage of vaccine and the need for separate delivery devices. In this study, the goals were to evaluate both the technical feasibility of using preservatives to develop a liquid multi-dose formulation and the primary packaging alternatives for orally delivered, liquid rotavirus vaccines. The feasibility evaluation included evaluation of commonly used preservatives for compatibility with rotavirus vaccines and stability testing of rotavirus vaccine in various primary containers, including Lameplast's plastic tubes, BD's oral dispenser version of Uniject™ (Uniject DP), rommelag's blow-fill-seal containers, and MEDInstill's multi-dose vial and pouch. These presentations were compared to a standard glass vial. The results showed that none of the preservatives tested were compatible with a live attenuated rotavirus vaccine because they had a detrimental effect on the viability of the virus. In the presence of preservatives, vaccine virus titers declined to undetectable levels within 1 month. The vaccine formulation without preservatives maintained a stability profile over 12 months in all primary containers

  20. [Whooping cough in an urban high school in Hungary. Conclusions of a local pertussis outbreak].

    Science.gov (United States)

    Schneider, Ferenc; Stánitz, Eva; Kalácska, Judit; Tompity, Tünde; Gábor, Beáta

    2009-08-16

    Although incidence of pertussis has been gradually decreased with the introduction of active immunization, total eradication is not possible. This has been shown by national and international data, as well. In the early 2000's, slow increase in incidence of pertussis was observed. To demonstrate the presence of Bordetella pertussis in the Hungarian population by presenting 17 cases of adolescent pertussis. Etiology of pertussis was confirmed by quantification of pertussis-antibodies in blood samples taken from permanently coughing patients in the firstly identified subject's vicinity which latter was explored by retrospective data collection. In the vicinity of the first identified patient epidemiologic research identified another 16 patients all of which were confirmed by serological tests. If permanent coughing is present, pertussis needs to be ruled out. Immunity against pertussis obtained by vaccination fades by the end of childhood. Bordetella pertussis circulates in the national population. A booster-vaccination against pertussis in the regular vaccination course for the 11-year old children is recommended. Pertussis in adolescents and in adults is mild and atypical, but in case of prolonged coughing it needs to be considered.

  1. Comparison of immune persistence among inactivated and live attenuated hepatitis a vaccines 2 years after a single dose

    Science.gov (United States)

    Zhang, Xiaoshu; An, Jing; Tu, Aixia; Liang, Xuefeng; Cui, Fuqiang; Zheng, Hui; Tang, Yu; Liu, Jianfeng; Wang, Xuxia; Zhang, Ningjing; Li, Hui

    2016-01-01

    ABSTRACT Objective: Compare immune persistence from one dose of each of 3 different hepatitis A vaccines when given to school-age children: a domestic, live attenuated hepatitis A vaccine (H2 vaccine); a domestic inactivated hepatitis A vaccine (Healive®); and an imported, inactivated hepatitis A vaccine (Havrix®),.Methods: School-age children were randomized into 1 of 4 groups to receive a single dose of a vaccine: H2 vaccine, Healive®, Havrix®, or hepatitis B vaccine [control]. Serum samples were collected 12 and 24 months after vaccination for measurement of anti-HAV IgG using microparticle enzyme immunoassay. Seropositivity was defined as ≥ 20 mUI/ml. We compared groups on seropositivity and geometric mean concentration (GMC). Results: Seropositive rates for the H2, Healive®, Havrix®, and control groups were 64%, 94.4%, 73%, and 1.0%, respectively, 12-months post-vaccination; and 63%, 95.6%, 72%, and 1.0%, respectively 24-months post-vaccination. Seropositivity was greater for Healive® than for H2 and Havrix® at 12 months (p-values a single dose of inactivated hepatitis A vaccine and live attenuated hepatitis A vaccine. PMID:27494260

  2. Production and efficacy of an attenuated live vaccine against contagious ovine ecthyma

    Directory of Open Access Journals (Sweden)

    Attilio Pini

    2008-09-01

    Full Text Available Contagious ecthyma is caused by the orf virus, a member of the family Poxviridae, genus Parapoxvirus. Morbidity in affected sheep flocks is approximately 100%, while mortality varies between 1% and 10%. A live attenuated vaccine was produced by the Istituto Zooprofilattico Sperimentale dell’Abruzzo e del Molise ‘G. Caporale’. Quality control was performed in accordance with the European Pharmacopoeia. A wild virus strain was attenuated through serial passages on primary chicken embryo fibroblast tissue cultures. The virus suspension was treated according to standard procedures and freeze dried. The immunising dose was 1 ml containing 104,5TCID50, administered intramuscularly. The safety of the vaccine was successfully tested by intramuscular inoculation of 20 susceptible sheep and 20 lambs with the routine dose, 10 times the immunising dose and two normal doses administered at seven-day intervals. The efficacy of the vaccine was tested using three groups of susceptible animals. The first group included 10 lambs and the second 10 adult sheep; the animals were immunised intramuscularly with 1 ml of the reconstituted vaccine. The third group, used as controls, included five sheep and five lambs. Serological reactivity was monitored by indirect enzyme-linked immunosorbent assay (ELISA. The animals were challenged 30 days later with a pathogenic strain administered intradermally along the labial area. Vaccinated animals did not show any clinical signs of disease, whereas all the controls developed typical signs of contagious ecthyma. To confirm the efficacy of the vaccine, a field trial was conducted in four flocks affected by the disease. The trial showed that the vaccine was able to block the normal course of the disease and induce rapid recovery.

  3. Live Attenuated Versus Inactivated Influenza Vaccine in Hutterite Children: A Cluster Randomized Blinded Trial.

    Science.gov (United States)

    Loeb, Mark; Russell, Margaret L; Manning, Vanessa; Fonseca, Kevin; Earn, David J D; Horsman, Gregory; Chokani, Khami; Vooght, Mark; Babiuk, Lorne; Schwartz, Lisa; Neupane, Binod; Singh, Pardeep; Walter, Stephen D; Pullenayegum, Eleanor

    2016-11-01

    Whether vaccinating children with intranasal live attenuated influenza vaccine (LAIV) is more effective than inactivated influenza vaccine (IIV) in providing both direct protection in vaccinated persons and herd protection in unvaccinated persons is uncertain. Hutterite colonies, where members live in close-knit, small rural communities in which influenza virus infection regularly occurs, offer an opportunity to address this question. To determine whether vaccinating children and adolescents with LAIV provides better community protection than IIV. A cluster randomized blinded trial conducted between October 2012 and May 2015 over 3 influenza seasons. (ClinicalTrials.gov: NCT01653015). 52 Hutterite colonies in Alberta and Saskatchewan, Canada. 1186 Canadian children and adolescents aged 36 months to 15 years who received the study vaccine and 3425 community members who did not. Children were randomly assigned according to community in a blinded manner to receive standard dosing of either trivalent LAIV or trivalent IIV. The primary outcome was reverse transcriptase polymerase chain reaction-confirmed influenza A or B virus in all participants (vaccinated children and persons who did not receive the study vaccine). Mean vaccine coverage among children in the LAIV group was 76.9% versus 72.3% in the IIV group. Influenza virus infection occurred at a rate of 5.3% (295 of 5560 person-years) in the LAIV group versus 5.2% (304 of 5810 person-years) in the IIV group. The hazard ratio comparing LAIV with IIV for influenza A or B virus was 1.03 (95% CI, 0.85 to 1.24). The study was conducted in Hutterite communities, which may limit generalizability. Immunizing children with LAIV does not provide better community protection against influenza than IIV. The Canadian Institutes for Health Research.

  4. Biomarkers of safety and immune protection for genetically modified live attenuated Leishmania vaccines against visceral leishmaniasis-Discovery and implications

    Directory of Open Access Journals (Sweden)

    Sreenivas eGannavaram

    2014-05-01

    Full Text Available Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, sub-unit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in L. donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen1-/- in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated

  5. Complete Genome Sequence of the Goatpox Virus Strain Gorgan Obtained Directly from a Commercial Live Attenuated Vaccine

    Science.gov (United States)

    Mathijs, Elisabeth; Vandenbussche, Frank; Haegeman, Andy; Al-Majali, Ahmad; De Clercq, Kris

    2016-01-01

    This is a report of the complete genome sequence of the goatpox virus strain Gorgan, which was obtained directly from a commercial live attenuated vaccine (Caprivac, Jordan Bio-Industries Centre). PMID:27738031

  6. Early diphtheria-tetanus-pertussis vaccination associated with higher female mortality and no difference in male mortality in a cohort of low birthweight children: an observational study within a randomised trial.

    Science.gov (United States)

    Aaby, Peter; Ravn, Henrik; Roth, Adam; Rodrigues, Amabelia; Lisse, Ida Maria; Diness, Birgitte Rode; Lausch, Karen Rokkedal; Lund, Najaaraq; Rasmussen, Julie; Biering-Sørensen, Sofie; Whittle, Hilton; Benn, Christine Stabell

    2012-08-01

    Studies from low-income countries have suggested that diphtheria-tetanus-pertussis (DTP) vaccine provided after Bacille Calmette-Guerin (BCG) vaccination may have a negative effect on female survival. The authors examined the effect of DTP in a cohort of low birthweight (LBW) infants. 2320 LBW newborns were visited at 2, 6 and 12 months of age to assess nutritional and vaccination status. The authors examined survival until the 6-month visit for children who were DTP vaccinated and DTP unvaccinated at the 2-month visit. Two-thirds of the children had received DTP at 2 months and 50 deaths occurred between the 2-month and 6-month visits. DTP vaccinated children had a better anthropometric status for all indices than DTP unvaccinated children. Small mid-upper arm circumference (MUAC) was the strongest predictor of mortality. The death rate ratio (DRR) for DTP vaccinated versus DTP unvaccinated children differed significantly for girls (DRR 2.45; 95% CI 0.93 to 6.45) and boys (DRR 0.53; 95% CI 0.23 to 1.20) (p=0.018, homogeneity test). Adjusting for MUAC, the overall effect for DTP vaccinated children was 2.62 (95% CI 1.34 to 5.09); DRR was 5.68 (95% CI 1.83 to 17.7) for girls and 1.29 (95% CI 0.56 to 2.97) for boys (p=0.023, homogeneity test). While anthropometric indices were a strong predictor of mortality among boys, there was little or no association for girls. Surprisingly, even though the children with the best nutritional status were vaccinated early, early DTP vaccination was associated with increased mortality for girls.

  7. Attenuation of CCl4-induced hepatic fibrosis in mice by vaccinating against TGF-β1.

    Directory of Open Access Journals (Sweden)

    Xiaobao Fan

    Full Text Available Transforming growth factor β1 (TGF-β1 is the pivotal pro-fibrogenic cytokine in hepatic fibrosis. Reducing the over-produced expression of TGF-β1 or blocking its signaling pathways is considered to be a promising therapeutic strategy for hepatic fibrosis. In this study, we evaluated the feasibility of attenuating hepatic fibrosis by vaccination against TGF-β1 with TGF-β1 kinoids. Two TGF-β1 kinoid vaccines were prepared by cross-linking TGF-β1-derived polypeptides (TGF-β1(25-[41-65] and TGF-β1(30-[83-112] to keyhole limpet hemocyanin (KLH. Immunization with the two TGF-β1 kinoids efficiently elicited the production of high-levels of TGF-β1-specific antibodies against in BALB/c mice as tested by enzyme-linked immunosorbent assay (ELISA and Western blotting. The antisera neutralized TGF-β1-induced growth-inhibition on mink lung epithelial cells (Mv1Lu and attenuated TGF-β1-induced Smad2/3 phosphorylation, α-SMA, collagen type 1 alpha 2 (COL1A2, plasminogen activator inhibitor-1 (PAI-1 and tissue inhibitor of metalloproteinase-1 (TIMP-1 expression in the rat hepatic stellate cell (HSC line, HSC-T6. Vaccination against TGF-β1 with the kinoids significantly suppressed CCl4-induced collagen deposition and the expression of α-SMA and desmin, attenuated hepatocyte apoptosis and accelerated hepatocyte proliferation in BALB/c mice. These results demonstrated that immunization with the TGF-β1 kinoids efficiently attenuated CCl4-induced hepatic fibrosis and liver injury. Our study suggests that vaccination against TGF-β1 might be developed into a feasible therapeutic approach for the treatment of chronic fibrotic liver diseases.

  8. Live Zika virus chimeric vaccine candidate based on a yellow fever 17-D attenuated backbone

    OpenAIRE

    Nougairede, Antoine; Klitting, Raphaelle; Aubry, Fabien; Gilles, Magali; Touret, Franck; De Lamballerie, Xavier

    2018-01-01

    Zika virus (ZIKV) recently dispersed throughout the tropics and sub-tropics causing epidemics associated with congenital disease and neurological complications. There is currently no commercial vaccine for ZIKV. Here we describe the initial development of a chimeric virus containing the prM/E proteins of a ZIKV epidemic strain incorporated into a yellow fever 17-D attenuated backbone. Using the versatile and rapid ISA (Infectious Subgenomic Amplicons) reverse genetics method, we compared diff...

  9. Estimated exposures to perfluorinated compounds in infancy predict attenuated vaccine antibody concentrations at age 5-years

    DEFF Research Database (Denmark)

    Grandjean, Philippe; Heilmann, Carsten; Weihe, Pal

    2017-01-01

    Perfluorinated alkylate substances (PFASs) are highly persistent and may cause immunotoxic effects. PFAS-associated attenuated antibody responses to childhood vaccines may be affected by PFAS exposures during infancy, where breastfeeding adds to PFAS exposures. Of 490 members of a Faroese birth...... the notion that the developing adaptive immune system is particularly vulnerable to immunotoxicity during infancy. This vulnerability appears to be the greatest during the first 6 months after birth, where PFAS exposures are affected by breast-feeding....

  10. Non-specific Effect of Vaccines: Immediate Protection against Respiratory Syncytial Virus Infection by a Live Attenuated Influenza Vaccine

    Directory of Open Access Journals (Sweden)

    Young J. Lee

    2018-01-01

    Full Text Available The non-specific effects (NSEs of vaccines have been discussed for their potential long-term beneficial effects beyond direct protection against a specific pathogen. Cold-adapted, live attenuated influenza vaccine (CAIV induces local innate immune responses that provide a broad range of antiviral immunity. Herein, we examined whether X-31ca, a donor virus for CAIVs, provides non-specific cross-protection against respiratory syncytial virus (RSV. The degree of RSV replication was significantly reduced when X-31ca was administered before RSV infection without any RSV-specific antibody responses. The vaccination induced an immediate release of cytokines and infiltration of leukocytes into the respiratory tract, moderating the immune perturbation caused by RSV infection. The potency of protection against RSV challenge was significantly reduced in TLR3-/- TLR7-/- mice, confirming that the TLR3/7 signaling pathways are necessary for the observed immediate and short-term protection. The results suggest that CAIVs provide short-term, non-specific protection against genetically unrelated respiratory pathogens. The additional benefits of CAIVs in mitigating acute respiratory infections for which vaccines are not yet available need to be assessed in future studies.

  11. Performance of high titre attenuated canine parvovirus vaccine in pups with maternally derived antibody.

    Science.gov (United States)

    Burtonboy, S; Charlier, P; Hertoghs, J; Lobmann, M; Wiseman, A; Woods, S

    1991-04-20

    The performance of live, attenuated, homologous, canine parvovirus vaccines was studied in 140 puppies aged from four to 11 weeks. In the presence of maternally derived antibody the ability of the vaccines to elicit a serological response, as determined by the haemagglutination inhibition test and a standardised ELISA, was found to be dose (infectious titre) related. An experimental vaccine containing 10(7.0) TCID50 of virus induced seroconversion rates of 95, 89, 82 and 44 per cent in dogs with haemagglutination inhibition antibody titres of less than or equal to 8, 16, 32 and greater than 32, respectively. The standardised ELISA appeared to be better than the haemagglutination inhibition test with respect to variability and subjectivity, especially when titres were low.

  12. Rational development of an attenuated recombinant cyprinid herpesvirus 3 vaccine using prokaryotic mutagenesis and in vivo bioluminescent imaging

    Science.gov (United States)

    Cyprinid herpesvirus 3 (CyHV-3) is causing severe economic losses worldwide in the carp industry, and a safe and efficacious attenuated vaccine compatible with mass vaccination is needed. We produced single deleted recombinants using prokaryotic mutagenesis. When producing a recombinant lacking open...

  13. Dismantling the Taboo against Vaccines in Pregnancy

    Directory of Open Access Journals (Sweden)

    Maurizio de Martino

    2016-06-01

    Full Text Available Vaccinating pregnant women in order to protect them, the fetus, and the child has become universal in no way at all. Prejudice in health professionals add to fears of women and their families. Both these feelings are not supported by even the smallest scientific data. Harmlessness for the mother and the child has been observed for seasonal, pandemic, or quadrivalent influenza, mono, combined polysaccharide or conjugated meningococcal or pneumococcal, tetanus toxoid, acellular pertussis, human papillomavirus, cholera, hepatitis A, Japanese encephalitis, rabies, anthrax, smallpox, yellow fever, mumps, measles and rubella combined, typhoid fever, inactivated or attenuated polio vaccines, and Bacillus Calmétte Guerin vaccines. Instead, the beneficial effects of influenza vaccine for the mother and the child as well as of pertussis vaccine for the child have been demonstrated. Obstetrician-gynecologists, general practitioners, and midwives must incorporate vaccination into their standard clinical care. Strong communication strategies effective at reducing parental vaccine hesitancy and approval of regulatory agencies for use of vaccines during pregnancy are needed. It must be clear that the lack of pre-licensure studies in pregnant women and, consequently, the lack of a statement about the use of the vaccine in pregnant women does not preclude its use in pregnancy.

  14. Anaplasma marginale attenuated by irradiation, its potential use as vaccine

    International Nuclear Information System (INIS)

    Gil, A.; Pupiales, N.; Castro, J.; Higuera, B.; Orrego, J.

    1986-01-01

    Five groups of 5 calves each were inoculated: group 1 (control) with 5 x 10 8 non-irradiated parasites (day 0) and group 2 with the same dose of irradiated (900 Gy) parasites on day 0. Both groups showed clinical signs of the infection, although group 2 was less severely affected. On day 41 group 3 was inoculated with blood (1 x 10 9 parasites) from an animal in group 2. These parasites were irradiated again (900 Gy) prior to inoculation. On day 59 group 4 was inoculated with blood (1 x 10 9 parasites) from the same animal in group 2. This inoculum was irradiated a second time (900 Gy) and the cells were washed and culture ''IN VITRO'' for 4 days prior to inoculation. Parasitaemia increased abruptly in group 3 (peak = 25%) concomitant with a sudden drop in hematocrit. Two animals died, the others required treatment. Group 4 had a transient and low parasitaemia (peak = 2%) and normal hematocrit values. On day 201 all animals including a new control (group 5) of 5 animals, were inoculated with 2 x 10 9 heterologous parasites. All 5 control animals reached 20% parasitaemia and averaged a -40% hematocrit decrease when treated. In contrast, the remaining animals had from -20% to normal hematocrit values and from 5.6% to non-detectable parasitaemias. All inoculated calves showed high antibody titers which increased once the parasitaemia was overcome, and after challenge. It appears that two (900 Gy) irradiations effectively attenuated A. marginale, conferring an active and long lasting protection. However, inoculum cells had to be washed and cultured to prevent hemolitic shock

  15. Immunogenicity, safety, and antibody persistence at 3, 5, and 10 years postvaccination in adolescents randomized to booster immunization with a combined tetanus, diphtheria, 5-component acellular pertussis, and inactivated poliomyelitis vaccine administered with a hepatitis B virus vaccine concurrently or 1 month apart.

    Science.gov (United States)

    Embree, Joanne; Law, Barbara; Voloshen, Tim; Tomovici, Antigona

    2015-03-01

    An understanding of the antibody persistence elicited by a combined tetanus, diphtheria, 5-component acellular pertussis, and inactivated poliovirus vaccine (Tdap-IPV) after adolescent vaccination is important to optimize booster dosing intervals. Our objectives were to compare the safety and immunogenicity of Tdap-IPV coadministered with hepatitis B vaccine (HepB) and sequential administration and evaluate humoral immunity at 3, 5, and 10 years after Tdap-IPV vaccination in adolescents. This phase II randomized, controlled, and open-label study enrolled 280 11- to 14-year-old adolescents with up to 10 years postvaccination follow-up. Group 1 (n = 145) received Tdap-IPV, followed by a HepB dose 1 month later, and group 2 (n = 135) received both vaccines simultaneously. No consistent increases in solicited reactions or unsolicited adverse events occurred with coadministration. All vaccinees attained seroprotective antibody levels at ≥0.01 IU/ml for diphtheria and tetanus, at a ≥1:8 dilution for poliovirus (serotypes 1, 2, and 3), and ≥10 mIU/ml for hepatitis B at 1 month postvaccination. Clinically relevant immunologic interactions did not occur with coadministration. For pertussis, all participants achieved seropositivity levels (at or above the lower limit of quantitation), and 72.7% to 95.8% had 4-fold increases in pertussis antibodies at 1 month postvaccination. At 10 years postvaccination, the remaining participants (62.8% of the original cohort) maintained seroprotective levels of ≥0.01 IU/ml for diphtheria and tetanus, a ≥1:8 dilution for all 3 poliovirus serotypes, and 74.1% to 98.2% maintained pertussis seropositivity levels depending on the antigen tested. There were no differences between the groups. These results support the coadministration of Tdap-IPV and HepB to adolescents and suggest that vaccination with Tdap-IPV can offer protection for 10 years after an adolescent booster vaccination. Copyright © 2015, American Society for Microbiology

  16. Low dose vaccination with attenuated Francisella tularensis strain SchuS4 mutants protects against tularemia independent of the route of vaccination.

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    Dedeke Rockx-Brouwer

    Full Text Available Tularemia, caused by the gram-negative bacterium Francisella tularensis, is a severe, sometimes fatal disease. Interest in tularemia has increased over the last decade due to its history as a biological weapon. In particular, development of novel vaccines directed at protecting against pneumonic tularemia has been an important goal. Previous work has demonstrated that, when delivered at very high inoculums, administration of live, highly attenuated strains of virulent F. tularensis can protect against tularemia. However, lower vaccinating inoculums did not offer similar immunity. One concern of using live vaccines is that the host may develop mild tularemia in response to infection and use of high inoculums may contribute to this issue. Thus, generation of a live vaccine that can efficiently protect against tularemia when delivered in low numbers, e.g. <100 organisms, may address this concern. Herein we describe the ability of three defined, attenuated mutants of F. tularensis SchuS4, deleted for FTT0369c, FTT1676, or FTT0369c and FTT1676, respectively, to engender protective immunity against tularemia when delivered at concentrations of approximately 50 or fewer bacteria. Attenuated strains for use as vaccines were selected by their inability to efficiently replicate in macrophages in vitro and impaired replication and dissemination in vivo. Although all strains were defective for replication in vitro within macrophages, protective efficacy of each attenuated mutant was correlated with their ability to modestly replicate and disseminate in the host. Finally, we demonstrate the parenteral vaccination with these strains offered superior protection against pneumonic tularemia than intranasal vaccination. Together our data provides proof of principle that low dose attenuated vaccines may be a viable goal in development of novel vaccines directed against tularemia.

  17. Immunity to schistosomiasis mansoni in guinea-pigs vaccinated with radiation-attenuated cercariae

    International Nuclear Information System (INIS)

    Gordon, J.R.; McLaren, D.J.

    1987-01-01

    The anti-schistosomular humoral responses of guinea-pigs vaccinated with radiation-attenuated cercariae of Schistosoma mansoni have been investigated in vitro. The sera of vaccinated animals contain schistosomulicidal complement-fixing antibodies which peak in titre at week 5 after vaccination and predominantly consist of IgG 2 and IgM antibodies. The ability of the serum to arm macrophages from normal animals to bind to schistosomula, also peaks in titre at week 5 and is associated with IgG 2 antibodies. Basophils from normal animals can be sensitized in vitro by vaccine serum to degranulate in the presence of schistosomular antigens. This anaphylactic antibody activity is associated with IgG 1 but not IgE antibodies, and peaks in titre at week 10. Three antigens (14 kD, 20 kD and 43 kD) are specifically and transiently detected by vaccine serum on Western blots of schistosomular proteins; these antigens are first discernible at week 4, but were virtually undetectable at week 12. (author)

  18. Biomarkers of safety and immune protection for genetically modified live attenuated leishmania vaccines against visceral leishmaniasis - discovery and implications.

    Science.gov (United States)

    Gannavaram, Sreenivas; Dey, Ranadhir; Avishek, Kumar; Selvapandiyan, Angamuthu; Salotra, Poonam; Nakhasi, Hira L

    2014-01-01

    Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood-borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, subunit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in Leishmania donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters, and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines, e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen(-/-) in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated in normal

  19. Biomarkers of Safety and Immune Protection for Genetically Modified Live Attenuated Leishmania Vaccines Against Visceral Leishmaniasis – Discovery and Implications

    Science.gov (United States)

    Gannavaram, Sreenivas; Dey, Ranadhir; Avishek, Kumar; Selvapandiyan, Angamuthu; Salotra, Poonam; Nakhasi, Hira L.

    2014-01-01

    Despite intense efforts there is no safe and efficacious vaccine against visceral leishmaniasis, which is fatal and endemic in many tropical countries. A major shortcoming in the vaccine development against blood-borne parasitic agents such as Leishmania is the inadequate predictive power of the early immune responses mounted in the host against the experimental vaccines. Often immune correlates derived from in-bred animal models do not yield immune markers of protection that can be readily extrapolated to humans. The limited efficacy of vaccines based on DNA, subunit, heat killed parasites has led to the realization that acquisition of durable immunity against the protozoan parasites requires a controlled infection with a live attenuated organism. Recent success of irradiated malaria parasites as a vaccine candidate further strengthens this approach to vaccination. We developed several gene deletion mutants in Leishmania donovani as potential live attenuated vaccines and reported extensively on the immunogenicity of LdCentrin1 deleted mutant in mice, hamsters, and dogs. Additional limited studies using genetically modified live attenuated Leishmania parasites as vaccine candidates have been reported. However, for the live attenuated parasite vaccines, the primary barrier against widespread use remains the absence of clear biomarkers associated with protection and safety. Recent studies in evaluation of vaccines, e.g., influenza and yellow fever vaccines, using systems biology tools demonstrated the power of such strategies in understanding the immunological mechanisms that underpin a protective phenotype. Applying similar tools in isolated human tissues such as PBMCs from healthy individuals infected with live attenuated parasites such as LdCen−/− in vitro followed by human microarray hybridization experiments will enable us to understand how early vaccine-induced gene expression profiles and the associated immune responses are coordinately regulated in normal

  20. The Role of Praziquantel- chemoprophylaxis and UV-attenuated Vaccine in Protecting Mice Against S. Mansoni Infection

    International Nuclear Information System (INIS)

    Gad, H.S.M.

    1999-01-01

    Potential control of schistosomiasis rely on multiple and integrated strategies, including vaccine production, chemotherapy and combination between chemotherapy and vaccination. The present work was conducted to evaluate the efficacy of combined PZQ- treatment with PZQ-chemoprophylaxis (PZQ-pretreatment) and UV-attenuated cercarial vaccination for the control of schistosomiasis. In the present work the induced levels of protection induced in vaccinated and vaccinated-PZQ-treated as well as, PZQ-pretreated and PZQ-pretreated followed by PZQ-treatment will be discussed. Results revealed that UV-Irradiated Vaccinated and vaccinated-PZQ-treated and PZQ-pretreated followed by PZQ-treated post challenged groups induced high levels of worm burdens reduction and mild pathological changes in both liver and intestine. Meanwhile, PZQ-pretreated alone failed to induce significant protection

  1. Radiotherapy for Pertussis: An Historical Assessment

    Directory of Open Access Journals (Sweden)

    Edward J. Calabrese PhD

    2017-05-01

    Full Text Available X-ray therapy was used to treat pertussis/whooping cough during a 13-year period from 1923 to 1936 in North America and Europe. Twenty studies from clinicians in the United States reported that approximately 1500 cases of pertussis were treated by X-ray therapy usually with less than 0.5 erythema dose. Young children (<3 years comprised about 70% to 80% of the cases, with the age of cases ranging from as young as 1 month to 50 years. In general, symptoms of severe coughing, vomiting episodes, and spasms were significantly relieved in about 85% of cases following up to 3 treatments, while about 15% of the cases showed nearly full relief after only 1 treatment. The X-ray therapy was also associated with a marked reduction in mortality of young (<3 years children by over 90%. Despite such reported clinical success from a wide range of experienced researchers, the use of X-rays for the treatment of pertussis in young children was controversial, principally due to concerns of exposure to the thymus and thyroid even with the availability of lead shielding. By the mid-1930s, the treatment of pertussis cases via vaccine therapy came to dominate the therapeutic arena, and the brief era of a radiotherapy option for the treatment of pertussis ended.

  2. Attenuation of Replication-Competent Adenovirus Serotype 26 Vaccines by Vectorization.

    Science.gov (United States)

    Maxfield, Lori F; Abbink, Peter; Stephenson, Kathryn E; Borducchi, Erica N; Ng'ang'a, David; Kirilova, Marinela M; Paulino, Noelix; Boyd, Michael; Shabram, Paul; Ruan, Qian; Patel, Mayank; Barouch, Dan H

    2015-11-01

    Replication-competent adenovirus (rcAd)-based vaccine vectors may theoretically provide immunological advantages over replication-incompetent Ad vectors, but they also raise additional potential clinical and regulatory issues. We produced replication-competent Ad serotype 26 (rcAd26) vectors by adding the E1 region back into a replication-incompetent Ad26 vector backbone with the E3 or E3/E4 regions deleted. We assessed the effect of vectorization on the replicative capacity of the rcAd26 vaccines. Attenuation occurred in a stepwise fashion, with E3 deletion, E4 deletion, and human immunodeficiency virus type 1 (HIV-1) envelope (Env) gene insertion all contributing to reduced replicative capacity compared to that with the wild-type Ad26 vector. The rcAd26 vector with E3 and E4 deleted and containing the Env transgene exhibited 2.7- to 4.4-log-lower replicative capacity than that of the wild-type Ad26 in vitro. This rcAd26 vector is currently being evaluated in a phase 1 clinical trial. Attenuation as a result of vectorization and transgene insertion has implications for the clinical development of replication-competent vaccine vectors. Copyright © 2015, Maxfield et al.

  3. Stabilization of Live Attenuated Influenza Vaccines by Freeze Drying, Spray Drying, and Foam Drying.

    Science.gov (United States)

    Lovalenti, Phillip M; Anderl, Jeff; Yee, Luisa; Nguyen, Van; Ghavami, Behnaz; Ohtake, Satoshi; Saxena, Atul; Voss, Thomas; Truong-Le, Vu

    2016-05-01

    The goal of this research is to develop stable formulations for live attenuated influenza vaccines (LAIV) by employing the drying methods freeze drying, spray drying, and foam drying. Formulated live attenuated Type-A H1N1 and B-strain influenza vaccines with a variety of excipient combinations were dried using one of the three drying methods. Process and storage stability at 4, 25 and 37°C of the LAIV in these formulations was monitored using a TCID50 potency assay. Their immunogenicity was also evaluated in a ferret model. The thermal stability of H1N1 vaccine was significantly enhanced through application of unique formulation combinations and drying processes. Foam dried formulations were as much as an order of magnitude more stable than either spray dried or freeze dried formulations, while exhibiting low process loss and full retention of immunogenicity. Based on long-term stability data, foam dried formulations exhibited a shelf life at 4, 25 and 37°C of >2, 1.5 years and 4.5 months, respectively. Foam dried LAIV Type-B manufactured using the same formulation and process parameters as H1N1 were imparted with a similar level of stability. Foam drying processing methods with appropriate selection of formulation components can produce an order of magnitude improvement in LAIV stability over other drying methods.

  4. A Reverse Genetics Approach for the Design of Methyltransferase-Defective Live Attenuated Avian Metapneumovirus Vaccines.

    Science.gov (United States)

    Zhang, Yu; Sun, Jing; Wei, Yongwei; Li, Jianrong

    2016-01-01

    Avian metapneumovirus (aMPV), also known as avian pneumovirus or turkey rhinotracheitis virus, is the causative agent of turkey rhinotracheitis and is associated with swollen head syndrome in chickens. aMPV belongs to the family Paramyxoviridae which includes many important human pathogens such as human respiratory syncytial virus (RSV), human metapneumovirus (hMPV), and human parainfluenza virus type 3 (PIV3). The family also includes highly lethal emerging pathogens such as Nipah virus and Hendra virus, as well as agriculturally important viruses such as Newcastle disease virus (NDV). For many of these viruses, there is no effective vaccine. Here, we describe a reverse genetics approach to develop live attenuated aMPV vaccines by inhibiting the viral mRNA cap methyltransferase. The viral mRNA cap methyltransferase is an excellent target for the attenuation of paramyxoviruses because it plays essential roles in mRNA stability, efficient viral protein translation and innate immunity. We have described in detail the materials and methods used to generate recombinant aMPVs that lack viral mRNA cap methyltransferase activity. We have also provided methods to evaluate the genetic stability, pathogenesis, and immunogenicity of live aMPV vaccine candidates in turkeys.

  5. Vaccination of children with a live-attenuated, intranasal influenza vaccine – analysis and evaluation through a Health Technology Assessment

    Directory of Open Access Journals (Sweden)

    Andersohn, Frank

    2014-10-01

    Full Text Available [english] Background: Influenza is a worldwide prevalent infectious disease of the respiratory tract annually causing high morbidity and mortality in Germany. Influenza is preventable by vaccination and this vaccination is so far recommended by the (STIKO as a standard vaccination for people from the age of 60 onwards. Up to date a parenterally administered trivalent inactivated vaccine (TIV has been in use almost exclusively. Since 2011 however a live-attenuated vaccine (LAIV has been approved additionally. Consecutively, since 2013 the STIKO recommends LAIV (besides TIV for children from 2 to 17 years of age, within the scope of vaccination by specified indications. LAIV should be preferred administered in children from 2 to 6 of age. The objective of this Health Technology Assessment (HTA is to address various research issues regarding the vaccination of children with LAIV. The analysis was performed from a medical, epidemiological and health economic perspective, as well as from an ethical, social and legal point of view.Method: An extensive systematic database research was performed to obtain relevant information. In addition a supplementary research by hand was done. Identified literature was screened in two passes by two independent reviewers using predefined inclusion and exclusion criteria. Included literature was evaluated in full-text using acknowledged standards. Studies were graded with the highest level of evidence (1++, if they met the criteria of Results: For the medical section, the age of the study participants ranges from 6 months to 17 years. Regarding study efficacy, in children aged 6 months to ≤7 years, LAIV is superior to placebo as well as to a vac-cination with TIV (Relative Risk Reduction – RRR – of laboratory confirmed influenza infection approx. 80% and 50%, respectively. In children aged >7 to 17 years (= 18th year of their lives, LAIV is superior to a vaccination with TIV (RRR 32%. For this age group, no

  6. Safety and efficacy of an attenuated Chinese QX-like infectious bronchitis virus strain as a candidate vaccine.

    Science.gov (United States)

    Zhao, Ye; Cheng, Jin-long; Liu, Xiao-yu; Zhao, Jing; Hu, Yan-xin; Zhang, Guo-zhong

    2015-10-22

    Infectious bronchitis (IB) is a highly contagious respiratory and urogenital disease of chickens caused by infectious bronchitis virus (IBV). This disease is of considerable economic importance and is primarily controlled through biosecurity and immunization with live attenuated and inactivated IB vaccines of various serotypes. In the present study, we tested the safety and efficacy of an attenuated predominant Chinese QX-like IBV strain. The results revealed that the attenuated strain has a clear decrease in pathogenicity for specific-pathogen-free (SPF) chickens compared with the parent strain. Strain YN-inoculated birds had clinical signs of varying severity with 30% mortality, while the attenuated group appeared healthy, with less tissue damage. The attenuated strain also had relatively low tissue replication rates and higher antibody levels. The superior protective efficacy of the attenuated strain was observed when vaccinated birds were challenged with a homologous or heterologous field IBV strain, indicating the potential of the attenuated YN (aYN) as a vaccine. Producing a vaccine targeting the abundant serotype in China is essential to reducing the economic impact of IB on the poultry industry. Copyright © 2015 Elsevier B.V. All rights reserved.

  7. PERTUSSIS IS COMING BACK? IMPROVEMENT OF FORGOTTEN CHILDHOOD INFECTION CONTROL

    Directory of Open Access Journals (Sweden)

    M. V. Fedoseenko

    2012-01-01

    Full Text Available Infection that more than 60 years ago was recognized one of the leading childhood diseases that caused infant mortality, is returning. Of course, with the introduction of vaccination against pertussis in the national programs, we rarely meet severe pertussis infection in our practice, considering that vaccinating children, we protect them. But why so far is this infectious disease remains a serious problem not only in Russia but throughout the world? Several global reasons contribute to the fact that until now vaccine-preventable diseases leads to a prolonged, exhausting cough in schoolchildren, deceiving the doctors with the correct diagnosis is still a real threat to infants. 

  8. Evaluation of live attenuated S79 mumps vaccine effectiveness in mumps outbreaks: a matched case-control study.

    Science.gov (United States)

    Fu, Chuan-xi; Nie, Jun; Liang, Jian-hua; Wang, Ming

    2009-02-05

    Mumps virus infection is a potentially serious viral infection of childhood and early adulthood. In China, live attenuated S(79) mumps vaccine has been licensed for pediatric use since 1990. The objective of this study was to determine the effectiveness of live attenuated S(79) mumps vaccine against clinical mumps in outbreaks. Cases were selected from mumps outbreaks in schools in Guangzhou between 2004 and 2005. Each case was matched by gender, age and classroom. Vaccination information was obtained from Children's EPI Administrative Computerized System. Vaccine effectiveness (VE) was calculated for 1 or 2 doses of S(79) vaccine with 95% confidence intervals (CI). One hundred and ninety-four cases and 194 controls were enrolled into the study. VE of the S(79) mumps vaccine for 1 dose versus 0 confer protection 80.4% (95% CI, 60.0%-90.4%) and VEs against mumps in outbreaks for 1 dose of mumps vaccine are similar among those children aged 4-9 years and aged over 10 years old. The live attenuated S(79) mumps vaccine can be effective in preventing clinical mumps outbreaks.

  9. Immunogenicity and safety of an acellular pertussis, diphtheria ...

    African Journals Online (AJOL)

    Objective. To assess the immunogenicity and safety data for a pentavalent combination vaccine containing acellular pertussis, inactivated poliovirus, and Haemophilus influenzae (Hib) polysaccharide-conjugate antigens. Methods. A DTaP-IPV//PRP~T vaccine (Pentaxim™) was given at 6, 10 and 14 weeks of age to 212 ...

  10. An effective AIDS vaccine based on live attenuated vesicular stomatitis virus recombinants.

    Science.gov (United States)

    Rose, N F; Marx, P A; Luckay, A; Nixon, D F; Moretto, W J; Donahoe, S M; Montefiori, D; Roberts, A; Buonocore, L; Rose, J K

    2001-09-07

    We developed an AIDS vaccine based on attenuated VSV vectors expressing env and gag genes and tested it in rhesus monkeys. Boosting was accomplished using vectors with glycoproteins from different VSV serotypes. Animals were challenged with a pathogenic AIDS virus (SHIV89.6P). Control monkeys showed a severe loss of CD4+ T cells and high viral loads, and 7/8 progressed to AIDS with an average time of 148 days. All seven vaccinees were initially infected with SHIV89.6P but have remained healthy for up to 14 months after challenge with low or undetectable viral loads. Protection from AIDS was highly significant (p = 0.001). VSV vectors are promising candidates for human AIDS vaccine trials because they propagate to high titers and can be delivered without injection.

  11. The yellow fever 17D virus as a platform for new live attenuated vaccines.

    Science.gov (United States)

    Bonaldo, Myrna C; Sequeira, Patrícia C; Galler, Ricardo

    2014-01-01

    The live-attenuated yellow fever 17D virus is one of the most outstanding human vaccines ever developed. It induces efficacious immune responses at a low production cost with a well-established manufacture process. These advantages make the YF17D virus attractive as a vector for the development of new vaccines. At the beginning of vector development studies, YF17D was genetically manipulated to express other flavivirus prM and E proteins, components of the viral envelope. While these 17D recombinants are based on the substitution of equivalent YF17D genes, other antigens from unrelated pathogens have also been successfully expressed and delivered by recombinant YF17D viruses employing alternative strategies for genetic manipulation of the YF17D genome. Herein, we discuss these strategies in terms of possibilities of single epitope or larger sequence expression and the main properties of these replication-competent viral platforms.

  12. Development and biological properties of a new live attenuated mumps vaccine.

    Science.gov (United States)

    Saika, Shizuko; Kidokoro, Minoru; Kubonoya, Hiroko; Ito, Kozo; Ohkawa, Tokitada; Aoki, Athuko; Nagata, Noriyo; Suzuki, Kazuyoshi

    2006-01-01

    To develop a new live attenuated mumps vaccine, a wild mumps Y7 strain isolated from a patient who developed mild parotitis was treated with nitrosoguanidine and ultraviolet, followed by selection of a temperature-sensitive clone. The selected clone, Y125, showed stable temperature-sensitivity in Vero cells. Intraspinal inoculation of marmosets with the Y125 produced only minimal histopathological changes, while intracerebral inoculation of neonatal rats revealed that the Y125 did not cause hydrocephalus. Both these effects of the Y125 were similar to those of the non-neurovirulent Jeryl Lynn strain. Furthermore, subcutaneous inoculation of the Y125 induced high levels of neutralizing antibodies in all Cercopithecus monkeys examined. Although the safety and immunogenicity should be confirmed in further field trials in humans, the present results indicate that the Y125 could be a promising vaccine candidate.

  13. Safety, immunogenicity, and protective efficacy of two doses of RIX4414 live attenuated human rotavirus vaccine in healthy infants.

    Science.gov (United States)

    Araujo, Eliete C; Clemens, Sue Ann C; Oliveira, Consuelo S; Justino, Maria Cleonice A; Rubio, Pilar; Gabbay, Yvone B; da Silva, Veronilce B; Mascarenhas, Joana D P; Noronha, Vânia L; Clemens, Ralf; Gusmão, Rosa Helena P; Sanchez, Nervo; Monteiro, Talita Antônia F; Linhares, Alexandre C

    2007-01-01

    To determine the safety, immunogenicity and efficacy of two doses of rotavirus vaccine in healthy Brazilian infants. A randomized, multicenter, double-blind, placebo-controlled trial was conducted in Brazil, Mexico and Venezuela. Infants received two oral doses of vaccine or placebo at 2 and 4 months of age, concurrently with routine immunizations, except for oral poliomyelitis vaccine (OPV). This paper reports results from Belém, Brazil, where the number of subjects per group and the viral vaccine titers were: 194 (10(4.7) focus forming units - FFU), 196 (10(5.2) FFU), 194 (10(5.8) FFU) and 194 (placebo). Anti-rotavirus (anti-RV) antibody response was assessed in 307 subjects. Clinical severity of gastroenteritis episodes was measured using a 20-point scoring system with a score of >or= 11 defined as severe GE. The rates of solicited general symptoms were similar in vaccine and placebo recipients. At 2 months after the second dose, a serum IgA response to RV occurred in 54.7 to 74.4% of vaccinees. No interference was seen in the immunogenicity of routine vaccines. Vaccine efficacy against any rotavirus gastroenteritis (RVGE) was 63.5% (95%CI 20.8-84.4) for the highest concentration (10(5.8) FFU). Efficacy was 81.5% (95%CI 44.5-95.4) against severe RVGE. At its highest concentration (10(5.8) FFU), RIX4414 provided 79.8% (95%CI 26.4-96.3) protection against severe RVGE by G9 strain. RIX4414 was highly immunogenic with a low reactogenicity profile and did not interfere with seroresponse to diphtheria, tetanus, pertussis, hepatitis B and Hib antigens. Two doses of RIX4414 provided significant protection against severe GE caused by RV.

  14. Implementation of pertussis immunization in health-care personnel.

    Science.gov (United States)

    Walther, Kathi; Burckhardt, Marie-Anne; Erb, Thomas; Heininger, Ulrich

    2015-04-21

    Infection with Bordetella pertussis is most severe in young infants who frequently acquire it from adults. Pertussis immunization in adults 25-29 years of age and all adults in close contact with infants vaccination campaign. Between April 2012 and March 2013 we provided information about the campaign to our staff through several channels and offered appointments for counseling and immunization. After checking indications and contraindications of responding health-care personnel (HCP), informed consent for tetanus-diphtheria-acellular pertussis component (Tdap) immunization was obtained. Specific adverse events (AE) were self-assessed by standardized diaries for 7 days. Statistical analyses were performed using a t-test and Mann-Whitney U-tests SPSS (V21). Of 852 HCP eligible for pertussis immunization, 427 (51%) responded. Of these, 72 (17%) had already received Tdap now, 38 (9%) were scheduled for vaccination and 12 (3%) declined. Diaries were returned by 272 (89%) of 304 vaccinees; 56 HCP reported ≥1 local AE, most frequently local swelling (8%), redness (2%), redness and swelling (7%), and fever (5=2%); no serious AE occurred. Comprehensive efforts were needed to achieve pertussis immunization coverage of ≥49% among all HCP in our institution. Good tolerability of the vaccine and continuous and individual information to HCP about the rationale and benefits of pertussis immunization contributed to this partial success, but increased efforts are needed to mobilize non-responding HCP. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Rapid strategy for screening by pyrosequencing of influenza virus reassortants--candidates for live attenuated vaccines.

    Science.gov (United States)

    Shcherbik, Svetlana V; Pearce, Nicholas C; Levine, Marnie L; Klimov, Alexander I; Villanueva, Julie M; Bousse, Tatiana L

    2014-01-01

    Live attenuated influenza vaccine viruses (LAIVs) can be generated by classical reassortment of gene segments between a cold adapted, temperature sensitive and attenuated Master Donor Virus (MDV) and a seasonal wild-type (wt) virus. The vaccine candidates contain hemagglutinin (HA) and neuraminidase (NA) genes derived from the circulating wt viruses and the remaining six genes derived from the MDV strains. Rapid, efficient selection of the viruses with 6∶2 genome compositions from the large number of genetically different viruses generated during reassortment is essential for the biannual production schedule of vaccine viruses. This manuscript describes a new approach for the genotypic analysis of LAIV reassortant virus clones based on pyrosequencing. LAIV candidate viruses were created by classical reassortment of seasonal influenza A (H3N2) (A/Victoria/361/2011, A/Ohio/02/2012, A/Texas/50/2012) or influenza A (H7N9) (A/Anhui/1/2013) wt viruses with the MDV A/Leningrad/134/17/57(H2N2). Using strain-specific pyrosequencing assays, mixed gene variations were detected in the allantoic progenies during the cloning procedure. The pyrosequencing analysis also allowed for estimation of the relative abundance of segment variants in mixed populations. This semi-quantitative approach was used for selecting specific clones for the subsequent cloning procedures. The present study demonstrates that pyrosequencing analysis is a useful technique for rapid and reliable genotyping of reassortants and intermediate clones during the preparation of LAIV candidates, and can expedite the selection of vaccine virus candidates.

  16. Rapid strategy for screening by pyrosequencing of influenza virus reassortants--candidates for live attenuated vaccines.

    Directory of Open Access Journals (Sweden)

    Svetlana V Shcherbik

    Full Text Available BACKGROUND: Live attenuated influenza vaccine viruses (LAIVs can be generated by classical reassortment of gene segments between a cold adapted, temperature sensitive and attenuated Master Donor Virus (MDV and a seasonal wild-type (wt virus. The vaccine candidates contain hemagglutinin (HA and neuraminidase (NA genes derived from the circulating wt viruses and the remaining six genes derived from the MDV strains. Rapid, efficient selection of the viruses with 6∶2 genome compositions from the large number of genetically different viruses generated during reassortment is essential for the biannual production schedule of vaccine viruses. METHODOLOGY/PRINCIPAL FINDINGS: This manuscript describes a new approach for the genotypic analysis of LAIV reassortant virus clones based on pyrosequencing. LAIV candidate viruses were created by classical reassortment of seasonal influenza A (H3N2 (A/Victoria/361/2011, A/Ohio/02/2012, A/Texas/50/2012 or influenza A (H7N9 (A/Anhui/1/2013 wt viruses with the MDV A/Leningrad/134/17/57(H2N2. Using strain-specific pyrosequencing assays, mixed gene variations were detected in the allantoic progenies during the cloning procedure. The pyrosequencing analysis also allowed for estimation of the relative abundance of segment variants in mixed populations. This semi-quantitative approach was used for selecting specific clones for the subsequent cloning procedures. CONCLUSIONS/SIGNIFICANCE: The present study demonstrates that pyrosequencing analysis is a useful technique for rapid and reliable genotyping of reassortants and intermediate clones during the preparation of LAIV candidates, and can expedite the selection of vaccine virus candidates.

  17. Rational development of an attenuated recombinant cyprinid herpesvirus 3 vaccine using prokaryotic mutagenesis and in vivo bioluminescent imaging.

    Science.gov (United States)

    Boutier, Maxime; Ronsmans, Maygane; Ouyang, Ping; Fournier, Guillaume; Reschner, Anca; Rakus, Krzysztof; Wilkie, Gavin S; Farnir, Frédéric; Bayrou, Calixte; Lieffrig, François; Li, Hong; Desmecht, Daniel; Davison, Andrew J; Vanderplasschen, Alain

    2015-02-01

    Cyprinid herpesvirus 3 (CyHV 3) is causing severe economic losses worldwide in common and koi carp industries, and a safe and efficacious attenuated vaccine compatible with mass vaccination is needed. We produced single deleted recombinants using prokaryotic mutagenesis. When producing a recombinant lacking open reading frame 134 (ORF134), we unexpectedly obtained a clone with additional deletion of ORF56 and ORF57. This triple deleted recombinant replicated efficiently in vitro and expressed an in vivo safety/efficacy profile compatible with use as an attenuated vaccine. To determine the role of the double ORF56-57 deletion in the phenotype and to improve further the quality of the vaccine candidate, a series of deleted recombinants was produced and tested in vivo. These experiments led to the selection of a double deleted recombinant lacking ORF56 and ORF57 as a vaccine candidate. The safety and efficacy of this strain were studied using an in vivo bioluminescent imaging system (IVIS), qPCR, and histopathological examination, which demonstrated that it enters fish via skin infection similar to the wild type strain. However, compared to the parental wild type strain, the vaccine candidate replicated at lower levels and spread less efficiently to secondary sites of infection. Transmission experiments allowing water contamination with or without additional physical contact between fish demonstrated that the vaccine candidate has a reduced ability to spread from vaccinated fish to naïve sentinel cohabitants. Finally, IVIS analyses demonstrated that the vaccine candidate induces a protective mucosal immune response at the portal of entry. Thus, the present study is the first to report the rational development of a recombinant attenuated vaccine against CyHV 3 for mass vaccination of carp. We also demonstrated the relevance of the CyHV 3 carp model for studying alloherpesvirus transmission and mucosal immunity in teleost skin.

  18. Safety issues from a Phase 3 clinical trial of a live-attenuated chimeric yellow fever tetravalent dengue vaccine.

    Science.gov (United States)

    Halstead, Scott B

    2018-02-26

    A tetravalent live-attenuated 3-dose vaccine composed of chimeras of yellow fever 17D and the four dengue viruses (CYD, also called Dengvaxia) completed phase 3 clinical testing in over 35,000 children leading to a recommendation that vaccine be administered to >/ = 9 year-olds residing in highly dengue- endemic countries. When clinical trial results were assessed 2 years after the first dose, vaccine efficacy among seropositives was high, but among seronegatives efficacy was marginal. Breakthrough dengue hospitalizations of vaccinated children occurred continuously over a period of 4-5 years post 3rd dose in an age distribution suggesting these children had been vaccinated when seronegative. This surmise was validated recently when the manufacturer reported that dengue NS1 IgG antibodies were absent in sera from hospitalized vaccinated children, an observation consistent with their having received Dengvaxia when seronegative. Based upon published efficacy data and in compliance with initial published recommendations by the manufacturer and WHO the Philippine government undertook to vaccinate 800,000-plus 9 year-olds starting in April 2016. Eighteen months later, dengue hospitalizations and a deaths were reported among vaccinated children. The benefits of administering Dengvaxia predicted by the manufacturer, WHO and others derive from scoring dengue hospitalizations of vaccinated children as vaccine failures rather than as vaccine enhanced dengue disease. Recommended regimens for administration of Dengvaxia should have been structured to warn of and avoid serious adverse events.

  19. [Production of pertussis toxin by Bordetella pertussis strains isolated from patients with whooping cough].

    Science.gov (United States)

    Zaĭtsev, E M; Mertsalova, N U; Shinkarev, A S; Mazurova, I K; Zakharova, N S

    2011-01-01

    To assess level of pertussin toxin (PT) production by vaccine strains of Bordetella pertussis and strains isolated from patients with whooping cough. Concentration of PT in supernatants of microbial cultures of 3 vaccine strains and 25 strains of B. pertussis isolated from patients with pertussis in 2001 - 2005 was measured with enzyme immunoassay using gamma-globulin fractions of rabbit antiserum to PT as immunosorbent or included in peroxidase conjugates. Level of PT production by strains isolated from infected persons varied from 3 +/- 0.5 to 64.8 +/- 12.2 ng/MFU/ml: in 9 strains--from 3 +/- 0.5 to 9.4 +/- 2.1 ng/MFU/ml, in 7--10.5 +/- 1.8 to 18.4 +/- 2.6 ng/MFU/ml, and in 9--23.6 +/- 4.5 to 64.8 +/- 12.2 ng/MFU/ml. B. pertussis strains isolated from patients were heterogeneous on level of PT production. Difference in expression of PT between strains were as high as 20-fold. Conditionally low, moderate and high levels of PT production had 9 (36%), 7 (28%), and 9 (36%) of 25 studied strains. Three vaccine strains had levels of toxin production similar to recently isolated strains with moderate level of its production.

  20. Live attenuated influenza vaccine use and safety in children and adults with asthma.

    Science.gov (United States)

    Duffy, Jonathan; Lewis, Melissa; Harrington, Theresa; Baxter, Roger; Belongia, Edward A; Jackson, Lisa A; Jacobsen, Steven J; Lee, Grace M; Naleway, Allison L; Nordin, James; Daley, Matthew F

    2017-04-01

    Live attenuated influenza vaccine (LAIV) might increase the risk of wheezing in persons with asthma or children younger than 5 years with a history of recurrent wheezing. To describe the use and assess the safety of LAIV in persons with asthma in the Vaccine Safety Datalink population. We identified persons with asthma using diagnosis codes and medication records in 7 health care organizations over 3 influenza seasons (2008-2009 through 2010-2011) and determined their influenza vaccination rates. Using the self-controlled risk interval method, we calculated the incidence rate ratio of medically attended respiratory events in the 14 days after LAIV compared with 29 to 42 days after vaccination in persons 2 through 49 years old. In our population of 6.3 million, asthma prevalence was 5.9%. Of persons with asthma, approximately 50% received any influenza vaccine but less than 1% received LAIV. The safety study included 12,354 LAIV doses (75% in children; 93% in those with intermittent or mild persistent asthma). The incidence rate ratio for inpatient and emergency department visits for lower respiratory events (including asthma exacerbation and wheezing) was 0.98 (95% confidence interval 0.63-1.51) and the incidence rate ratio for upper respiratory events was 0.94 (95% confidence interval 0.48-1.86). The risk of lower respiratory events was similar for intermittent and mild persistent asthma, across age groups, and for seasonal trivalent LAIV and 2009 H1N1 pandemic monovalent LAIV. LAIV use in asthma was mostly in persons with intermittent or mild persistent asthma. LAIV was not associated with an increased risk of medically attended respiratory adverse events. Published by Elsevier Inc.

  1. Development of live attenuated Streptococcus agalactiae as potential vaccines by selecting for resistance to sparfloxacin.

    Science.gov (United States)

    Pridgeon, Julia W; Klesius, Phillip H

    2013-05-31

    To develop attenuated bacteria as potential live vaccines, sparfloxacin was used in this study to modify 40 isolates of Streptococcus agalactiae. Majority of S. agalactiae used in this study were able to develop at least 80-fold resistance to sparfloxacin. When the virulence of the sparfloxacin-resistant S. agalactiae isolates were tested in 10-12g Nile tilapia by intraperitoneal injection at dose of 2×10(7)CFU/fish, 31 were found to be avirulent to fish. Of the 31 avirulent sparfloxacin-resistant S. agalactiae isolates, 30 provided 75-100% protection to 10-12g Nile tilapia against challenges with a virulent S. agalactiae isolate Sag 50. When the virulence of the 30 sparfloxacin-resistant S. agalactiae isolates was tested in 3-5g Nile tilapia by intraperitoneal injection at dose of 2×10(7)CFU/fish, six were found to be avirulent to 3-5g Nile tilapia. Of the six avirulent sparfloxacin-resistant S. agalactiae isolates, four provided 3-5g Nile tilapia 100% protection against challenges with homologous isolates, including Sag 97-spar isolate that was non-hemolytic. However, Sag 97-spar failed to provide broad cross-protection against challenges with heterologous isolates. When Nile tilapia was vaccinated with a polyvalent vaccine consisting of 30 sparfloxacin-resistant S. agalactiae isolates at dose of 2×10(6)CFU/fish, the polyvalent vaccine provided significant (PS. agalactiae. Taken together, our results suggest that a polyvalent vaccine consisting of various strains of S. agalactiae might be essential to provide broader protection to Nile tilapia against infections caused by S. agalactiae. Published by Elsevier Ltd.

  2. Immunogenicity and Safety of the HZ/su Adjuvanted Herpes Zoster Subunit Vaccine in Adults Previously Vaccinated With a Live Attenuated Herpes Zoster Vaccine.

    Science.gov (United States)

    Grupping, Katrijn; Campora, Laura; Douha, Martine; Heineman, Thomas C; Klein, Nicola P; Lal, Himal; Peterson, James; Vastiau, Ilse; Oostvogels, Lidia

    2017-12-12

    Protection against herpes zoster (HZ) induced by the live attenuated zoster vaccine Zostavax (ZVL) wanes within 3-7 years. Revaccination may renew protection. We assessed whether (re)vaccination with the adjuvanted HZ subunit vaccine candidate (HZ/su) induced comparable immune responses in previous ZVL recipients and ZVL-naive individuals (HZ-NonVac). In an open-label, multicenter study, adults ≥65 years of age, vaccinated with ZVL ≥5 years previously (HZ-PreVac), were matched to ZVL-naive adults (HZ-NonVac). Participants received 2 doses of HZ/su 2 months apart. The primary objective of noninferiority of the humoral immune response 1 month post-dose 2 was considered demonstrated if the upper limit of the 95% confidence interval (CI) of the adjusted anti-glycoprotein E geometric mean concentration (GMC) ratio of HZ-NonVac over HZ-PreVac was <1.5. HZ/su cellular immunogenicity, reactogenicity, and safety were also assessed. In 430 participants, humoral immune response to HZ/su was noninferior in HZ-PreVac compared with HZ-NonVac (adjusted GMC ratio, 1.04 [95% CI, .92-1.17]). Cellular immunogenicity, reactogenicity, and safety appeared to be comparable between groups. HZ/su was well-tolerated, with no safety concerns raised within 1 month post-dose 2. HZ/su induces a strong immune response irrespective of prior vaccination with ZVL, and may be an attractive option to revaccinate prior ZVL recipients. NCT02581410. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  3. Major histocompatibility complex-linked immune response of young chickens vaccinated with an attenuated live infectious bursal disease virus vaccine followed by an infection

    DEFF Research Database (Denmark)

    Juul-Madsen, Helle; Nielsen, O.L.; Krogh-Maibom, T.

    2002-01-01

    The influence of the MHC on infectious bursal disease virus (IBDV) vaccine response in chickens was investigated in three different chicken lines containing four different MHC haplotypes. Two MHC haplotypes were present in all three lines with one haplotype (1319) shared between the lines. Line I...... further contains the BW1 haplotype isolated from a Red jungle Fowl. Line 131 further contains the B131 haplotype isolated from a meat-type chicken, Finally, Line 21 further contains the international B21 haplotype. The chickens were vaccinated with live attenuated commercial IBDV vaccine at 3 wk of age...

  4. Live attenuated Francisella novicida vaccine protects against Francisella tularensis pulmonary challenge in rats and non-human primates.

    Directory of Open Access Journals (Sweden)

    Ping Chu

    2014-10-01

    Full Text Available Francisella tularensis causes the disease tularemia. Human pulmonary exposure to the most virulent form, F. tularensis subsp. tularensis (Ftt, leads to high morbidity and mortality, resulting in this bacterium being classified as a potential biothreat agent. However, a closely-related species, F. novicida, is avirulent in healthy humans. No tularemia vaccine is currently approved for human use. We demonstrate that a single dose vaccine of a live attenuated F. novicida strain (Fn iglD protects against subsequent pulmonary challenge with Ftt using two different animal models, Fischer 344 rats and cynomolgus macaques (NHP. The Fn iglD vaccine showed protective efficacy in rats, as did a Ftt iglD vaccine, suggesting no disadvantage to utilizing the low human virulent Francisella species to induce protective immunity. Comparison of specific antibody profiles in vaccinated rat and NHP sera by proteome array identified a core set of immunodominant antigens in vaccinated animals. This is the first report of a defined live attenuated vaccine that demonstrates efficacy against pulmonary tularemia in a NHP, and indicates that the low human virulence F. novicida functions as an effective tularemia vaccine platform.

  5. Antibody response in animals immunized after oral delivery of attenuated liver hepatitis a vaccine

    International Nuclear Information System (INIS)

    Long Runxiang; Hou Zongliu; Xie Zhongping; Ding Xuefeng; Pan Yue; Huang Cheng; Zhang Ming; Yang Lixian

    2006-01-01

    The microspheres were prepared by encapsulating live attenuated hepatitis A vaccine with PLA/PLG, and the rhesus monkeys and mice were immunized by such microspheres through oral route. Then serum was collected to detect the HAV-IgM, HAV-IgG, HAV-IgA with EIA, so as to find a convenient immunization way. Results showed that HAV-IgG in rhesus monkeys was detected in the 3rd week and reached a peak value (1267mlU/mL), and then decreased by degrees. HAV-IgM titer was 1:4000. After an oral booster was given, the HAV-IgG level increased, and HAV-IgM titer was 1:1000. The level reached 1244mIU/mL after challenge with wild virus strain, and HAV-IgM was 1:100. HAV-IgM was detected in the control group only after challenge with wild virus strain. HAV-IgG in mice was detected in the 2nd week and reached a peak value in the 4th week. HAV S-IgA was detected in the 1st week and reached a peak value in the 4th week. Antibody response was induced in the rhesus monkeys after oral delivery of the biodegradable microspheres containing live attenuated HA vaccine. The results in mice were similar with the report but the anti-HAV was present earlier as compared with rhesus monkeys. (authors)

  6. Vaccination of chicks against Plasmodium gallinaceum by erythrocytic and exoerythrocytic parasites attenuated by gamma irradiation

    International Nuclear Information System (INIS)

    Hughes, H.P.A.; Dixon, B.

    1980-01-01

    Plasmodium gallinaceum-infected blood which received up to 24 krad during exposure to gamma-rays from a cobalt-60 source produced infections of normal course and duration when injected into chickens. The prepatent period advanced with increasing exposure of infected blood to radiation, suggesting some degree of attenuation. At 26, 28 and 30 krad, the infections were transient and the parasites were morphologically abnormal. It is thought that the amount of radiation required to render the parasites non-viable is about 45 krad for an inoculum of 10 6 parasites. There is evidence that exoerythrocytic stages may be more susceptible to gamma-rays than are blood parasites. Chickens were inoculated three times, over a period of four weeks, with vaccines prepared from gamma-irradiated infected blood and brain tissue. Half the birds which had been inoculated with attenuated parasitized blood exhibited mild infections during vaccination, and they were the only birds to show at challenge immunity to both homologous blood and exoerythrocytic parasites. (author)

  7. Live attenuated measles virus vaccine therapy for locally established malignant glioblastoma tumor cells

    Directory of Open Access Journals (Sweden)

    Al-Shammari AM

    2014-05-01

    Full Text Available Ahmed M Al-Shammari,1 Farah E Ismaeel,2 Shahlaa M Salih,2 Nahi Y Yaseen11Experimental Therapy Department, Iraqi Center for Cancer and Medical Genetic Researches, Mustansiriya University, 2Departments of Biotechnology, College of Science, Al-Nahrain University, Baghdad, IraqAbstract: Glioblastoma multiforme is the most aggressive malignant primary brain tumor in humans, with poor prognosis. A new glioblastoma cell line (ANGM5 was established from a cerebral glioblastoma multiforme in a 72-year-old Iraqi man who underwent surgery for an intracranial tumor. This study was carried out to evaluate the antitumor effect of live attenuated measles virus (MV Schwarz vaccine strain on glioblastoma multiforme tumor cell lines in vitro. Live attenuated MV Schwarz strain was propagated on Vero, human rhabdomyosarcoma, and human glioblastoma-multiform (ANGM5 cell lines. The infected confluent monolayer appeared to be covered with syncytia with granulation and vacuolation, as well as cell rounding, shrinkage, and large empty space with cell debris as a result of cell lysis and death. Cell lines infected with virus have the ability for hemadsorption to human red blood cells after 72 hours of infection, whereas no hemadsorption of uninfected cells is seen. Detection of MV hemagglutinin protein by monoclonal antibodies in infected cells of all cell lines by immunocytochemistry assay gave positive results (brown color in the cytoplasm of infected cells. Cell viability was measured after 72 hours of infection by 3-(4,5-Dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide assay. Results showed a significant cytotoxic effect for MV (P≤0.05 on growth of ANGM5 and rhabdomyosarcoma cell lines after 72 hours of infection. Induction of apoptosis by MV was assessed by measuring mitochondrial membrane potentials in tumor cells after 48, 72, and 120 hours of infection. Apoptotic cells were counted, and the mean percentage of dead cells was significantly higher after 48, 72

  8. Assessment of vaccination with schistosomules attenuated by using different doses of γ-radiation on experimental schistosomiasis mansoni

    International Nuclear Information System (INIS)

    Mohamed, E.N.H.

    2009-01-01

    Current strategies for the control of schistosomiasis are based primarily on chemotherapy but successful vaccination against infection has been also demonstrated in several host parasite models.The present study was designed to asses the immunogenic effects of the vaccination with autogenic targets in the form of schistosomula attenuated by different doses of γ-radiation (15, 20, 25 kilo rad) in mice challenged with S. mansoni cercariae as regard parasitological, histological, biochemical and immunological aspects.

  9. Identification of sequence changes in live attenuated goose parvovirus vaccine strains developed in Asia and Europe.

    Science.gov (United States)

    Shien, J-H; Wang, Y-S; Chen, C-H; Shieh, H K; Hu, C-C; Chang, P-C

    2008-10-01

    Live attenuated vaccines have been used for control of the disease caused by goose parvovirus (GPV), but the mechanism involved in attenuation of GPV remains elusive. This report presents the complete nucleotide sequences of two live attenuated strains of GPV (82-0321V and VG32/1) that were independently developed in Taiwan and Europe, together with the parental strain of 82-0321V and a field strain isolated in Taiwan in 2006. Sequence comparisons showed that 82-0321V and VG32/1 had multiple deletions and substitutions in the inverted terminal repeats region when compared with their parental strain or the field virus, but these changes did not affect the formation of the hairpin structure essential for viral replication. Moreover, 82-0321V and VG32/1 had five amino acid changes in the non-structural protein, but these changes were located at positions distant from known functional motifs in the non-structural protein. In contrast, 82-0321V had nine changes and VG32/1 had 11 changes in their capsid proteins (VP1), and the majority of these changes occurred at positions close to the putative receptor binding sites of VP1, as predicted using the structure of adeno-associated virus 2 as the model system. Taken together, the results suggest that changes in sequence near the receptor binding sites of VP1 might be responsible for attenuation of GPV. This is the first report of complete nucleotide sequences of GPV other than the virulent B strain, and suggests a possible mechanism for attenuation of GPV.

  10. Development of a Live Attenuated Bivalent Oral Vaccine Against Shigella sonnei Shigellosis and Typhoid Fever.

    Science.gov (United States)

    Wu, Yun; Chakravarty, Sumana; Li, Minglin; Wai, Tint T; Hoffman, Stephen L; Sim, B Kim Lee

    2017-01-15

    Shigella sonnei and Salmonella Typhi cause significant morbidity and mortality. We exploited the safety record of the oral, attenuated S. Typhi vaccine (Ty21a) by using it as a vector to develop a bivalent oral vaccine to protect against S. sonnei shigellosis and typhoid fever. We recombineered the S. sonnei form I O-antigen gene cluster into the Ty21a chromosome to create Ty21a-Ss, which stably expresses S. sonnei form I O antigen. To enhance survivability in the acid environment of the stomach, we created an acid-resistant strain, Ty21a-AR-Ss, by inserting Shigella glutaminase-glutamate decarboxylase systems coexpressed with S. sonnei form I O-antigen gene. Mice immunized intranasally with Ty21a-AR-Ss produced antibodies against S. sonnei and S. Typhi, and survived lethal intranasal S. sonnei challenge. This paves the way for proposed good manufacturing practices manufacture and clinical trials intended to test the clinical effectiveness of Ty21a-AR-Ss in protecting against S. sonnei shigellosis and typhoid fever, as compared with the current Ty21a vaccine. © The Author 2016. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail journals.permissions@oup.com.

  11. Attenuated Mycobacterium tuberculosis SO2 vaccine candidate is unable to induce cell death.

    Directory of Open Access Journals (Sweden)

    Adriana Aporta

    Full Text Available It has been proposed that Mycobacterium tuberculosis virulent strains inhibit apoptosis and trigger cell death by necrosis of host macrophages to evade innate immunity, while non-virulent strains induce typical apoptosis activating a protective host response. As part of the characterization of a novel tuberculosis vaccine candidate, the M. tuberculosis phoP mutant SO2, we sought to evaluate its potential to induce host cell death. The parental M. tuberculosis MT103 strain and the current vaccine against tuberculosis Bacillus Calmette-Guérin (BCG were used as comparators in mouse models in vitro and in vivo. Our data reveal that attenuated SO2 was unable to induce apoptotic events neither in mouse macrophages in vitro nor during lung infection in vivo. In contrast, virulent MT103 triggers typical apoptotic events with phosphatidylserine exposure, caspase-3 activation and nuclear condensation and fragmentation. BCG strain behaved like SO2 and did not induce apoptosis. A clonogenic survival assay confirmed that viability of BCG- or SO2-infected macrophages was unaffected. Our results discard apoptosis as the protective mechanism induced by SO2 vaccine and provide evidence for positive correlation between classical apoptosis induction and virulent strains, suggesting apoptosis as a possible virulence determinant during M. tuberculosis infection.

  12. Biodistribution and safety of a live attenuated tetravalent dengue vaccine in the cynomolgus monkey.

    Science.gov (United States)

    Ravel, Guillaume; Mantel, Nathalie; Silvano, Jeremy; Rogue, Alexandra; Guy, Bruno; Jackson, Nicholas; Burdin, Nicolas

    2017-10-13

    The first licensed dengue vaccine is a recombinant, live, attenuated, tetravalent dengue virus vaccine (CYD-TDV; Sanofi Pasteur). This study assessed the biodistribution, shedding, and toxicity of CYD-TDV in a non-human primate model as part of the nonclinical safety assessment program for the vaccine. Cynomolgus monkeys were given one subcutaneous injection of either one human dose (5log 10 CCID 50 /serotype) of CYD-TDV or saline control. Study endpoints included clinical observations, body temperature, body weight, food consumption, clinical pathology, immunogenicity, and post-mortem examinations including histopathology. Viral load, distribution, persistence, and shedding in tissues and body fluids were evaluated by quantitative reverse transcriptase polymerase chain reaction. The subcutaneous administration of CYD-TDV was well tolerated. There were no toxicological findings other than expected minor local reactions at the injection site. A transient low level of CYD-TDV viral RNA was detected in blood and the viral genome was identified primarily at the injection site and in the draining lymph nodes following immunization. These results, together with other data from repeat-dose toxicity and neurovirulence studies, confirm the absence of toxicological concern with CYD-TDV and corroborate clinical study observations. Copyright © 2017 Elsevier Ltd. All rights reserved.

  13. Old Disease and New Challenges: Major Obstacles of Current Strategies in the Prevention of Pertussis

    Science.gov (United States)

    Sedighi, Iraj; Karimi, Abdollah; Amanati, Ali

    2016-01-01

    Context Universal immunization against Bordetella pertussis has partially controlled the burden of the disease and its transmission. However, according to recent data, the epidemiology of this vaccine-preventable disease has changed. Now, younger infants, adolescents, and adults are at greater risk of infection. This article has studied the interaction between the various factors involved in the changing epidemiology of pertussis and the major obstacles faced by the current strategies in its prevention. Evidence Acquisition In this narrative review, the most recently published sources of information on pertussis control measures, consisting of textbooks and articles, have been reviewed. We focused on the more recent data about the changing epidemiology or pertussis in Scopus through the use of the MeSH-term words [pertussis] or [whooping cough] and [epidemiology] or [outbreak] or [resurgence], but our search was not restricted to this particular strategy; we also tried to find all of the most recent available data in the general field through other means. Results Primary and booster doses of the pertussis vaccine seem to partially control transmission of the disease, but despite the different preventive strategies available, pertussis continues to cause mortality and morbidity among high-risk groups. Conclusions Adding booster doses of acellular pertussis vaccine to the current national immunization practices with whole-cell vaccines for young adults and pregnant women seems to be a good option for controlling mortality and morbidity among high-risk groups such as very young infants. PMID:27729960

  14. Pertussis outbreak in Polish shooters with adverse event analysis

    Directory of Open Access Journals (Sweden)

    Monika Skrzypiec-Spring

    2017-04-01

    Full Text Available In addition to different injuries, infections are the most common reason for giving up training altogether or reducing its volume and intensity, as well as a lack of opportunities to participate in sports competitions. Nowadays, a slow but constant re‑emergence of pertussis, especially among teenagers and young adults, including athletes, can be observed. This paper describes an outbreak of pertussis among professional Polish shooters, focusing on the transmission of Bordetella pertussis infection between members of the national team, its influence on performance capacity and adverse event analysis. From 9 June, 2015 to 31 July, 2015, a total of 4 confirmed and suspected cases of pertussis were reported among members of the Polish Sport Shooting National Team, their relatives and acquaintances. Pertussis significantly decreased exercise performance of the first athlete, a 35-year-old woman, interrupted her training, and finally resulted in failure to win a medal or quota place. Pertussis also significantly decreased performance of the second athlete, a 25-year-old shooter. The other cases emerged in their families. Whooping cough is a real threat to athletes and should be prevented. Preventive measures include appropriate immunization, constant medical supervision, as well as early isolation, diagnostic tests and treatment of all infected sport team members. Regular administration of booster doses of the acellular pertussis vaccine (Tdpa every 5 years seems reasonable.

  15. Evidence of Increase in Mortality After the Introduction of Diphtheria–Tetanus–Pertussis Vaccine to Children Aged 6–35 Months in Guinea-Bissau: A Time for Reflection?

    Directory of Open Access Journals (Sweden)

    Peter Aaby

    2018-03-01

    Full Text Available BackgroundWhole-cell diphtheria–tetanus–pertussis (DTP and oral polio vaccine (OPV were introduced to children in Guinea-Bissau in 1981. We previously reported that DTP in the target age group from 3 to 5 months of age was associated with higher overall mortality. DTP and OPV were also given to older children and in this study we tested the effect on mortality in children aged 6–35 months.MethodsIn the 1980s, the suburb Bandim in the capital of Guinea-Bissau was followed with demographic surveillance and tri-monthly weighing sessions for children under 3 years of age. From June 1981, routine vaccinations were offered at the weighing sessions. We calculated mortality hazard ratio (HR for DTP-vaccinated and DTP-unvaccinated children aged 6–35 months using Cox proportional hazard models. Including this study, the introduction of DTP vaccine and child mortality has been studied in three studies; we made a meta-estimate of these studies.ResultsAt the first weighing session after the introduction of vaccines, 6–35-month-old children who received DTP vaccination had better weight-for-age z-scores (WAZ than children who did not receive DTP; one unit increase in WAZ was associated with an odds ratio of 1.32 (95% CI = 1.13–1.55 for receiving DTP vaccination. Though lower mortality compared with not being DTP-vaccinated was, therefore, expected, DTP vaccination was associated with a non-significant trend in the opposite direction, the HR being 2.22 (0.82–6.04 adjusted for WAZ. In a sensitivity analysis, including all children weighed at least once before the vaccination program started, DTP (±OPV as the most recent vaccination compared with live vaccines or no vaccine was associated with a HR of 1.89 (1.00–3.55. In the three studies of the introduction of DTP in rural and urban Guinea-Bissau, DTP-vaccinated children had an HR of 2.14 (1.42–3.23 compared to DTP-unvaccinated children; this effect was separately significant for

  16. Pan-Influenza A Protection by Prime-Boost Vaccination with Cold-Adapted Live-Attenuated Influenza Vaccine in a Mouse Model.

    Science.gov (United States)

    Jang, Yo Han; Kim, Joo Young; Byun, Young Ho; Son, Ahyun; Lee, Jeong-Yoon; Lee, Yoon Jae; Chang, Jun; Seong, Baik Lin

    2018-01-01

    Influenza virus infections continually pose a major public health threat with seasonal epidemics and sporadic pandemics worldwide. While currently licensed influenza vaccines provide only strain-specific protection, antigenic drift and shift occasionally render the viruses resistant to the host immune responses, which highlight the need for a vaccine that provides broad protection against multiple subtypes. In this study, we suggest a vaccination strategy using cold-adapted, live attenuated influenza vaccines (CAIVs) to provide a broad, potent, and safe cross-protection covering antigenically distinct hemagglutinin (HA) groups 1 and 2 influenza viruses. Using a mouse model, we tested different prime-boost combinations of CAIVs for their ability to induce humoral and T-cell responses, and protective efficacy against H1 and H5 (HA group 1) as well as H3 and H7 (HA group 2) influenza viruses. Notably, even in the absence of antibody-mediated neutralizing activity or HA inhibitory activity in vitro , CAIVs provided a potent protection against heterologous and heterosubtypic lethal challenges in vivo . Heterologous combination of prime (H1)-boost (H5) vaccine strains showed the most potent cross-protection efficacy. In vivo depletion experiments demonstrated not only that T cells and natural killer cells contributed to the cross-protection, but also the involvement of antibody-dependent mechanisms for the cross-protection. Vaccination-induced antibodies did not enhance the infectivity of heterologous viruses, and prime vaccination did not interfere with neutralizing antibody generation by the boost vaccination, allaying vaccine safety concerns associated with heterogeneity between the vaccines and challenge strains. Our data show that CAIV-based strategy can serve as a simple but powerful option for developing a "truly" universal influenza vaccine providing pan-influenza A protection, which has not been achieved yet by other vaccine strategies. The promising results

  17. Pan-Influenza A Protection by Prime–Boost Vaccination with Cold-Adapted Live-Attenuated Influenza Vaccine in a Mouse Model

    Science.gov (United States)

    Jang, Yo Han; Kim, Joo Young; Byun, Young Ho; Son, Ahyun; Lee, Jeong-Yoon; Lee, Yoon Jae; Chang, Jun; Seong, Baik Lin

    2018-01-01

    Influenza virus infections continually pose a major public health threat with seasonal epidemics and sporadic pandemics worldwide. While currently licensed influenza vaccines provide only strain-specific protection, antigenic drift and shift occasionally render the viruses resistant to the host immune responses, which highlight the need for a vaccine that provides broad protection against multiple subtypes. In this study, we suggest a vaccination strategy using cold-adapted, live attenuated influenza vaccines (CAIVs) to provide a broad, potent, and safe cross-protection covering antigenically distinct hemagglutinin (HA) groups 1 and 2 influenza viruses. Using a mouse model, we tested different prime–boost combinations of CAIVs for their ability to induce humoral and T-cell responses, and protective efficacy against H1 and H5 (HA group 1) as well as H3 and H7 (HA group 2) influenza viruses. Notably, even in the absence of antibody-mediated neutralizing activity or HA inhibitory activity in vitro, CAIVs provided a potent protection against heterologous and heterosubtypic lethal challenges in vivo. Heterologous combination of prime (H1)–boost (H5) vaccine strains showed the most potent cross-protection efficacy. In vivo depletion experiments demonstrated not only that T cells and natural killer cells contributed to the cross-protection, but also the involvement of antibody-dependent mechanisms for the cross-protection. Vaccination-induced antibodies did not enhance the infectivity of heterologous viruses, and prime vaccination did not interfere with neutralizing antibody generation by the boost vaccination, allaying vaccine safety concerns associated with heterogeneity between the vaccines and challenge strains. Our data show that CAIV-based strategy can serve as a simple but powerful option for developing a “truly” universal influenza vaccine providing pan-influenza A protection, which has not been achieved yet by other vaccine strategies. The promising

  18. Live-Attenuated Bacterial Vectors: Tools for Vaccine and Therapeutic Agent Delivery

    Directory of Open Access Journals (Sweden)

    Ivan Y. C. Lin

    2015-11-01

    Full Text Available Genetically attenuated microorganisms, including pathogenic and commensal bacteria, can be engineered to carry and deliver heterologous antigens to elicit host immunity against both the vector as well as the pathogen from which the donor gene is derived. These live attenuated bacterial vectors have been given much attention due to their capacity to induce a broad range of immune responses including localized mucosal, as well as systemic humoral and/or cell-mediated immunity. In addition, the unique tumor-homing characteristics of these bacterial vectors has also been exploited for alternative anti-tumor vaccines and therapies. In such approach, tumor-associated antigen, immunostimulatory molecules, anti-tumor drugs, or nucleotides (DNA or RNA are delivered. Different potential vectors are appropriate for specific applications, depending on their pathogenic routes. In this review, we survey and summarize the main features of the different types of live bacterial vectors and discussed the clinical applications in the field of vaccinology. In addition, different approaches for using live attenuated bacterial vectors for anti-cancer therapy is discussed, and some promising pre-clinical and clinical studies in this field are outlined.

  19. [Pertussis trend in children under one year of age in the Czech Republic in 1997-2013].

    Science.gov (United States)

    Fabiánová, K; Šebestová, H; Beneš, Č; Zavadilová, J; Křížová, P; Kříž, B

    2014-11-01

    To characterize the epidemiological situation of pertussis in children under one year of age in the Czech Republic in 1997-2013. The study cohort consisted of children under one year of age with laboratory confirmed pertussis reported to the communicable disease system from 1997 to 2013. A total of 265 pertussis cases were reported in children under one year of age over the study period. Selected demographic data, need for hospitalization, and vaccination history were evaluated in the study cohort. Children under one year of age have shown a steady upward trend in reported cases of pertussis since the 1990s. The reported incidence of pertussis in this age group was the lowest in 1998 (1.1/100,000 population) and the highest in 2013 (31.3/100,000). In 1997-2013, 265 pertussis cases were reported in children under one year of age, 128 females and 137 males, to the communicable disease system in the Czech Republic. Most of these children, nearly 77%, developed pertussis within the first four months of life. Of the 265 children, 79% were not vaccinated before the onset of the disease and 21% were immunized with at least one dose of pertussis vaccine before developing the disease. As many as 75% of the children with pertussis needed hospitalization. Most of them, nearly 81%, were hospitalized with pertussis in the first four months of life and 90% of them in the first six months of life. In 1997-2013, an upward trend was observed in pertussis cases in children under one year of age. Most children developed the disease within the first four months of life while not vaccinated against pertussis. This fact unambiguously supports the "cocoon" strategy, i.e. vaccination of the closest contacts of the child, and a booster dose at 25 years of age. At the same time, a question arises whether to provide vaccination to pregnant women.

  20. Molecularly engineered live-attenuated chimeric West Nile/dengue virus vaccines protect rhesus monkeys from West Nile virus

    International Nuclear Information System (INIS)

    Pletnev, Alexander G.; St Claire, Marisa; Elkins, Randy; Speicher, Jim; Murphy, Brian R.; Chanock, Robert M.

    2003-01-01

    Two molecularly engineered, live-attenuated West Nile virus (WN) vaccine candidates were highly attenuated and protective in rhesus monkeys. The vaccine candidates are chimeric viruses (designated WN/DEN4) bearing the membrane precursor and envelope protein genes of WN on a backbone of dengue 4 virus (DEN4) with or without a deletion of 30 nucleotides (Δ30) in the 3' noncoding region of DEN4. Viremia in WN/DEN4- infected monkeys was reduced 100-fold compared to that in WN- or DEN4-infected monkeys. WN/DEN4-3'Δ30 did not cause detectable viremia, indicating that it is even more attenuated for monkeys. These findings indicate that chimerization itself and the presence of the Δ30 mutation independently contribute to the attenuation phenotype for nonhuman primates. Despite their high level of attenuation in monkeys, the chimeras induced a moderate-to-high titer of neutralizing antibodies and prevented viremia in monkeys challenged with WN. The more attenuated vaccine candidate, WN/DEN4-3'Δ30, will be evaluated first in our initial clinical studies

  1. Preventing Pertussis (Whooping Cough)

    Science.gov (United States)

    ... causes a whooping sound. They may gag on mucus and throw up after they cough. Not every ... your baby through the placenta and your breast milk. Your baby can get protection from pertussis for ...

  2. Pertussis Frequently Asked Questions

    Science.gov (United States)

    ... driving force behind the large scale outbreaks or epidemics. However, their parents are putting them at greater risk of getting a serious pertussis infection and then possibly spreading it to other family or community members. We ...

  3. Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

    Energy Technology Data Exchange (ETDEWEB)

    Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver [Robert Koch-Institut, Berlin (Germany); Plesker, Roland; Coulibaly, Cheick; Cichutek, Klaus; Mühlebach, Michael D. [Paul-Ehrlich-Institut, Langen (Germany); Bannert, Norbert; Kurth, Reinhard [Robert Koch-Institut, Berlin (Germany); Norley, Stephen, E-mail: NorleyS@rki.de [Robert Koch-Institut, Berlin (Germany)

    2016-02-15

    Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.

  4. Suppressing active replication of a live attenuated simian immunodeficiency virus vaccine does not abrogate protection from challenge

    International Nuclear Information System (INIS)

    Gabriel, Benjamin; Fiebig, Uwe; Hohn, Oliver; Plesker, Roland; Coulibaly, Cheick; Cichutek, Klaus; Mühlebach, Michael D.; Bannert, Norbert; Kurth, Reinhard; Norley, Stephen

    2016-01-01

    Although safety concerns preclude the use of live attenuated HIV vaccines in humans, they provide a useful system for identifying the elusive correlates of protective immunity in the SIV/macaque animal model. However, a number of pieces of evidence suggest that protection may result from prior occupancy of susceptible target cells by the vaccine virus rather than the immune response. To address this, we developed a Nef-deletion variant of an RT-SHIV whose active replication could be shut off by treatment with RT-inhibitors. Groups of macaques were inoculated with the ∆Nef-RT-SHIV and immune responses allowed to develop before antiretroviral treatment and subsequent challenge with wild-type SIVmac239. Vaccinated animals either resisted infection fully or significantly controlled the subsequent viremia. However, there was no difference between animals undergoing replication of the vaccine virus and those without. This strongly suggests that competition for available target cells does not play a role in protection. - Highlights: • A Nef-deleted RT-SHIV was used as a live attenuated vaccine in macaques. • Vaccine virus replication was shut down to investigate its role in protection. • Ongoing vaccine virus replication did not appear to be necessary for protection. • An analysis of T- and B-cell responses failed to identify a correlate of protection.

  5. Protective efficacy of a live attenuated anti-coccidial vaccine administered to 1-day-old chickens.

    Science.gov (United States)

    Crouch, C F; Andrews, S J; Ward, R G; Francis, M J

    2003-06-01

    The efficacy of a live attenuated anti-coccidial vaccine, Paracox-5, administered to 1-day-old chicks was investigated by assessing protection against changes in weight gain following virulent challenge. Vaccinated birds were challenged independently 28 days later with each of the component species (Eimeria acervulina, Eimeria maxima, Eimeria mitis or Eimeria tenella), and protection was demonstrated against associated reduction in weight gain and lesion formation. In addition, an improvement in bird performance, in terms of feed conversion ratio, was also observed following vaccination. Furthermore, under conditions designed to more closely mimic those in the field and using hatchery spray administration, protection against a mixed virulent challenge introduced by 'seeder birds' was demonstrated evenly across a flock of broiler birds within 21 days after vaccination. These data demonstrate that Paracox-5 vaccine will protect broiler chickens against the adverse effects on performance induced by Eimeria spp.

  6. Live, Attenuated Influenza A H5N1 Candidate Vaccines Provide Broad Cross-Protection in Mice and Ferrets

    Science.gov (United States)

    Mills, Kimberly L; Jin, Hong; Duke, Greg; Lu, Bin; Luke, Catherine J; Murphy, Brian; Swayne, David E; Kemble, George; Subbarao, Kanta

    2006-01-01

    Background Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic. Methods and Findings Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA) and a wild-type (wt) N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca) influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2), were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 106 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3) that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses. Conclusions The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans. PMID:16968127

  7. Live, attenuated influenza A H5N1 candidate vaccines provide broad cross-protection in mice and ferrets.

    Directory of Open Access Journals (Sweden)

    Amorsolo L Suguitan

    2006-09-01

    Full Text Available Recent outbreaks of highly pathogenic influenza A H5N1 viruses in humans and avian species that began in Asia and have spread to other continents underscore an urgent need to develop vaccines that would protect the human population in the event of a pandemic.Live, attenuated candidate vaccines possessing genes encoding a modified H5 hemagglutinin (HA and a wild-type (wt N1 neuraminidase from influenza A H5N1 viruses isolated in Hong Kong and Vietnam in 1997, 2003, and 2004, and remaining gene segments derived from the cold-adapted (ca influenza A vaccine donor strain, influenza A/Ann Arbor/6/60 ca (H2N2, were generated by reverse genetics. The H5N1 ca vaccine viruses required trypsin for efficient growth in vitro, as predicted by the modification engineered in the gene encoding the HA, and possessed the temperature-sensitive and attenuation phenotypes specified by the internal protein genes of the ca vaccine donor strain. More importantly, the candidate vaccines were immunogenic in mice. Four weeks after receiving a single dose of 10(6 50% tissue culture infectious doses of intranasally administered vaccines, mice were fully protected from lethality following challenge with homologous and antigenically distinct heterologous wt H5N1 viruses from different genetic sublineages (clades 1, 2, and 3 that were isolated in Asia between 1997 and 2005. Four weeks after receiving two doses of the vaccines, mice and ferrets were fully protected against pulmonary replication of homologous and heterologous wt H5N1 viruses.The promising findings in these preclinical studies of safety, immunogenicity, and efficacy of the H5N1 ca vaccines against antigenically diverse H5N1 vaccines provide support for their careful evaluation in Phase 1 clinical trials in humans.

  8. Cost of production of live attenuated dengue vaccines: a case study of the Instituto Butantan, Sao Paulo, Brazil.

    Science.gov (United States)

    Mahoney, R T; Francis, D P; Frazatti-Gallina, N M; Precioso, A R; Raw, I; Watler, P; Whitehead, P; Whitehead, S S

    2012-07-06

    A vaccine to prevent dengue disease is urgently needed. Fortunately, a few tetravalent candidate vaccines are in the later stages of development and show promise. But, if the cost of these candidates is too high, their beneficial potential will not be realized. The price of a vaccine is one of the most important factors affecting its ultimate application in developing countries. In recent years, new vaccines such as those for human papilloma virus and pneumococcal disease (conjugate vaccine) have been introduced with prices in developed countries exceeding $50 per dose. These prices are above the level affordable by developing countries. In contrast, other vaccines such as those against Japanese encephalitis (SA14-14-2 strain vaccine) and meningitis type A have prices in developing countries below one dollar per dose, and it is expected that their introduction and use will proceed more rapidly. Because dengue disease is caused by four related viruses, vaccines must be able to protect against all four. Although there are several live attenuated dengue vaccine candidates under clinical evaluation, there remains uncertainty about the cost of production of these tetravalent vaccines, and this uncertainty is an impediment to rapid progress in planning for the introduction and distribution of dengue vaccines once they are licensed. We have undertaken a detailed economic analysis, using standard industrial methodologies and applying generally accepted accounting practices, of the cost of production of a live attenuated vaccine, originally developed at the US National Institutes of Health (National Institute of Allergy and Infectious Diseases), to be produced at the Instituto Butantan in Sao Paulo, Brazil. We determined direct costs of materials, direct costs of personnel and labor, indirect costs, and depreciation. These were analyzed assuming a steady-state production of 60 million doses per year. Although this study does not seek to compute the price of the final

  9. Molecular epidemiology of Bordetella pertussis in Cambodia determined by direct genotyping of clinical specimens.

    Science.gov (United States)

    Moriuchi, Takumi; Vichit, Ork; Vutthikol, Yong; Hossain, Md Shafiqul; Samnang, Chham; Toda, Kohei; Grabovac, Varja; Hiramatsu, Yukihiro; Otsuka, Nao; Shibayama, Keigo; Kamachi, Kazunari

    2017-09-01

    This study sought to determine the genotypes of circulating Bordetella pertussis, the causative agent of pertussis, in Cambodia by direct molecular typing of clinical specimens. DNA extracts from nasopharyngeal swabs obtained from 82 pertussis patients in 2008-2016 were analyzed by multilocus variable-number tandem repeat analysis (MLVA). B. pertussis virulence-associated allelic genes (ptxA, prn, and fim3) and the pertussis toxin promoter ptxP were also investigated by DNA sequence-based typing. Forty-four DNA extracts (54%) yielded a complete MLVA profile, and these were sorted into 8 MLVA types (MT18, MT26, MT27, MT29, MT43, MT72, MT95, and MT200). MT27 and MT29, which are common in developed countries, were the predominant strain types (total 73%). The predominant profile of virulence-associated allelic genes was the combination of ptxP3/ptxA1/prn2/fim3A (48%). MT27 strains were detected during the entire study period, whereas MT29 strains were only found in 2014-2016. The B. pertussis population in Cambodia, where a whole-cell pertussis vaccine (WCV) has been continuously used, resembled those observed previously in developed countries where acellular pertussis vaccines are used. Circulating B. pertussis strains in Cambodia were distinct from those in other countries using WCVs. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  10. Updated data on effective and safe immunizations with live-attenuated vaccines for children after living donor liver transplantation.

    Science.gov (United States)

    Shinjoh, Masayoshi; Hoshino, Ken; Takahashi, Takao; Nakayama, Tetsuo

    2015-01-29

    Although immunizations using live-attenuated vaccines are not recommended for children post-liver transplant due to their theoretical risks, they will inevitably encounter vaccine-preventable viral diseases upon returning to real-life situations. The window of opportunity for vaccination is usually limited prior to transplantation because these children often have unstable disease courses. Also, vaccine immunity does not always persist after transplantation. Beginning in 2002, subcutaneous immunizations with four individual live-attenuated vaccines (measles, rubella, varicella, and mumps) to pediatric patients following living donor liver transplantation (LDLT) were performed for those who fulfilled the clinical criteria, including humoral and cell-mediated immunity. Written informed consent was collected. We included the study on 70 immunizations for 18 cases that we reported in 2008 (Shinjoh et al., 2008). A total of 196 immunizations were administered to 48 pediatric post-LDLT recipients. Of these, 144 were first immunizations and 52 were repeated immunizations following LDLT. The seroconversion rates at the first dose for measles (AIK-C), rubella (TO-336), varicella (Oka), and mumps (Hoshino) were 100% (36/36), 100% (35/35), 70% (23/33), and 75% (24/32), respectively. Antibody levels did not fall over time in patients immunized with rubella vaccine. Three mild cases of breakthrough varicella were observed. Two cases with transient parotid gland swelling were observed after mumps immunization. Two admissions because of fever at 2-3 weeks after the measles vaccine were reported but the patients had no symptoms of measles. Immunizations using selected live-attenuated vaccines were safe and effective for post-LDLT children who were not severely immunosuppressed. However, with the exception of rubella, repeated immunization may be necessary. Copyright © 2014 Elsevier Ltd. All rights reserved.

  11. PENETAPAN STANDAR NASIONAL DARI VAKSIN DPT: Penetapan Standar Nasional Vaksin Pertussis

    Directory of Open Access Journals (Sweden)

    Muljanti Prijanto

    2012-09-01

    Full Text Available To check the potency of DPT vaccine, standard preparations of the components, namely Adsorbed Diphtheria Toxoid, Pertussis Vaccine, and Adsorbed Tetanus Toxoid are necessary. Since WHO International Standard Preparations are distributed only in limited amounts, WHO has suggested that each member country shold develop a National Standard, which is to be matched with International Standard Preparations. An Indonesian National Standard of DPT vaccine (lot 1 has been prepared and lyophilized at the National Institute of Health in Tokyo. The potency of the National Standard of Pertussis Vaccine was determined by Active Mouse Protection Test (AMPT. After several experiments, the potency of the National Standard of Pertussis Vaccine has been decided of being 12 IU/ml. Using the same standard preparations, namely the National Standards, it is hoped that from a lot of DPT vaccine, similar results of potency could be achieved when determined by Government Vaccine Quality Control laboratory and the Manufacturer's laboratory.

  12. Characterization of two Achromobacter xylosoxidans isolates from patients with pertussis-like symptoms

    Institute of Scientific and Technical Information of China (English)

    Fiorella Orellana-Peralta; Michelle Jacinto; Maria J Pons; Cludia Gomes; Carlos Bada; Isabel Reyes; Juana del Valle Mendoza; Joaquim Ruiz

    2015-01-01

    Objective:To characterize two Achromobacter xylosoxidans recovered from 2 patients diagnosed with pertussis during a Bordetella pertussis surveillance program. Methods:Nasopharyngeal swabs from 2 children under 1 year of age with clinical suspicion of pertussis were analyzed by culture and PCR. Results:Two Achromobacter xylosoxidans A8, closely related to Bordetella spp. were recovered from 2 patients diagnosed of pertussis, both carrying the ptxA gene and IS418 the pertussis toxin encoding gene. Subsequently, antibiotic susceptibility was evaluated by disk-diffusion method and by PCR. Conclusions:Although more detailed studies are needed, the present data highlight the possibility that Achromobacter xylosoxidans, closely related Bordetella pertussis microorganisms and not covered under the vaccine umbrella, might also result in cases of whooping cough. Thereby further surveillance is necessary to determine the extension and relevance of their pathogenic role in order to discriminate their real public health implication.

  13. Whooping cough in Pakistan: Bordetella pertussis vs Bordetella parapertussis in 2005-2009.

    Science.gov (United States)

    Bokhari, Habib; Said, Fahad; Syed, Muhammad A; Mughal, Amjad; Kazi, Yasmeen F; Heuvelman, Kees; Mooi, Frits R

    2011-10-01

    Pertussis, or whooping cough, is an acute respiratory disease mainly affecting infants and children and is caused by Bordetella pertussis and Bordetella parapertussis. The aim of this study was to investigate the share of Bordetella species from potential whooping cough cases during 2005-2009. Eight hundred and two samples from suspected pertussis cases were collected, mainly from 2 provinces of Pakistan. Bacterial culture, identification, DNA extraction and routinely used polymerase chain reaction (PCR) methods using IS1001, IS1002 and IS481 were used to identify the Bordetella species. The results were unexpected, because all of the isolates collected from the different cities were identified as B. parapertussis (7.4%); B. pertussis was not isolated from any sample. However, PCR results indicated the presence of a small percentage (0.6%) of B. pertussis among the total cases studied. This study suggests that vaccines to protect against both B. pertussis and B. parapertussis should be considered.

  14. Assessing the Evidence for Maternal Pertussis Immunization: A Report From the Bill & Melinda Gates Foundation Symposium on Pertussis Infant Disease Burden in Low- and Lower-Middle-Income Countries.

    Science.gov (United States)

    Sobanjo-Ter Meulen, Ajoke; Duclos, Philippe; McIntyre, Peter; Lewis, Kristen D C; Van Damme, Pierre; O'Brien, Katherine L; Klugman, Keith P

    2016-12-01

    Implementation of effective interventions has halved maternal and child mortality over the past 2 decades, but less progress has been made in reducing neonatal mortality. Almost 45% of under-5 global mortality now occurs in infants <1 month of age, with approximately 86% of neonatal deaths occurring in low- and lower-middle-income countries (LMICs). As an estimated 23% of neonatal deaths globally are due to infectious causes, maternal immunization (MI) is one intervention that may reduce mortality in the first few months of life, when direct protection often relies on passively transmitted maternal antibodies. Despite all countries including pertussis-containing vaccines in their routine childhood immunization schedules, supported through the Expanded Programme on Immunization, pertussis continues to circulate globally. Although based on limited robust epidemiologic data, current estimates derived from modeling implicate pertussis in 1% of under-5 mortality, with infants too young to be vaccinated at highest risk of death. Pertussis MI programs have proven effective in reducing infant pertussis mortality in high-income countries using tetanus-diphtheria-acellular pertussis (Tdap) vaccines in their maternal and infant programs; however, these vaccines are cost-prohibitive for routine use in LMICs. The reach of antenatal care programs to deliver maternal pertussis vaccines, particularly with respect to infants at greatest risk of pertussis, needs to be further evaluated. Recognizing that decisions on the potential impact of pertussis MI in LMICs need, as a first step, robust contemporary mortality data for early infant pertussis, a symposium of global key experts was held. The symposium reviewed current evidence and identified knowledge gaps with respect to the infant pertussis disease burden in LMICs, and discussed proposed strategies to assess the potential impact of pertussis MI. © The Author 2016. Published by Oxford University Press for the Infectious Diseases

  15. Post-marketing safety surveillance for inactivated and live-attenuated Japanese encephalitis vaccines in China, 2008-2013.

    Science.gov (United States)

    Wu, Wendi; Liu, Dawei; Li, Keli; Nuorti, J Pekka; Nohynek, Hanna M; Xu, Disha; Ye, Jiakai; Zheng, Jingshan; Wang, Huaqing

    2017-06-22

    Two types of Japanese encephalitis (JE) vaccines, inactivated JE vaccine (JE-I) and live-attenuated JE vaccine (JE-L), are available and used in China. In particular, one JE-L, produced by a domestic manufacturer in China, was prequalified by WHO in 2013. We assessed the safety of JE vaccines in China during 2008-2013 using the Chinese National Adverse Events Following Immunization Information System (CNAEFIS) data. We retrieved AEFI reporting data about JE vaccines from CNAEFIS, 2008-2013, examined demographic characteristics of AEFI cases, and used administrative data on vaccine doses as denominator to calculate and compare crude reporting rates. We also used disproportionality reporting analysis between JE-I and JE-L to assess potential safety signals. A total of 34,879 AEFIs related with JE-I and JE-L were reported, with a ratio of male to female as 1.3:1; 361 (1.0%) cases were classified as serious. JE vaccines were administered concurrently with one or more other vaccines in 13,592 (39.0%) of cases. The overall AEFI reporting rates were 214.4 per million vaccination doses for JE-L and 176.9 for JE-I (rate ratio [RR]: 1.2, 95% confidence interval [CI]: 1.1-1.3) in 2010-2013. Febrile convulsions (FC) following JE-I was found as a signal of disproportionate reporting (SDR). However, there was no significant difference between the reporting rates of FC of JE-I and JE-L (0.3 per million vaccination doses for JE-L, 0.4 for JE-I, p=0.05). While our analysis did not find apparent safety concern of JE vaccines in China, further study should consider JE-I vaccines and febrile convulsion, and taking more sensitive methods to detect signals. Copyright © 2017. Published by Elsevier Ltd.

  16. Characterization of field isolates of Suid herpesvirus 1 (Aujeszky's disease virus) as derivatives of attenuated vaccine strains

    DEFF Research Database (Denmark)

    Christensen, Laurids Siig; Medveczky, I.; Strandbygaard, Bertel

    1992-01-01

    Field isolates of suid herpesvirus 1 (Aujeszky's disease virus) from Poland and Hungary were identified by restriction fragment pattern analysis as derivatives of attenuated vaccine strains. The Polish isolates were found to be related to the BUK-TK-900 strain (Suivac A) which is widely used...

  17. Generation and Characterization of Live Attenuated Influenza A(H7N9 Candidate Vaccine Virus Based on Russian Donor of Attenuation.

    Directory of Open Access Journals (Sweden)

    Svetlana Shcherbik

    Full Text Available Avian influenza A (H7N9 virus has emerged recently and continues to cause severe disease with a high mortality rate in humans prompting the development of candidate vaccine viruses. Live attenuated influenza vaccines (LAIV are 6:2 reassortant viruses containing the HA and NA gene segments from wild type influenza viruses to induce protective immune responses and the six internal genes from Master Donor Viruses (MDV to provide temperature sensitive, cold-adapted and attenuated phenotypes.LAIV candidate A/Anhui/1/2013(H7N9-CDC-LV7A (abbreviated as CDC-LV7A, based on the Russian MDV, A/Leningrad/134/17/57 (H2N2, was generated by classical reassortment in eggs and retained MDV temperature-sensitive and cold-adapted phenotypes. CDC-LV7A had two amino acid substitutions N123D and N149D (H7 numbering in HA and one substitution T10I in NA. To evaluate the role of these mutations on the replication capacity of the reassortants in eggs, the recombinant viruses A(H7N9RG-LV1 and A(H7N9RG-LV2 were generated by reverse genetics. These changes did not alter virus antigenicity as ferret antiserum to CDC-LV7A vaccine candidate inhibited hemagglutination by homologous A(H7N9 virus efficiently. Safety studies in ferrets confirmed that CDC-LV7A was attenuated compared to wild-type A/Anhui/1/2013. In addition, the genetic stability of this vaccine candidate was examined in eggs and ferrets by monitoring sequence changes acquired during virus replication in the two host models. No changes in the viral genome were detected after five passages in eggs. However, after ten passages additional mutations were detected in the HA gene. The vaccine candidate was shown to be stable in the ferret model; post-vaccination sequence data analysis showed no changes in viruses collected in nasal washes present at day 5 or day 7.Our data indicate that the A/Anhui/1/2013(H7N9-CDC-LV7A reassortant virus is a safe and genetically stable candidate vaccine virus that is now available for

  18. Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ

    International Nuclear Information System (INIS)

    Barkhouse, Darryll A.; Faber, Milosz; Hooper, D. Craig

    2015-01-01

    Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4 RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment. - Highlights: • IFNγ expression improves attenuated rabies virus safety and immunogenicity. • IFNγ expression is safer and more immunogenic than doubling glycoprotein expression. • Co-infection with IFNγ-expressing RABV prevents wild-type rabies virus lethality. • Vaccine safety and efficacy is additive for IFNγ and double glycoprotein expression

  19. Pre- and post-exposure safety and efficacy of attenuated rabies virus vaccines are enhanced by their expression of IFNγ

    Energy Technology Data Exchange (ETDEWEB)

    Barkhouse, Darryll A. [Department of Cancer Biology, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Faber, Milosz [Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Department of Microbiology and Immunology 1020 Locust St., Jefferson Alumni Hall, Room 465, Philadelphia, PA 19107 (United States); Hooper, D. Craig, E-mail: douglas.hooper@jefferson.edu [Department of Cancer Biology, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Department of Neurological Surgery, 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States); Center for Neurovirology 1020 Locust St., Jefferson Alumni Hall, Room 454, Philadelphia, PA 19107 (United States)

    2015-01-01

    Consistent with evidence of a strong correlation between interferon gamma (IFNγ) production and rabies virus (RABV) clearance from the CNS, we recently demonstrated that engineering a pathogenic RABV to express IFNγ highly attenuates the virus. Reasoning that IFNγ expression by RABV vaccines would enhance their safety and efficacy, we reverse-engineered two proven vaccine vectors, GAS and GASGAS, to express murine IFNγ. Mortality and morbidity were monitored during suckling mice infection, immunize/challenge experiments and mixed intracranial infections. We demonstrate that GASγ and GASγGAS are significantly attenuated in suckling mice compared to the GASGAS vaccine. GASγ better protects mice from lethal DRV4 RABV infection in both pre- and post-exposure experiments compared to GASGAS. Finally, GASγGAS reduces post-infection neurological sequelae, compared to control, during mixed intracranial infection with DRV4. These data show IFNγ expression by a vaccine vector can enhance its safety while increasing its efficacy as pre- and post-exposure treatment. - Highlights: • IFNγ expression improves attenuated rabies virus safety and immunogenicity. • IFNγ expression is safer and more immunogenic than doubling glycoprotein expression. • Co-infection with IFNγ-expressing RABV prevents wild-type rabies virus lethality. • Vaccine safety and efficacy is additive for IFNγ and double glycoprotein expression.

  20. Estimated exposures to perfluorinated compounds in infancy predict attenuated vaccine antibody concentrations at age 5-years

    DEFF Research Database (Denmark)

    Grandjean, Philippe; Heilmann, Carsten; Weihe, Pal

    2017-01-01

    Perfluorinated alkylate substances (PFASs) are highly persistent and may cause immunotoxic effects. PFAS-associated attenuated antibody responses to childhood vaccines may be affected by PFAS exposures during infancy, where breastfeeding adds to PFAS exposures. Of 490 members of a Faroese birth...... cohort, 275 and 349 participated in clinical examinations and provided blood samples at ages 18 months and 5 years. PFAS concentrations were measured at birth and at the clinical examinations. Using information on duration of breastfeeding, serum-PFAS concentration profiles during infancy were estimated......, with decreases by up to about 20% for each two-fold higher exposure, while associations for serum concentrations at ages 18 months and 5 years were weaker. Modeling of serum-PFAS concentration showed levels for age 18 months that were similar to those measured. Concentrations estimated for ages 3 and 6 months...

  1. Screening for viral extraneous agents in live-attenuated avian vaccines by using a microbial microarray and sequencing

    DEFF Research Database (Denmark)

    Olesen, Majken Lindholm; Jørgensen, Lotte Leick; Blixenkrone-Møller, Merete

    2018-01-01

    The absence of extraneous agents (EA) in the raw material used for production and in finished products is one of the principal safety elements related to all medicinal products of biological origin, such as live-attenuated vaccines. The aim of this study was to investigate the applicability...... of the Lawrence Livermore Microbial detection array version 2 (LLMDAv2) combined with whole genome amplification and sequencing for screening for viral EAs in live-attenuated vaccines and specific pathogen-free (SPF) eggs.We detected positive microarray signals for avian endogenous retrovirus EAV-HP and several...... viruses belonging to the Alpharetrovirus genus in all analyzed vaccines and SPF eggs. We used a microarray probe mapping approach to evaluate the presence of intact retroviral genomes, which in addition to PCR analysis revealed that several of the positive microarray signals were most likely due to cross...

  2. Development of live attenuated Streptococcus agalactiae vaccine for tilapia via continuous passage in vitro.

    Science.gov (United States)

    Li, L P; Wang, R; Liang, W W; Huang, T; Huang, Y; Luo, F G; Lei, A Y; Chen, M; Gan, X

    2015-08-01

    Fish Streptococcus agalactiae (S. agalactiae) seriously harms the world's aquaculture industry and causes huge economic losses. This study aimed to develop a potential live attenuated vaccine of S. agalactiae. Pre-screened vaccine candidate strain S. agalactiae HN016 was used as starting material to generate an attenuated strain S. agalactiae YM001 by continuous passage in vitro. The biological characteristics, virulence, and stability of YM001 were detected, and the protective efficacy of YM001 immunization in tilapia was also determined. Our results indicated that the growth, staining, characteristics of pulsed-field gel electrophoresis (PFGE) genotype, and virulence of YM001 were changed significantly as compared to the parental strain HN016. High doses of YM001 by intraperitoneal (IP) injection (1.0 × 10(9) CFU/fish) and oral gavage (1.0 × 10(10) CFU/fish) respectively did not cause any mortality and morbidity in tilapia. The relative percent survivals (RPSs) of fishes immunized with YM001 (1.0 × 10(8) CFU/fish, one time) via injection, immersion, and oral administration were 96.88, 67.22, and 71.81%, respectively, at 15 days, and 93.61, 60.56, and 53.16%, respectively, at 30 days. In all tests with 1-3 times of immunization in tilapia, the dosages at 1 × 10(8) and 1 × 10(9) CFU/fish displayed the similar best results, whereas the immunoprotection of the dosages at 1 × 10(6) and 1 × 10(7) CFU/fish declined significantly (P 0.05). The level of protective antibody elicited by oral immunization was significantly higher compared to that of the control group (P S. agalactiae strain YM001; oral immunization of tilapia with this strain produced a good immune protection. Copyright © 2015 Elsevier Ltd. All rights reserved.

  3. Revaccination of Guinea Pigs With the Live Attenuated Mycobacterium tuberculosis Vaccine MTBVAC Improves BCG's Protection Against Tuberculosis.

    Science.gov (United States)

    Clark, Simon; Lanni, Faye; Marinova, Dessislava; Rayner, Emma; Martin, Carlos; Williams, Ann

    2017-09-01

    The need for an effective vaccine against human tuberculosis has driven the development of different candidates and vaccination strategies. Novel live attenuated vaccines are being developed that promise greater safety and efficacy than BCG against tuberculosis. We combined BCG with the vaccine MTBVAC to evaluate whether the efficacy of either vaccine would be affected upon revaccination. In a well-established guinea pig model of aerosol infection with Mycobacterium tuberculosis, BCG and MTBVAC delivered via various prime-boost combinations or alone were compared. Efficacy was determined by a reduction in bacterial load 4 weeks after challenge. Efficacy data suggests MTBVAC-associated immunity is longer lasting than that of BCG when given as a single dose. Long and short intervals between BCG prime and MTBVAC boost resulted in improved efficacy in lungs, compared with BCG given alone. A shorter interval between MTBVAC prime and BCG boost resulted in improved efficacy in lungs, compared with BCG given alone. A longer interval resulted in protection equivalent to that of BCG given alone. These data indicate that, rather than boosting the waning efficacy of BCG, a vaccination schedule involving a combination of the 2 vaccines yielded stronger immunity to M. tuberculosis infection. This work supports development of MTBVAC use as a revaccination strategy to improve on the effects of BCG in vaccinated people living in tuberculosis-endemic countries. © The Author 2017. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.

  4. Antigenic characterization of a formalin-inactivated poliovirus vaccine derived from live-attenuated Sabin strains.

    Science.gov (United States)

    Tano, Yoshio; Shimizu, Hiroyuki; Martin, Javier; Nishimura, Yorihiro; Simizu, Bunsiti; Miyamura, Tatsuo

    2007-10-10

    A candidate inactivated poliovirus vaccine derived from live-attenuated Sabin strains (sIPV), which are used in the oral poliovirus vaccine (OPV), was prepared in a large-production scale. The modification of viral antigenic epitopes during the formalin inactivation process was investigated by capture ELISA assays using type-specific and antigenic site-specific monoclonal antibodies (MoAbs). The major antigenic site 1 was modified during the formalin inactivation of Sabin 1. Antigenic sites 1-3 were slightly modified during the formalin inactivation of Sabin 2 strain. Sites 1 and 3 were altered on inactivated Sabin 3 virus. These alterations were different to those shown by wild-type Saukett strain, used in conventional IPV (cIPV). It has been previously reported that type 1 sIPV showed higher immunogenicity to type 1 cIPV whereas types 2 and 3 sIPV induced lower level of immunogenicity than their cIPV counterparts. Our results suggest that the differences in epitope structure after formalin inactivation may account, at least in part, for the observed differences in immunogenicity between Sabin and wild-type inactivated poliovaccines.

  5. Safety of live attenuated influenza vaccine in atopic children with egg allergy.

    Science.gov (United States)

    Turner, Paul J; Southern, Jo; Andrews, Nick J; Miller, Elizabeth; Erlewyn-Lajeunesse, Michel

    2015-08-01

    Live attenuated influenza vaccine (LAIV) is an intranasal vaccine recently incorporated into the United Kingdom immunization schedule. However, it contains egg protein and, in the absence of safety data, is contraindicated in patients with egg allergy. Furthermore, North American guidelines recommend against its use in asthmatic children. We sought to assess the safety of LAIV in children with egg allergy. We performed a prospective, multicenter, open-label, phase IV intervention study involving 11 secondary/tertiary centers in the United Kingdom. Children with egg allergy (defined as a convincing clinical reaction to egg within the past 12 months and/or >95% likelihood of clinical egg allergy as per published criteria) were recruited. LAIV was administered under medical supervision, with observation for 1 hour and telephone follow-up 72 hours later. Four hundred thirty-three doses were administered to 282 children with egg allergy (median, 4.9 years; range, 2-17 years); 115 (41%) had experienced prior anaphylaxis to egg. A physician's diagnosis of asthma/recurrent wheezing was noted in 67%, and 51% were receiving regular preventer therapy. There were no systemic allergic reactions (upper 95% CI for population, 1.3%). Eight children experienced mild self-limiting symptoms, which might have been due an IgE-mediated allergic reaction. Twenty-six (9.4%; 95% CI for population, 6.2% to 13.4%) children experienced lower respiratory tract symptoms within 72 hours, including 13 with parent-reported wheeze. None of these episodes required medical intervention beyond routine treatment. In contrast to current recommendations, LAIV appears to be safe for use in children with egg allergy. Furthermore, the vaccine appears to be well tolerated in children with a diagnosis of asthma or recurrent wheeze. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  6. Adult pertussis is unrecognized public health problem in Thailand.

    Science.gov (United States)

    Siriyakorn, Nirada; Leethong, Pornvimol; Tantawichien, Terapong; Sripakdee, Saowalak; Kerdsin, Anusak; Dejsirilert, Surang; Paitoonpong, Leilani

    2016-01-25

    Although pertussis has been considered a disease of childhood, it is also recognized as an important respiratory tract infection in adolescents and adults. However, in countries with routine vaccination against pertussis with high coverage, pertussis is not usually taken into consideration for the etiology of prolonged cough in adults. Previous studies in a variety of populations in developed countries have documented that pertussis is quite common, ranging from 2.9 to 32% of adolescents and adults with prolonged cough. The anticipation and early recognition of this change in the epidemiology is important because the affected adolescents and adults act as reservoirs of the disease and source of infection to the vulnerable population of infants, for whom the disease can be life threatening. We conducted a prospective study to determine the prevalence of pertussis in Thai adults with prolonged cough. Seventy-six adult patients with a cough lasting for more than 2 weeks (range, 14-180 days) were included in the present study. The data regarding medical history and physical examination were carefully analyzed. Nasopharyngeal swabs from all patients were obtained for the detection of deoxyribonucleic acid of Bordetella pertussis by the polymerase chain reaction (PCR) method. Paired serum samples were collected and tested for IgG antibody against pertussis toxin by using an ELISA method. Of 76 adult patients, 14 patients (18.4%) with the mean age of 59 (range, 28-85) years and the mean duration of cough of 34 (range, 14-120) days had laboratory evidence of acute pertussis infection. One patient was diagnosed by the PCR method, while the rest had serological diagnosis. Whooping cough is a significantly associated symptom of patients with chronic cough who had laboratory evidence of pertussis. (p < .05, odds ratio 3.75, 95% confidence interval: 1.00, 14.06) CONCLUSION: Pertussis is being increasingly recognized as a cause of prolonged, distressing cough among adults in

  7. [History of development of the live poliomyelitis vaccine from Sabin attenuated strains in 1959 and idea of poliomyelitis eradication].

    Science.gov (United States)

    Lashkevich, V A

    2013-01-01

    In 1958 Poliomyelitis Institute in Moscow and Institute of Experimental Medicine in St. Petersburg received from A. Sabin the attenuated strains of poliomyelitis virus. The characteristics of the strains were thoroughly studied by A. A. Smorodintsev and coworkers. They found that the virulence of the strains fluctuated slightly in 10 consecutive passages through the intestine of the non-immune children. A part of the Sabin material was used by A. A. Smorodintsev and M. P. Chumakov in the beginning of 1959 for immunizing approximately 40000 children in Estonia, Lithuania, and Latvia. Epidemic poliomyelitis rate in these republics decreased from approximately 1000 cases yearly before vaccination to less than 20 in the third quarter of 1959. This was a convincing proof of the efficacy and safety of the vaccine from the attenuated Sabin strains. In 1959, according to A. Sabin's recommendation, a technology of live vaccine production was developed at the Poliomyelitis Institute, and several experimental lots of vaccine were prepared. In the second part of 1959, 13.5 million children in USSR were immunized. The epidemic poliomyelitis rate decreased 3-5 times in different regions without paralytic cases, which could be attributed to the vaccination. These results were the final proof of high efficiency and safety of live poliomyelitis vaccine from the attenuated Sabin strains. Based on these results, A. Sabin and M. P. Chumakov suggested in 1960 the idea of poliomyelitis eradication using mass immunization of children with live vaccine. 72 million persons up to 20 years old were vaccinated in USSR in 1960 with a 5 times drop in the paralytic rate. 50-year-long use of live vaccine results in poliomyelitis eradication in almost all countries worldwide. More than 10 million children were rescued from the death and palsy. Poliomyelitis eradication in a few countries where it still exists depends not on medical services but is defined by the attitude of their leaders to fight

  8. The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine (Dengvaxia): A Model Comparison Study.

    Science.gov (United States)

    Flasche, Stefan; Jit, Mark; Rodríguez-Barraquer, Isabel; Coudeville, Laurent; Recker, Mario; Koelle, Katia; Milne, George; Hladish, Thomas J; Perkins, T Alex; Cummings, Derek A T; Dorigatti, Ilaria; Laydon, Daniel J; España, Guido; Kelso, Joel; Longini, Ira; Lourenco, Jose; Pearson, Carl A B; Reiner, Robert C; Mier-Y-Terán-Romero, Luis; Vannice, Kirsten; Ferguson, Neil

    2016-11-01

    Large Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia) over the first 25 mo following vaccination. Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-naïve vaccinees. We here report predictions from eight independent modelling groups on the long-term safety, public health impact, and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterised by seroprevalence levels among 9-y-olds (SP9). These predictions were conducted for the World Health Organization to inform their recommendations on optimal use of this vaccine. The models adopted, with small variations, a parsimonious vaccine mode of action that was able to reproduce quantitative features of the observed trial data. The adopted mode of action assumed that vaccination, similarly to natural infection, induces transient, heterologous protection and, further, establishes a long-lasting immunogenic memory, which determines disease severity of subsequent infections. The default vaccination policy considered was routine vaccination of 9-y-old children in a three-dose schedule at 80% coverage. The outcomes examined were the impact of vaccination on infections, symptomatic dengue, hospitalised dengue, deaths, and cost-effectiveness over a 30-y postvaccination period. Case definitions were chosen in accordance with the Phase III trials. All models predicted that in settings with moderate to high dengue endemicity (SP9 ≥ 50%), the default vaccination policy would reduce the burden of dengue disease for the population by 6%-25% (all simulations: -3%-34%) and in high-transmission settings (SP9 ≥ 70%) by 13%-25% (all simulations: 10%- 34%). These endemicity levels are representative of the participating sites in

  9. The Long-Term Safety, Public Health Impact, and Cost-Effectiveness of Routine Vaccination with a Recombinant, Live-Attenuated Dengue Vaccine (Dengvaxia: A Model Comparison Study.

    Directory of Open Access Journals (Sweden)

    Stefan Flasche

    2016-11-01

    Full Text Available Large Phase III trials across Asia and Latin America have recently demonstrated the efficacy of a recombinant, live-attenuated dengue vaccine (Dengvaxia over the first 25 mo following vaccination. Subsequent data collected in the longer-term follow-up phase, however, have raised concerns about a potential increase in hospitalization risk of subsequent dengue infections, in particular among young, dengue-naïve vaccinees. We here report predictions from eight independent modelling groups on the long-term safety, public health impact, and cost-effectiveness of routine vaccination with Dengvaxia in a range of transmission settings, as characterised by seroprevalence levels among 9-y-olds (SP9. These predictions were conducted for the World Health Organization to inform their recommendations on optimal use of this vaccine.The models adopted, with small variations, a parsimonious vaccine mode of action that was able to reproduce quantitative features of the observed trial data. The adopted mode of action assumed that vaccination, similarly to natural infection, induces transient, heterologous protection and, further, establishes a long-lasting immunogenic memory, which determines disease severity of subsequent infections. The default vaccination policy considered was routine vaccination of 9-y-old children in a three-dose schedule at 80% coverage. The outcomes examined were the impact of vaccination on infections, symptomatic dengue, hospitalised dengue, deaths, and cost-effectiveness over a 30-y postvaccination period. Case definitions were chosen in accordance with the Phase III trials. All models predicted that in settings with moderate to high dengue endemicity (SP9 ≥ 50%, the default vaccination policy would reduce the burden of dengue disease for the population by 6%-25% (all simulations: -3%-34% and in high-transmission settings (SP9 ≥ 70% by 13%-25% (all simulations: 10%- 34%. These endemicity levels are representative of the

  10. Multiple antigens of Yersinia pestis delivered by live recombinant attenuated Salmonella vaccine strains elicit protective immunity against plague.

    Science.gov (United States)

    Sanapala, Shilpa; Rahav, Hannah; Patel, Hetal; Sun, Wei; Curtiss, Roy

    2016-05-05

    Based on our improved novel Salmonella vaccine delivery platform, we optimized the recombinant attenuated Salmonella typhimurium vaccine (RASV) χ12094 to deliver multiple Yersinia pestis antigens. These included LcrV196 (amino acids, 131-326), Psn encoded on pYA5383 and F1 encoded in the chromosome, their synthesis did not cause adverse effects on bacterial growth. Oral immunization with χ12094(pYA5383) simultaneously stimulated high antibody titers to LcrV, Psn and F1 in mice and presented complete protection against both subcutaneous (s.c.) and intranasal (i.n.) challenges with high lethal doses of Y. pestis CO92. Moreover, no deaths or other disease symptoms were observed in SCID mice orally immunized with χ12094(pYA5383) over a 60-day period. Therefore, the trivalent S. typhimurium-based live vaccine shows promise for a next-generation plague vaccine. Copyright © 2016 Elsevier Ltd. All rights reserved.

  11. The seroepidemiology of pertussis in Australia during an epidemic period.

    Science.gov (United States)

    Cagney, M; MacIntyre, C R; McIntyre, P; Puech, M; Giammanco, A

    2006-12-01

    Studying the epidemiology of pertussis and impact of differing vaccine schedules is difficult because of differing methods of case ascertainment. The advent of internationally standardized serological diagnosis for recent infection has allowed comparison of age-specific pertussis infection among European countries and was applied in Australia at the time of a major national epidemic. In 1997 and 1998, a nationally representative serum bank using residual sera from diagnostic laboratories was established. Measurement of pertussis toxin (PT) IgG level was conducted by a reference laboratory using an enzyme-linked immunosorbent assay standardized for a number of European countries. A titre of 125 EU/ml was interpreted as indicative of recent pertussis infection. The serological data were correlated with age, gender, region and disease epidemiology in Australia. The highest prevalence of recent pertussis infection was in the 5-9 years age group, and the lowest in 1-4 and 25-64 years age groups. In the 5-14 years age group, 29.7% (5-9 years) and 14.6% (10-14 years) of the sample had serological evidence of recent infection, correlating with the pattern of epidemic notifications. The 15- to 24-year-olds had similar high titres but the same notification rate as 25- to 44-year-olds, suggesting ascertainment bias may result in under-notification in the former age group. The prevalence of high titres observed was up to 20-fold higher than some European countries during a similar time period. Although vaccination has reduced the transmission of pertussis in the youngest and most vulnerable age group, pertussis is still endemic in Australia, particularly in older children and the elderly. The Australian vaccination schedule has been changed in an attempt to address this problem, by spacing doses more widely, with the fifth dose at 15-17 years of age. Seroepidemiology for pertussis offers the potential to compare patterns of pertussis between countries and examine the impact of

  12. Characteristics of pertussis outbreaks in Catalonia, Spain, 1997 to 2010.

    Science.gov (United States)

    Crespo, Inma; Broner, Sonia; Soldevila, Núria; Martínez, Ana; Godoy, Pere; Sala-Farré, Maria-Rosa; Company, Maria; Rius, Cristina; Domínguez, Angela; Group Of Catalonia, The Pertussis Working

    2015-01-01

    In Catalonia, pertussis outbreaks must be reported to the Department of Health. This study analyzed pertussis outbreaks between 1997 and 2010 in general and according to the characteristics of the index cases. The outbreak rate, hospitalization rate and incidence of associated cases and their 95%CI were calculated. Index cases were classified in two groups according to age (<15 years and ≥15 years) and the vaccine type received: whole cell vaccine (DTwP) or acellular vaccine (DTaP). During the study period, 230 outbreaks were reported. The outbreak rate was 2.43 × 10(-6) persons-year, and outbreaks ranged from 2 to 32 cases, with a median duration of 18 days. There were 771 associated cases, with an incidence rate of 0.8 × 10(-5) persons-year.   After classifying outbreaks according to the age of the index case, 126 outbreaks (1.3 × 10(-6) persons-year) had an index case aged <15 y and 87 (0.87 × 10(-6) person-year) had an index case aged ≥15 y (RR = 1.44, 95%CI 1.10-1.90; P = 0.007). Between 2003 and 2010, after the introduction of the acellular vaccine, the index case was vaccinated with DTwP vaccine in 25 outbreaks (0.43 × 10(-6) persons-year) and with DTaP vaccine in 32 outbreaks (0.55 × 10(-6) person-year) (RR = 0.78, 95%CI 0.46-1.31; P = 0.35). Of cases, 37.2% were correctly vaccinated, suggesting waning immunity of pertussis vaccine protection and endogenous circulation of pertussis. A greater number of outbreaks had an index case aged <15 y. No changes in the disease incidence, associated cases and hospitalization rate were observed after the introduction of DTaP.

  13. Temperature-sensitive mutations for live-attenuated Rift Valley fever vaccines: Implications from other RNA viruses

    Directory of Open Access Journals (Sweden)

    Shoko eNishiyama

    2015-08-01

    Full Text Available Rift Valley fever (RVF is a mosquito-borne zoonotic disease endemic to the African continent. RVF is characterized by high rate of abortions in ruminants and hemorrhagic fever, encephalitis or blindness in humans. RVF is caused by the Rift Valley fever virus (RVFV: genus Phlebovirus, family Bunyaviridae. Vaccination is the only known effective strategy to prevent the disease, but there are no licensed RVF vaccines available for humans. A live-attenuated vaccine candidate derived from the wild-type pathogenic Egyptian ZH548 strain, MP-12, has been conditionally licensed for veterinary use in the United States. MP-12 displays a temperature-sensitive (ts phenotype and does not replicate at 41oC. The ts mutation limits viral replication at a specific body temperature and may lead to an attenuation of the virus. Here we will review well-characterized ts mutations for RNA viruses, and further discuss the potential in designing novel live-attenuated vaccines for RVF.

  14. Evaluation of synthetic infection-enhancing lipopeptides as adjuvants for a live-attenuated canine distemper virus vaccine administered intra-nasally to ferrets.

    Science.gov (United States)

    Nguyen, D Tien; Ludlow, Martin; van Amerongen, Geert; de Vries, Rory D; Yüksel, Selma; Verburgh, R Joyce; Osterhaus, Albert D M E; Duprex, W Paul; de Swart, Rik L

    2012-07-20

    Inactivated paramyxovirus vaccines have been associated with hypersensitivity responses upon challenge infection. For measles and canine distemper virus (CDV) safe and effective live-attenuated virus vaccines are available, but for human respiratory syncytial virus and human metapneumovirus development of such vaccines has proven difficult. We recently identified three synthetic bacterial lipopeptides that enhance paramyxovirus infections in vitro, and hypothesized these could be used as adjuvants to promote immune responses induced by live-attenuated paramyxovirus vaccines. Here, we tested this hypothesis using a CDV vaccination and challenge model in ferrets. Three groups of six animals were intra-nasally vaccinated with recombinant (r) CDV(5804P)L(CCEGFPC) in the presence or absence of the infection-enhancing lipopeptides Pam3CSK4 or PHCSK4. The recombinant CDV vaccine virus had previously been described to be over-attenuated in ferrets. A group of six animals was mock-vaccinated as control. Six weeks after vaccination all animals were challenged with a lethal dose of rCDV strain Snyder-Hill expressing the red fluorescent protein dTomato. Unexpectedly, intra-nasal vaccination of ferrets with rCDV(5804P)L(CCEGFPC) in the absence of lipopeptides resulted in good immune responses and protection against lethal challenge infection. However, in animals vaccinated with lipopeptide-adjuvanted virus significantly higher vaccine virus loads were detected in nasopharyngeal lavages and peripheral blood mononuclear cells. In addition, these animals developed significantly higher CDV neutralizing antibody titers compared to animals vaccinated with non-adjuvanted vaccine. This study demonstrates that the synthetic cationic lipopeptides Pam3CSK4 and PHCSK4 not only enhance paramyxovirus infection in vitro, but also in vivo. Given the observed enhancement of immunogenicity their potential as adjuvants for other live-attenuated paramyxovirus vaccines should be considered

  15. Pertussis: clinical and bacteriological diagnosis of six cases

    Directory of Open Access Journals (Sweden)

    Arellano Penagos Mario

    2014-07-01

    Full Text Available ertussis is an endemic disease in our population. Every 3 to 4 years, pertussis has an epidemic pattern even in countries with good health conditions. Antipertussis vaccine first dose is adminis- tered at the age of 2 months; a second and third dose are given at 4 and 6 months of age. This vaccine has an 8 to 10 year protective effect, for which reason it is suggested that pregnant women in the third trimester should be vaccinated in order to prevent pertussis in newborns. It should also be administered to older people to avoid turning them into asymptomatic carriers. Clinic manifestations are easily identifiable due to respiratory symptoms, especially to the particular characteristics of the cough. The diagnosis is supported by the presence of leukocytosis (predominantly lymphocytes and by certain thoracic radiologic findings. The diagnosis is confirmed with a positive culture for Bordetella pertussis or with a polymerase chain reaction (PCR. In a non complicated clinic course macrolides are still the best therapeutic choice. Nonetheless clinic observation is highly recom- mended in order to avoid complications. Redefinition of vaccine programs against Bordetella pertussis in Mexican population is recommended and also to notify the presence of the disease to the corresponding health authorities.

  16. Dynamics of Pertussis Transmission in the United States

    Science.gov (United States)

    Magpantay, F. M. G.; Rohani, P.

    2015-01-01

    Past patterns of infectious disease transmission set the stage on which modern epidemiologic dynamics are played out. Here, we present a comprehensive account of pertussis (whooping cough) transmission in the United States during the early vaccine era. We analyzed recently digitized weekly incidence records from Morbidity and Mortality Weekly Reports from 1938 to 1955, when the whole-cell pertussis vaccine was rolled out, and related them to contemporary patterns of transmission and resurgence documented in monthly incidence data from the National Notifiable Diseases Surveillance System. We found that, during the early vaccine era, pertussis epidemics in US states could be categorized as 1) annual, 2) initially annual and later multiennial, or 3) multiennial. States with predominantly annual cycles tended to have higher per capita birth rates, more household crowding, more children per family, and lower rates of school attendance than the states with multiennial cycles. Additionally, states that exhibited annual epidemics during 1938–1955 have had the highest recent (2001–2010) incidence, while those states that transitioned from annual cycles to multiennial cycles have had relatively low recent incidence. Our study provides an extensive picture of pertussis epidemiology in the United States dating back to the onset of vaccination, a back-story that could aid epidemiologists in understanding contemporary transmission patterns. PMID:26022662

  17. Protection of macaques with diverse MHC genotypes against a heterologous SIV by vaccination with a deglycosylated live-attenuated SIV.

    Directory of Open Access Journals (Sweden)

    Chie Sugimoto

    Full Text Available HIV vaccine development has been hampered by issues such as undefined correlates of protection and extensive diversity of HIV. We addressed these issues using a previously established SIV-macaque model in which SIV mutants with deletions of multiple gp120 N-glycans function as potent live attenuated vaccines to induce near-sterile immunity against the parental pathogenic SIVmac239. In this study, we investigated the protective efficacy of these mutants against a highly pathogenic heterologous SIVsmE543-3 delivered intravenously to rhesus macaques with diverse MHC genotypes. All 11 vaccinated macaques contained the acute-phase infection with blood viral loads below the level of detection between 4 and 10 weeks postchallenge (pc, following a transient but marginal peak of viral replication at 2 weeks in only half of the challenged animals. In the chronic phase, seven vaccinees contained viral replication for over 80 weeks pc, while four did not. Neutralizing antibodies against challenge virus were not detected. Although overall levels of SIV specific T cell responses did not correlate with containment of acute and chronic viral replication, a critical role of cellular responses in the containment of viral replication was suggested. Emergence of viruses with altered fitness due to recombination between the vaccine and challenge viruses and increased gp120 glycosylation was linked to the failure to control SIV. These results demonstrate the induction of effective protective immune responses in a significant number of animals against heterologous virus by infection with deglycosylated attenuated SIV mutants in macaques with highly diverse MHC background. These findings suggest that broad HIV cross clade protection is possible, even in hosts with diverse genetic backgrounds. In summary, results of this study indicate that deglycosylated live-attenuated vaccines may provide a platform for the elucidation of correlates of protection needed for a

  18. Seroepidemiology of pertussis among elementary school children in northern Taiwan.

    Science.gov (United States)

    Kuo, Ching-Chia; Huang, Yhu-Chering; Hsieh, Yu-Chia; Huang, Ya-Ling; Huang, Yu-Chiau; Hung, Yung-Tai

    2017-06-01

    Pertussis has been considered a vaccine-preventable "childhood disease", but a shift in age distribution has been reported worldwide. We conducted a seroepidemiological study in 2013 in Taiwan to elucidate the seroprevalence of pertussis among elementary school children. With a multilevel randomized method, which included 14 variables (4 population variables, 4 socio-educational variables, and 6 medical facilities' variables), the 29 executive districts of New Taipei City, Taiwan, were categorized into five strata. From each stratum, the number of school children as well as the number of elementary schools were proportionally selected. Enzyme immunoassay was applied for pertussis immunoglobulin-G measurement. A total of 936 children from 14 schools were recruited. Most participants (98.89%) received at least three doses of acellular diphtheria-tetanus-pertussis vaccine. The overall seropositive rate for pertussis was 33.97%. The seropositive rate was highest for students in Grade 1 (49.36%) and then declined with time, except for Grade 6 students. Students from Grade 1 to Grade 4 had a significant higher seropositive rate (37.18% vs. 27.56%, p = 0.002) than those from Grade 5 to Grade 6, but a lower geometric mean titer (18.71 NovaTec Unit/mL vs. 20.04 NovaTec Unit/mL, p = 0.20). For the class grades, geometric mean titers were positively correlated with seroprevalence (p Taiwan were seropositive for pertussis, a rate lower than expected. Seroprevalence declined with increasing class grades except for Grade 6. The current national immunization program may not provide adequate protection for children against pertussis. Copyright © 2015. Published by Elsevier B.V.

  19. Pertussis Serodiagnosis in Belgium from 1990 to 2009 ▿

    Science.gov (United States)

    Vincent, Muriel; Rodeghiero, Caroline; Eylenbosch, Romain; Mans, Yvan; Swalus-Steenhouwer, Jeannine; Piérard, Denis; Huygen, Kris; Vanhoof, Raymond

    2011-01-01

    Diagnosis of pertussis by culture and PCR is most sensitive when performed on nasopharyngeal specimens collected pertussis in Belgium from 1990 to 2009. In total, 13,163 patients were analyzed for Bordetella pertussis-specific antibodies by agglutination, complement fixation, immunofluorescence, and ELISA. The number of positive pertussis cases detected by serodiagnosis ranged between 50 and 150 annually. The mean age of positive cases increased from 9.9 years in 1990 to 33.9 years in 2009. Whereas from 1990 to 2003, children and young adolescents made up the majority of cases, from 2004 onwards, cases were detected in all age groups and the distribution became bimodal, with a first peak at the age of 10 to 20 years and a second at the age of 35 to 50 years. In contrast, patients diagnosed since 2001 by PCR and/or culture were mostly children younger than 1 year of age. Despite extensive childhood vaccination campaigns, whooping cough is still present in Belgium. Our findings confirm the potential role of adults in the continued transmission of pertussis and strongly warrant booster or cocoon vaccinations in older age groups. PMID:21346057

  20. Estimated exposures to perfluorinated compounds in infancy predict attenuated vaccine antibody concentrations at age 5-years.

    Science.gov (United States)

    Grandjean, Philippe; Heilmann, Carsten; Weihe, Pal; Nielsen, Flemming; Mogensen, Ulla B; Timmermann, Amalie; Budtz-Jørgensen, Esben

    2017-12-01

    Perfluorinated alkylate substances (PFASs) are highly persistent and may cause immunotoxic effects. PFAS-associated attenuated antibody responses to childhood vaccines may be affected by PFAS exposures during infancy, where breastfeeding adds to PFAS exposures. Of 490 members of a Faroese birth cohort, 275 and 349 participated in clinical examinations and provided blood samples at ages 18 months and 5 years. PFAS concentrations were measured at birth and at the clinical examinations. Using information on duration of breastfeeding, serum-PFAS concentration profiles during infancy were estimated. As outcomes, serum concentrations of antibodies against tetanus and diphtheria vaccines were determined at age 5. Data from a previous cohort born eight years earlier were available for pooled analyses. Pre-natal exposure showed inverse associations with the antibody concentrations five years later, with decreases by up to about 20% for each two-fold higher exposure, while associations for serum concentrations at ages 18 months and 5 years were weaker. Modeling of serum-PFAS concentration showed levels for age 18 months that were similar to those measured. Concentrations estimated for ages 3 and 6 months showed the strongest inverse associations with antibody concentrations at age 5 years, particularly for tetanus. Joint analyses showed statistically significant decreases in tetanus antibody concentrations by 19-29% at age 5 for each doubling of the PFAS exposure in early infancy. These findings support the notion that the developing adaptive immune system is particularly vulnerable to immunotoxicity during infancy. This vulnerability appears to be the greatest during the first 6 months after birth, where PFAS exposures are affected by breast-feeding.

  1. The epidemiological impact of childhood influenza vaccination using live-attenuated influenza vaccine (LAIV) in Germany: predictions of a simulation study

    Science.gov (United States)

    2014-01-01

    Background Routine annual influenza vaccination is primarily recommended for all persons aged 60 and above and for people with underlying chronic conditions in Germany. Other countries have already adopted additional childhood influenza immunisation programmes. The objective of this study is to determine the potential epidemiological impact of implementing paediatric influenza vaccination using intranasally administered live-attenuated influenza vaccine (LAIV) in Germany. Methods A deterministic age-structured model is used to simulate the population-level impact of different vaccination strategies on the transmission dynamics of seasonal influenza in Germany. In our base-case analysis, we estimate the effects of adding a LAIV-based immunisation programme targeting children 2 to 17 years of age to the existing influenza vaccination policy. The data used in the model is based on published evidence complemented by expert opinion. Results In our model, additional vaccination of children 2 to 17 years of age with LAIV leads to the prevention of 23.9 million influenza infections and nearly 16 million symptomatic influenza cases within 10 years. This reduction in burden of disease is not restricted to children. About one third of all adult cases can indirectly be prevented by LAIV immunisation of children. Conclusions Our results demonstrate that vaccinating children 2–17 years of age is likely associated with a significant reduction in the burden of paediatric influenza. Furthermore, annual routine childhood vaccination against seasonal influenza is expected to decrease the incidence of influenza among adults and older people due to indirect effects of herd protection. In summary, our model provides data supporting the introduction of a paediatric influenza immunisation programme in Germany. PMID:24450996

  2. Memory T-cell immune response in healthy young adults vaccinated with live attenuated influenza A (H5N2) vaccine.

    Science.gov (United States)

    Chirkova, T V; Naykhin, A N; Petukhova, G D; Korenkov, D A; Donina, S A; Mironov, A N; Rudenko, L G

    2011-10-01

    Cellular immune responses of both CD4 and CD8 memory/effector T cells were evaluated in healthy young adults who received two doses of live attenuated influenza A (H5N2) vaccine. The vaccine was developed by reassortment of nonpathogenic avian A/Duck/Potsdam/1402-6/68 (H5N2) and cold-adapted A/Leningrad/134/17/57 (H2N2) viruses. T-cell responses were measured by standard methods of intracellular cytokine staining of gamma interferon (IFN-γ)-producing cells and a novel T-cell recognition of antigen-presenting cells by protein capture (TRAP) assay based on the trogocytosis phenomenon, namely, plasma membrane exchange between interacting immune cells. TRAP enables the detection of activated trogocytosis-positive T cells after virus stimulation. We showed that two doses of live attenuated influenza A (H5N2) vaccine promoted both CD4 and CD8 T-memory-cell responses in peripheral blood of healthy young subjects in the clinical study. Significant differences in geometric mean titers (GMTs) of influenza A (H5N2)-specific IFN-γ(+) cells were observed at day 42 following the second vaccination, while peak levels of trogocytosis(+) T cells were detected earlier, on the 21st day after the second vaccination. The inverse correlation of baseline levels compared to postvaccine fold changes in GMTs of influenza-specific CD4 and CD8 T cells demonstrated that baseline levels of these specific cells could be considered a predictive factor of vaccine immunogenicity.

  3. Attenuated Recombinant Influenza A Virus Expressing HPV16 E6 and E7 as a Novel Therapeutic Vaccine Approach.

    Directory of Open Access Journals (Sweden)

    Christoph Jindra

    Full Text Available Persistent infection with high-risk human papillomavirus (HPV types, most often HPV16 and HPV18, causes all cervical and most anal cancers, and a subset of vulvar, vaginal, penile and oropharyngeal carcinomas. Two prophylactic virus-like particle (VLPs-based vaccines, are available that protect against vaccine type-associated persistent infection and associated disease, yet have no therapeutic effect on existing lesions or infections. We have generated recombinant live-attenuated influenza A viruses expressing the HPV16 oncogenes E6 and E7 as experimental immunotherapeutic vaccine candidates. The influenza A virus life cycle lacks DNA intermediates as important safety feature. Different serotypes were generated to ensure efficient prime and boost immunizations. The immune response to vaccination in C57BL/6 mice was characterized by peptide ELISA and IFN-γ ELISpot, demonstrating induction of cell-mediated immunity to HPV16 E6 and E7 oncoproteins. Prophylactic and therapeutic vaccine efficacy was analyzed in the murine HPV16-positive TC-1 tumor challenge model. Subcutaneous (s.c. prime and boost vaccinations of mice with recombinant influenza A serotypes H1N1 and H3N2, followed by challenge with TC-1 cells resulted in complete protection or significantly reduced tumor growth as compared to control animals. In a therapeutic setting, s.c. vaccination of mice with established TC-1 tumors decelerated tumor growth and significantly prolonged survival. Importantly, intralesional vaccine administration induced complete tumor regression in 25% of animals, and significantly reduced tumor growth in 50% of mice. These results suggest recombinant E6E7 influenza viruses as a promising new approach for the development of a therapeutic vaccine against HPV-induced disease.

  4. Effect of live attenuated vaccines on the course of experimental allergic encephalomyelitis. A pilot study.

    Science.gov (United States)

    Caspary, E A

    1977-01-01

    The clinical severity of EAE is enhanced by pre-treatment with distemper, measles and BCG vaccine, measles vaccine gives a more severe onset of disease. Rubella vaccine and TAB leads to mild disease which recurs on re-treatment with the appropriate vaccine. These findings and their possible significance in MS are briefly discussed.

  5. Cold-Adapted Viral Attenuation (CAVA): Highly Temperature Sensitive Polioviruses as Novel Vaccine Strains for a Next Generation Inactivated Poliovirus Vaccine.

    Science.gov (United States)

    Sanders, Barbara P; de Los Rios Oakes, Isabel; van Hoek, Vladimir; Bockstal, Viki; Kamphuis, Tobias; Uil, Taco G; Song, Yutong; Cooper, Gillian; Crawt, Laura E; Martín, Javier; Zahn, Roland; Lewis, John; Wimmer, Eckard; Custers, Jerome H H V; Schuitemaker, Hanneke; Cello, Jeronimo; Edo-Matas, Diana

    2016-03-01

    The poliovirus vaccine field is moving towards novel vaccination strategies. Withdrawal of the Oral Poliovirus Vaccine and implementation of the conventional Inactivated Poliovirus Vaccine (cIPV) is imminent. Moreover, replacement of the virulent poliovirus strains currently used for cIPV with attenuated strains is preferred. We generated Cold-Adapted Viral Attenuation (CAVA) poliovirus strains by serial passage at low temperature and subsequent genetic engineering, which contain the capsid sequences of cIPV strains combined with a set of mutations identified during cold-adaptation. These viruses displayed a highly temperature sensitive phenotype with no signs of productive infection at 37°C as visualized by electron microscopy. Furthermore, decreases in infectious titers, viral RNA, and protein levels were measured during infection at 37°C, suggesting a block in the viral replication cycle at RNA replication, protein translation, or earlier. However, at 30°C, they could be propagated to high titers (9.4-9.9 Log10TCID50/ml) on the PER.C6 cell culture platform. We identified 14 mutations in the IRES and non-structural regions, which in combination induced the temperature sensitive phenotype, also when transferred to the genomes of other wild-type and attenuated polioviruses. The temperature sensitivity translated to complete absence of neurovirulence in CD155 transgenic mice. Attenuation was also confirmed after extended in vitro passage at small scale using conditions (MOI, cell density, temperature) anticipated for vaccine production. The inability of CAVA strains to replicate at 37°C makes reversion to a neurovirulent phenotype in vivo highly unlikely, therefore, these strains can be considered safe for the manufacture of IPV. The CAVA strains were immunogenic in the Wistar rat potency model for cIPV, inducing high neutralizing antibody titers in a dose-dependent manner in response to D-antigen doses used for cIPV. In combination with the highly productive

  6. Pertussis: Disease Villain!

    Centers for Disease Control (CDC) Podcasts

    2014-05-22

    In this podcast for kids, the Kidtastics talk about pertussis, or whooping cough-what it is and how to protect yourself from it.  Created: 5/22/2014 by National Center for Immunization and Respiratory Diseases (NCIRD).   Date Released: 5/22/2014.

  7. In a randomized trial, the live attenuated tetravalent dengue vaccine TV003 is well-tolerated and highly immunogenic in subjects with flavivirus exposure prior to vaccination.

    Directory of Open Access Journals (Sweden)

    Stephen S Whitehead

    2017-05-01

    Full Text Available Infection caused by the four serotypes of dengue virus (DENV-1-4 is a leading cause of mosquito-borne disease. Clinically-severe dengue disease is more common when secondary dengue infection occurs following prior infection with a heterologous dengue serotype. Other flaviviruses such as yellow fever virus, Japanese encephalitis virus, and Zika virus, can also elicit antibodies which are cross-reactive to DENV. As candidate dengue vaccines become available in endemic settings and for individuals who have received other flavivirus vaccines, it is important to examine vaccine safety and immunogenicity in these flavivirus-experienced populations. We performed a randomized, controlled trial of the National Institutes of Health live attenuated tetravalent dengue vaccine candidate (TV003 in fifty-eight individuals with prior exposure to flavivirus infection or vaccine. As in prior studies of this vaccine in flavivirus-naive volunteers, flavivirus-experienced subjects received two doses of vaccine six months apart and were followed closely for clinical events, laboratory changes, viremia, and neutralizing antibody titers. TV003 was well tolerated with few adverse events other than rash, which was predominately mild. Following one dose, 87% of vaccinees had an antibody response to all four serotypes (tetravalent response, suggesting a robust immune response. In addition, 76% of vaccinees were viremic; mean peak titers ranged from 0.68–1.1 log10 PFU/mL and did not differ by serotype. The second dose of TV003 was not associated with viremia, rash, or a sustained boost in antibody titers indicating that a single dose of the vaccine is likely sufficient to prevent viral replication and thus protect against disease. In comparison to the viremia and neutralizing antibody response elicited by TV003 in flavivirus-naïve subjects from prior studies, we found that subjects who were flavivirus-exposed prior to vaccination exhibited slightly higher DENV-3 viremia

  8. Engineering and preclinical evaluation of attenuated nontyphoidal Salmonella strains serving as live oral vaccines and as reagent strains.

    Science.gov (United States)

    Tennant, Sharon M; Wang, Jin-Yuan; Galen, James E; Simon, Raphael; Pasetti, Marcela F; Gat, Orit; Levine, Myron M

    2011-10-01

    While nontyphoidal Salmonella (NTS) has long been recognized as a cause of self-limited gastroenteritis, it is becoming increasingly evident that multiple-antibiotic-resistant strains are also emerging as important causes of invasive bacteremia and focal infections, resulting in hospitalizations and deaths. We have constructed attenuated Salmonella enterica serovar Typhimurium and Salmonella enterica serovar Enteritidis strains that can serve as live oral vaccines and as "reagent strains" for subunit vaccine production in a safe and economical manner. Prototype attenuated vaccine strains CVD 1921 and CVD 1941, derived from the invasive wild-type strains S. Typhimurium I77 and S. Enteritidis R11, respectively, were constructed by deleting guaBA, encoding guanine biosynthesis, and clpP, encoding a master protease regulator. The clpP mutation resulted in a hyperflagellation phenotype. An additional deletion in fliD yielded reagent strains CVD 1923 and CVD 1943, respectively, which export flagellin monomers. Oral 50% lethal dose (LD₅₀) analyses showed that the NTS vaccine strains were all highly attenuated in mice. Oral immunization with CVD 1921 or CVD 1923 protected mice against lethal challenge with wild-type S. Typhimurium I77. Immunization with CVD 1941 but not CVD 1943 protected mice against lethal infection with S. Enteritidis R11. Immune responses induced by these strains included high levels of serum IgG anti-lipopolysaccharide (LPS) and anti-flagellum antibodies, with titers increasing progressively during the immunization schedule. Since S. Typhimurium and S. Enteritidis are the most common NTS serovars associated with invasive disease, these findings can pave the way for development of a highly effective, broad-spectrum vaccine against invasive NTS.

  9. Newcastle disease virus-attenuated vaccine co-contaminated with fowl adenovirus and chicken infectious anemia virus results in inclusion body hepatitis-hydropericardium syndrome in poultry.

    Science.gov (United States)

    Su, Qi; Li, Yang; Meng, Fanfeng; Cui, Zhizhong; Chang, Shuang; Zhao, Peng

    2018-05-01

    Inclusion body hepatitis-hydropericardium syndrome (IBH-HPS) induced by fowl adenovirus type 4 (FAdV-4) has caused huge economic losses to the poultry industry of China, but the source of infection for different flocks, especially flocks with high biological safety conditions, has remained unclear. This study tested the pathogenicity of Newcastle disease virus (NDV)-attenuated vaccine from a large-scale poultry farm in China where IBH-HPS had appeared with high mortality. Analysis revealed that the NDV-attenuated vaccine in use from the abovementioned poultry farm was simultaneously contaminated with FAdV-4 and chicken infectious anemia virus (CIAV). The FAdV and CIAV isolated from the vaccine were purified for the artificial preparation of an NDV-attenuated vaccine singly contaminated with FAdV or CIAV, or simultaneously contaminated with both of them. Seven-day-old specific pathogen-free chicks were inoculated with the artificially prepared contaminated vaccines and tested for corresponding indices. The experiments showed that no hydropericardium syndrome (HPS) and corresponding death occurred after administering the NDV-attenuated vaccine singly contaminated with FAdV or CIAV, but a mortality of 75% with IBH-HPS was commonly found in birds after administering the NDV-attenuated vaccine co-contaminated with FAdV and CIAV. In conclusion, this study found the co-contamination of FAdV-4 and CIAV in the same attenuated vaccine and confirmed that such a contaminated attenuated vaccine was a significant source of infection for outbreaks of IBH-HPS in some flocks. Copyright © 2018 Elsevier B.V. All rights reserved.

  10. Irradiation-attenuated anti-parasite vaccines in ruminants. Present status and future prospects

    International Nuclear Information System (INIS)

    Taylor, M.G.

    1981-01-01

    The only commercially available irradiated anti-parasite vaccine is Dictol, the anti-Dictyocaulus viviparus vaccine, which is still being widely used in cattle 20 years after its introduction. Several other similar helminth vaccines which showed promise early in their development or use have now been abandoned for reasons both scientific and commercial. Nevertheless, there is still active interest in the development of irradiated vaccines for fascioliasis and schistosomiasis, as recent field trials have shown that irradiated metacercarial and schistosomular vaccines are effective against F. hepatica and S. bovis in cattle. There are no commercially available irradiated vaccines against protozoal diseases. Although experiments showed that irradiated vaccines were effective against Babesia bigemina and Theileria parva in cattle, interest in these has waned as other forms of live vaccines have been introduced. Vaccination against African trypanosomiasis remains an intractable problem, because of the multiplicity of naturally occurring antigenically distinct strains. (author)

  11. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... and Extremus posters videos mono pertussis Silence the Sounds of Pertussis Acalla los Sonidos de la Tos ... know has hbv/hcv standard precautions Silence the Sounds of Pertussis spokespeople who we are Your Choice! ...

  12. Reversion to virulence and efficacy of an attenuated canarypox vaccine in Hawai'i 'Amakihi (Hemignathus Virens)

    Science.gov (United States)

    Atkinson, Carter T.; Wiegand, Kimberly C.; Triglia, Dennis; Jarvi, Susan I.

    2012-01-01

    Vaccines may be effective tools for protecting small populations of highly susceptible endangered, captive-reared, or translocated Hawaiian honeycreepers from introduced Avipoxvirus, but their efficacy has not been evaluated. An attenuated Canarypox vaccine that is genetically similar to one of two passerine Avipoxvirus isolates from Hawai‘i and distinct from Fowlpox was tested to evaluate whether Hawai‘i ‘Amakihi (Hemignathus virens) can be protected from wild isolates of Avipoxvirus from the Hawaiian Islands. Thirty-one (31) Hawai‘i ‘Amakihi were collected from high-elevation habitats on Mauna Kea Volcano, where pox transmission is rare, and randomly divided into two groups. One group was vaccinated with Poximune C®, whereas the other group received a sham vaccination with sterile water. Four of 15 (27%) vaccinated birds developed life-threatening disseminated lesions or lesions of unusually long duration, whereas one bird never developed a vaccine-associated lesion or “take.” After vaccine lesions healed, vaccinated birds were randomly divided into three groups of five and challenged with either a wild isolate of Fowlpox (FP) from Hawai‘i, a Hawai‘i ‘Amakihi isolate of a Canarypox-like virus (PV1), or a Hawai‘i ‘Amakihi isolate of a related, but distinct, passerine Avipoxvirus (PV2). Similarly, three random groups of five unvaccinated ‘Amakihi were challenged with the same virus isolates. Vaccinated and unvaccinated ‘Amakihi challenged with FP had transient infections with no clinical signs of infection. Mortality in vaccinated ‘Amakihi challenged with PV1 and PV2 ranged from 0% (0/5) for PV1 to 60% (3/5) for PV2. Mortality in unvaccinated ‘Amakihi ranged from 40% (2/5) for PV1 to 100% (5/5) for PV2. Although the vaccine provided some protection against PV1, both potential for vaccine reversion and low efficacy against PV2 preclude its use in captive or wild honeycreepers.

  13. Rational design of human metapneumovirus live attenuated vaccine candidates by inhibiting viral mRNA cap methyltransferase.

    Science.gov (United States)

    Zhang, Yu; Wei, Yongwei; Zhang, Xiaodong; Cai, Hui; Niewiesk, Stefan; Li, Jianrong

    2014-10-01

    The paramyxoviruses human respiratory syncytial virus (hRSV), human metapneumovirus (hMPV), and human parainfluenza virus type 3 (hPIV3) are responsible for the majority of pediatric respiratory diseases and inflict significant economic loss, health care costs, and emotional burdens. Despite major efforts, there are no vaccines available for these viruses. The conserved region VI (CR VI) of the large (L) polymerase proteins of paramyxoviruses catalyzes methyltransferase (MTase) activities that typically methylate viral mRNAs at positions guanine N-7 (G-N-7) and ribose 2'-O. In this study, we generated a panel of recombinant hMPVs carrying mutations in the S-adenosylmethionine (SAM) binding site in CR VI of L protein. These recombinant viruses were specifically defective in ribose 2'-O methylation but not G-N-7 methylation and were genetically stable and highly attenuated in cell culture and viral replication in the upper and lower respiratory tracts of cotton rats. Importantly, vaccination of cotton rats with these recombinant hMPVs (rhMPVs) with defective MTases triggered a high level of neutralizing antibody, and the rats were completely protected from challenge with wild-type rhMPV. Collectively, our results indicate that (i) amino acid residues in the SAM binding site in the hMPV L protein are essential for 2'-O methylation and (ii) inhibition of mRNA cap MTase can serve as a novel target to rationally design live attenuated vaccines for hMPV and perhaps other paramyxoviruses, such as hRSV and hPIV3. Human paramyxoviruses, including hRSV, hMPV, and hPIV3, cause the majority of acute upper and lower respiratory tract infections in humans, particularly in infants, children, the elderly, and immunocompromised individuals. Currently, there is no licensed vaccine available. A formalin-inactivated vaccine is not suitable for these viruses because it causes enhanced lung damage upon reinfection with the same virus. A live attenuated vaccine is the most promising

  14. Comparison of the live attenuated yellow fever vaccine 17D-204 strain to its virulent parental strain Asibi by deep sequencing.

    Science.gov (United States)

    Beck, Andrew; Tesh, Robert B; Wood, Thomas G; Widen, Steven G; Ryman, Kate D; Barrett, Alan D T

    2014-02-01

    The first comparison of a live RNA viral vaccine strain to its wild-type parental strain by deep sequencing is presented using as a model the yellow fever virus (YFV) live vaccine strain 17D-204 and its wild-type parental strain, Asibi. The YFV 17D-204 vaccine genome was compared to that of the parental strain Asibi by massively parallel methods. Variability was compared on multiple scales of the viral genomes. A modeled exploration of small-frequency variants was performed to reconstruct plausible regions of mutational plasticity. Overt quasispecies diversity is a feature of the parental strain, whereas the live vaccine strain lacks diversity according to multiple independent measurements. A lack of attenuating mutations in the Asibi population relative to that of 17D-204 was observed, demonstrating that the vaccine strain was derived by discrete mutation of Asibi and not by selection of genomes in the wild-type population. Relative quasispecies structure is a plausible correlate of attenuation for live viral vaccines. Analyses such as these of attenuated viruses improve our understanding of the molecular basis of vaccine attenuation and provide critical information on the stability of live vaccines and the risk of reversion to virulence.

  15. Study of the safety, immunogenicity and efficacy of attenuated and killed Leishmania (Leishmania major vaccines in a rhesus monkey (Macaca mulatta model of the human disease

    Directory of Open Access Journals (Sweden)

    VF Amaral

    2002-10-01

    Full Text Available We have compared the efficacy of two Leishmania (Leishmania major vaccines, one genetically attenuated (DHFR-TS deficient organisms, the other inactivated [autoclaved promastigotes (ALM with bacillus Calmete-Guérin (BCG], in protecting rhesus macaques (Macaca mulatta against infection with virulent L. (L. major. Positive antigen-specific recall proliferative response was observed in vaccinees (79% in attenuated parasite-vaccinated monkeys, versus 75% in ALM-plus-BCG-vaccinated animals, although none of these animals exhibited either augmented in vitro gamma interferon (IFN-g production or positive delayed-type hypersensitivity (DTH response to the leishmanin skin test prior to the challenge. Following challenge, there were significant differences in blastogenic responses (p < 0.05 between attenuated-vaccinated monkeys and naïve controls. In both vaccinated groups very low levels of antibody were found before challenge, which increased after infective challenge. Protective immunity did not follow vaccination, in that monkeys exhibited skin lesion at the site of challenge in all the groups. The most striking result was the lack of pathogenicity of the attenuated parasite, which persisted in infected animals for up to three months, but were incapable of causing disease under the conditions employed. We concluded that both vaccine protocols used in this study are safe in primates, but require further improvement for vaccine application.

  16. Attenuated Salmonella enterica Serovar Typhi and Shigella flexneri 2a Strains Mucosally Deliver DNA Vaccines Encoding Measles Virus Hemagglutinin, Inducing Specific Immune Responses and Protection in Cotton Rats

    OpenAIRE

    Pasetti, Marcela F.; Barry, Eileen M.; Losonsky, Genevieve; Singh, Mahender; Medina-Moreno, Sandra M.; Polo, John M.; Ulmer, Jeffrey; Robinson, Harriet; Sztein, Marcelo B.; Levine, Myron M.

    2003-01-01

    Measles remains a leading cause of child mortality in developing countries. Residual maternal measles antibodies and immunologic immaturity dampen immunogenicity of the current vaccine in young infants. Because cotton rat respiratory tract is susceptible to measles virus (MV) replication after intranasal (i.n.) challenge, this model can be used to assess the efficacy of MV vaccines. Pursuing a new measles vaccine strategy that might be effective in young infants, we used attenuated Salmonella...

  17. Mexico introduces pentavalent vaccine.

    Science.gov (United States)

    1999-08-01

    Combination vaccines have been introduced in Mexico. The national immunization program has incorporated the measles-mumps-rubella (MMR) vaccines in 1998, and the pentavalent vaccine in 1999. The two categories of antigen composition in combination vaccines are: 1) multiple different antigenic types of a single pathogen, such as the 23 valent pneumococcal polysaccharide vaccine, and 2) antigens from different pathogens causing different diseases, such as the DPT and MMR vaccines. Pentavalent vaccines are included in the second category. The vaccine protects against diphtheria, tetanus, pertussis, hepatitis B, and other diseases produced by Haemophilus influenzae type b (Hib). Combined diphtheria, tetanus, pertussis, hepatitis B, and Haemophilus influenza type b (DTP-HB/Hib) vaccine has been distributed to 87% of Mexican children under 1 year of age. Over 800,000 doses of pentavalent vaccine have been administered.

  18. Rational design of a live attenuated dengue vaccine: 2'-o-methyltransferase mutants are highly attenuated and immunogenic in mice and macaques.

    Directory of Open Access Journals (Sweden)

    Roland Züst

    Full Text Available Dengue virus is transmitted by Aedes mosquitoes and infects at least 100 million people every year. Progressive urbanization in Asia and South-Central America and the geographic expansion of Aedes mosquito habitats have accelerated the global spread of dengue, resulting in a continuously increasing number of cases. A cost-effective, safe vaccine conferring protection with ideally a single injection could stop dengue transmission. Current vaccine candidates require several booster injections or do not provide protection against all four serotypes. Here we demonstrate that dengue virus mutants lacking 2'-O-methyltransferase activity are highly sensitive to type I IFN inhibition. The mutant viruses are attenuated in mice and rhesus monkeys and elicit a strong adaptive immune response. Monkeys immunized with a single dose of 2'-O-methyltransferase mutant virus showed 100% sero-conversion even when a dose as low as 1,000 plaque forming units was administrated. Animals were fully protected against a homologous challenge. Furthermore, mosquitoes feeding on blood containing the mutant virus were not infected, whereas those feeding on blood containing wild-type virus were infected and thus able to transmit it. These results show the potential of 2'-O-methyltransferase mutant virus as a safe, rationally designed dengue vaccine that restrains itself due to the increased susceptibility to the host's innate immune response.

  19. Public health impact and cost-effectiveness of intranasal live attenuated influenza vaccination of children in Germany.

    Science.gov (United States)

    Damm, Oliver; Eichner, Martin; Rose, Markus Andreas; Knuf, Markus; Wutzler, Peter; Liese, Johannes Günter; Krüger, Hagen; Greiner, Wolfgang

    2015-06-01

    In 2011, intranasally administered live attenuated influenza vaccine (LAIV) was approved in the EU for prophylaxis of seasonal influenza in 2-17-year-old children. Our objective was to estimate the potential epidemiological impact and cost-effectiveness of an LAIV-based extension of the influenza vaccination programme to healthy children in Germany. An age-structured dynamic model of influenza transmission was developed and combined with a decision-tree to evaluate different vaccination strategies in the German health care system. Model inputs were based on published literature or were derived by expert consulting using the Delphi technique. Unit costs were drawn from German sources. Under base-case assumptions, annual routine vaccination of children aged 2-17 years with LAIV assuming an uptake of 50% would prevent, across all ages, 16 million cases of symptomatic influenza, over 600,000 cases of acute otitis media, nearly 130,000 cases of community-acquired pneumonia, nearly 1.7 million prescriptions of antibiotics and over 165,000 hospitalisations over 10 years. The discounted incremental cost-effectiveness ratio was 1,228 per quality-adjusted life year gained from a broad third-party payer perspective (including reimbursed direct costs and specific transfer payments), when compared with the current strategy of vaccinating primarily risk groups with the conventional trivalent inactivated vaccine. Inclusion of patient co-payments and indirect costs in terms of productivity losses resulted in discounted 10-year cost savings of 3.4 billion. In conclusion, adopting universal influenza immunisation of healthy children and adolescents would lead to a substantial reduction in influenza-associated disease at a reasonable cost to the German statutory health insurance system. On the basis of the epidemiological and health economic simulation results, a recommendation of introducing annual routine influenza vaccination of children 2-17 years of age might be taken into

  20. Public health impact and cost effectiveness of mass vaccination with live attenuated human rotavirus vaccine (RIX4414) in India: model based analysis.

    Science.gov (United States)

    Rose, Johnie; Hawthorn, Rachael L; Watts, Brook; Singer, Mendel E

    2009-09-25

    To examine the public health impact of mass vaccination with live attenuated human rotavirus vaccine (RIX4414) in a birth cohort in India, and to estimate the cost effectiveness and affordability of such a programme. Decision analytical Markov model encompassing all direct medical costs. Infection risk and severity depended on age, number of previous infections, and vaccination history; probabilities of use of inpatient and outpatient health services depended on symptom severity. Published clinical, epidemiological, and economic data. When possible, parameter estimates were based on data specific for India. Population Simulated Indian birth cohort followed for five years. Decrease in rotavirus gastroenteritis episodes (non-severe and severe), deaths, outpatient visits, and admission to hospital; incremental cost effectiveness ratio of vaccination expressed as net cost in 2007 rupees per life year saved. In the base case, vaccination prevented 28,943 (29.7%) symptomatic episodes, 6981 (38.2%) severe episodes, 164 deaths (41.0%), 7178 (33.3%) outpatient visits, and 812 (34.3%) admissions to hospital per 100,000 children. Vaccination cost 8023 rupees (about pound100, euro113, $165) per life year saved, less than India's per capita gross domestic product, a common criterion for cost effectiveness. The net programme cost would be equivalent to 11.6% of the 2006-7 budget of the Indian Department of Health and Family Welfare. Model results were most sensitive to variations in access to outpatient care for those with severe symptoms. If this parameter was increased to its upper limit, the incremental cost effectiveness ratio for vaccination still fell between one and three times the per capita gross domestic product, meeting the World Health Organization's criterion for "cost effective" interventions. Uncertainty analysis indicated a 94.7% probability that vaccination would be cost effective according to a criterion of one times per capita gross domestic product per life

  1. Nosocomial pertussis infection of infants: still a risk in 2009.

    Science.gov (United States)

    Paterson, Jennifer M; Sheppeard, Vicky

    2010-12-01

    The Sydney West Centre for Population Health investigated a confirmed pertussis infection in a health care worker on a maternity ward and identified pertussis infection in 4 neonates cared for by this case. This report describes the public health intervention to identify and prevent further cases. Of the 4 neonates, three were laboratory-confirmed cases and one was diagnosed on clinical grounds alone. All were cared for by the infected worker during only one shift and developed symptoms six to 16 days afterwards. No other possible source of infection was identified. This investigation highlights the need to maintain awareness, particularly amongst staff working with neonates, that pertussis infection can arise despite complete vaccination. Thus it is important to investigate new coughing illnesses and exclude symptomatic staff from contact with neonates until pertussis infection is excluded or effectively treated. The burden on the health system arising from a pertussis infection in a health care worker in a high-risk setting is also described with the hospitalisation of 4 infants, and prophylactic antibiotics given to 73 new mothers, infants and health care workers.

  2. Pertussis: A Review of Disease Epidemiology Worldwide and in Italy

    Directory of Open Access Journals (Sweden)

    Giovanni Gabutti

    2012-12-01

    Full Text Available Pertussis continues to be a relevant public-health issue. The high coverage rates achieved have decreased the spread of the pathogen, but the waning of immunity implies a relevant role of adolescents and adults in the infective dynamics as they may represent a significant source of infection for unvaccinated or incompletely immunized newborns. The passive surveillance system is affected by many limitations. The underestimation of pertussis in adolescents, young adults and adults is mainly related to the atypical clinical characteristics of cases and the lack of lab confirmation. The real epidemiological impact of pertussis is not always perceived, anyway, the unavailability of comprehensive data should not hamper the adoption of active prophylactic interventions aimed at preventing the impact of waning immunity on pertussis. To avoid an increase of the mean age of acquisition of the infection, a booster dose of low-antigen content combined vaccine should be adopted in adolescents and adults. A decreased risk of infection in newborns can be achieved with the cocoon strategy, although the debate on this aspect is still open and enhanced surveillance and further studies are needed to fine-tune the pertussis prevention strategy.

  3. Epidemiology of pertussis in Casablanca (Morocco): contribution of conventional and molecular diagnosis tools.

    Science.gov (United States)

    Katfy, Khalid; Guiso, Nicole; Diawara, Idrissa; Zerouali, Khalid; Slaoui, Bouchra; Jouhadi, Zineb; Zineddine, Abdelhadi; Belabbes, Houria; Elmdaghri, Naima

    2017-05-16

    Pertussis, a vaccine preventable disease, is still responsible of significant morbidity and mortality around the world, mostly in newborns. The aim of the present study was (1) to introduce pertussis surveillance in the major pediatric hospital of Casablanca (2) to analyze the prevalence of pertussis among children under 14 years of age and their entourage in Casablanca, Morocco. This is a prospective and non-case controlled study, including children suspected of Pertussis admitted at the Abderrahim Harouchi Pediatric Hospital in Casablanca, from January 2013 to June 2015. Nasopharyngeal samples were obtained for Bordetella spp. culture and Real time PCR detection (RT-PCR) with specific primers of Bordetella spp., B. pertussis, B. parapertussis and B. holmesii. The detection of Bordetella spp. was also performed in some household contacts of the children suspected of pertussis. During the 2.5-years period, a total of 282 samples were collected from hospitalized children (156) and in some of their contacts (126). Among 156 samples from the children (from whom 57% were under 2 month of age), Bordetella DNA was detected in 61% (96/156) by RT-PCR. Among these positive samples, 91.7% (88/96) corresponded to B. pertussis DNA. Furthermore, in 39.5% (38/96) of the Bordetella positive samples, B. holmesii DNA was also detected. B. parapertussis DNA was detected in only one sample (1/156). Out of the 156 samples collected from the hospitalized children, only 48 were tested by culture, and 4 B. pertussis were isolated (8.3%). Among the 126 samples from the contacts of the children, mostly mothers (115 cases), Bordetella DNA was detected in 47% (59/126), 90% (53/59) being B. pertussis DNA. Moreover, B. holmesii DNA was also detected in 18.6% (11/59) of the Bordetella positive samples, and coexistence of B. pertussis and B. holmesii DNA in 36.5% (35/96). Two B. pertussis were isolated by culture performed on 43 samples of the contacts of the children (4.6%). This study

  4. Two studies evaluating the safety and immunogenicity of a live, attenuated Shigella flexneri 2a vaccine (SC602) and excretion of vaccine organisms in North American volunteers.

    Science.gov (United States)

    Katz, David E; Coster, Trinka S; Wolf, Marcia K; Trespalacios, Fernando C; Cohen, Dani; Robins, Guy; Hartman, Antoinette B; Venkatesan, Malabi M; Taylor, David N; Hale, Thomas L

    2004-02-01

    We report the first community-based evaluation of Shigella flexneri 2a strain SC602, a live, oral vaccine strain attenuated by deletion of the icsA (virG) plasmid virulence gene, given at 10(4) CFU. The primary objectives of this trial were to determine the safety and immunogenicity of the vaccine and to determine the duration of colonization. Four of 34 volunteers experienced transient fevers, and three reported diarrhea during the first 3 days of the study. Half of the volunteers mounted a positive serum immunoglobulin A (IgA) response to S. flexneri lipopolysaccharide. All but one of the volunteers excreted the vaccine in their stools for 1 to 33 days, and this excretion was often intermittent. Data from the community-based study were supplemented with an inpatient trial in which three volunteers received 10(3) and nine received 10(4) CFU. All volunteers who received 10(3) CFU excreted SC602 and had an IgA antibody-secreting cell response. Two of these had a serum IgA response. Six of the nine volunteers who received 10(4) CFU excreted SC602. One vaccinee had a transient fever and two met the definition of diarrhea. Six volunteers that received 10(4) CFU had an antibody-secreting cell response, and four had a serum IgA response. SC602 has now been tested at 10(4) CFU in a total of 58 volunteers. The cumulative results of these clinical trials, reported here and previously (Coster et al., Infect. Immun. 67:3437-3443, 1999), have demonstrated that SC602 is a substantially attenuated candidate vaccine that can evoke protection against the most severe symptoms of shigellosis in a stringent human challenge model of disease.

  5. Oral Polio Vaccination and Hospital Admissions With Non-Polio Infections in Denmark

    DEFF Research Database (Denmark)

    Sørup, Signe; Stensballe, Lone G; Krause, Tyra Grove

    2016-01-01

    Background.  Live vaccines may have nonspecific beneficial effects on morbidity and mortality. This study examines whether children who had the live-attenuated oral polio vaccine (OPV) as the most recent vaccine had a different rate of admissions for infectious diseases than children with inactiv......Background.  Live vaccines may have nonspecific beneficial effects on morbidity and mortality. This study examines whether children who had the live-attenuated oral polio vaccine (OPV) as the most recent vaccine had a different rate of admissions for infectious diseases than children...... with inactivated diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b vaccine (DTaP-IPV-Hib) or live measles-mumps-rubella vaccine (MMR) as their most recent vaccine. Methods.  A nationwide, register-based, retrospective cohort study of 137 403 Danish children born 1997-1999, who had received 3 doses...... of DTaP-IPV-Hib, were observed from 24 months (first OPV dose) to 36 months of age. Results.  Oral polio vaccine was associated with a lower rate of admissions with any type of non-polio infection compared with DTaP-IPV-Hib as most recent vaccine (adjusted incidence rate ratio [IRR], 0.85; 95% confidence...

  6. [Whooping cough in Spain. Current epidemiology, prevention and control strategies. Recommendations by the Pertussis Working Group].

    Science.gov (United States)

    Campins, Magda; Moreno-Pérez, David; Gil-de Miguel, Angel; González-Romo, Fernando; Moraga-Llop, Fernando A; Arístegui-Fernández, Javier; Goncé-Mellgren, Anna; Bayas, José M; Salleras-Sanmartí, Lluís

    2013-04-01

    A large increase of pertussis incidence has been observed in recent years in countries with high vaccination coverage. Outbreaks of pertussis are increasingly being reported. The age presentation has a bipolar distribution: infants younger 6months that have not initiated or completed a vaccination schedule, and adolescents and adults, due to the lost of natural or vaccine immunity over time. These epidemiological changes justify the need to adopt new vaccination strategies in order to protect young infants and to reduce pertussis incidence in all age groups. Adolescents and adults immunization must be a priority. In the first group, strategy is easy to implement, and with a very low additional cost (to replace dT vaccine by dTap one). Adult vaccination may be more difficult to implement; dT vaccine decennial booster should be replaced by dTap. The immunization of household contacts of newborn infants (cocooning) is the strategy that has a most important impact on infant pertussis. Recently, pregnant women vaccination (after 20weeks of gestation) has been recommended in some countries as the most effective way to protect the newborn. Copyright © 2012 Elsevier España, S.L. All rights reserved.

  7. Lymphocyte receptors for pertussis toxin

    Energy Technology Data Exchange (ETDEWEB)

    Clark, C.G.; Armstrong, G.D. (Univ. of Alberta, Edmonton (Canada))

    1990-12-01

    We have investigated human T-lymphocyte receptors for pertussis toxin by affinity isolation and photoaffinity labeling procedures. T lymphocytes were obtained from peripheral human blood, surface iodinated, and solubilized in Triton X-100. The iodinated mixture was then passed through pertussis toxin-agarose, and the fractions were analyzed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis. Autoradiography of the fixed, dried gels revealed several bands in the pertussis toxin-bound fraction that were not observed in fractions obtained from histone or fetuin-agarose. Further investigations employed a photoaffinity labeling reagent, sulfosuccinimidyl 2-(p-azido-salicylamido)-1,3'-dithiopropionate, to identify pertussis toxin receptors in freshly isolated peripheral blood monocytic cells, T lymphocytes, and Jurkat cells. In all three cell systems, the pertussis toxin affinity probe specifically labeled a single protein species with an apparent molecular weight of 70,000 that was not observed when the procedure was performed in the presence of excess unmodified pertussis toxin. A protein comparable in molecular weight to the one detected by the photoaffinity labeling technique was also observed among the species that bound to pertussis toxin-agarose. The results suggest that pertussis toxin may bind to a 70,000-Da receptor in human T lymphocytes.

  8. Production of cell culture (MDCK) derived live attenuated influenza vaccine (LAIV) in a fully disposable platform process.

    Science.gov (United States)

    George, Meena; Farooq, Masiha; Dang, Thi; Cortes, Bernadette; Liu, Jonathan; Maranga, Luis

    2010-08-15

    The majority of influenza vaccines are manufactured using embryonated hens' eggs. The potential occurrence of a pandemic outbreak of avian influenza might reduce or even eliminate the supply of eggs, leaving the human population at risk. Also, the egg-based production technology is intrinsically cumbersome and not easily scalable to provide a rapid worldwide supply of vaccine. In this communication, the production of a cell culture (Madin-Darby canine kidney (MDCK)) derived live attenuated influenza vaccine (LAIV) in a fully disposable platform process using a novel Single Use Bioreactor (SUB) is presented. The cell culture and virus infection was maintained in a disposable stirred tank reactor with PID control of pH, DO, agitation, and temperature, similar to traditional glass or stainless steel bioreactors. The application of this technology was tested using MDCK cells grown on microcarriers in proprietary serum free medium and infection with 2006/2007 seasonal LAIV strains at 25-30 L scale. The MDCK cell growth was optimal at the agitation rate of 100 rpm. Optimization of this parameter allowed the cells to grow at a rate similar to that achieved in the conventional 3 L glass stirred tank bioreactors. Influenza vaccine virus strains, A/New Caledonia/20/99 (H1N1 strain), A/Wisconsin/67/05 (H3N2 strain), and B/Malaysia/2506/04 (B strain) were all successfully produced in SUB with peak virus titers > or =8.6 log(10) FFU/mL. This result demonstrated that more than 1 million doses of vaccine can be produced through one single run of a small bioreactor at the scale of 30 L and thus provided an alternative to the current vaccine production platform with fast turn-around and low upfront facility investment, features that are particularly useful for emerging and developing countries and clinical trial material production.

  9. Immunity to canine adenovirus respiratory disease: a comparison of attenuated CAV-1 and CAV-2 vaccines.

    Science.gov (United States)

    Cornwell, H J; Koptopoulos, G; Thompson, H; McCandlish, I A; Wright, N G

    1982-01-09

    Four litters of puppies were divided into three groups. One group was vaccinated with a live CAV-1 vaccine and another with a live CAV-2 vaccine. Throat swabs were collected from two dogs in each of these groups to monitor the possible excretion of vaccine virus, but none was found. Both groups, together with the third group of unvaccinated controls, were challenged 17 days later with an aerosol of virulent CAV-2. One dog from each group was killed on the third, fourth, seventh, ninth, 11th and 14th days after challenge. The unvaccinated dogs developed a clinical disease characterised by anorexia, dullness, coughing and tachypnoea. The lungs were consolidated and histological examination revealed the main lesion to be a severe necrotising bronchiolitis. Large amounts of virus were present in the respiratory tissues of these dogs and high titres of virus were isolated from throat swabs. In contrast, both groups of vaccinated dogs remained clinically almost normal with minimal lesions, present for a much shorter period of time. Virus was found on day 4 in the respiratory tissues of one dog vaccinated with CAV-1 but the other vaccinated animals contained little or no virus. In general, the degree of protection afforded by CAV-1 vaccine seemed similar to that provided by CAV-2 vaccine.

  10. Early protection events in swine immunized with an experimental live attenuated classical swine fever marker vaccine, FlagT4G.

    Directory of Open Access Journals (Sweden)

    Lauren G Holinka

    Full Text Available Prophylactic vaccination using live attenuated classical swine fever (CSF vaccines has been a very effective method to control the disease in endemic regions and during outbreaks in previously disease-free areas. These vaccines confer effective protection against the disease at early times post-vaccination although the mechanisms mediating the protection are poorly characterized. Here we present the events occurring after the administration of our in-house developed live attenuated marker vaccine, FlagT4Gv. We previously reported that FlagT4Gv intramuscular (IM administered conferred effective protection against intranasal challenge with virulent CSFV (BICv as early as 7 days post-vaccination. Here we report that FlagT4Gv is able to induce protection against disease as early as three days post-vaccination. Immunohistochemical testing of tissues from FlagT4Gv-inoculated animals showed that tonsils were colonized by the vaccine virus by day 3 post-inoculation. There was a complete absence of BICv in tonsils of FlagT4Gv-inoculated animals which had been intranasal (IN challenged with BICv 3 days after FlagT4Gv infection, confirming that FlagT4Gv inoculation confers sterile immunity. Analysis of systemic levels of 19 different cytokines in vaccinated animals demonstrated an increase of IFN-α three days after FlagT4Gv inoculation compared with mock infected controls.

  11. Isolation of an attenuated myxoma virus field strain that can confer protection against myxomatosis on contacts of vaccinates.

    Science.gov (United States)

    Bárcena, J; Pagès-Manté, A; March, R; Morales, M; Ramírez, M A; Sánchez-Vizcaíno, J M; Torres, J M

    2000-01-01

    Twenty MV strains obtained from a survey of field strains currently circulating throughout Spain were analyzed for their virulence and horizontal spreading among rabbits by contact transmission. A virus strain with suitable characteristics to be used as a potential vaccine against myxomatosis in wild rabbit populations was selected. Following inoculation, the selected MV strain elicited high levels of MV specific antibodies and induced protection of rabbits against a virulent MV challenge. Furthermore, the attenuated MV was transmitted to 9 out of 16 uninoculated rabbits by contact, inducing protection against myxomatosis.

  12. Human Transcriptome Response to Immunization with Live- Attenuated Venezuelan equine encephalitis Virus Vaccine (TC 83): Analysis of Whole Blood

    Science.gov (United States)

    2016-11-21

    natural killer cell 33 signaling, and B-cell development. Biomarkers were identified that differentiate between 34 vaccinees and control subjects...risk laboratory personnel.8 The first vaccine, 68 TC-83, is a live-attenuated virus developed in 1961 by serial passage of the virulent Trinidad 69...HSP90AA1), the ERK5 Signaling pathway 220 (e.g., IL6ST, NRAS, RRAS2, ATF2), the Natural Killer Cell Signaling pathway (e.g., KLRC2, 221 FYN, PRKC1

  13. [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

  14. Evaluation of the immune response in Shitou geese (Anser anser domesticus) following immunization with GPV-VP1 DNA-based and live attenuated vaccines.

    Science.gov (United States)

    Deng, Shu-xuan; Cai, Ming-sheng; Cui, Wei; Huang, Jin-lu; Li, Mei-li

    2014-01-01

    Goose parvovirus (GPV) is a highly contagious and deadly disease for goslings and Muscovy ducklings. To compare the differences in immune response of geese immunized with GPV-VP1 DNA-based and live attenuated vaccines. Shitou geese were immunized once with either 20 μg pcDNA-GPV-VP1 DNA gene vaccine by gene gun bombardment via intramuscular injection, or 300 μg by i.m. injection, or 300 μL live attenuated vaccine by i.m. injection, whereas 300 μg pcDNA3.1 (+) i.m. or 300 μL saline i.m. were used as positive and negative controls, respectively. Each group comprised 28 animals. Peripheral blood samples were collected from 2-210 days after immunization and the proliferation of T lymphocytes, the number of CD4(+) and CD8(+) T cells and the level of IgG assessed. Statistical analysis was performed using a one-way analysis of variance with group multiple comparisons via Tukey's test. The pcDNA-GPV-VP1 DNA and attenuated vaccine induced cellular and humoral responses, and there were no differences between the 20 and 300 μg group in the responses of proliferation of T lymphocyte and the CD8(+) T-cell. However, as to CD4(+) T-cell response and humoral immunity, the 20 μg group performed better than the 300 μg group, which induced better cellular and humoral immunity than live attenuated vaccine. This study showed that it is possible to induce both cellular and humoral response using DNA-based vaccines and that the pcDNA-GPV-VP1 DNA gene vaccine induced better cellular and humoral immunity than live attenuated vaccine.

  15. Re-emergence of diphtheria and pertussis: implications for Nigeria.

    Science.gov (United States)

    Sadoh, A E; Oladokun, R E

    2012-11-26

    In the prevaccine era pertussis and diphtheria were responsible for significant morbidity and mortality in children. In the United States of America more than 125,000 cases of diphtheria with 10,000 deaths were reported annually in the 1920s. In the same period about 1.7 million cases of pertussis with 73,000 deaths were also reported. Vaccination against these two diseases has caused remarkable reduction in the morbidity and mortality from these diseases both in developed and developing countries. The initial vaccines were the combined diphtheria toxoid and whole cell pertussis vaccine. The recent reported increases in the incidence of these two diseases in countries, which maintain high childhood vaccination coverage is a source of concern not only to these countries but also for developing countries with weak immunization programmes. Nigeria for example reported 11,281 cases of pertussis, the second highest number of cases worldwide in 2009. Waning immunity in adult and adolescent populations has been reported and epidemiologically, more cases are being reported in adults and adolescents. Also a high proportion of pertussis cases are being reported in infants and most of these infant cases are linked to adult/adolescent sources. Recent approaches to control of these diseases include booster doses of combined diphtheria, tetanus and acellular pertussis vaccine while the cocooning strategy (which is immunizing every person who is likely to have contact with a given infant such as mother, father, grandparents and health care workers) is being used in a number of countries. For developing countries including Nigeria where the capacity for making the diagnosis of both diseases is limited, strengthening of routine immunization as well as diagnostic capacity is imperative. Research to determine current levels of immunity in children, adolescents and adults is required. This will enable the determination of the need for booster doses and the age at which such boosters

  16. Eventos adversos pós-vacina contra a difteria, coqueluche e tétano e fatores associados à sua gravidade Adverse events following diphtheria, pertussis and tetanus vaccinations and factors associated with severity

    Directory of Open Access Journals (Sweden)

    Fabiana Ramos Martin de Freitas

    2007-12-01

    Full Text Available OBJETIVO: Avaliar os eventos adversos pós-vacina contra a difteria, coqueluche e tétano (EAPV-DPT e os fatores associados à sua gravidade. MÉTODOS: Estudo transversal com componente descritivo e analítico, abrangendo os eventos adversos pós-vacina DPT notificados no Estado de São Paulo, de 1984 a 2001, entre crianças menores de sete anos de idade. A definição de caso foi a adotada pela vigilância de EAPV-DPT; os dados obtidos foram originados da vigilância passiva desses eventos. No cálculo das taxas, o numerador foram os EAPV e o denominador o número de doses aplicadas. A associação entre a gravidade dos EAPV-DPT e as exposições de interesse foi investigada pelas estimativas não ajustadas e ajustadas da odds ratio, com os respectivos intervalos de 95% de confiança, usando regressão logística não condicional. RESULTADOS: Identificaram-se 10.059 EAPV-DPT relativos a 6.266 crianças, apresentando um ou mais EAPV, 29,5% foram internadas e em 68,2% houve contra-indicação das doses subseqüentes de DPT. Cerca de 75% dos eventos ocorreram nas primeiras seis horas após a aplicação da vacina. Os eventos mais freqüentes foram: febreOBJECTIVE: To analyze adverse events following vaccinations against diphtheria, pertussis and tetanus (AEFV-DPT and to investigate factors associated with event severity. METHODS: A cross-sectional study was carried out with a descriptive and analytical component covering AEFV-DPT that were notified in the State of São Paulo, Brazil, between 1984 and 2001, among children less than seven years old. Cases were defined as used in AEFV-DPT surveillance; the data source was AEFV-DPT passive surveillance. In calculating the rates, the numerator was the number of AEFV-DPT and as denominator was the number of doses applied. The association between severity of AEFV-DPT and the exposures of interest was investigated by means of non-adjusted and adjusted estimates of odds ratios, with their respective 95

  17. Enrollment in YFV Vaccine Trial: An Evaluation of Recruitment Outcomes Associated with a Randomized Controlled Double-Blind Trial of a Live Attenuated Yellow Fever Vaccine.

    Science.gov (United States)

    Frew, Paula M; Shapiro, Eve T; Lu, Lu; Edupuganti, Srilatha; Keyserling, Harry L; Mulligan, Mark J

    2013-04-15

    This investigation evaluated several factors associated with diverse participant enrollment of a clinical trial assessing safety, immunogenicity, and comparative viremia associated with administration of 17-D live, attenuated yellow fever vaccine given alone or in combination with human immune globulin. We obtained baseline participant information (e.g., sociodemographic, medical) and followed recruitment outcomes from 2005 to 2007. Of 355 potential Yellow Fever vaccine study participants, 231 cases were analyzed. Strong interest in study participation was observed among racial and ethnically diverse persons with 36.34% eligible following initial study screening, resulting in 18.75% enrollment. The percentage of white participants increased from 63.66% (prescreened sample) to 81.25% (enrollment group). The regression model was significant with white race as a predictor of enrollment (OR=2.744, 95% CI=1.415-5.320, p=0.003).In addition, persons were more likely to enroll via direct outreach and referral mechanisms compared to mass advertising (OR=2.433, 95% CI=1.102-5.369). The findings indicate that racially diverse populations can be recruited to vaccine clinical trials, yet actual enrollment may not reflect that diversity.

  18. DNA vaccines encoding proteins from wild-type and attenuated canine distemper virus protect equally well against wild-type virus challenge.

    Science.gov (United States)

    Nielsen, Line; Jensen, Trine Hammer; Kristensen, Birte; Jensen, Tove Dannemann; Karlskov-Mortensen, Peter; Lund, Morten; Aasted, Bent; Blixenkrone-Møller, Merete

    2012-10-01

    Immunity induced by DNA vaccines containing the hemagglutinin (H) and nucleoprotein (N) genes of wild-type and attenuated canine distemper virus (CDV) was investigated in mink (Mustela vison), a highly susceptible natural host of CDV. All DNA-immunized mink seroconverted, and significant levels of virus-neutralizing (VN) antibodies were present on the day of challenge with wild-type CDV. The DNA vaccines also primed the cell-mediated memory responses, as indicated by an early increase in the number of interferon-gamma (IFN-γ)-producing lymphocytes after challenge. Importantly, the wild-type and attenuated CDV DNA vaccines had a long-term protective effect against wild-type CDV challenge. The vaccine-induced immunity induced by the H and N genes from wild-type CDV and those from attenuated CDV was comparable. Because these two DNA vaccines were shown to protect equally well against wild-type virus challenge, it is suggested that the genetic/antigenic heterogeneity between vaccine strains and contemporary wild-type strains are unlikely to cause vaccine failure.

  19. A live attenuated cold-adapted influenza A H7N3 virus vaccine provides protection against homologous and heterologous H7 viruses in mice and ferrets

    International Nuclear Information System (INIS)

    Joseph, Tomy; McAuliffe, Josephine; Lu, Bin; Vogel, Leatrice; Swayne, David; Jin, Hong; Kemble, George; Subbarao, Kanta

    2008-01-01

    The appearance of human infections caused by avian influenza A H7 subtype viruses underscores their pandemic potential and the need to develop vaccines to protect humans from viruses of this subtype. A live attenuated H7N3 virus vaccine was generated by reverse genetics using the HA and NA genes of a low pathogenicity A/chicken/BC/CN-6/04 (H7N3) virus and the six internal protein genes of the cold-adapted A/Ann Arbor/6/60 ca (H2N2) virus. The reassortant H7N3 BC 04 ca vaccine virus was temperature sensitive and showed attenuation in mice and ferrets. Intranasal immunization with one dose of the vaccine protected mice and ferrets when challenged with homologous and heterologous H7 viruses. The reassortant H7N3 BC 04 ca vaccine virus showed comparable levels of attenuation, immunogenicity and efficacy in mice and ferret models. The safety, immunogenicity, and efficacy of this vaccine in mice and ferrets support the evaluation of this vaccine in clinical trials

  20. Post-licensure, phase IV, safety study of a live attenuated Japanese encephalitis recombinant vaccine in children in Thailand.

    Science.gov (United States)

    Chotpitayasunondh, Tawee; Pruekprasert, Pornpimol; Puthanakit, Thanyawee; Pancharoen, Chitsanu; Tangsathapornpong, Auchara; Oberdorfer, Peninnah; Kosalaraksa, Pope; Prommalikit, Olarn; Tangkittithaworn, Suwimon; Kerdpanich, Phirangkul; Techasaensiri, Chonnamet; Korejwo, Joanna; Chuenkitmongkol, Sunate; Houillon, Guy

    2017-01-05

    Japanese encephalitis is a mosquito-borne viral disease endemic in most countries in Asia. A recombinant live, attenuated Japanese encephalitis virus vaccine, JE-CV, is licensed in 14 countries, including Thailand, for the prevention of Japanese encephalitis in adults and children. This was a prospective, phase IV, open-label, multicentre, safety study of JE-CV conducted from November 2013 to April 2015, to evaluate rare serious adverse events (AEs). JE-CV was administered to 10,000 healthy children aged 9months to vaccination. Serious AEs (SAEs), including AEs of special interest, up to 60days after administration were evaluated. Immediate Grade 3 systemic AEs up to 30min after JE-CV administration were also described. The median age of participants was 1.1years in Group 1 and 3.8years in Group 2. SAEs were reported in 204 (3.0%) participants in Group 1 and 59 (1.9%) participants in Group 2. Among a total of 294 SAEs in 263 participants, only three events occurring in two participants were considered related to vaccination. All three cases were moderate urticaria, none of which met the definition of AEs of special interest for hypersensitivity. AEs of special interest were reported in 28 (0.4%) participants in Group 1 and 4 (0.1%) participants in Group 2; none were considered related to vaccination. Febrile convulsion was the most frequently reported AE of special interest: 25 (0.4%) participants in Group 1; and 2 (vaccination. Our study did not identify any new safety concerns with JE-CV and confirms its good safety profile. This study was registered on www.clinicaltrials.gov (NCT01981967; Universal Trial Number: U1111-1127-7052). Copyright © 2016 The Authors. Published by Elsevier Ltd.. All rights reserved.

  1. Varicella-Zoster Virus-Specific Cellular Immune Responses to the Live Attenuated Zoster Vaccine in Young and Older Adults.

    Science.gov (United States)

    Weinberg, Adriana; Canniff, Jennifer; Rouphael, Nadine; Mehta, Aneesh; Mulligan, Mark; Whitaker, Jennifer A; Levin, Myron J

    2017-07-15

    The incidence and severity of herpes zoster (HZ) increases with age. The live attenuated zoster vaccine generates immune responses similar to HZ. We compared the immune responses to zoster vaccine in young and older to adults to increase our understanding of the immune characteristics that may contribute to the increased susceptibility to HZ in older adults. Young (25-40 y; n = 25) and older (60-80 y; n = 33) adults had similar magnitude memory responses to varicella-zoster virus (VZV) ex vivo restimulation measured by responder cell-frequency and flow cytometry, but the responses were delayed in older compared with young adults. Only young adults had an increase in dual-function VZV-specific CD4 + and CD8 + T cell effectors defined by coexpression of IFN-γ, IL-2, and CD107a after vaccination. In contrast, older adults showed marginal increases in VZV-specific CD8 + CD57 + senescent T cells after vaccination, which were already higher than those of young adults before vaccination. An increase in VZV-stimulated CD4 + CD69 + CD57 + PD1 + and CD8 + CD69 + CD57 + PD1 + T cells from baseline to postvaccination was associated with concurrent decreased VZV-memory and CD8 + effector responses, respectively, in older adults. Blocking the PD1 pathway during ex vivo VZV restimulation increased the CD4 + and CD8 + proliferation, but not the effector cytokine production, which modestly increased with TIM-3 blockade. We conclude that high proportions of senescent and exhausted VZV-specific T cells in the older adults contribute to their poor effector responses to a VZV challenge. This may underlie their inability to contain VZV reactivation and prevent the development of HZ. Copyright © 2017 by The American Association of Immunologists, Inc.

  2. Cold-adapted live attenuated influenza vaccines developed in Russia: Can they contribute to meeting the needs for influenza control in other countries?

    International Nuclear Information System (INIS)

    Kendal, Alan P.

    1997-01-01

    It is now more than 30 years since the first cold-adapted influenza viruses were developed in Russia as potential live, attenuated vaccines. In the past 15-20 years considerable experience has been gained from Russian and joint Russian-US laboratory and clinical studies with type A monovalent and bivalent vaccines prepared with genetic reassortant viruses derived from one of these cold-adapted viruses in particular, A/Leningrad/134/57. More recent experiences include use of trivalent cold-adapted vaccines with a type B component. The overall high level of safety of individual and combined vaccines in pre-school and school-aged children, with illness reductions in open field trials equivalent to that seen with inactivated vaccines, is such as to suggest that practical measures might now be justified to facilitate expansion of the use of these vaccines to other countries. It is proposed that further experimentation with the Russian cold-adapted live attenuated vaccines should be focused on issues that will relate to the public health perspective, i.e. selection of the single best candidate type A and B vaccines for intense study using as criteria their potential for meeting licensing requirements outside Russia, and documenting the clinical protective efficacy of a single vaccine dose compared to two doses as studied until now. Resolution of these issues is important to ensure that costs for future live vaccine production, control, and utilization will be kept at lowest levels so that expanded use of live vaccines will have maximum cost-benefit and affordability. To guide those interested in these issues, examples are given of populations for whom a licensed live cold-adapted vaccine might be considered, together with indications of extra data needed to fully validate each suggested use

  3. Use of the live attenuated Japanese Encephalitis vaccine SA 14-14-2 in children: A review of safety and tolerability studies.

    Science.gov (United States)

    Ginsburg, Amy Sarah; Meghani, Ankita; Halstead, Scott B; Yaich, Mansour

    2017-10-03

    Japanese encephalitis (JE) is the leading cause of viral neurological disease and disability in Asia. Some 50-80% of children with clinical JE die or have long-term neurologic sequelae. Since there is no cure, human vaccination is the only effective long-term control measure, and the World Health Organization recommends that at-risk populations receive a safe and effective vaccine. Four different types of JE vaccines are currently available: inactivated mouse brain-derived vaccines, inactivated Vero cell vaccines, live attenuated SA 14-14-2 vaccines and a live recombinant (chimeric) vaccine. With the rapidly increasing demand for and availability and use of JE vaccines, countries face an important decision in the selection of a JE vaccine. This article provides a comprehensive review of the available safety literature for the live attenuated SA 14-14-2 JE vaccine (LAJEV), the most widely used new generation JE vaccine. With well-established effectiveness data, a single dose of LAJEV protects against clinical JE disease for at least 5 years, providing a long duration of protection compared with inactivated mouse brain-derived vaccines. Since 1988, about 700 million doses of the LAJEV have been distributed globally. Our review found that LAJEV is well tolerated across a wide age range and can safely be given to children as young as 8 months of age. While serious adverse events attributable to LAJEV have been reported, independent experts have not found sufficient evidence for causality based on the available data.

  4. Horizontal transmission of the Leningrad-3 live attenuated mumps vaccine virus.

    Science.gov (United States)

    Atrasheuskaya, A V; Neverov, A A; Rubin, S; Ignatyev, G M

    2006-03-06

    Here we describe symptomatic transmission of the Leningrad-3 mumps vaccine virus from healthy vaccinees to previously vaccinated contacts. Throat swab and serum samples were taken from six symptomatic mumps cases and from 13 family contacts. Assessment of serum IgG and IgM anti-mumps virus antibodies and IgG avidity testing was performed using commercial test kits. Sera neutralizing antibodies were measured by plaque reduction neutralization assay using the L-3 vaccine mumps virus as the target. All six of the symptomatic mumps cases and three contact subjects tested positive for mumps by RT-PCR. The genomic sequences tested (F, SH and HN genes) of all nine of these samples were identical to the L-3 mumps vaccine strain. All 13 contacts were asymptomatic; however clear serological evidence of mumps infection was found in some of them. The likely epidemiological source of the transmitted L-3 mumps virus was children who were recently vaccinated at the schools attended by the six symptomatic mumps patients described here. The L-3 mumps vaccine virus can be shed and transmitted horizontally, even to subjects previously vaccinated with the same virus.

  5. Genomic analysis of an attenuated Chlamydia abortus live vaccine strain reveals defects in central metabolism and surface proteins.

    Science.gov (United States)

    Burall, L S; Rodolakis, A; Rekiki, A; Myers, G S A; Bavoil, P M

    2009-09-01

    Comparative genomic analysis of a wild-type strain of the ovine pathogen Chlamydia abortus and its nitrosoguanidine-induced, temperature-sensitive, virulence-attenuated live vaccine derivative identified 22 single nucleotide polymorphisms unique to the mutant, including nine nonsynonymous mutations, one leading to a truncation of pmpG, which encodes a polymorphic membrane protein, and two intergenic mutations potentially affecting promoter sequences. Other nonsynonymous mutations mapped to a pmpG pseudogene and to predicted coding sequences encoding a putative lipoprotein, a sigma-54-dependent response regulator, a PhoH-like protein, a putative export protein, two tRNA synthetases, and a putative serine hydroxymethyltransferase. One of the intergenic mutations putatively affects transcription of two divergent genes encoding pyruvate kinase and a putative SOS response nuclease, respectively. These observations suggest that the temperature-sensitive phenotype and associated virulence attenuation of the vaccine strain result from disrupted metabolic activity due to altered pyruvate kinase expression and/or alteration in the function of one or more membrane proteins, most notably PmpG and a putative lipoprotein.

  6. Cost-effectiveness analysis of intranasal live attenuated vaccine (LAIV versus injectable inactivated influenza vaccine (TIV for Canadian children and adolescents

    Directory of Open Access Journals (Sweden)

    Tarride JE

    2012-10-01

    Full Text Available Jean-Eric Tarride,1,2 Natasha Burke,1,2 Camilla Von Keyserlingk,1,2 Daria O'Reilly,1,2 Feng Xie,1,2 Ron Goeree1,21Programs for Assessment of Technology in Health (PATH Research Institute, St Joseph's Healthcare Hamilton, Hamilton, 2Department of Clinical Epidemiology and Biostatistics, Faculty of Health Sciences, McMaster University, Hamilton, Ontario, CanadaBackground: Influenza affects all age groups and is common in children. Between 15% and 42% of preschool- and school-aged children experience influenza each season. Recently, intranasal live attenuated influenza vaccine, trivalent (LAIV has been approved in Canada.Objective: The objective of this study was to determine the cost-effectiveness of LAIV compared with that of the injectable inactivated influenza vaccine, trivalent (TIV in Canadian children and adolescents from both a payer (eg. Ministry of Health perspective and a societal perspective.Methods: A cost-effectiveness model comparing LAIV and TIV in children aged 24–59 months old was supplemented by primary (ie, a survey of 144 Canadian physicians and secondary (eg, literature data to model children aged 2–17 years old. Parameter uncertainty was addressed through univariate and probability analyses.Results: Although LAIV increased vaccination costs when compared to TIV, LAIV reduced the number of influenza cases and lowered the number of hospitalizations, emergency room visits, outpatient visits, and parents’ days lost from work. The estimated offsets in direct and societal costs saved were CAD$4.20 and CAD$35.34, respectively, per vaccinated child aged 2–17 years old. When costs and outcomes were considered, LAIV when compared to TIV, was the dominant strategy. At a willingness to pay of CAD$50,000 per quality adjusted life year gained, or CAD$100,000 per quality adjusted life year gained, the probabilistic results indicated that the probability of LAIV being cost-effective was almost 1.Conclusions: LAIV reduces the burden

  7. The Diagnostic Value of ELISA Method for Pertussis in Children

    Directory of Open Access Journals (Sweden)

    O. P. Popova

    2016-01-01

    Full Text Available Because of low effectiveness of laboratory methods for diagnosing pertussis it is important to look for new ways of verification of this infection. The article presents the analysis of the diagnostic value of ELISA method, which involves the identification of antibodies of different isotypes (IgM, IgG, IgA to pertussis toxoid (PT and filamentous haemagglutinin (FHA. The study included 279 children: 114 were under 1 year of age, 165 — older than 1 year. The pertussis was confirmed in 74.3 ± 2.6% of patients by using ELISA method. A significant proportion of seronegative patients (46.1 ± 6.2 per cent was revealed in the group of patients under 1 year. The pattern of production of antibodies in unvaccinated children was different. It depended on the age of the children and timing of illness. A low proportion of diagnostically significant indicators of IgM-antibodies at 2—3 weeks of illness was typical for patients under 1 year of age (e.g. 6.7 ± 6.5% as compared to 20.0 ± 7.9% and 50.0 ± 15.3 — 1—3 and 4—6 years of age. The diagnosis of pertussis in children under 1 year of age was confirmed mainly by the detection of IgG, starting from the 4th week of the disease. In the examination of vaccinated children diagnostically significant levels of IgA and IgG were identified (even in the late stages of the disease. Thus, the results of the analysis show special significance of using ELISA method for the diagnosis of pertussis in vaccinated children.

  8. Live Attenuated Recombinant Vaccine Protects Nonhuman Primates Against Ebola and Marburg Viruses

    National Research Council Canada - National Science Library

    Jones, Steven M; Feldmann, Heinz; Stroher, Ute; Geisbert, Joan B; Fernando, Lisa; Grolla, Allen; Klenk, Hans-Dieter; Sullivan, Nancy J; Volchkov, Viktor E; Fritz, Elizabeth A; Daddario, Kathleen M; Hensley, Lisa E; Jahrling, Peter B; Geisbert, Thomas W

    2005-01-01

    Vaccines and therapies are urgently needed to address public health needs stemming from emerging pathogens and biological threat agents such as the filoviruses Ebola virus (EBOV) and Marburg virus (MARV...

  9. Cell-associated flagella enhance the protection conferred by mucosally-administered attenuated Salmonella Paratyphi A vaccines.

    Directory of Open Access Journals (Sweden)

    Orit Gat

    2011-11-01

    Full Text Available Antibiotic-resistant Salmonella enterica serovar Paratyphi A, the agent of paratyphoid A fever, poses an emerging public health dilemma in endemic areas of Asia and among travelers, as there is no licensed vaccine. Integral to our efforts to develop a S. Paratyphi A vaccine, we addressed the role of flagella as a potential protective antigen by comparing cell-associated flagella with exported flagellin subunits expressed by attenuated strains.S. Paratyphi A strain ATCC 9150 was first deleted for the chromosomal guaBA locus, creating CVD 1901. Further chromosomal deletions in fliD (CVD 1901D or flgK (CVD 1901K were then engineered, resulting in the export of unpolymerized FliC, without impairing its overall expression. The virulence of the resulting isogenic strains was examined using a novel mouse LD(50 model to accommodate the human-host restricted S. Paratyphi A. The immunogenicity of the attenuated strains was then tested using a mouse intranasal model, followed by intraperitoneal challenge with wildtype ATCC 9150.Mucosal (intranasal immunization of mice with strain CVD 1901 expressing cell-associated flagella conferred superior protection (vaccine efficacy [VE], 90% against a lethal intraperitoneal challenge, compared with the flagellin monomer-exporting mutants CVD 1901K (30% VE or CVD 1901D (47% VE. The superior protection induced by CVD 1901 with its cell-attached flagella was associated with an increased IgG2a:IgG1 ratio of FliC-specific antibodies with enhanced opsonophagocytic capacity.Our results clearly suggest that enhanced anti-FliC antibody-mediated clearance of S. Paratyphi A by phagocytic cells, induced by vaccines expressing cell-associated rather than exported FliC, might be contributing to the vaccine-induced protection from S. Paratyphi A challenge in vivo. We speculate that an excess of IgG1 anti-FliC antibodies induced by the exported FliC may compete with the IgG2a subtype and block binding to specific phagocyte Fc

  10. An aerial baiting system for the distribution of attenuated or recombinant rabies vaccines for foxes, raccoons, and skunks.

    Science.gov (United States)

    Johnston, D H; Voigt, D R; MacInnes, C D; Bachmann, P; Lawson, K F; Rupprecht, C E

    1988-01-01

    An aerial baiting system was developed to deliver oral rabies vaccines to wild carnivore vectors of rabies, e.g., red fox, striped skunk, and raccoon. The bait consists of a polyethylene bag that contains either a 30-g hamburger ball or a 25-mL cube of polyurethane sponge coated with a wax-beef tallow mixture containing 100-150 mg of tetracycline as a biomarker. Attractants used with the sponge were added to the bag (e.g., liver slurry, cheeses, fish oils, or fruits). Baits (greater than 80,000) were dropped from light aircraft at densities of 18-120 baits/km2 over test areas in Ontario and Pennsylvania. Rates of bait acceptance were assessed by the presence of fluorescent tetracycline deposits in the teeth of animals obtained from hunters and trappers. Bait acceptance reached 74% in foxes, 54% in skunks, 43% in raccoons, and 85% in coyotes in the Ontario trials; bait acceptance by raccoons in a small trial in Pennsylvania reached 76%. Also, 66% of juvenile foxes that ate baits ate a second bait 7 or more days after eating the first, thus giving the potential for a booster effect. The cost of aerial distribution of bait (excluding cost of bait and vaccine) in Canadian dollars was $1.45/km2. The aerial distribution system is capable of economically reaching a high proportion of foxes, skunks, and raccoons over large areas. Trials with attenuated ERA (Evelyn-Rokitnicki-Abelseth) vaccines are under way in Ontario.

  11. A recombinant live attenuated tetravalent vaccine for the prevention of dengue.

    Science.gov (United States)

    Guy, Bruno; Noriega, Fernando; Ochiai, R Leon; L'azou, Maïna; Delore, Valentine; Skipetrova, Anna; Verdier, François; Coudeville, Laurent; Savarino, Stephen; Jackson, Nicholas

    2017-07-01

    Dengue is an important and still growing public health problem associated with substantial morbidity, as well as significant social and economic impact. The present review describes the main features and development of the first dengue vaccine (CYD-TDV, Dengvaxia®), which has been licensed by several dengue-endemic countries in Asia and Latin America for use in populations above 9 years of age. Areas covered: The review focuses on the large clinical development of CYD-TDV, which includes in particular two pivotal phase III efficacy trials conducted in Asia and Latin America and supported vaccine licensure. Based on these clinical data, the WHO Strategic Advisory Group of Experts (SAGE) on Immunization recommended considering introduction of the vaccine in geographic settings (national or subnational) with high burden of disease. Long-term safety follow-up studies of the efficacy trials are currently ongoing, and post-licensure studies will evaluate the vaccine effectiveness and safety in 'real-life' following vaccine introduction. Expert commentary: During vaccine development, a number of complexities were tackled, innovation pursued, and risk managed. These aspects, as well as the potential impact of CYD-TDV on public health are also discussed.

  12. Immunization status of Iranian military recruits against Bordetella pertussis infection (whooping cough).

    Science.gov (United States)

    Izadi, Morteza; Afsharpaiman, Shahla; Jonaidi Jafari, Nematollah; Ranjbar, Reza; Gooya, Mohammad Mahdi; Robat Sarpooshi, Javad; Esfahani, Ali Akbar; Soheylipoor, Hamid

    2011-03-21

    Military recruits are susceptible to respiratory pathogens because of increased antibiotic resistance and the lack of an effective vaccine. The goal of the current study was to determine the immunological status of the Bordetella pertussis among conscripts in Iranian military garrisons. The study population consisted of 424 conscripts aged 18 to 21 years who enrolled for military service. They were selected using cluster stratified sampling from all military garrisons in Tehra, Iran. To determine the seroprevalence of infection, blood specimens from all recruits were collected and stored at - 20 °C until assayed. All serum samples were screened for immunoglobulin G (IgG) antibodies against Bordetella pertussis toxin (PT) and by using enzyme-linked immunosorbent assay (ELISA). The overall prevalence of B. pertussis seropositivity in military recruits was 60.6. Only 55.0% of the recruits had low awareness about the record of vaccination against B. pertussis during childhood. Among 424 studied individuals, 48 recruits (11.3%) had a positive history of whooping cough; prevalence of seropositivity in these recruits was 70.0%. Among these subjects, 61.7% were referred to a physician for treatment and only 39.6% of them were administered anti-pertussis therapy. Our study showed that military conscripts in Tehran garrisons were not serologically immune to pertussis and also confirmed the low awareness about vaccination and medical history related to pertussis infection in this high-risk subgroup of the Iranian population. Routine acellular booster vaccination, particularly before 18 years of age, is recommended.

  13. Live attenuated measles vaccine expressing HIV-1 Gag virus like particles covered with gp160ΔV1V2 is strongly immunogenic

    International Nuclear Information System (INIS)

    Guerbois, Mathilde; Moris, Arnaud; Combredet, Chantal; Najburg, Valerie; Ruffie, Claude; Fevrier, Michele; Cayet, Nadege; Brandler, Samantha; Schwartz, Olivier; Tangy, Frederic

    2009-01-01

    Although a live attenuated HIV vaccine is not currently considered for safety reasons, a strategy inducing both T cells and neutralizing antibodies to native assembled HIV-1 particles expressed by a replicating virus might mimic the advantageous characteristics of live attenuated vaccine. To this aim, we generated a live attenuated recombinant measles vaccine expressing HIV-1 Gag virus-like particles (VLPs) covered with gp160ΔV1V2 Env protein. The measles-HIV virus replicated efficiently in cell culture and induced the intense budding of HIV particles covered with Env. In mice sensitive to MV infection, this recombinant vaccine stimulated high levels of cellular and humoral immunity to both MV and HIV with neutralizing activity. The measles-HIV virus infected human professional antigen-presenting cells, such as dendritic cells and B cells, and induced efficient presentation of HIV-1 epitopes and subsequent activation of human HIV-1 Gag-specific T cell clones. This candidate vaccine will be next tested in non-human primates. As a pediatric vaccine, it might protect children and adolescents simultaneously from measles and HIV.

  14. Investigation of Pertussis Cases in a Texas County, 2008-2012.

    Science.gov (United States)

    Staudt, Amanda; Mangla, Anil T; Alamgir, Hasanat

    2015-07-01

    Within the past 25 years, there has been a dramatic increase in the incidence of pertussis cases in the United States. As such, this investigation reports on the high-risk groups and describes risk factors of pertussis cases in a large Texas county. This study was a cross-sectional analysis of data collected by health department employees using the Texas Department of State Health Service's Pertussis Case Track Record, which is the standard investigation form for collecting vital information on pertussis cases. We extracted and analyzed county-level data for a 5-year period (2008-2012). The study population at risk included all current residents in this county, and cases included all who were clinically diagnosed as having confirmed or probable pertussis cases that were reported to the health department according to the Centers for Disease Control and Prevention case definition. The vaccination status of a case was defined as fully vaccinated, partially vaccinated, or not vaccinated. A total of 198 probable and confirmed pertussis cases were included in this analysis. Most of the cases were infants younger than 1 year old (n = 107). The largest category of cases was not vaccinated and of the rest, 32.8% were partially vaccinated, 17.2% had unknown vaccination status, and 13.1% were fully vaccinated. Only 48 (24.2%) sources of exposure were identified and they included fathers (14.6%), sisters (14.6%), brothers (14.6%), other children (14.6%), and mothers (12.5%). Many sources of exposure (n = 26, 54.1%) were unaware of their vaccination history. Hispanics accounted for 84.5% of cases in the younger than 1 year old group and 88.9% of cases were in the 1 to 2 years old group. With respect to race/ethnicity and vaccination status of the cases, 39.46% of Hispanics, 32% of whites, and 50% of blacks were reported to be unvaccinated. Increasing pertussis vaccination coverage among children, as well as providing booster shots to adults with special attention on the

  15. Protection against Pertussis in Humans Correlates to Elevated Serum Antibodies and Memory B Cells

    Directory of Open Access Journals (Sweden)

    Valentina Marcellini

    2017-09-01

    Full Text Available Pertussis is a respiratory infection caused by Bordetella pertussis that may be particularly severe and even lethal in the first months of life when infants are still too young to be vaccinated. Adults and adolescents experience mild symptoms and are the source of infection for neonates. Adoptive maternal immunity does not prevent pertussis in the neonate. We compared the specific immune response of mothers of neonates diagnosed with pertussis and mothers of control children. We show that women have pre-existing pertussis-specific antibodies and memory B cells and react against the infection with a recall response increasing the levels specific serum IgG, milk IgA, and the frequency of memory B cells of all isotypes. Thus, the maternal immune system is activated in response to pertussis and effectively prevents the disease indicating that the low levels of pre-formed serum antibodies are insufficient for protection. For this reason, memory B cells play a major role in the adult defense. The results of this study suggest that new strategies for vaccine design should aim at increasing long-lived plasma cells and their antibodies.

  16. Substitutions at residues 300 and 389 of the VP2 capsid protein serve as the minimal determinant of attenuation for canine parvovirus vaccine strain 9985-46.

    Science.gov (United States)

    Sehata, Go; Sato, Hiroaki; Yamanaka, Morimasa; Takahashi, Takuo; Kainuma, Risa; Igarashi, Tatsuhiko; Oshima, Sho; Noro, Taichi; Oishi, Eiji

    2017-11-01

    Identifying molecular determinants of virulence attenuation in live attenuated canine parvovirus (CPV) vaccines is important for assuring their safety. To this end, we identified mutations in the attenuated CPV 9985-46 vaccine strain that arose during serial passage in Crandell-Rees feline kidney cells by comparison with the wild-type counterpart, as well as minimal determinants of the loss of virulence. Four amino acid substitutions (N93K, G300V, T389N and V562L) in VP2 of strain 9985-46 significantly restricted infection in canine A72 cells. Using an infectious molecular clone system, we constructed isogenic CPVs of the parental virulent 9985 strain carrying single or double mutations. We observed that only a single amino acid substitution in VP2, G300V or T389N, attenuated the virulent parental virus. Combinations of these mutations further attenuated CPV to a level comparable to that of 9985-46. Strains with G300V/T389N substitutions did not induce clinical symptoms in experimentally infected pups, and their ability to infect canine cells was highly restricted. We found that another G300V/V562L double mutation decreased affinity of the virus for canine cells, although its pathogenicity to dogs was maintained. These results indicate that mutation of residue 300, which plays a critical role in host tropism, is not sufficient for viral attenuation in vivo, and that attenuation of 9985-46 strain is defined by at least two mutations in residues 300 and 389 of the VP2 capsid protein. This finding is relevant for quality control of the vaccine and provides insight into the rational design of second-generation live attenuated vaccine candidates.

  17. Expression of the Surface Glycoproteins of Human Parainfluenza Virus Type 3 by Bovine Parainfluenza Virus Type 3, a Novel Attenuated Virus Vaccine Vector

    OpenAIRE

    Haller, Aurelia A.; Miller, Tessa; Mitiku, Misrach; Coelingh, Kathleen

    2000-01-01

    Bovine parainfluenza virus type 3 (bPIV3) is being evaluated as an intranasal vaccine for protection against human PIV3 (hPIV3). In young infants, the bPIV3 vaccine appears to be infectious, attenuated, immunogenic, and genetically stable, which are desirable characteristics for an RNA virus vector. To test the potential of the bPIV3 vaccine strain as a vector, an infectious DNA clone of bPIV3 was assembled and recombinant bPIV3 (r-bPIV3) was rescued. r-bPIV3 displayed a temperature-sensitive...

  18. Maternal uptake of pertussis cocooning strategy and other pregnancy related recommended immunizations.

    Science.gov (United States)

    Wong, C Y; Thomas, N J; Clarke, M; Boros, C; Tuckerman, J; Marshall, H S

    2015-01-01

    Maternal immunization is an important strategy to prevent severe morbidity and mortality in mothers and their offspring. This study aimed to identify whether new parents were following immunization recommendations prior to pregnancy, during pregnancy, and postnatally. A cross-sectional survey was conducted by a questionnaire administered antenatally to pregnant women attending a maternity hospital with a follow-up telephone interview at 8-10 weeks post-delivery. Factors associated with uptake of pertussis vaccination within the previous 5 y or postnatally and influenza vaccination during pregnancy were explored using log binomial regression models. A total of 297 pregnant women completed the questionnaire. For influenza vaccine, 20.3% were immunized during pregnancy and 3.0% postnatally. For pertussis vaccine, 13.1% were vaccinated within 5 y prior to pregnancy and 31 women received the vaccine postnatally, 16 (51.6%) received the vaccine >4 weeks after delivery. Receiving a recommendation from a healthcare provider (HCP) was an independent predictor for receipt of both pertussis (RR 2.07, p immunization is low and likely due to poor knowledge of availability, language barriers and lack of recommendations from HCPs. Strategies to improve maternal vaccine uptake should include education about recommended vaccines for both HCPs and parents and written information in a variety of languages.

  19. Pertussis Reinfection in an Adult: A Cause of Persistent Cough Not to Be Ignored

    Directory of Open Access Journals (Sweden)

    Theocharis Koufakis

    2017-01-01

    Full Text Available Pertussis is traditionally considered as a disease of the childhood; however, accumulating evidence suggests a stable increase of its incidence among adults and adolescents, during the last decades. Despite the fact that reinfection after natural disease or vaccination is not uncommon, the index of clinical suspicion of pertussis diagnosis in adults remains low. In this article, we report a case of pertussis reinfection 30 years after natural infection, which was complicated by pneumonia, and we discuss our diagnostic and therapeutic approach, aiming to raise clinicians’ degree of suspicion regarding pertussis diagnosis in adults. Prompt recognition and appropriate therapy of adult patients can result in the effective control of the symptoms, prevention of severe complications, and spread of the infection to children; thus, they are of great clinical and public health importance.

  20. The possible use of 60Co irradiation attenuated vaccine for the control of human Leishmaniasis in Ethiopia. Part of a coordinated programme on the use of nuclear techniques in the preparation of vaccines against parasitic diseases

    International Nuclear Information System (INIS)

    Lemma, A.

    1977-10-01

    Radiation effects and the evaluation of radiation-attenuated organisms as vaccines was studied with Leishmania enriettii infections in guinea pigs. The use of heat-killed or live but radiation-attenuated promastigotes with or without the concurrent use of BCG as adjuvant failed to elicit protection to challenge with normal virulent organisms. The effects of varying several factors such as irradiation dose, internal from vaccination to challenge, and the use of irradiated macrophages infected with leishmanial organisms failed to elicit protective immunity

  1. Replacement of the Ectodomains of the Hemagglutinin-Neuraminidase and Fusion Glycoproteins of Recombinant Parainfluenza Virus Type 3 (PIV3) with Their Counterparts from PIV2 Yields Attenuated PIV2 Vaccine Candidates

    OpenAIRE

    Tao, Tao; Skiadopoulos, Mario H.; Davoodi, Fatemeh; Riggs, Jeffrey M.; Collins, Peter L.; Murphy, Brian R.

    2000-01-01

    We sought to develop a live attenuated parainfluenza virus type 2 (PIV2) vaccine strain for use in infants and young children, using reverse genetic techniques that previously were used to rapidly produce a live attenuated PIV1 vaccine candidate. The PIV1 vaccine candidate, designated rPIV3-1cp45, was generated by substituting the full-length HN and F proteins of PIV1 for those of PIV3 in the attenuated cp45 PIV3 vaccine candidate (T. Tao et al., J. Virol. 72:2955–2961, 1998; M. H. Skiadopoul...

  2. WHO informal consultation on quality, safety and efficacy specifications for live attenuated rotavirus vaccines Mexico City, Mexico, 8-9 February 2005.

    Science.gov (United States)

    Wood, David

    2005-12-01

    Rotavirus vaccines are at an advanced stage of development but there are as yet no WHO recommendations on production and quality control to provide regulatory guidance. A meeting of experts was convened by WHO and PAHO/AMRO to review the scientific basis for production and quality control of rotavirus vaccines, and to discuss specific measures to assure the safety and efficacy of rotavirus vaccines. The meeting was attended by 25 experts from 14 countries, drawn from academia, public health, national regulatory authorities and vaccine producers. It was agreed that existing guidance for other live virus vaccines provides a very good basis for product characterization, especially for source materials and control of production. The basis for attenuation of current vaccines or vaccine candidates is not known but, at least for the vaccines based on the Jennerian approach of using animal (bovine) rotaviruses, is likely to be multigenic. The risk of intussusception in humans is influenced by genetic background and age. Recent analyzes of large vaccine safety trials found that certain strains of vaccine virus were not associated with intussusception, although in these trials the first dose of vaccine was not administered to children over 3 months of age. Since age is a risk factor for intussusception, this may suggest that early delivery of the first dose of vaccine is desirable. However, maternal antibodies may mitigate against early delivery of the first vaccine dose. Factors which could affect vaccine efficacy or safety include strain diversity, malnutrition, other enteric infections, parasitic infection or immune suppression. It was concluded that data from clinical trials conducted in one part of the world would not necessarily be predictive of vaccine efficacy in other places. It was agreed that in nonclinical evaluations there was a need to use oral dosing for toxicity studies and, because rotavirus is non-neurovirulent, that there was no need for an animal

  3. Infectivity of attenuated poxvirus vaccine vectors and immunogenicity of a raccoonpox vectored rabies vaccine in the Brazilian Free-tailed bat (Tadarida brasiliensis)

    Science.gov (United States)

    Stading, Benjamin; Osorio, Jorge E.; Velasco-Villa, Andres; Smotherman, Michael; Kingstad-Bakke, Brock; Rocke, Tonie E.

    2016-01-01

    Bats (Order Chiroptera) are an abundant group of mammals with tremendous ecological value as insectivores and plant dispersers, but their role as reservoirs of zoonotic diseases has received more attention in the last decade. With the goal of managing disease in free-ranging bats, we tested modified vaccinia Ankara (MVA) and raccoon poxvirus (RCN) as potential vaccine vectors in the Brazilian Free-tailed bat (Tadarida brasiliensis), using biophotonic in vivo imaging and immunogenicity studies. Animals were administered recombinant poxviral vectors expressing the luciferase gene (MVA-luc, RCN-luc) through oronasal (ON) or intramuscular (IM) routes and subsequently monitored for bioluminescent signal indicative of viral infection. No clinical illness was noted after exposure to any of the vectors, and limited luciferase expression was observed. Higher and longer levels of expression were observed with the RCN-luc construct. When given IM, luciferase expression was limited to the site of injection, while ON exposure led to initial expression in the oral cavity, often followed by secondary replication at another location, likely the gastric mucosa or gastric associated lymphatic tissue. Viral DNA was detected in oral swabs up to 7 and 9 days post infection (dpi) for MVA and RCN, respectively. While no live virus was detected in oral swabs from MVA-infected bats, titers up to 3.88 x 104 PFU/ml were recovered from oral swabs of RCN-infected bats. Viral DNA was also detected in fecal samples from two bats inoculated IM with RCN, but no live virus was recovered. Finally, we examined the immunogenicity of a RCN based rabies vaccine (RCN-G) following ON administration. Significant rabies neutralizing antibody titers were detected in the serum of immunized bats using the rapid fluorescence focus inhibition test (RFFIT). These studies highlight the safety and immunogenicity of attenuated poxviruses and their potential use as vaccine vectors in bats.

  4. Revaccination with Live Attenuated Vaccines Confer Additional Beneficial Nonspecific Effects on Overall Survival

    DEFF Research Database (Denmark)

    Benn, Christine S; Fisker, Ane B; Whittle, Hilton C

    2016-01-01

    BACKGROUND: Live vaccines against measles (MV), tuberculosis (BCG), polio (OPV) and smallpox reduce mortality more than explained by target-disease prevention. The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in presence of maternal antibodies. We therefore hypothesi......BACKGROUND: Live vaccines against measles (MV), tuberculosis (BCG), polio (OPV) and smallpox reduce mortality more than explained by target-disease prevention. The beneficial nonspecific effects (NSEs) of MV are strongest when MV is given in presence of maternal antibodies. We therefore...

  5. Mast cell activator compound 48/40 is not an effective adjuvant for UV-attenuated Toxoplasma gondii vaccine.

    Science.gov (United States)

    Li, Xi; Chen, Shengjie; Huang, Shiguang; Lu, Fangli

    2017-08-01

    Toxoplasma gondii (T. gondii, Tg) is a globally distributed parasitic protozoan causing different forms of toxoplasmosis in humans. Mast cells (MCs) play a role during T. gondii infection. Several studies suggest that MC activator compound 48/80 (C48/80) may be an effective vaccine adjuvant resulting in a potent and protective antigen-specific immune response against bacteria or virus infections. The present study was performed to determine whether C48/80 had adjuvant activity for ultraviolet (UV)-attenuated T. gondii vaccine to induce protective immune responses against T. gondii in mouse model. Kunming mice were divided into the following groups: naive mice, naive mice administrated with C48/80 intraperitoneal (i.p.) injection, mice infected by i.p. injection of 10 4 T. gondii RH strain alone (Tg group), mice infected with 10 4 RH tachyzoites plus C48/80 administration (Tg + C48/80), mice immunized with UV-Tg alone, and mice immunized with UV-Tg plus C48/80 administration (UV-Tg + C48/80). All the vaccinated mice were challenged with 10 4 tachyzoites of T. gondii RH strain at the same time as the primary infection. The survival rates, liver histopathologies, liver parasite burdens, and mRNA expression levels of Th1 and Th2 cytokines in the livers and spleens detected by quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR) were compared among the aforementioned groups after primary infection or challenge infection. The results showed that, compared to the Tg group or Tg + C48/80 group, the UV-Tg + Tg group and UV-Tg + C48/80 + Tg group had significantly prolonged survival time, lower liver histopathological scores, decreased liver parasite burdens, and increased levels of Th1 and Th2 cytokines in the livers and spleens. There was no significant difference of survival time between the UV-Tg + Tg group and the UV-Tg + C48/80 + Tg group; however, the UV-Tg + C48/80 + Tg group showed higher parasite burden, more severe

  6. Pertussis prevalence and its determinants among children with persistent cough in urban Uganda.

    Directory of Open Access Journals (Sweden)

    Vincent Kayina

    Full Text Available We determined prevalence of pertussis infection and its associated host and environmental factors to generate information that would guide strategies for disease control.In a cross-sectional study, 449 children aged 3 months to 12 years with persistent cough lasting ≥14 days were enrolled and evaluated for pertussis using DNA polymerase chain reaction (PCR and ELISA serology tests.Pertussis prevalence was 67 (15% (95% Confidence Interval (CI: 12-18 and 81 (20% (95% CI: 16-24 by PCR and ELISA, respectively among 449 participating children. The prevalence was highest in children with >59 months of age despite high vaccination coverage of 94% in this age group. Study demographic and clinical characteristics were similar between pertussis and non-pertussis cases. Of the 449 children, 133 (30% had a coughing household member and 316 (70% did not. Among 133 children that had a coughing household member, sex of child, sharing bed with a coughing household member and having a coughing individual in the neighborhood were factors associated with pertussis. Children that had shared a bed with a coughing household individual had seven-fold likelihood of having pertussis compared to children that did not (odds ratio (OR 7.16 (95% CI: 1.24-41.44. Among the 316 children that did not have a coughing household member, age 40 years of age were the factors associated with pertussis. Age 59 months of age, suggesting the possibility of waning immunity. The factors associated with pertussis varied by presence or absence of a coughing household member.

  7. Live attenuated tetravalent (G1-G4) bovine-human reassortant rotavirus vaccine (BRV-TV): Randomized, controlled phase III study in Indian infants.

    Science.gov (United States)

    Saluja, Tarun; Palkar, Sonali; Misra, Puneet; Gupta, Madhu; Venugopal, Potula; Sood, Ashwani Kumar; Dhati, Ravi Mandyam; Shetty, Avinash; Dhaded, Sangappa Malappa; Agarkhedkar, Sharad; Choudhury, Amlan; Kumar, Ramesh; Balasubramanian, Sundaram; Babji, Sudhir; Adhikary, Lopa; Dupuy, Martin; Chadha, Sangeet Mohan; Desai, Forum; Kukian, Darshna; Patnaik, Badri Narayan; Dhingra, Mandeep Singh

    2017-06-16

    Rotavirus remains the leading cause of diarrhoea among children rotavirus vaccine (BRV-TV) over the licensed human-bovine pentavalent rotavirus vaccine RV5. Phase III single-blind study (parents blinded) in healthy infants randomized (1:1) to receive three doses of BRV-TV or RV5 at 6-8, 10-12, and 14-16weeks of age. All concomitantly received a licensed diphtheria, tetanus, pertussis, hepatitis B, Haemophilus influenzae type b conjugate vaccine (DTwP-HepB-Hib) and oral polio vaccine (OPV). Immunogenic non-inferiority was evaluated in terms of the inter-group difference in anti-rotavirus serum IgA seroresponse (primary endpoint), and seroprotection/seroresponse rates to DTwP-HepB-Hib and OPV vaccines. Seroresponse was defined as a ≥4-fold increase in titers from baseline to D28 post-dose 3. Non-inferiority was declared if the difference between groups (based on the lower limit of the 95% confidence interval [CI]) was above -10%. Each subject was evaluated for solicited adverse events 7days and unsolicited & serious adverse events 28days following each dose of vaccination. Of 1195 infants screened, 1182 were randomized (590 to BRV-TV; 592 to RV5). Non-inferiority for rotavirus serum IgA seroresponse was not established: BRV-TV, 47.1% (95%CI: 42.8; 51.5) versus RV5, 61.2% (95%CI: 56.8; 65.5); difference between groups, -14.08% (95%CI: -20.4; -7.98). Serum IgA geometric mean concentrations at D28 post-dose 3 were 28.4 and 50.1U/ml in BRV-TV and RV5 groups, respectively. For all DTwP-HepB-Hib and OPV antigens, seroprotection/seroresponse was elicited in both groups and the -10% non-inferiority criterion between groups was met. There were 16 serious adverse events, 10 in BRV-TV group and 6 in RV5 group; none were classified as vaccine related. Both groups had similar vaccine safety profiles. BRV-TV was immunogenic but did not meet immunogenic non-inferiority criteria to RV5 when administered concomitantly with routine pediatric antigens in infants. Copyright © 2017

  8. Vaccine-induced inflammation attenuates the vascular responses to mental stress

    NARCIS (Netherlands)

    Paine, N.J.; Ring, C.; Bosch, J.A.; Drayson, M.T.; Aldred, S.; Veldhuijzen van Zanten, J.J.C.S.

    2014-01-01

    Inflammation is associated with poorer vascular function, with evidence to suggest that inflammation can also impair the vascular responses to mental stress. This study examined the effects of vaccine-induced inflammation on vascular responses to mental stress in healthy participants. Eighteen male

  9. Assessment of Radiation-Attenuated Vaccine or Thyme Oil Treatment on Controlling DNA Damage and Nitric Oxide Synthesis in Brain of Rat Infected with Toxocara canis

    International Nuclear Information System (INIS)

    Amin, M.M.; Hafez, E.N.; Abd Raboo, M.A.

    2016-01-01

    Toxocara canis is a worldwide zoonotic roundworm that infects a number of hosts including humans. It exhibits marked affinity to the nervous tissues. This study deals with the changes in the brain of Toxocara canis infected rats regarding parasitological, nitric oxide (NO) level and DNA damage compared to the effect of vaccination with gamma radiation-attenuated embryonated egg or thyme oil treatment. Eighty rats were classified into four groups (twenty each): GI (normal control); GII infected with 2500 T. canis infective eggs/ml/rat (infected control); GIII vaccinated with 800 Gy gamma-attenuated embryonated eggs (vaccinated group) and GIV infected with 2500 T. canis eggs and treated with thyme oil (thyme treated group). At the 14th day post-infection, ten rats from each group were sacrificed and the remaining were re-infected (challenged) with the same number of eggs. At the 14th days post challenge, brain tissues were taken for larval recovery, nitric oxide level evaluation and DNA damage using fragmentation and comet assay. The results exhibited a significant decrease in larval count and nitric oxide level with less damage in brain cells in thyme treated and gamma radiation-attenuated vaccinated groups compared to control infected group. It is also, concluded that vaccination using γ- rays is more effective in protection compared to using thyme oil.

  10. The yellow fever 17D vaccine virus: molecular basis of viral attenuation and its use as an expression vector

    Directory of Open Access Journals (Sweden)

    Galler R.

    1997-01-01

    Full Text Available The yellow fever (YF virus is the prototype flavivirus. The use of molecular techniques has unraveled the basic mechanisms of viral genome structure and expression. Recent trends in flavivirus research include the use of infectious clone technology with which it is possible to recover virus from cloned cDNA. Using this technique, mutations can be introduced at any point of the viral genome and their resulting effect on virus phenotype can be assessed. This approach has opened new possibilities to study several biological viral features with special emphasis on the issue of virulence/attenuation of the YF virus. The feasibility of using YF virus 17D vaccine strain, for which infectious cDNA is available, as a vector for the expression of heterologous antigens is reviewed

  11. Effective cancer vaccine platform based on attenuated salmonella and a type III secretion system.

    Science.gov (United States)

    Xu, Xin; Hegazy, Wael A H; Guo, Linjie; Gao, Xiuhua; Courtney, Amy N; Kurbanov, Suhrab; Liu, Daofeng; Tian, Gengwen; Manuel, Edwin R; Diamond, Don J; Hensel, Michael; Metelitsa, Leonid S

    2014-11-01

    Vaccines explored for cancer therapy have been based generally on injectable vector systems used to control foreign infectious pathogens, to which the immune system evolved to respond naturally. However, these vectors may not be effective at presenting tumor-associated antigens (TAA) to the immune system in a manner that is sufficient to engender antitumor responses. We addressed this issue with a novel orally administered Salmonella-based vector that exploits a type III secretion system to deliver selected TAA in the cytosol of professional antigen-presenting cells in situ. A systematic comparison of candidate genes from the Salmonella Pathogenicity Island 2 (SPI2) locus was conducted in the vaccine design, using model antigens and a codon-optimized form of the human TAA survivin (coSVN), an oncoprotein that is overexpressed in most human cancers. In a screen of 20 SPI2 promoter:effector combinations, a PsifB::sseJ combination exhibited maximal potency for antigen translocation into the APC cytosol, presentation to CD8 T cells, and murine immunogenicity. In the CT26 mouse model of colon carcinoma, therapeutic vaccination with a lead PsifB::sseJ-coSVN construct (p8032) produced CXCR3-dependent infiltration of tumors by CD8 T cells, reversed the CD8:Treg ratio at the tumor site, and triggered potent antitumor activity. Vaccine immunogenicity and antitumor potency were enhanced by coadministration of the natural killer T-cell ligand 7DW8-5, which heightened the production of IL12 and IFNγ. Furthermore, combined treatment with p8032 and 7DW8-5 resulted in complete tumor regression in A20 lymphoma-bearing mice, where protective memory was demonstrated. Taken together, our results demonstrate how antigen delivery using an oral Salmonella vector can provide an effective platform for the development of cancer vaccines. ©2014 American Association for Cancer Research.

  12. One Family's Struggles with Pertussis (Whooping Cough)

    Medline Plus

    Full Text Available ... GETVAXED print ads go to GETVAXED.ORG cme Immunizations Pertussis (Whooping Cough) One family's struggles with pertussis ... not possible without a visit to your doctor. Immunizations stop disease from spreading. Check with your family ...

  13. Pertussis (Whooping Cough)

    Science.gov (United States)

    ... guidelines, articles... Pregnant? Help Protect Your Baby from Whooping Cough frame support disabled and/or not supported in ... the disease. Also available on YouTube. Pregnancy and Whooping Cough Learn more about whooping cough vaccination during pregnancy… ...

  14. Attenuated Salmonella enterica serovar Typhi and Shigella flexneri 2a strains mucosally deliver DNA vaccines encoding measles virus hemagglutinin, inducing specific immune responses and protection in cotton rats.

    Science.gov (United States)

    Pasetti, Marcela F; Barry, Eileen M; Losonsky, Genevieve; Singh, Mahender; Medina-Moreno, Sandra M; Polo, John M; Ulmer, Jeffrey; Robinson, Harriet; Sztein, Marcelo B; Levine, Myron M

    2003-05-01

    Measles remains a leading cause of child mortality in developing countries. Residual maternal measles antibodies and immunologic immaturity dampen immunogenicity of the current vaccine in young infants. Because cotton rat respiratory tract is susceptible to measles virus (MV) replication after intranasal (i.n.) challenge, this model can be used to assess the efficacy of MV vaccines. Pursuing a new measles vaccine strategy that might be effective in young infants, we used attenuated Salmonella enterica serovar Typhi CVD 908-htrA and Shigella flexneri 2a CVD 1208 vaccines to deliver mucosally to cotton rats eukaryotic expression plasmid pGA3-mH and Sindbis virus-based DNA replicon pMSIN-H encoding MV hemagglutinin (H). The initial i.n. dose-response with bacterial vectors alone identified a well-tolerated dosage (1 x 10(9) to 7 x 10(9) CFU) and a volume (20 micro l) that elicited strong antivector immune responses. Animals immunized i.n. on days 0, 28, and 76 with bacterial vectors carrying DNA plasmids encoding MV H or immunized parenterally with these naked DNA vaccine plasmids developed MV plaque reduction neutralizing antibodies and proliferative responses against MV antigens. In a subsequent experiment of identical design, cotton rats were challenged with wild-type MV 1 month after the third dose of vaccine or placebo. MV titers were significantly reduced in lung tissue of animals immunized with MV DNA vaccines delivered either via bacterial live vectors or parenterally. Since attenuated serovar Typhi and S. flexneri can deliver measles DNA vaccines mucosally in cotton rats, inducing measles immune responses (including neutralizing antibodies) and protection, boosting strategies can now be evaluated in animals primed with MV DNA vaccines.

  15. Comparative genomic analysis of Brucella abortus vaccine strain 104M reveals a set of candidate genes associated with its virulence attenuation.

    Science.gov (United States)

    Yu, Dong; Hui, Yiming; Zai, Xiaodong; Xu, Junjie; Liang, Long; Wang, Bingxiang; Yue, Junjie; Li, Shanhu

    2015-01-01

    The Brucella abortus strain 104M, a spontaneously attenuated strain, has been used as a vaccine strain in humans against brucellosis for 6 decades in China. Despite many studies, the molecular mechanisms that cause the attenuation are still unclear. Here, we determined the whole-genome sequence of 104M and conducted a comprehensive comparative analysis against the whole genome sequences of the virulent strain, A13334, and other reference strains. This analysis revealed a highly similar genome structure between 104M and A13334. The further comparative genomic analysis between 104M and A13334 revealed a set of genes missing in 104M. Some of these genes were identified to be directly or indirectly associated with virulence. Similarly, a set of mutations in the virulence-related genes was also identified, which may be related to virulence alteration. This study provides a set of candidate genes associated with virulence attenuation in B.abortus vaccine strain 104M.

  16. Effectiveness of Japanese encephalitis SA 14-14-2 live attenuated vaccine among Indian children: Retrospective 1:4 matched case-control study.

    Science.gov (United States)

    Tandale, Babasaheb V; Khan, Siraj A; Kushwaha, Komal P; Rahman, Helina; Gore, Milind M

    2018-04-24

    We estimate the effectiveness of Japanese encephalitis (JE) SA 14-14-2 live-attenuated vaccination single dose campaign among children aged 1-15 years in India during 2006-07. Acute encephalitis syndrome (AES) cases hospitalized following vaccination campaigns during the years 2006-08 were investigated retrospectively. The laboratory-confirmed JE cases were detected from the surveillance laboratories based on anti-JE IgM antibody by ELISA or viral RNA detection by RT-PCR in sera or cerebrospinal fluid. Consent was sought from parents or guardians. Four community controls were chosen randomly per case during house-to-house survey employing individual matching on age, gender and residence during the risk period. Vaccination history was enquired from the child's guardian and verified from vaccination card at home or records at health centre. Conditional logistic regression was conducted on matched case-control sets. We studied 149 cases and matched 596 controls. Vaccination effectiveness was 43.8% (95% CI, 1.9-67.8) based on vaccination card or record. However, effectiveness was 72.2% (95% CI, 56.2-82.4) based on parental history or card/record. Vaccination effectiveness in Assam state was higher than in Uttar Pradesh state. We concluded that the single subcutaneous dose of SA 14-14-2 JE vaccine provided moderate effectiveness in Indian children. Copyright © 2018 The Authors. Published by Elsevier Ltd.. All rights reserved.

  17. Compliance with diphtheria, tetanus, and pertussis immunisation in Bangladesh

    DEFF Research Database (Denmark)

    Zeitlyn, S; Rahman, A K; Nielsen, B H

    1992-01-01

    OBJECTIVE: To evaluate factors associated with non-compliance with having second vaccination against diphtheria, tetanus, and pertussis in a treatment centre in Dhaka to determine which children were most at risk of not completing immunisation. DESIGN: Cohort study of infants given first dose...... of the vaccine and followed up six weeks later to ascertain compliance with having second dose. Factors associated with non-compliance were evaluated. SETTING: Dhaka treatment centre of the International Centre for Diarrhoeal Disease Research, Bangladesh. SUBJECTS: 136 unimmunised children aged 6 weeks to 23...... of immunisation, and she was given clear instructions to bring the child back after four weeks for the second dose. MAIN OUTCOME MEASURE: Rate of non-compliance with advice to return child for second vaccination. RESULTS: 46 of 113 children (41%) received the second dose of the vaccine. Factors most closely...

  18. Identification of Brucella melitensis Rev.1 vaccine-strain genetic markers: Towards understanding the molecular mechanism behind virulence attenuation.

    Science.gov (United States)

    Issa, Mohammad Nouh; Ashhab, Yaqoub

    2016-09-22

    Brucella melitensis Rev.1 is an avirulent strain that is widely used as a live vaccine to control brucellosis in small ruminants. Although an assembled draft version of Rev.1 genome has been available since 2009, this genome has not been investigated to characterize this important vaccine. In the present work, we used the draft genome of Rev.1 to perform a thorough genomic comparison and sequence analysis to identify and characterize the panel of its unique genetic markers. The draft genome of Rev.1 was compared with genome sequences of 36 different Brucella melitensis strains from the Brucella project of the Broad Institute of MIT and Harvard. The comparative analyses revealed 32 genetic alterations (30 SNPs, 1 single-bp insertion and 1 single-bp deletion) that are exclusively present in the Rev.1 genome. In silico analyses showed that 9 out of the 17 non-synonymous mutations are deleterious. Three ABC transporters are among the disrupted genes that can be linked to virulence attenuation. Out of the 32 mutations, 11 Rev.1 specific markers were selected to test their potential to discriminate Rev.1 using a bi-directional allele-specific PCR assay. Six markers were able to distinguish between Rev.1 and a set of control strains. We succeeded in identifying a panel of 32 genome-specific markers of the B. melitensis Rev.1 vaccine strain. Extensive in silico analysis showed that a considerable number of these mutations could severely affect the function of the associated genes. In addition, some of the discovered markers were able to discriminate Rev.1 strain from a group of control strains using practical PCR tests that can be applied in resource-limited settings. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Disodium cromoglycate may act as a novel adjuvant for UV-attenuated Toxoplasma gondii vaccine in mouse model.

    Science.gov (United States)

    Li, Xi; Wu, Yifan; Huang, Shiguang; Lu, Fangli

    2018-06-01

    We have proven the beneficial effects during acute Toxoplasma gondii infection when mast cells were inhibited by disodium cromoglycate (DSCG). Here we investigated the adjuvant effect of DSCG on the protective efficacy of UV-attenuated T. gondii (UV-Tg) vaccine. Mice were infected with 10 2 Tg alone or infected with 10 2 Tg plus DSCG (Tg + DSCG), immunized with 10 5 UV-Tg and challenged with 10 2 Tg (UV-Tg + Tg) or immunized with 10 5 UV-Tg plus DSCG and challenged with 10 2 Tg (UV-Tg + DSCG + Tg). Compared to Tg group, Tg + DSCG, UV-Tg + Tg, and UV-Tg + DSCG + Tg showed significantly prolonged survival times, decreased parasite burdens, reduced liver histopathologies, and increased levels of Th1 and Th2 cytokines and IL-17 in the livers and spleens by using quantitative real-time reverse transcription-polymerase chain reaction (qRT-PCR). Compared to UV-Tg + Tg, UV-Tg + DSCG + Tg had significantly longer survival time, lower tissue parasite burden and histopathological score, and higher levels of Th1 and Th2 cytokines and IL-17 in the livers or spleens. Our data suggest that DSCG may play an adjuvant role in the immunization induced by UV-attenuated T. gondii in mice, by promoting cellular immune response against T. gondii challenge. Copyright © 2018 Elsevier B.V. All rights reserved.

  20. Lipopolysaccharide-specific memory B cell responses to an attenuated live cholera vaccine are associated with protection against Vibrio cholerae infection.

    Science.gov (United States)

    Haney, Douglas J; Lock, Michael D; Gurwith, Marc; Simon, Jakub K; Ishioka, Glenn; Cohen, Mitchell B; Kirkpatrick, Beth D; Lyon, Caroline E; Chen, Wilbur H; Sztein, Marcelo B; Levine, Myron M; Harris, Jason B

    2018-05-11

    The single-dose live attenuated vaccine CVD 103-HgR protects against experimental Vibrio cholerae infection in cholera-naïve adults for at least 6 months after vaccination. While vaccine-induced vibriocidal seroconversion is associated with protection, vibriocidal titers decline rapidly from their peak 1-2 weeks after vaccination. Although vaccine-induced memory B cells (MBCs) might mediate sustained protection in individuals without detectable circulating antibodies, it is unknown whether oral cholera vaccination induces a MBC response. In a study that enrolled North American adults, we measured lipopolysaccharide (LPS)- and cholera toxin (CtxB)-specific MBC responses to PXVX0200 (derived from the CVD 103-HgR strain) and assessed stool volumes following experimental Vibrio cholerae infection. We then evaluated the association between vaccine-induced MBC responses and protection against cholera. There was a significant increase in % CT-specific IgG, % LPS-specific IgG, and % LPS-specific IgA MBCs which persisted 180 days after vaccination as well as a significant association between vaccine-induced increase in % LPS-specific IgA MBCs and lower post-challenge stool volume (r = -0.56, p < 0.001). Oral cholera vaccination induces antigen-specific MBC responses, and the anamnestic LPS-specific responses may contribute to long-term protection and provide correlates of the duration of vaccine-induced protection. NCT01895855. Copyright © 2018 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  1. Vaccination coverage and out-of-sequence vaccinations in rural Guinea-Bissau

    DEFF Research Database (Denmark)

    Hornshøj, Linda; Benn, Christine Stabell; Fernandes, Manuel

    2012-01-01

    OBJECTIVE: The WHO aims for 90% coverage of the Expanded Program on Immunization (EPI), which in Guinea-Bissau included BCG vaccine at birth, three doses of diphtheria-tetanus-pertussis vaccine (DTP) and oral polio vaccine (OPV) at 6, 10 and 14 weeks and measles vaccine (MV) at 9 months when...

  2. Antibody response in cattle after vaccination with inactivated and attenuated rabies vaccines Resposta imune humoral anti-rábica em bovinos imunizados com vacina inativada e atenuada

    Directory of Open Access Journals (Sweden)

    Andréa de Cássia RODRIGUES da SILVA

    2000-04-01

    Full Text Available Despite the absence of current official reports showing the number of cattle infected by rabies, it is estimated that nearly 30,000 bovines are lost each year in Brazil. In order to minimize the important economic losses, control of the disease is achieved by eliminating bat colonies and by herd vaccination. In this study, we compare the antibody response in cattle elicited by vaccination with an attenuated ERA vaccine (AEvac and an inactivated-adjuvanted PV (IPVvac vaccine. The antibody titers were appraised by cell-culture neutralization test and ELISA, and the percentage of seropositivity was ascertained for a period of 180 days. IPVvac elicited complete seropositivity rates from day 30 to day 150, and even on day 180, 87% of the sera showed virus-neutralizing antibody titers (VNA higher than 0.5IU/ml. There were no significant differences between the VNA titers and seropositivity rates obtained with IPVvac in the two methods tested. AEvac, however, elicited significantly lower titers than those observed in the group receiving inactivated vaccine. In addition, the profiles of antirabies IgG antibodies, evaluated by ELISA, and VNA, appraised by cell-culture neutralization test, were slightly different, when both vaccines were compared.A raiva bovina, transmitida principalmente pelo morcego hematófago Desmodus rotundus, é endêmica em várias regiões do Brasil, com um crescente número de casos sendo registrados anualmente. O controle desta infecção em bovinos é feito pelo controle de colônias de morcegos hematófagos e pela vacinação dos rebanhos. Embora as vacinas inativadas sejam mais seguras e mais estáveis que as vacinas atenuadas, estas últimas são ainda amplamente utilizadas em muitas regiões do país, por se acreditar que confiram imunidade mais duradoura. Neste estudo, foram comparadas as respostas anticórpicas de dois grupos de bovinos imunizados com uma vacina atenuada e uma inativada disponíveis comercialmente. Os

  3. Pertussis outbreak in Papua New Guinea: the challenges of response in a remote geo-topographical setting

    Directory of Open Access Journals (Sweden)

    William Lagani

    2012-10-01

    Full Text Available Introduction: A large outbreak of pertussis was detected during March 2011 in Goilala, a remote district of the Central Province in Papua New Guinea, characterized by rugged topography with no road access from the provincial headquarters. This outbreak investigation highlights the difficulties in reporting and responding to outbreaks in these settings.Method: The suspected pertussis cases, reported by health workers from the Ononge health centre area, were investigated and confirmed for the presence of Bordetella pertussis DNA using the polymerase chain reaction (PCR method.Results: There were 205 suspected pertussis cases, with a case-fatality rate (CFR of 3%. All cases were unvaccinated. The Central Province conducted a response vaccination programme providing 65% of children less than five years of age with diphtheria–pertussis-tetanus-HepB-Hib vaccine at a cost of US$ 12.62 per child.Discussion: The incurred cost of vaccination in response to this outbreak was much higher than the US$ 3.80 per child for routine outreach patrol. To prevent further outbreaks of vaccine-preventable diseases in these areas, local health centres must ensure routine vaccination is strengthened through the “Reaching Every District” initiative of the National Department of Health.

  4. Concomitant or sequential administration of live attenuated Japanese encephalitis chimeric virus vaccine</