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Sample records for toxoid conjugate vaccine

  1. Meningococcal serogroups A, C, W-135, and Y tetanus toxoid conjugate vaccine: a new conjugate vaccine against invasive meningococcal disease.

    PubMed

    Hedari, Carine P; Khinkarly, Rima W; Dbaibo, Ghassan S

    2014-01-01

    Invasive meningococcal disease is a serious infection that occurs worldwide. It is caused by Neisseria meningitidis, of which six serogroups (A, B, C, W-135, X, and Y) are responsible for most infections. The case fatality rate of meningococcal disease remains high and can lead to significant sequelae. Vaccination remains the best strategy to prevent meningococcal disease. Polysaccharide vaccines were initially introduced in the late 1960s but their limitations (poor immunogenicity in infants and toddlers and hyporesponsiveness after repeated doses) have led to the development and use of meningococcal conjugate vaccines, which overcome these limitations. Two quadrivalent conjugated meningococcal vaccines - MenACWY-DT (Menactra(®)) and MenACWY-CRM197 (Menveo(®)) - using diphtheria toxoid or a mutant protein, respectively, as carrier proteins have already been licensed in the US. Recently, a quadrivalent meningococcal vaccine conjugated to tetanus toxoid (MenACWY-TT; Nimenrix(®)) was approved for use in Europe in 2012. The immunogenicity of MenACWY-TT, its reactogenicity and safety profile, as well as its coadministration with other vaccines are discussed in this review. Clinical trials showed that MenACWY-TT was immunogenic in children above the age of 12 months, adolescents, and adults, and has an acceptable reactogenicity and safety profile. Its coadministration with several other vaccines that are commonly used in children, adolescents, and adults did not affect the immunogenicity of MenACWY-TT or the coadministered vaccine, nor did it affect its reactogenicity and safety. Other studies are now ongoing in order to determine the immunogenicity, reactogenicity, and safety of MenACWY-TT in infants from the age of 6 weeks. PMID:24729718

  2. Meningococcal vaccine A,C,W135,Y: conjugated to tetanus toxoid.

    PubMed

    2013-12-01

    A meningococcal vaccine conjugated to protein CRM 197 (Menveo) is the standard vaccine for immunisation against invasive meningococcal infections caused by serogroups A, C, W135 andY, beginning at age 2 years. Nimenrix, another vaccine against meningococcal groups A, C,W135 and Y, conjugated to tetanus toxoid, was authorised for use in the European Union, starting at age 1 year. The two tetravalent meningococcal conjugate vaccines have not been compared in head-to-head trials. Four immunogenicity studies compared the tetravalent conjugate vaccine Nimenrix with an unconjugated tetravalent meningococcal vaccine in children and adults aged 2 to 55 years. The results showed that Nimenrix was more immunogenic than the unconjugated vaccine. Two immunogenicity studies showed that Nimenrix was at least as immunogenic as monovalent (group C) meningococcal conjugate vaccines in children aged from 1 to 2 years and from 2 to 10 years. In one study, prior vaccination with an unconjugated tetravalent meningococcal vaccine had little impact on the immunogenicity of a booster dose of the conjugate vaccine Nimenrix. Concomitant administration with other vaccines does not affect the immunogenicity of Nimenrix. Nimenrix causes more frequent local and systemic adverse reactions than the unconjugated tetravalent meningococcal vaccine and monovalent group C meningococcal conjugate vaccines. In children over 2 years of age, Nimenrix has no advantages over Menveo for vaccination against meningococcal serogroups A, C, W135 andY. In contrast, between the ages of 1 and 2 years, Nimenrix is the only vaccine with established immunogenicity. In addition, it has an acceptable harm-benefit balance. PMID:24600724

  3. Structural correlates of carrier protein recognition in tetanus toxoid-conjugated bacterial polysaccharide vaccines

    PubMed Central

    Lockyer, Kay; Gao, Fang; Derrick, Jeremy P.; Bolgiano, Barbara

    2015-01-01

    An analysis of structure-antibody recognition relationships in nine licenced polysaccharide-tetanus toxoid (TT) conjugate vaccines was performed. The panel of conjugates used included vaccine components to protect against disease caused by Haemophilus influenzae type b, Neisseria meningitidis groups A, C, W and Y and Streptococcus pneumoniae serotype 18C. Conformation and structural analysis included size exclusion chromatography with multi-angle light scattering to determine size, and intrinsic fluorescence spectroscopy and fluorescence quenching to evaluate the protein folding and exposure of Trp residues. A capture ELISA measured the recognition of TT epitopes in the conjugates, using four rat monoclonal antibodies: 2 localised to the HC domain, and 2 of which were holotoxoid conformation-dependent. The conjugates had a wide range of average molecular masses ranging from 1.8 × 106 g/mol to larger than 20 × 106 g/mol. The panel of conjugates were found to be well folded, and did not have spectral features typical of aggregated TT. A partial correlation was found between molecular mass and epitope recognition. Recognition of the epitopes either on the HC domain or the whole toxoid was not necessarily hampered by the size of the molecule. Correlation was also found between the accessibility of Trp side chains and polysaccharide loading, suggesting also that a higher level of conjugated PS does not necessarily interfere with toxoid accessibility. There were different levels of carrier protein Trp side-chain and epitope accessibility that were localised to the HC domain; these were related to the saccharide type, despite the conjugates being independently manufactured. These findings extend our understanding of the molecular basis for carrier protein recognition in TT conjugate vaccines. PMID:25640334

  4. Pseudomonas aeruginosa PAO-1 Lipopolysaccharide-Diphtheria Toxoid Conjugate Vaccine: Preparation, Characterization and Immunogenicity

    PubMed Central

    Najafzadeh, Faezeh; Shapouri, Reza; Rahnema, Mehdi; Rokhsartalab Azar, Shadi; Kianmehr, Anvarsadat

    2015-01-01

    Background: Treatment of Pseudomonas aeruginosa PAO-1 infections through immunological means has been proved to be efficient and protective. Objectives: The purpose of this study was to produce a conjugate vaccine composed of detoxified lipopolysaccharide (D-LPS) P. aeruginosa and diphtheria toxoid (DT). Materials and Methods: Firstly, LPS was purified and characterized from P. aeruginosa PAO1 and then detoxified. D-LPS was covalently coupled to DT as a carrier protein via amidation method with adipic acid dihydrazide (ADH) as a spacer molecule and 1-ethyl-3- (3-dimethylaminopropyl) carbodiimide (EDAC) as a linker. The molar ratio of LPS to DT in the prepared conjugate was 3:1. The immunogenicity of D-LPS-DT conjugate vaccine in mice model was evaluated as well. Results: The conjugate was devoid of endotoxin activity and 0.125 U/mL of D-LPS was acceptable for immunization. D-LPS-DT conjugate was nonpyrogenic for rabbits and nontoxic for mice. Mice immunization with D-LPS-DT conjugate vaccine elicited the fourfold higher IgG antibody compared to D-LPS. Anti-LPS IgG antibody was predominantly IgG1 subclass and then IgG3, IgG2a and IgG2b, respectively. Conclusions: Vaccine based on the conjugation of P. aeruginosa PAO-1 LPS with DT increased anti-LPS antibodies and had a significant potential to protect against Pseudomonas infections. PMID:26301059

  5. Synthesis, characterization and immunological properties of Escherichia coli 0157:H7 lipopolysaccharide- diphtheria toxoid conjugate vaccine

    PubMed Central

    Rokhsartalab-Azar, Shadi; Shapouri, Reza; Rahnema, Mehdi; Najafzadeh, Faezeh

    2015-01-01

    Background and Objective: Escherichia coli O157:H7, an emerging pathogen, causes severe enteritis and the extraintestinal complication of hemolytic-uremic syndrome. The goal of this study was to evaluate the conjugate of E. coli O157: H7 lipopolysaccharide (LPS) with diphtheria toxoid (DT) as a candidate vaccine in mice model. Material and Methods: LPS from E. coli O157:H7 was extracted by hot phenol method and then detoxified. Purified LPS was coupled to DT with adipic acid dihydrazide (ADH) as a spacer and 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide (EDAC) as a linker. The coupling molar ratio of LPS to DT was 3:1. Clinical evaluation of E. coli O157:H7 LPS-DT conjugate was also performed. Results: The conjugate was devoid of endotoxin activity and indicated 0.125 U/ml of D-LPS. Mice immunization with D-LPS DT conjugate elicited fourfold higher IgG antibody in comparison to D-LPS. Also, in vivo protection of mice with conjugate provided high protection against the LD50 of E. coli O157:H7, which indicated a good correlation with the IgG titer. Conclusion: Our results showed that the suggested vaccine composed of E. coli O157:H7 LPS and DT had a significant potential to protect against E. coli infections. PMID:26668702

  6. Effects of early vaccination with a gonadotropin releasing factor analog-diphtheria toxoid conjugate on boar taint and growth performance of male pigs.

    PubMed

    Kantas, D; Papatsiros, V; Tassis, P; Tzika, E; Pearce, M C; Wilson, S

    2014-05-01

    The aim of this study was to evaluate safety (in terms of detecting possible adverse clinical effects attributable to vaccination), efficacy, and effects on growth performance of a gonadotropin releasing factor analog-diphtheria toxoid conjugate (commercially distributed as Improvac; Zoetis, Zaventem, Belgium) in male pigs raised in a commercial Greek farm. A total of 1,230 male pigs was enrolled in 16 weekly batches and allocated to 3 groups: barrows (castrated on the next day after birth [study Day 0]), pigs vaccinated with the above-mentioned product, and intact boars. Vaccinated pigs were injected subcutaneously with 2 mL of the anti-gonadotropin releasing factor (GnRF) vaccine at 9 to 11 wk of age (60-78 d) and 15 to 17 wk of age (102-120 d) and slaughtered at 22 to 25 wk of age (152-176 d). No clinical abnormalities or adverse events attributable to vaccination occurred. Mean BW of vaccinated pigs was 6% greater compared with barrows at slaughter (P < 0.0001). The vaccinated pigs had greater ADG than barrows from castration to slaughter (8%). In detail, a lower ADG from first to second vaccination (-12%; P < 0.0001) and a 27% greater ADG from second vaccination to slaughter (P < 0.0001) were observed. The ADG of vaccinated pigs and intact boars was not significantly different throughout the study, except from first to second vaccination (boars greater; P = 0.0059) and second vaccination to slaughter (vaccinates greater; P = 0.0390). Feed conversion ratio of barrows was 11 and 8% greater compared with vaccinated pigs (P = 0.0005) and boars (P = 0.0062) from first to second vaccination but was 23 to 26% lower compared with vaccinated pigs (P < 0.0001) and intact boars (P < 0.0001) from first vaccination to slaughter and 7 to 9.5% lower from the second vaccination to slaughter (P = 0.0029 and P = 0.0003 for vaccinates and intact boars, respectively). At slaughter, the belly fat androstenone concentration of all vaccinated pigs and 64% of intact boars was below 200 ng/g. Belly fat skatole concentration was below 20 ng/g in samples from all groups. In conclusion, vaccination against GnRF using the GnRF analog-diphtheria toxoid conjugate tested did not induce adverse clinical effects, proved effective, and compared with physical castration, resulted in greater BW at slaughter and improved ADG and feed conversion ratio from first vaccination to slaughter. PMID:24663199

  7. A cholera toxoid-insulin conjugate as an oral vaccine against spontaneous autoimmune diabetes.

    PubMed

    Bergerot, I; Ploix, C; Petersen, J; Moulin, V; Rask, C; Fabien, N; Lindblad, M; Mayer, A; Czerkinsky, C; Holmgren, J; Thivolet, C

    1997-04-29

    Mucosally induced immunological tolerance is an attractive strategy for preventing or treating illnesses resulting from untoward inflammatory immune reactions against self- or non-self-antigens. Oral administration of relevant autoantigens and allergens has been reported to delay or suppress onset of clinical disease in a number of experimental autoimmune and allergic disorders. However, the approach often requires repeated feeding of large amounts of tolerogens over long periods and is only partly effective in animals already systemically sensitized to the ingested antigen such as in animals already harboring autoreactive T cells, and thus presumably also in humans with an autoimmune disease. We have recently shown that oral administration of microgram amounts of antigen coupled to cholera toxin B subunit (CTB), can effectively suppress systemic T cell reactivity in naive as well as in immune animals. We now report that feeding small amounts (2-20 microg) of human insulin conjugated to CTB can effectively suppress beta cell destruction and clinical diabetes in adult nonobese diabetic (NOD) mice. The protective effect could be transferred by T cells from CTB-insulin-treated animals and was associated with reduced lesions of insulitis. Furthermore, adoptive co-transfer experiments involving injection of Thy-1,2 recipients with diabetogenic T cells from syngeneic mice and T cells from congenic Thy-1,1 mice fed with CTB-insulin demonstrated a selective recruitment of Thy-1,1 donor cells in the peripancreatic lymph nodes concomitant with reduced islet cell infiltration. These results suggest that protection against autoimmune diabetes can be achieved by feeding minute amounts of a pancreas islet cell autoantigen linked to CTB and appears to involve the selective migration and retention of protective T cells into lymphoid tissues draining the site of organ injury. PMID:9114038

  8. Elevated levels of maternal anti-tetanus toxin antibodies do not suppress the immune response to a Haemophilus influenzae type b polyribosylphosphate-tetanus toxoid conjugate vaccine.

    PubMed Central

    Panpitpat, C.; Thisyakorn, U.; Chotpitayasunondh, T.; Fürer, E.; Que, J. U.; Hasler, T.; Cryz, S. J.

    2000-01-01

    Reported are the effects of elevated levels of anti-tetanus antibodies on the safety and immune response to a Haemophilus influenzae type b polyribosylphosphate (PRP)-tetanus toxoid conjugate (PRP-T) vaccine. A group of Thai infants (n = 177) born to women immunized against tetanus during pregnancy were vaccinated with either a combined diphtheria-tetanus-pertussis (DTP) PRP-T vaccine or DTP and a PRP-conjugate vaccine using Neisseria meningitidis group B outer-membrane proteins as a carrier (PedVax HIB). Although most infants possessed high titres (> 1 IU/ml) of anti-tetanus antibodies, the DTP-PRP-T combined vaccine engendered an excellent antibody response to all vaccine components. In both vaccine groups > 98% of infants attained anti-PRP antibody titres > or = 0.15 microgram/ml. The geometric mean anti-PRP antibody titres were 5.41 micrograms/ml and 2.1 micrograms/ml for infants immunized with three doses of PRP-T versus two doses of PedVax HIB vaccines, respectively (P < 0.005). Similarly, the proportion of infants who achieved titres > or = 1 microgram/ml was higher in the PRP-T group (87.8%) than in the group immunized with PedVax HIB (74.2%) (P = 0.036). A subgroup analysis showed that there was no significant difference in the anti-PRP antibody response for infants exhibiting either < 1 IU of anti-tetanus antibody per millilitre or > or = 1 IU/ml at baseline. These finding indicate that pre-existing anti-carrier antibody does not diminish the immune response to the PRP moiety. All infants possessed protective levels of anti-D and anti-T antibody levels after immunization. PMID:10812736

  9. Protein carriers of conjugate vaccines

    PubMed Central

    Pichichero, Michael E

    2013-01-01

    The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products. PMID:23955057

  10. Randomized trial to assess the immunogenicity, safety and antibody persistence up to three years after a single dose of a tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine in toddlers.

    PubMed

    Vesikari, Timo; Forstén, Aino; Boutriau, Dominique; Bianco, Véronique; Van der Wielen, Marie; Miller, Jacqueline M

    2012-12-01

    Effective vaccines offering broad protection to toddlers, who are at high risk for invasive meningococcal disease, are needed. Here, the immunogenicity, safety and antibody persistence of the tetravalent meningococcal ACWY tetanus toxoid conjugate vaccine (MenACWY-TT) were evaluated in toddlers. Healthy participants aged 12 to 23 mo (n = 304) were randomized (3:1) to receive one dose of MenACWY-TT or a monovalent meningococcal serogroup C conjugate vaccine (MenC-CRM 197). Serum bactericidal activity was evaluated with assays using rabbit (rSBA) and human (hSBA) complement up to three years post-vaccination. MenACWY-TT was demonstrated to be non-inferior to MenC-CRM 197 in terms of immunogenicity to serogroup C, and the pre-specified immunogenicity criteria for serogroups A, W-135 and Y were met. Exploratory analyses suggested that rSBA geometric mean titers (GMTs), hSBA GMTs and proportions of toddlers with rSBA titers ? 1:128 and hSBA titers ? 1:4 and ? 1:8 were higher for all serogroups at one month post-vaccination with MenACWY-TT compared with MenC-CRM 197. At three years post-vaccination, at least 90.8% and 73.6% of MenACWY-TT recipients retained rSBA titers ? 1:8 for all serogroups and hSBA titers ? 1:4 for serogroups C, W-135 and Y, respectively, but the percentages of toddlers with hSBA titers ? 1:4 for serogroup A decreased to 21.8%. In both groups, grade 3 adverse events were infrequently reported and no serious adverse events were considered causally related to vaccination. These results suggest that one single dose of MenACWY-TT induces a robust and persistent immune response and has an acceptable safety profile in toddlers. PMID:23032159

  11. Immunogenicity of one, two or three doses of a meningococcal C conjugate vaccine conjugated to tetanus toxoid, given as a three-dose primary vaccination course in UK infants at 2, 3 and 4 months of age with acellular pertussis-containing DTP/Hib vaccine.

    PubMed

    Southern, J; Crowley-Luke, A; Borrow, R; Andrews, N; Miller, E

    2006-01-12

    Reduction of the number of injections necessary to confer protection in the infant schedule would reduce discomfort, improve cost-effectiveness and create space for the addition of new vaccinations in the future. This study assessed the immunogenicity of one, two or three doses of meningococcal C conjugate vaccine conjugated to tetanus toxoid (MCC-TT) [Neis-VacC] given concomitantly with a combined diphtheria/tetanus/acellular pertussis/Haemophilus influenzae type b -TT conjugate (DTaP-Hib-TT) [Infanrix-Hib] vaccine at 2, 3 and 4 months of age. A total of 106 healthy UK infants were enrolled and randomised into two groups, one in which blood was taken after the first and third dose and the other after the second and third dose. The meningococcal serogroup C serum bactericidal antibody (SBA) geometric mean titre (GMT) rose significantly from post-first dose (491, 95% CI 275, 877) to post-second dose (1052, 95% CI 774, 1433) (p=0.03), with no significant change after the third dose (1024, 95% CI 768, 1366). An SBA titre of >or=8 was achieved by 92% after the first dose and 100% after the second and third doses. The Hib IgG geometric mean concentration (GMC) rose significantly after each dose: post-first (0.14 microg/ml 95% CI 0.10, 0.18), post-second (0.54 microg/ml, 95% CI 0.33, 0.90), post-third (2.04 microg/ml, 95% CI 1.52, 2.74). The Hib GMC after the third dose was higher than reported previously when this DTaP/Hib was given either on its own or concomitantly with a MCC-CRM conjugate vaccine according to the UK 2, 3 and 4 month schedule. This suggests some enhancement of the response to a Hib-TT vaccine by concomitant administration of MCC-TT. These results suggest that a reduced number of doses of MCC-TT would be adequate in infancy if given concomitantly with an acellular pertussis-containing vaccine. PMID:16112255

  12. Protein carriers of conjugate vaccines: characteristics, development, and clinical trials.

    PubMed

    Pichichero, Michael E

    2013-12-01

    The immunogenicity of polysaccharides as human vaccines was enhanced by coupling to protein carriers. Conjugation transformed the T cell-independent polysaccharide vaccines of the past to T cell-dependent antigenic vaccines that were much more immunogenic and launched a renaissance in vaccinology. This review discusses the conjugate vaccines for prevention of infections caused by Hemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis. Specifically, the characteristics of the proteins used in the construction of the vaccines including CRM, tetanus toxoid, diphtheria toxoid, Neisseria meningitidis outer membrane complex, and Hemophilus influenzae protein D are discussed. The studies that established differences among and key features of conjugate vaccines including immunologic memory induction, reduction of nasopharyngeal colonization and herd immunity, and antibody avidity and avidity maturation are presented. Studies of dose, schedule, response to boosters, of single protein carriers with single and multiple polysaccharides, of multiple protein carriers with multiple polysaccharides and conjugate vaccines administered concurrently with other vaccines are discussed along with undesirable consequences of conjugate vaccines. The clear benefits of conjugate vaccines in improving the protective responses of the immature immune systems of young infants and the senescent immune systems of the elderly have been made clear and opened the way to development of additional vaccines using this technology for future vaccine products. PMID:23955057

  13. Association of postpartum maternal tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine administration and timeliness of infant immunization.

    PubMed

    Kaur, Ishminder; George, Krissa J; Pena-Ricardo, Carolina; Kelly, Barbara A; Watson, Barbara

    2013-11-01

    A retrospective cohort study was conducted on infants of mothers delivering at an inner-city hospital in October 2009 where postpartum maternal tetanus toxoid, reduced diptheria toxoid and acellular pertussis (Tdap) vaccination had been initiated in May 2008. We compared mothers and infants in a Tdap intervention group discharged July 2008 (n=250) with a pre-Tdap control group discharged July 2007 (n=238). Postpartum maternal Tdap impacted positively timeliness of early infant immunization. PMID:23694833

  14. Technical Development of a New Meningococcal Conjugate Vaccine

    PubMed Central

    Frasch, Carl E.; Kapre, Subhash V.; Lee, Che-Hung; Préaud, Jean-Marie

    2015-01-01

    Background.?Group A Neisseria meningitidis has been a major cause of bacterial meningitis in the sub-Saharan region of Africa in the meningitis belt. Neisseria meningitidis is an encapsulated pathogen, and antibodies against the capsular polysaccharide are protective. Polysaccharide–protein conjugate vaccines have proven to be highly effective against several different encapsulated bacterial pathogens. Purified polysaccharide vaccines have been used to control group A meningococcal (MenA) epidemics with minimal success. Methods.?A monovalent MenA polysaccharide–tetanus toxoid conjugate was therefore developed. This vaccine was developed by scientists working with the Meningitis Vaccine Project, a partnership between PATH and the World Health Organization. Results.?A high-efficiency conjugation method was developed in the Laboratory of Bacterial Polysaccharides in the Center for Biologics Evaluation and Research and transferred to the Serum Institute of India, Ltd, which then developed methods for purification of the group A polysaccharide and used its tetanus toxoid as the carrier protein to produce the now-licensed, highly effective MenAfriVac conjugate vaccine. Conclusions.?Although many years of application of meningococcal polysaccharide vaccines have had minimal success in preventing meningococcal epidemics in the meningitis belt of Africa, our collaborative efforts to develop a MenA conjugate vaccine yielded a safe and highly effective vaccine. PMID:26553667

  15. Brazilian meningococcal C conjugate vaccine: Scaling up studies.

    PubMed

    Bastos, Renata Chagas; de Souza, Iaralice Medeiros; da Silva, Milton Neto; Silva, Flavia de Paiva; Figueira, Elza Scott; Leal, Maria de Lurdes; Jessouroun, Ellen; Junior, José Godinho da Silva; Medronho, Ricardo de Andrade; da Silveira, Ivna Alana Freitas Brasileiro

    2015-08-20

    Several outbreaks caused by Neisseria meningitidis group C have been occurred in different regions of Brazil. A conjugate vaccine for Neisseria meningitidis was produced by chemical linkage between periodate-oxidized meningococcal C polysaccharide and hydrazide-activated monomeric tetanus toxoid via a modified reductive amination conjugation method. Vaccine safety and immunogenicity tested in Phase I and II trials showed satisfactory results. Before starting Phase III trials, vaccine production was scaled up to obtain industrial lots under Good Manufacture Practices (GMP). Comparative analysis between data obtained from industrial and pilot scales of the meningococcal C conjugate bulk showed similar execution times in the scaling up production process without significant losses or alterations in the quality attributes of purified compounds. In conclusion, scale up was considered satisfactory and the Brazilian meningococcal conjugate vaccine production aiming to perform Phase III trials is feasible. PMID:25865466

  16. Update on the use of meningococcal serogroup C CRM197-conjugate vaccine (Meningitec) against meningitis.

    PubMed

    Badahdah, Al-Mamoon; Rashid, Harunor; Khatami, Ameneh

    2016-01-01

    Meningitec is a CRM197-conjugated meningococcal serogroup C (MenC) vaccine, first licensed in 1999. It has been used as a primary and booster vaccine in infants, toddlers, older children and adults, and has been shown to be immunogenic and well-tolerated in all age groups, including premature infants. Vaccine effectiveness has been demonstrated using combined data on all three licensed MenC conjugate vaccines. Evidence from clinical trials, however, suggests that the different MenC conjugate vaccines behave differently with respect to the induction and persistence of bactericidal antibody and generation of immune memory. It appears that Meningitec has a less favorable immunologic profile compared particularly to tetanus toxoid (TT) MenC conjugate vaccines. Data from comparative trials have raised interesting questions on priming of the immune system by conjugate vaccines, particularly in infants. The results from these and other studies are reviewed here with specific focus on Meningitec. PMID:26560735

  17. Antibody and clinical responses in volunteers to immunization with malaria peptide-diptheria toxoid conjugates.

    PubMed

    Ramasamy, R; Wijesundere, D A; Nagendran, K; Ramasamy, M S

    1995-02-01

    Twenty residue peptides from the 185-200-kD and 45-kD merozoite surface antigens of the malaria parasite Plasmodium falciparum were covalently linked to diphtheria toxoid as a carrier and used to immunize human volunteers with aluminium hydroxide as an adjuvant. Significant antibody levels were elicited by two boosting injections. The antibodies reacted with acetone-methanol fixed merozoite membranes in an immunofluorescence assay, but no inhibition of merozoite reinvasion could be detected in in vitro cultures containing the antibodies. Antibody levels against the immunizing peptides declined markedly within 77 days after the third injection. No hypersensitivity was observed against the peptides. However, the volunteers developed hypersensitivity against diphteria toxoid, and in particular a pronounced type III (Arthus) hypersensitivity after three injections with the toxoid. This effect might appear to limit the use of peptide-diphtheria toxoid conjugates for human immunization. Several biochemical, haematological and immunological tests done on the volunteers showed no other adverse effects from the immunizations. PMID:7851007

  18. Different Dynamics for IgG and IgA Memory B Cells in Adolescents following a Meningococcal Serogroup C Tetanus Toxoid Conjugate Booster Vaccination Nine Years after Priming: A Role for Priming Age?

    PubMed Central

    Stoof, Susanne P.; Buisman, Anne-Marie; van Rooijen, Debbie M.; Boonacker, Rianne; van der Klis, Fiona R. M.; Sanders, Elisabeth A. M.; Berbers, Guy A. M.

    2015-01-01

    Background Antibody levels wane rapidly after Meningococcal serogroup C conjugate (MenCC) vaccination in young children, rendering the need for an adolescent booster dose. It is not clear whether circulating memory B cells are associated with persistence of MenC-specific antibody levels. Methods Measurement of MenC-specific IgG and IgA memory B cells and levels of serum and salivary MenC-specific IgG and IgA in healthy 10-, 12- and 15-year-olds prior to and one month and one year after a MenCC booster vaccination. All participants had received a primary MenCC vaccination nine years earlier. Results The number of circulating MenC-specific IgG memory B cells prior to booster was low and not predictive for MenC-specific IgG responses in serum or saliva post-booster, whereas the number of MenC-specific IgA memory B cells pre-booster positively correlated with MenC-specific IgA levels in saliva post-booster (R = 0.5, P<0.05). The booster induced a clear increase in the number of MenC-specific IgG and IgA memory B cells. The number of MenC-PS-specific IgG memory B cells at 1 month post-booster was highest in the 12-year-olds. The number of MenC-specific memory B cells at one month post-booster showed no correlation with the rate of MenC-specific antibody decay throughout the first year post-booster. Conclusions Circulating MenC-specific IgA memory B cells correlate with IgA responses in saliva, whereas circulating MenC-specific IgG memory B cells are not predictive for MenC-specific IgG responses in serum or saliva. Our results are suggestive for age-dependent differences in pre-existing memory against MenC. PMID:26458006

  19. Novel synthetic (poly)glycerolphosphate-based antistaphylococcal conjugate vaccine.

    PubMed

    Chen, Quanyi; Dintaman, Jay; Lees, Andrew; Sen, Goutam; Schwartz, David; Shirtliff, Mark E; Park, Saeyoung; Lee, Jean C; Mond, James J; Snapper, Clifford M

    2013-07-01

    Staphylococcal infections are a major source of global morbidity and mortality. Currently there exists no antistaphylococcal vaccine in clinical use. Previous animal studies suggested a possible role for purified lipoteichoic acid as a vaccine target for eliciting protective IgG to several Gram-positive pathogens. Since the highly conserved (poly)glycerolphosphate backbone of lipoteichoic acid is a major antigenic target of the humoral immune system during staphylococcal infections, we developed a synthetic method for producing glycerol phosphoramidites to create a covalent 10-mer of (poly)glycerolphosphate for potential use in a conjugate vaccine. We initially demonstrated that intact Staphylococcus aureus elicits murine CD4(+) T cell-dependent (poly)glycerolphosphate-specific IgM and IgG responses in vivo. Naive mice immunized with a covalent conjugate of (poly)glycerolphosphate and tetanus toxoid in alum plus CpG-oligodeoxynucleotides produced high secondary titers of serum (poly)glycerolphosphate-specific IgG. Sera from immunized mice enhanced opsonophagocytic killing of live Staphylococcus aureus in vitro. Mice actively immunized with the (poly)glycerolphosphate conjugate vaccine showed rapid clearance of staphylococcal bacteremia in vivo relative to mice similarly immunized with an irrelevant conjugate vaccine. In contrast to purified, natural lipoteichoic acid, the (poly)glycerolphosphate conjugate vaccine itself exhibited no detectable inflammatory activity. These data suggest that a synthetic (poly)glycerolphosphate-based conjugate vaccine will contribute to active protection against extracellular Gram-positive pathogens expressing this highly conserved backbone structure in their membrane-associated lipoteichoic acid. PMID:23649092

  20. Novel Synthetic (Poly)Glycerolphosphate-Based Antistaphylococcal Conjugate Vaccine

    PubMed Central

    Chen, Quanyi; Dintaman, Jay; Lees, Andrew; Sen, Goutam; Schwartz, David; Shirtliff, Mark E.; Park, Saeyoung; Lee, Jean C.; Mond, James J.

    2013-01-01

    Staphylococcal infections are a major source of global morbidity and mortality. Currently there exists no antistaphylococcal vaccine in clinical use. Previous animal studies suggested a possible role for purified lipoteichoic acid as a vaccine target for eliciting protective IgG to several Gram-positive pathogens. Since the highly conserved (poly)glycerolphosphate backbone of lipoteichoic acid is a major antigenic target of the humoral immune system during staphylococcal infections, we developed a synthetic method for producing glycerol phosphoramidites to create a covalent 10-mer of (poly)glycerolphosphate for potential use in a conjugate vaccine. We initially demonstrated that intact Staphylococcus aureus elicits murine CD4+ T cell-dependent (poly)glycerolphosphate-specific IgM and IgG responses in vivo. Naive mice immunized with a covalent conjugate of (poly)glycerolphosphate and tetanus toxoid in alum plus CpG-oligodeoxynucleotides produced high secondary titers of serum (poly)glycerolphosphate-specific IgG. Sera from immunized mice enhanced opsonophagocytic killing of live Staphylococcus aureus in vitro. Mice actively immunized with the (poly)glycerolphosphate conjugate vaccine showed rapid clearance of staphylococcal bacteremia in vivo relative to mice similarly immunized with an irrelevant conjugate vaccine. In contrast to purified, natural lipoteichoic acid, the (poly)glycerolphosphate conjugate vaccine itself exhibited no detectable inflammatory activity. These data suggest that a synthetic (poly)glycerolphosphate-based conjugate vaccine will contribute to active protection against extracellular Gram-positive pathogens expressing this highly conserved backbone structure in their membrane-associated lipoteichoic acid. PMID:23649092

  1. [Pneumococcal vaccines. New conjugate vaccines for adults].

    PubMed

    Campins Martí, Magda

    2015-11-01

    Pneumococcal infections are a significant cause of morbidity and mortality, and are one of the 10 leading causes of death worldwide. Children under 2 years have a higher incidence rate, followed by adults over 64 years. The main risk group are individuals with immunodeficiency, and those with anatomical or functional asplenia, but can also affect immunocompetent persons with certain chronic diseases. Significant progress has been made in the last 10 years in the prevention of these infections. Until a few years ago, only the 23-valent non-conjugate pneumococcal vaccine was available. Its results were controversial in terms of efficacy and effectiveness, and with serious limitations on the type of immune response induced. The current possibility of using the 13-valent conjugate vaccine in adults has led to greater expectations in improving the prevention of pneumococcal disease in these age groups. PMID:26474708

  2. Development and characterization of Haemophilus influenzae type b conjugate vaccine prepared using different polysaccharide chain lengths.

    PubMed

    Rana, R; Dalal, J; Singh, D; Kumar, N; Hanif, S; Joshi, N; Chhikara, M K

    2015-05-28

    Capsular polysaccharide conjugates of Haemophilus influenzae type b (Hib) are important components of several mono- or multi-valent childhood vaccines. However, their access to the most needy people is limited due to their high cost. As a step towards developing a cost effective and more immunogenic Hib conjugate vaccine, we present a method for the preparation of Hib capsular polysaccharide (PRP)-tetanus toxoid (TT) conjugates using optimized PRP chain length and conjugation conditions. Reactive aldehyde groups were introduced into the polysaccharides by controlled periodate oxidation of the native polysaccharide, which were subsequently covalently linked to hydrazide derivatized tetanus toxoid by means of reductive amination. Native polysaccharides were reduced to average 100 or 50kDa polysaccharide and 10kDa oligosaccharides in a controlled manner. Various conjugates were prepared using Hib polysaccharide and oligosaccharide yielding conjugates with polysaccharide to protein ratios in the range of 0.25-0.5 (w/w) and free saccharide levels of less than 10%. Immunization of Sprague Dawley rats with the conjugates elicited specific antibodies to PRP. The low molecular weight PRP-TT conjugates were found to be more immunogenic as compared to their high molecular weight counterparts and the PRP-TT reference vaccine. PMID:25907408

  3. Antibody response to a delayed booster dose of anthrax vaccine and botulinum toxoid.

    PubMed

    Pittman, Phillip R; Hack, Dallas; Mangiafico, Joseph; Gibbs, Paul; McKee, Kelly T; Friedlander, Arthur M; Sjogren, Maria H

    2002-05-15

    We evaluated the prevalence and concentration of serum antibodies 18-24 months after primary inoculation with anthrax and botulinum vaccines, and assessed the reactogenicity and immunogenicity of a significantly delayed booster dose of these vaccines. Five hundred and eight male active-duty military personnel received one, two or three inoculations with anthrax vaccine and/or botulinum toxoid in 1990/1991 in preparation for Operations Desert Shield/Desert Storm. Subjects were vaccinated with the licensed anthrax vaccine, adsorbed (AVA) and pentavalent (ABCDE) botulinum toxoid (PBT) BB-IND 3723. Anthrax protective antigen (PA) IgG antibody was measured in serum using an immunocapture enzyme-linked immunosorbent assay (ELISA). A mouse neutralization test was used to determine the titer of Clostridium botulinum type A antitoxin in serum samples. The prevalence of anti-PA IgG was 30% in individuals 18-24 months after priming with one, two or three doses of AVA. After boosting, 99% of volunteers had detectable anti-PA IgG; only two individuals failed to respond. The prevalence of antibodies against botulinum toxin type A was 28% 18-24 months after initial priming. Following boosting, 99% of volunteers had serum titers >0.02IU/ml, and 97% responded with titers > or =0.25IU/ml. Systemic reactions to booster vaccinations could not be specifically ascribed to one or the other vaccine, but were generally mild and of brief duration. Forty-five percent of volunteers reported one or more systemic reactions over the course of 7 days. Injection site reactions of any kind occurred in 25% of AVA recipients and in 16% of PBT recipients; persistence of local reactions beyond 7 days was infrequent. While the kinetics and durability of immune responses must be studied, these findings suggest that booster doses of anthrax vaccine and botulinum toxoid sufficient to stimulate a robust anamnestic response may be given at times distant from receipt of the primary inoculations. PMID:11972980

  4. Pneumococcal Conjugate Vaccine: What You Need to Know

    MedlinePLUS

    VACCINE INFORMATION STATEMENT Pneumococcal Conjugate Vaccine (PCV13) What You Need to Know Many Vaccine Information Statements are available in Spanish and other languages. See www. immunize. org/ ...

  5. Tetanus toxoid and CCL3 improve DC vaccines in mice and glioblastoma patients

    PubMed Central

    Mitchell, Duane A.; Batich, Kristen A.; Gunn, Michael D.; Huang, Min-Nung; Sanchez-Perez, Luis; Nair, Smita K.; Congdon, Kendra L.; Reap, Elizabeth A.; Archer, Gary E.; Desjardins, Annick; Friedman, Allan H.; Friedman, Henry S.; Herndon, James E.; Coan, April; McLendon, Roger E.; Reardon, David A.; Vredenburgh, James J.; Bigner, Darell D.; Sampson, John H.

    2015-01-01

    Upon stimulation, dendritic cells (DCs) mature and migrate to draining lymph nodes to induce immune responses1. As such, autologous DCs generated ex vivo have been pulsed with tumor antigens and injected back into patients as immunotherapy. While DC vaccines have shown limited promise in the treatment of patients with advanced cancers2–4 including glioblastoma (GBM),5–7 the factors dictating DC vaccine efficacy remain poorly understood. Here we demonstrate that pre-conditioning the vaccine site with a potent recall antigen such as tetanus/diphtheria (Td) toxoid can significantly improve the lymph node homing and efficacy of tumor antigen-specific DCs. To assess the impact of vaccine site pre-conditioning in humans, we randomized patients with GBM to pre-conditioning with mature DCs8 or Td unilaterally before bilateral vaccination with Cytomegalovirus pp65 RNA-pulsed DCs. We and other laboratories have shown that pp65 is expressed in > 90% of GBM specimens but not surrounding normal brain9–12, providing an unparalleled opportunity to subvert this viral protein as a tumor-specific target. Patients given Td had enhanced DC migration bilaterally and significantly improved survival. In mice, Td pre-conditioning also enhanced bilateral DC migration and suppressed tumor growth in a manner dependent on the chemokine CCL3. Our clinical studies and corroborating investigations in mice suggest that pre-conditioning with a potent recall antigen may represent a viable strategy to improve antitumor immunotherapy. PMID:25762141

  6. Modulation of Benzo[a]pyrene induced immunotoxicity in mice actively immunized with a B[a]P-diphtheria toxoid conjugate

    SciTech Connect

    Schellenberger, Mario T.; Grova, Nathalie; Willieme, Stephanie; Farinelle, Sophie; Prodhomme, Emmanuel J.F.

    2009-10-01

    Benzo[a]pyrene (B[a]P) is a small molecular weight carcinogen and the prototype of polycyclic aromatic hydrocarbons (PAHs). While these compounds are primarily known for their carcinogenicity, B[a]P and its metabolites are also toxic for mammalian immune cells. To develop a prophylactic immune strategy against detrimental effects of B[a]P, we have immunized mice with a B[a]P-diphtheria toxoid conjugate vaccine. We showed that high levels of antibodies against B[a]P and its metabolites modulate the redistribution of these PAHs in the blood. After immunization, increased levels of B[a]P and its metabolites were recovered in the blood. B[a]P significantly suppressed the proliferative response of both T and B cells after a sub-acute administration, an effect that was completely reversed by vaccination. In immunized mice also the immunotoxic effect of B[a]P on IFN-{gamma}, IL-12, TNF-{alpha} production and the reduced B cell activation was restored. Finally, our results showed that specific antibodies inhibited the induction of Cyp1a1 by B[a]P in lymphocytes and Cyp1b1 in the liver, enzymes that are known to convert the procarcinogen B[a]P to the ultimate DNA-adduct forming metabolite, a major risk factor of chemical carcinogenesis. Thus, we demonstrate that vaccination with a B[a]P conjugate vaccine based on a carrier protein used in licensed human vaccines reduces immunotoxicity and possibly other detrimental effects associated with B[a]P.

  7. 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

    NASA Astrophysics Data System (ADS)

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

    2004-09-01

    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.

  8. Serogroup A meningococcal conjugate vaccines in Africa.

    PubMed

    Kristiansen, Paul A; Jørgensen, Hannah J; Caugant, Dominique A

    2015-11-01

    Serogroup A meningococcal epidemics have been a recurrent public health problem, especially in resource-poor countries of Africa. Recently, the administration in mass vaccination campaigns of a single dose of the monovalent meningococcal conjugate vaccine, MenAfriVac, to the 1-29 year-old population of sub-Saharan Africa has prevented epidemics of meningitis caused by serogroup A Neisseria meningitidis. This strategy has also been shown to provide herd protection of the non-vaccinated population. Development of meningococcal conjugate vaccines covering other serogroups and enhanced use of the pneumococcal and Haemophilus influenzae type b conjugate vaccines must be pursued to fully control bacterial meningitis in sub-Saharan Africa. PMID:26358167

  9. Haemophilus influenzae type b vaccine formulation and risk of childhood leukaemia.

    PubMed

    Groves, F; Sinha, D; Auvinen, A

    2002-08-27

    Incidence of childhood leukaemia was studied among subjects of a vaccine trial in Finland comparing the polysaccharide-diptheria toxoid conjugate and oligosaccharide-CRM197 conjugate Haemophilus influenzae type b conjugate vaccine formulations. Eighty cases of childhood leukaemia were detected: 35 among children on the polysaccharide-diptheria toxoid conjugate arm, and 45 among children on the oligosaccharide-CRM197 conjugate arm, which was not statistically significant. PMID:12189546

  10. 21 CFR 522.1083 - Gonadotropin releasing factor analog-diphtheria toxoid conjugate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...DRUG ADMINISTRATION, DEPARTMENT OF HEALTH AND HUMAN SERVICES (CONTINUED) ANIMAL DRUGS, FEEDS, AND RELATED PRODUCTS IMPLANTATION OR INJECTABLE DOSAGE FORM NEW ANIMAL DRUGS § 522.1083 Gonadotropin releasing factor analog-diphtheria toxoid...

  11. A novel approach to generate a recombinant toxoid vaccine against Clostridium difficile

    PubMed Central

    Flint, Mike; Kalyan, Narender; Johnson, Erik; Witko, Susan E.; Kotash, Cheryl; Zhao, Ping; Megati, Shakuntala; Yurgelonis, Irina; Lee, Phillip Kwok; Matsuka, Yury V.; Severina, Elena; Deatly, Anne; Sidhu, Mini; Jansen, Kathrin U.; Minton, Nigel P.; Anderson, Annaliesa S.

    2013-01-01

    The Clostridium difficile toxins A and B are primarily responsible for symptoms of C. difficile associated disease and are prime targets for vaccine development. We describe a plasmid-based system for the production of genetically modified toxins in a non-sporulating strain of C. difficile that lacks the toxin genes tcdA and tcdB. TcdA and TcdB mutations targeting established glucosyltransferase cytotoxicity determinants were introduced into recombinant plasmids and episomally expressed toxin mutants purified from C. difficile transformants. TcdA and TcdB mutants lacking glucosyltransferase and autoproteolytic processing activities were ~10?000-fold less toxic to cultured human IMR-90 cells than corresponding recombinant or native toxins. However, both mutants retained residual cytotoxicity that could be prevented by preincubating the antigens with specific antibodies or by formalin treatment. Such non-toxic formalin-treated mutant antigens were immunogenic and protective in a hamster model of infection. The remaining toxicity of untreated TcdA and TcdB mutant antigens was associated with cellular swelling, a phenotype consistent with pore-induced membrane leakage. TcdB substitution mutations previously shown to block vesicular pore formation and toxin translocation substantially reduced residual toxicity. We discuss the implications of these results for the development of a C. difficile toxoid vaccine. PMID:23629868

  12. Modulation of benzo[a]pyrene induced neurotoxicity in female mice actively immunized with a B[a]P–diphtheria toxoid conjugate

    SciTech Connect

    Schellenberger, Mario T.; Grova, Nathalie; Farinelle, Sophie; Willième, Stéphanie; Muller, Claude P.

    2013-09-01

    Benzo[a]pyrene (B[a]P) is a small molecular weight carcinogen and the prototype of polycyclic aromatic hydrocarbons (PAHs). While these compounds are primarily known for their carcinogenicity, B[a]P and its metabolites are also neurotoxic for mammalian species. To develop a prophylactic immune strategy against detrimental effects of B[a]P, female Balb/c mice immunized with a B[a]P–diphtheria toxoid (B[a]P–DT) conjugate vaccine were sub-acutely exposed to 2 mg/kg B[a]P and behavioral performances were monitored in tests related to learning and memory, anxiety and motor coordination. mRNA expression of the NMDA receptor (NR1, 2A and 2B subunits) involved in the above behavioral functions was measured in 5 brain regions. B[a]P induced NMDA1 expression in three (hippocampus, amygdala and cerebellum) of five brain regions investigated, and modulated NMDA2 in two of the five brain regions (frontal cortex and cerebellum). Each one of these B[a]P-effects was reversed in mice that were immunized against this PAH, with measurable consequences on behavior such as anxiety, short term learning and memory. Thus active immunization against B[a]P with a B[a]P–DT conjugate vaccine had a protective effect and attenuated the pharmacological and neurotoxic effects even of high concentrations of B[a]P. - Highlights: • B[a]P-antibodies attenuated B[a]P induced NMDA expression in several brain regions. • B[a]P had measurable consequences on anxiety, short term learning and memory. • B[a]P immunization attenuated the pharmacological and neurotoxic effects of B[a]P. • Vaccination may also provide some protection against chemical carcinogenesis.

  13. An adolescent-adult formulation tetanus and diptheria toxoids adsorbed combined with acellular pertussis vaccine has comparable immunogenicity but less reactogenicity in children 4-6 years of age than a pediatric formulation acellular pertussis vaccine and diphtheria and tetanus toxoids adsorbed combined with inactivated poliomyelitis vaccine.

    PubMed

    Langley, Joanne M; Predy, Gerald; Guasparini, R; Law, Barbara; Diaz-Mitoma, Francisco; Whitstitt, Paul; Tapiero, Bruce; Dionne, Marc; Tomovici, A; Mills, Elaine; Halperin, Scott A

    2007-01-22

    In Canada, the fifth dose of the routine childhood immunization schedule against diphtheria, tetanus, pertussis and polio is given at 4-6 years of age. Up to 30% of children may have significant local reactions (redness, swelling) and this may be related to pertussis and diphtheria antigen content. We sought to determine if a combination product with lower content of pertussis and diphtheria toxoids (dTap) would result in fewer local reactions and not have inferior immunogenicity to a combination vaccine with higher pertussis and diphtheria content (diphtheria-tetanus-acellular pertussis-inactivated polio virus, DTaP-IPV). Healthy children aged 4-6 years with complete primary immunization series and a fourth dose of diphtheria and tetanus toxoids component pertussis inactivated polio and Haemophilus influenzae type B conjugate vaccine were randomized to one dose of dTap, followed in 4-6 weeks by one dose of IPV or control DTaP-IPV. Immediate reactions within 30 min, solicited injection site and systemic reactions within 14 days, and unsolicited adverse events (AE) within 6 weeks post-vaccination were monitored. Serum was collected prior to immunization, and 4-6 weeks after vaccine for diphtheria, tetanus and pertussis antibodies (Ab). Sample size was designed to detect > or =10% difference in injection site erythema, pain or swelling between groups 593 children at eight Canadian sites completed the study; no participant withdrew because of an AE. All safety endpoints on days 0-14 were less frequent in children randomized to the dTap than DTaP-IPV group: erythema (34.6% versus 51.7%), swelling (24.2% versus 33.8%) and pain (39.6% versus 67.2%). Fever was also less common (8.72% versus 16.9%). All children in both study groups had seroprotective Ab levels to diphtheria and tetanus at 4-6 weeks (> or =0.10 IU/mL). The majority of children in each vaccine arm had a four-fold increase in pertussis antibodies. Fever and injection site reactions are less common in 4-6 year-old-children who receive a dTap vaccine compared to DTaP-IPV, without inferior immunogenicity. PMID:17045366

  14. In vivo Evaluation of Single Dose Tetanus Toxoid Vaccine Formulation with Chitosan Microspheres.

    PubMed

    Manivannan, R; Dhanaraj, S A; Rao, Y Udaya Bhaskara; Balasubramaniam, A; Gowrishankar, N L; Jawahar, N; Jubie, S

    2008-01-01

    Chitosan adsorbed microspheres containing tetanus toxoid were prepared in the size range of 10 mum to 75 mum, by emulsion-cross linking technique at different speeds of agitation. The amount of tetanus toxoid incorporated into chitosan microspheres were estimated by limes flocculation test and in vivo evaluation of tetanus toxoid adsorbed chitosan microspheres were determined by toxin neutralization method using albino mice. The results of in vivo release for the batches of 10 mum and 25 mum correlates with the results of in vitro in which both the batches passes the limit of IP standard (4 Lf) where as, for the batches of 50 mum and 75 mum, the in vitro release of tetanus toxoid was 2 Lf. But our in vivo studies for the batches of 50 mum and 75 mum fail to pass the limit stated in IP. The release of tetanus toxoid from the chitosan microspheres was found to be sustained for the period of 6 months. PMID:20390074

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

    PubMed

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

    2010-07-01

    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. PMID:20119724

  16. The Peptide Vaccine Combined with Prior Immunization of a Conventional Diphtheria-Tetanus Toxoid Vaccine Induced Amyloid ? Binding Antibodies on Cynomolgus Monkeys and Guinea Pigs

    PubMed Central

    Yano, Akira; Ito, Kaori; Miwa, Yoshikatsu; Kanazawa, Yoshito; Chiba, Akiko; Iigo, Yutaka; Kashimoto, Yoshinori; Kanda, Akira; Murata, Shinji; Makino, Mitsuhiro

    2015-01-01

    The reduction of brain amyloid beta (A?) peptides by anti-A? antibodies is one of the possible therapies for Alzheimer's disease. We previously reported that the A? peptide vaccine including the T-cell epitope of diphtheria-tetanus combined toxoid (DT) induced anti-A? antibodies, and the prior immunization with conventional DT vaccine enhanced the immunogenicity of the peptide. Cynomolgus monkeys were given the peptide vaccine subcutaneously in combination with the prior DT vaccination. Vaccination with a similar regimen was also performed on guinea pigs. The peptide vaccine induced anti-A? antibodies in cynomolgus monkeys and guinea pigs without chemical adjuvants, and excessive immune responses were not observed. Those antibodies could preferentially recognize A?40, and A?42 compared to A? fibrils. The levels of serum anti-A? antibodies and plasma A? peptides increased in both animals and decreased the brain A?40 level of guinea pigs. The peptide vaccine could induce a similar binding profile of anti-A? antibodies in cynomolgus monkeys and guinea pigs. The peptide vaccination could be expected to reduce the brain A? peptides and their toxic effects via clearance of A? peptides by generated antibodies. PMID:26539559

  17. Role of endotoxin in alterations of hepatic drug metabolism by diphtheria and tetanus toxoids and pertussis vaccine adsorbed.

    PubMed Central

    Ansher, S; Thompson, W; Snoy, P; Habig, W

    1992-01-01

    Administration of diphtheria and tetanus toxoids and pertussis vaccine adsorbed (DTP vaccine) or endotoxin (LPS) resulted in marked alterations in hepatic drug-metabolizing enzymes in endotoxin-responsive (R) and non-endotoxin-responsive (NR) mice. A single human dose (0.5 ml) of DTP vaccine increased hexobarbital-induced sleep times to 1.6- to 1.8-fold above those of controls in both strains of mice. This effect persisted for 7 days. In contrast, Bordetella pertussis LPS-treated mice showed an increase at 1 day (3.0-fold for R mice and 1.5-fold for NR mice), which returned to control levels by day 7. Furthermore, cytochrome P-450 levels were decreased 30 to 40% 24 h after DTP vaccine administration in both R and NR mice, while after LPS administration they were decreased 30% in R mice and less than 10% in NR mice. Both spleen and liver weights of R and NR mice were increased 7 to 14 days following DTP vaccine administration. However, LPS treatment had no apparent effect on liver weights, and spleen weights of R mice were elevated from days 3 to 7. Histopathologic tissue examination showed random, multifocal inflammation with hepatocyte necrosis after DTP vaccine administration to both R and NR mice and an absence of lesions in LPS-treated mice. Premixing LPS with polymyxin eliminated the increased sleep times, but premixing DTP vaccine with polymyxin did not affect the increased sleep times. Levels of tumor necrosis factor and interleukin-6 in plasma of R mice were markedly increased after DTP and LPS treatment, while NR mice had reduced increases. These results suggest that LPS contributes to the alterations in R and NR mice seen within the first 24 h of vaccine administration but that it is not likely to contribute to the effects observed at later time points. Images PMID:1500188

  18. 13-valent pneumococcal conjugate vaccine (PCV13).

    PubMed

    Jefferies, Johanna M C; Macdonald, Emily; Faust, Saul N; Clarke, Stuart C

    2011-10-01

    The thirteen valent pneumococcal conjugate vaccine (PCV13, Prevenar 13(TM)) is the broader coverage successor to the highly effective seven valent vaccine (PCV7, Prevenar(TM)) which has reduced rates of pneumococcal disease in many countries. Despite the success of PCV7, pneumococcal disease due to non-PCV7 serotypes remains a threat in many settings, in particular many developing countries with a high burden of pneumococcal disease where serotype 1 and 5 are among the most common serotypes. Disease due to certain non-PCV7 serotypes, in particular serotype 19A has also begun to increase in incidence in countries with widespread use of PCV7. PCV13 consists of thirteen pneumococcal capsular polysaccharides individually conjugated to the diphtheria-derived protein carrier CRM(197). In addition to serotypes 4, 6B, 9V, 14, 18C, 19F and 23F included in PCV7, PCV13 also includes serotypes 1, 3, 5, 6A, 7F and 19A. PCV13 was licensed on the basis of non-inferiority trials and has proved to be at least as safe and effective as PCV7. PCV13 replaced PCV7 in the childhood immunisation schedules of the USA and UK in 2010 and is being rolled out to an increasing number of developing countries during 2011. Here we review the current literature regarding this vaccine, describing safety, efficacy, global serotype coverage and use and future directions. PMID:21941097

  19. Acellular pertussis diphtheria-tetanus-pertussis vaccine containing separately purified pertussis toxoid, filamentous haemagglutinin and 69 kDa outer membrane protein as a booster in children.

    PubMed

    Kanra, G; Ceyhan, M; Vandevoorde, D; Bogaerts, H

    1993-06-01

    In two double-blind, randomized, comparative studies involving a total of 218 children, an acellular pertussis (DTPa) vaccine containing diphtheria and tetanus toxoids and pertussis components filamentous haemagglutinin (FHA), pertussis toxoid (PT), and 69 kDa outer membrane protein (69 kDa OMP) was administered as a booster to 17-month-old and 5-year-old children with a history of routine whole-cell diphtheria-tetanus-pertussis (DTPw) vaccination. The control groups in these studies received DTPw vaccine. Among 17-month-old toddlers, significantly lower proportions of DTPa vaccine recipients had local pain (7.3%), redness (14.5%) and swelling (9.1%) than DTPw vaccine recipients (23.6%, 30.9% and 23.6%, respectively). A trend toward fewer local reactions was also seen in 5-year-old children vaccinated with DTPa in private practice and public clinics although differences were not statistically significant. Fever (rectal temperature > or = 38 degrees C) was reported more frequently for DTPw vaccine recipients in both age groups. While no differences existed between groups in terms of geometric mean antibody titres (GMTs) prior to booster vaccination, anti-PT antibody GMTs were higher among DTPa vaccine recipients than among DTPw vaccine recipients after booster vaccination. The difference was statistically significant in 5-year-old subjects. Furthermore, significantly higher anti-FHA and anti-69 kDa OMP GMTs were seen in DTPa vaccine recipients in both age groups. In pre-vaccination seropositive subjects and in pre-vaccination seronegative subjects the rate of immune response to pertussis antigens was higher for DTPa than for DTPw vaccine recipients with the exception of the rate of response induced to 69 kDa OMP in 5-year-old children.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8335014

  20. Synthesis and characterization of lipooligosaccharide-based conjugate vaccines for serotype B Moraxella catarrhalis.

    PubMed

    Yu, Shengqing; Gu, Xin-Xing

    2005-05-01

    Moraxella catarrhalis is an important cause of otitis media in children and respiratory tract infections in the elderly. Lipooligosaccharide (LOS) is a major surface antigen of the bacterium that elicits bactericidal antibodies. Serological studies show that three major LOS types (A, B, and C) have been identified among clinical isolates. Our previous studies demonstrated that the type A LOS-based conjugates were immunogenic in animals. In this study, LOS from type B strain 26397 was detoxified and conjugated to tetanus toxoid (TT) or a cross-reactive mutant (CRM) of diphtheria toxin to form detoxified LOS (dLOS)-TT and dLOS-CRM, respectively, as vaccine candidates. The molar ratios of dLOS to TT and CRM in the conjugates were 43:1 and 19:1, respectively, while both weight ratios were around 0.9. The antigenicity of the conjugates was similar to that of the LOS, as determined by enzyme-linked immunosorbent assay using a rabbit antiserum to strain 26397. Subcutaneous immunization with each conjugate elicited a 180- to 230-fold rise of serum anti-LOS immunoglobulin G in mice and >2,000-fold rise in rabbits. In addition, both mouse and rabbit antisera showed elevated complement-mediated bactericidal activity against the homologous strain, and a representative rabbit antiserum showed bactericidal activity against nine of twelve clinical isolates studied. The bactericidal activity of the rabbit antiserum can be fully inhibited by the type B LOS but not the A or C LOS. These results indicate that the type B LOS-based conjugates can be used as vaccine components for further investigation. PMID:15845482

  1. Immunochemical characterization of synthetic hexa-, octa- and decasaccharide conjugate vaccines for Vibrio cholerae O:1 Serotype Ogawa with emphasis on antigenic density and chain length

    PubMed Central

    Ftacek, Peter; Nelson, Victor; Szu, Shousun C.

    2013-01-01

    Cholera remains to be a global health problem without suitable vaccines for endemic control or outbreak relief. Here we describe a new parenteral vaccine based on neoglyco-conjugate of synthetic fragments of O-specific polysaccharide (O-SP) of Vibrio cholerae O1, serotype Ogawa. Hexa-, octa- and decasaccharides of the O-SP with carboxylic acid at the reducing end were chemically synthesized and conjugated to tetanus toxoid (TT). The conjugates prepared by a novel linking scheme consisted of 17-atom linker of hydrazide and alkyl bonds elicited robust serum IgG anti-LPS responses with vibriocidal activities in mice. There is a length dependence in immune response with decasaccharide conjugates elicited the highest anti-LPS IgG. There seems to be an indication that regardless of the carbohydrate chain length, a molar ratio of 230±10 monosaccharide units per TT induced high antibody response. The conjugates also elicited cross-reactive antibodies to serotype Inaba. The formulation of the proposed cholera conjugate vaccine, similar to other licensed polysaccharide vaccine, is suitable for children immunization. A parenteral cholera vaccine could overcome the diminishing immunogenicity in most of oral vaccines due to the gastrointestinal complexity and environmental enteropathy in children living in impoverished environment and could be considered for global cholera immunization. PMID:23955520

  2. Preclinical evaluation of group B Neisseria meningitidis and Escherichia coli K92 capsular polysaccharide-protein conjugate vaccines in juvenile rhesus monkeys.

    PubMed Central

    Devi, S J; Zollinger, W D; Snoy, P J; Tai, J Y; Costantini, P; Norelli, F; Rappuoli, R; Frasch, C E

    1997-01-01

    We reported the first use of group B meningococcal conjugate vaccines in a nonhuman primate model (S. J. N. Devi, C. E. Frasch, W. Zollinger, and P. J. Snoy, p. 427-429, in J. S. Evans, S. E. Yost, M. C. J. Maiden, and I. M. Feavers, ed., Proceedings of the Ninth International Pathogenic Neisseria Conference, 1994). Three different group B Neisseria meningitidis capsular polysaccharide (B PS)-protein conjugate vaccines and an Escherichia coli K92 capsular polysaccharide-tetanus toxoid (K92-TT) conjugate vaccine are here evaluated for safety and relative immunogenicities in juvenile rhesus monkeys with or without adjuvants. Monkeys were immunized intramuscularly with either B PS-cross-reactive material 197 conjugate, B PS-outer membrane vesicle (B-OMV) conjugate, or N-propionylated B PS-outer membrane protein 3 (N-pr. B-OMP3) conjugate vaccine with or without adjuvants at weeks 0, 6, and 14. A control group of monkeys received one injection of the purified B PS alone, and another group received three injections of B PS noncovalently complexed with OMV. Antibody responses as measured by enzyme-linked immunosorbent assay varied among individual monkeys. All vaccines except B PS and the K92-TT conjugate elicited a twofold or greater increase in total B PS antibodies after one immunization. All vaccines, including the K92-TT conjugate, elicited a rise in geometric mean B PS antibody levels of ninefold or more over the preimmune levels following the third immunization. Antibodies elicited by N-pr. B-OMP3 and B-OMV conjugates were directed to the N-propionylated or to the spacer-containing B PS antigens as well as to the native B PS complexed with methylated human serum albumin. None of the vaccines caused discernible safety-related symptoms. PMID:9038314

  3. Kinetics of antibody persistence following administration of a combination meningococcal serogroup C and haemophilus influenzae type b conjugate vaccine in healthy infants in the United Kingdom primed with a monovalent meningococcal serogroup C vaccine.

    PubMed

    Borrow, Ray; Andrews, Nick; Findlow, Helen; Waight, Pauline; Southern, Joanna; Crowley-Luke, Annette; Stapley, Lorraine; England, Anna; Findlow, Jamie; Miller, Elizabeth

    2010-01-01

    The kinetics of antibody persistence following the administration of a combination meningococcal serogroup C and Haemophilus influenzae type b (Hib) conjugate vaccine (Menitorix) in the second year of life in children primed with two doses of one of three monovalent meningococcal serogroup C (MCC) vaccines was investigated. The study subjects were administered either Menitorix at 12 to 15 months of age, followed by the seven-valent pneumococcal conjugate vaccine (PCV7) and the measles, mumps, and rubella vaccine 4 to 6 weeks later, or all three vaccines concomitantly at 12 to 15 months of age. Blood samples were collected before and 1, 2, 12, and 24 months after the boosting. Sera were analyzed for meningococcal serogroup C serum bactericidal antibody (SBA) and IgG as well as Hib-polyribosylribitol phosphate (PRP)-specific IgG. The antibody persistence data from this study were compared to those of a prior study of Southern et al. (Clin. Vaccine Immunol. 14:1328-1333, 2007) in which children were given three primary doses of a vaccine containing both the MCC and the Hib vaccines but were boosted only with a Hib conjugate vaccine. The magnitude of the meningococcal SBA geometric mean titer was higher for those subjects primed with the MCC vaccine conjugated to tetanus toxoid (NeisVac-C) than for those primed with one of two MCC vaccines conjugated to CRM(197) (Menjugate or Meningitec) up to 1 year following boosting. Two years after boosting, the percentages of subjects with putatively protective SBA titers of > or =8 for children primed with NeisVac-C, Menjugate, and Meningitec were 43%, 22%, and 23%, respectively. Additional booster doses of the MCC vaccine may be required in the future to maintain good antibody levels; however, there is no immediate need for a booster during adolescence, as mathematical modeling has shown that persisting herd immunity is likely to control disease for a number of years. PMID:19906895

  4. Adsorption of Toll-Like Receptor 4 Agonist to Alum-Based Tetanus Toxoid Vaccine Dampens Pro-T Helper 2 Activities and Enhances Antibody Responses

    PubMed Central

    Bortolatto, Juliana; Mirotti, Luciana; Rodriguez, Dunia; Gomes, Eliane; Russo, Momtchilo

    2015-01-01

    Aluminum salts gels (alum) are TLR-independent adjuvants and have been used to boost antibody responses in alum-based vaccines such as diphtheria, pertussis, and tetanus toxoid (DPT) triple vaccine. However, the pro-Th2 activity of alum-based vaccine formulations has not been fully appreciated. Here we found that alum-based tetanus toxoid (TT) vaccine was biased toward a Th-2 profile as shown by TT-induced airway eosinophilic inflammation, type 2 cytokine production, and high levels of IgE anaphylactic antibodies. The adsorption into alum of prototypic TLR4 agonists such as lipopolysaccharides (LPS) derived from Escherichia coli consistently dampened TT-induced Th2 activities without inducing IFN? or Th1-like responses in the lung. Conversely, adsorption of monophosphoryl lipid A (MPLA) extracted from Salmonella minnesota, which is a TIR-domain-containing adapter-inducing interferon-?- (TRIF-) biased TLR4 agonist, was less effective in decreasing Th-2 responses. Importantly, in a situation with antigenic competition (OVA plus TT), TT-specific IgG1 or IgG2a was decreased compared with TT sensitization. Notably, LPS increased the production of IgG1 and IgG2a TT-specific antibodies. In conclusion, the addition of LPS induces a more robust IgG1 and IgG2a TT-specific antibody production and concomitantly decreases Th2-cellular and humoral responses, indicating a potential use of alum/TLR-based vaccines. PMID:26380316

  5. Evaluation of the safety and immunogenicity in United Kingdom laboratory workers of a combined Haemophilus influenzae type b and meningococcal capsular group C conjugate vaccine

    PubMed Central

    2014-01-01

    Background Although a combined Haemophilus influenzae type b (Hib)/meningococcal capsular group C (MenC) conjugate vaccine with a tetanus toxoid carrier protein (Hib/MenC-TT) is not licensed for use in those above 2 years of age due to lack of data on safety and efficacy, certain patient groups at high risk of MenC and/or Hib disease are recommended to receive it. Laboratory workers working with Hib and/or MenC cultures may be at a potentially increased risk of acquiring infectious diseases and vaccination is therefore an important safety consideration. We undertook a clinical trial to investigate the safety and immunogenicity of Hib/MenC-TT vaccine in this cohort. Methods A total of 33 subjects were recruited to the trial, all of whom were vaccinated. Serology was completed on samples taken at baseline and four weeks following vaccination to determine MenC specific IgG, MenC serum bactericidal antibody (SBA), anti-Hib polyribosylribitol phosphate (PRP) IgG and anti-tetanus toxoid IgG responses. Results At baseline, high proportions of subjects had protective antibody concentrations against MenC, Hib and tetanus due to previous vaccination and/or natural exposure. Vaccination induced?>?3, 10 and 220 fold increases in geometric mean concentrations for MenC SBA, anti-tetanus toxoid IgG and anti-Hib PRP IgG, respectively. Following vaccination, 97% of subjects had putative protective SBA titres???8, 100% had short term protective anti-Hib PRP IgG concentrations???0.15 ?g/mL and 97% had protective anti-tetanus toxoid concentrations???0.1 IU/mL. No safety concerns were reported with minor local reactions being reported by 21% of subjects. Conclusions Immunological responses determined in this trial are likely a combination of primary and secondary responses due to previous vaccination and natural exposure. Subjects were a representative cross-section of laboratory workers, enabling us to conclude that a single dose of Hib/MenC-TT was safe and immunogenic in healthy adults providing the evidence that this vaccine may be used for providing protection in an occupational setting. PMID:25071861

  6. Patterns of binding of aluminum-containing adjuvants to Haemophilus influenzae type b and meningococcal group C conjugate vaccines and components

    PubMed Central

    Otto, Robert B.D.; Burkin, Karena; Amir, Saba Erum; Crane, Dennis T.; Bolgiano, Barbara

    2015-01-01

    The basis of Haemophilus influenzae type b (Hib) and Neisseria meningitidis serogroup C (MenC) glycoconjugates binding to aluminum-containing adjuvants was studied. By measuring the amount of polysaccharide and protein in the non-adsorbed supernatant, the adjuvant, aluminum phosphate, AlPO4, was found to be less efficient than aluminum hydroxide, Al(OH)3 at binding to the conjugates, at concentrations relevant to licensed vaccine formulations and when equimolar. At neutral pH, binding of TT conjugates to AlPO4 was facilitated through the carrier protein, with only weak binding of AlPO4 to CRM197 being observed. There was slightly higher binding of either adjuvant to tetanus toxoid conjugates, than to CRM197 conjugates. This was verified in AlPO4 formulations containing DTwP–Hib, where the adsorption of TT-conjugated Hib was higher than CRM197-conjugated Hib. At neutral pH, the anionic Hib and MenC polysaccharides did not appreciably bind to AlPO4, but did bind to Al(OH)3, due to electrostatic interactions. Phosphate ions reduced the binding of the conjugates to the adjuvants. These patterns of adjuvant adsorption can form the basis for future formulation studies with individual and combination vaccines containing saccharide-protein conjugates. PMID:26194164

  7. [Evaluation of the vaccination of 3-month-old infants with Haemophilus influenzae type B (Hi b) capsular polysaccharide conjugated to tetanus protein (PRT-T) Pediatric Group of the Lyon Region].

    PubMed

    Langue, J; Fritzell, B; Preziozi, M P; Houmeau, P

    1991-01-01

    Haemophilus influenzae type b (Hi b) is responsible for severe invasive infections, particularly meningitis, in children under 5 years of age, with the greatest frequency between 6 and 18 months. The antigenicity of Hib is related to its capsular polysaccharide (polyribosyl-ribitol-phosphate or PRP) which is at the origin of the production of bactericide anti-PRP antibodies. Vaccine using PRP alone have been shown to be well tolerated and immunogenic, but only in children above 2 years of age. We vaccinated 365 infants starting at the age of 3 months with a vaccine using a PRP-tetanus toxoid conjugate (PRP-T), coupled with the DTP pertussis vaccine. Local and general tolerance was found to be very good. Quantitative serum antibody measurements showed excellent immunogenicity. None of the vaccinated infants presented an invasive Hib infection. It therefore appears that early systematic vaccination of infants with PRP-T vaccine should be encouraged. PMID:1667038

  8. Challenges and Opportunities While Developing a Group A Meningococcal Conjugate Vaccine Within a Product Development Partnership: A Manufacturer's Perspective From the Serum Institute of India

    PubMed Central

    Kulkarni, Prasad S.; Socquet, Muriel; Jadhav, Suresh S.; Kapre, Subhash V.; LaForce, F. Marc; Poonawalla, Cyrus S.

    2015-01-01

    Background.?In 2002, the Meningitis Vaccine Project (MVP) chose the Serum Institute of India, Ltd (SIIL), as its manufacturing partner to establish a product development partnership (PDP) with the Meningitis Vaccine Project (MVP). MVP was a collaboration between PATH and the World Health Organization (WHO) to develop meningococcal conjugate vaccines for sub-Saharan Africa. Method.?From the outset, SIIL recognized that a partnership with MVP carried some risk but also offered important opportunities for accessing new conjugate vaccine technology and know-how. Over 3 years, SIIL successfully accepted technology transfer for the group A meningococcal polysaccharide from SynCo Bio Partners and a conjugation method from the US Food and Drug Administration. Results.?SIIL successfully scaled up production of a group A meningococcal conjugate vaccine that used SIIL tetanus toxoid as the carrier protein. Phase 1 studies began in India in 2005, followed by phase 2/3 studies in Africa and India. A regulatory dossier was submitted to the Indian authorities in April 2009 and WHO in September 2009. Export license was granted in December 2009, and WHO prequalification was obtained in June 2010. Vaccine was introduced at public scale in Burkina Faso that December. The group A meningococcal conjugate vaccine was named MenAfriVac, and is the first internationally qualified vaccine developed outside of big pharma. Conclusions.?The project proved to be a sound investment for SIIL and is a concrete example of the potential for PDPs to provide needed products for resource-poor countries. PMID:26553678

  9. Conjugate-like immunogens produced as protein capsular matrix vaccines

    PubMed Central

    Thanawastien, Ann; Cartee, Robert T.; Griffin, Thomas J.; Killeen, Kevin P.; Mekalanos, John J.

    2015-01-01

    Capsular polysaccharides are the primary antigenic components involved in protective immunity against encapsulated bacterial pathogens. Although immunization of adolescents and adults with polysaccharide antigens has reduced pathogen disease burden, pure polysaccharide vaccines have proved ineffective at conferring protective immunity to infants and the elderly, age cohorts that are deficient in their adaptive immune responses to such antigens. However, T-cell–independent polysaccharide antigens can be converted into more potent immunogens by chemically coupling to a “carrier protein” antigen. Such “conjugate vaccines” efficiently induce antibody avidity maturation, isotype switching, and immunological memory in immunized neonates. These immune responses have been attributed to T-cell recognition of peptides derived from the coupled carrier protein. The covalent attachment of polysaccharide antigens to the carrier protein is thought to be imperative to the immunological properties of conjugate vaccines. Here we provide evidence that covalent attachment to carrier proteins is not required for conversion of T-independent antigens into T-dependent immunogens. Simple entrapment of polysaccharides or a d-amino acid polymer antigen in a cross-linked protein matrix was shown to be sufficient to produce potent immunogens that possess the key characteristics of conventional conjugate vaccines. The versatility and ease of manufacture of these antigen preparations, termed protein capsular matrix vaccines (PCMVs), will likely provide improvements in the manufacture of vaccines designed to protect against encapsulated microorganisms. This in turn could improve the availability of such vaccines to the developing world, which has shown only a limited capacity to afford the cost of conventional conjugate vaccines. PMID:25699685

  10. Subclass compositions of immunoglobulin G to pertussis toxin in patients with whooping cough, in healthy individuals, and in recipients of a pertussis toxoid vaccine.

    PubMed

    Zackrisson, G; Lagergård, T; Trollfors, B

    1989-07-01

    The subclass composition of serum immunoglobulin G (IgG) antibodies against pertussis toxin was studied in 108 serum samples obtained during various stages of disease from 75 patients with whooping cough. IgG1 and IgG3 antibodies were detected in 92 and 42% of the samples, respectively, while only a few contained IgG2 or IgG4 antibodies. Similarly, IgG1 antibodies were predominant in serum samples from healthy children and adults, many of whom had a history of whooping cough several years earlier. Of 85 children and 30 adults with detectable levels of total IgG, 65 and 14 had IgG1 antibodies, respectively, while only 9 of them had IgG3 antibodies. Again, very few sera contained IgG2 or IgG4 antibodies. In contrast, 13 children vaccinated with an acellular aluminum-adsorbed pertussis toxoid vaccine responded mainly with IgG1 and IgG4 antibodies. In conclusion, this study showed that the subclass composition of IgG antibodies to pertussis toxin after natural infection consists mainly of IgG1 and to a certain extent of IgG3, while an aluminum-adsorbed pertussis toxoid induces IgG1 and IgG4 antibodies. PMID:2768444

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

    MedlinePLUS

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

  12. Cancer Vaccine Composed of Oligonucleotides Conjugated to Apoptotic Tumor Cells

    Cancer.gov

    NCI Scientists have discovered that conjugating CpG ODNs to apoptotic tumor cells to improve vaccine activity by ensuring that the ODN remains associated with the tumor antigen so that both are internalized by professional antigen presenting cells. The strategy eliminates the need to define specific tumor-associated antigens, substituting instead the entire tumor cell (which in the absence of CpG ODN is poorly immunogenic).

  13. Impacts of the 13-Valent Pneumococcal Conjugate Vaccine in Children

    PubMed Central

    Esposito, Susanna; Principi, Nicola

    2015-01-01

    Applications of the heptavalent pneumococcal conjugate vaccine (PCV7) in the pediatric immunization schedule have dramatically reduced the incidence of pneumococcal diseases in both vaccinated children and unvaccinated individuals of all ages. However, increased infections caused by non-PCV7 serotypes have been reported by several groups. To overcome this problem, new vaccines covering more serotypes including the emerging serotypes have been developed. The 13-valent pneumococcal conjugate vaccine (PCV13) currently covers the 7 PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F) and 6 additional serotypes 1, 3, 5, 6A, 7F, and 19A. After the first year of PCV13 applications in the immunization schedule in young children, global evaluation studies demonstrated that PCV13 provided a wider coverage and more effective prevention than PCV7 against invasive pneumococcal diseases (IPDs), mucosal pneumococcal diseases, and pneumococcal carriage. We reviewed the effects of PCV13 in the control of pneumococcal diseases in children based on previous studies. PMID:26351648

  14. Results from a Randomized Clinical Trial of Coadministration of RotaTeq, a Pentavalent Rotavirus Vaccine, and NeisVac-C, a Meningococcal Serogroup C Conjugate Vaccine ? †

    PubMed Central

    Vesikari, Timo; Karvonen, Aino; Borrow, Ray; Kitchin, Nick; Baudin, Martine; Thomas, Stéphane; Fiquet, Anne

    2011-01-01

    RotaTeq (Merck & Co. Inc./Sanofi Pasteur MSD) is a three-dose, oral pentavalent rotavirus vaccine for the immunization of infants from 6 weeks of age for the prevention of rotavirus gastroenteritis. The primary objective of the present trial was to demonstrate that RotaTeq can be coadministered with meningococcal serogroup C conjugate vaccine (MenCC; NeisVac-C; Baxter Healthcare) to healthy infants without impairing the protective immune responses to MenCC. This was an open-label, randomized, comparative study conducted in Finland. The study was designed to assess concomitant versus sequential administration of RotaTeq and MenCC on the immune response to both vaccines. Healthy infants (n = 247), aged 6 to 7 weeks, were recruited. Coadministration of MenCC with RotaTeq was noninferior to sequential administration for the seroprotection rate against meningococcal serogroup C (the proportion of infants with a serum bactericidal antibody titer using baby rabbit complement of ?8 was 100% in both groups). The other responses to MenCC (titer of ?1:128, ?4-fold increase in titer, and geometric mean titers [GMTs]) and the responses to RotaTeq (IgA and SNA response to G1 to G4 and P1A[8], GMTs, and ?3-fold increase in titer) were comparable between groups, including a ?3-fold IgA increase in >96% of the infants in both groups. Concomitant administration of the first doses of MenCC, diphtheria and tetanus toxoids and acellular pertussis vaccine, inactivated poliovirus vaccine, and Haemophilus influenzae type b conjugate vaccine (DTaP-IPV-Hib), and RotaTeq was associated with a higher rate of vomiting and diarrhea than concomitant administration of MenCC and DTaP-IPV-Hib, but that was not observed after the second concomitant administration. The convenience of concomitant administration of RotaTeq and MenCC may, however, outweigh the additive effect of mostly mild adverse events reported after the individual administration of each vaccine. These results support the coadministration of RotaTeq and MenCC. PMID:21389149

  15. Preparation and testing of a Vi conjugate vaccine using pneumococcal surface protein A (PspA) from Streptococcus pneumoniae as the carrier protein.

    PubMed

    Kothari, Neha; Genschmer, Kristopher R; Kothari, Sudeep; Kim, Jeong Ah; Briles, David E; Rhee, Dong Kwon; Carbis, Rodney

    2014-09-29

    In the current study pneumococcal surface protein A (PspA) was conjugated to Vi capsular polysaccharide from Salmonella Typhi to make available a vaccine against typhoid fever that has the potential to also provide broad protection from Streptococcus pneumoniae. High yielding production processes were developed for the purification of PspAs from families 1 and 2. The purified PspAs were conjugated to Vi with high recovery of both Vi and PspA. The processes developed especially for PspA family 2 could readily be adapted for large scale production under cGMP conditions. Previously we have shown that conjugation of diphtheria toxoid (DT) to Vi polysaccharide improves the immune response to Vi but can also enhance the response to DT. In this study it was shown that conjugation of PspA to Vi enhanced the anti-PspA response and that PspA was a suitable carrier protein as demonstrated by the characteristics of a T-cell dependent response to the Vi. We propose that a bivalent vaccine consisting of PspA from families 1 and 2 bound to Vi polysaccharide would protect against typhoid fever and has the potential to also protect against pneumococcal disease and should be considered for use in developing countries. PMID:25171842

  16. Lessons learned during the development and transfer of technology related to a new Hib conjugate vaccine to emerging vaccine manufacturers.

    PubMed

    Hamidi, A; Boog, C; Jadhav, S; Kreeftenberg, H

    2014-07-16

    The incidence of Haemophilus Influenzae type b (Hib) disease in developed countries has decreased since the introduction of Hib conjugate vaccines in their National Immunization Programs (NIP). In countries where Hib vaccination is not applied routinely, due to limited availability and high cost of the vaccines, invasive Hib disease is still a cause of mortality. Through the development of a production process for a Hib conjugate vaccine and related quality control tests and the transfer of this technology to emerging vaccine manufacturers in developing countries, a substantial contribution was made to the availability and affordability of Hib conjugate vaccines in these countries. Technology transfer is considered to be one of the fastest ways to get access to the technology needed for the production of vaccines. The first Hib conjugate vaccine based on the transferred technology was licensed in 2007, since then more Hib vaccines based on this technology were licensed. This paper describes the successful development and transfer of Hib conjugate vaccine technology to vaccine manufacturers in India, China and Indonesia. By describing the lessons learned in this process, it is hoped that other technology transfer projects can benefit from the knowledge and experience gained. PMID:24923635

  17. Preclinical evaluation of a Haemophilus influenzae type b conjugate vaccine process intended for technology transfer.

    PubMed

    Hamidi, Ahd; Verdijk, Pauline; Kreeftenberg, Hans

    2014-01-01

    Introduction of Haemophilus influenzae type b (Hib) vaccine in low- and middle-income countries has been limited by cost and availability of Hib conjugate vaccines for a long time. It was previously recognized by the Institute for Translational Vaccinology (Intravacc, originating from the former Vaccinology Unit of the National Institute of Public Health [RIVM] and the Netherlands Vaccine Institute [NVI]) that local production of a Hib conjugate vaccine would increase the affordability and sustainability of the vaccine and thereby help to speed up Hib introduction in these countries. A new affordable and a non-infringing production process for a Hib conjugate vaccine was developed, including relevant quality control tests, and the technology was transferred to a number of vaccine manufacturers in India, Indonesia, and China. As part of the Hib technology transfer project managed by Intravacc, a preclinical toxicity study was conducted in the Netherlands to test the safety and immunogenicity of this new Hib conjugate vaccine. The data generated by this study were used by the technology transfer partners to accelerate the clinical development of the new Hib conjugate vaccine. A repeated dose toxicity and local tolerance study in rats was performed to assess the reactogenicity and immunogenicity of a new Hib conjugate vaccine compared to a licensed vaccine. The results showed that the vaccine was well tolerated and immunogenic in rats, no major differences in both safety and immunogenicity in rats were found between the vaccine produced according to the production process developed by Intravacc and the licensed one. Rats may be useful to verify the immunogenicity of Hib conjugate vaccines and for preclinical evaluation. In general, nonclinical evaluation of the new Hib conjugate vaccine, including this proof of concept (safety and immunogenicity study in rats), made it possible for technology transfer partners, having implemented the original process with no changes in the manufacturing process and vaccine formulation, to start directly with phase 1 clinical trials. PMID:25483504

  18. [Medical indications and effectiveness of the pneumococcal conjugate vaccine].

    PubMed

    Reinert, R R

    2006-04-01

    Streptococcus pneumoniae is a leading cause of bacterial pneumonia, meningitis, sinusitis, and acute otitis media in children and adults worldwide. Especially in the age group of < 2 years the incidence of invasive pneumococcal is high. The vulnerability of children to S. pneumoniae can also be demonstrated by the high rate of sequelae (> 20 % in Germany) and the high mortality (7.5 %) in pneumococcal meningitis. A 7-valent pneumococcal conjugate vaccine that was shown to be highly efficacious in preventing invasive pneumococcal disease in infants in the USA was licensed in Europe in 2001. It is expected that broad usage of the vaccine would reduce the incidence of invasive pneumococcal disease and the levels of pneumococcal resistance significantly. PMID:16615030

  19. Invasive Pneumococcal Disease 3 Years after Introduction of 10-Valent Pneumococcal Conjugate Vaccine, the Netherlands.

    PubMed

    Knol, Mirjam J; Wagenvoort, Gertjan H J; Sanders, Elisabeth A M; Elberse, Karin; Vlaminckx, Bart J; de Melker, Hester E; van der Ende, Arie

    2015-11-01

    Three years after a 7-valent pneumococcal conjugate vaccine was replaced by a 10-valent pneumococcal conjugate vaccine in the Netherlands, we observed a decrease in incidence of invasive pneumococcal disease caused by Streptococcus pneumoniae serotypes 1, 5, and 7F. Our data do not support or exclude cross-protection against serotype 19A. PMID:26488415

  20. Invasive Pneumococcal Disease 3 Years after Introduction of 10-Valent Pneumococcal Conjugate Vaccine, the Netherlands

    PubMed Central

    Wagenvoort, Gertjan H.J.; Sanders, Elisabeth A.M.; Elberse, Karin; Vlaminckx, Bart J.; de Melker, Hester E.; van der Ende, Arie

    2015-01-01

    Three years after a 7-valent pneumococcal conjugate vaccine was replaced by a 10-valent pneumococcal conjugate vaccine in the Netherlands, we observed a decrease in incidence of invasive pneumococcal disease caused by Streptococcus pneumoniae serotypes 1, 5, and 7F. Our data do not support or exclude cross-protection against serotype 19A. PMID:26488415

  1. Overview of the development and current use of CRM(197) conjugate vaccines for pediatric use.

    PubMed

    Shinefield, Henry R

    2010-06-17

    Glycoconjugate vaccines have been proven safe and effective against various diseases in children. Although these vaccines have a history of effectiveness, there are still many unanswered questions to be addressed, including conjugate interference when multiple vaccines are administered at one time, expansion of serotype coverage, effectiveness in special populations, and issues relating to conjugate vaccine use in the developing world. This paper focuses on the use of CRM(197) as a carrier protein, contrasting it to other carrier proteins used in single-antigen pediatric vaccines as well as identifying areas for future study. PMID:20452430

  2. The Impact of Age on the Efficacy of 13-valent Pneumococcal Conjugate Vaccine in Elderly.

    PubMed

    van Werkhoven, Cornelis H; Huijts, Susanne M; Bolkenbaas, Marieke; Grobbee, Diederick E; Bonten, Marc J M

    2015-12-15

    In a post hoc analysis of the Community-Acquired Pneumonia (CAP) immunization Trial in Adults the model-predicted 13-valent pneumococcal conjugate vaccine efficacy for preventing vaccine-type specific CAP and Invasive Pneumococcal Disease declined from 65% to 40% for subjects being 65 and 75 year olds at the time of vaccination, respectively. PMID:26265498

  3. Pneumococcal Infection among Children before Introduction of 13-Valent Pneumococcal Conjugate Vaccine, Cambodia.

    PubMed

    Turner, Paul; Turner, Claudia; Suy, Kuong; Soeng, Sona; Ly, Sokeng; Miliya, Thyl; Goldblatt, David; Day, Nicholas P J

    2015-11-01

    Vaccination of children with pneumococcal conjugate vaccine (PCV13) was initiated in Cambodia in 2015. To determine baseline data, we collected samples from children in 2013 and 2014. PCV13 serotypes accounted for 62.7% of colonizing organisms in outpatients and 88.4% of invasive pneumococci overall; multidrug resistance was common. Thus, effectiveness of vaccination should be high. PMID:26488597

  4. Pneumococcal Infection among Children before Introduction of 13-Valent Pneumococcal Conjugate Vaccine, Cambodia

    PubMed Central

    Turner, Claudia; Suy, Kuong; Soeng, Sona; Ly, Sokeng; Miliya, Thyl; Goldblatt, David; Day, Nicholas P.J.

    2015-01-01

    Vaccination of children with pneumococcal conjugate vaccine (PCV13) was initiated in Cambodia in 2015. To determine baseline data, we collected samples from children in 2013 and 2014. PCV13 serotypes accounted for 62.7% of colonizing organisms in outpatients and 88.4% of invasive pneumococci overall; multidrug resistance was common. Thus, effectiveness of vaccination should be high. PMID:26488597

  5. Carrier priming with CRM 197 or diphtheria toxoid has a different impact on the immunogenicity of the respective glycoconjugates: biophysical and immunochemical interpretation.

    PubMed

    Pecetta, S; Lo Surdo, P; Tontini, M; Proietti, D; Zambonelli, C; Bottomley, M J; Biagini, M; Berti, F; Costantino, P; Romano, M R

    2015-01-01

    Glycoconjugate vaccines play an enormous role in preventing infectious diseases. The main carrier proteins used in commercial conjugate vaccines are the non-toxic mutant of diphtheria toxin (CRM197), diphtheria toxoid (DT) and tetanus toxoid (TT). Modern childhood routine vaccination schedules include the administration of several vaccines simultaneously or in close sequence, increasing the concern that the repeated exposure to conjugates based on these carrier proteins might interfere with the anti-polysaccharide response. Extending previous observations we show here that priming mice with CRM197 or DT does not suppress the response to the carbohydrate moiety of CRM197 meningococcal serogroup A (MenA) conjugates, while priming with DT can suppress the response to DT-MenA conjugates. To explain these findings we made use of biophysical and immunochemical techniques applied mainly to MenA conjugates. Differential scanning calorimetry and circular dichroism data revealed that the CRM197 structure was altered by the chemical conjugation, while DT and the formaldehyde-treated form of CRM197 were less impacted, depending on the degree of glycosylation. Investigating the binding and avidity properties of IgGs induced in mice by non-conjugated carriers, we found that CRM197 induced low levels of anti-carrier antibodies, with decreased avidity for its MenA conjugates and poor binding to DT and respective MenA conjugates. In contrast, DT induced high antibody titers able to bind with comparable avidity both the protein and its conjugates but showing very low avidity for CRM197 and related conjugates. The low intrinsic immunogenicity of CRM197 as compared to DT, the structural modifications induced by glycoconjugation and detoxification processes, resulting in conformational changes in CRM197 and DT epitopes with consequent alteration of the antibody recognition and avidity, might explain the different behavior of CRM197 and DT in a carrier priming context. PMID:25448110

  6. Vaccines (immunizations) - overview

    MedlinePLUS

    ... The flu vaccine is an example. Toxoid vaccines contain a toxin or chemical made by the bacteria ... are the diphtheria and tetanus vaccines. Biosynthetic vaccines contain manmade substances that are very similar to pieces ...

  7. Determining trace amounts and the origin of formaldehyde impurity in Neisseria meningitidis A/C/Y/W-135-DT conjugate vaccine formulated in isotonic aqueous 1× PBS by improved C18-UPLC method.

    PubMed

    Gudlavalleti, Seshu K; Crawford, Erika N; Tran, Nhi N; Orten, Dana J; Harder, Jeffery D; Reddy, Jeeri R

    2015-03-25

    The ability to accurately measure and report trace amounts of residual formaldehyde impurity in a vaccine product is not only critical in the product release but also a regulatory requirement. In many bacterial or viral vaccine manufacturing procedures, formaldehyde is used either at a live culture inactivation step or at a protein de-toxification step or at both. Reported here is a validated and improved C18-UPLC method (developed based on previously published C-8 HPLC method) to determine the traces of formaldehyde process impurity in a liquid form Neisseria meningitidis A/C/Y/W-135-DT conjugate vaccine formulated in isotonic aqueous 1× PBS. UPLC C-18 column and the conditions described distinctly resolved the 2,4-DNPH-HCHO adduct from the un-reacted 2,4-DNPH as detected by TUV detector at 360 nm. This method was shown to be compatible with PBS formulation and extremely sensitive (with a quantitation limit of 0.05 ppm) and aided to determine formaldehyde contamination sources by evaluating the in-process materials as a track-down analysis. Final nanogram levels of formaldehyde in the formulated single dose vialed vaccine mainly originated from the diphtheria toxoid carrier protein used in the production of the conjugate vaccine, whereas relative contribution from polysaccharide API was minimal. PMID:25668795

  8. Serogroup C meningococcal conjugate vaccines: new preparations. Effective from age two months.

    PubMed

    2003-04-01

    (1) Two unconjugated polyoside vaccines are available in France for the prevention of meningococcal infections: Vaccine meningococcique A+C from Pasteur Vaccines (against serogroups A and C) and Menomune from Aventis Pasteur MSD (against serogroups A, C, Y and W-135). Neither vaccine is effective in children under the age of two years. (2) 2002 saw the arrival of two conjugated vaccines directed solely against serogroup C meningococci and designed to protect infants from two months of age. Meningitec, marketed by Wyeth-Lederlé, is adsorbed to aluminium phosphate. The other conjugate vaccine is adsorbed to aluminium hydroxide and marketed under two names: Meninvact (Aventis Pasteur MSD) and Menjugate (Socopharm). (3) Immunogenicity studies have shown three advantages of conjugate vaccines over polyoside vaccines, namely a serologic response from as early as two months of age; a higher antibody titre 6 months after vaccination; and a larger increase in the antibody titre after booster injections. (4) Two-year follow-up data on a mass vaccination campaign launched in the United Kingdom in 1999 with Meningitec and Menjugate show that both vaccines have short-term efficacy in infants, children and adolescents. There was about an 80% fall in the number of invasive infections due to group C meningococci among vaccines, no such fall among unvaccinated subjects of the same age, and no major increase in the incidence of infections due to other serogroups. The number of deaths due to documented meningococcal infection showed a similar fall. (5) Most known adverse effects of these conjugate vaccines are mild and similar to those of other standard vaccines. They do not appear to be more frequent than with standard vaccines. Severe allergic reactions have occasionally been observed. A few deaths have followed vaccination with these products but appear to have been coincidental. There is no evidence that the two conjugate vaccines differ in terms of adverse effects. (6) Meningitec (suspension for injection) is more convenient to use than Meninvact and Menjugate (powders for injection). (7) Unlike the other companies concerned, Aventis Pasteur MSD failed to provide us with any documentation on their vaccine. (8) In practice, when specific vaccination against serogroup C meningococci is required (for case contacts or in areas of high incidence), Meningitec is currently the vaccine of choice. If Meningitec stocks are inadequate to deal with an outbreak, the second-line choice is Menjugate. PMID:12675020

  9. Effect of a serogroup A meningococcal conjugate vaccine (PsA–TT) on serogroup A meningococcal meningitis and carriage in Chad: a community study

    PubMed Central

    Daugla, DM; Gami, JP; Gamougam, K; Naibei, N; Mbainadji, L; Narbé, M; Toralta, J; Kodbesse, B; Ngadoua, C; Coldiron, ME; Fermon, F; Page, A-L; Djingarey, MH; Hugonnet, S; Harrison, OB; Rebbetts, LS; Tekletsion, Y; Watkins, ER; Hill, D; Caugant, DA; Chandramohan, D; Hassan-King, M; Manigart, O; Nascimento, M; Woukeu, A; Trotter, C; Stuart, JM; Maiden, MCJ; Greenwood, BM

    2013-01-01

    Summary Background A serogroup A meningococcal polysaccharide–tetanus toxoid conjugate vaccine (PsA–TT, MenAfriVac) was licensed in India in 2009, and pre-qualified by WHO in 2010, on the basis of its safety and immunogenicity. This vaccine is now being deployed across the African meningitis belt. We studied the effect of PsA–TT on meningococcal meningitis and carriage in Chad during a serogroup A meningococcal meningitis epidemic. Methods We obtained data for the incidence of meningitis before and after vaccination from national records between January, 2009, and June, 2012. In 2012, surveillance was enhanced in regions where vaccination with PsA–TT had been undertaken in 2011, and in one district where a reactive vaccination campaign in response to an outbreak of meningitis was undertaken. Meningococcal carriage was studied in an age-stratified sample of residents aged 1–29 years of a rural area roughly 13–15 and 2–4 months before and 4–6 months after vaccination. Meningococci obtained from cerebrospinal fluid or oropharyngeal swabs were characterised by conventional microbiological and molecular methods. Findings Roughly 1·8 million individuals aged 1–29 years received one dose of PsA–TT during a vaccination campaign in three regions of Chad in and around the capital N'Djamena during 10 days in December, 2011. The incidence of meningitis during the 2012 meningitis season in these three regions was 2·48 per 100?000 (57 cases in the 2·3 million population), whereas in regions without mass vaccination, incidence was 43·8 per 100?000 (3809 cases per 8·7 million population), a 94% difference in crude incidence (p<0·0001), and an incidence rate ratio of 0·096 (95% CI 0·046–0·198). Despite enhanced surveillance, no case of serogroup A meningococcal meningitis was reported in the three vaccinated regions. 32 serogroup A carriers were identified in 4278 age-stratified individuals (0·75%) living in a rural area near the capital 2–4 months before vaccination, whereas only one serogroup A meningococcus was isolated in 5001 people living in the same community 4–6 months after vaccination (adjusted odds ratio 0·019, 95% CI 0·002–0·138; p<0·0001). Interpretation PSA–TT was highly effective at prevention of serogroup A invasive meningococcal disease and carriage in Chad. How long this protection will persist needs to be established. Funding The Bill & Melinda Gates Foundation, the Wellcome Trust, and Médecins Sans Frontères. PMID:24035220

  10. Vaccine-preventable disease and immunization in the developing world.

    PubMed

    Bart, K J; Lin, K F

    1990-06-01

    Vaccines have given health care providers control over a substantial portion of the morbidity and mortality in the developing world. Global efforts have immunized two-thirds of the world's children with DTP and polio vaccines; 72% have received BCG and 59% measles vaccine; but only 29% of pregnant women have received two doses of tetanus toxoid. In addition, vaccines against yellow fever, Japanese encephalitis, hepatitis B, rubella, and mumps and meningococcal polysaccharide vaccine are being used in specific regions of the world. New vaccine candidates will enhance the vaccine armamentarium over the next decade to include the causes of pneumonia, diarrhea, and meningitis: Haemophilus influenzae type b, pneumococcal and meningococcal protein conjugate vaccines, typhoid and rotavirus vaccine. Genetically engineered vaccine vehicles, genetic reassortants, and genetic deletions are being investigated as new vaccine candidates. PMID:2190145

  11. Indirect cohort analysis of 10-valent pneumococcal conjugate vaccine effectiveness against vaccine-type and vaccine-related invasive pneumococcal disease.

    PubMed

    Verani, Jennifer R; Domingues, Carla Magda A Santos; Moraes, José Cassio de

    2015-11-17

    We applied the indirect cohort method to estimate effectiveness of 10-valent pneumococcal conjugate vaccine (PCV10) among young children in Brazil. Cases of invasive pneumococcal disease (IPD), i.e., Streptococcus pneumoniae, detected in normally sterile fluid identified through laboratory-based surveillance and previously enrolled in a matched case-control effectiveness study are included. We estimated PCV10 effectiveness using multivariable logistic regression comparing PCV10 vaccination among children with vaccine-type or vaccine-related IPD vs. children with non-vaccine-type disease. The adjusted effectiveness of ?1 doses against vaccine-type (72.8%, 95% confidence interval [CI] [44.1, 86.7]) and vaccine-related (61.3%, 95%CI [14.5, 82.5]) IPD were similar to the effectiveness observed in the original case-control study (which required enrollment >1200 controls). We also found significant protection of ?1 dose against individual vaccine serotypes (14, 6B, 23F, 18C) and against vaccine-related serotype 19A. The indirect cohort methods leverages existing surveillance is a feasible approach for evaluating pneumococcal conjugate vaccines, particularly in resource-limited settings. PMID:26469718

  12. Pneumococcal Meningitis Vaccine Breakthroughs and Failures After Routine 7-Valent and 13-Valent Pneumococcal Conjugate Vaccination in Children in France.

    PubMed

    Godot, Cécile; Levy, Corinne; Varon, Emmanuelle; Picard, Capucine; Madhi, Fouad; Cohen, Robert

    2015-10-01

    We collected cases of pneumococcal meningitis vaccine breakthrough (VBT) and vaccine failure (VF) from 2003 to 2013 after the implementation of pneumococcal conjugate vaccines (PCVs) in France. VBT accounted for 3.2% of the cases (PCV7 era: 24 of 943, PCV13 era: 15 of 290) and VF 0.6% (PCV7 era: 6 of 943, PCV13 era: 2 of 290). VBT and VF are rare and occur in most cases in children younger than 2 years. The serotype 19F was the most frequent cause even after the introduction of PCV13. PMID:26181894

  13. Effect of Pneumococcal Conjugate Vaccine on Pneumococcal Meningitis

    PubMed Central

    Hsu, Heather E.; Shutt, Kathleen A.; Moore, Matthew R.; Beall, Bernard W.; Bennett, Nancy M.; Craig, Allen S.; Farley, Monica M.; Jorgensen, James H.; Lexau, Catherine A.; Petit, Susan; Reingold, Arthur; Schaffner, William; Thomas, Ann; Whitney, Cynthia G.; Harrison, Lee H.

    2015-01-01

    Background Invasive pneumococcal disease declined among children and adults after the introduction of the pediatric heptavalent pneumococcal conjugate vaccine (PCV7) in 2000, but its effect on pneumococcal meningitis is unclear. Methods We examined trends in pneumococcal meningitis from 1998 through 2005 using active, population-based surveillance data from eight sites in the United States. Isolates were grouped into PCV7 serotypes (4, 6B, 9V, 14, 18C, 19F, and 23F), PCV7-related serotypes (6A, 9A, 9L, 9N, 18A, 18B, 18F, 19B, 19C, 23A, and 23B), and non-PCV7 serotypes (all others). Changes in the incidence of pneumococcal meningitis were assessed against baseline values from 1998–1999. Results We identified 1379 cases of pneumococcal meningitis. The incidence declined from 1.13 cases to 0.79 case per 100,000 persons between 1998–1999 and 2004–2005 (a 30.1% decline, P<0.001). Among persons younger than 2 years of age and those 65 years of age or older, the incidence decreased during the study period by 64.0% and 54.0%, respectively (P<0.001 for both groups). Rates of PCV7-serotype meningitis declined from 0.66 case to 0.18 case (a 73.3% decline, P<0.001) among patients of all ages. Although rates of PCV7-related–serotype disease decreased by 32.1% (P = 0.08), rates of non-PCV7–serotype disease increased from 0.32 to 0.51 (an increase of 60.5%, P<0.001). The percentages of cases from non-PCV7 serotypes 19A, 22F, and 35B each increased significantly during the study period. On average, 27.8% of isolates were nonsusceptible to penicillin, but fewer isolates were nonsusceptible to chloramphenicol (5.7%), meropenem (16.6%), and cefotaxime (11.8%). The proportion of penicillin-nonsusceptible isolates decreased between 1998 and 2003 (from 32.0% to 19.4%, P = 0.01) but increased between 2003 and 2005 (from 19.4% to 30.1%, P = 0.03). Conclusions Rates of pneumococcal meningitis have decreased among children and adults since PCV7 was introduced. Although the overall effect of the vaccine remains substantial, a recent increase in meningitis caused by non-PCV7 serotypes, including strains nonsusceptible to antibiotics, is a concern. PMID:19144940

  14. [CONTEMPORARY CONCEPTION OF IMMUNE RESPONSE ACTIVATION MECHA- NISM BY CONJUGATED POLYSACCHARIDE VACCINES].

    PubMed

    Kolesnikov, A V; Kozyr, A V; Schemyakin, I G; Dyatlov, I A

    2015-01-01

    Vaccination remains the most effective method of control of spread of a whole range of infections of both viral and bacterial nature. Many bacterial pathogens (Streptococcus pneumoniae, Neisseria meningitidis and Haemophilus influenzae) carry polysaccharide capsule on the surface, that is one of the elements of protection from host organism immune system. At the same time, vaccination with bacteria exopolysaccharides (EPS) ensures infection neutralization. Effectiveness of such vaccine prophylaxis is limited by age of the vaccinated, intensity and duration of the immunity, development of secondary immune response. EPS conjugation with protein antigens was known for a long time to ensure activation of T-cell immunity against EPS and formation of secondary immune response. However, detailed studies of mechanism of immunity modulation by a protein partner as part of a glycoconjugate has not been carried out. T-lymphocyte activation was traditionally thought to occur exclusively due to peptide presentation, that are products of processing of protein component of the conjugate. Recently, information, accumulated in the field of natural carbohydrate, glycolipid and glycoprotein antigen presentation to T-cells, has generated interest in studying mechanisms of cell immunity activation by conjugated vaccines. Progress in this field, as well as development of novel chemical and biochemical, including combinative technologies of synthesis and study of these molecules, opens new opportunities for detailed understanding of mechanism of action for conjugated vaccines and creation of glycoconjugates with increased effectiveness of protective action. PMID:26259279

  15. Cost-effectiveness of adult pneumococcal conjugate vaccination in the Netherlands.

    PubMed

    Mangen, Marie-Josée J; Rozenbaum, Mark H; Huijts, Susanne M; van Werkhoven, Cornelis H; Postma, Douwe F; Atwood, Mark; van Deursen, Anna M M; van der Ende, Arie; Grobbee, Diederick E; Sanders, Elisabeth A M; Sato, Reiko; Verheij, Theo J M; Vissink, Conrad E; Bonten, Marc J M; de Wit, G Ardine

    2015-11-01

    The Community-Acquired Pneumonia Immunization Trial in Adults (CAPiTA) demonstrated the efficacy of 13-valent pneumococcal conjugate vaccine (PCV13) in preventing vaccine-type community-acquired pneumonia and vaccine-type invasive pneumococcal disease in elderly subjects. We examined the cost-effectiveness of PCV13 vaccination in the Netherlands.Using a Markov-type model, incremental cost-effectiveness ratios (ICER) of PCV13 vaccination in different age- and risk-groups for pneumococcal disease were evaluated using a societal perspective. Estimates of quality-adjusted life-years (QALYs), costs, vaccine efficacy and epidemiological data were based on the CAPiTA study and other prospective studies. The base-case was PCV13 vaccination of adults aged 65-74?years compared to no vaccination, assuming no net indirect effects in base-case due to paediatric 10-valent pneumococcal conjugate vaccine use. Analyses for age- and risk-group specific vaccination strategies and for different levels of hypothetical herd effects from a paediatric PCV programme were also conducted.The ICER for base-case was €8650 per QALY (95% CI 5750-17?100). Vaccination of high-risk individuals aged 65-74?years was cost-saving and extension to medium-risk individuals aged 65-74?years yielded an ICER of €2900. Further extension to include medium- and high-risk individuals aged ?18?years yielded an ICER of €3100.PCV13 vaccination is highly cost-effective in the Netherlands. The transferability of our results to other countries depends upon vaccination strategies already implemented in those countries. PMID:26160871

  16. Safety and immunogenicity of three different formulations of a liquid hexavalent diphtheria-tetanus-acellular pertussis-inactivated poliovirus-Haemophilus influenzae b conjugate-hepatitis B vaccine at 2, 4, 6 and 12-14 months of age.

    PubMed

    Diaz-Mitoma, Francisco; Halperin, Scott A; Tapiero, Bruce; Hoffenbach, Agnes; Zappacosta, Pamela S; Radley, David; Bradshaw, Susan; Martin, Jason C; Boslego, John W; Hesley, Teresa M; Bhuyan, Prakash K; Silber, Jeffrey L

    2011-02-01

    The current recommended infant vaccination schedules require many injections at multiple sites, which increase stress for infants and parents and may create challenges to vaccination compliance. Therefore, combination vaccines, which reduce the number of injections at each medical visit, can be an essential method to improve compliance. The objective of this study was to assess the safety and immunogenicity of an investigational, liquid, hexavalent, pediatric vaccine at 2, 4, 6, and 12-14 months of age. In this multicenter, open-label controlled study, 756 infants were randomized in approximately equal numbers to receive 0.5mL intramuscular dose of diptheria-tetanus-pertussis-polio-Haemophilus influenzae type b+hepatitis B vaccine, or 1 of 3 double-blind investigational formulations. All formulations included a hepatitis B surface antigen (HBsAg) concentration of 10?g/0.5mL. The three hexavalent vaccine formulations used in this study contained either Hib polyribosylribitol phosphate (PRP) conjugate component (tetanus toxoid [PRP-T, 12?g] or Neisseria meningitidis outer membrane protein complex [PRP-OPMC, 3?g or 6?g]): a minimum acceptable postdose 3 antibody response rate for each antigen was defined by the lower limit of a 95% confidence interval exceeding a prespecified target. Rates of adverse events (AEs) were similar among groups, with a trend for increased solicited vaccine-related injection-site reactions (pain, erythema, swelling) with increasing PRP-OMPC dose. No serious vaccine-related AEs were reported in the investigational groups. Both PRP-OMPC formulations met prespecified acceptability criteria for all antigens: PRP, HBsAg, pertussis, diphtheria, tetanus and poliovirus. The PRP-T formulation met the acceptability criterion for antibody responses to all antigens other than PRP at postdose 3. Postdose 4 responses were adequate for all antigens in all formulations. All vaccine formulations were well-tolerated. Both PRP-OMPC formulations met prespecified immunogenicity criteria of PRP-OMPC evaluation. PMID:21134456

  17. Self-adjuvanting polymer-peptide conjugates as therapeutic vaccine candidates against cervical cancer.

    PubMed

    Liu, Tzu-Yu; Hussein, Waleed M; Jia, Zhongfan; Ziora, Zyta M; McMillan, Nigel A J; Monteiro, Michael J; Toth, Istvan; Skwarczynski, Mariusz

    2013-08-12

    Dendrimers are structurally well-defined, synthetic polymers with sizes and physicochemical properties often resembling those of biomacromolecules (e.g., proteins). As a result, they are promising candidates for peptide-based vaccine delivery platforms. Herein, we established a synthetic pathway to conjugate a human papillomavirus (HPV) E7 protein-derived peptide antigen to a star-polymer to create a macromolecular vaccine candidate to treat HPV-related cancers. These conjugates were able to reduce tumor growth and eradicate E7-expressing TC-1 tumors in mice after a single immunization, without the help of any external adjuvant. PMID:23837675

  18. 75 FR 48707 - Proposed Vaccine Information Materials for Pneumococcal Conjugate Vaccine and Human...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-11

    ...HPV (Human Papillomavirus Virus) Vaccine (Gardasil[supreg]): What...woman has been infected with the virus, the vaccine might not work as well or might...HPV (Human Papillomavirus Virus) Vaccine (Cervarix[supreg]):...

  19. Assessment of the stability and immunogenicity of meningococcal oligosaccharide C-CRM197 conjugate vaccines.

    PubMed

    Ho, M M; Bolgiano, B; Corbel, M J

    2000-11-22

    In this stability study, meningococcal C-CRM(197) conjugate vaccines from two different manufacturers that differ in oligosaccharide chain length, number of conjugation sites, conjugation chemistry, manufacturing process and formulation were used. Both the bulk concentrated and final fill preparations were incubated at -20, 4, 23, 37 or 55 degrees C for 5 weeks or subjected to ten cycles of freeze-thawing. The structural stability, hydrodynamic size and integrity of the treated vaccines were monitored by size exclusion chromatography (FPLC-SEC), high performance anion exchange chromatography coupled with pulsed amperometric detection (HPAEC-PAD) and fluorescence spectroscopy techniques. The data showed that the structural stability of the oligosaccharide chains and of the protein carrier varied between the two conjugates. The experimental immunogenicity was not severely affected by repeated freeze-thawing, incubation at -20 or 4 degrees C, but one developed conformational changes in the protein carrier when incubated at 23 degrees C or above, although the integrity of the oligosaccharide structure was maintained. This was not associated with any reduction in primary IgG or IgM antibody responses to meningococcal C polysaccharide. In the other conjugate vaccine, exposure to 55 degrees C resulted in the release of a substantial proportion of free saccharide that was accompanied by significant reduction in both IgG and IgM antibody responses to immunisation in the model system. In conclusion, the two meningococcal C-CRM(197) conjugate vaccines were stable when stored at the recommended temperatures, although their structural stability and subsequent immunogenicity were influenced by their conjugation chemistry and formulation. PMID:11115692

  20. Human Infant Memory B Cell and CD4+ T Cell Responses to HibMenCY-TT Glyco-Conjugate Vaccine

    PubMed Central

    Fuery, Angela; Richmond, Peter C.; Currie, Andrew J.

    2015-01-01

    Carrier-specific T cell and polysaccharide-specific B cell memory responses are not well characterised in infants following glyco-conjugate vaccination. We aimed to determine if the number of Meningococcal (Men) C- and Y- specific memory B cells and; number and quality of Tetanus Toxoid (TT) carrier-specific memory CD4+ T cells are associated with polysaccharide-specific IgG post HibMenCY-TT vaccination. Healthy infants received HibMenCY-TT vaccine at 2, 4 and 6 months with a booster at 12 months. Peripheral blood mononuclear cells were isolated and polysaccharide-specific memory B cells enumerated using ELISpot. TT-specific memory CD4+ T cells were detected and phenotyped based on CD154 expression and intracellular TNF-?, IL-2 and IFN-? expression following stimulation. Functional polysaccharide-specific IgG titres were measured using the serum bactericidal activity (SBA) assay. Polysaccharide-specific Men C- but not Men Y- specific memory B cell frequencies pre-boost (12 months) were significantly associated with post-boost (13 months) SBA titres. Regression analysis showed no association between memory B cell frequencies post-priming (at 6 or 7 months) and SBA at 12 months or 13 months. TT-specific CD4+ T cells were detected at frequencies between 0.001 and 0.112 as a percentage of CD3+ T cells, but their numbers were not associated with SBA titres. There were significant negative associations between SBA titres at M13 and cytokine expression at M7 and M12. Conclusion: Induction of persistent polysaccharide-specific memory B cells prior to boosting is an important determinant of secondary IgG responses in infants. However, polysaccharide-specific functional IgG responses appear to be independent of the number and quality of circulating carrier-specific CD4+ T cells after priming. PMID:26191794

  1. The impact of protein-conjugate polysaccharide vaccines: an endgame for meningitis?

    PubMed Central

    Maiden, Martin C. J.

    2013-01-01

    The development and implementation of conjugate polysaccharide vaccines against invasive bacterial diseases, specifically those caused by the encapsulated bacteria Neisseria meningitidis, Haemophilus influenzae and Streptococcus pneumoniae, has been one of the most effective public health innovations of the last 25 years. These vaccines have resulted in significant reductions in childhood morbidity and mortality worldwide, with their effectiveness due in large part to their ability to induce long-lasting immunity in a range of age groups. At the population level this immunity reduces carriage and interrupts transmission resulting in herd immunity; however, these beneficial effects can be counterbalanced by the selection pressures that immunity against carriage can impose, potentially promoting the emergence and spread of virulent vaccine escape variants. Studies following the implementation of meningococcal serogroup C vaccines improved our understanding of these effects in relation to the biology of accidental pathogens such as the meningococcus. This understanding has enabled the refinement of the implementation of conjugate polysaccharide vaccines against meningitis-associated bacteria, and will be crucial in maintaining and improving vaccine control of these infections. To date there is little evidence for the spread of virulent vaccine escape variants of the meningococcus and H. influenzae, although this has been reported in pneumococci. PMID:23798695

  2. Purification and characterization of a Shigella conjugate vaccine, produced by glycoengineering Escherichia coli.

    PubMed

    Ravenscroft, Neil; Haeuptle, Micha A; Kowarik, Michael; Fernandez, Fabiana S; Carranza, Paula; Brunner, Andreas; Steffen, Michael; Wetter, Michael; Keller, Sacha; Ruch, Corina; Wacker, Michael

    2016-01-01

    Shigellosis remains a major cause of diarrheal disease in developing countries and causes substantial morbidity and mortality in children. Glycoconjugate vaccines consisting of bacterial surface polysaccharides conjugated to carrier proteins are the most effective vaccines for controlling invasive bacterial infections. Nevertheless, the development of a multivalent conjugate vaccine to prevent Shigellosis has been hampered by the complex manufacturing process as the surface polysaccharide for each strain requires extraction, hydrolysis, chemical activation and conjugation to a carrier protein. The use of an innovative biosynthetic Escherichia coli glycosylation system substantially simplifies the production of glycoconjugates. Herein, the Shigella dysenteriae type 1 (Sd1) O-polysaccharide is expressed and its functional assembly on an E. coli glycosyl carrier lipid is demonstrated by HPLC analysis and mass spectrometry. The polysaccharide is enzymatically conjugated to specific asparagine residues of the carrier protein by co-expression of the PglB oligosaccharyltransferase and the carrier protein exotoxin A (EPA) from Pseudomonas aeruginosa. The extraction and purification of the Shigella glycoconjugate (Sd1-EPA) and its detailed characterization by the use of physicochemical methods including NMR and mass spectrometry is described. The report shows for the first time that bioconjugation provides a newly developed and improved approach to produce an Sd1 glycoconjugate that can be characterized using state-of-the-art techniques. In addition, this generic process together with the analytical methods is ideally suited for the production of additional Shigella serotypes, allowing the development of a multivalent Shigella vaccine. PMID:26353918

  3. Impact of infant 13-valent pneumococcal conjugate vaccine on serotypes in adult pneumonia

    E-print Network

    Rodrigo, Chamira; Bewick, Thomas; Sheppard, Carmen; Greenwood, Sonia; Mckeever, Tricia M; Trotter, Caroline L; Slack, Mary; George, Robert; Lim, Wei Shen

    2015-03-18

    of the study. Between the pre- and post PCV13 periods of the study, the incidence of CAP due to serotypes included in the 7-valent pneumococcal conjugate vaccine declined by 88% (IRR 0.12, 95%CI0.08-0.20,p<0.001), and CAP due to the additional 6 serotypes...

  4. Aetiology of paediatric pneumonia after the introduction of pneumococcal conjugate vaccine

    PubMed Central

    Elemraid, Mohamed A.; Sails, Andrew D.; Eltringham, Gary J.A.; Perry, John D.; Rushton, Stephen P.; Spencer, David A.; Thomas, Matthew F.; Eastham, Katherine M.; Hampton, Fiona; Gennery, Andrew R.; Clark, Julia E.

    2013-01-01

    We describe the aetiology of community-acquired pneumonia in children before and after the introduction of the pneumococcal conjugate vaccination (PCV) programme in 2006. Prospective studies were conducted in 2001–2002 (pre-vaccine) and 2009–2011 (post-vaccine) of children aged 0–16 years with radiologically confirmed pneumonia seen in hospital. Investigations included culture, serology, immunofluorescence antibody and urine antigen testing, with an increased use of PCR assays and expanded panels of pathogens in the post-vaccine study. 241 and 160 children were enrolled in the pre- and post-vaccine studies, respectively (73% aged <5 years). Identification of a causative pathogen was higher post-vaccination (61%) than pre-vaccination (48.5%) (p=0.019). Rates of bacterial infections were not different between post- and pre-vaccine studies (17.5% versus 24%, p=0.258). Viral (31%) and mixed (12.5%) infections were found more often post-vaccination (19.5%, p=0.021) than pre-vaccination (5%, p=0.015). Rates of identified pneumococcal infections were comparable between pre- and post-vaccine studies (14.7% versus 17.4%, p=0.557). Diagnosis of pneumococcal infection post-vaccination improved when PCR was used compared to culture (21.6% versus 6%, p=0.0004). Serotypes included in PCV13 but not PCV7 were identified in 75% (18 out of 24) post-vaccination. Infection with nonvaccine pneumococcal serotypes continues to be a significant cause of pneumonia in children in the UK. PMID:23598951

  5. Cost-effectiveness analysis of pneumococcal conjugate vaccine 13-valent in older adults in Colombia

    PubMed Central

    2014-01-01

    Background Nowadays, there are two vaccination strategies in Colombia to prevent pneumococcal diseases in people over 50 years. Our aim is to estimate cost-effectiveness of pneumococcal conjugate vaccine 13-valent (PCV13) versus pneumococcal polysaccharide vaccine 23-valent (PPSV23) to prevent pneumococcal diseases and their related mortality in people over 50 years old in Colombia. Methods A Markov model was developed with national data, including pneumococcal serotypes distribution in Colombia between 2005 and 2010. Vaccination of a cohort was simulated and a five year time horizon was assumed. Analysis was done from a perspective of a third party payer. Direct costs were provided by a national insurance company; sensitive univariate and probabilistic analysis were done for epidemiological and clinical effectiveness parameters and costs. Results PCV13 avoids 3 560 deaths by pneumococcal infections versus PPSV23 and 4 255 deaths versus no vaccine. PCV13 prevents 79 633 cases by all-cause pneumonia versus PPSV23 and 81 468 cases versus no vaccine. Total costs (healthcare and vaccines costs) with PCV13 would be U.S. $ 97,587,113 cheaper than PPSV23 and it would save U.S. $ 145,196,578 versus no vaccine. Conclusion PCV13 would be a cost-saving strategy in the context of a mass vaccination program in Colombia to people over 50 years old because it would reduce burden of disease and specific mortality by pneumococcal diseases, besides, it saves money versus PPSV23. PMID:24679135

  6. Pneumococcal conjugate vaccine - what you need to know

    MedlinePLUS

    ... who has ever had a life-threatening allergic reaction to a dose of this vaccine, to an ... and go away on their own, but serious reactions are also possible. Reported problems associated with PCV13 ...

  7. Phase I clinical trial of O-Acetylated pectin conjugate, a plant polysaccharide based typhoid vaccine

    PubMed Central

    Szu, Shousun C.; Lin, Kimi F-Y; Hunt, Steven; Chu, Chiayung; Thinh, Nguyen Duc

    2014-01-01

    Background Typhoid fever remains an important cause of morbidity and mortality in the developing countries. Vi capsular polysaccharide conjugate vaccine demonstrated safety and efficacy in young children in high endemic regions. A novel typhoid conjugate vaccine based on plant polysaccharide pectin was studied in a phase I trial. Methods Fruit pectin, having the same carbohydrate backbone structure as Vi, was purified from citrus peel and used as the polysaccharide source to prepare a semi-synthetic typhoid conjugate vaccine. Pectin was chemically O-acetylated (OAcPec) to antigenically resemble Vi and conjugated to carrier protein rEPA, a recombinant exoprotein A from Pseudomonas aeruginosa. 25 healthy volunteers, 18–45 years old, were injected once with OAcPec-rEPA. Safety and IgG antibodies reactive with Vi and pectin were analyzed. Results No vaccine associated serious adverse reaction was reported. Six weeks after the injection of OAcPec-rEPA, 64% of the volunteers elicited >4 fold rise of anti-Vi IgG. At 26 weeks the level declined, but the difference between the levels at 6 and 26 weeks are not statistically significant. There is a direct correlation between the level of anti-Vi IgG before and after the injection (R2 = 0.96). The anti-Vi IgG can be absorbed by Vi, but not by pectin. There was no corresponding increase of anti-pectin after the injection, indicating the antibody response to OAcPec-rEPA was specific to Vi. There is no Vi-rEPA data in US adults for comparison of immune responses. The OAcPec-rEPA elicited significantly less IgG anti-Vi in US adults than those by Vi-rEPA in Vietnamese adults. Conclusion The O-acetylated pectin conjugate, a plant based typhoid vaccine, is safe and immunogenic in adult volunteers. PMID:24657719

  8. Non-interference between two protein carriers when used with the same polysaccharide for pneumococcal conjugate vaccines in 2-year-old children.

    PubMed

    Anderson, Porter; Treanor, John; Porcelli, Susan; Pichichero, Michael

    2003-03-28

    The carriers tetanus toxoid (T) and diphtheria CRM-197 (C) were compared in conjugate vaccines using identical coupling chemistry and polysaccharide (PS) loading, for safety and immunogenicity in 2-year-old children. Also tested were a mixture of halved doses of both carriers bearing the same PS serotypes. For this study, PS types 6A, 14, 19F, and 23F (separately) were coupled to T or C by reductive amination at PS/protein ratios of 0.50+/-0.18. With each carrier the four PS types were combined, giving the tetravalent vaccines "T-6, -14, -19, -23" or "C-6, -14, -19, -23" containing 50 microg of the carrier and roughly 20 microg total PS per ml of saline (no adjuvant). The children received primary (1') injections of 50 microg (protein) of either vaccine or a mixture of 25 microg of both; identical secondary (2') injections were given 2 months afterwards. Sera were taken before the 1' and 2' and 1 month post-2', and serum IgG responses to the four PS were determined by ELISA. For geometric mean (GM) post-1' antibody, "C-6, -14, -19, -23" exceeded "T-6, -14, -19, -23" for type 19F; for 2' antibody, "T-6, -14, -19, -23" exceeded "C-6, -14, -19, -23" for type 14, but "C-6, -14, -19, -23" and the T/C mixture exceeded "T-6, -14, -19, -23" for the type 23F response. No other differences were significant. Analyzed by individual fold-rises, "C-6, -14, -19, -23" and the T/C mixture exceeded "T-6, -14, -19, -23" for types 19F and 23F. Thus, there was no consistent difference between the T and C carriers; rather, the results differed by serotype. When a mixture of halved doses of "T-6, -14, -19, -23" and "C-6, -14, -19, -23" was injected, neither negative nor positive interference with the PS antibody responses was found. Anticipating multivalent PS conjugate vaccines of the future to be used in infancy, this strategy would have two hypothetical advantages worth further investigation-avoiding "carrier epitopic overload" by reducing each carrier dosage and recruiting T-helper activity by both carriers for each PS. PMID:12615453

  9. Risk Assessment and Meningococcal A Conjugate Vaccine Introduction in Africa: The District Prioritization Tool

    PubMed Central

    Cibrelus, Laurence; Lingani, Clément; Fernandez, Katya; Djingarey, Mamoudou H.; Perea, William A.; Hugonnet, Stéphane

    2015-01-01

    Background.?A group A meningococcal (MenA) conjugate vaccine has progressively been introduced in the African meningitis belt since 2010. A country-wide risk assessment tool, the District Prioritization Tool (DPT), was developed to help national stakeholders combine existing data and local expertise to define priority geographical areas where mass vaccination campaigns should be conducted. Methods.?DPT uses an Excel-supported offline tool that was made available to the countries proposed for immunization campaigns. It used quantitative–qualitative methods, relying predominantly on evidence-based risk scores complemented by expert opinion. Results.?DPT was used by most of the countries that introduced the group A conjugate vaccine. Surveillance data enabled the computation of severity scores for meningitis at the district level (magnitude, intensity, and frequency). District data were scaled regionally to facilitate phasing decisions. DPT also assessed the country's potential to conduct efficient preventive immunization campaigns while paying close attention to the scope of the geographic extension of the campaigns. The tool generated meningitis district profiles that estimated the number of vaccine doses needed. In each assessment, local meningitis experts contributed their knowledge of local risk factors for meningitis epidemics to refine the final prioritization decisions. Conclusions.?DPT proved to be a useful and flexible tool that codified information and streamlined discussion among stakeholders while facilitating vaccine distribution decisions after 2011. DPT methodology may be tailored to prioritize vaccine interventions for other diseases. PMID:26553673

  10. Nasopharyngeal Bacterial Carriage in the Conjugate Vaccine Era with a Focus on Pneumococci

    PubMed Central

    Devine, V. T.; Jefferies, J. M.; Clarke, S. C.; Faust, S. N.

    2015-01-01

    Seven-valent pneumococcal conjugate vaccine (PCV7) was included in the UK national immunisation program in 2006, and this was replaced by thirteen-valent PCV in 2010. During this time, the carriage of vaccine-type Streptococcus pneumoniae decreased but pneumococcal carriage remained stable due to increases in non-vaccine-type S. pneumoniae. Carriage studies have been undertaken in various countries to monitor vaccine-type replacement and to help predict the serotypes, which may cause invasive disease. There has been less focus on how conjugate vaccines indirectly affect colonization of other nasopharyngeal bacteria. If the nasopharynx is treated as a niche, then bacterial dynamics are accepted to occur. Alterations in these dynamics have been shown due to seasonal changes, antibiotic use, and sibling/day care interaction. It has been shown that, following PCV7 introduction, an eradication of pneumococcal vaccine types has resulted in increases in the abundance of other respiratory pathogens including Haemophilus influenzae and Staphylococcus aureus. These changes are difficult to attribute to PCV7 introduction alone and these studies do not account for further changes due to PCV13 implementation. This review aims to describe nasopharyngeal cocarriage of respiratory pathogens in the PCV era. PMID:26351646

  11. Higher Tetanus Toxoid Immunity 2 Years After PsA-TT Introduction in Mali

    PubMed Central

    Basta, Nicole E.; Borrow, Ray; Berthe, Abdoulaye; Onwuchekwa, Uma; Dembélé, Awa Traoré Eps; Almond, Rachael; Frankland, Sarah; Patel, Sima; Wood, Daniel; Nascimento, Maria; Manigart, Olivier; Trotter, Caroline L.; Greenwood, Brian; Sow, Samba O.

    2015-01-01

    Background.?In 2010, mass vaccination with a then-new meningococcal A polysaccharide–tetanus toxoid protein conjugate vaccine (PsA-TT, or MenAfriVac) was undertaken in 1- to 29-year-olds in Bamako, Mali. Whether vaccination with PsA-TT effectively boosts tetanus immunity in a population with heterogeneous baseline tetanus immunity is not known. We assessed the impact of PsA-TT on tetanus toxoid (TT) immunity by quantifying age- and sex-specific immunity prior to and 2 years after introduction. Methods.?Using a household-based, age-stratified design, we randomly selected participants for a prevaccination serological survey in 2010 and a postvaccination survey in 2012. TT immunoglobulin G (IgG) antibodies were quantified and geometric mean concentrations (GMCs) pre- and postvaccination among all age groups targeted for vaccination were compared. The probability of TT IgG levels ?0.1 IU/mL (indicating short-term protection) and ?1.0 IU/mL (indicating long-term protection) by age and sex was determined using logistic regression models. Results.?Analysis of 793 prevaccination and 800 postvaccination sera indicated that while GMCs were low pre–PsA-TT, significantly higher GMCs in all age–sex strata were observed 2 years after PsA-TT introduction. The percentage with short-term immunity increased from 57.1% to 88.4% (31.3-point increase; 95% confidence interval [CI], 26.6–36.0;, P < .0001) and with long-term immunity increased from 20.0% to 58.5% (38.5-point increase; 95% CI, 33.7–43.3; P < .0001) pre- and postvaccination. Conclusions.?Significantly higher TT immunity was observed among vaccine-targeted age groups up to 2 years after Mali's PsA-TT mass vaccination campaign. Our results, combined with evidence from clinical trials, strongly suggest that conjugate vaccines containing TT such as PsA-TT should be considered bivalent vaccines because of their ability to boost tetanus immunity. PMID:26553691

  12. A Conjugate Vaccine Attenuates Morphine- and Heroin-Induced Behavior in Rats

    PubMed Central

    Li, Qian-Qian; Sun, Cheng-Yu; Luo, Yi-Xiao; Xue, Yan-Xue; Meng, Shi-Qiu; Xu, Ling-Zhi; Chen, Na; Deng, Jia-Hui; Zhai, Hai-Feng; Kosten, Thomas R.; Shi, Jie

    2015-01-01

    Background: Currently approved medications for opioid addiction have shown clinical efficacy, but undesired side effects, dependence induced by the medications themselves, and low treatment compliance necessitate the need for novel therapies. Methods: A novel morphine-keyhole limpet hemocyanin conjugate vaccine was synthesized with 6-glutarylmorphine as the hapten and a lengthened linker of 6 carbon atoms. The titer and specificity of the triggered antibody were assessed by enzyme-linked immunosorbent assay. The effects of the vaccine on the morphine-induced elevation of dopamine levels in the nucleus accumbens were determined by high-performance liquid chromatography. The effects of the vaccine on morphine-induced locomotor sensitization and heroin-primed reinstatement of heroin self-administration were also assessed. Results: After subcutaneous administration in rats, the vaccine triggered a high antibody titer, with comparable specificity for morphine, 6-acetylmorphine, and heroin, but no interaction with dissimilar therapeutic opioid compounds, including buprenorphine, naloxone, and nalorphine, was observed. The vaccine significantly prevented the elevation of dopamine levels in the nucleus accumbens induced by a single morphine challenge. Moreover, the vaccine prevented the expression of morphine-induced locomotor sensitization and heroin-primed reinstatement of heroin seeking, suggesting its potential for preventing relapse. Conclusion: These results demonstrate that active immunization with the present vaccine induces a robust morphine/heroin-specific antibody response in rats and attenuates the behavioral effects of morphine and heroin. PMID:25522425

  13. Immunogenicity and safety of the 13-valent pneumococcal conjugate vaccine in HIV-infected individuals naive to pneumococcal vaccination

    PubMed Central

    Bhorat, As’ad E.; Madhi, Shabir A.; Laudat, France; Sundaraiyer, Vani; Gurtman, Alejandra; Jansen, Kathrin U.; Scott, Daniel A.; Emini, Emilio A.; Gruber, William C.; Schmoele-Thoma, Beate

    2015-01-01

    Objective: Immunocompromised individuals are at an increased risk of pneumococcal disease. Vaccination is recommended as an important strategy to reduce risk of pneumococcal disease in HIV-infected individuals. This study evaluated the safety and immunogenicity of three 13-valent pneumococcal conjugate vaccine (PCV13) doses followed by one dose of 23-valent pneumococcal polysaccharide vaccine (PPSV23) at 1-month intervals in pneumococcal vaccine-naive, HIV-infected individuals. Design: This was a phase 3, open-label, single-arm study. Methods: Pneumococcal vaccine-naive, HIV-infected individuals at least 6 years of age with CD4+ T-cell count at least 200?cells/?l and viral load less than 50?000?copies/ml received three doses of PCV13 followed by one dose of PPSV23 at 1-month intervals. Serotype-specific antipneumococcal immune responses were assessed by IgG geometric mean concentrations (GMCs) and opsonophagocytic activity (OPA) assay geometric mean titres (GMTs) after each dose. Local reactions at the PCV13 injection site, systemic and other adverse events were collected. Results: Three hundred and one individuals were enrolled and vaccinated; 279 completed the study. Statistically significant increases in IgG GMCs and OPA GMTs were observed for all serotypes after dose 1 of PCV13 compared with prevaccine levels. GMCs and GMTs were comparable or only modestly increased for all serotypes after PCV13 doses 2 and 3 and after PPSV23. The majority of local reactions and systemic events were mild to moderate in severity. Conclusion: A three-dose regimen of PCV13 was well tolerated in pneumococcal vaccine-naive, HIV-infected individuals. Significant immune responses to all serotypes were observed following the first dose of PCV13, with only modest increases in antibody titres following subsequent PCV13 or PPSV23 administration. PMID:25888646

  14. How to compare the efficacy of conjugate vaccines to prevent acute otitis media?

    PubMed

    De Wals, Philippe; Erickson, Lonny; Poirier, Béatrice; Pépin, Jacques; Pichichero, Michael E

    2009-05-11

    Although the currently available 7-valent pneumococcal conjugate vaccine (PCV7-CRM(197)) has been primarily designed for the prevention of invasive pneumococcal disease, it has also demonstrated the potential to prevent acute otitis media (AOM) and its associated complications. A candidate 11-valent pneumococcal conjugate vaccine (PCV11-HiD), which utilizes Haemophilus influenzae (Hi)-derived protein D as a carrier has demonstrated the ability to prevent AOM caused by not only vaccine serotypes of Streptococcus pneumoniae (Sp), but also those caused by Hi. The methodological, clinical, and epidemiological factors influencing results of vaccine trials for AOM prevention were reviewed and a model-based approach was developed, in order to assess the relative efficacy of different vaccine formulations. Six randomized trials having AOM as a measured outcome were identified. Vaccine efficacy (VE) ranged from -1% to 34% for all-cause AOM and between 56% and 64% for AOM caused by vaccine-type Sp. Using otopathogen-specific VE rates from the FinOM and POET trials and otopathogen distributions observed in three relatively unbiased studies, VE against all-cause AOM episodes under different scenarios was modeled. The most important factor explaining variation in VE estimates was bacterial replacement, which was present in the PCV7-CRM(197) FinOM study but not in the PCV11-HiD POET study. Another contributing factor was increased protection conferred against Hi AOM by protein D. Geographical variation in the distribution of otopathogens was a third factor explaining differences between trials. More studies on the current aetiology of AOM need to be performed to accurately predict the marginal benefit of a switch from PCV7-CRM(197) to the newly licensed PCV10-HiD-DiT or to the future PCV13-CRM(197). PMID:19366579

  15. Salivary antibodies following parenteral immunization of infants with a meningococcal serogroup A and C conjugated vaccine.

    PubMed Central

    Borrow, R.; Fox, A. J.; Cartwright, K.; Begg, N. T.; Jones, D. M.

    1999-01-01

    Bacterial and viral salivary antibody testing is proving sensitive and specific, useful for epidemiological studies, and is simple and non-invasive. Salivary serogroup C polysaccharide-specific (SC PS-S) IgA and IgG were determined as a proportion of total salivary IgA and IgG in a group of UK infants who were recipients of a conjugated A/C meningococcal PS vaccine. Geometric mean concentrations (GMCs) of salivary SC PS-S IgG per mg of total IgG (microg/mg) were 0.1 pre-vaccination, rising to 8.2 post first, 16.1 post second and 29.3 post third dose of vaccine. For IgA, the corresponding GMCs in ng/mg were 0.1, 82.8, 69.6 and 91.2. Significant correlations (P < 0.0001) were found between serum Ig and salivary IgG SC PS-S antibody for pre-vaccine and 1 month post each dose of vaccine suggesting that SC PS-S IgG in saliva was largely derived from serum. Of the five infants whose sera were analysed for isotype-specific responses, only traces of IgM and IgA were measurable suggesting that the SC PS-S IgA was locally produced. These findings suggests that the widespread use of meningococcal conjugate vaccines is likely to reduce nasopharyngeal carriage and may thereby induce herd immunity in the vaccinated population. PMID:10579438

  16. Effectively introducing a new meningococcal A conjugate vaccine in Africa: the Burkina Faso experience.

    PubMed

    Djingarey, Mamoudou H; Barry, Rodrigue; Bonkoungou, Mete; Tiendrebeogo, Sylvestre; Sebgo, Rene; Kandolo, Denis; Lingani, Clement; Preziosi, Marie-Pierre; Zuber, Patrick L F; Perea, William; Hugonnet, Stéphane; Dellepiane de Rey Tolve, Nora; Tevi-Benissan, Carole; Clark, Thomas A; Mayer, Leonard W; Novak, Ryan; Messonier, Nancy E; Berlier, Monique; Toboe, Desire; Nshimirimana, Deo; Mihigo, Richard; Aguado, Teresa; Diomandé, Fabien; Kristiansen, Paul A; Caugant, Dominique A; Laforce, F Marc

    2012-05-30

    A new Group A meningococcal (Men A) conjugate vaccine, MenAfriVac™, was prequalified by the World Health Organization (WHO) in June 2010. Because Burkina Faso has repeatedly suffered meningitis epidemics due to Group A Neisseria meningitidis special efforts were made to conduct a country-wide campaign with the new vaccine in late 2010 and before the onset of the next epidemic meningococcal disease season beginning in January 2011. In the ensuing five months (July-November 2010) the following challenges were successfully managed: (1) doing a large safety study and registering the new vaccine in Burkina Faso; (2) developing a comprehensive communication plan; (3) strengthening the surveillance system with particular attention to improving the capacity for real-time polymerase chain reaction (PCR) testing of spinal fluid specimens; (4) improving cold chain capacity and waste disposal; (5) developing and funding a sound campaign strategy; and (6) ensuring effective collaboration across all partners. Each of these issues required specific strategies that were managed through a WHO-led consortium that included all major partners (Ministry of Health/Burkina Faso, Serum Institute of India Ltd., UNICEF, Global Alliance for Vaccines and Immunization, Meningitis Vaccine Project, CDC/Atlanta, and the Norwegian Institute of Public Health/Oslo). Biweekly teleconferences that were led by WHO ensured that problems were identified in a timely fashion. The new meningococcal A conjugate vaccine was introduced on December 6, 2010, in a national ceremony led by His Excellency Blaise Compaore, the President of Burkina Faso. The ensuing 10-day national campaign was hugely successful, and over 11.4 million Burkinabes between the ages of 1 and 29 years (100% of target population) were vaccinated. African national immunization programs are capable of achieving very high coverage for a vaccine desired by the public, introduced in a well-organized campaign, and supported at the highest political level. The Burkina Faso success augurs well for further rollout of the Men A conjugate vaccine in meningitis belt countries. PMID:22607898

  17. Effects of Vaccination with 10-Valent Pneumococcal Non-Typeable Haemophilus influenza Protein D Conjugate Vaccine (PHiD-CV) on the Nasopharyngeal Microbiome of Kenyan Toddlers

    PubMed Central

    Feazel, Leah M.; Santorico, Stephanie A.; Robertson, Charles E.; Bashraheil, Mahfudh; Scott, J. Anthony G.

    2015-01-01

    Objective Pneumococcal conjugate vaccines reduce the prevalence of vaccine serotypes carried in the nasopharynx. Because this could alter carriage of other potential pathogens, we assessed the nasopharyngeal microbiome of children who had been vaccinated with 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV). Methods Profiles of the nasopharyngeal microbiota of 60 children aged 12-59 months, who had been randomized to receive 2 doses of PHiD-CV (n=30) or Hepatitis A vaccine (n=30) 60 days apart, were constructed by 16S rRNA gene pyrosequencing of swab specimens collected before vaccination and 180 days after dose 1. Results Prior to vaccination, Moraxella catarrhalis (median of 12.3% of sequences/subject), Streptococcus pneumoniae (4.4%) and Corynebacterium spp. (5.6%) were the most abundant nasopharyngeal bacterial species. Vaccination with PHiD-CV did not significantly alter the species composition, abundance, or prevalence of known pathogens. Distinct microbiomes were identified based on the abundances of Streptococcus, Moraxella, and Haemophilus species. These microbiomes shifted in composition over the study period and were independent of age, sex, school attendance, antibiotic exposure, and vaccination. Conclusions Vaccination of children with two doses of PHiD-CV did not significantly alter the nasopharyngeal microbiome. This suggests limited replacement carriage with pathogens other than non-vaccine strains of S. pneumoniae. Trial Registration clinicaltrials.gov NCT01028326 PMID:26083474

  18. 9 CFR 113.114 - Tetanus Toxoid.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...Products 1 2014-01-01 2014-01-01 false Tetanus Toxoid. 113.114 Section 113.114 Animals... Inactivated Bacterial Products § 113.114 Tetanus Toxoid. Tetanus Toxoid shall be produced from a culture of...

  19. 9 CFR 113.114 - Tetanus Toxoid.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...Products 1 2013-01-01 2013-01-01 false Tetanus Toxoid. 113.114 Section 113.114 Animals... Inactivated Bacterial Products § 113.114 Tetanus Toxoid. Tetanus Toxoid shall be produced from a culture of...

  20. Mutant Native Outer Membrane Vesicles Combined with a Serogroup A Polysaccharide Conjugate Vaccine for Prevention of Meningococcal Epidemics in Africa

    PubMed Central

    Pajon, Rolando; Fergus, Andrew M.; Granoff, Dan M.

    2013-01-01

    Background The meningococcal serogroup A (MenA) polysaccharide conjugate vaccine used in Sub-Saharan Africa does not prevent disease caused by MenW or MenX strains, which also cause epidemics in the region. We investigated the vaccine-potential of native outer membrane vesicles with over-expressed factor H-binding protein (NOMV-fHbp), which targeted antigens in African meningococcal strains, and was combined with a MenA polysaccharide conjugate vaccine. Methodology/Principal Findings The NOMV-fHbp vaccine was prepared from a mutant African MenW strain with PorA P1.5,2, attenuated endotoxin (?LpxL1), deleted capsular genes, and over-expressed fHbp in variant group 1. The NOMV-fHbp was adsorbed with Al(OH)3 and used to reconstitute a lyophilized MenA conjugate vaccine, which normally is reconstituted with liquid MenC, Y and W conjugates in a meningococcal quadrivalent conjugate vaccine (MCV4-CRM, Novartis). Mice immunized with the NOMV-fHbp vaccine alone developed serum bactericidal (human complement) activity against 13 of 15 African MenA strains tested; 10 of 10 African MenX strains, 7 of 7 African MenW strains, and 6 of 6 genetically diverse MenB strains with fHbp variant group 1 (including 1 strain from The Gambia). The combination NOMV-fHbp/MenA conjugate vaccine elicited high serum bactericidal titers against the two MenA strains tested that were resistant to bactericidal antibodies elicited by the NOMV-fHbp alone; the combination elicited higher titers against the MenA and MenW strains than those elicited by a control MCV4-CRM vaccine (P<0.05); and high titers against MenX and MenB strains. For most strains, the titers elicited by a control NOMV-fHbp knock out vaccine were <1?10 except when the strain PorA matched the vaccine (titers >1?000). Conclusion/Significance The NOMV-fHbp/MenA conjugate vaccine provided similar or higher coverage against MenA and MenW strains than a quadrivalent meningococcal conjugate vaccine, and extended protection against MenX strains responsible for epidemics in Africa, and MenB strains with fHbp in variant group 1. PMID:23805230

  1. Modeling the impact of the 7-valent pneumococcal conjugate vaccine in Chinese infants: an economic analysis of a compulsory vaccination

    PubMed Central

    2014-01-01

    Background The purpose of this study was to compare, from a Chinese societal perspective, the projected health benefits, costs, and cost-effectiveness of adding pneumococcal conjugate heptavalent vaccine (PCV-7) to the routine compulsory child immunization schedule. Methods A decision-tree model, with data and assumptions adapted for relevance to China, was developed to project the health outcomes of PCV-7 vaccination (compared with no vaccination) over a 5-year period as well as a lifetime. The vaccinated birth cohort included 16,000,000 children in China. A 2?+?1 dose schedule at US$136.51 per vaccine dose was used in the base-case analysis. One-way sensitivity analysis was used to test the robustness of the model. The impact of a net indirect effect (herd immunity) was evaluated. Outcomes are presented in terms of the saved disease burden, costs, quality-adjusted life years (QALYs) and incremental cost-effectiveness ratio. Results In a Chinese birth cohort, a PCV-7 vaccination program would reduce the number of pneumococcus-related infections by at least 32% and would prevent 2,682 deaths in the first 5 years of life, saving $1,190 million in total costs and gaining an additional 9,895 QALYs (discounted by 3%). The incremental cost per QALY was estimated to be $530,354. When herd immunity was taken into account, the cost per QALY was estimated to be $95,319. The robustness of the model was influenced mainly by the PCV-7 cost per dose, effectiveness herd immunity and incidence of pneumococcal diseases. With and without herd immunity, the break-even costs in China were $29.05 and $25.87, respectively. Conclusions Compulsory routine infant vaccination with PCV-7 is projected to substantially reduce pneumococcal disease morbidity, mortality, and related costs in China. However, a universal vaccination program with PCV-7 is not cost-effective at the willingness-to-pay threshold that is currently recommended for China by the World Health Organization. PMID:24507480

  2. Altered Memory T-Cell Responses to Bacillus Calmette-Guerin and Tetanus Toxoid Vaccination and Altered Cytokine Responses to Polyclonal Stimulation in HIV-Exposed Uninfected Kenyan Infants

    PubMed Central

    Garcia-Knight, Miguel A.; Nduati, Eunice; Hassan, Amin S.; Gambo, Faith; Odera, Dennis; Etyang, Timothy J.; Hajj, Nassim J.; Berkley, James Alexander

    2015-01-01

    Implementation of successful prevention of mother-to-child transmission of HIV strategies has resulted in an increased population of HIV-exposed uninfected (HEU) infants. HEU infants have higher rates of morbidity and mortality than HIV-unexposed (HU) infants. Numerous factors may contribute to poor health in HEU infants including immunological alterations. The present study assessed T-cell phenotype and function in HEU infants with a focus on memory Th1 responses to vaccination. We compared cross-sectionally selected parameters at 3 and 12 months of age in HIV-exposed (n = 42) and HU (n = 28) Kenyan infants. We measured ex vivo activated and bulk memory CD4 and CD8 T-cells and regulatory T-cells by flow cytometry. In addition, we measured the magnitude, quality and memory phenotype of antigen-specific T-cell responses to Bacillus Calmette-Guerin and Tetanus Toxoid vaccine antigens, and the magnitude and quality of the T cell response following polyclonal stimulation with staphylococcal enterotoxin B. Finally, the influence of maternal disease markers on the immunological parameters measured was assessed in HEU infants. Few perturbations were detected in ex vivo T-cell subsets, though amongst HEU infants maternal HIV viral load positively correlated with CD8 T cell immune activation at 12 months. Conversely, we observed age-dependent differences in the magnitude and polyfunctionality of IL-2 and TNF-? responses to vaccine antigens particularly in Th1 cells. These changes mirrored those seen following polyclonal stimulation, where at 3 months, cytokine responses were higher in HEU infants compared to HU infants, and at 12 months, HEU infant cytokine responses were consistently lower than those seen in HU infants. Finally, reduced effector memory Th1 responses to vaccine antigens were observed in HEU infants at 3 and 12 months and higher central memory Th1 responses to M. tuberculosis antigens were observed at 3 months only. Long-term monitoring of vaccine efficacy and T-cell immunity in this vulnerable population is warranted. PMID:26569505

  3. Effect of Pneumococcal Conjugate Vaccination in Uruguay, a Middle-Income Country

    PubMed Central

    García Gabarrot, Gabriela; López Vega, Mariana; Pérez Giffoni, Gabriel; Hernández, Silvia; Cardinal, Pablo; Félix, Viviana; Gabastou, Jean Marc; Camou, Teresa

    2014-01-01

    Background In 2008, a 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine childhood immunization program in Uruguay, with a 2+1 schedule. In 2010, PCV13 replaced PCV7, and the same 2+1 schedule was used. The effect of these pneumococcal vaccines on the incidence of invasive pneumococcal infections (IPD) and on serotype distribution was analyzed retrospectively, based on passive national laboratory surveillance. Methods Data from 1,887 IPD isolates from 5 years before and 5 years after PCV7 introduction (7 before and 3 after PCV13 introduction) was examined to assess the incidence rate per 100,000 age-specific population of all IPD, PCV7-serotypes, and PCV13-serotypes associated IPD among children <2 years and 2 to 4 years old, and patients ?5 years old. Trends of frequency for each serotype were also analyzed. Results Comparison of pre-vaccination (2003–2007) and post-vaccination (2008–2012) periods showed a significant decrease in IPD incidence among children <2 years old (IR 68.7 to IR 29.6, p<0.001) and children 2 to 4 years (p<0.04). IPD caused by serotypes in PCV7 was reduced by 95.6% and IPD caused by 6 serotypes added in PCV13 was reduced by 83.9% in children <5 years old. Indirect effects of both conjugate vaccines were observed among patients ?5 years old one year after the introduction of each vaccine, in 2010 for PCV7 and in 2012 for PCV13. Nevertheless, for reasons that still need to be explained, perhaps due to ascertainment bias, total IPD in this group increased after 2007. In 2012, the relative frequency of vaccine serotypes among vaccinated and unvaccinated population declined, except for serotype 3. Non vaccine serotypes with increasing frequency were identified, in rank order: 12F, 8, 24F, 22F, 24A, 15C, 9N, 10A and 33. Conclusion Consecutive immunization with PCV7 and PCV13 has significantly reduced IPD in children <5 years of age in Uruguay. PMID:25375647

  4. Two or three primary dose regime for Haemophilus influenzae type b conjugate vaccine: meta-analysis of randomized controlled trials

    PubMed Central

    Thumburu, Kiran K.; Das, Rashmi Ranjan; Jaiswal, Nishant; Agarwal, Amit; Kumar, Ajay; Kaur, Harpreet

    2015-01-01

    Haemophilus influenzae type b (Hib) is an important cause of meningitis and pneumonia in children. Despite the availability of Hib conjugate vaccine, many countries are still to implement it in their immunization schedule. Before introducing the vaccine in routine immunization programs, it is important to know not only the cumulative efficacy but also the efficacy of each vaccine dose. The primary objective of this review is to find whether two primary dose schedule of Hib vaccine is equally efficacious as the standard three primary dose schedule. A highly sensitive online search was run using the terms ‘Haemophilus Vaccines’ or ‘Haemophilus influenzae type b’ and ‘conjugate vaccine’, and Medline (Ovid), PubMed, Embase, CENTRAL and Scopus were explored for prospective randomized controlled studies. Data were extracted in a predesigned proforma and analyzed using RevMan software. Nine randomized studies were included in the analysis. Pooled vaccine efficacy using a fixed effects model against confirmed invasive Hib disease following the 3, 2 and 1 primary dose schedule were 82% [95% confidence interval (CI) 73-87], 79% (95% CI 54–90) and 65% (95% CI 23–84), respectively, and the overall efficacy was 80% (95% CI 72–85). To conclude, we found that Hib conjugate vaccine is highly efficacious and that the two dose regime is as good as the three dose regime. [The protocol was registered with PROSPERO (CRD42013004490)]. PMID:25984342

  5. Synthesis of a conjugate vaccine composed of pneumococcus type 14 capsular polysaccharide bound to pertussis toxin.

    PubMed Central

    Schneerson, R; Levi, L; Robbins, J B; Bryla, D M; Schiffman, G; Lagergard, T

    1992-01-01

    Type 14 is one of the common types isolated from patients of all ages with infections caused by Streptococcus pneumoniae. Its capsular polysaccharide (Pn14) is composed of a neutrally charged tetrasaccharide repeat unit. Pn14 does not elicit protective levels of antibodies in infants and children and is a less than optimal immunogen of the 23-valent vaccine for adults. Pertussis toxin (PT) is both a virulence factor and protective antigen of Bordetella pertussis: it is not soluble at neutral pH and forms insoluble complexes with acidic polysaccharides. Both Pn14 and PT are potential components of vaccines for infants and children. Accordingly, a synthetic scheme was devised to prepare a conjugate of Pn14 and PT. An adipic acid hydrazide derivative of Pn14 was bound to PT at pH 3.9 by carbodiimide-mediated condensation. The conjugation procedure inactivated the PT as assayed by CHO cell and histamine-sensitizing activity. The Pn14-PT conjugate elicited antibodies in mice to Pn14 at levels estimated to be protective in humans and elicited neutralizing antibodies to PT. We plan to evaluate Pn14-PT clinically. PMID:1500160

  6. Impact of conjugate Haemophilus influenzae type b (Hib) vaccine introduction in South Africa.

    PubMed Central

    von Gottberg, A.; de Gouveia, L.; Madhi, S. A.; du Plessis, M.; Quan, V.; Soma, K.; Huebner, R.; Flannery, B.; Schuchat, A.; Klugman, Kp

    2006-01-01

    OBJECTIVE: To analyse trends in reported invasive Haemophilus influenzae disease in South Africa within the first five years of introduction of conjugate Haemophilus influenzae type b (Hib) vaccine in the routine child immunization schedule. METHODS: We used national laboratory-based surveillance data to identify cases of invasive H. influenzae disease between July 1999 and June 2004, and submitted isolates for serotyping and antimicrobial susceptibility testing. FINDINGS: The absolute number of Hib cases (reported to the national surveillance system) among children below one year of age decreased by 65%, from 55 cases in 1999-2000 to 19 cases in 2003-04. Enhanced surveillance initiated in 2003, identified human immunodeficiency virus (HIV)-infection and incomplete vaccination as contributing factors for Hib transmission. The total number of laboratory-confirmed cases of H. influenzae remained unchanged because non-type b disease was being increasingly reported to the surveillance system concomitant with system enhancements. Children with non-typable disease were more likely to be HIV-positive (32 of 34, 94%) than children with Hib disease (10 of 14, 71%), P = 0.051. Recent Hib isolates were more likely to be multidrug resistant (2% in 1999-2000 versus 19% in 2003-04, P = 0.001). CONCLUSION: Data from a newly established national laboratory-based surveillance system showed a decrease in Hib disease burden among South African children following conjugate vaccine introduction and identified cases of non-typable disease associated with HIV infection. PMID:17128361

  7. Long-term impact of pneumococcal polysaccharide vaccination on nasopharyngeal carriage in children previously vaccinated with various pneumococcal conjugate vaccine regimes.

    PubMed

    Boelsen, Laura K; Dunne, Eileen M; Lamb, Karen E; Bright, Kathryn; Cheung, Yin Bun; Tikoduadua, Lisi; Russell, Fiona M; Mulholland, E Kim; Licciardi, Paul V; Satzke, Catherine

    2015-10-13

    Previously, the Fiji Pneumococcal Project (FiPP) evaluated reduced dose immunization schedules that incorporated pneumococcal protein conjugate and/or polysaccharide vaccine (PCV7 and 23vPPV, respectively). Immune hyporesponsiveness was observed in children vaccinated with 23vPPV at 12 months of age compared with children who did not receive 23vPPV. Here we assess the long-term impact of 23vPPV vaccination on nasopharyngeal carriage rates and densities of Streptococcus pneumoniae, Haemophilus influenzae, Staphylococcus aureus and Moraxella catarrhalis. Nasopharyngeal swabs (n=194) were obtained from healthy children who participated in FiPP (now aged 5-7 years). S. pneumoniae were isolated and identified by standard culture-based methods, and serotyped using latex agglutination and the Quellung reaction. Carriage rates and densities of S. pneumoniae, H. influenzae, S. aureus and M. catarrhalis were determined using real-time quantitative PCR. There were no differences in the rate or density of S. pneumoniae, H. influenzae or M. catarrhalis carriage by PCV7 dose or 23vPPV vaccination in the vaccinated participants overall. However, differences were observed between the two main ethnic groups: Fijian children of Indian descent (Indo-Fijian) were less likely to carry S. pneumoniae, H. influenzae and M. catarrhalis, and there was evidence of a higher carriage rate of S. aureus compared with indigenous Fijian (iTaukei) children. Polysaccharide vaccination appeared to have effects that varied between ethnic groups, with 23vPPV vaccination associated with a higher carriage rate of S. aureus in iTaukei children, while there was a lower carriage rate of S. pneumoniae associated with 23vPPV vaccination in Indo-Fijian children. Overall, polysaccharide vaccination had no long-term impact on pneumococcal carriage, but may have impacted on S. aureus carriage and have varying effects in ethnic groups, suggesting current WHO vaccine schedule recommendations against the use of 23vPPV in children under two years of age are appropriate. PMID:26232540

  8. Syncope after vaccination--United States, January 2005-July 2007.

    PubMed

    2008-05-01

    Syncope (vasovagal reaction), or fainting, can be triggered by various stimuli, including medical procedures. Syncope has been documented to occur after vaccination, most commonly among adolescents, and can result in hospitalization for a medical evaluation or because of injury. During 2005 and 2006, the Advisory Committee on Immunization Practices (ACIP) recommended use of three newly licensed vaccines for adolescents: the quadrivalent human papillomavirus recombinant vaccine (HPV) (Gardasil(R), Merck & Co., Inc., Whitehouse Station, New Jersey) in a 3-dose series, the quadrivalent meningococcal conjugate vaccine (MCV4) (Menactra, Sanofi Pasteur, Inc., Swiftwater, Pennsylvania) in a single dose, and the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine (Tdap) (Adacel, Sanofi Pasteur; Boostrix, GlaxoSmithKline Biologicals, Research Triangle Park, North Carolina) in a single dose. To describe trends in occurrence of postvaccination syncope, CDC and the Food and Drug Administration (FDA) analyzed data from the Vaccine Adverse Event Reporting System (VAERS) for January 1, 2005-July 31, 2007, and compared the results with VAERS reports received during January 1, 2002-December 31, 2004. The findings indicated that, since 2005, reports to VAERS regarding postvaccination syncope have increased, primarily among females aged 11-18 years, and rarely, subsequent serious injuries have occurred. To prevent syncope-related injuries, vaccine providers should follow the ACIP recommendation to strongly consider observing patients for 15 minutes after vaccination. PMID:18451756

  9. 9 CFR 113.114 - Tetanus Toxoid.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Tetanus Toxoid. 113.114 Section 113... Bacterial Products § 113.114 Tetanus Toxoid. Tetanus Toxoid shall be produced from a culture of Clostridium... purified and concentrated. Each serial of biological product containing tetanus toxoid fraction shall...

  10. 9 CFR 113.114 - Tetanus Toxoid.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Tetanus Toxoid. 113.114 Section 113... Bacterial Products § 113.114 Tetanus Toxoid. Tetanus Toxoid shall be produced from a culture of Clostridium... purified and concentrated. Each serial of biological product containing tetanus toxoid fraction shall...

  11. Automated capillary Western dot blot method for the identity of a 15-valent pneumococcal conjugate vaccine.

    PubMed

    Hamm, Melissa; Ha, Sha; Rustandi, Richard R

    2015-06-01

    Simple Western is a new technology that allows for the separation, blotting, and detection of proteins similar to a traditional Western except in a capillary format. Traditionally, identity assays for biological products are performed using either an enzyme-linked immunosorbent assay (ELISA) or a manual dot blot Western. Both techniques are usually very tedious, labor-intensive, and complicated for multivalent vaccines, and they can be difficult to transfer to other laboratories. An advantage this capillary Western technique has over the traditional manual dot blot Western method is the speed and the automation of electrophoresis separation, blotting, and detection steps performed in 96 capillaries. This article describes details of the development of an automated identity assay for a 15-valent pneumococcal conjugate vaccine, PCV15-CRM197, using capillary Western technology. PMID:25813208

  12. Using the tetravalent meningococcal polysaccharide-protein conjugate vaccine in the prevention of meningococcal disease

    PubMed Central

    Kimmel, Sanford R

    2008-01-01

    Invasive meningococcal disease occurs worldwide causing an estimated 50,000–135,000 deaths each year in addition to significant sequelae. In developed countries the disease is usually sporadic but outbreaks and epidemics, usually due to serogroups B and C, have occurred. In the US, an increasing number of cases are due to serogroup Y. In developing nations, epidemics due to serogroups A and more recently W-135, are common. The tetravalent meningococcal conjugate vaccine to serogroups A, C, Y, and W-135 (MCV4) has been demonstrated to be highly immunogenic and promote immune memory. This article will describe the rationale for the vaccine and its potential role to significantly decrease mortality and morbidity of meningococcal disease in those areas and populations at greatest risk from these serogroups. PMID:19209256

  13. 75 FR 7281 - Pediatric Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-18

    ... (rotavirus vaccine, live, oral), Kinrix (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed and Inactivated Poliovirus Vaccine), Pentacel [Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed, Inactivated Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccine], and...

  14. VACCINE INFORMATION STATEMENT Meningococcal Vaccines

    E-print Network

    VACCINE INFORMATION STATEMENT Meningococcal Vaccines What You Need to Know Many Vaccine of meningococcal vaccine is important for people at highest risk. 2 Meningococcal vaccine There are two kinds of meningococcal vaccine in the U.S.: · Meningococcal conjugate vaccine (MCV4) is the preferred vaccine for people

  15. Pneumococcal conjugate vaccine provides early protective antibody responses in children after related and unrelated allogeneic hematopoietic stem cell transplantation.

    PubMed

    Meisel, Roland; Kuypers, Lisa; Dirksen, Uta; Schubert, Ralf; Gruhn, Bernd; Strauss, Gabriele; Beutel, Karin; Groll, Andreas H; Duffner, Ulrich; Blütters-Sawatzki, Renate; Holter, Wolfgang; Feuchtinger, Tobias; Grüttner, Hans-Peter; Schroten, Horst; Zielen, Stefan; Ohmann, Christian; Laws, Hans-Jürgen; Dilloo, Dagmar

    2007-03-15

    Following allogeneic hematopoietic stem cell transplantation (alloHSCT), children are at risk of life-threatening pneumococcal infections. Whereas vaccination with polysaccharide vaccines fails to elicit protective immunity in most alloHSC transplant recipients, pneumococcal conjugate vaccines may effectively prevent invasive disease by eliciting T-cell-dependent antibody responses. Here, we report safety and immunogenicity in 53 children immunized with a regimen of 3 consecutive doses of a heptavalent pneumococcal conjugate vaccine (7vPCV) in monthly intervals starting 6 to 9 months after alloHSCT. Immunization was well tolerated with no vaccine-related serious adverse events. Serologic response rates evaluable in 43 patients ranged from 41.9% to 86.0% and 58.1% to 93.0% after 2 and 3 vaccinations, respectively, with 55.8% and 74.4% of patients achieving protective antibody levels to all 7 vaccine serotypes. Our study provides the first evidence that vaccination with 7vPCV is safe and elicits protective antipneumococcal antibody responses in pediatric recipients of related or unrelated donor alloHSC transplants within the first year following transplantation. This trial was registered at www.clinicaltrials.gov as NCT00169728. PMID:17090650

  16. Immunogenicity and safety of a CRM-conjugated meningococcal ACWY vaccine administered concomitantly with routine vaccines starting at 2 months of age

    PubMed Central

    Nolan, Terry M; Nissen, Michael D; Naz, Aftab; Shepard, Julie; Bedell, Lisa; Hohenboken, Matthew; Odrljin, Tatjana; Dull, Peter M

    2014-01-01

    Background: Infants are at the highest risk for meningococcal disease and a broadly protective and safe vaccine is an unmet need in this youngest population. We evaluated the immunogenicity and safety of a 4-dose infant/toddler regimen of MenACWY-CRM given at 2, 4, 6, and 12 months of age concomitantly with pentavalent diphtheria-tetanus-acellular pertussis-Hemophilus influenzae type b-inactivated poliovirus-combination vaccine (DTaP-IPV/Hib), hepatitis B vaccine (HBV), 7- or 13-valent conjugate pneumococcal vaccine (PCV), and measles, mumps, and rubella vaccine (MMR). Results: Four doses of MenACWY-CRM induced hSBA titers ?8 in 89%, 95%, 97%, and 96% of participants against serogroups A, C, W-135, and Y, respectively. hSBA titers ?8 were present in 76–98% of participants after the first 3 doses. A categorical linear analysis incorporating vaccine group and study center showed responses to routine vaccines administered with MenACWY-CRM were non-inferior to routine vaccines alone, except for seroresponse to the pertussis antigen fimbriae. The reactogenicity profile was not affected when MenACWY-CRM was administered concomitantly with routine vaccines. Conclusion: MenACWY-CRM administered with routine concomitant vaccinations in young infants was well tolerated and induced highly immunogenic responses against each of the serogroups without significant interference with the immune responses to routine infant vaccinations. Methods: Healthy 2 month old infants were randomized to receive MenACWY-CRM with routine vaccines (n = 258) or routine vaccines alone (n = 271). Immunogenicity was assessed by serum bactericidal assay using human complement (hSBA). Medically attended adverse events (AEs), serious AEs (SAEs) and AEs leading to study withdrawal were collected throughout the study period. PMID:24220326

  17. HEPTAVALENT PNEUMOCOCCAL CONJUGATE VACCINE IMMUNOGENICITY IN VERY-LOW-BIRTH-WEIGHT, PREMATURE INFANTS

    PubMed Central

    D’Angio, Carl T.; Heyne, Roy J.; O’Shea, T. Michael; Schelonka, Robert L.; Shankaran, Seetha; Duara, Shahnaz; Goldberg, Ronald N.; Stoll, Barbara J.; Van Meurs, Krisa P.; Vohr, Betty R.; Das, Abhik; Li, Lei; Burton, Robert L.; Hastings, Betty; Phelps, Dale L.; Sanchez, Pablo J.; Carlo, Waldemar A.; Stevenson, David K.; Higgins, Rosemary D.

    2010-01-01

    Background The heptavalent pneumococcal-CRM197 conjugate vaccine (PCV-7) has been incompletely studied in very-low-birth-weight (VLBW, ?1500 grams) infants. Objective To assess PCV-7 immunogenicity in VLBW, premature infants. We hypothesized that the frequency of post-vaccine antibody concentrations ?0.15 µg/mL would vary directly with birth weight. Methods This was a multi-center observational study. Infants 401–1500 grams birth weight and <32 0/7 weeks gestation, stratified by birth weight, were enrolled from 9 NICHD Neonatal Research Network centers. Infants received PCV-7 at 2, 4 and 6 months after birth and had blood drawn 4–6 weeks following the third dose. Antibodies against the 7 vaccine serotypes were measured by enzyme-linked immunosorbent assay. Results Of 369 enrolled infants, 244 completed their primary vaccine series by 8 months and had serum obtained. Subjects were 27.8 ± 2.2 (mean ± standard deviation) weeks gestation and 1008 ± 282 grams birth weight. Twenty-six percent had bronchopulmonary dysplasia and 16% had received postnatal glucocorticoids. Infants 1001–1500 grams birth weight were more likely than those 401–1000 grams to achieve antibody concentrations ?0.15 µg/mL against the least two immunogenic serotypes (6B: 96% v. 85%, P = 0.003 and 23F: 97% v. 88%, P = 0.009). In multiple logistic regression analysis, lower birth weight, postnatal glucocorticoid use, lower weight at blood draw and Caucasian race were each independently associated with antibody concentrations <0.35 µg/mL against serotypes 6B and/or 23F. Conclusion When compared with larger premature infants, infants weighing ?1000 grams at birth have similar antibody responses to most, but not all, PCV-7 vaccine serotypes. PMID:20234331

  18. Safety and immunogenicity of a single intramuscular dose of a tetanus-diphtheria toxoid (Td) vaccine (BR-TD-1001) in healthy Korean adult subjects.

    PubMed

    Hong, Taegon; Chung, Yong-Ju; Kim, Tae-Yeon; Kim, Ik-Hwan; Choe, Yong-Kyung; Lee, Jongtae; Jeon, Sangil; Han, Seunghoon; Yim, Dong-Seok

    2015-10-01

    BR-TD-1001 was developed as a booster for the immunity maintenance of diphtheria and tetanus. The aim of this study was to evaluate the safety and immunogenicity of BR-TD-1001 (test vaccine) in comparison with placebo and an active comparator in healthy Korean adults. A randomized, double-blind, placebo-controlled, active comparator, phase I clinical trial was conducted. Fifty subjects were randomly assigned to one of 3 treatment groups in a ratio of 2:2:1, and were administered a single intramuscular dose of test vaccine, active comparator, or placebo, respectively. All subjects were monitored for 4 weeks after injection. The antibody titers of the patients 2 and 4 weeks after vaccination were compared with the baseline. The frequencies of all adverse events including adverse drug reactions in the test group were not statistically different from those of the other treatment groups (P = 0.4974, 0.3061). No serious adverse event occurred, and no subject was withdrawn from the study for safety. The seroprotection rates against both tetanus and diphtheria at 4 weeks after vaccination were over 0.95. For anti-tetanus antibody, the geometric mean titer in the test group was significantly higher than those of the other groups (P = 0.0364, 0.0033). The geometric mean titer of anti-diphtheria antibody in the test group was significantly higher than the value of the placebo (P = 0.0347) while it was not for the value of the active comparator (P = 0.8484). In conclusion, BR-TD-1001 was safe, well-tolerated, and showed sufficient immunogenicity as a booster for diphtheria and tetanus. PMID:26091286

  19. Effects of Infant Pneumococcal Conjugate Vaccination on Serotype Distribution in Invasive Pneumococcal Disease among Children and Adults in Germany

    PubMed Central

    van der Linden, Mark; Falkenhorst, Gerhard; Perniciaro, Stephanie; Imöhl, Matthias

    2015-01-01

    This study describes the effects of the introduction of universal infant pneumococcal conjugate vaccination in 2006 on invasive pneumococcal disease (IPD) among children and adults in Germany with a focus on the dynamics of serotype distribution in vaccinated and non-vaccinated age groups. Over a period of 22 years (1992–2014), microbiological diagnostic laboratories from all over Germany have been sending isolates of IPD cases to the German National Reference Center for Streptococci on a voluntary basis. Streptococcus pneumoniae isolates were serotyped using Neufeld’s Quellung method. Among children <16 years, the proportion of PCV7 serotypes among isolates from IPD cases decreased from 61.8% before vaccination (1997–2006) to 23.5% in the early vaccination period (2007–2010; p = 1.30E-72) and sank further to 5.2% in the late vaccination period (2010–2014; p = 4.59E-25). Similar reductions were seen for the separate age groups <2 years, 2-4 years and 5-15 years. Among adults, the proportion of PCV7 serotypes decreased from 43.4% in the pre-vaccination period (1992–2006) to 24.7% (p = 3.78E-88) in the early vaccination period and 8.2% (p = 5.97E-161) in the late vaccination period. Both among children and among adults, the non-PCV7 serotypes 1, 3, 7F and 19A significantly increased in the early vaccination period. After the switch from PCV7 to PVC10/PCV13 for infant vaccination in 2010, serotypes 1, 6A and 7F significantly decreased. A decrease in serotype 19A was only observed in 2013–2014, as compared to 2010–2011 (children p = 4.16E-04, adults p = 6.98E-06). Among adults, serotype 3, which strongly increased in the early vaccination period (p = 4.44E-15), remained at a constant proportion in the late vaccination period. The proportion of non-PCV13 vaccine serotypes increased over the whole vaccination period, with serotypes 10A, 12F, 23B, 24F and 38 most significantly increasing among children and serotypes 6C, 12F, 15A, 22F and 23B increasing among adults. Eight years of childhood pneumococcal conjugate vaccination have had a strong effect on the pneumococcal population in Germany, both among the target group for vaccination as well as among older children and adults. PMID:26132078

  20. Invasive pneumococcal disease in children 5 years after conjugate vaccine introduction--eight states, 1998-2005.

    PubMed

    2008-02-15

    Streptococcus pneumoniae (pneumococcus) is a major cause of meningitis, pneumonia, and bacteremia, especially among young children and older adults. Before the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced in the United States in 2000, the seven pneumococcal serotypes covered by the vaccine (4, 6B, 9V, 14, 18C, 19F, and 23F) caused 80% of invasive pneumococcal disease (IPD) cases among young children, and the incidence of IPD was relatively stable. In October 2000, the Advisory Committee on Immunization Practices recommended PCV7 for all children aged <2 years and for older children at increased risk for IPD. Introduction of PCV7 in the United States led to substantial reductions in the incidence of IPD among the target population of children aged <5 years. Use of the vaccine also reduced IPD among unvaccinated populations through reductions in nasopharyngeal colonization and transmission of vaccine-type pneumococci from vaccinated children (i.e., indirect, or herd, effects of PCV7). To evaluate the effect of continued PCV7 use on IPD incidence among children aged <5 years in the United States, CDC analyzed population- and laboratory-based surveillance data. Results of that analysis indicated that in 2005, overall IPD rates among children aged <5 years were 77% lower, and an estimated 13,000 fewer cases of IPD occurred, compared with the years preceding vaccine introduction (1998-1999). Although IPD caused by PCV7 serotypes declined through 2005, overall IPD rates leveled off beginning in 2002, primarily because of increases in the incidence of IPD caused by non-PCV7 serotype 19A. Given these trends, use of expanded-valency conjugate vaccines might further reduce IPD incidence. Continued surveillance is needed to guide development of future formulations of conjugate vaccines and to monitor the effects of continued vaccine use. PMID:18272956

  1. Poor memory B cell generation contributes to non-protective responses to DTaP vaccine antigens in otitis-prone children.

    PubMed

    Basha, S; Pichichero, M E

    2015-12-01

    We recently identified a cohort of children with recurrent episodes of acute otitis media (AOM) who fail to generate protective antibody titres to otopathogens and several vaccine antigens. In this study we determined the antibody levels against DTaP vaccine antigens, diphtheria toxoid (DT), tetanus toxoid (TT) and acellular pertussis toxoid (PT) in sera from 15 stringently defined otitis-prone (sOP) children and 20 non-otitis-prone (NOP) children. We found significantly lower concentrations of immunoglobulin (Ig)G antibodies against vaccine antigens in the serum of sOP children compared to age-matched NOP children. To elucidate immunological cellular responses to the vaccines in these children, we investigated memory B cell responses to DTaP vaccination. We used fluorescently conjugated vaccine antigens to label antigen receptors on the surface of memory B cells and examined the frequency of antigen-specific CD19(+) CD27(+) memory B cells in the peripheral blood. sOP children showed a significantly lower percentage of antigen-specific CD19(+) CD27(+) memory B cells than NOP children. We also found a linear correlation between the frequencies of memory B cells and circulating IgG titres for DT, TT and PT proteins. To our knowledge, this is the first study to show significant differences in memory B cell responses to DTaP vaccine antigens and their correlation with the circulating antibodies in young children with recurrent AOM. PMID:26138025

  2. Cost-effectiveness of new pneumococcal conjugate vaccines in Turkey: a decision analytical model

    PubMed Central

    2012-01-01

    Background Streptococcus pneumoniae infections, which place a considerable burden on healthcare resources, can be reduced in a cost-effective manner using a 7-valent pneumococcal conjugate vaccine (PCV-7). We compare the cost effectiveness of a 13-valent PCV (PCV-13) and a 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) with that of PCV-7 in Turkey. Methods A cost-utility analysis was conducted and a decision analytical model was used to estimate the proportion of the Turkish population <10 years old that would experience 10 mutually exclusive outcomes over the course of 1 year from a perspective of a healthcare system. Model outcomes were adjusted according to the population demographics and region-specific serotype distribution in Turkey. Health outcomes and direct healthcare costs were simulated for PCV-7, PCV-13 and PHiD-CV. Results PCV-13 and PHiD-CV are projected to have a substantial impact on pneumococcal disease in Turkey versus PCV-7, with 2,223 and 3,156 quality-adjusted life years (QALYs) and 2,146 and 2,081 life years, respectively, being saved under a 3+1 schedule. Projections of direct medical costs showed that a PHiD-CV vaccination programme would provide the greatest cost savings, offering additional savings of US$11,718,813 versus PCV-7 and US$8,235,010 versus PCV-13. Probabilistic sensitivity analysis showed that PHiD-CV dominated PCV-13 in terms of QALYs gained and cost savings in 58.3% of simulations. Conclusion Under the modeled conditions, PHiD-CV would provide the most cost-effective intervention for reducing pneumococcal disease in Turkish children. PMID:23137037

  3. Genetic conjugation of components in two pneumococcal fusion protein vaccines enhances paediatric mucosal immune responses.

    PubMed

    Pope, Caroline; Oliver, Elizabeth H; Ma, Jiangtao; Langton Hewer, Claire; Mitchell, Tim J; Finn, Adam

    2015-03-30

    Streptococcus pneumoniae colonises the upper respiratory tract and can cause pneumonia, meningitis and otitis media. Existing pneumococcal conjugate vaccines are expensive to produce and only protect against 13 of the 90+ pneumococcal serotypes; hence there is an urgent need for the development of new vaccines. We have shown previously in mice that pneumolysin (Ply) and a non-toxic variant (?6Ply) enhance antibody responses when genetically fused to pneumococcal surface adhesin A (PsaA), a potentially valuable effect for future vaccines. We investigated this adjuvanticity in human paediatric mucosal primary immune cell cultures. Adenoidal mononuclear cells (AMNC) from children aged 0-15 years (n=46) were stimulated with conjugated, admixed or individual proteins, cell viability and CD4+ T-cell proliferative responses were assessed using flow cytometry and cytokine secretion was measured using multiplex technology. Proliferation of CD4+ T-cells in response to PsaAPly, was significantly higher than responses to individual or admixed proteins (p=0.002). In contrast, an enhanced response to PsaA?6Ply compared to individual or admixed proteins only occurred at higher concentrations (p<0.01). Evaluation of cytotoxicity suggested that responses occurred when Ply-induced cytolysis was inhibited, either by fusion or mutation, but importantly an additional toxicity independent immune enhancing effect was also apparent as a result of fusion. Responses were MHC class II dependent and had a Th1/Th17 profile. Genetic fusion of ?6Ply to PsaA significantly modulates and enhances pro-inflammatory CD4+ T-cell responses without the cytolytic effects of some other pneumolysoids. Membrane binding activity of such proteins may confer valuable adjuvant properties as fusion may assist ?6Ply to deliver PsaA to the APC surface effectively, contributing to the initiation of anti-pneumococcal CD4+ T-cell immunity. PMID:25698489

  4. Respiratory infection and otitis media visits in relation to pneumococcal conjugate vaccine use in Saskatchewan

    PubMed Central

    Khuc, Ngoc-Hang; Tan, Ben; Tuchscherer, Rosalie; Rawson, Nigel SB; De Wals, Philippe

    2013-01-01

    BACKGROUND: In Saskatchewan, pneumococcal conjugate vaccination (PCV) was offered to high-risk children in 2002 and to all infants in 2005. OBJECTIVE: To describe trends in the frequency of medical visits for lower respiratory tract infection (LRI) and otitis media (OM) in relation to PCV use during the period 1990 to 2008. METHODS: Statistics regarding the number of children covered by the health insurance plan, PCV administration, and medical visits with a diagnostic code associated with LRI and OM were provided by Saskatchewan Health. Monthly rates were analyzed using dynamic state space models. RESULTS: In all series, there was a marked seasonal cycle and some higher-than-expected winter peak values, possibly associated with epidemics of specific respiratory viruses. Three abrupt decreases in baseline rate were observed for LRI and the final one, in February 2007, could be related to the increased proportion of children vaccinated with PCV. There was no statistical correlation between PCV use and OM visit frequency. CONCLUSION: Many environmental, biological and administrative factors may influence health services use, and an effect of low magnitude of a particular vaccine pertaining to nonspecific outcomes could be obscured in time-series analyses. PMID:24489558

  5. Clinical Safety and Immunogenicity of Tumor-Targeted, Plant-Made Id-KLH Conjugate Vaccines for Follicular Lymphoma

    PubMed Central

    Tusé, Daniel; Ku, Nora; Bendandi, Maurizio; Becerra, Carlos; Collins, Robert; Langford, Nyla; Sancho, Susana Inogés; López-Díaz de Cerio, Ascensión; Pastor, Fernando; Kandzia, Romy; Thieme, Frank; Jarczowski, Franziska; Krause, Dieter; Ma, Julian K.-C.; Pandya, Shan; Klimyuk, Victor; Gleba, Yuri; Butler-Ransohoff, John E.

    2015-01-01

    We report the first evaluation of plant-made conjugate vaccines for targeted treatment of B-cell follicular lymphoma (FL) in a Phase I safety and immunogenicity clinical study. Each recombinant personalized immunogen consisted of a tumor-derived, plant-produced idiotypic antibody (Ab) hybrid comprising the hypervariable regions of the tumor-associated light and heavy Ab chains, genetically grafted onto a common human IgG1 scaffold. Each immunogen was produced in Nicotiana benthamiana plants using twin magnICON vectors expressing the light and heavy chains of the idiotypic Ab. Each purified Ab was chemically linked to the carrier protein keyhole limpet hemocyanin (KLH) to form a conjugate vaccine. The vaccines were administered to FL patients over a series of ?6 subcutaneous injections in conjunction with the adjuvant Leukine (GM-CSF). The 27 patients enrolled in the study had previously received non-anti-CD20 cytoreductive therapy followed by ?4 months of immune recovery prior to first vaccination. Of 11 patients who became evaluable at study conclusion, 82% (9/11) displayed a vaccine-induced, idiotype-specific cellular and/or humoral immune response. No patients showed serious adverse events (SAE) related to vaccination. The fully scalable plant-based manufacturing process yields safe and immunogenic personalized FL vaccines that can be produced within weeks of obtaining patient biopsies. PMID:26425548

  6. [Impact of a conjugated anti meningococcal A vaccine on notification of bacterial meningitis in West Burkina Faso (2009-2012)].

    PubMed

    Ouangraoua, S; Schlumberger, M; Yaro, S; Ouédraogo, A S; Sanou, S; Drabo, A; Yaméogo, T M; Ouedraogo, R

    2014-02-01

    Burkina Faso is a sub-saharan African country completely included in the meningococcal meningitis belt. The western part of the country suffered from many meningococcal A epidemics, in spite of reactive collective campaigns with polysaccharide A vaccine. On 6th December 2010, Burkina Faso was the first African country to conduct a collective vaccination campaign of all the 1-29 years old population with a new conjugated meningococcal Avaccine (MenAfriVac™). Before this campaign, in Western Burkina (4,064,928 inhabitants, 27.5% of total population), a rehearsal of the staff of all peripheral medical laboratories has been conducted, with delivery of laboratory equipment, reactants, and possibility to transfer CSF specimens at the central level to confirm bacteriologic species in cause by latex, culture and PCR analysis. For this campaign, an administrative coverage of 100.3% was reached. A nearly complete disappearance of meningitis due to meningococcus A was recorded, but an increase of cases due to meningococcus X, W135. With the increase of quality of surveillance, and MenAfriVac™ vaccination showed its beneficial effect on meningococcus A meningitis. If we want however to impact on the number of recorded acute bacteriological meningitis, we will have to use multi-antigenic, if possible conjugated, meningococcal vaccines against locally circulating meningococcal species, the number of pneumococcal meningitis being contained by the recent inclusion in EPI of a 13-valent conjugated pneumococcal vaccine. PMID:24390976

  7. Meningococcal Serogroup A, C, W135 and Y Conjugated Vaccine: A Cost-Effectiveness Analysis in the Netherlands

    PubMed Central

    van der Ende, Arie; Westra, Tjalke A.; Postma, Maarten J.

    2013-01-01

    Background In 2002, vaccination with a serogroup C meningococcal conjugate vaccine (MenC) was introduced in the Netherlands for all children aged 14 months. Despite its success, herd immunity may wane over time. Recently, a serogroup A,C,W135,Y meningococcal conjugate vaccine (MenACWY) was licensed for use in subjects of 12 months of age and above. Objectives To evaluate the cost-effectiveness of meningococcal vaccination at 14 months and an additional vaccination at the age of 12 years, both with the MenACWY vaccine. Methods A decision analysis cohort model, with 185,000 Dutch newborns, was used to evaluate the cost-effectiveness of different immunization strategies. For strategies including a vaccination at 12 years of age, an additional cohort with adolescents aged 12 years was followed. The incremental cost-effectiveness ratio (ICER) was estimated for the current disease incidence and for a scenario when herd immunity is lost. Results Vaccination with MenACWY at 14 months is cost-saving. Vaccinating with MenACWY at 14 months and at 12 years would prevent 7 additional cases of meningococcal serogroup A,C,W135,Y disease in the birth cohort and adolescent cohort followed for 99 years compared to the current vaccine schedule of a single vaccination with MenC at 14 months. With the current incidence, this strategy resulted in an ICER of €635,334 per quality adjusted life year. When serogroup C disease incidence returns to pre-vaccination levels due to a loss of vaccine-induced herd-immunity, vaccination with MenACWY at 14 months and at 12 years would be cost-saving. Conclusions Routine vaccination with MenACWY is cost-saving. With the current epidemiology, a booster-dose with MenACWY is not likely cost-effective. When herd immunity is lost, a booster-dose has the potential of being cost-effective. A dynamic model should be developed for more precise estimation of the cost-effectiveness of the prevention of disappearance of herd immunity. PMID:23741448

  8. Cost effectiveness of pediatric pneumococcal conjugate vaccines: a comparative assessment of decision-making tools

    PubMed Central

    2011-01-01

    Background Several decision support tools have been developed to aid policymaking regarding the adoption of pneumococcal conjugate vaccine (PCV) into national pediatric immunization programs. The lack of critical appraisal of these tools makes it difficult for decision makers to understand and choose between them. With the aim to guide policymakers on their optimal use, we compared publicly available decision-making tools in relation to their methods, influential parameters and results. Methods The World Health Organization (WHO) requested access to several publicly available cost-effectiveness (CE) tools for PCV from both public and private provenance. All tools were critically assessed according to the WHO's guide for economic evaluations of immunization programs. Key attributes and characteristics were compared and a series of sensitivity analyses was performed to determine the main drivers of the results. The results were compared based on a standardized set of input parameters and assumptions. Results Three cost-effectiveness modeling tools were provided, including two cohort-based (Pan-American Health Organization (PAHO) ProVac Initiative TriVac, and PneumoADIP) and one population-based model (GlaxoSmithKline's SUPREMES). They all compared the introduction of PCV into national pediatric immunization program with no PCV use. The models were different in terms of model attributes, structure, and data requirement, but captured a similar range of diseases. Herd effects were estimated using different approaches in each model. The main driving parameters were vaccine efficacy against pneumococcal pneumonia, vaccine price, vaccine coverage, serotype coverage and disease burden. With a standardized set of input parameters developed for cohort modeling, TriVac and PneumoADIP produced similar incremental costs and health outcomes, and incremental cost-effectiveness ratios. Conclusions Vaccine cost (dose price and number of doses), vaccine efficacy and epidemiology of critical endpoint (for example, incidence of pneumonia, distribution of serotypes causing pneumonia) were influential parameters in the models we compared. Understanding the differences and similarities of such CE tools through regular comparisons could render decision-making processes in different countries more efficient, as well as providing guiding information for further clinical and epidemiological research. A tool comparison exercise using standardized data sets can help model developers to be more transparent about their model structure and assumptions and provide analysts and decision makers with a more in-depth view behind the disease dynamics. Adherence to the WHO guide of economic evaluations of immunization programs may also facilitate this process. Please see related article: http://www.biomedcentral.com/1741-7007/9/55 PMID:21569402

  9. Reasons for instability of bacterial vaccines.

    PubMed

    Corbel, M J

    1996-01-01

    Stability problems in relation to bacterial vaccines vary widely between different types of product. Killed whole cell bacterial vaccines including pertussis, cholera and typhoid vaccines generally show a high degree of stability of potency. Reversion to toxicity may occur in incompletely inactivated pertussis vaccines. Live attenuated vaccines such as BCG and Ty21a typhoid vaccines lose potency through loss of viability when exposed to adverse conditions. Both vaccines are susceptible to ultra violet radiation but Ty21a also has low thermal stability. Its fragility is probably a consequence of multiple mutations affecting structural and metabolic factors. Diphtheria and tetanus toxoids generally show high stability of potency. Reversion to toxicity may occur if the toxoiding process is inadequate. Decline in potency may result from exposure to adverse conditions, such as freezing, that affect the interaction with the adjuvant. Similar problems may be encountered with purified subunit vaccines such as acellular pertussis preparations. Some components, in particular pertussis toxin and filamentous haemagglutinin, show inherent low stability and degrade on storage at refrigerator temperatures unless stabilized by a protein cross-linking agent. Bacterial proteases carried over from the cell cultures may also be responsible for degradation of purified components. Purified bacterial polysaccharides usually show high stability if freeze-dried under appropriate conditions. Catalytic degradation may occur however, if the stabilizers are of inadequate purity. Polysaccharide-protein conjugates such as Haemophilus influenzae b (Hib) polyribosylribityl phosphate-protein conjugates show high thermal stability if freeze dried. In the liquid state, such conjugates tend to degrade by hydrolysis of the polysaccharide chains. Combined vaccines may present special stability problems because of the interaction of the various components in the liquid state. It can be difficult to freeze-dry some components of such vaccines, particularly aluminium hydroxide-adsorbed diphtheria-tetanus-pertussis (DTP) components. Slow release vaccines based on polyglycolide-factolide microspheres may show suboptimal stability of encapsulated antigen under both in vitro conditions as a result of gradual acidification through polymer hydrolysis. Vaccines based on the use of live recombinant strains to express heterologous protective antigens may present special stability problems. Apart from the carrier strains, heterologous genes carried on plasmids may be subject to spontaneous deletion under adverse conditions. These issues have received relatively little attention hitherto but are likely to achieve greater prominence as development of such preparations proceeds. PMID:8854008

  10. Immunogenicity of reduced dose priming schedules of serogroup C meningococcal conjugate vaccine followed by booster at 12 months in infants: open label randomised controlled trial

    PubMed Central

    Khatami, Ameneh; McKenna, Jennifer; Campbell, Danielle; Attard-Montalto, Simon; Birks, Jacqueline; Voysey, Merryn; White, Catherine; Finn, Adam; Macloed, Emma; Faust, Saul N; Kent, Alison Louise; Heath, Paul T; Borrow, Ray; Snape, Matthew D; Pollard, Andrew J

    2015-01-01

    Objective To determine whether the immunogenicity of a single dose infant priming schedule of serogroup C meningococcal (MenC) conjugate vaccine is non-inferior to a two dose priming schedule when followed by a booster dose at age 12 months. Design Phase IV open label randomised controlled trial carried out from July 2010 until August 2013 Setting Four centres in the United Kingdom and one centre in Malta. Participants Healthy infants aged 6-12 weeks followed up until age 24 months. Interventions In the priming phase of the trial 509 infants were randomised in a 10:10:7:4 ratio into four groups to receive either a single MenC-cross reacting material 197 (CRM) dose at 3 months; two doses of MenC-CRM at 3 and 4 months; a single MenC-polysaccharide-tetanus toxoid (TT) dose at 3 months; or no MenC doses, respectively. Haemophilus influenzae type b (Hib)-MenC-TT vaccine was administered to all infants at 12 months of age. All infants also received the nationally routinely recommended vaccines. Blood samples were taken at age 5, 12, 13, and 24 months. Main outcome measure MenC serum bactericidal antibody assay with rabbit complement (rSBA) one month after the Hib-MenC-TT vaccine. Non-inferiority was met if the lower 95% confidence limit of the difference in the mean log10 MenC rSBA between the single dose MenC-CRM and the two dose MenC-CRM groups was >?0.35. Results The primary objective was met: after a Hib-MenC-TT booster dose at 12 months of age the MenC rSBA geometric mean titres induced in infants primed with a single MenC-CRM dose were not inferior to those induced in participants primed with two MenC-CRM doses in infancy (660 (95% confidence interval 498 to 876) v 295 (220 to 398)) with a corresponding difference in the mean log10 MenC rSBA of 0.35 (0.17 to 0.53) that showed superiority of the single over the two dose schedule). Exploration of differences between the priming schedules showed that one month after Hib-MenC-TT vaccination, MenC rSBA ?1:8 was observed in >96% of participants previously primed with any of the MenC vaccine schedules in infancy and in 83% of those who were not vaccinated against MenC in infancy. The MenC rSBA geometric mean titres induced by the Hib-MenC-TT boost were significantly higher in children who were primed with one rather than two MenC-CRM doses in infancy. Only priming with MenC-TT, however, induced robust MenC bactericidal antibody after the Hib-MenC-TT booster that persisted until 24 months of age. Conclusions MenC vaccination programmes with two MenC infant priming doses could be reduced to a single priming dose without reducing post-boost antibody titres. When followed by a Hib-MenC-TT booster dose, infant priming with a single MenC-TT vaccine dose induces a more robust antibody response than one or two infant doses of MenC-CRM. Bactericidal antibody induced by a single Hib-MenC-TT conjugate vaccine dose at 12 months of age (that is, a toddler only schedule), without infant priming, is not well sustained at 24 months. Because of rapid waning of MenC antibody, programmes using toddler only schedules will still need to rely on herd protection to protect infants and young children. Trial registration Eudract No: 2009-016579-31; NCT01129518; study ID: 2008_06 (http://clinicaltrials.gov). PMID:25832102

  11. Childhood meningitis in the conjugate vaccine era: a prospective cohort study.

    PubMed

    Sadarangani, Manish; Willis, Louise; Kadambari, Seilesh; Gormley, Stuart; Young, Zoe; Beckley, Rebecca; Gantlett, Katherine; Orf, Katharine; Blakey, Sarah; Martin, Natalie G; Kelly, Dominic F; Heath, Paul T; Nadel, Simon; Pollard, Andrew J

    2015-03-01

    Bacterial conjugate vaccines have dramatically changed the epidemiology of childhood meningitis; viral causes are increasingly predominant, but the current UK epidemiology is unknown. This prospective study recruited children under 16?years of age admitted to 3 UK hospitals with suspected meningitis. 70/388 children had meningitis-13 bacterial, 26 viral and 29 with no pathogen identified. Group B Streptococcus was the most common bacterial pathogen. Infants under 3?months of age with bacterial meningitis were more likely to have a reduced Glasgow Coma Score and respiratory distress than those with viral meningitis or other infections. There were no discriminatory clinical features in older children. Cerebrospinal fluid (CSF) white blood cell count and plasma C-reactive protein at all ages, and CSF protein in infants <3?months of age, distinguished between bacterial meningitis and viral meningitis or other infections. Improved diagnosis of non-bacterial meningitis is urgently needed to reduce antibiotic use and hospital stay. PMID:25256088

  12. Cost-utility analysis of 10- and 13-valent pneumococcal conjugate vaccines: Protection at what price in the Thai context?

    PubMed Central

    Kulpeng, Wantanee; Leelahavarong, Pattara; Rattanavipapong, Waranya; Sornsrivichai, Vorasith; Baggett, Henry C.; Meeyai, Aronrag; Punpanich, Warunee; Teerawattananon, Yot

    2015-01-01

    Objective This study aims to evaluate the costs and outcomes of offering the 10-valent pneumococcal conjugate vaccine (PCV10) and 13-valent pneumococcal conjugate vaccine (PCV13) in Thailand compared to the current situation of no PCV vaccination. Methods Two vaccination schedules were considered: two-dose primary series plus a booster dose (2 + 1) and three-dose primary series plus a booster dose (3 + 1). A cost-utility analysis was conducted using a societal perspective. A Markov simulation model was used to estimate the relevant costs and health outcomes for a lifetime horizon. Costs were collected and values were calculated for the year 2010. The results were reported as incremental cost-effectiveness ratios (ICERs) in Thai Baht (THB) per quality adjusted life year (QALY) gained, with future costs and outcomes being discounted at 3% per annum. One-way sensitivity analysis and probabilistic sensitivity analysis using a Monte Carlo simulation were performed to assess parameter uncertainty. Results Under the base case-scenario of 2 + 1 dose schedule and a five-year protection, without indirect vaccine effects, the ICER for PCV10 and PCV13 were THB 1,368,072 and THB 1,490,305 per QALY gained, respectively. With indirect vaccine effects, the ICER of PCV10 was THB 519,399, and for PCV13 was THB 527,378. The model was sensitive to discount rate, the change in duration of vaccine protection and the incidence of pneumonia for all age groups. Conclusions At current prices, PCV10 and PCV13 are not cost-effective in Thailand. Inclusion of indirect vaccine effects substantially reduced the ICERs for both vaccines, but did not result in cost effectiveness. PMID:23588084

  13. Safety and tolerability of 13-valent pneumococcal conjugate vaccine in the elderly

    PubMed Central

    Durando, Paolo; Rosselli, Roberto; Cremonesi, Ilaria; Orsi, Andrea; Albanese, Erika; Barberis, Ilaria; Paganino, Chiara; Trucchi, Cecilia; Martini, Mariano; Marensi, Lorenzo; Turello, Valter; Study Group, the Ligurian Pneumococcal; Bregante, Alessandro; Cacciani, Roberto; Iudici, Rocco; La Marca, Diego; Pedano, Leonardo; Petrucci, Amadio Franco; Santolini, Maria; Sbisà, Valentina; Zacconi, Monica

    2014-01-01

    Background In September 2011 the European Medical Agency authorized the use of 13-valent pneumococcal conjugate vaccine (PCV13) in adults aged ?50 years. The same occurred in the US in December 2011 when the Food and Drug Administration approved the use of PCV13 in the same target age-group with indication for the prevention of invasive pneumococcal diseases and community acquired pneumonia sustained by the serotypes contained in the vaccine. The Liguria Region, in Italy, implemented in 2013 an active and free of charge immunization strategy with PCV13 among adults affected by specific risk conditions and the elderly aged ?70 years. Methods An observational study was performed in order to assess the safety and tolerability of PCV13 among elderly dwelling in the metropolitan area of Genoa, the capital city of Liguria Region. Eligible subjects, who received PCV13 following the public health immunization campaign at the Local Health Unit 3 of Genoa, provided a written informed consent to take part in the study. Eight-hundred-seventy-one subjects were enrolled between October 2013 and May 2014: all were monitored by qualified healthcare personnel for at least 30 min after vaccination at the outpatient clinics, in order to assess any possible sudden reaction. The occurrence of a series of local and systemic solicited reactions and of any unsolicited Adverse Events (AEs) was monitored using a self-administered clinical diary and by regular phone contacts up to 14 and 21 d following immunization, respectively. Moreover, a 6-months follow-up following vaccination was planned in order to monitor Severe Adverse Events (SAEs). Results No sudden reaction occurred in vaccinees at the outpatient clinics. Pain (27.4%) was the most frequent reaction reported by subjects at the injection site, while new muscle pain (13.6%), fatigue (10.7%), and headache (9.9%) resulted the most common systemic reactions. Rates of the main reactions reported in this on-field study resulted generally lower than those registered in clinical trials performed in the elderly. The incidence of fever (2.2%) following vaccination was low at values superimposable to that reported in previous studies. Conclusion This observational study showed a good safety and tolerability of PCV13 among the elderly in routine clinical practice further confirming the evidence coming from clinical trials in the same age-group. PMID:25483531

  14. Impact of Pneumococcal Conjugate Vaccine Administration in Pediatric Older Age Groups in Low and Middle Income Countries: A Systematic Review

    PubMed Central

    Bonner, Kimberly; Welch, Emily; Elder, Kate; Cohn, Jennifer

    2015-01-01

    Introduction Pneumococcal conjugate vaccine (PCV) is included in the World Health Organization’s routine immunization schedule and is recommended by WHO for vaccination in high-risk children up to 60 months. However, many countries do not recommend vaccination in older age groups, nor have donors committed to supporting extended age group vaccination. To better inform decision-making, this systematic review examines the direct impact of extended age group vaccination in children over 12 months in low and middle income countries. Methods An a priori protocol was used. Using pre-specified terms, a search was conducted using PubMed, LILACS, Cochrane Infectious Diseases Group Specialized Register, Cochrane Central Register of Controlled Trials, CAB Abstracts, clinicaltrials.gov and the International Symposium on Pneumococci and Pneumococcal Diseases abstracts. The primary outcome was disease incidence, with antibody titers and nasopharyngeal carriage included as secondary outcomes. Results Eighteen studies reported on disease incidence, immune response, and nasopharyngeal carriage. PCV administered after 12 months of age led to significant declines in invasive pneumococcal disease. Immune response to vaccine type serotypes was significantly higher for those vaccinated at older ages than the unimmunized at the established 0.2ug/ml and 0.35ug/ml thresholds. Vaccination administered after one year of age significantly reduced VT carriage with odds ratios ranging from 0.213 to 0.69 over four years. A GRADE analysis indicated that the studies were of high quality. Discussion PCV administration in children over 12 months leads to significant protection. The direct impact of PCV administration, coupled with the large cohort of children missed in first year vaccination, indicates that countries should initiate or expand PCV immunization for extended age group vaccinations. Donors should support implementation of PCV as part of delayed or interrupted immunization for older children. For countries to effectively implement extended age vaccinations, access to affordably-priced PCV is critical. PMID:26332848

  15. 75 FR 7281 - Pediatric Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-02-18

    ...live, oral), Kinrix (Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed...Vaccine), Pentacel [Diphtheria and Tetanus Toxoids and Acellular Pertussis Adsorbed...Poliovirus and Haemophilus b Conjugate (Tetanus Toxoid Conjugate) Vaccine], and...

  16. Influence of Pneumococcal Conjugate Vaccine on Acute Otitis Media with Severe Middle Ear Inflammation: A Retrospective Multicenter Study.

    PubMed

    Sugino, Hirotoshi; Tsumura, Shigeru; Kunimoto, Masaru; Noda, Masuhiro; Chikuie, Daisuke; Noda, Chieko; Yamashita, Mariko; Watanabe, Hiroshi; Ishii, Hidemasa; Tashiro, Toru; Iwata, Kazuhiro; Kono, Takashi; Tsumura, Kaoru; Sumiya, Takahiro; Takeno, Sachio; Hirakawa, Katsuhiro

    2015-01-01

    The Japanese guidelines for acute otitis media in children recommend classifying acute otitis media by age, manifestations and local findings, and also recommend myringotomy for moderate-grade cases with severe local findings, severe-grade cases, and treatment-resistant cases. The heptavalent pneumococcal conjugate vaccine was released in Japan in February 2010. In Hiroshima City, public funding allowing free inoculation with this vaccine was initiated from January 2011, and the number of vaccinated individuals has since increased dramatically. This study investigated changes in the number of myringotomies performed to treat acute otitis media during the 5-year period from January 2008 to December 2012 at two hospitals and five clinics in the Asa Area of Hiroshima City, Japan. A total of 3,165 myringotomies for acute otitis media were performed. The rate of procedures per child-year performed in <5-year-old children decreased by 29.1% in 2011 and by 25.2% in 2012 compared to the mean rate performed in the 3 years prior to the introduction of public funding. A total of 895 myringotomies were performed for 1-year-old infants. The rate of myringotomies per child-year performed for acute otitis media in 1-year-old infants decreased significantly in the 2 years after the introduction of public funding for heptavalent pneumococcal conjugate vaccine compared to all years before introduction (p<0.000001). Our results suggest a benefit of heptavalent pneumococcal conjugate vaccine for acute otitis media in reducing the financial burden of myringotomy. In addition, this vaccine may help prevent acute otitis media with severe middle ear inflammation in 1-year-old infants. PMID:26348230

  17. Influence of Pneumococcal Conjugate Vaccine on Acute Otitis Media with Severe Middle Ear Inflammation: A Retrospective Multicenter Study

    PubMed Central

    Sugino, Hirotoshi; Tsumura, Shigeru; Kunimoto, Masaru; Noda, Masuhiro; Chikuie, Daisuke; Noda, Chieko; Yamashita, Mariko; Watanabe, Hiroshi; Ishii, Hidemasa; Tashiro, Toru; Iwata, Kazuhiro; Kono, Takashi; Tsumura, Kaoru; Sumiya, Takahiro; Takeno, Sachio; Hirakawa, Katsuhiro

    2015-01-01

    The Japanese guidelines for acute otitis media in children recommend classifying acute otitis media by age, manifestations and local findings, and also recommend myringotomy for moderate-grade cases with severe local findings, severe-grade cases, and treatment-resistant cases. The heptavalent pneumococcal conjugate vaccine was released in Japan in February 2010. In Hiroshima City, public funding allowing free inoculation with this vaccine was initiated from January 2011, and the number of vaccinated individuals has since increased dramatically. This study investigated changes in the number of myringotomies performed to treat acute otitis media during the 5-year period from January 2008 to December 2012 at two hospitals and five clinics in the Asa Area of Hiroshima City, Japan. A total of 3,165 myringotomies for acute otitis media were performed. The rate of procedures per child-year performed in <5-year-old children decreased by 29.1% in 2011 and by 25.2% in 2012 compared to the mean rate performed in the 3 years prior to the introduction of public funding. A total of 895 myringotomies were performed for 1-year-old infants. The rate of myringotomies per child-year performed for acute otitis media in 1-year-old infants decreased significantly in the 2 years after the introduction of public funding for heptavalent pneumococcal conjugate vaccine compared to all years before introduction (p<0.000001). Our results suggest a benefit of heptavalent pneumococcal conjugate vaccine for acute otitis media in reducing the financial burden of myringotomy. In addition, this vaccine may help prevent acute otitis media with severe middle ear inflammation in 1-year-old infants. PMID:26348230

  18. Regulatory Pathways That Facilitated Timely Registration of a New Group A Meningococcal Conjugate Vaccine for Africa's Meningitis Belt Countries

    PubMed Central

    Dellepiane, Nora; Akanmori, Bartholomew Dicky; Gairola, Sunil; Jadhav, Suresh S.; Parker, Cathy; Rodriguez, Carmen; Srivastava, Swati

    2015-01-01

    Background.?Through its normative and public health leadership roles, the World Health Organization (WHO) plays a key role in the availability of vaccine products in low-and middle-income countries. The recent introduction of a new group A meningococcal conjugate vaccine, PsA-TT (MenAfriVac), in Africa exemplifies this process. WHO requires that any new vaccine to be introduced in countries for public health reasons and supplied through United Nations centralized mechanisms be licensed by the national regulatory agency (NRA) in the producing country, then prequalified and given a marketing authorization in the user countries. Methods.?PsA-TT was manufactured by the Serum Institute of India, Ltd (SIIL), which submitted a license application in April 2009 to the Drug Controller General of India (DCGI), the Indian NRA responsible for licensing vaccines. WHO encouraged the DCGI to establish a collaboration with Health Canada's Centre for Vaccine Evaluation for the review. Through this collaborative effort, registration was facilitated and in December 2009 an export license was granted to SIIL, which subsequently submitted an application for WHO prequalification. Results.?Given the importance of the vaccine, WHO “fast tracked” the prequalification review, and after a detailed review and site visit, WHO prequalification was granted to PsA-TT in June 2010. Country use of the new vaccine could not occur until the vaccine was a registered product in each country seeking its use. WHO facilitated country reviews by conducting regulatory training exercises (in French and English) for country NRA staff, which used the PsA-TT registration as a case study. Conclusions.?PsA-TT was gradually registered in African countries as vaccine introduction proceeded. The regulatory pathway for this new group A meningococcal conjugate vaccine proved to be a useful training opportunity both in India and Africa, because the availability of the vaccine was a high African public health priority, as well as for WHO as a case study to facilitate registration of vaccines based on reliance on other regulatory bodies. PMID:26553671

  19. Safety and tolerability of 13-valent pneumococcal conjugate vaccine in healthy Chinese adults, children and infants

    PubMed Central

    Zhu, Fengcai; Hu, Yuemei; Liang, Qi; Young, Mariano; Zhou, Xin; Chen, Zhangjing; Liang, John Z.; Gruber, William C.; Scott, Daniel A.

    2015-01-01

    Objective: Pneumococcal disease is a global problem, including in China. The objective of this study was to provide safety data for single-dose 13-valent pneumococcal conjugate vaccine (PCV13) in Chinese subjects, needed to begin a phase III safety and immunogenicity study in Chinese infants. Methods: Healthy Chinese adults (18?55 years), children (3?5 years), and infants (42–98 days) received a single dose of PCV13 in this open-label safety study. Local reactions and systemic events were collected for 7 days via an electronic diary; adverse events were recorded for 1 month after vaccination. Results: All 72 (24 per group) screened subjects (58.3% males; mean ± standard deviation [SD] age: 43.3 ± 9.1 years [adults], 4.5 ± 0.7 years [children], and 79.6 ± 15.2 days [infants]) were enrolled, received vaccine, and completed the study. The most frequently reported local reactions per group were pain at the injection site (n = 23 adults [95.8%]), tenderness (n = 18 children [75%]), and swelling (n = 6 infants [25%]), none of which were severe. The mean duration of each local reaction was ?2.0 days in infants and ?2.4 days in children but in adults was 3.3 days for pain at the injection site and 9 days each for redness and swelling. Systemic events in adults were muscle pain (n = 5), fatigue (n = 3), and headache and joint pain (n = 1 each). One child and seven infants had disturbed sleep (increased or decreased). One adult and one child had mild fever (37.7–38.5°C, as per China Food and Drug Administration guidelines). No subject used antipyretic medication. One adverse event (bronchopneumonia in an infant) was reported, which was serious, severe, and unrelated to vaccination. There were no deaths. Conclusions: A single dose of PCV13 was safe and well tolerated in healthy Chinese adults, children, and infants. This study provided the safety data to enable a phase III safety and immunogenicity registration trial in Chinese infants to proceed.

  20. Stabilization of tetanus toxoid formulation containing aluminium hydroxide adjuvant against agitation.

    PubMed

    Solanki, Vipul A; Jain, Nishant K; Roy, Ipsita

    2012-02-28

    The aggregation of tetanus toxoid leads to reduced bioavailability of the vaccine and failure of immunization programmes in many parts of the globe. One of the main reasons for denaturation and aggregation of tetanus toxoid formulations is agitation of the protein during transport. We have identified that agitation leads to collapse of the gel matrix of aluminium hydroxide which is used as an adjuvant in these preparations. This results in desorption of the toxoid from the matrix, which then loses its antigenicity due to agitation-induced denaturation of the protein. We show that incorporation of some compatible osmolytes like sorbitol, glucose and arginine, but not trehalose, is able to protect the adjuvant matrix from degradation, and retain the integrity of the vaccine preparation in terms of its antigenicity. PMID:22155287

  1. Protein Antigens Increase the Protective Efficacy of a Capsule-Based Vaccine against Staphylococcus aureus in a Rat Model of Osteomyelitis

    PubMed Central

    Lattar, Santiago M.; Noto Llana, Mariángeles; Denoël, Philippe; Germain, Sophie; Buzzola, Fernanda R.; Lee, Jean C.

    2014-01-01

    Staphylococcus aureus is an invasive bacterial pathogen, and antibiotic resistance has impeded adequate control of infections caused by this microbe. Moreover, efforts to prevent human infections with single-component S. aureus vaccines have failed. In this study, we evaluated the protective efficacy in rats of vaccines containing both S. aureus capsular polysaccharides (CPs) and proteins. The serotypes 5 CP (CP5) and 8 CP (CP8) were conjugated to tetanus toxoid and administered to rats alone or together with domain A of clumping factor A (ClfA) or genetically detoxified alpha-toxin (dHla). The vaccines were delivered according to a preventive or a therapeutic regimen, and their protective efficacy was evaluated in a rat model of osteomyelitis. Addition of dHla (but not ClfA) to the CP5 or CP8 vaccine induced reductions in bacterial load and bone morphological changes compared with immunization with either conjugate vaccine alone. Both the prophylactic and therapeutic regimens were protective. Immunization with dHla together with a pneumococcal conjugate vaccine used as a control did not reduce staphylococcal osteomyelitis. The emergence of unencapsulated or small-colony variants during infection was negligible and similar for all of the vaccine groups. In conclusion, addition of dHla to a CP5 or CP8 conjugate vaccine enhanced its efficacy against S. aureus osteomyelitis, indicating that the inclusion of multiple antigens will likely enhance the efficacy of vaccines against both chronic and acute forms of staphylococcal disease. PMID:24126523

  2. Microparticulate ?-glucan vaccine conjugates phagocytized by dendritic cells activate both naïve CD4 and CD8 T cells in vitro.

    PubMed

    Berner, Vanessa K; duPre, Sally A; Redelman, Doug; Hunter, Kenneth W

    2015-01-01

    Microparticulate ?-glucan (MG) conjugated to vaccine antigen has been shown to serve as an effective adjuvant in vivo. To further study antigen presentation by MG:vaccine conjugates, bone marrow-derived dendritic cells (BMDC) were treated with MG conjugated to ovalbumin (OVA), then interacted with splenocytes from DO11.10 transgenic mice expressing an OVA peptide-specific T cell receptor. BMDC treated with MG:OVA induced significantly higher numbers of activated (CD25+CD69+) OVA-specific CD4+ T cells than BMDC treated with OVA alone. BMDC treated with MG:OVA upregulated CD86 and CD40 expression as well as MG alone, indicating that conjugation of OVA does not alter the immunostimulatory capacity of MG. Activation of CD8+ OVA-specific OT-1 cells showed that MG:OVA is also capable of enhancing cross-presentation by BMDC to CD8+ cytotoxic T cells. These results show that MG acts as an adjuvant to enhance antigen presentation by dendritic cells to naïve, antigen-specific CD4 and CD8 T cells. PMID:26549577

  3. 9 CFR 113.115 - Staphylococcus Aureus Bacterin-Toxoid.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...2014-01-01 2014-01-01 false Staphylococcus Aureus Bacterin-Toxoid. 113.115 Section...Bacterial Products § 113.115 Staphylococcus Aureus Bacterin-Toxoid. Staphylococcus Aureus Bacterin-Toxoid shall be...

  4. 9 CFR 113.115 - Staphylococcus Aureus Bacterin-Toxoid.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...2013-01-01 2013-01-01 false Staphylococcus Aureus Bacterin-Toxoid. 113.115 Section...Bacterial Products § 113.115 Staphylococcus Aureus Bacterin-Toxoid. Staphylococcus Aureus Bacterin-Toxoid shall be...

  5. pertussis vaccines that induce antitoxin immunity and that are widely used in

    E-print Network

    Read, Andrew

    pertussis vaccines that induce antitoxin immunity and that are widely used in human populations argue against these predictions. The introduction of diphtheria toxoid vaccine at the beginning with long-standing and thorough diphtheria- toxoid vaccination programmes, whereas the tox C. diphtheriae

  6. An assessment of the screening method to evaluate vaccine effectiveness: the case of 7-valent pneumococcal conjugate vaccine in the United States.

    PubMed

    Cohen, Adam L; Taylor, Thomas; Farley, Monica M; Schaffner, William; Lesher, Lindsey J; Gershman, Kenneth A; Bennett, Nancy M; Reingold, Arthur; Thomas, Ann; Baumbach, Joan; Harrison, Lee H; Petit, Susan; Beall, Bernard; Zell, Elizabeth; Moore, Matthew

    2012-01-01

    The screening method, which employs readily available data, is an inexpensive and quick means of estimating vaccine effectiveness (VE). We compared estimates of effectiveness of heptavalent pneumococcal conjugate vaccine (PCV7) against invasive pneumococcal disease (IPD) using the screening and case-control methods. Cases were children aged 19-35 months with pneumococcus isolated from normally sterile sites residing in Active Bacterial Core surveillance areas in the United States. Case-control VE was estimated for 2001-2004 by comparing the odds of vaccination among cases and community controls. Screening-method VE for 2001-2009 was estimated by comparing the proportion of cases vaccinated to National Immunization Survey-derived coverage among the general population. To evaluate the plausibility of screening-method VE findings, we estimated attack rates among vaccinated and unvaccinated persons. We identified 1,154 children with IPD. Annual population PCV7 coverage with ?1 dose increased from 38% to 97%. Case-control VE for ?1 dose was estimated as 75% against all-serotype IPD (annual range: 35-83%) and 91% for PCV7-type IPD (annual range: 65-100%). By the screening method, the overall VE was 86% for ?1 dose (annual range: -240-70%) against all-serotype IPD and 94% (annual range: 62-97%) against PCV7-type IPD. As cases of PCV7-type IPD declined during 2001-2005, estimated attack rates for all-serotype IPD among vaccinated and unvaccinated individuals became less consistent than what would be expected with the estimated effectiveness of PCV7. The screening method yields estimates of VE that are highly dependent on the time period during which it is used and the choice of outcome. The method should be used cautiously to evaluate VE of PCVs. PMID:22870248

  7. Active Surveillance for Adverse Events After a Mass Vaccination Campaign With a Group A Meningococcal Conjugate Vaccine (PsA-TT) in Mali

    PubMed Central

    Vannice, Kirsten S.; Keita, Modibo; Sow, Samba O.; Durbin, Anna P.; Omer, Saad B.; Moulton, Lawrence H.; Yaméogo, Téné M.; Zuber, Patrick L. F.; Onwuchekwa, Uma; Sacko, Massambou; Diomandé, Fabien V. K.; Halsey, Neal A.

    2015-01-01

    Background.?The monovalent meningococcal A conjugate vaccine (PsA-TT, MenAfriVac) was developed for use in the “meningitis belt” of sub-Saharan Africa. Mali was 1 of 3 countries selected for early introduction. As this is a new vaccine, postlicensure surveillance is particularly important to identify and characterize possible safety issues. Methods.?The national vaccination campaign was phased from September 2010 to November 2011. We conducted postlicensure safety surveillance for PsA-TT in 40 government clinics from southern Mali serving approximately 400 000 people 1–29 years of age. We conducted analyses with individual-level data and population-level data, and we calculated rates of adverse events using the conditional exact test, a modified vaccine cohort risk interval method, and a modified self-controlled case series method for each outcome of interest, including 18 prespecified adverse events and 18 syndromic categories. Results.?An increased rate of clinic visits for fever within 3 days after vaccination was found using multiple methods for all age groups. Although other signals were found with some methods, complete assessment of all other prespecified outcomes and syndromic categories did not reveal that PsA-TT was consistently associated with any other health problem. Conclusions.?No new safety concerns were identified in this study. These results are consistent with prelicensure data and other studies indicating that PsA-TT is safe. The approach presented could serve as a model for future active postlicensure vaccine safety monitoring associated with large-scale immunization campaigns in low-income countries. PMID:26553680

  8. Safety and immunogenicity of meningococcal ACWY CRM197-conjugate vaccine in children, adolescents and adults in Russia.

    PubMed

    Ilyina, Natalia; Kharit, Susanna; Namazova-Baranova, Leila; Asatryan, Asmik; Benashvili, Mayya; Tkhostova, Elmira; Bhusal, Chiranjiwi; Arora, Ashwani Kumar

    2014-01-01

    Neisseria meningitidis is the leading cause of bacterial invasive infections in people aged <15 years in the Russian Federation. The aim of this phase III, multicenter, open-label study was to assess the immunogenicity and safety of the quadrivalent meningococcal CRM197-conjugate vaccine MenACWY when administered to healthy Russian subjects aged 2 years and above. A total of 197 subjects were immunized with a single dose of the vaccine, and serogroup-specific serum bactericidal activity was measured pre and 1-month post-vaccination with human complement (hSBA) serum titers. Regardless of baseline serostatus, 1 month after a single dose of MenACWY-CRM197 85% (95%CI, 79-90%) of subjects showed serologic response against serogroup A, 74% (67-80%) against serogroup C, 60% (53-67%) against serogroup W, and 83% (77-88%) against serogroup Y. The percentage of subjects with hSBA titers ? 1:8 1 month after vaccination was 89% (83-93%) against serogroup A, 84% (78-89%) against serogroup C, 97% (93-99%) against serogroup W, and 88% (82-92%) against serogroup Y. Comparable results were obtained across all subjects: children (2 to 10 years), adolescents (11 to 17 years), and adults (?18 years). The MenACWY-CRM197 vaccine showed an acceptable safety profile and was well tolerated across all age groups, with no serious adverse events or deaths reported during the study. In conclusion, a single dose of meningococcal MenACWY-CRM197 vaccine is immunogenic and has an acceptable safety profile, provides a broad protection against the most frequent epidemic serogroups, and is a suitable alternative to currently available unconjugated monovalent or bivalent polysaccharide vaccines in Russia. PMID:25424958

  9. Enhanced immunogenicity of multivalent MUC1 glycopeptide antitumour vaccines based on hyperbranched polymers.

    PubMed

    Glaffig, M; Palitzsch, B; Stergiou, N; Schüll, C; Straßburger, D; Schmitt, E; Frey, H; Kunz, H

    2015-10-28

    Enhancing the immunogenicity of an antitumour vaccine still poses a major challenge. It depends upon the selected antigen and the mode of its presentation. We here describe a fully synthetic antitumour vaccine, which addresses both aspects. For the antigen, a tumour-associated MUC1 glycopeptide as B-cell epitope was synthesised and linked to the immunostimulating T-cell epitope P2 derived from tetanus toxoid. The MUC1-P2 conjugate is presented multivalently on a hyperbranched polyglycerol to the immune system. In comparison to a related vaccine of lower multivalency, this vaccine exposing more antigen structures on the hyperbranched polymer induced significantly stronger immune responses in mice and elicited IgG antibodies of distinctly higher affinity to epithelial tumour cells. PMID:26299280

  10. Antibody and Plasmablast Response to 13-Valent Pneumococcal Conjugate Vaccine in Chronic Lymphocytic Leukemia Patients – Preliminary Report

    PubMed Central

    Pasiarski, Marcin; Rolinski, Jacek; Grywalska, Ewelina; Stelmach-Goldys, Agnieszka; Korona-Glowniak, Izabela; Gozdz, Stanislaw; Hus, Iwona; Malm, Anna

    2014-01-01

    Background Chronic lymphocytic leukemia (CLL) leads to significant immune system dysfunction. The predominant clinical presentation in 50% of patients involves recurrent, often severe, infections. Infections are also the most common (60–80%) cause of deaths in CLL patients. The scope of infections varies with the clinical stage of the disease. Treatment-naive patients typically present with respiratory tract infections caused by encapsulated bacteria Streptococcus pneumoniae and Haemophilus influenzae. Since 2012, the 13-valent pneumococcal conjugate vaccine (PCV13) has been recommended in the United States and some EU countries for pneumococcal infection prevention in patients with CLL (besides the long-standing standard, 23-valent pneumococcal polysaccharide vaccine, PPV23). The aim of this study was to compare the immune response to PCV13 in 24 previously untreated CLL patients and healthy subjects. Methods Both groups were evaluated for: the levels of specific pneumococcal antibodies, the levels of IgG and IgG subclasses and selected peripheral blood lymphocyte subpopulations including the frequency of plasmablasts before and after immunization. Results Adequate response to vaccination, defined as an at least two-fold increase in specific pneumococcal antibody titers versus pre-vaccination baseline titers, was found in 58.3% of CLL patients and 100% of healthy subjects. Both the CLL group and the control group demonstrated a statistically significant increase in the IgG2 subclass levels following vaccination (P?=?0.0301). After vaccination, the frequency of plasmablasts was significantly lower (P<0.0001) in CLL patients in comparison to that in controls. Patients who responded to vaccination had lower clinical stage of CLL as well as higher total IgG, and IgG2 subclass levels. No significant vaccine-related side effects were observed. Conclusions PCV13 vaccination in CLL patients is safe and induces an effective immune response in a considerable proportion of patients. To achieve an optimal vaccination response, the administration of PCV13 is recommended as soon as possible following CLL diagnosis. PMID:25506837

  11. Estimation of Invasive Pneumococcal Disease Dynamics Parameters and the Impact of Conjugate Vaccination in

    E-print Network

    Vaccination in Australia K. L. Sutton1,2 , H. T. Banks2 , and C. Castillo-Ch´avez1 1 Department of Mathematics and mortality worldwide. Recent advances in the development of vaccines for these infections have raised of pneumococcal infection dynamics in a population with partial vaccination. The parameters obtained

  12. Stabilization of tetanus toxoid formulation containing aluminium hydroxide adjuvant against freeze-thawing.

    PubMed

    Solanki, Vipul A; Jain, Nishant K; Roy, Ipsita

    2011-07-29

    Exposure to subzero temperature leads to loss of vaccine potency. This can happen due to degradation of adjuvant surface and/or inactivation of the antigen. When adsorbed on aluminium hydroxide and subjected to freeze-thawing, tetanus toxoid was desorbed from the gel matrix and the preparation was found to lose its antigenicity. Analyses showed that the gel particles were denatured after freezing. When freeze-thawing was carried out in the presence of glucose, sorbitol and arginine, the degradation of gel particles was inhibited. A higher fraction of the protein could be retained on the gel. However, the antigenicity of these preparations was quite low. In the presence of trehalose, the protein could be partially retained on aluminium hydroxide. Being a cryoprotectant, trehalose was also able to inhibit the freezing-induced denaturation of tetanus toxoid, which resulted in retention of antigenicity of the adjuvanted toxoid. PMID:21605644

  13. A cost-effectiveness analysis of a 10-valent pneumococcal conjugate vaccine in children in six Latin American countries

    PubMed Central

    2013-01-01

    Background A recently developed 10-valent pneumococcal non-typeable H influenzae protein D-conjugate vaccine (PHiD-CV) is expected to afford protection against more than two thirds of isolates causing IPD in children in Latin America, and also against acute otitis media caused by both Spn and NTHi. The objective of this study is to assess the cost-effectiveness of PHiD-CV in comparison to non-vaccination in children under 10 years of age in Argentina, Brazil, Chile, Colombia, Mexico and Peru. Methods We used a static, deterministic, compartmental simulation model. The dosing regimen considered included three vaccine doses (at 2 months, 4 months and 6 months) and a booster dose (at 13 months) (3?+?1 schedule). Model outcomes included number of cases prevented, deaths averted, quality-adjusted life-years (QALYs) gained and costs. Discount for costs and benefits of long term sequelae was done at 3.5%, and currency reported in 2008-2009 U$S varying between countries. Results The largest effect in case prevention was observed in pneumococcal meningitis (from 27% in Peru to 47% in Colombia), neurologic sequelae after meningitis (from 38% in Peru to 65% in Brazil) and bacteremia (from 42% in Argentina to 49% in Colombia). The proportion of predicted deaths averted annually ranged from 18% in Peru to 33% in Brazil. Overall, the health benefits achieved with PHiD-CV vaccination resulted in a lower QALY loss (from 15% lower in Peru to 26% in Brazil). At a cost of USD 20 per vaccine dose, vaccination was cost-effective in all countries, from being cost saving in Chile to a maximum Incremental Cost-effectiveness Ratio of 7,088 US$ Dollars per QALY gained. Results were robust in the sensitivity analysis, and scenarios with indirect costs affected results more than those with herd immunity. Conclusions The incorporation of the 10-valent pneumococcal conjugate vaccine into routine infant immunization programs in Latin American countries could be a cost-effective strategy to improve infant population health in the region. PMID:24004943

  14. Vaccination with Haemophilus influenzae type b meningococcal protein conjugate vaccine reduces oropharyngeal carriage of Haemophilus influenzae type b among American Indian children.

    PubMed

    Takala, A K; Santosham, M; Almeido-Hill, J; Wolff, M; Newcomer, W; Reid, R; Käyhty, H; Esko, E; Mäkelä, P H

    1993-07-01

    The effect of Haemophilus influenzae type b (Hib) meningococcal protein conjugate vaccine (Hib-OMPC; Merck, Sharp & Dohme) on oropharyngeal (OP) carriage of Hib was evaluated in Navajo and Apache Indian children, who are known to be at high risk for invasive Hib disease. We obtained 1423 OP swabs at well child visits from 1321 children 3 months to 4 years of age: 293 of the swabs were obtained from children before the administration of any Hib-OMPC; 1119 were taken after the primary vaccination series; and 11 after the booster dose. Swabs were tested for the presence of Hib capsular polysaccharide antigen by enzyme-linked immunosorbent assay. Forty of 1423 swabs were positive for Hib. Among the 40 positive swabs 5 (13%) were obtained from children who had received Hib-OMPC vaccine appropriate for age at swabbing, compared with 500 of 1383 (36%) of negative swabs. Children who were OP carriers of Hib were older than noncarriers (mean age, 13 and 9 months, respectively) and a greater proportion of carriers (48%) had symptoms of respiratory infection at the time of swabbing than noncarriers (30%). These variables were significantly related to increased risk of OP carriage of Hib when incorporated jointly in a logistic regression model: not vaccinated according to age (odds ratio 2.7, 95% confidence interval 1.00 to 7.05); increase of age in months (odds ratio 1.1, 95% confidence interval 1.02-1.10); and respiratory infection symptoms present (odds ratio 2.0, 95% confidence interval 1.06-3.77). Thus besides preventing invasive Hib disease, appropriate vaccination with Hib-OMPC appears to reduce OP carriage of Hib. PMID:8346004

  15. Effect of the 13-valent Pneumococcal Conjugate Vaccine on Nasopharyngeal Colonization by Streptococcus pneumoniae — Alaska, 2008–2012

    PubMed Central

    Gounder, Prabhu P.; Bruce, Michael G.; Bruden, Dana JT.; Singleton, Rosalyn J.; Rudolph, Karen; Hurlburt, Debby A.; Hennessy, Thomas W.; Wenger, Jay

    2015-01-01

    Background In 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) replaced a 7-valent vaccine (PCV7) that contained all PCV7 serotypes plus 6 additional serotypes (PCV6+). We conducted annual surveys from 2008–2012 to determine the effect of PCV13 on colonization by pneumococcal serotypes. Methods We obtained nasopharyngeal swabs for pneumococcal identification and serotyping from residents of all ages at 8 rural villages and children age <60 months at 2 urban clinics. We conducted interviews/medical records review for all participants. Results A total of 18,207 nasopharyngeal swabs (rural=16,098; urban=2,109) were collected. From 2008–2012, 84% of rural and 90% of urban children age <5 years were age-appropriately vaccinated with a PCV. Overall pneumococcal colonization prevalence remained stable among rural (66%) and urban (35%) children age <5 years, and adults age ?18 years (14%). Colonization by PCV6+ serotypes declined significantly among rural children age <5 years, urban children age <5, and adults age ?18 over the course of the study (25%–5%, 22%–9%, 22%–6%, respectively). Conclusions PCV13 was rapidly introduced into the Alaska childhood immunization schedule and reduced colonization by PCV6+ serotypes among children. Unvaccinated adults also experienced comparable reductions in vaccine serotype colonization indicating substantial indirect protection from PCV13. PMID:24273178

  16. A bivalent conjugate vaccine containing PspA families 1 and 2 has the potential to protect against a wide range of Streptococcus pneumoniae strains and Salmonella Typhi.

    PubMed

    Kothari, Neha; Kothari, Sudeep; Choi, Young Joo; Dey, Ayan; Briles, David E; Rhee, Dong Kwon; Carbis, Rodney

    2015-02-01

    Previously we showed that conjugation of pneumococcal surface protein A (PspA) to Vi capsular polysaccharide from Salmonella Typhi enhanced the anti-PspA response without the need to add adjuvant. In the current study conjugates consisting of the ? helical regions of PspA families 1 or 2 bound to Vi were used to vaccinate mice to test their ability to protect against a lethal intravenous challenge of a range of various strains of Streptococcus pneumoniae. Conjugate vaccine containing PspA family 1 provided good protection from PspA family 1 challenge strains but offered very little protection against PspA family 2 challenge strains. Similarly, PspA family 2 conjugates provided good protection from PspA family 2 challenge strains and poor protection against PspA family 1 challenge strains. This observation was supported by the low levels of cross-reactivity of PspA antibodies seen in ELISA plates coated with the heterologous PspA family. Cytokine profiles showed a mixed Th1/Th2 response to Vi and the Vi-PspA conjugates. IgG subclass analysis of the anti-Vi response showed a shift from predominantly IgG2a/3 to IgG1 after conjugation to PspA was consistent with other polysaccharide conjugate vaccines. The results demonstrate that conjugation of the ? helical region of PspA to Vi enhances its capacity to induce a protective immune response and that a vaccine based on the ? helical region of PspA should contain PspA from both families 1 and 2 to achieve broad cross-protection. PMID:25545593

  17. Systematic Review of the Effect of Pneumococcal Conjugate Vaccine Dosing Schedules on Immunogenicity

    PubMed Central

    2014-01-01

    Background: Despite the breadth of studies demonstrating benefits of pneumococcal conjugate vaccine (PCV), uncertainty remains regarding the optimal PCV dosing schedule in infants. Methods: We conducted a systematic literature review of PCV immunogenicity published from 1994 to 2010 (supplemented post hoc with studies from 2011). Studies included for analysis evaluated ?2 doses of 7-valent or higher product (excluding Aventis-Pasteur PCV11) administered to nonhigh-risk infants ?6 months of age. Impact of PCV schedule on geometric mean antibody concentration (GMC) and proportion of subjects over 0.35 mcg/mL were assessed at various time points; the GMC 1 month postdose 3 (for various dosing regimens) for serotypes 1, 5, 6B, 14, 19F and 23F was assessed in detail using random effects linear regression, adjusted for product, acellular diphtheria-tetanus-pertussis/whole-cell diphtheria- tetanus-pertussis coadministration, laboratory method, age at first dose and geographic region. Results: From 61 studies, we evaluated 13 two-dose (2+0) and 65 three-dose primary schedules (3+0) without a booster dose, 11 “2+1” (2 primary plus booster) and 42 “3+1” schedules. The GMC after the primary series was higher following 3-dose schedules compared with 2-dose schedules for all serotypes except for serotype 1. Pre- and postbooster GMCs were generally similar regardless of whether 2 or 3 primary doses were given. GMCs were significantly higher for all serotypes when dose 3 was administered in the second year (2+1) compared with ?6 months of age (3+0). Conclusions: While giving the third dose in the second year of life produces a higher antibody response than when given as part of the primary series in the first 6 months, the lower GMC between the 2-dose primary series and booster may result in less disease protection for infants in that interval than those who completed the 3-dose primary series. Theoretical advantages of higher antibodies induced by giving the third dose in the second year of life, such as increased protection against serotype 1 disease, longer duration of protection or more rapid induction of herd effects, need to be evaluated in practice. PMID:24336054

  18. Birth control vaccines: the progress continues.

    PubMed

    1992-01-01

    During 1986-1988, the WHO Special Programme of Research, Development and Research Training in Human Reproduction used the diphtheria toxoid as a carrier for a fragment of the human chorionic gonadotropin (hCG) molecule (a conjugate immunogen) and an immunostimulant in a phase I clinical trial of this prototype antifertility vaccine in sterilized women. Between 1990 and 1991, it conducted teratology studies in rats and rabbits to determine whether the vaccine causes fetal abnormalities. The vaccine did not adversely affect either the animals or their fetuses. Clinical trials of the vaccine's effectiveness (phase II trials) are scheduled for 1992. At least 2 injections several weeks apart, are needed to produce an anti-hCG immune response which is only effective for 3-6 months, however. So the same components of the original vaccine were placed in a polymer to deliver the vaccine slowly over a prolonged and predetermined time frame. WHO hoped that this advanced vaccine would raise effective immunity levels long enough to last for at least 1 year after 1 injection. WHO is conducting dose-response and toxicity studies of this prototype vaccine in rabbits and baboons to identify the optimal dose which would elicit an effective immunity level over a desired period of time and would be safe for testing in humans. WHO hopes to begin a phase I clinical trial with this advanced anti-hCG vaccine in late 1992. WHO anticipates that the preclinical and clinical trials will reveal a need for further modifications and improvements. WHO is supported multicenter research on antitrophoblast vaccines which target membrane cells of the preimplantation embryo since 1985. It uses monoclonal antibodies (MABs) and recombinant DNA technology to identify and isolate surface molecules. So far this research has tested 15,000 MABs but is centering on 9 MAbs. A study in baboons showed that 1 MAB reduced fertility, even though researchers could only use minute amounts of the protein in the injection. PMID:12286012

  19. Antibiotic susceptibility rates of invasive pneumococci before and after the introduction of pneumococcal conjugate vaccination in Germany.

    PubMed

    Imöhl, Matthias; Reinert, Ralf René; van der Linden, Mark

    2015-10-01

    Continuous nationwide surveillance of invasive pneumococcal disease (IPD) was conducted in Germany. A total of 22,208 isolates from invasive pneumococcal disease were collected between July 1, 1992 and June 30, 2013. The present study was conducted to analyze changes in antimicrobial susceptibility and pneumococcal vaccine coverage after the introduction of pneumococcal conjugate vaccination in Germany. Most of the isolates originated from adults ?16 years (82.5%), while 17.5% were obtained from children <16 years. Penicillin resistance was observed in 7.2% of meningitis cases both among children and adults during the entire study period. In the post-PCV13 period, the resistance rate was 11.3% in children and 10.0% in adults, which is higher than in the pre-PCV7 and post-PCV7 periods. In the non-meningitis group, an overall penicillin nonsusceptibility rate (intermediate resistance and resistance) of 0.5% was detected both among children and adults. Nonsusceptibility rates among children were 6.3% (pre-PCV7), 7.6% (post-PCV7) and 9.0% (post-PCV13). The corresponding nonsusceptibility rates among adults were 4.4%, 6.0% and 7.9%, respectively. Concerning cefotaxime, in meningitis cases 0.8% of all isolates were intermediate and 0.5% resistant among children, while among adults, 0.9% were intermediate and 0.2% resistant. In non meningitis cases, cefotaxime nonsusceptibility rates were 0.5% in children and 0.3% in adults. Macrolide nonsusceptibility rates were lower in the post-PCV13 period (children 8.2%; adults 8.8%) than in the post-PCV7 period (children 17.3%; adults 13.0%) and the pre-PCV7 period (children 24.8%; adults 13.3%). In the pre-PCV7 period, macrolide resistance was mainly caused by M-phenotype clones carrying the mefA gene. In the post-PCV7/13 period, ermB (MLSb-phenotype) was the dominant resistance marker. Overall nonsusceptibility rates were 5.5% for clindamycin (intermediate 0.3%, resistant 5.2%), 0.7% for levofloxacin (intermediate 0.4%, resistant 0.3%), 8.5% for tetracycline (intermediate 0.6%, resistant 7.9%) and 11.0% for trimethoprim-sulfamethoxazole (SXT) (intermediate 5.7%, resistant 5.3%). In summary, childhood pneumococcal conjugate vaccination has had a strong effect on the pneumococcal population in Germany, both among vaccinated children as well as among non-vaccinated children and adults. Serotypes included in the pneumococcal conjugate vaccines have strongly diminished, while some non-vaccine serotypes have gained importance, particularly with respect to antibiotic resistance. However, concerning antibiotic non-susceptibility the most outstanding change over the years is the decline in macrolide resistance, especially among children. PMID:26324014

  20. Impact of More Than a Decade of Pneumococcal Conjugate Vaccine Use on Carriage and Invasive Potential in Native American Communities

    PubMed Central

    Scott, Jennifer R.; Millar, Eugene V.; Lipsitch, Marc; Moulton, Lawrence H.; Weatherholtz, Robert; Perilla, Mindy J.; Jackson, Delois M.; Beall, Bernard; Craig, Mariddie J.; Reid, Raymond; Santosham, Mathuram

    2012-01-01

    Background.?We assessed the impact of 12 years of pneumococcal conjugate vaccine (PCV7) use on pneumococcal nasopharyngeal carriage and serotype-specific invasive disease potential among Native Americans. Methods.?Families were enrolled in a carriage study from 2006 to 2008; nasopharyngeal specimens and risk factor information were collected monthly for 7 visits. Pneumococcal carriage prevalence was compared with that before (1998–2000) and during (2001–2002) PCV7 introduction. We compared invasive disease incidence and carriage prevalence before and after PCV7 introduction to estimate changes in serotype-specific invasive potential. Results.?We enrolled 1077 subjects from 302 households. There was an absolute reduction in carriage prevalence of 8.0% (95% confidence interval [CI], 4.5%–11.4%) in children aged <5 years and 3.1% (95% CI, 1.1%–5.1%) in adults. In children aged <5 years, vaccine-serotype carriage prevalence decreased by 22.8% (95% CI, 20.1%–25.3%), and nonvaccine serotype (NVT) increased by 15.9% (95% CI, 12.4%–19.3%). No significant change was detected in serotype-specific invasive potential after PCV7 introduction. Conclusions.?Pneumococcal carriage prevalence decreased in all ages since PCV7 introduction; vaccine-serotype carriage has been nearly eliminated, whereas the prevalence of NVT carriage has increased. The increase in the NVT invasive disease rate seems to be proportional to the increase in colonization prevalence. PMID:22128315

  1. Introduction and Rollout of a New Group A Meningococcal Conjugate Vaccine (PsA-TT) in African Meningitis Belt Countries, 2010–2014

    PubMed Central

    Djingarey, Mamoudou H.; Diomandé, Fabien V. K.; Barry, Rodrigue; Kandolo, Denis; Shirehwa, Florence; Lingani, Clement; Novak, Ryan T.; Tevi-Benissan, Carol; Perea, William; Preziosi, Marie-Pierre; LaForce, F. Marc

    2015-01-01

    Background.?A group A meningococcal conjugate vaccine (PsA-TT) was developed specifically for the African “meningitis belt” and was prequalified by the World Health Organization (WHO) in June 2010. The vaccine was first used widely in Burkina Faso, Mali, and Niger in December 2010 with great success. The remaining 23 meningitis belt countries wished to use this new vaccine. Methods.?With the help of African countries, WHO developed a prioritization scheme and used or adapted existing immunization guidelines to mount PsA-TT vaccination campaigns. Vaccine requirements were harmonized with the Serum Institute of India, Ltd. Results.?Burkina Faso was the first country to fully immunize its 1- to 29-year-old population in December 2010. Over the next 4 years, vaccine coverage was extended to 217 million Africans living in 15 meningitis belt countries. Conclusions.?The new group A meningococcal conjugate vaccine was well received, with country coverage rates ranging from 85% to 95%. The rollout proceeded smoothly because countries at highest risk were immunized first while attention was paid to geographic contiguity to maximize herd protection. Community participation was exemplary. PMID:26553672

  2. The impact of new technologies on vaccines.

    PubMed

    Talwar, G P; Diwan, M; Razvi, F; Malhotra, R

    1999-01-01

    Vast changes are taking place in vaccinology consequent to the introduction of new technologies. Amongst the vaccines included in the Expanded Programme of Immunization (EPI), the pertussis vaccine has been replaced by acellular purified fractions devoid of side-effects. Non-pathogenic but immunogenic mutants of tetanus and diptheria toxins are likely to replace the toxoids. An effective vaccine against hepatitis B prepared by recombinant technology is in large-scale use. Conjugated vaccines against Haemophilus influenzae b, S. pneumococcus and meningococcus are now available, as also vaccines against mumps, rubella and measles. Combination vaccines have been devised to limit the number of injections. Vaccine delivery systems have been developed to deliver multiple doses of the vaccine at a single contact point. A genetically-engineered oral vaccine for typhoid imparts better and longer duration of immunity. Oral vaccines for cholera and other enteric infections are under clinical trials. The nose as a route for immunization is showing promise for mucosal immunity and for anti-inflammatory experimental vaccines against multiple sclerosis and insulin-dependent diabetes mellitus. The range of vaccines has expanded to include pathogens resident in the body such as Helicobacter pylori (duodenal ulcer), S. mutans (dental caries), and human papilloma virus (carcinoma of the cervix). An important progress is the recognition that DNA alone can constitute the vaccines, inducing both humoral and cell-mediated immune responses. A large number of DNA vaccines have been made and shown interesting results in experimental animals. Live recombinant vaccines against rabies and rinderpest have proven to be highly effective for controlling these infections in the field, and those for AIDS are under clinical trial. Potent adjuvants have added to the efficacy of the vaccines. New technologies have emerged to 'humanize' mouse monoclonals by genetic engineering and express these efficiently in plants. These recombinant antibodies are opening out an era of highly specific and safe therapeutic interventions. Human recombinant antibodies would be invaluable for treating patients with terminal tetanus and rabies. Antibodies are already in use for treatment of cancer, rheumatoid arthritis and allergies. An advantage of preformed antibodies directed at a defined target and given in adequate amounts is the certainty of efficacy in every recipient, in contrast to vaccines, where the quality and quantum of immune response varies from individual to individual. PMID:10732430

  3. Complex cytokine responses to hepatitis B surface antigen and tetanus toxoid in responders, nonresponders and subjects naive to

    E-print Network

    Alper, Chester A.

    Complex cytokine responses to hepatitis B surface antigen and tetanus toxoid in responders, nonresponders and subjects naive to hepatitis B surface antigen Charles E. Larsena, c , Jianhua Xua, e , Susan; accepted 23 February 2000 Abstract Some human subjects vaccinated with hepatitis B surface antigen (HBs

  4. Pneumonia hospitalizations among young children before and after introduction of pneumococcal conjugate vaccine--United States, 1997-2006.

    PubMed

    2009-01-16

    Streptococcus pneumoniae is the leading bacterial cause of community-acquired pneumonia hospitalizations and an important cause of bacteremia and meningitis, especially among young children and older adults. A 7-valent pneumococcal conjugate vaccine (PCV7) was licensed and the Advisory Committee on Immunization Practices formulated recommendations for its use in infants and children in February 2000. Vaccination coverage rapidly increased during the second half of 2000, in part through funding by CDC's Vaccines for Children program. Subsequently, active population- and laboratory-based surveillance demonstrated substantial reductions in invasive pneumococcal disease (IPD) among children and adults. In addition, decreases in hospitalizations and ambulatory-care visits for all-cause pneumonia also were reported. To gauge whether the effects of PCV7 on reducing pneumonia continue, CDC is monitoring pneumonia hospitalizations by using data from the Nationwide Inpatient Sample. This report provides an update for 2005 and 2006, the most recent years for which information is available. In 2005 and 2006, the incidence rates for all-cause pneumonia hospitalizations among children aged <2 years were 9.1 per 1,000 and 8.1 per 1,000, respectively. In 2006, the rate for all-cause pneumonia among children aged <2 years was approximately 35% lower than during 1997--1999. Most of this decrease occurred soon after the vaccine was licensed in 2000, and the rates have remained relatively stable since then. The rate for all-cause pneumonia among children aged 2--4 years did not change after PCV7 licensure and has remained stable. Continued monitoring of pneumonia-related hospitalizations among children is needed to track the effects of pneumococcal immunization programs. PMID:19145219

  5. Vaccinations

    MedlinePLUS

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

  6. The Diversity of Meningococcal Carriage Across the African Meningitis Belt and the Impact of Vaccination With a Group A Meningococcal Conjugate Vaccine

    PubMed Central

    2015-01-01

    Background.?Study of meningococcal carriage is essential to understanding the epidemiology of Neisseria meningitidis infection. Methods.?Twenty cross-sectional carriage surveys were conducted in 7 countries in the African meningitis belt; 5 surveys were conducted after introduction of a new serogroup A meningococcal conjugate vaccine (MenAfriVac). Pharyngeal swab specimens were collected, and Neisseria species were identified by microbiological and molecular techniques. Results.?A total of 1687 of 48 490 participants (3.4%; 95% confidence interval [CI], 3.2%–3.6%) carried meningococci. Carriage was more frequent in individuals aged 5–14 years, relative to those aged 15–29 years (adjusted odds ratio [OR], 1.41; 95% CI, 1.25–1.60); in males, relative to females (adjusted OR, 1.17; 95% CI, 1.10–1.24); in individuals in rural areas, relative to those in urban areas (adjusted OR, 1.44; 95% CI, 1.28–1.63); and in the dry season, relative to the rainy season (adjusted OR, 1.54; 95% CI, 1.37–1.75). Forty-eight percent of isolates had genes encoding disease-associated polysaccharide capsules; genogroup W predominated, and genogroup A was rare. Strain diversity was lower in countries in the center of the meningitis belt than in Senegal or Ethiopia. The prevalence of genogroup A fell from 0.7% to 0.02% in Chad following mass vaccination with MenAfriVac. Conclusions.?The prevalence of meningococcal carriage in the African meningitis belt is lower than in industrialized countries and is very diverse and dynamic, even in the absence of vaccination. PMID:25858956

  7. Depressive symptoms and immune response to meningococcal conjugate vaccine in early adolescence.

    PubMed

    O'Connor, Thomas G; Moynihan, Jan A; Wyman, Peter A; Carnahan, Jennifer; Lofthus, Gerry; Quataert, Sally A; Bowman, Melissa; Caserta, Mary T

    2014-11-01

    Research findings in psychoneuroimmunology document reliable, bidirectional linkages among psychological processes, the nervous system, and the immune system. However, available data are based almost entirely on animal and adult human studies; the application to children and adolescents is uncertain. We capitalized on the experimental leverage provided by a routine vaccination to examine the link between mood symptoms and the immune response to a vaccine challenge in early adolescence. One hundred twenty-six 11-year-olds for whom vaccine response data were available were assessed at prevaccination and 4 weeks, 3 months, and 6 months following vaccination; self-report ratings of depression and anxiety as well as measures of psychosocial and somatic risk were assessed prior to vaccine response. Analyses indicated that children's internalizing mood symptoms were associated with elevated and persistently higher antibody responses, with evidence extending to two of the four serogroups. The associations remained after controlling for multiple possible confounders (social class, body mass index, sleep, psychosocial risk, and pubertal status). The observed enhanced vaccine response associated with depressive and anxious symptoms in early adolescence may reflect an important developmental difference in immune system-brain interplay between adults and children, and it underscores the need for further developmental studies of psychoneuroimmunology. PMID:25422979

  8. Modulation of immune response to group C meningococcal conjugate vaccine given intranasally to mice together with the LTK63 mucosal adjuvant and the trimethyl chitosan delivery system.

    PubMed

    Baudner, Barbara C; Morandi, Maurizio; Giuliani, Marzia M; Verhoef, J Coos; Junginger, Hans E; Costantino, Paolo; Rappuoli, Rino; Del Giudice, Giuseppe

    2004-03-01

    Previous work had shown that the immunogenicity of conjugate vaccine against group C meningococci (CRM-MenC) is enhanced when it is delivered intranasally (inl) with mucosal adjuvants, such as mutants of the Escherichia coli enterotoxin (LT), and with delivery systems such as chitosan derivatives. We show, in mice, that the concomitant use of limiting doses of the fully nontoxic LTK63 mutant as a mucosal adjuvant and of the trimethyl derivative of chitosan as a delivery system allows the reduction of each of the components for the induction of antibody and bactericidal responses to CRM-MenC conjugate vaccine delivered inl at titers similar to or higher than those induced by parenteral immunization. These data could affect the design of efficacious mucosal vaccines and their safety. PMID:14976599

  9. Cost-effectiveness of a 3-dose pneumococcal conjugate vaccine program in the province of Quebec, Canada.

    PubMed

    Poirier, Béatrice; De Wals, Philippe; Petit, Geneviève; Erickson, Lonny J; Pépin, Jacques

    2009-11-23

    In the province of Quebec, Canada, the pneumococcal 7-valent conjugate vaccine (PCV-7) was licensed in 2001 and a publicly funded program was implemented in 2004, recommending 3 doses for healthy children. An economic analysis was performed both from a health care and societal perspective. Outcomes possibly prevented by PCV-7 and observed in 2006-2007 were compared to expected frequencies based on rates measured before PCV-7 use. Annual program costs were close to $21M for the health system and $23M for society. Approximately 20,000 infections were prevented annually and estimated economic benefits were $5M for the health system and $23M for society, using a 3% per annum discounting rate. The incremental cost-effectiveness ratio was $18,000 per QALY gained for the health system and the program was close to the break-even threshold in a societal perspective. PMID:19786137

  10. Economic evaluation of vaccination programme of 13-valent pneumococcal conjugate vaccine to the birth cohort in Japan.

    PubMed

    Hoshi, Shu-ling; Kondo, Masahide; Okubo, Ichiro

    2013-06-01

    Japan is now preparing to incorporate PCV-7 into the national childhood immunisation programme. Our recently published economic evaluation of using PCV-7 to the birth cohort suggests that the cost to gain one QALY is lower than the WHO's cost-effectiveness criterion for intervention. However, many countries have started to introduce PCV-13 into their national immunisation schedule replacing PCV-7 for preventing pneumococcal diseases among young children. These raise the need to appraise the 'value for money' of replacing PCV-7 with PCV-13 vaccination programme in Japan. We conducted a cost-effectiveness analysis with Markov model and calculated incremental cost effectiveness ratios (ICERs). Our base-case analyses, which assumed both PCVs have no net indirect effect and set the cost of PCV-7/PCV-13 per shot at ¥10,000 (US$125)/¥13,000 (US$163). The results show that in Base-case A (assumed PCV-13 has no additional protection against AOM compared to PCV-7), replacing PCV-7 with PCV-13 will cost ¥37,722,901 (US$471,536) or ¥35,584,455 (US$444,850) per QALY when the caregiver's productivity loss is not included or is included, respectively. While in Base-case B (assumed PCV-13 has additional protection against AOM compared to PCV-7), ¥343,830 (US$4298) per QALY or more QALY is gained by saving money without or with caregiver's productivity loss, respectively. We also find that, in Base-case B if cost per PCV-13 shot is equal to or less than that ¥17,000, then a PCV-13 vaccination programme offered to the birth cohort in Japan is likely to be a socially acceptable option compared to the current PCV-7 vaccination programme. Furthermore, if cost per PCV-13 shot is equal to or less than ¥12,000, replacing PCV-7 with PCV-13 will save money and gain more QALYs. While in Base-case A, the replacement can only be socially acceptable if cost per PCV-13 shot is equal to or less than ¥11,000. PMID:23588088

  11. Nasopharyngeal flora in children with acute otitis media before and after implementation of 7 valent pneumococcal conjugate vaccine in France

    PubMed Central

    2012-01-01

    Background Several studies have investigated the impact of 7-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal (Sp) and staphylococcal (Sa) nasopharyngeal (NP) carriage. Few have investigated the impact on Haemophilus influenzae (Hi) and Moraxella catarrhalis (Mc) carriage. We aimed to compare the NP carriage rates in young children with acute otitis media (AOM) before and after PCV7 implementation in France. Methods Prior to PCV7 implementation, we performed 4 successive randomized trials with NP samples. These studies compared several antibiotic regimens for treating AOM in young children (6 to 30 months). After PCV7 implementation, to assess the impact of the vaccination program on NP flora, young children with AOM were enrolled in a prospective surveillance study. In each study, we obtained an NP sample to analyze the carriage rates of Sp, Hi, Mc and Sa and the factors influencing the carriage. Standardized history and physical examination findings were recorded; the methods used for NP swabs (sampling and cultures) were the same in all studies. Results We enrolled 4,405 children (mean age 13.9 months, median 12.8). Among the 2,598 children enrolled after PCV7 implementation, 98.3% were vaccinated with PCV7. In comparing the pre- and post-PCV7 periods, we found a slight but non-significant decrease in carriage rates of pneumococcus (AOR = 0.85 [0.69;1.05]), H. influenzae (AOR = 0.89 [0.73;1.09]) and S. aureus (AOR = 0.92 [0.70;1.19]). By contrast, the carriage rate of M. catarrhalis increased slightly but not significantly between the 2 periods (AOR = 1.08 [0.95;1.2]). Among Sp carriers, the proportion of PCV7 vaccine types decreased from 66.6% to 10.7% (P < 0.001), penicillin intermediate-resistant strains increased from 30.3% to 43.4% (P < 0.001), and penicillin-resistant strains decreased greatly from 22.8% to 3.8% (P < 0.001). The proportion of Hi ß-lactamase-producing strains decreased from 38.6% to 17.1% (P < 0.001). Conclusion The carriage rates of otopathogen species (Sp, Hi, Mc) and Sa did not significantly change in children with AOM after PCV7 implementation in France. However, we observed significant changes in carriage rates of PCV7 vaccine serotypes and penicillin non-susceptible Sp. PMID:22397629

  12. Invasive and noninvasive Streptococcus pneumoniae capsule and surface protein diversity following the use of a conjugate vaccine.

    PubMed

    Croney, Christina M; Nahm, Moon H; Juhn, Steven K; Briles, David E; Crain, Marilyn J

    2013-11-01

    The 13-valent pneumococcal conjugate vaccine (PCV13) was introduced in the United States in 2010 for the prevention of invasive pneumococcal disease (IPD) and otitis media. While many studies have reported its potential efficacy for IPD, not much is known about the epidemiology of noninvasive disease following its introduction. We characterized the capsular types and surface protein genes of noninvasive pediatric pneumococcal isolates collected between 2002 and 2010 (n = 1,058) at Children's of Alabama following the introduction of PCV7 and tested a subset of noninvasive and previously characterized IPD isolates for the presence of the pspA, pspC, and rrgC genes, which encode protection-eliciting proteins. PCV7 serotypes had dramatically decreased by 2010 (P < 0.0001), and only 50% of all noninvasive infections were caused by the PCV13 capsular serotypes. Serotype 19A accounted for 32% of the noninvasive isolates, followed by serotypes 35B (9%), 19F (7%), and 6C (6%). After 7 years of PCV7 usage, there were no changes in the frequencies of the pspA or pspC genes; 96% of the strains were positive for family 1 or 2 pspA genes, and 81% were also positive for pspC. Unexpectedly, more noninvasive than invasive strains were positive for rrgC (P < 0.0001), and the proportion of rrgC-positive strains in 2008 to 2010 was greater than that in 2002 to 2008 (IPD, P < 0.02; noninvasive, P < 0.001). Serotypes 19F, 19A, and 35B were more frequently rrgC positive (P < 0.005) than other serotypes. A vaccine containing antigens, such as PspA, PspC, and/or RrgC, can provide coverage against most non-PCV13-type pneumococci. Continued surveillance is critical for optimal future vaccine development. PMID:24006139

  13. Stimulation of immune systems by conjugated polymers and their potential as an alternative vaccine adjuvant

    NASA Astrophysics Data System (ADS)

    Gong, Hua; Xiang, Jian; Xu, Ligeng; Song, Xuejiao; Dong, Ziliang; Peng, Rui; Liu, Zhuang

    2015-11-01

    Recently, conjugated polymers have been widely explored in the field of nanomedicine. Careful evaluations of their biological effects are thus urgently needed. Hereby, we systematically evaluated the biological effects of different types of conjugated polymers on macrophages and dendritic cells (DCs), which play critical roles in the innate and adaptive immune systems, respectively. While naked poly-(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS) exhibits a high level of cytotoxicity, polyethylene glycol (PEG) modified PEDOT:PSS (PEDOT:PSS-PEG) shows greatly reduced toxicity to various types of cells. To our surprise, PEGylation of PEDOT:PSS could obviously enhance the cellular uptake of these nanoparticles, leading to subsequent immune stimulations of both macrophages and DCs. In contrast, another type of conjugated polymer, polypyrrole (PPy), is found to be an inert material with neither significant cytotoxicity nor noticeable immune-stimulation activity. Interestingly, utilizing ovalbumin (OVA) as a model antigen, it is further uncovered in our ex vivo experiment that PEDOT:PSS-PEG may serve as an adjuvant to greatly enhance the immunogenicity of OVA upon simple mixing. Our study on the one hand suggests the promise of developing novel nano-adjuvants based on conjugated polymers, and on the other hand highlights the importance of careful evaluations of the impacts of any new nanomaterials developed for nanomedicine on the immune systems.Recently, conjugated polymers have been widely explored in the field of nanomedicine. Careful evaluations of their biological effects are thus urgently needed. Hereby, we systematically evaluated the biological effects of different types of conjugated polymers on macrophages and dendritic cells (DCs), which play critical roles in the innate and adaptive immune systems, respectively. While naked poly-(3,4-ethylenedioxythiophene):poly(4-styrenesulfonate) (PEDOT:PSS) exhibits a high level of cytotoxicity, polyethylene glycol (PEG) modified PEDOT:PSS (PEDOT:PSS-PEG) shows greatly reduced toxicity to various types of cells. To our surprise, PEGylation of PEDOT:PSS could obviously enhance the cellular uptake of these nanoparticles, leading to subsequent immune stimulations of both macrophages and DCs. In contrast, another type of conjugated polymer, polypyrrole (PPy), is found to be an inert material with neither significant cytotoxicity nor noticeable immune-stimulation activity. Interestingly, utilizing ovalbumin (OVA) as a model antigen, it is further uncovered in our ex vivo experiment that PEDOT:PSS-PEG may serve as an adjuvant to greatly enhance the immunogenicity of OVA upon simple mixing. Our study on the one hand suggests the promise of developing novel nano-adjuvants based on conjugated polymers, and on the other hand highlights the importance of careful evaluations of the impacts of any new nanomaterials developed for nanomedicine on the immune systems. Electronic supplementary information (ESI) available. See DOI: 10.1039/c5nr06081h

  14. Early trends in invasive pneumococcal disease in children following the introduction of 13-valent pneumococcal conjugate vaccine: results from eight years of active surveillance in a Mexican hospital

    PubMed Central

    Rivas-Landeros, R.M.; Volker-Soberanes, M.L.

    2014-01-01

    Background: In May 2012, universal vaccination with the 13-valent pneumococcal conjugate vaccine (PCV-13) was introduced for all children in the Tijuana region of Mexico, with a coverage of 80%. Method: Between October 2005 and September 2013 active surveillance was undertaken for all invasive pneumococcal diseases (IPDs) in children admitted to the Tijuana General Hospital. Results: Following PCV-13 implementation, there was a 75% reduction in overall IPD, and no cases of serotype 19A, pneumococcal meningitis, and pneumococcal-associated deaths. Conclusions: These results are the first to show the effectiveness of PCV-13 in Mexico. PMID:25364508

  15. Serotype-Specific Changes in Invasive Pneumococcal Disease after Pneumococcal Conjugate Vaccine Introduction: A Pooled Analysis of Multiple Surveillance Sites

    PubMed Central

    Feikin, Daniel R.; Kagucia, Eunice W.; Loo, Jennifer D.; Link-Gelles, Ruth; Puhan, Milo A.; Cherian, Thomas; Levine, Orin S.; Whitney, Cynthia G.; O’Brien, Katherine L.; Moore, Matthew R.

    2013-01-01

    Background Vaccine-serotype (VT) invasive pneumococcal disease (IPD) rates declined substantially following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) into national immunization programs. Increases in non-vaccine-serotype (NVT) IPD rates occurred in some sites, presumably representing serotype replacement. We used a standardized approach to describe serotype-specific IPD changes among multiple sites after PCV7 introduction. Methods and Findings Of 32 IPD surveillance datasets received, we identified 21 eligible databases with rate data ?2 years before and ?1 year after PCV7 introduction. Expected annual rates of IPD absent PCV7 introduction were estimated by extrapolation using either Poisson regression modeling of pre-PCV7 rates or averaging pre-PCV7 rates. To estimate whether changes in rates had occurred following PCV7 introduction, we calculated site specific rate ratios by dividing observed by expected IPD rates for each post-PCV7 year. We calculated summary rate ratios (RRs) using random effects meta-analysis. For children <5 years old, overall IPD decreased by year 1 post-PCV7 (RR 0·55, 95% CI 0·46–0·65) and remained relatively stable through year 7 (RR 0·49, 95% CI 0·35–0·68). Point estimates for VT IPD decreased annually through year 7 (RR 0·03, 95% CI 0·01–0·10), while NVT IPD increased (year 7 RR 2·81, 95% CI 2·12–3·71). Among adults, decreases in overall IPD also occurred but were smaller and more variable by site than among children. At year 7 after introduction, significant reductions were observed (18–49 year-olds [RR 0·52, 95% CI 0·29–0·91], 50–64 year-olds [RR 0·84, 95% CI 0·77–0·93], and ?65 year-olds [RR 0·74, 95% CI 0·58–0·95]). Conclusions Consistent and significant decreases in both overall and VT IPD in children occurred quickly and were sustained for 7 years after PCV7 introduction, supporting use of PCVs. Increases in NVT IPD occurred in most sites, with variable magnitude. These findings may not represent the experience in low-income countries or the effects after introduction of higher valency PCVs. High-quality, population-based surveillance of serotype-specific IPD rates is needed to monitor vaccine impact as more countries, including low-income countries, introduce PCVs and as higher valency PCVs are used. Please see later in the article for the Editors' Summary PMID:24086113

  16. Nanoparticle and polysaccharide conjugate: a potential candidate vaccine to improve immunological stimuli.

    PubMed

    Devi, K Sanjana P; Sahoo, Banalata; Behera, Birendra; Maiti, Tapas K

    2015-01-01

    Active polysaccharides isolated from various fungal sources have been implicated to stimulate immune response against various pathogens as well as self anomalies such as cancer. Therefore, the nuanced approach presented in our work was to blend polysaccharides derived from Pleurotus ostreatus with biocompatible ferrite nanoparticles and thereafter investigate the enhanced immune functionality of the polysaccharide-nanoparticle composite. A Schiff base reductive amination reaction occurred between the aldehyde group of the polysaccharide and the amine group of the nanoparticles in the presence of a strong reducing agent such as sodium cyanoborohydride to form a stable amide bond between the two conjugating molecules. The multifaceted conjugate was characterized by physiochemical techniques such as electron microscopy, FTIR, VSM and DLS measurements. This particulate form of the polysaccharide showed a marked escalation in the production of free radicals such as reactive oxygen and nitrogen species in murine macrophages as compared to the soluble form. Animal based experiments demonstrated a reduction in tumor volume and augmentation in the proliferation of splenocytes in particulate or conjugated polysaccharide treated mice. Furthermore, molecular signaling studies showed a high upregulation in p-p38 and p-MEK molecules in particulate polysaccharide treated RAW264.7 cells suggesting a cellular downstream mechanistic regulation behind the immunostimulative response. PMID:25450832

  17. Safety Monitoring in Group A Meningococcal Conjugate Vaccine Trials: Description, Challenges, and Lessons

    PubMed Central

    Enwere, Godwin C.; Paranjape, Gandhali; Kulkarni, Prasad S.; Ginde, Manisha; Hartmann, Katharina; Viviani, Simonetta; Chaumont, Julie; Martellet, Lionel; Makadi, Marie-Francoise; Ivinson, Karen; Marchetti, Elisa; Herve, Jacques; Kertson, Kim; LaForce, F. Marc; Preziosi, Marie-Pierre

    2015-01-01

    Background.?The determination of the safety profile of any vaccine is critical to its widespread use in any population. In addition, the application of international guidelines to fit local context could be a challenging but important step toward obtaining quality safety data. Methods.?In clinical studies of PsA-TT (MenAfriVac), safety was monitored immediately after vaccination, at 4–7 days for postimmunization local and systemic reactions, within 28 days for adverse events, and throughout the duration of study for serious adverse events. Initial and ongoing training of sites' staff were undertaken during the studies, and a data and safety monitoring board reviewed all the data during and after the studies. Results.?The safety of PsA-TT was evaluated according to international standards despite obvious challenges in remote areas where these studies were conducted. These challenges included the need for uniformity of methods, timely reporting in the context of frequent communication problems, occurrence of seasonal diseases such as malaria and rotavirus diarrhea, and healthcare systems that required improvement. Conclusions.?The trials of PsA-TT highlighted the value of a robust vaccine development plan and design so that lessons learned in initial studies were incorporated into the subsequent ones, initial training and periodic retraining, strict monitoring of all procedures, and continuous channel of communication with all stakeholders that enabled the application of international requirements to local settings, with high quality of data. PMID:26553681

  18. Vaccines

    MedlinePLUS Videos and Cool Tools

    Vaccinations are injections of antigens into the body. Once the antigens enter the blood, they circulate along ... suppressor T cells stop the attack. After a vaccination, the body will have a memory of an ...

  19. Real time and accelerated stability studies of Tetanus toxoid manufactured in public sector facilities of Pakistan.

    PubMed

    Parveen, Ghazala; Hussain, Shahzad; Malik, Farnaz; Begum, Anwar; Mahmood, Sidra; Raza, Naeem

    2013-11-01

    Tetanus is an acute illness represented by comprehensive increased inflexibility and spastic spasms of skeletal muscles. The poor quality tetanus toxoid vaccine can raise the prevalence of neonatal tetanus. WHO has taken numerous steps to assist national regulatory authorities and vaccine manufacturers to ensure its quality and efficacy. It has formulated international principles for stability evaluation of each vaccine, which are available in the form of recommendations and guidelines. The aim of present study was to ensure the stability of tetanus vaccines produced by National Institute of Health, Islamabad, Pakistan by employing standardized methods to ensure constancy of tetanus toxoid at elevated temperature, if during storage/transportation cold chain may not be maintained in hot weather. A total of three batches filled during full-scale production were tested. All Stability studies determination were performed on final products stored at 2-8°C and elevated temperatures in conformance with the ICH Guideline of Stability Testing of Biological Products. These studies gave comparison between real time shelf-life stability and accelerated stability studies. The findings indicate long?term thermo stability and prove that this tetanus vaccine can remain efficient under setting of routine use when suggested measures for storage and handling are followed in true spirit. PMID:24191338

  20. Diphtheria and tetanus toxoid microencapsulation into conventional and end-group alkylated PLA/PLGAs.

    PubMed

    Johansen, P; Tamber, H; Merkle, H P; Gander, B

    1999-05-01

    The feasibility of biodegradable polyester microspheres (MS) for single injection vaccines will greatly depend on the toxoid stability within the MS exposed to in vivo conditions. This study examined the effects of polymer type and co-encapsulated additives on diphtheria (Dtxd) and tetanus (Ttxd) toxoid entrapment and stability. The co-encapsulated stabilizers influenced significantly the entrapment of Dtxd and Ttxd in PLA/PLGA MS. Typically, 5% BSA or trehalose decreased the amount of Dtxd entrapped in spray-dried MS, whereas BSA increased the entrapment in coacervated MS. Further, the entrapment of Dtxd decreased as a function of polymer hydrophobicity in spray-dried MS. Without additives, approx. 64, 43 and 16% entrapment efficiency of ELISA-reactive antigen was obtained for 14-17 kDa PLGA 50:50, PLGA 75:25 and PLA, respectively. The novel end-group stearylated 1-PLAs were only processed by coacervation. Satisfactory entrapment of 30-60% Dtxd was obtained. Here, albumin was a prerequisite for toxoid encapsulation, as BSA-free formulations produced strong toxoid precipitation. Furthermore, protein burst release increased with the more hydrophobic polymers, with Dtxd, Ttxd and the co-encapsulated BSA following a similar pattern and magnitude. This investigation also revealed that the method of protein extraction from the microspheres (O/W-partition or polymer hydrolysis) as well as the analytical methods (HPLC or ELISA) strongly influenced the determined amount of encapsulated toxoid and BSA. In conclusion, the study revealed the complexity of antigen microencapsulation when using different preparation and analytical techniques, as well as different types of materials. PMID:10382103

  1. Response to Pneumococcal (PNCRM7) and Haemophilus influenza conjugate vaccines (HIB) in pediatric and adult recipients of an allogeneic hematopoietic cell transplantation (alloHCT)

    PubMed Central

    Pao, Mary; Papadopoulos, Esperanza B; Chou, Joanne; Glenn, Heller; Castro-Malaspina, Hugo; Jakubowski, Ann A; Kernan, Nancy A; Perales, Miguel A; Prockop, Susan; Scaradavou, Andromachi; vanDenBrink, Marcel R; Young, James W; O'Reilly, Richard J; Small, Trudy N

    2008-01-01

    Young children and allogeneic HCT recipients respond poorly to polysaccharide antigens rendering them susceptible to severe infections due to encapsulated bacteria. This study evaluated the responses of 127 HCT patients, median age: 23.0 years, vaccinated with PnCRM7 and HIB, two conjugate vaccines highly immunogenic in healthy children. Median time to vaccination was 1.1 years after HCT. Sixty-two percent of patients responded to PNCRM7 (45/51 children, 34/76 adults, p<0.001). Overall response to HIB was 86% including 77% of PNCRM7 non-responders. Although PNCRM7 response was adversely affected by older age (p<0.001), individuals ?50 years old responded significantly better if vaccinated following acquisition of specific minimal milestones of immune competence, CD4 >200/ul, IgG >500 mg/dl, PHA within 60% lower limit of normal (11/19 vs 0/8, p<0.006). A similar trend was observed in patients with limited chronic GVHD. In all patients, higher levels of circulating CD4+CD45RA cells correlated with improved PNCRM7 response. These data demonstrate that PNCRM7 is immunogenic in allogeneic HCT patients, including older adults, but suggest that vaccination at fixed intervals after HCT, irrespective of immune competence, may limit its effectiveness. Prospective, multi-center trials assessing the best strategy to administer this vaccine and its impact on pneumococcal infections following transplantation are warranted. PMID:18721765

  2. Molecular attributes of conjugate antigen influence function of antibodies induced by anti-nicotine vaccine in mice and non-human primates.

    PubMed

    McCluskie, Michael J; Thorn, Jennifer; Mehelic, Paul R; Kolhe, Parag; Bhattacharya, Keshab; Finneman, Jari I; Stead, David R; Piatchek, Michele Bailey; Zhang, Ningli; Chikh, Ghania; Cartier, Janna; Evans, Dana M; Merson, James R; Davis, Heather L

    2015-04-01

    Anti-nicotine vaccines aim to prevent nicotine entering the brain, and thus reduce or eliminate the reward that drives nicotine addiction. Those tested in humans to date have failed to improve quit rates over placebo, possibly because antibody (Ab) responses were insufficient to sequester enough nicotine in the blood in the majority of subjects. We have previously shown in mice that the carrier, hapten and linker used in the nicotine conjugate antigen each influence the function (nicotine-binding capacity) of the Ab induced. Herein we have evaluated immunogenicity in mice of 27 lots of NIC7-CRM, a conjugate of 5-aminoethoxy-nicotine (Hapten 7) and a mutant nontoxic form of diphtheria toxin (CRM197), that differed in three antigen attributes, namely hapten load (number of haptens conjugated to each molecule of CRM197), degree of conjugate aggregation and presence of adducts (small molecules attached to CRM197 via a covalent bond during the conjugation process). A range of functional responses (reduced nicotine in the brain of immunized animals relative to non-immunized controls) were obtained with the different conjugates, which were adjuvanted with aluminum hydroxide and CpG TLR9 agonist. Trends for better functional responses in mice were obtained with conjugates having a hapten load of 11 to 18, a low level of high molecular mass species (HMMS) (i.e., not aggregated) and a low level of adducts and a more limited testing in cynomolgus monkeys confirmed these results. Thus hapten load, conjugate aggregation and presence of adducts are key antigen attributes that can influence Ab function induced by NIC7-CRM. PMID:25737198

  3. Molecular Characterization of Invasive Meningococcal Isolates from Countries in the African Meningitis Belt before Introduction of a Serogroup A Conjugate Vaccine

    PubMed Central

    Caugant, Dominique A.; Kristiansen, Paul A.; Wang, Xin; Mayer, Leonard W.; Taha, Muhamed-Kheir; Ouédraogo, Rasmata; Kandolo, Denis; Bougoudogo, Flabou; Sow, Samba; Bonte, Laurence

    2012-01-01

    Background The serogroup A conjugate meningococcal vaccine, MenAfriVac, was introduced in mass vaccination campaigns in December 2010 in Burkina Faso, Mali and Niger. In the coming years, vaccination will be extended to other African countries at risk of epidemics. To document the molecular characteristics of disease-causing meningococcal strains circulating in the meningitis belt of Africa before vaccine introduction, the World Health Organization Collaborating Centers on Meningococci in Europe and United States established a common strain collection of 773 isolates from cases of invasive meningococcal disease collected between 2004 and 2010 from 13 sub-Saharan countries. Methodology All isolates were characterized by multilocus sequence typing, and 487 (62%) were also analyzed for genetic variation in the surface antigens PorA and FetA. Antibiotic susceptibility was tested for part of the collection. Principal Findings Only 19 sequence types (STs) belonging to 6 clonal complexes were revealed. ST-5 clonal complex dominated with 578 (74.8%) isolates. All ST-5 complex isolates were remarkably homogeneous in their PorA (P1.20,9) and FetA (F3-1) and characterized the serogroup A strains which have been responsible for most epidemics during this time period. Sixty-eight (8.8%) of the 773 isolates belonged to the ST-11 clonal complex which was mainly represented by serogroup W135, while an additional 38 (4.9%) W135 isolates belonged to the ST-175 complex. Forty-eight (6.2%) serogroup X isolates from West Africa belonged to the ST-181 complex, while serogroup X cases in Kenya and Uganda were caused by an unrelated clone, ST-5403. Serogroup X, ST-181, emerged in Burkina Faso before vaccine introduction. Conclusions In the seven years preceding introduction of a new serogroup A conjugate vaccine, serogroup A of the ST-5 clonal complex was identified as the predominant disease-causing strain. PMID:23029368

  4. Association of pneumococcal conjugate vaccination with rates of ventilation tube insertion in Denmark: population-based register study

    PubMed Central

    Groth, Christina; Thomsen, Reimar W; Ovesen, Therese

    2015-01-01

    Objective To examine if the introduction of pneumococcal conjugate vaccine (PCV) in Denmark was associated with a decrease in the rate of ventilation tube (VT) insertions performed by office-based practising ear, nose and throat (ENT) specialists. Design Population-based register study based on prospectively collected data. Setting Central Denmark Region. Data on VT insertions performed by any office-based practising ENT specialist in the region were collected from the National Health Service Registry. Participants All children below the age of 2?years with a first-time VT insertion from 2001 through 2011. Main outcome measures Age-stratified and gender-stratified standardised incidence rates of first-time VT insertion, and incidence rate ratio for PCV period 2008–2011 compared with pre-PCV period 2001–2007. Results The annual incidence rate of first-time VT insertion in small children increased steadily from 64/1000 person-years in 2001 to 100/1000 person-years in 2011. The incidence rate ratio was 1.27 (95% CI 1.24 to 1.30) in the PCV period compared with the pre-PCV period. Conclusions The introduction of PCV into the Danish childhood immunisation programme in 2007 was not associated with a subsequent decrease in the rate of VT insertions among children below the age of 2?years. Instead, the rate continued to rise, as before the introduction of PCV. Trial registration number Danish Data Protection Agency: 2007-58-0010. PMID:26048205

  5. Reduced incidence of invasive pneumococcal disease after introduction of the 13-valent conjugate vaccine in Navarre, Spain, 2001-2013.

    PubMed

    Guevara, Marcela; Ezpeleta, Carmen; Gil-Setas, Alberto; Torroba, Luis; Beristain, Xabier; Aguinaga, Aitziber; García-Irure, José Javier; Navascués, Ana; García-Cenoz, Manuel; Castilla, Jesús

    2014-05-01

    Pneumococcal conjugate vaccines (PCVs) were licensed for use in children and became available for private purchase in Spain in 2001 (PCV7), 2009 (PCV10) and 2010 (PCV13). This study evaluates changes in the incidence of invasive pneumococcal disease (IPD) and the pattern of serotypes isolated in Navarre, Spain, between the period of use of PCV7 (2004-2009) and that of PCV13 (2010-2013). The percentage of children <2 years who received at least one dose of PCV in these periods ranged from 25 to 61% and 61 to 78%, respectively. Between the periods 2004-2009 and 2010-2013 IPD incidence declined by 37%, from 14.9 to 9.4 cases/100,000 inhabitants (p<0.001). In children <5 years it fell by 69% (p<0.001), in persons aged 5-64 years, by 34% (p<0.001), and in those ? 65, by 23% (p=0.024). The incidence of cases due to PCV13 serotypes declined by 81% (p<0.001) in children <5 years and by 52% (p<0.001) in the whole population. No significant changes were seen in the distribution of clinical presentations or in disease severity. The incidence of IPD has declined and the pattern of serotypes causing IPD has changed notably in children and moderately in adults following the replacement of PCV7 by PCV13. PMID:24674661

  6. Immunogenicity and safety of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) co-administered with DTPa vaccine in Japanese children: A randomized, controlled study.

    PubMed

    Iwata, Satoshi; Kawamura, Naohisa; Kuroki, Haruo; Tokoeda, Yasunobu; Miyazu, Mitsunobu; Iwai, Asayuki; Oishi, Tomohiro; Sato, Tomohide; Suyama, Akari; François, Nancy; Shafi, Fakrudeen; Ruiz-Guiñazú, Javier; Borys, Dorota

    2015-01-01

    This phase III, randomized, open-label, multicenter study (NCT01027845) conducted in Japan assessed the immunogenicity, safety, and reactogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, given intramuscularly) co-administered with diphtheria-tetanus-acellular pertussis vaccine (DTPa, given subcutaneously). Infants (N=360 ) were randomized (2:1) to receive either PHiD-CV and DTPa (PHiD-CV group) or DTPa alone (control group) as 3-dose primary vaccination (3-4-5 months of age) and booster vaccination (17-19 months of age). Immune responses were measured before and one month after primary/booster vaccination and adverse events (AEs) were recorded. Post-primary immune responses were non-inferior to those in pivotal/efficacy European or Latin American pneumococcal protein D-conjugate vaccine studies. For each PHiD-CV serotype, at least 92.6% of infants post-primary vaccination and at least 97.7% of children post-booster had pneumococcal antibody concentrations ?0.2 ?g/ml, and at least 95.4% post-primary and at least 98.1% post-booster had opsonophagocytic activity (OPA) titers ?8 . Geometric mean antibody concentrations and OPA titers (except OPA titer for 6B) were higher post-booster than post-priming for each serotype. All PHiD-CV-vaccinated children had anti-protein D antibody concentrations ?100 EL.U/ml one month post-primary/booster vaccination and all were seroprotected/seropositive against each DTPa antigen. Redness and irritability were the most common solicited AEs in both groups. Incidences of unsolicited AEs were comparable between groups. Serious AEs were reported for 47 children (28 in PHiD-CV group); none were assessed as vaccine-related. In conclusion, PHiD-CV induced robust immune responses and was well tolerated when co-administered with DTPa in a 3-dose priming plus booster regimen to Japanese children. PMID:25830489

  7. Ethical Challenges and Lessons Learned During the Clinical Development of a Group A Meningococcal Conjugate Vaccine

    PubMed Central

    Martellet, Lionel; Sow, Samba O.; Diallo, Aldiouma; Hodgson, Abraham; Kampmann, Beate; Hirve, Siddhivinayak; Tapia, Milagritos; Haidara, Fadima Cheick; Ndiaye, Assane; Diarra, Bou; Ansah, Patrick Odum; Akinsola, Adebayo; Idoko, Olubukola T.; Adegbola, Richard A.; Bavdekar, Ashish; Juvekar, Sanjay; Viviani, Simonetta; Enwere, Godwin C.; Marchetti, Elisa; Chaumont, Julie; Makadi, Marie-Francoise; Pallardy, Flore; Kulkarni, Prasad S.; Preziosi, Marie-Pierre; LaForce, F. Marc

    2015-01-01

    Background.?The group A meningococcal vaccine (PsA-TT) clinical development plan included clinical trials in India and in the West African region between 2005 and 2013. During this period, the Meningitis Vaccine Project (MVP) accumulated substantial experience in the ethical conduct of research to the highest standards. Methods.?Because of the public–private nature of the sponsorship of these trials and the extensive international collaboration with partners from a diverse setting of countries, the ethical review process was complex and required strategic, timely, and attentive communication to ensure the smooth review and approval for the clinical studies. Investigators and their site teams fostered strong community relationships prior to, during, and after the studies to ensure the involvement and the ownership of the research by the participating populations. As the clinical work proceeded, investigators and sponsors responded to specific questions of informed consent, pregnancy testing, healthcare, disease prevention, and posttrial access. Results.?Key factors that led to success included (1) constant dialogue between partners to explore and answer all ethical questions; (2) alertness and preparedness for emerging ethical questions during the research and in the context of evolving international ethics standards; and (3) care to assure that approaches were acceptable in the diverse community contexts. Conclusions.?Many of the ethical issues encountered during the PsA-TT clinical development are familiar to groups conducting field trials in different cultural settings. The successful approaches used by the MVP clinical team offer useful examples of how these problems were resolved. Clinical Trials Registration.?ISRCTN17662153 (PsA-TT-001); ISRTCN78147026 (PsA-TT-002); ISRCTN87739946 (PsA-TT-003); ISRCTN46335400 (PsA-TT-003a); ISRCTN82484612 (PsA-TT-004); CTRI/2009/091/000368 (PsA-TT-005); PACTR ATMR2010030001913177 (PsA-TT-006); PACTR201110000328305 (PsA-TT-007). PMID:26553670

  8. Risk of Injection-Site Abscess among Infants Receiving a Preservative-Free, Two-Dose Vial Formulation of Pneumococcal Conjugate Vaccine in Kenya.

    PubMed

    Burton, Deron C; Bigogo, Godfrey M; Audi, Allan O; Williamson, John; Munge, Kenneth; Wafula, Jackline; Ouma, Dominic; Khagayi, Sammy; Mugoya, Isaac; Mburu, James; Muema, Shadrack; Bauni, Evasius; Bwanaali, Tahreni; Feikin, Daniel R; Ochieng, Peter M; Mogeni, Ondari D; Otieno, George A; Olack, Beatrice; Kamau, Tatu; Van Dyke, Melissa K; Chen, Robert; Farrington, Paddy; Montgomery, Joel M; Breiman, Robert F; Scott, J Anthony G; Laserson, Kayla F

    2015-01-01

    There is a theoretical risk of adverse events following immunization with a preservative-free, 2-dose vial formulation of 10-valent-pneumococcal conjugate vaccine (PCV10). We set out to measure this risk. Four population-based surveillance sites in Kenya (total annual birth cohort of 11,500 infants) were used to conduct a 2-year post-introduction vaccine safety study of PCV10. Injection-site abscesses occurring within 7 days following vaccine administration were clinically diagnosed in all study sites (passive facility-based surveillance) and, also, detected by caregiver-reported symptoms of swelling plus discharge in two sites (active household-based surveillance). Abscess risk was expressed as the number of abscesses per 100,000 injections and was compared for the second vs first vial dose of PCV10 and for PCV10 vs pentavalent vaccine (comparator). A total of 58,288 PCV10 injections were recorded, including 24,054 and 19,702 identified as first and second vial doses, respectively (14,532 unknown vial dose). The risk ratio for abscess following injection with the second (41 per 100,000) vs first (33 per 100,000) vial dose of PCV10 was 1.22 (95% confidence interval [CI] 0.37-4.06). The comparator vaccine was changed from a 2-dose to 10-dose presentation midway through the study. The matched odds ratios for abscess following PCV10 were 1.00 (95% CI 0.12-8.56) and 0.27 (95% CI 0.14-0.54) when compared to the 2-dose and 10-dose pentavalent vaccine presentations, respectively. In Kenya immunization with PCV10 was not associated with an increased risk of injection site abscess, providing confidence that the vaccine may be safely used in Africa. The relatively higher risk of abscess following the 10-dose presentation of pentavalent vaccine merits further study. PMID:26509274

  9. Risk of Injection-Site Abscess among Infants Receiving a Preservative-Free, Two-Dose Vial Formulation of Pneumococcal Conjugate Vaccine in Kenya

    PubMed Central

    Burton, Deron C.; Bigogo, Godfrey M.; Audi, Allan O.; Williamson, John; Munge, Kenneth; Wafula, Jackline; Ouma, Dominic; Khagayi, Sammy; Mugoya, Isaac; Mburu, James; Muema, Shadrack; Bauni, Evasius; Bwanaali, Tahreni; Feikin, Daniel R.; Ochieng, Peter M.; Mogeni, Ondari D.; Otieno, George A.; Olack, Beatrice; Kamau, Tatu; Van Dyke, Melissa K.; Chen, Robert; Farrington, Paddy; Montgomery, Joel M.; Breiman, Robert F.; Scott, J. Anthony G.; Laserson, Kayla F.

    2015-01-01

    There is a theoretical risk of adverse events following immunization with a preservative-free, 2-dose vial formulation of 10-valent-pneumococcal conjugate vaccine (PCV10). We set out to measure this risk. Four population-based surveillance sites in Kenya (total annual birth cohort of 11,500 infants) were used to conduct a 2-year post-introduction vaccine safety study of PCV10. Injection-site abscesses occurring within 7 days following vaccine administration were clinically diagnosed in all study sites (passive facility-based surveillance) and, also, detected by caregiver-reported symptoms of swelling plus discharge in two sites (active household-based surveillance). Abscess risk was expressed as the number of abscesses per 100,000 injections and was compared for the second vs first vial dose of PCV10 and for PCV10 vs pentavalent vaccine (comparator). A total of 58,288 PCV10 injections were recorded, including 24,054 and 19,702 identified as first and second vial doses, respectively (14,532 unknown vial dose). The risk ratio for abscess following injection with the second (41 per 100,000) vs first (33 per 100,000) vial dose of PCV10 was 1.22 (95% confidence interval [CI] 0.37–4.06). The comparator vaccine was changed from a 2-dose to 10-dose presentation midway through the study. The matched odds ratios for abscess following PCV10 were 1.00 (95% CI 0.12–8.56) and 0.27 (95% CI 0.14–0.54) when compared to the 2-dose and 10-dose pentavalent vaccine presentations, respectively. In Kenya immunization with PCV10 was not associated with an increased risk of injection site abscess, providing confidence that the vaccine may be safely used in Africa. The relatively higher risk of abscess following the 10-dose presentation of pentavalent vaccine merits further study. PMID:26509274

  10. Development and introduction of a ready-to-use pediatric pentavalent vaccine to meet and sustain the needs of developing countries--Quinvaxem®: the first 5 years.

    PubMed

    Schmid, D A; Macura-Biegun, A; Rauscher, M

    2012-09-28

    Quinvaxem(®) injection (DTwP-HepB-Hib fully-liquid combined vaccine) is a ready-to-use, preservative-free, fully-liquid combined vaccine containing diphtheria and tetanus toxoids, Bordetella pertussis inactivated cellular suspension, hepatitis B surface antigen (HBsAg), and Haemophilus influenzae type b conjugated oligosaccharide. The vaccine was the first ready-to-use, fully-liquid pentavalent vaccine to gain WHO pre-qualification status in 2006. The immunogenicity and safety of Quinvaxem(®) was assessed in four clinical trials and a large post-marketing surveillance study. Quinvaxem(®) was found to be highly immunogenic in each of the primary vaccination studies and was also shown to be suitable as a booster with the advantage that it could be given concomitantly with measles vaccine. Quinvaxem(®) has become a cornerstone in EPI vaccination programs. To further support the needs of EPI vaccination processes and developing countries, a simple, all-in-one, compact, prefilled, auto-disabled Uniject(®) injection system has been chosen and optimized as a potential new presentation for Quinvaxem(®). Hopefully, Quinvaxem(®) in the Uniject(®) presentation will help vaccination programs in developing countries to achieve more. PMID:22889824

  11. Use of Prior Vaccinations for the Development of New Vaccines

    NASA Astrophysics Data System (ADS)

    Etlinger, H. M.; Gillessen, D.; Lahm, H.-W.; Matile, H.; Schonfeld, H.-J.; Trzeciak, A.

    1990-07-01

    There is currently a need for vaccine development to improve the immunogenicity of protective epitopes, which themselves are often poorly immunogenic. Although the immunogenicity of these epitopes can be enhanced by linking them to highly immunogenic carriers, such carriers derived from current vaccines have not proven to be generally effective. One reason may be related to epitope-specific suppression, in which prior vaccination with a protein can inhibit the antibody response to new epitopes linked to the protein. To circumvent such inhibition, a peptide from tetanus toxoid was identified that, when linked to a B cell epitope and injected into tetanus toxoid-primed recipients, retained sequences for carrier but not suppressor function. The antibody response to the B cell epitope was enhanced. This may be a general method for taking advantage of previous vaccinations in the development of new vaccines.

  12. Development of a conjugate vaccine against invasive pneumococcal disease based on capsular polysaccharides coupled with PspA/family 1 protein of Streptococcus pneumoniae.

    PubMed

    Lin, Haiying; Peng, Yonghui; Lin, ZiLin; Zhang, Shuangling; Guo, Yanghao

    2015-01-01

    The efforts were focused on exploring alternative pneumococcal vaccine strategies, aimed at addressing the shortcomings of existing formulations, without compromising efficacy. Our strategy involved the use of the carrier protein, pneumococcal surface protein A (PspA), conjugated with capsular polysaccharides (CPS), to provide effective and non-serotype-dependent protection. In this study, we generated a stable Escherichia coli construct expressing functional PspA from a capsular serotype 6B strain and confirmed it belonging to family 1, which was conjugated with CPS. The distribution of anti-CPS antibody response was almost completely of IgG2a subclass followed by IgG3 and low level of IgG1 subclass, but that of anti-PspA IgG subclass antibodies was almost equal IgG1 and IgG2a subclasses. Though PspA was less conspicuous on the surface of pneumococci than the capsule, the antibodies induced with CPS-rPspA conjugate possessed more accessibility to the surface of Streptococcus pneumoniae serotype 6B and 19F (the same family 1 PspA). By survival experiment, the result suggested that the level of cross-protection after immunized with the conjugate was more measurable within the same family 1. The CPS-rPspA conjugate not only induced CPS-specific protection but also provided PspA specific cross-protection. PMID:25959527

  13. A Cross-Sectional Observational Study of Pneumococcal Carriage in Children, Their Parents, and Older Adults Following the Introduction of the 7-Valent Pneumococcal Conjugate Vaccine

    PubMed Central

    Hamaluba, Mainga; Kandasamy, Rama; Ndimah, Susan; Morton, Richard; Caccamo, Marisa; Robinson, Hannah; Kelly, Sarah; Field, Aimee; Norman, Lily; Plested, Emma; Thompson, Ben A.V.; Zafar, Azhar; Kerridge, Simon A.; Lazarus, Rajeka; John, Tessa; Holmes, Jane; Fenlon, Shannon N.; Gould, Katherine A.; Waight, Pauline; Hinds, Jason; Crook, Derrick; Snape, Matthew D.; Pollard, Andrew J.

    2015-01-01

    Abstract Using nasopharyngeal carriage as a marker of vaccine impact, pneumococcal colonization and its relation to invasive disease were examined in children, their parents, and older adults in the United Kingdom following introduction of 7-valent pneumococcal conjugate vaccine (PCV7) and prior to 13-valent pneumococcal conjugate vaccine (PCV13). A cross-sectional observational study was conducted, collecting nasopharyngeal swabs from children aged 25 to 55 months who had previously received 3 doses of PCV7, their parents, and adults aged ?65 years. Pneumococcal serotyping was conducted according to World Health Organization guidelines with nontypeable isolates further analyzed by molecular serotyping. A national invasive disease surveillance program was conducted throughout the corresponding period. Pneumococcus was isolated from 47% of children, 9% of parents, and 2.2% of older adults. For these groups, the percentage of serotypes covered by PCV7 were 1.5%, 0.0%, and 15.4%, with a further 20.1%, 44.4%, and 7.7% coverage added by those in PCV13. In each group, the percentage of disease due to serotypes covered by PCV7 were 1.0%, 7.4% and 5.1% with a further 65.3%, 42.1%, and 61.4% attributed to those in PCV13. The prevalence of carriage is the highest in children, with direct vaccine impact exemplified by low carriage and disease prevalence of PCV7 serotypes in vaccinated children, whereas the indirect effects of herd protection are implied by similar observations in unvaccinated parents and older adults. PMID:25569650

  14. Safety and Immunogenicity of Neonatal Pneumococcal Conjugate Vaccination in Papua New Guinean Children: A Randomised Controlled Trial

    PubMed Central

    Phuanukoonnon, Suparat; Francis, Jacinta; Jacoby, Peter; Siba, Peter M.; Alpers, Michael P.; Reeder, John C.; Holt, Patrick G.; Richmond, Peter C.; Lehmann, Deborah

    2013-01-01

    Background Approximately 826,000 children, mostly young infants, die annually from invasive pneumococcal disease. A 6-10-14-week schedule of pneumococcal conjugate vaccine (PCV) is efficacious but neonatal PCV may provide earlier protection and better coverage. We conducted an open randomized controlled trial in Papua New Guinea to compare safety, immunogenicity and priming for memory of 7-valent PCV (PCV7) given in a 0-1-2-month (neonatal) schedule with that of the routine 1-2-3-month (infant) schedule. Methods We randomized 318 infants at birth to receive PCV7 in the neonatal or infant schedule or no PCV7. All infants received 23-valent pneumococcal polysaccharide vaccine (PPV) at age 9 months. Serotype-specific serum IgG for PCV7 (VT) serotypes and non-VT serotypes 2, 5 and 7F were measured at birth and 2, 3, 4, 9, 10 and 18 months of age. Primary outcomes were geometric mean concentrations (GMCs) and proportions with concentration ?0.35 µg/ml of VT serotype-specific pneumococcal IgG at age 2 months and one month post-PPV. Results We enrolled 101, 105 and 106 infants, respectively, into neonatal, infant and control groups. Despite high background levels of maternally derived antibody, both PCV7 groups had higher GMCs than controls at age 2 months for serotypes 4 (p<0.001) and 9V (p<0.05) and at age 3 months for all VTs except 6B. GMCs for serotypes 4, 9V, 18C and 19F were significantly higher (p<0.001) at age 2 months in the neonatal (one month post-dose2 PCV7) than in the infant group (one month post-dose1 PCV7). PPV induced significantly higher VT antibody responses in PCV7-primed than unprimed infants, with neonatal and infant groups equivalent. High VT and non-VT antibody concentrations generally persisted to age 18 months. Conclusions PCV7 is well-tolerated and immunogenic in PNG neonates and young infants and induces immunologic memory to PPV booster at age 9 months with antibody levels maintained to age 18 months. Trial Registration ClinicalTrials.gov NCT00219401NCT00219401 PMID:23451070

  15. Nasopharyngeal Carriage and Transmission of Streptococcus pneumoniae in American Indian Households after a Decade of Pneumococcal Conjugate Vaccine Use

    PubMed Central

    Mosser, Jonathan F.; Grant, Lindsay R.; Millar, Eugene V.; Weatherholtz, Robert C.; Jackson, Delois M.; Beall, Bernard; Craig, Mariddie J.; Reid, Raymond; Santosham, Mathuram; O'Brien, Katherine L.

    2014-01-01

    Background Young children played a major role in pneumococcal nasopharyngeal carriage, acquisition, and transmission in the era before pneumococcal conjugate vaccine (PCV) use. Few studies document pneumococcal household dynamics in the routine-PCV7 era. Methods We investigated age-specific acquisition, household introduction, carriage clearance, and intra-household transmission in a prospective, longitudinal, observational cohort study of pneumococcal nasopharyngeal carriage in 300 American Indian households comprising 1,072 participants between March 2006 and March 2008. Results Pneumococcal acquisition rates were 2–6 times higher in children than adults. More household introductions of new pneumococcal strains were attributable to children <9 years than adults ?17 years (p<0.001), and older children (2–8 years) than younger children (<2 years) (p<0.008). Compared to children <2 years, carriage clearance was more rapid in older children (2–4 years, HRclearance 1.53 [95% CI: 1.22, 1.91]; 5–8 years, HRclearance 1.71 [1.36, 2.15]) and adults (HRclearance 1.75 [1.16, 2.64]). Exposure to serotype-specific carriage in older children (2–8 years) most consistently increased the odds of subsequently acquiring that serotype for other household members. Conclusions In this community with a high burden of pneumococcal colonization and disease and routine PCV7 use, children (particularly older children 2–8 years) drive intra-household pneumococcal transmission: first, by acquiring, introducing, and harboring pneumococcus within the household, and then by transmitting acquired serotypes more efficiently than household members of other ages. PMID:24465365

  16. Population snapshot of Streptococcus pneumoniae causing invasive disease in South Africa prior to introduction of pneumococcal conjugate vaccines.

    PubMed

    Ndlangisa, Kedibone M; du Plessis, Mignon; Wolter, Nicole; de Gouveia, Linda; Klugman, Keith P; von Gottberg, Anne

    2014-01-01

    We determined the sequence types of isolates that caused invasive pneumococcal disease (IPD) prior to routine use of pneumococcal conjugate vaccines (PCV) in South Africa. PCV-13 serotypes and 6C isolates collected in 2007 (1 461/2 437, 60%) from patients of all ages as part of on-going, national, laboratory-based surveillance for IPD, were selected for genetic characterization. In addition, all 134 non-PCV isolates from children <2 years were selected for characterization. Sequence type diversity by serotype and age category (children <5 years vs. individuals ?5 years) was assessed for PCV serotypes using Simpson's index of diversity. Similar genotypes circulated among isolates from children and adults and the majority of serotypes were heterogeneous. While globally disseminated clones were common among some serotypes (e.g., serotype 1 [clonal complex (CC) 217, 98% of all serotype 1] and 14 [CC230, 43%)]), some were represented mainly by clonal complexes rarely reported elsewhere (e.g., serotype 3 [CC458, 60%] and 19A [CC2062, 83%]). In children <2 years, serotype 15B and 8 were the most common serotypes among non-PCV isolates (16% [22/134] and 15% [20/134] isolates, respectively). Sequence type 7052 and 53 were most common among serotypes 15B and 8 isolates and accounted for 58% (7/12) and 64% (9/14) of the isolates, respectively. Serotype 19F, 14, 19A and 15B had the highest proportions of penicillin non-susceptible isolates. Genotypes rarely reported in other parts of the world but common among some of our serotypes highlight the importance of our data as these genotypes may emerge post PCV introduction. PMID:25233455

  17. Pseudomonas aeruginosa flagellin as an adjuvant: superiority of a conjugated form of flagellin versus a mixture with a human immunodeficiency virus type 1 vaccine candidate in the induction of immune responses.

    PubMed

    Delavari, Safura; Sohrabi, Mojtaba; Ardestani, Mehdi Shafiee; Faezi, Sobhan; Tebianian, Majid; Taghizadeh, Morteza; Shajiei, Arezoo; Hosseini, Seyed Younes; Moghaddampour, Masoud; Mahdavi, Mehdi

    2015-11-01

    In the present study, the adjuvant activity of flagellin was compared, in the conjugated and mixed forms, against a peptide vaccine from human immunodeficiency virus type 1 (HIV-1) p24-Nef vaccine candidate. Mice were immunized with the HIV-1 p24-Nef peptide with flagellin in both conjugated and mixed forms. Lymphocyte proliferation, CTL activity, and IL-4 and IFN-? cytokines were evaluated by bromodeoxyuridine, carboxyfluorescein succinimidyl ester and ELISA methods, respectively. At the same time, the frequency of IFN-?-producing T-lymphocytes, as well as total and isotype-specific antibodies, were assessed by ELISPOT and indirect ELISA, respectively. Our experimental results showed that the immunized mice with the HIV-1 p24-Nef conjugated or mixed forms of flagellin led to increases in the proliferative responses and Th1 cytokine pattern. The conjugated form of vaccine led to increased CTL activity and a Th1 cytokine pattern of immune responses, as well as an IgM isotype of humoral responses in comparison with the mixed form. The flagellin-conjugated vaccine seems to be more potent in increasing vaccine immunogenicity. PMID:26404477

  18. Do Pneumococcal Conjugate Vaccines Represent Good Value for Money in a Lower-Middle Income Country? A Cost-Utility Analysis in the Philippines

    PubMed Central

    Haasis, Manuel Alexander; Ceria, Joyce Anne; Kulpeng, Wantanee; Teerawattananon, Yot; Alejandria, Marissa

    2015-01-01

    Objectives The objective of this study is to assess the value for money of introducing pneumococcal conjugate vaccines as part of the immunization program in a lower-middle income country, the Philippines, which is not eligible for GAVI support and lower vaccine prices. It also includes the newest clinical evidence evaluating the efficacy of PCV10, which is lacking in other previous studies. Methods A cost-utility analysis was conducted. A Markov simulation model was constructed to examine the costs and consequences of PCV10 and PCV13 against the current scenario of no PCV vaccination for a lifetime horizon. A health system perspective was employed to explore different funding schemes, which include universal or partial vaccination coverage subsidized by the government. Results were presented as incremental cost-effectiveness ratios (ICERs) in Philippine peso (Php) per QALY gained (1 USD = 44.20 Php). Probabilistic sensitivity analysis was performed to determine the impact of parameter uncertainty. Results With universal vaccination at a cost per dose of Php 624 for PCV10 and Php 700 for PCV13, both PCVs are cost-effective compared to no vaccination given the ceiling threshold of Php 120,000 per QALY gained, yielding ICERs of Php 68,182 and Php 54,510 for PCV10 and PCV13, respectively. Partial vaccination of 25% of the birth cohort resulted in significantly higher ICER values (Php 112,640 for PCV10 and Php 84,654 for PCV13) due to loss of herd protection. The budget impact analysis reveals that universal vaccination would cost Php 3.87 billion to 4.34 billion per annual, or 1.6 to 1.8 times the budget of the current national vaccination program. Conclusion The inclusion of PCV in the national immunization program is recommended. PCV13 achieved better value for money compared to PCV10. However, the affordability and sustainability of PCV implementation over the long-term should be considered by decision makers. PMID:26131961

  19. 9 CFR 113.115 - Staphylococcus Aureus Bacterin-Toxoid.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 9 Animals and Animal Products 1 2012-01-01 2012-01-01 false Staphylococcus Aureus Bacterin-Toxoid... REQUIREMENTS Inactivated Bacterial Products § 113.115 Staphylococcus Aureus Bacterin-Toxoid. Staphylococcus... Staphylococcus aureus which has been inactivated and is nontoxic. Each serial of biological product...

  20. 9 CFR 113.115 - Staphylococcus Aureus Bacterin-Toxoid.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false Staphylococcus Aureus Bacterin-Toxoid... REQUIREMENTS Inactivated Bacterial Products § 113.115 Staphylococcus Aureus Bacterin-Toxoid. Staphylococcus... Staphylococcus aureus which has been inactivated and is nontoxic. Each serial of biological product...

  1. 9 CFR 113.115 - Staphylococcus Aureus Bacterin-Toxoid.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 9 Animals and Animal Products 1 2013-01-01 2013-01-01 false Staphylococcus Aureus Bacterin-Toxoid... REQUIREMENTS Inactivated Bacterial Products § 113.115 Staphylococcus Aureus Bacterin-Toxoid. Staphylococcus... Staphylococcus aureus which has been inactivated and is nontoxic. Each serial of biological product...

  2. 9 CFR 113.115 - Staphylococcus Aureus Bacterin-Toxoid.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 9 Animals and Animal Products 1 2014-01-01 2014-01-01 false Staphylococcus Aureus Bacterin-Toxoid... REQUIREMENTS Inactivated Bacterial Products § 113.115 Staphylococcus Aureus Bacterin-Toxoid. Staphylococcus... Staphylococcus aureus which has been inactivated and is nontoxic. Each serial of biological product...

  3. 9 CFR 113.115 - Staphylococcus Aureus Bacterin-Toxoid.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false Staphylococcus Aureus Bacterin-Toxoid... REQUIREMENTS Inactivated Bacterial Products § 113.115 Staphylococcus Aureus Bacterin-Toxoid. Staphylococcus... Staphylococcus aureus which has been inactivated and is nontoxic. Each serial of biological product...

  4. Antimicrobial Resistance among Isolates Causing Invasive Pneumococcal Disease before and after Licensure of Heptavalent Conjugate Pneumococcal Vaccine

    PubMed Central

    Karnezis, Tom Theodore; Smith, Ann; Whittier, Susan; Haddad, Joseph; Saiman, Lisa

    2009-01-01

    Background The impact of the pneumococcal conjugate vaccine (PCV-7) on antibiotic resistance among pneumococcal strains causing invasive pneumococcal disease (IPD) has varied in different locales in the United States. We assessed trends in IPD including trends for IPD caused by penicillin non-susceptible strains before and after licensure of PCV-7 and the impact of the 2008 susceptibility breakpoints for penicillin on the epidemiology of resistance. Methodology/Principal Findings We performed a retrospective review of IPD cases at Morgan Stanley Children's Hospital of NewYork-Presbyterian, Columbia University Medical Center. Subjects were ?18 years of age with Streptococcus pneumoniae isolated from sterile body sites from January 1995–December 2006. The rate of IPD from 1995–1999 versus 2002–2006 significantly decreased from 4.1 (CI95 3.4, 4.8) to 1.7 (CI95 1.3, 2.2) per 1,000 admissions. Using the breakpoints in place during the study period, the proportion of penicillin non-susceptible strains increased from 27% to 49% in the pre- vs. post-PCV-7 era, respectively (p?=?0.001), although the rate of IPD caused by non-susceptible strains did not change from 1995–1999 (1.1 per 1,000 admissions, CI95 0.8, 1.5) when compared with 2002–2006 (0.8 per 1,000 admissions, CI95 0.6, 1.2). In the multivariate logistic regression model controlling for the effects of age, strains causing IPD in the post-PCV-7 era were significantly more likely to be penicillin non-susceptible compared with strains in the pre-PCV-7 era (OR 2.46, CI95 1.37, 4.40). However, using the 2008 breakpoints for penicillin, only 8% of strains were non-susceptible in the post-PCV-7 era. Conclusions/Significance To date, there are few reports that document an increase in the relative proportion of penicillin non-susceptible strains of pneumococci causing IPD following the introduction of PCV-7. Active surveillance of pneumococcal serotypes and antibiotic resistance using the new penicillin breakpoints is imperative to assess potential changes in the epidemiology of IPD. PMID:19536335

  5. Injectable polymer microspheres enhance immunogenicity of a contraceptive peptide vaccine

    PubMed Central

    Cui, Chengji; Stevens, Vernon C.; Schwendeman, Steven P.

    2007-01-01

    Advanced contraceptive peptide vaccines suffer from the unavailability of adjuvants capable of enhancing the antibody response with acceptable safety. We sought to overcome this limitation by employing two novel poly(lactic-co-glycolic acid) (PLGA) microsphere formulations to deliver a synthetic human chorionic gonadotropin (hCG) peptide antigen co-synthesized with a T-cell epitope from tetanus toxoid, C-TT2-CTP35: surface-conjugated immunogen to induce phagocytosis; and encapsulated peptide to provide a depot effect, with MgCO3 co-encapsulated in the polymer to neutralize acidity from the biodegrading PLGA polyester. A single immunization of encapsulated peptide in rabbits elicited a stronger antibody response with equivalent duration relative to a positive control — three injections of the peptide administered in a squalene-based water-in-oil emulsion. Surface-conjugated peptide was less effective but enhanced antibody levels at 1/5 the dose, relative to soluble antigen. Most remarkable and unexpected was the finding that co-encapsulation of base was essential to attain the powerful adjuvant effect of the PLGA – MgCO3 system, as the MgCO3-free microspheres were completely ineffective. A promising contraceptive hCG peptide vaccine with acceptable side effects (i.e., local tissue reactions) was achieved by minimizing PLGA and MgCO3 doses, without significantly affecting antibody response. PMID:16996662

  6. 9 CFR 113.112 - Clostridium Perfringens Type D Toxoid and Bacterin-Toxoid.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... distilled water; adjusting the pH to 7.2; autoclaving at 250 °F for 25 minutes; and storing at 4 °C until... and Bacterin-Toxoid. 113.112 Section 113.112 Animals and Animal Products ANIMAL AND PLANT HEALTH... Plant Health Inspection Service. The antitoxin unit value shall be stated on the label. (v)...

  7. 9 CFR 113.111 - Clostridium Perfringens Type C Toxoid and Bacterin-Toxoid.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... the pH to 7.2; autoclaving at 250 °F for 25 minutes; and storing at 4 °C until used. (2) Each of at... and Bacterin-Toxoid. 113.111 Section 113.111 Animals and Animal Products ANIMAL AND PLANT HEALTH... perfringens Beta Antitoxin Standard and which is either supplied by or acceptable to Animal and Plant...

  8. 9 CFR 113.112 - Clostridium Perfringens Type D Toxoid and Bacterin-Toxoid.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... distilled water; adjusting the pH to 7.2; autoclaving at 250 °F for 25 minutes; and storing at 4 °C until... and Bacterin-Toxoid. 113.112 Section 113.112 Animals and Animal Products ANIMAL AND PLANT HEALTH... Plant Health Inspection Service. The antitoxin unit value shall be stated on the label. (v)...

  9. 9 CFR 113.111 - Clostridium Perfringens Type C Toxoid and Bacterin-Toxoid.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... the pH to 7.2; autoclaving at 250 °F for 25 minutes; and storing at 4 °C until used. (2) Each of at... and Bacterin-Toxoid. 113.111 Section 113.111 Animals and Animal Products ANIMAL AND PLANT HEALTH... perfringens Beta Antitoxin Standard and which is either supplied by or acceptable to Animal and Plant...

  10. Predictors to parental knowledge about childhood immunisation/EPI vaccines in two health districts in Cameroon prior to the introduction of 13-valent Pneumococcal Conjugate Vaccines (PCV-13)

    PubMed Central

    Libwea, John Njuma; Kobela, Marie; Ollgren, Jukka; Emah, Irene; Tchio, Robert; Nohynek, Hanna

    2014-01-01

    Introduction Pneumonia is vaccine-preventable, but the increasing death toll resulting from the disease in Sub-Saharan Africa is alarming. Several factors account for vaccine failing to reach every child, besides incomplete vaccine coverage. Most of these include the perceptions of parents/guardians and healthcare providers. Previous studies on the introduction of new vaccines have focused on experimental trials, coverage figures and vaccine efficacy in developed countries. Little is known on the factors which may hinder the implementation process despite the huge challenges this may encounter in developing countries. This study described the knowledge, attitude and practices (KAP) of parents/guardians on pneumonia and immunisations/EPI vaccines; identify predictive parental socio-economic/demographic characteristics that of good knowledge on pneumonia infections, routine EPI vaccines and the PCV-13. Finally, the study described health center personnel perceptions about immunisations. Methods The WHO's immunisation coverage cluster survey design was used, involving parents/guardians (n = 205) of children aged 0-59 months and health centre personnel (n = 13) directly concerned with vaccination activities between July-September 2010 in two health districts in Yaounde, Cameroon. Descriptive statistics and multivariate logistic models were used to analyse the parental/guardian data while the health personnel data was only analysed descriptively using SPSS version 17.0. Results Only 19% of the parents/guardians were aware of the availability of the PCV-13. Logistic modelling identified important associations between parental socio-economic/demographic factors and good knowledge on pneumonia disease burden and prevention. Conclusion According to parents/guardians a short and clear message on the dangers of pneumonia and the need for prevention provided to parents/guardians during sensitisation/out-reach campaigns and use of social network avenues would be primordial, if the PCV-13 is to reach every child. PMID:25396013

  11. Worldwide Haemophilus influenzae Type b Disease at the Beginning of the 21st Century: Global Analysis of the Disease Burden 25 Years after the Use of the Polysaccharide Vaccine and a Decade after the Advent of Conjugates

    PubMed Central

    Peltola, Heikki

    2000-01-01

    Vaccination against Haemophilus influenzae type b (Hib) diseases began a quarter of a century ago with a polysaccharide vaccine; this vaccine was followed by four different conjugates 10 years later. In this review, the burden of global Hib disease is quantified following this 25-year period of vaccine availability to determine the potential impact of conjugate vaccines. This task was accomplished by analysis of data available in 10 languages in 75 geographical regions of over 50 countries. All severe Hib diseases, not only meningitis, were characterized, and special attention was paid to the most vulnerable age group, i.e., children aged 0 to 4 years. Prior to vaccination, the weighted worldwide incidence of meningitis in patients younger than 5 years was 57/100,000, and for all Hib diseases except nonbacteremic pneumonia, it was 71/100,000, indicating 357,000 and 445,000 cases per year, respectively. At least 108,500 of these children died. For all age groups combined, there were 486,000 cases of Hib disease, excluding pneumonia, with 114,200 deaths and probably an equal number of sequelae per annum. If the figures for nonbacteremic pneumonia are included, a conservative estimate is that over 2.2 million cases of infection and 520,000 deaths from Hib disease occurred worldwide, but the true numbers might have been greater. Despite these large numbers and availability of safe and efficacious vaccines, only 38,000 cases annually are prevented—a meager 8% or less than a 2% reduction in cases, depending on whether nonbacteremic pneumonia is included in the calculations. Although vaccination has had great success in some affluent countries, the current level of activity has had a very small impact globally. The use of conjugates, preferably with a reduced number of doses and in combination with other vaccines or perhaps in fractional doses, should be extended to less privileged countries, where most Hib disease occurs. PMID:10756001

  12. The Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA): what is the future of pneumococcal conjugate vaccination in elderly?

    PubMed

    van Werkhoven, Cornelis H; Bonten, Marc J M

    2015-01-01

    Pneumococcal community-acquired pneumonia (PCAP) and invasive pneumococcal disease (IPD) are important causes of morbidity and mortality in elderly. In the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA), a randomized double-blind placebo-controlled trial of 84,496 community-dwelling immunocompetent adults over 65 years of age, the 13-valent pneumococcal conjugate vaccine (PCV13) reduced the incidence of first episode of vaccine-type (VT) PCAP with 38 and of VT-IPD with 76% in the modified intention-to-treat population. In The Netherlands, where PCV7 immunization of newborns was introduced in 2007 and replaced by PCV10 in 2011, introduction of PCV13 immunization of elderly--based on 2012 data--would be highly cost effective. However, this is probably different in countries where the VT disease burden has declined more, for instance due to herd effects following child immunization with PCV13. Apart from cost-effectiveness analyses, ethical aspects of PCAP prevention should be taken into account in policy making for pneumococcal vaccination in elderly. PMID:26347153

  13. Immunization with the conjugate vaccine Vi-CRM??? against Salmonella typhi induces Vi-specific mucosal and systemic immune responses in mice.

    PubMed

    Fiorino, Fabio; Ciabattini, Annalisa; Rondini, Simona; Pozzi, Gianni; Martin, Laura B; Medaglini, Donata

    2012-09-21

    Typhoid fever is a public health problem, especially among young children in developing countries. To address this need, a glycoconjugate vaccine Vi-CRM???, composed of the polysaccharide antigen Vi covalently conjugated to the non-toxic mutant of diphtheria toxin CRM???, is under development. Here, we assessed the antibody and cellular responses, both local and systemic, following subcutaneous injection of Vi-CRM???. The glycoconjugate elicited Vi-specific serum IgG titers significantly higher than unconjugated Vi, with prevalence of IgG1 that persisted for at least 60 days after immunization. Vi-specific IgG, but not IgA, were present in intestinal washes. Lymphocytes proliferation after restimulation with Vi-CRM??? was observed in spleen and mesenteric lymph nodes. These data confirm the immunogenicity of Vi-CRM??? and demonstrate that the vaccine-specific antibody and cellular immune responses are present also in the intestinal tract, thus strengthening the suitability of Vi-CRM??? as a promising candidate vaccine against Salmonella Typhi. PMID:22705173

  14. Safety and immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Chilean children.

    PubMed

    Lagos, Rosanna E; Muñoz, Alma E; Levine, Myron M; Lepetic, Alejandro; François, Nancy; Yarzabal, Juan Pablo; Schuerman, Lode

    2011-05-01

    The safety and immunogenicity of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV, Synflorix™) were assessed in 240 healthy Chilean children randomized to receive 3 doses of PHiD-CV (PHiD-CV group) or hepatitis A vaccine (HAV control group) at 2-4-6 months of age. All were offered 1 HAV dose at 12 months (outside study). The PHiD-CV group received a second HAV dose at 18-21 months and PHiD-CV booster at 20-23 months. The HAV control group received 2 PHiD-CV catch-up doses at 18-21 and 20-23 months. Adverse events were recorded and pneumococcal antibody responses and opsonophagocytic activity (OPA) were measured. Both PHiD-CV vaccination schedules were well tolerated and immunogenic against the pneumococcal vaccine serotypes and protein D. The reactogenicity of PHiD-CV primary, booster and catch-up doses was in line with previous PHiD-CV studies, although generally higher than with HAV. For each vaccine serotype, the percentage of subjects with antibody concentrations ?0.2 µg/ml (GSK's 22F-inhibition ELISA) was at least 93.2% following 3 PHiD-CV primary doses and at least 97.4% post-booster; percentages with OPA titers ?8 were at least 91.7% post-booster. After 2-dose catch-up, at least 94.3% of children had antibody concentrations ?0.2 µg/ml against each serotype except 6B (84.3%); at least 95.2% had OPA titers ?8 except against serotypes 1, 5 and 6B. In conclusion, the safety profiles of 2 PHiD-CV vaccination schedules (3-dose primary plus booster and 2-dose catch-up) were in line with previous studies and PHiD-CV was immunogenic for all 10 vaccine serotypes and protein D. PMID:21441782

  15. Child vaccination, part 2: childhood vaccination procedures.

    PubMed

    Zimmerman, R K; Burns, I T

    2000-09-01

    In 1996, the Advisory Committee on Immunization Practices (ACIP), the American Academy of Family Physicians (AAFP), the American Academy of Pediatrics (AAP), and the American Medical Association recommended a well-child office visit at age 11 to 12 years to check vaccination status. Vaccination status should be assessed for varicella, hepatitis B, the second dose of measles-mumps-rubella (MMR) vaccine, and tetanus-diptheria (Td) toxoid if not given in the past 5 years. Adolescent patients should be screened for high-risk conditions indicating the need for influenza, pneumococcal, or hepatitis A vaccines. The Accelerated Immunization Schedule and Minimal Interval Table should be consulted for children who are behind schedule. PMID:11032191

  16. Recent trends in pediatric bacterial meningitis in Japan--a country where Haemophilus influenzae type b and Streptococcus pneumoniae conjugated vaccines have just been introduced.

    PubMed

    Shinjoh, Masayoshi; Iwata, Satoshi; Yagihashi, Tatsuhiko; Sato, Yoshitake; Akita, Hironobu; Takahashi, Takao; Sunakawa, Keisuke

    2014-08-01

    To investigate the trends in incidence and the characteristics of bacterial meningitis in Japan where Haemophilus influenzae type b (Hib) vaccine and 7-valent pneumococcal conjugated vaccine (PCV7) were introduced in 2008 and 2010, respectively, which was 5-20 years after their introduction in western countries. The nationwide Japanese survey of pediatric and neonatal bacterial meningitis was performed in 2011 and 2012. We analyzed the epidemiological and clinical data, and compared the information obtained in the previous nationwide survey database. We also investigated the risk factors for disease outcome. In the 2011-2012 surveys, 357 patients were evaluated. H. influenzae, Streptococcus pneumoniae, Streptococcus agalactiae and Escherichia coli were the main organisms. The number of patients hospitalized with bacterial meningitis per 1000 admissions decreased from 1.31 in 2009 to 0.43 in 2012 (p < 0.001). The incidence of H. influenzae and S. pneumoniae meningitis also decreased from 0.66 to 0.08 (p < 0.001), and 0.30 to 0.06 (p < 0.001), respectively. Only 0-2 cases with Neisseria meningitidis were reported each year throughout 2001-2012. The median patient age was 10-12 months in 2001-2011, and became lower in 2012 (2 month old) (p < 0.001). The fatality rate for S. agalactiae is the highest (5.9% (11/187)) throughout 2001-2012 among the four organisms. Risk factors for death and sequelae were convulsions at onset, low CSF glucose, S. agalactiae etiology, and persistent positive CSF culture. Hib vaccine and PCV7 decreased the rate of bacterial meningitis. Earlier introduction of these vaccines may have prevented bacterial meningitis among Japanese children. PMID:24855913

  17. Efficacy of Pneumococcal Nontypable Haemophilus influenzae Protein D Conjugate Vaccine (PHiD-CV) in Young Latin American Children: A Double-Blind Randomized Controlled Trial

    PubMed Central

    Tregnaghi, Miguel W.; Sáez-Llorens, Xavier; López, Pio; Abate, Hector; Smith, Enrique; Pósleman, Adriana; Calvo, Arlene; Wong, Digna; Cortes-Barbosa, Carlos; Ceballos, Ana; Tregnaghi, Marcelo; Sierra, Alexandra; Rodriguez, Mirna; Troitiño, Marisol; Carabajal, Carlos; Falaschi, Andrea; Leandro, Ana; Castrejón, Maria Mercedes; Lepetic, Alejandro; Lommel, Patricia; Hausdorff, William P.; Borys, Dorota; Guiñazú, Javier Ruiz; Ortega-Barría, Eduardo; Yarzábal, Juan P.; Schuerman, Lode

    2014-01-01

    Background The relationship between pneumococcal conjugate vaccine–induced antibody responses and protection against community-acquired pneumonia (CAP) and acute otitis media (AOM) is unclear. This study assessed the impact of the ten-valent pneumococcal nontypable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) on these end points. The primary objective was to demonstrate vaccine efficacy (VE) in a per-protocol analysis against likely bacterial CAP (B-CAP: radiologically confirmed CAP with alveolar consolidation/pleural effusion on chest X-ray, or non-alveolar infiltrates and C-reactive protein ? 40 µg/ml); other protocol-specified outcomes were also assessed. Methods and Findings This phase III double-blind randomized controlled study was conducted between 28 June 2007 and 28 July 2011 in Argentine, Panamanian, and Colombian populations with good access to health care. Approximately 24,000 infants received PHiD-CV or hepatitis control vaccine (hepatitis B for primary vaccination, hepatitis A at booster) at 2, 4, 6, and 15–18 mo of age. Interim analysis of the primary end point was planned when 535 first B-CAP episodes, occurring ?2 wk after dose 3, were identified in the per-protocol cohort. After a mean follow-up of 23 mo (PHiD-CV, n?=?10,295; control, n?=?10,201), per-protocol VE was 22.0% (95% CI: 7.7, 34.2; one-sided p?=?0.002) against B-CAP (conclusive for primary objective) and 25.7% (95% CI: 8.4%, 39.6%) against World Health Organization–defined consolidated CAP. Intent-to-treat VE was 18.2% (95% CI: 5.5%, 29.1%) against B-CAP and 23.4% (95% CI: 8.8%, 35.7%) against consolidated CAP. End-of-study per-protocol analyses were performed after a mean follow-up of 28–30 mo for CAP and invasive pneumococcal disease (IPD) (PHiD-CV, n?=?10,211; control, n?=?10,140) and AOM (n?=?3,010 and 2,979, respectively). Per-protocol VE was 16.1% (95% CI: ?1.1%, 30.4%; one-sided p?=?0.032) against clinically confirmed AOM, 67.1% (95% CI: 17.0%, 86.9%) against vaccine serotype clinically confirmed AOM, 100% (95% CI: 74.3%, 100%) against vaccine serotype IPD, and 65.0% (95% CI: 11.1%, 86.2%) against any IPD. Results were consistent between intent-to-treat and per-protocol analyses. Serious adverse events were reported for 21.5% (95% CI: 20.7%, 22.2%) and 22.6% (95% CI: 21.9%, 23.4%) of PHiD-CV and control recipients, respectively. There were 19 deaths (n?=?11,798; 0.16%) in the PHiD-CV group and 26 deaths (n?=?11,799; 0.22%) in the control group. A significant study limitation was the lower than expected number of captured AOM cases. Conclusions Efficacy was demonstrated against a broad range of pneumococcal diseases commonly encountered in young children in clinical practice. Trial registration www.ClinicalTrials.gov NCT00466947 Please see later in the article for the Editors' Summary PMID:24892763

  18. Novel quadrivalent meningococcal A, C, W-135 and Y glycoconjugate vaccine for the broader protection of adolescents and adults.

    PubMed

    Pace, David

    2010-11-01

    Meningococcal meningitis and septicemia are a persistent public health concern owing to the associated mortality and devastating long-term sequelae. People of all ages may be affected, with the disease burden being higher in at-risk groups. Vaccination is the most rational approach to the prevention of invasive meningococcal disease. A novel quadrivalent meningococcal (Men) serogroup A, C, W-135 and Y polysaccharide-protein conjugate vaccine (MenACWY-CRM), has recently been licensed for use in individuals aged at least 11 years old in the USA, Canada and Europe. One dose of MenACWY-CRM is well tolerated, and induces robust immunity to all constituent vaccine serogroups in 11-65 year old individuals. MenACWY-CRM was found to be noninferior to the quadrivalent meningococcal ACWY-diphtheria toxoid glycoconjugate vaccine, which is also licensed in the USA and Canada. In Europe, MenACWY-CRM is the first quadrivalent meningococcal glycoconjugate vaccine available to provide broader protection against Neisseria meningitidis serogroups A, C, W-135 and Y. PMID:21133685

  19. Mannan-Abeta28 conjugate prevents Abeta-plaque deposition, but increases microhemorrhages in the brains of vaccinated Tg2576 (APPsw) mice

    PubMed Central

    Petrushina, Irina; Ghochikyan, Anahit; Mkrtichyan, Mikayel; Mamikonyan, Grigor; Movsesyan, Nina; Ajdari, Rodmehr; Vasilevko, Vitaly; Karapetyan, Adrine; Lees, Andrew; Agadjanyan, Michael G; Cribbs, David H

    2008-01-01

    Background New pre-clinical trials in AD mouse models may help to develop novel immunogen-adjuvant configurations with the potential to avoid the adverse responses that occurred during the clinical trials with AN-1792 vaccine formulation. Recently, we have pursued an alternative immunization strategy that replaces QS21 the Th1 type adjuvant used in the AN-1792 clinical trial with a molecular adjuvant, mannan that can promote a Th2-polarized immune response through interactions with mannose-binding and CD35/CD21 receptors of the innate immune system. Previously we established that immunization of wild-type mice with mannan-A?28 conjugate promoted Th2-mediated humoral and cellular immune responses. In the current study, we tested the efficacy of this vaccine configuration in amyloid precursor protein (APP) transgenic mice (Tg2576). Methods Mannan was purified, activated and chemically conjugated to A?28 peptide. Humoral immune responses induced by the immunization of mice with mannan-A?28 conjugate were analyzed using a standard ELISA. A?42 and A?40 amyloid burden, cerebral amyloid angiopathy (CAA), astrocytosis, and microgliosis in the brain of immunized and control mice were detected using immunohistochemistry. Additionally, cored plaques and cerebral vascular microhemorrhages in the brains of vaccinated mice were detected by standard histochemistry. Results Immunizations with low doses of mannan-A?28 induced potent and long-lasting anti-A? humoral responses in Tg2576 mice. Even 11 months after the last injection, the immunized mice were still producing low levels of anti-A? antibodies, predominantly of the IgG1 isotype, indicative of a Th2 immune response. Vaccination with mannan-A?28 prevented A? plaque deposition, but unexpectedly increased the level of microhemorrhages in the brains of aged immunized mice compared to two groups of control animals of the same age either injected with molecular adjuvant fused with an irrelevant antigen, BSA (mannan-BSA) or non-immunized mice. Of note, mice immunized with mannan-A?28 showed a trend toward elevated levels of CAA in the neocortex and in the leptomeninges compared to that in mice of both control groups. Conclusion Mannan conjugated to A?28 provided sufficient adjuvant activity to induce potent anti-A? antibodies in APP transgenic mice, which have been shown to be hyporesponsive to immunization with A? self-antigen. However, in old Tg2576 mice there were increased levels of cerebral microhemorrhages in mannan-A?28 immunized mice. This effect was likely unrelated to the anti-mannan antibodies induced by the immunoconjugate, because control mice immunized with mannan-BSA also induced antibodies specific to mannan, but did not have increased levels of cerebral microhemorrhages compared with non-immunized mice. Whether these anti-mannan antibodies increased the permeability of the blood brain barrier thus allowing elevated levels of anti-A? antibodies entry into cerebral perivascular or brain parenchymal spaces and contributed to the increased incidence of microhemorrhages remains to be investigated in the future studies. PMID:18823564

  20. Decreasing incidence and changes in serotype distribution of invasive pneumococcal disease in persons aged under 18 years since introduction of 10-valent and 13-valent conjugate vaccines in Portugal, July 2008 to June 2012.

    PubMed

    Aguiar, S I; Brito, M J; Horacio, A N; Lopes, J P; Ramirez, M; Melo-Cristino, J

    2014-01-01

    The 10-valent pneumococcal conjugate vaccine (PCV10) became available in Portugal in mid-2009 and the 13-valent vaccine (PCV13) in early 2010. The incidence of invasive pneumococcal disease (IPD) in patients aged under 18 years decreased from 8.19 cases per 100,000 in 2008–09 to 4.52/100,000 in 2011–12. However, IPD incidence due to the serotypes included in the 7-valent conjugate vaccine (PCV7) in children aged under two years remained constant. This fall resulted from significant decreases in the number of cases due to: (i) the additional serotypes included in PCV10 and PCV13 (1, 5, 7F; from 37.6% to 20.6%), particularly serotype 1 in older children; and (ii) the additional serotypes included in PCV13 (3, 6A, 19A; from 31.6% to 16.2%), particularly serotype 19A in younger children. The decrease in serotype 19A before vaccination indicates that it was not triggered by PCV13 administration. The decrease of serotype 1 in all groups, concomitant with the introduction of PCV10, is also unlikely to have been triggered by vaccination, although PCVs may have intensified and supported these trends. PCV13 serotypes remain major causes of IPD, accounting for 63.2% of isolates recovered in Portugal in 2011–12, highlighting the potential role of enhanced vaccination in reducing paediatric IPD in Portugal. PMID:24698140

  1. 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) induces memory B cell responses in healthy Kenyan toddlers

    PubMed Central

    Muema, D M; Nduati, E W; Uyoga, M; Bashraheil, M; Scott, J A G; Hammitt, L L; Urban, B C

    2015-01-01

    Memory B cells are long-lived and could contribute to persistence of humoral immunity by maintaining the plasma-cell pool or making recall responses upon re-exposure to an antigen. We determined the ability of a pneumococcal conjugate vaccine to induce anti-pneumococcal memory B cells. Frequencies of memory B cells against pneumococcal capsular polysaccharides from serotypes 1, 6B, 14, 19F and 23F were determined by cultured B cell enzyme-linked immunospot (ELISPOT) in 35 children aged 12–23 months who received pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV). The relationships between plasma antibodies and memory B cell frequencies were also assessed. After two doses of PHiD-CV, the proportion of subjects with detectable memory B cells against pneumococcal capsular polysaccharides increased significantly for serotypes 1 (3–45%; P?

  2. Anti-nicotine vaccines: Comparison of adjuvanted CRM197 and Qb-VLP conjugate formulations for immunogenicity and function in non-human primates.

    PubMed

    McCluskie, Michael J; Thorn, Jennifer; Gervais, David P; Stead, David R; Zhang, Ningli; Benoit, Michelle; Cartier, Janna; Kim, In-Jeong; Bhattacharya, Keshab; Finneman, Jari I; Merson, James R; Davis, Heather L

    2015-12-01

    Anti-nicotine vaccines comprise nicotine-like haptens conjugated to a carrier protein plus adjuvant(s). Unfortunately, those tested clinically have failed to improve overall long term quit rates. We had shown in mice that carrier, hapten, linker, hapten load (number of haptens per carrier molecule), aggregation and adducts, as well as adjuvants influence the function of antibodies (Ab) induced. Herein, we tested an optimized antigen, NIC7-CRM, comprised of 5-aminoethoxy-nicotine (NIC7) conjugated to genetically detoxified diphtheria toxin (CRM197), with hapten load of ~16, no aggregation (~100% monomer) and minimal adducts. NIC7-CRM was tested in non-human primates (NHP) and compared to NIC-VLP, which has the same hapten and carrier as the clinical-stage CYT002-NicQb but a slightly different linker and lower hapten load. With alum as sole adjuvant, NIC7-CRM was superior to NIC-VLP for Ab titer, avidity and ex vivo function (83% and 27% nicotine binding at 40ng/mL respectively), but equivalent for in vivo function after intravenous [IV] nicotine challenge (brain levels reduced ~10%). CpG adjuvant added to NIC7-CRM/alum further enhanced the Ab responses and both ex vivo function (100% bound) and in vivo function (~80% reduction in brain). Thus, both optimal antigen design and CpG adjuvant were required to achieve a highly functional vaccine. The compelling NHP data with NIC7-CRM with alum/CpG supported human testing, currently underway. PMID:26404190

  3. Safety and Immunogenicity of Improved Shigella O-Specific Polysaccharide-Protein Conjugate Vaccines in Adults in Israel

    PubMed Central

    Passwell, Justen H.; Harlev, Efrat; Ashkenazi, Shai; Chu, Chiayung; Miron, Dan; Ramon, Reut; Farzan, Naheed; Shiloach, Joseph; Bryla, Dolores A.; Majadly, Fathy; Roberson, Robin; Robbins, John B.; Schneerson, Rachel

    2001-01-01

    Data suggest that the O-specific polysaccharide (O-SP) domain of the lipopolysaccharide (LPS) of Shigella species is both an essential virulence factor and a protective antigen and that a critical level of serum immunoglobulin G (IgG) to this antigen will confer immunity to shigellosis. Because covalent attachment of polysaccharides to proteins increases their immunogenicity, especially in infants and in young children, the O-SP of Shigella species were bound to medically useful proteins, and the safety and immunogenicity of the resultant conjugates were confirmed in adults and 4- to 7-year-old children. Succinylation of the carrier protein improved the immunogenicity of Shigella conjugates in mice and increased their yield. Based on these results, a clinical trial of O-SP conjugates of Shigella sonnei and Shigella flexneri 2a bound to succinylated mutant Pseudomonas aeruginosa exotoxin A (rEPAsucc) or native or succinylated Corynebacterium diphtheriae toxin mutant (CRM9 or CRM9succ) was conducted in healthy adults. The conjugates were safe and immunogenic. S. sonnei-CRM9, S. sonnei-CRM9succ, and S. sonnei-rEPAsucc elicited significant rises of geometric mean (GM) IgG anti-LPS within 1 week of injection (P < 0.001). At 26 weeks, the GM anti-LPS levels elicited by these three conjugates were similar and higher than their prevaccination levels (P < 0.0001). GM IgG anti-LPS levels elicited by S. flexneri 2a-rEPAsucc were significantly higher than those elicited by S. flexneri 2a-rCRM9succ at all intervals after injection. At 26 weeks, the levels of IgG anti-LPS in vaccinees were higher than their prevaccination levels (P < 0.0001). The serum antibody responses were specific, as there was no significant rise of anti-LPS to the heterologous O-SP in any vaccinee. Both conjugates elicited statistically significant rises of serum antibodies to the injected carrier protein. At 6 months, these five Shigella conjugates elicited higher fold rises than similar conjugates (D. N. Taylor et al., Infect. Immun. 61:3678–3687, 1993). Based on these data, we chose S. sonnei-CRM9 and S. flexneri 2a-rEPAsucc for evaluation in children. PMID:11179298

  4. The Diversity of Meningococcal Carriage Across the African Meningitis Belt and the Impact of Vaccination With a Group A Meningococcal Conjugate Vaccine

    E-print Network

    MenAfriCar Consortium

    2015-04-09

    Yamuah; Centre de Recherche Médicale et Sanitaire, Niamey, Niger (member of the International Network of Pasteur Institutes): Rahamatou Moustapha Boukary, Jean- Marc Collard (PI), Ibrahim Dan Dano, Ibrahim Habiboulaye, Bassira Issaka, Jean-François Jusot... of meningococcal vaccination on pharyngeal carriage of meningococci. Trop Med Int Health 2007; 12:1409–21. 25. Virji M. Pathogenic neisseriae: surface modulation, pathogenesis and infection control. Nat Rev Microbiol 2009; 7:274–86. 26. Collard JM, Issaka B...

  5. Differences in Homing Potentials of Streptococcus pneumoniae–Specific Plasmablasts in Pneumococcal Pneumonia and After Pneumococcal Polysaccharide and Pneumococcal Conjugate Vaccinations

    PubMed Central

    Palkola, Nina V.; Pakkanen, Sari H.; Kantele, Jussi M.; Pakarinen, Laura; Puohiniemi, Ritvaleena; Kantele, Anu

    2015-01-01

    Background.?Mucosal immune mechanisms in the upper and lower respiratory tracts may serve a critical role in preventing pneumonia due to Streptococcus pneumoniae. Streptococcus pneumoniae–specific plasmablasts presumably originating in the lower respiratory tract have recently been found in the circulation in patients with pneumonia. The localization of an immune response can be evaluated by exploring homing receptors on such plasmablasts, yet no data have thus far described homing receptors in pneumonia. Methods.?The expression of ?4?7, L-selectin, and cutaneous lymphocyte antigen (CLA) on S. pneumoniae–specific plasmablasts was examined in patients with pneumonia (n = 16) and healthy volunteers given pneumococcal polysaccharide vaccine (PPV; n = 14) or pneumococcal conjugate vaccine (PCV; n = 11). Results.?In patients with pneumonia, the proportion of S. pneumoniae–specific plasmablasts expressing L-selectin was high, the proportion expressing ?4?7 was moderate, and the proportion expressing CLA was low. The homing receptor ?4?7 was expressed more frequently in the pneumonia group than in the PPV (P = .000) and PCV (P = .029) groups, L-selectin was expressed more frequently in the PPV group than in the PCV group (P = .014); and CLA was expressed more frequently in the pneumonia group than in the PPV group (P = .001). Conclusions.?The homing receptor profile in patients with pneumonia was unique yet it was closer to that in PCV recipients than in PPV recipients. These data suggest greater mucosal localization for immune response in natural infection, which is clinically interesting, especially considering the shortcomings of vaccines in protecting against noninvasive pneumonia. PMID:25838267

  6. Evaluation of the efficacy of immunocastration vaccine composed of gonadotrophin-releasing hormone conjugated with Salmonella typhimurium flagellin in rats.

    PubMed

    Song, Y J; Kim, D G; Nam, H M; Lee, J B; Park, S Y; Song, C S; Seo, K H; Kim, H M; Choi, I S

    2012-08-01

    Immunocastration is an alternative method to replace surgical castration that is commonly performed in domestic and pet animals. In this study, a new immunocastration vaccine was developed, and its efficacy was evaluated in male rats. Six tandem copies of gonadotrophin-releasing hormone (GnRH) peptide were genetically fused to Salmonella typhimurium flagellin fljB (STF2) that is a ligand of toll-like receptor 5 (TLR5). The recombinant STF2-GnRH protein expressed in Escherichia coli was used as the immunocastration vaccine. Sixteen male rats were equally assigned to four groups. Excluding the control rats, three groups were immunized with 100, 200 and 400 ?g of the STF2-GnRH vaccine, respectively. All of the immunized rats developed significantly higher titres of antibodies to GnRH than the control rats. The size and weight of both testes and epididymides from the immunized rats were significantly smaller than those of the control rats. Testicular tissues in the immunized rats demonstrated atrophy of seminiferous tubules and decreased numbers of both spermatogonia and spermatocytes. These data indicate that the newly developed STF2-GnRH vaccine has a potent immunogenicity to GnRH and efficiently suppresses the development of testes in rats. PMID:22044754

  7. Secular trends (1990-2013) in serotypes and associated non-susceptibility of S. pneumoniae isolates causing invasive disease in the pre-/post-era of pneumococcal conjugate vaccines in Spanish regions without universal paediatric pneumococcal vaccination.

    PubMed

    Fenoll, Asunción; Granizo, Juan-José; Giménez, María-José; Yuste, José; Aguilar, Lorenzo

    2015-10-13

    This study analyzed temporal trends of non-susceptibility/serotypes in invasive pneumococci from Spanish regions where pneumococcal conjugate vaccines (PCVs) were not included in paediatric immunization programmes. All invasive pneumococcal isolates voluntarily sent to the Spanish Reference Laboratory for Pneumococci (January 1990-December 2013) from hospitals located in target study regions were analyzed by age group. The PCV estimated coverage in children <24 months was correlated with 13-valent PCV (PCV13) serotypes trends. A total of 28,124 invasive isolates were analyzed: 3138 (11.2%) from children <24 months, 2161 (7.7%) from children 24-59 months, 781 (2.8%) from children 5-14 years, and 22,044 (78.4%) from adults. The estimated coverage increased from 17.6% (2002) to around 40% (2010-2013). The percentage of PCV13 serotypes among all isolates over time followed a cubic significant trend (R(2)=0.884), with an increasing trend up to 2001 followed by a decrease (more prominent from 2010 onwards). The estimated PCVs coverage was significantly correlated with the decrease in the percentage of PCV13 isolates in children <24 months (r(2)=0.824) and in adults (r(2)=0.786), mainly due to decreases in serotypes 1 and 7F in adults, and in serogroup 6 and serotypes 7F and 19A in children <24 months. None of the non-PCV13 serotypes stood out with substantial increases in the last period. This study showed that the different serotypes (and its associated non-susceptibility trends) were not equally affected by low PCVs disposition. Lack of impact in certain serotypes as serotype 1 (in children 24-59 months), 6C (in all age groups), and 19A (in adults) suggests the need for increasing vaccine coverage in the target vaccine population to increase direct and indirect protection. PMID:26341563

  8. Direct Comparison of Immunogenicity Induced by 10- or 13-Valent Pneumococcal Conjugate Vaccine around the 11-Month Booster in Dutch Infants

    PubMed Central

    Wijmenga-Monsuur, Alienke J.; van Westen, Els; Knol, Mirjam J.; Jongerius, Riet M. C.; Zancolli, Marta; Goldblatt, David; van Gageldonk, Pieter G. M.; Tcherniaeva, Irina; Berbers, Guy A. M.; Rots, Nynke Y.

    2015-01-01

    Background & Aims Since 2009/10, a 10- and a 13-valent pneumococcal conjugate vaccine (PCV) are available, but only the 10-valent vaccine is now being used for the children in the Netherlands. As the vaccines differ in number of serotypes, antigen concentration, and carrier proteins this study was designed to directly compare quantity and quality of the antibody responses induced by PCV10 and PCV13 before and after the 11-month booster. Methods Dutch infants (n = 132) were immunized with either PCV10 or PCV13 and DTaP-IPV-Hib-HepB at the age of 2, 3, 4 and 11 months. Blood samples were collected pre-booster and post-booster at one week and one month post-booster for quantitative and qualitative immunogenicity against 13 pneumococcal serotypes, as well as quantitative immunogenicity against diphtheria, tetanus, pertussis and Haemophilus influenzae type b. We compared immunogenicity induced by PCV13 and PCV10 for their ten shared serotypes. Results One month post-booster, pneumococcal serotype-specific IgG geometric mean concentrations (GMCs) for the PCV13 group were higher compared with the PCV10 group for six serotypes, although avidity was lower. Serotype 19F showed the most distinct difference in IgG and, in contrast to other serotypes, its avidity was higher in the PCV13 group. One week post-booster, opsonophagocytosis for serotype 19F did not differ significantly between the PCV10- and the PCV13 group. Conclusion Both PCV10 and PCV13 were immunogenic and induced a booster response. Compared to the PCV10 group, the PCV13 group showed higher levels for serotype 19F GMCs and avidity, pre- as well as post-booster, although opsonophagocytosis did not differ significantly between groups. In our study, avidity is not correlated to opsonophagocytotic activity (OPA) and correlations between IgG and OPA differ per serotype. Therefore, besides assays to determine IgG GMCs, assays to detect opsonophagocytotic activity, i.e., the actual killing of the pneumococcus, are important for PCV evaluation. How differences between the two vaccines relate to long-term protection requires further investigation. Trial Registration www.trialregister.nl NTR3069 PMID:26658902

  9. Decrease in Hospitalizations for Pneumonia in Children under Five Years of Age in an Indian Reservation in Panama after the Introduction of the Heptavalent Pneumococcal Conjugate Vaccine (PCV7)

    PubMed Central

    Nieto Guevara, Javier; Daza, Carlos

    2013-01-01

    This study quantifies the impact of Heptavalent-Pneumococcal Conjugate Vaccine (PCV7) in Panama on indigenous children younger than 5 years old, based on clinical pneumonia cases. This study demonstrates a significant 41.2% reduction in hospitalizations and 38.6% reduction in referrals for pneumonia following the introduction of PCV7. Burden of disease from pneumonia appears reduced in the ?12-month- and 13-to-24-month-old groups. PMID:23762081

  10. Evaluation of indirect enzyme-linked immunosorbent assays and IgG avidity assays using a protein A-peroxidase conjugate for serological distinction between Brucella abortus S19-vaccinated and -infected cows.

    PubMed

    Pajuaba, Ana C A M; Silva, Deise A O; Mineo, José R

    2010-04-01

    This study aimed to evaluate the use of protein A-peroxidase (horseradish peroxidase [HRPO]) in indirect enzyme-linked immunosorbent assays (iELISAs) and IgG avidity assays for serological distinction between Brucella abortus S19-vaccinated and -infected cows. Four groups were analyzed: GI, 41 nonvaccinated seropositive cows; GII, 79 S19-vaccinated heifers analyzed at 3 months postvaccination; GIII, 105 S19-vaccinated cows analyzed after 24 months of age; and GIV, 278 nonvaccinated seronegative cows. IgG levels and avidity to B. abortus smooth lipopolysaccharide (S-LPS) were determined using anti-bovine IgG-HRPO or protein A-HRPO conjugates. Similar levels of IgG anti-S-LPS were found with GI using both conjugates. Lower IgG levels were detected with GII, GIII, and GIV using protein A-HRPO. Both conjugates showed high performance in discriminating GI from GIII, with high sensitivity (Se; 97.6%) and specificity (Sp; 97.1%). Protein A-HRPO was better in distinguishing GI from GIV (Se, 97.6%; Sp, 94.6%) and GI from GII (Se, 80.5%; Sp, 94.9%). Protein A-HRPO excluded a higher number of positive samples with GII and GIV. IgG avidity showed that protein A-HRPO, but not anti-IgG-HRPO, was able to distinguish nonvaccinated from vaccinated cattle, showing a higher avidity index (AI) with GI than with GII, with 78% of serum samples in GII showing an AI of <50%. Therefore, the iELISA using B. abortus S-LPS antigen and protein A-HRPO conjugate for preferential detection of the IgG2 subclass was shown to be suitable for serological distinction between S19-vaccinated and -infected cows. Also, antibodies generated after vaccination showed lower avidity, suggesting a role for the IgG2 subclass as an antibody of higher-affinity maturation after infection, constituting an additional tool for differentiating vaccinated from infected cattle. PMID:20147498

  11. Safety and Immunogenicity of Quadrivalent Meningococcal Conjugate Vaccine in 2 to 10 Year-Old Human Immunodeficiency Virus-Infected Children

    PubMed Central

    Siberry, George K.; Warshaw, Meredith G.; Williams, Paige L.; Spector, Stephen A.; Decker, Michael D.; Jean-Philippe, Patrick; Yogev, Ram; Heckman, Barbara E.; Manzella, Adam; Roa, Jhoanna; Nachman, Sharon; Lujan-Zilbermann, Jorge

    2011-01-01

    Background HIV-infected children are at increased risk of meningococcal infection and poor response to quadrivalent meningococcal conjugate vaccine (MCV4), but MCV4 has not been studied in pre-adolescent HIV-infected children. Methods The P1065 trial enrolled 2-10 year-old HIV-infected children with CD4 ?25% to receive MCV4 at entry and at week 24. Rates of response (?4-fold rise in rabbit serum bactericidal antibody [rSBA]) against each meningococcal serogroup [A, C, Y, W-135], geometric mean titers (GMT), and rates of seroprotection (rSBA titer ?1:128) were determined from sera obtained at entry and weeks 4, 24, 28 and 72. Adverse events (AE) were assessed for 6 weeks after each MCV4 dose. Results At entry, 47% of the 59 participants were male, 56% black, 31% Latino, median age was 6 years, 88% were receiving antiretroviral therapy, and 75% had viral load <400 copies/mL. There were no serious AEs within 6 weeks after MCV4 doses; all vaccination reactions were mild. Response after a single MCV4 dose was high to serogroup A (92%) and W-135 (98%); responses improved after a second dose for serogroup C (43% to 80%) [p<0.0001] and Y (76% to 84%) [p=0.38]. By week 72, seroprotection rates were 93%, 91%, 78% and 46% for serogroups W-135, Y, A and C, respectively. Conclusions Two doses of MCV4 were safe and immunogenic in 2-10 year-old HIV-infected children. The second dose increased the proportion of children who made a response to serogroup C. Seroprotection waned substantially for serogroups A and C within one year of last MCV4 dose. PMID:21987006

  12. Laboratory surveillance of invasive pneumococcal disease in New South Wales, Australia, before and after introduction of 7-valent conjugate vaccine: reduced disease, but not antibiotic resistance rates.

    PubMed

    Oftadeh, S; Gidding, H F; Gilbert, G L

    2013-09-01

    We compared serotype distributions of Streptococcus pneumoniae isolates from patients aged <5 and o5 years with invasive pneumococcal disease in New South Wales, Australia, and antibiotic susceptibilities of isolates from the <5 years age group only, before (2002–2004) and after(2005–2009) introduction of the 7-valent pneumococcal conjugate vaccine (PCV7). Overall, there were significant decreases in the mean annual number of referred isolates (770 vs. 515) and the proportion belonging to PCV7 serotypes (74% vs. 38%), but non-PCV7 serotypes, particularly 19A, increased (5% vs. 18%). All changes were more marked in the <5 years age group.Susceptibility testing of isolates from the <5 years age group showed variation in resistance between serotypes, but significant overall increases in penicillin non-susceptibility (23% vs. 31%),ceftriaxone resistance (2% vs. 12%) and multidrug resistance (4% vs. 7%) rates ; erythromycin resistance fell (32% vs. 25%). Continued surveillance is needed to monitor changes following the introduction of 13-valent PCV in 2012. PMID:23010351

  13. Economic Evaluation of Immunisation Programme of 23-Valent Pneumococcal Polysaccharide Vaccine and the Inclusion of 13-Valent Pneumococcal Conjugate Vaccine in the List for Single-Dose Subsidy to the Elderly in Japan

    PubMed Central

    Hoshi, Shu-ling; Kondo, Masahide; Okubo, Ichiro

    2015-01-01

    Background Currently in Japan, both 23-valent pneumococcal polysaccharide vaccine (PPSV–23) and 13-valent pneumococcal conjugate vaccine (PCV–13) are available for the elderly for the prevention of S. pneumoniae-related diseases. PPSV–23 was approved in 1988, while the extended use of PCV–13 was approved for adults aged 65 and older in June 2014. Despite these two vaccines being available, the recently launched national immunisation programme for the elderly only subsidised PPSV–23. The framework of the current immunisation programme lasts for five years. The elderly population eligible for the subsidised PPSV–23 shot for the 1st year are those aged 65, 70, 75, 80, 85, 90, 95 and ?100. While from the 2nd year to the 5th year, those who will age 65, 70, 75, 80, 85, 90, 95 and 100 will receive the same subsidised shot. Methods We performed economic evaluations to (1) evaluate the efficiency of alternative strategies of PPSV–23 single-dose immunisation programme, and (2) investigate the efficiency of PCV–13 inclusion in the list for single-dose pneumococcal vaccine immunisation programme. Three alternative strategies were created in this study, namely: (1) current PPSV–23 strategy, (2) 65 to 80 (as “65–80 PPSV–23 strategy”), and (3) 65 and older (as “?65 PPSV–23 strategy”). We constructed a Markov model depicting the S. pneumoniae-related disease course pathways. The transition probabilities, utility weights to estimate quality adjusted life year (QALY) and disease treatment costs were either calculated or cited from literature. Cost of per shot of vaccine was ¥8,116 (US$74; US$1 = ¥110) for PPSV–23 and ¥10,776 (US$98) for PCV–13. The model runs for 15 years with one year cycle after immunisation. Discounting was at 3%. Results Compared to current PPSV–23 strategy, 65–80 PPSV–23 strategy cost less but gained less, while the incremental cost-effectiveness ratios (ICERs) of ?65 PPSV–23 strategy was ¥5,025,000 (US$45,682) per QALY gained. PCV–13 inclusion into the list for single-dose subsidy has an ICER of ¥377,000 (US$3,427) per QALY gained regardless of the PCV–13 diffusion level. These ICERs were found to be cost-effective since they are lower than the suggested criterion by WHO of three times GDP (¥11,000,000 or US$113,636 per QALY gained), which is the benchmark used in judging the cost-effectiveness of an immunisation programmne. Conclusions The results suggest that switching current PPSV–23 strategy to ?65 PPSV–23 strategy or including PCV–13 into the list for single-dose subsidy to the elderly in Japan has value for money. PMID:26444287

  14. Bacillus anthracis Capsular Conjugates Elicit Chimpanzee Polyclonal Antibodies That Protect Mice from Pulmonary Anthrax.

    PubMed

    Chen, Zhaochun; Schneerson, Rachel; Lovchik, Julie A; Dai, Zhongdong; Kubler-Kielb, Joanna; Agulto, Liane; Leppla, Stephen H; Purcell, Robert H

    2015-08-01

    The immunogenicity of Bacillus anthracis capsule (poly-?-D-glutamic acid [PGA]) conjugated to recombinant B. anthracis protective antigen (rPA) or to tetanus toxoid (TT) was evaluated in two anthrax-naive juvenile chimpanzees. In a previous study of these conjugates, highly protective monoclonal antibodies (MAbs) against PGA were generated. This study examines the polyclonal antibody response of the same animals. Preimmune antibodies to PGA with titers of >10(3) were detected in the chimpanzees. The maximal titer of anti-PGA was induced within 1 to 2 weeks following the 1st immunization, with no booster effects following the 2nd and 3rd immunizations. Thus, the anti-PGA response in the chimpanzees resembled a secondary immune response. Screening of sera from nine unimmunized chimpanzees and six humans revealed antibodies to PGA in all samples, with an average titer of 10(3). An anti-PA response was also observed following immunization with PGA-rPA conjugate, similar to that seen following immunization with rPA alone. However, in contrast to anti-PGA, preimmune anti-PA antibody titers and those following the 1st immunization were ?300, with the antibodies peaking above 10(4) following the 2nd immunization. The polyclonal anti-PGA shared the MAb 11D epitope and, similar to the MAbs, exerted opsonophagocytic killing of B. anthracis. Most important, the PGA-TT-induced antibodies protected mice from a lethal challenge with virulent B. anthracis spores. Our data support the use of PGA conjugates, especially PGA-rPA targeting both toxin and capsule, as expanded-spectrum anthrax vaccines. PMID:26041039

  15. MenAfriVac as an Antitetanus Vaccine

    PubMed Central

    Borrow, Ray; Tang, Yuxiao; Yakubu, Ahmadu; Kulkarni, Prasad S.; LaForce, F. Marc

    2015-01-01

    Background.?The group A meningococcal conjugate vaccine, PsA-TT, uses tetanus toxoid (TT) as a carrier protein (PsA-TT). TT as a carrier protein in other conjugate vaccines is known to be immunogenic and generates a robust anti-TT response. Methods.?Clinical studies in Africa assessed whether PsA-TT generated tetanus serologic responses when tested in African populations (toddlers to adults). Second, the high acceptance of PsA-TT mass immunization campaigns in the 1- to 29-year age group meant that a sizeable fraction of women of reproductive age received PsA-TT. Incidence data for neonatal tetanus were reviewed for countries with and without PsA-TT campaigns to check whether this had any impact on the incidence. Results.?PsA-TT generated robust tetanus serologic responses in 1- to 29-year-olds, similar to those expected after a booster dose of TT. Neonatal cases of tetanus fell by 25% in countries that completed PsA-TT campaigns in 1- to 29-year-olds. Conclusions.?Although these data are not yet definitive, they are consistent with the hypothesis that improved community immunity to tetanus as a result of the PsA-TT campaigns may be having an impact on the incidence of neonatal tetanus in sub-Saharan Africa. Clinical Trials Registration.?ISRCTN17662153 (PsA-TT 001); ISRTCN78147026 (PsA-TT 002); ISRCTN87739946 (PsA-TT 003); ISRCTN46335400 (PsA-TT 003a); ISRCTN82484612 (PsA-TT 004); CTRI/2009/091/000368 (PsA-TT 005); PACTR ATMR2010030001913177 (PsA-TT 006); and PACTR201110000328305 (PsA-TT 007). PMID:26553690

  16. 78 FR 12763 - Pediatric Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2013-02-25

    ...W-135) Polysaccharide Diphtheria Toxoid Conjugate Vaccine], MOXEZA (moxifloxacin ophthalmic solution 0.5%), NATROBA (spinosad), NEXIUM (esomeprazole magnesium), NEXIUM IV (esomeprazole sodium), UROXATRAL (alfuzosin hydrochloride), and...

  17. Evaluation of the Induction of Immune Memory following Infant Immunisation with Serogroup C Neisseria meningitidis Conjugate Vaccines – Exploratory Analyses within a Randomised Controlled Trial

    PubMed Central

    Khatami, Ameneh; Clutterbuck, Elizabeth A.; Thompson, Amber J.; McKenna, Jennifer A.; Pace, David; Birks, Jacqueline; Snape, Matthew D.; Pollard, Andrew J.

    2014-01-01

    Aim We measured meningococcal serogroup C (MenC)-specific memory B-cell responses in infants by Enzyme-Linked Immunospot (ELISpot) following different MenC conjugate vaccine schedules to investigate the impact of priming on immune memory. Methods Infants aged 2 months were randomised to receive 1 or 2 doses of MenC-CRM197 at 3 or 3 and 4 months, 1 dose of MenC-TT at 3 months, or no primary MenC doses. All children received a Haemophilus influenzae type b (Hib)-MenC booster at 12 months. Blood was drawn at 5, 12, 12 months +6 days and 13 months of age. Results Results were available for 110, 103, 76 and 44 children from each group respectively. Following primary immunisations, and prior to the 12-month booster, there were no significant differences between 1- or 2-dose primed children in the number of MenC memory B-cells detected. One month following the booster, children primed with 1 dose MenC-TT had more memory B-cells than children primed with either 1-dose (p?=?0.001) or 2-dose (p<0.0001) MenC-CRM197. There were no differences in MenC memory B-cells detected in children who received 1 or 2 doses of MenC-CRM197 in infancy and un-primed children. Conclusions MenC-specific memory B-cell production may be more dependent on the type of primary vaccine used than the number of doses administered. Although the mechanistic differences between MenC-CRM197 and MenC-TT priming are unclear, it is possible that structural differences, including the carrier proteins, may underlie differential interactions with B- and T-cell populations, and thus different effects on various memory B-cell subsets. A MenC-TT/Hib-MenC-TT combination for priming/boosting may offer an advantage in inducing more persistent antibody. Trial Registration EU Clinical Trials Register 2009-016579-31 ClinicalTrials.gov NCT01129518 PMID:25020050

  18. Impact of the Pneumococcal Conjugate Vaccine and Antibiotic Use on Nasopharyngeal Colonization by Antibiotic Nonsusceptible Streptococcus pneumoniae — Alaska, 2000–2010

    PubMed Central

    Gounder, Prabhu P.; Brewster, Melissa; Bruce, Michael G.; Bruden, Dana JT.; Rudolph, Karen; Hurlburt, Debby A.; Hennessy, Thomas W.

    2015-01-01

    Background We describe the relative impact of the heptavalent pneumococcal conjugate vaccine (PCV7, introduced 2001) and antibiotic use on colonization by antibiotic resistant pneumococci in urban Alaskan children during 2000–2010. Methods We obtained nasopharyngeal swab specimens from a convenience sample of children aged <5 years at clinics annually during 2000–2004 and 2008–2010. PCV7 status and antibiotic use <90 days before enrollment was determined by interview/medical records review. Pneumococci were characterized by serotype and susceptibility to penicillin (PCN). Isolates with full PCN resistance (PCN-R) or intermediate PCN resistance (PCN-I) were classified as PCN-NS. Results We recruited 3,496 children (median: 452/year). During 2000–2010, a range of 18–29%/year of children used PCN/amoxicillin (p-value for trend [p] = 0.09); the proportion age-appropriately vaccinated with PCV7 increased (0%–90%; p <0.01). Among pneumococcal isolates, the PCV7-serotype proportion decreased (53%–<1%; p <0.01) and non-PCV7–serotype proportion increased (43%–95%; p <0.01). PCN-R pneumococcal colonization prevalence decreased (23%–9%, p <0.01) and PCN-I pneumococcal colonization prevalence increased (13%–24%, p <0.01); overall PCN-NS pneumococcal colonization prevalence was unchanged. PCN-NS among colonizing PCV7-type and non-PCV7-type pneumococci remained unchanged; a mean of 31%/year of PCV7-type and 10%/year of non-PCV7-type isolates were PCN-R, and 10%/year of PCV7 and 20%/year of non-PCV7-type isolates were PCN-I. Conclusions Overall PCN-NS pneumococcal colonization remained unchanged during 2000–2010 because increased colonization by predominantly PCN-I non-PCV7 serotypes offset decreased colonization by predominantly PCN-R PCV7 serotypes. Proportion PCN-NS did not increase within colonizing pneumococcal serotype-groups (PCV7 versus non-PCV7) despite stable penicillin use in our population. PMID:26226443

  19. A Cholera Conjugate Vaccine Containing O-specific Polysaccharide (OSP) of V. cholerae O1 Inaba and Recombinant Fragment of Tetanus Toxin Heavy Chain (OSP:rTTHc) Induces Serum, Memory and Lamina Proprial Responses against OSP and Is Protective in Mice

    PubMed Central

    Eckhoff, Grace; Charles, Richelle C.; Alam, Mohammad Murshid; Sultana, Tania; Rashu, Md. Rasheduzzaman; Berger, Amanda; Gonzalez-Escobedo, Geoffrey; Mandlik, Anjali; Bhuiyan, Taufiqur Rahman; Leung, Daniel T.; LaRocque, Regina C.; Harris, Jason B.; Calderwood, Stephen B.; Qadri, Firdausi; Vann, W. F.; Ková?, Pavol; Ryan, Edward T.

    2015-01-01

    Background Vibrio cholerae is the cause of cholera, a severe watery diarrhea. Protection against cholera is serogroup specific. Serogroup specificity is defined by the O-specific polysaccharide (OSP) component of lipopolysaccharide (LPS). Methodology Here we describe a conjugate vaccine for cholera prepared via squaric acid chemistry from the OSP of V. cholerae O1 Inaba strain PIC018 and a recombinant heavy chain fragment of tetanus toxin (OSP:rTTHc). We assessed a range of vaccine doses based on the OSP content of the vaccine (10-50 ?g), vaccine compositions varying by molar loading ratio of OSP to rTTHc (3:1, 5:1, 10:1), effect of an adjuvant, and route of immunization. Principle Findings Immunized mice developed prominent anti-OSP and anti-TT serum IgG responses, as well as vibriocidal antibody and memory B cell responses following intramuscular or intradermal vaccination. Mice did not develop anti-squarate responses. Intestinal lamina proprial IgA responses targeting OSP occurred following intradermal vaccination. In general, we found comparable immune responses in mice immunized with these variations, although memory B cell and vibriocidal responses were blunted in mice receiving the highest dose of vaccine (50 ?g). We found no appreciable change in immune responses when the conjugate vaccine was administered in the presence or absence of immunoadjuvant alum. Administration of OSP:rTTHc resulted in 55% protective efficacy in a mouse survival cholera challenge model. Conclusion We report development of an Inaba OSP:rTTHc conjugate vaccine that induces memory responses and protection against cholera in mice. Development of an effective cholera conjugate vaccine that induces high level and long-term immune responses against OSP would be beneficial, especially in young children who respond poorly to polysaccharide antigens. PMID:26154421

  20. Modified Carbohydrate Cancer Vaccines for Breaking Immune Self-Tolerance

    E-print Network

    Miller, Isaac Andrew

    2010-01-01

    of  the   work  in  the  cancer  vaccine  field  focuses  the  work  in  the  carbohydrate-­? based  cancer  vaccine  work  to  synthesize  a  panel  of  STn-­?based   conjugate  cancer  vaccines.    

  1. Genetic and antigenic characterization of Canadian invasive Neisseria meningitidis serogroup C (MenC) case isolates in the post-MenC conjugate vaccine era, 2009-2013.

    PubMed

    Tsang, Raymond S W; Hoang, Linda; Tyrrell, Gregory; Horsman, Greg; Wylie, John; Jamieson, Frances B; Lefebvre, Brigitte; Taha, Muhamed-Kheir

    2015-02-01

    We previously reported a shift in the electrophoretic type (ET) of invasive MenC in Canada from predominantly ET-15 to ET-37 in the post-MenC conjugate vaccine period. This study sought to confirm this trend by examining all culture-confirmed invasive MenC case isolates in Canada in the period from 1 January 2009 to 31 December 2013. Of the 50 MenC isolates, 18 belonged to ET-15, 28 belonged to ET-37 (but not ET-15), and four belonged to other clonal types. Analysis of the serotype and serosubtype antigens, porA and fetA gene sequences provided data to show that invasive MenC belonging to ET-15 and ET-37 were two very different subpopulations within the ST-11 clonal complex. Sequence analysis of the fHbp genes suggested that 12 different types of factor H-binding protein were found among the ET-15 isolates while 86?% of ET-37 isolates were found to have fHbp genes predicted to encode peptide 22. The nadA gene in 12 MenC isolates was disrupted due to IS1301 insertion and 11 of these 12 isolates belonged to ET-15. Ten per cent of the invasive MenC were found to have a frame-shift mutation in their fHbp genes that predicted no fHbp produced. Significant diversity and frame-shift mutations of fHbp genes were found in invasive MenC strains in Canada. PMID:25627205

  2. Maternal Supplementation with LGG Reduces Vaccine-Specific Immune Responses in Infants at High-Risk of Developing Allergic Disease

    PubMed Central

    Licciardi, Paul V.; Ismail, Intan H.; Balloch, Anne; Mui, Milton; Hoe, Edwin; Lamb, Karen; Tang, Mimi L. K.

    2013-01-01

    Probiotics are defined as live micro-organisms that when administered in adequate amounts confer a health benefit on the host. Among their pleiotropic effects, inhibition of pathogen colonization at the mucosal surface as well as modulation of immune responses are widely recognized as the principal biological activities of probiotic bacteria. In recent times, the immune effects of probiotics have led to their application as vaccine adjuvants, offering a novel strategy for enhancing the efficacy of current vaccines. Such an approach is particularly relevant in regions where infectious disease burden is greatest and where access to complete vaccination programs is limited. In this study, we report the effects of the probiotic, Lactobacillus rhamnosus GG (LGG) on immune responses to tetanus, Haemophilus influenzae type b (Hib) and pneumococcal conjugate (PCV7) vaccines in infants. This study was conducted as part of a larger clinical trial assessing the impact of maternal LGG supplementation in preventing the development of atopic eczema in infants at high-risk for developing allergic disease. Maternal LGG supplementation was associated with reduced antibody responses against tetanus, Hib, and pneumococcal serotypes contained in PCV7 (N?=?31) compared to placebo treatment (N?=?30) but not total IgG levels. Maternal LGG supplementation was also associated with a trend to increased number of tetanus toxoid-specific T regulatory in the peripheral blood compared to placebo-treated infants. These findings suggest that maternal LGG supplementation may not be beneficial in terms of improving vaccine-specific immunity in infants. Further clinical studies are needed to confirm these findings. As probiotic immune effects can be species/strain specific, our findings do not exclude the potential use of other probiotic bacteria to modulate infant immune responses to vaccines. PMID:24324465

  3. RESPONSE OF CALVES PERSISTENTLY INFECTED WITH NONCYTOPATHIC BOVINE VIRAL DIARRHEA VIRUS (BVDV) SUBTYPE 1B AFTER VACCINATION WITH HETEROLOGOUS BVDV STRAINS IN MODIFIED LIVE VIRUS VACCINES AND MANNHEIMIA HAEMOLYTICA BACTERIA-TO

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Seronegative calves persistently infected (PI) with bovine viral diarrhea virus (BVDV) subtype 1b were vaccinated with each of four modified live virus (MLV) BVDV vaccines and a Mannheimia haemolytica bacterin-toxoid. Nasal swabs and peripheral blood leukocytes (PBL) were collected for virus isolati...

  4. Nanoparticle-detained toxins for safe and effective vaccination

    NASA Astrophysics Data System (ADS)

    Hu, Che-Ming J.; Fang, Ronnie H.; Luk, Brian T.; Zhang, Liangfang

    2013-12-01

    Toxoid vaccines--vaccines based on inactivated bacterial toxins--are routinely used to promote antitoxin immunity for the treatment and prevention of bacterial infections. Following chemical or heat denaturation, inactivated toxins can be administered to mount toxin-specific immune responses. However, retaining faithful antigenic presentation while removing toxin virulence remains a major challenge and presents a trade-off between efficacy and safety in toxoid development. Here, we show a nanoparticle-based toxin-detainment strategy that safely delivers non-disrupted pore-forming toxins for immune processing. Using erythrocyte membrane-coated nanoparticles and staphylococcal ?-haemolysin, we demonstrate effective virulence neutralization via spontaneous particle entrapment. Compared with vaccination with heat-denatured toxin, mice vaccinated with the nanoparticle-detained toxin showed superior protective immunity against toxin-mediated adverse effects. We find that the non-disruptive detoxification approach benefited the immunogenicity and efficacy of toxoid vaccines. We anticipate that this study will open new possibilities in the preparation of antitoxin vaccines against the many virulence factors that threaten public health.

  5. Feasibility and challenges in the development of immunocontraceptive vaccine based on zona pellucida glycoproteins.

    PubMed

    Choudhury, Sangeeta; Srivastava, Neelu; Narwal, P S; Rath, Archana; Jaiswal, Sonika; Gupta, Satish K

    2007-01-01

    The zona pellucida (ZP) glycoproteins play a crucial role during fertilization and thus are considered as important target antigens for the development of immunocontraceptive vaccines aiming to inhibit fertility at a pre-fertilization stage. In order to evaluate the immunocontraceptive potential of ZP glycoproteins, bonnet monkey (Macaca radiata) ZP2, ZP3 and ZP4 have been cloned and expressed using either E. coli or baculovirus expression systems. Active immunization studies with the recombinant ZP glycoproteins in female baboons (Papio anubis) and bonnet monkeys revealed curtailment of fertility. In order to minimize the ovarian pathology, synthetic peptides corresponding to B cell epitopes that are devoid of 'oophoritogenic' T cell epitopes were designed and their in vitro immunocontraceptive potential explored. There are several issues that need to be addressed before ZP glycoproteins based immunocontraceptive vaccines become feasible for use in humans. Nonetheless, the utility of such a vaccine is imminent for controlling wild life population. In this direction, active immunization of female non-descript dogs with recombinant canine ZP3 conjugated to diphtheria toxoid led to curtailment of fertility. Further, canine ZP3 has also been expressed in insect cells as a fusion protein with rabies virus glycoprotein G (RV-G), an antigen that is involved in providing protection against rabies. The immunogenicity of such a recombinant protein and its potential to curtail fertility was explored both in female mice and dogs. Simultaneously, DNA vaccine encoding canine ZP3 and RV-G have been made and evaluated for their immunogenicity. The results obtained so far, current shortcomings and the possible ways to circumvent these have been discussed in the present manuscript. PMID:17566293

  6. Induction of Protective Serum Meningococcal Bactericidal and Diphtheria-Neutralizing Antibodies and Mucosal Immunoglobulin A in Volunteers by Nasal Insufflations of the Neisseria meningitidis Serogroup C Polysaccharide-CRM197 Conjugate Vaccine Mixed with Chitosan

    PubMed Central

    Huo, Zhiming; Sinha, Ruchi; McNeela, Edel A.; Borrow, Ray; Giemza, Rafaela; Cosgrove, Catherine; Heath, Paul T.; Mills, Kingston H. G.; Rappuoli, Rino; Griffin, George E.; Lewis, David J. M.

    2005-01-01

    Thirty-six healthy volunteers received either a single intramuscular injection of Neisseria meningitidis serogroup C polysaccharide (MCP)-CRM197 conjugate vaccine in alum or two nasal insufflations 28 days apart of the same vaccine powder, without alum, mixed with chitosan. Nasal immunization was well tolerated, with fewer symptoms reported than after intramuscular injection. The geometric mean concentrations of MCP-specific immunoglobulin G (IgG) after one nasal immunization were 3.25 ?g/ml in naïve subjects and 14.4 ?g/ml in subjects previously immunized parenterally, compared with 4.30 ?g/ml in naïve subjects immunized intramuscularly. The geometric mean titer of serum bactericidal antibody (SBA) rose 24-fold after two nasal immunizations in naïve subjects and was comparable to parenteral immunization (1,080 versus 1,625). All subjects achieved SBA titers associated with protection after two nasal immunizations: even those with titers of <8 at entry. A single nasal immunization boosted the SBA titer to ?128 in 96% of previously immunized subjects, and two immunizations achieved this level in 92% of naive subjects. MCP-specific IgG levels were ?70% IgG2 and ?20% IgG1 after nasal or intramuscular immunization. Increases in CRM197-specific IgG and diphtheria toxin-neutralizing activity were observed after nasal or intramuscular immunization, with balanced IgG1/IgG2 and higher IgG4. Significant MCP-specific secretory IgA was detected in nasal wash only after nasal immunization and predominantly on the immunized side. Simple nasal insufflation of existing MCP-CRM197 conjugate vaccines in chitosan offers an inexpensive but effective needle-free prime and boost against serogroup C N. meningitidis and diphtheria. PMID:16299322

  7. Pneumococcal Conjugate Vaccine (PCV7)

    MedlinePLUS

    What is pneumococcal disease?Infection with Streptococcus pneumoniae bacteria can make children very sick. It causes blood infections, pneumonia, and bacterial meningitis, mostly in young children. (Meningitis is an infection ...

  8. Vaccination Against Staphylococcus aureus Pneumonia

    PubMed Central

    Spaulding, Adam R.; Salgado-Pabón, Wilmara; Merriman, Joseph A.; Stach, Christopher S.; Ji, Yinduo; Gillman, Aaron N.; Peterson, Marnie L.; Schlievert, Patrick M.

    2014-01-01

    Background.?Staphylococcus aureus causes serious infections in both hospital and community settings. Attempts have been made to prevent human infection through vaccination against bacterial cell-surface antigens; thus far all have failed. Here we show that superantigens and cytolysins, when used in vaccine cocktails, provide protection from S. aureus USA100–USA400 intrapulmonary challenge. Methods.?Rabbits were actively vaccinated (wild-type toxins or toxoids) or passively immunized (hyperimmune serum) against combinations of superantigens (toxic shock syndrome toxin 1, enterotoxins B and C, and enterotoxin-like X) and cytolysins (?-, ?-, and ?-toxins) and challenged intrapulmonarily with multiple strains of S. aureus, both methicillin-sensitive and methicillin-resistant. Results.?Active vaccination against a cocktail containing bacterial cell-surface antigens enhanced disease severity as tested by infective endocarditis. Active vaccination against secreted superantigens and cytolysins resulted in protection of 86 of 88 rabbits when challenged intrapulmonarily with 9 different S. aureus strains, compared to only 1 of 88 nonvaccinated animals. Passive immunization studies demonstrated that production of neutralizing antibodies was an important mechanism of protection. Conclusions.?The data suggest that vaccination against bacterial cell-surface antigens increases disease severity, but vaccination against secreted virulence factors provides protection against S. aureus. These results advance our understanding of S. aureus pathogenesis and have important implications in disease prevention. PMID:24357631

  9. Cattle Vaccines 

    E-print Network

    Faries Jr., Floron C.

    2005-11-11

    Vaccines deliver antigens that stimulate the body's production of antibodies in response to disease. Cattle can be vaccinated with noninfectious or infectious vaccines. The types of vaccine products, proper handling of vaccines, and vaccination...

  10. A novel ICOS-independent, but CD28- and SAP-dependent, pathway of T cell-dependent, polysaccharide-specific humoral immunity in response to intact Streptococcus pneumoniae versus pneumococcal conjugate vaccine.

    PubMed

    Chen, Quanyi; Cannons, Jennifer L; Paton, James C; Akiba, Hisaya; Schwartzberg, Pamela L; Snapper, Clifford M

    2008-12-15

    Polysaccharide (PS)- and protein-specific murine IgG responses to intact Streptococcus pneumoniae (Pn) are both dependent on CD4(+) T cell help, B7-dependent costimulation, and CD40/CD40 ligand interactions. However, the primary PS-specific, relative to protein-specific, IgG response terminates more rapidly, requires a shorter period of T cell help and B7-dependent costimulation, and fails to generate memory. In light of the critical role for ICOS/ICOS ligand interactions in sustaining T cell-dependent Ig responses and promoting germinal center reactions, we hypothesized that this interaction was nonessential for PS-specific IgG responses to Pn. We now demonstrate that ICOS(-/-), relative to wild-type, mice elicit a normal PS-specific IgG isotype response to Pn, despite marked inhibition of both the primary and secondary IgG anti-protein (i.e., PspA, PspC, and PsaA) response. A blocking anti-ICOS ligand mAb injected during primary Pn immunization inhibits both the primary anti-protein response and the generation of protein-specific memory, but has no effect when injected during secondary immunization. In contrast to Pn, both PS- and protein-specific IgG responses to a pneumococcal conjugate vaccine are inhibited in ICOS(-/-) mice. ICOS(-/-) mice immunized with intact Pn or conjugate exhibit nearly complete abrogation in germinal center formation. Finally, although mice that lack the adaptor molecule SAP (SLAM-associated protein) resemble ICOS(-/-) mice (and can exhibit decreased ICOS expression), we observe that the PS-specific, as well as protein-specific, IgG responses to both Pn and conjugate are markedly defective in SAP(-/-) mice. These data define a novel T cell-, SAP-, and B7-dependent, but ICOS-independent, extrafollicular pathway of Ig induction. PMID:19050242

  11. Transcutaneous Immunization with a Vibrio cholerae O1 Ogawa Synthetic Hexasaccharide Conjugate following Oral Whole-Cell Cholera Vaccination Boosts Vibriocidal Responses and Induces Protective Immunity in Mice

    PubMed Central

    Tarique, A. A.; Kalsy, A.; Arifuzzaman, M.; Rollins, S. M.; Charles, R. C.; Leung, D. T.; Harris, J. B.; LaRocque, R. C.; Sheikh, A.; Bhuiyan, M. S.; Saksena, R.; Clements, J. D.; Calderwood, S. B.; Qadri, F.; Ková?, P.

    2012-01-01

    A shortcoming of currently available oral cholera vaccines is their induction of relatively short-term protection against cholera compared to that afforded by wild-type disease. We were interested in whether transcutaneous or subcutaneous boosting using a neoglycoconjugate vaccine made from a synthetic terminal hexasaccharide of the O-specific polysaccharide of Vibrio cholerae O1 (Ogawa) coupled to bovine serum albumin as a carrier (CHO-BSA) could boost lipopolysaccharide (LPS)-specific and vibriocidal antibody responses and result in protective immunity following oral priming immunization with whole-cell cholera vaccine. We found that boosting with CHO-BSA with immunoadjuvantative cholera toxin (CT) or Escherichia coli heat-labile toxin (LT) following oral priming with attenuated V. cholerae O1 vaccine strain O395-NT resulted in significant increases in serum anti-V. cholerae LPS IgG, IgM, and IgA (P < 0.01) responses as well as in anti-Ogawa (P < 0.01) and anti-Inaba (P < 0.05) vibriocidal titers in mice. The LPS-specific IgA responses in stool were induced by transcutaneous (P < 0.01) but not subcutaneous immunization. Immune responses following use of CT or LT as an adjuvant were comparable. In a neonatal mouse challenge assay, immune serum from boosted mice was associated with 79% protective efficacy against death. Our results suggest that transcutaneous and subcutaneous boosting with a neoglycoconjugate following oral cholera vaccination may be an effective strategy to prolong protective immune responses against V. cholerae. PMID:22357651

  12. Evaluation of a Subunit H5 Vaccine and an Inactivated H5N2 Avian Influenza Marker Vaccine in Ducks Challenged with Vietnamese H5N1 Highly Pathogenic Avian Influenza Virus

    PubMed Central

    Chua, Tze-Hoong; Leung, Connie Y. H.; Fang, H. E.; Chow, Chun-Kin; Ma, Siu-Kit; Sia, Sin-Fun; Ng, Iris H. Y.; Fenwick, Stanley G.; James, Cassandra M.; Chua, Sin Bin; Chew, Siang Thai; Kwang, Jimmy; Peiris, J. S. M.; Ellis, Trevor M.

    2010-01-01

    The protective efficacy of a subunit avian influenza virus H5 vaccine based on recombinant baculovirus expressed H5 haemagglutinin antigen and an inactivated H5N2 avian influenza vaccine combined with a marker antigen (tetanus toxoid) was compared with commercially available inactivated H5N2 avian influenza vaccine in young ducks. Antibody responses, morbidity, mortality, and virus shedding were evaluated after challenge with a Vietnamese clade 1 H5N1 HPAI virus [A/VN/1203/04 (H5N1)] that was known to cause a high mortality rate in ducks. All three vaccines, administered with water-in-oil adjuvant, provided significant protection and dramatically reduced the duration and titer of virus shedding in the vaccinated challenged ducks compared with unvaccinated controls. The H5 subunit vaccine was shown to provide equivalent protection to the other two vaccines despite the H5 antibody responses in subunit vaccinated ducks being significantly lower prior to challenge. Ducks vaccinated with the H5N2 marker vaccine consistently produced antitetanus toxoid antibody. The two novel vaccines have attributes that would enhance H5N1 avian influenza surveillance and control by vaccination in small scale and village poultry systems. PMID:23074648

  13. Diphtheria toxoid conformation in the context of its nanoencapsulation within liposomal particles sandwiched by chitosan.

    PubMed

    Rescia, Vanessa C; Ramos, Henrique R; Takata, Célia S; de Araujo, Pedro S; da Costa, Maria H B

    2011-06-01

    Chitosan (?-(1-4)-amino-2-deoxy-?-D-glucan) is a deacetylated form of chitin, a polysaccharide from crustacean shells. Its unique characteristics, such as positive charge, biodegradability, biocompatibility, nontoxicity, and rigid structure, make this macromolecule ideal for an oral vaccine delivery system. We prepared reverse-phase evaporation vesicles (REVs) sandwiched by chitosan (Chi) and polyvinylic alcohol (PVA). However, in this method, there are still some problems to be circumvented related to protein stabilization. During the inverted micelle phase of protein nanoencapsulation, hydrophobic interfaces are expanded, leading to interfacial adsorption, followed by protein unfolding and aggregation. Here, spectroscopic and immunological techniques were used to ascertain the effects of the Hoffmeister series ions on diphtheria toxoid (Dtxd) stability during the inverted micelle phase. A correlation was established between the salts used in aqueous solutions and the changes in Dtxd solubility and conformation. Dtxd ?-helical content was quite stable, which led us to conclude that encapsulation occurred without protein aggregation or without exposition of hydrophobic residues. Dtxd aggregation was 98% avoided by the kosmotropic, PO(2-)(4). This ion was used to prepare a stable Dtxd and immunologically recognized REV-Chi-PVA formulation in the presence of 50 mM of PO(2-)(4). Under these conditions, the Dtxd retained its immunological identity. Therefore, we could obtain the maximum Dtxd solubility and stability after contact with CH(3)CO(2)C(2)H(5) to begin its nanoencapsulation within ideal conditions. This was a technological breakthrough, because a simple solution, such as salt, addition avoided heterologous protein use. PMID:20522003

  14. Impact of 10- and 13-valent pneumococcal conjugate vaccines on incidence of invasive pneumococcal disease in children aged under 16 years in Germany, 2009 to 2012.

    PubMed

    Weiss, S; Falkenhorst, G; van der Linden, M; Imohl, M; von Kries, R

    2015-01-01

    We assessed the impact of 10-valent and 13-valent pneumococcal vaccines (PCV10 and PCV13), which were introduced in Germany in 2009, on the incidence of meningitis and non-meningitis invasive pneumococcal disease (IPD) in children aged?under?16 years in a population previously vaccinated with a seven-valent vaccine (PCV7). Surveillance of IPD (isolation of Streptococcus pneumonia from a normally sterile body site) is based on data from two independent reporting sources: hospitals and laboratories. IPD incidence was estimated by capture-recapture analysis. Incidence rate ratios (IRRs) were calculated for 2009 and 2012, thus comparing pre- and post-PCV10 and PCV13 data. IPD incidence caused by serotypes included in PCV13 decreased in all age and diagnosis groups. A rise in non-vaccine serotype incidence was seen only in children aged under two years. The overall impact varied by age group and infection site: for meningitis IPD in children?aged under?2, 2-4 and 5-15 years, incidence changed by?3% (95% CI: -31 to?52), -60% (95% CI: -81 to -17) and -9% (95% CI: -46 to?53), respectively. A more pronounced incidence reduction was observed for non-meningitis IPD: -30% (95% CI: -46 to -7), -39% (95% CI: -54 to -20) and -83% (95% CI: -89 to -73) in children aged under?2, 2-4 and 5-15 years, respectively. A higher tropism of the additional serotypes for non-meningitis IPD may be a potential explanation. The heterogeneous findings emphasise the need for rigorous surveillance PMID:25788255

  15. 21 CFR 522.1083 - Gonadotropin releasing factor analog-diphtheria toxoid conjugate.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...2014-04-01 2014-04-01 false Gonadotropin releasing factor analog-diphtheria...FORM NEW ANIMAL DRUGS § 522.1083 Gonadotropin releasing factor analog-diphtheria...solution contains 0.2 milligrams (mg) gonadotropin releasing factor...

  16. 21 CFR 522.1083 - Gonadotropin releasing factor analog-diphtheria toxoid conjugate.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...2013-04-01 2013-04-01 false Gonadotropin releasing factor analog-diphtheria...FORM NEW ANIMAL DRUGS § 522.1083 Gonadotropin releasing factor analog-diphtheria...solution contains 0.2 milligrams (mg) gonadotropin releasing factor...

  17. Fertility regulating and immunotherapeutic vaccines reaching human trials stage.

    PubMed

    Talwar, G P

    1997-01-01

    The progress and current status of vaccines which induce antibodies against human chorionic gonadotrophin (HCG) and luteinizing hormone-releasing hormone (LHRH) are reviewed. Three vaccines devised against HCG have undergone phase I clinical trials documenting their safety, and reversibility. One of these, the heterospecies dimer (HSD)-HCG vaccine has also completed phase II efficacy trials in sexually active women of proven fertility. Immunization with the vaccine prevents pregnancy, as long as the antibody titres remain > or =50 ng/ml HCG bioneutralization capacity. There is no disturbance of menstrual regularity and women continue to ovulate normally. The antibody response is predominantly against an epitope in the core part of beta-HCG. Fertility is regained at titres <35 ng. These observations have laid the scientific foundations of a birth control vaccine. Research suggests the feasibility of making a cost-effective recombinant vaccine. The carriers tetanus toxoid (TT) and diptheria toxoid (DT) can be advantageously replaced by peptide determinants recognizing T, not B cells. In addition to optional fertility control, HCG vaccines may have tumour growth inhibition potential in lung cancers which produce HCG. The vaccine against LHRH can be used in both males and females. As it is a structurally conserved molecule, the same vaccine is applicable to both animals and humans. Antibodies against LHRH block the generation of gametes and sex steroids, with the result that the vaccine can be used for fertility control (domestic pets, prolongation of lactation amenorrhoea); as well as for sex hormone-dependent cancers. Phase I/phase II clinical trials have been conducted with the LHRH vaccine in advanced metastazing carcinoma of prostate patients with encouraging results. Bioeffective monoclonal antibodies have been developed against both LHRH and HCG. These can be 'humanized' and produced cost-effectively in bacteria and plants, thus paving the way for passive use of such antibodies for immunotherapy of cancers and fertility control. PMID:9459276

  18. Protection of mice from group A streptococcal infection by intranasal immunisation with a peptide vaccine that contains a conserved M protein B cell epitope and lacks a T cell autoepitope.

    PubMed

    Olive, Colleen; Clair, Timothy; Yarwood, Penny; Good, Michael F

    2002-06-21

    Infection with group A streptococci (GAS) can lead to rheumatic fever (RF) and rheumatic heart disease (RHD) which are a major health concern particularly in indigenous populations worldwide, and especially in Australian Aboriginals. A primary route of GAS infection is via the upper respiratory tract, and therefore, a major goal of research is the development of a mucosal-based GAS vaccine. The majority of the research to date has focused on the GAS M protein since immunity to GAS is mediated by M protein type-specific opsonic antibodies. There are two major impediments to the development of a vaccine-the variability in M proteins and the potential for the induction of an autoimmune response. To develop a safe and broad-based vaccine, we have therefore focused on the GAS M protein conserved C-region, and have identified peptides, J8 and the closely related J8 peptide (J14), which may be important in protective immunity to GAS infection. Using a mucosal animal model system, our data have shown a high degree of throat GAS colonisation in B10.BR mice 24h following intranasal immunisation with the mucosal adjuvant, cholera toxin B subunit (CTB), and/or diptheria toxoid (dT) carrier, or PBS alone, and challenge with the M1 GAS strain. However, GAS colonisation of the throat was significantly reduced following intranasal immunisation of mice with the vaccine candidate J8 conjugated to dT or J14-dT when administered with CTB. Moreover, J8-dT/CTB and J14-dT/CTB-immunised mice had a significantly higher survival when compared to CTB and PBS-immunised control mice. These data indicate that immunity to GAS infection can be evoked by intranasal immunisation with a GAS M protein C-region peptide vaccine that contains a protective B cell epitope and lacks a T cell autoepitope. PMID:12034109

  19. [Selected research problems of anthrax vaccine development].

    PubMed

    Zakowska, Dorota; Kocik, Janusz; Bartoszcze, Micha?

    2009-01-01

    The threat of bioterrorism with B. anthracis against civilian population is one of major concern. After successful bioterroristic attack in 2001 in US renewed research interest has prompted in the development of new and more effective vaccine against anthrax. There are two licensed vaccines against anthrax--AVA-Bio-Thrax US and UK--sterile culture filtrate prepared by alum precipitation. Both vaccines are based on PA antigen. There are several concerns regarding PA based vaccines. They require six sc injections and yearly booster, high rates of local reaction after vaccination is observed, the immunity is not long lasting, vaccination do not protect animals against different strains of B. anthracis. New strategies in the development of anthrax vaccines have been presented (recombinant PA, subunits vaccine, mutants, conjugated). Using proteomic approaches new antigens have been also identified as candidates for future vaccines. More effective and easy to perform methods of vaccination have been reviewed. PMID:20120948

  20. Serotype distribution of invasive Streptococcus pneumoniae in Canada after the introduction of the 13-valent pneumococcal conjugate vaccine, 2010-2012.

    PubMed

    Demczuk, Walter H B; Martin, Irene; Griffith, Averil; Lefebvre, Brigitte; McGeer, Allison; Lovgren, Marguerite; Tyrrell, Gregory J; Desai, Shalini; Sherrard, Lindsey; Adam, Heather; Gilmour, Matthew; Zhanel, George G

    2013-12-01

    The introduction of the 7-valent pneumococcal vaccine (PCV7) in Canada was very effective in reducing invasive pneumococcal disease (IPD) in children; however, increases of non-PCV7 serotypes have subsequently offset some of these reductions. A 13-valent pneumococcal vaccine (PCV13) targeting additional serotypes was implemented between 2010 and 2011, and in 2012 changes in the incidence of disease and the distribution of IPD serotypes began to emerge. The incidence of IPD in children <5 years of age declined from 18.0 to 14.2 cases per 100?000 population between 2010 and 2012; however, the incidence in ages ?5 years remained relatively unchanged over the 3-year period, at about 9.7 cases per 100?000 population. From 2010 to 2012, PCV13 serotypes declined significantly from 66% (224/339) to 41% (101/244, p < 0.001) in children <5 years of age, and from 54% (1262/2360) to 43% (1006/2353, p < 0.001) in children ?5 years of age. Serotypes 19A, 7F, 3, and 22F were the most common serotypes in 2012, with 19A decreasing from 19% (521/2727) to 14% (364/2620, p < 0.001), 7F decreasing from 14% (389/2727) to 12% (323/2620, p = 0.04), and 22F increasing from 7% (185/2727) to 11% (279/2620, p < 0.001) since 2010. Serotype 3 increased from 7% (23/339) to 10% (24/244) in <5-year-olds (p = 0.22) over the 3-year period. The highest rates of antimicrobial resistance were observed with clarithromycin (23%), penicillin using meningitis breakpoints (12%), clindamycin (8%), and trimethoprim-sulfamethoxazole (6%). Shifts in the distribution of IPD serotypes and reductions in the incidence of disease suggest that current immunization programs in Canada are effective in reducing the burden of IPD in children. While we acknowledge the limited data on the effectiveness of the PCV13 vaccine, to our knowledge, this study represents one of the first descriptions of the potential impact of the PCV13 vaccine in the Canadian population. Continued surveillance will be important to recognize replacement serotypes, to determine the extent of herd immunity effects in nonpaediatric populations, and to assess the overall effectiveness of PCV13 in reducing IPD in Canada. PMID:24313450

  1. Vaccination and otitis media.

    PubMed

    Karma, P

    2002-01-01

    Acute otitis media (AOM) caused by Streptococcus pneumoniae, Haemophilus influenzae or Moraxella catarrhalis may induce specific systemic and/or local immune responses, which may protect from otitis media caused by the same bacteria. However, earlier clinical trials with pneumococcal capsular polysaccharide vaccines have not been successful in preventing AOM. Recently developed pneumococcal polysaccharide-protein conjugates proved immunogenic even in infants, and a heptavalent pneumococcal CRM 197 conjugate vaccine gave a 57% reduction in the number of pneumococcal AOM episodes caused by the vaccine serotypes in infants in Finland. H. influenzae causing AOM is noncapsulated, and like M. catarrhalis, calls for another kind of vaccine development. Suitable vaccine candidates are not yet available but are under development and being tested for immunogenicity and safety. In some trials influenza vaccines have shown protection from AOM during respective viral epidemics. Passive immunoprophylaxis might be an important alternative for immunocompromised children, although this approach has not been successful so far. Mucosal immunization and the advent of DNA and gene technology will open new interesting prospects in the future. PMID:12021498

  2. Population-Level Persistence of Immunity 2 Years After the PsA-TT Mass-Vaccination Campaign in Mali

    PubMed Central

    Basta, Nicole E.; Borrow, Ray; Berthe, Abdoulaye; Dembélé, Awa Traoré Eps; Onwuchekwa, Uma; Townsend, Kelly; Boukary, Rahamatou M.; Mabey, Lesley; Findlow, Helen; Bai, Xilian; Sow, Samba O.

    2015-01-01

    Background.?In 2010, Africa's first preventive meningococcal mass vaccination campaign was launched using a newly developed Neisseria meningitidis group A (NmA) polysaccharide–tetanus toxoid conjugate vaccine, PsA-TT (MenAfriVac), designed specifically for the meningitis belt. Given PsA-TT's recent introduction, the duration of protection against meningococcal group A is unknown. Methods.?We conducted a household-based, age-stratified seroprevalence survey in Bamako, Mali, in 2012, 2 years after the vaccination campaign targeted all 1- to 29-year-olds. Randomly selected participants who had been eligible for PsA-TT provided a blood sample and responded to a questionnaire. Sera were analyzed to assess NmA-specific serum bactericidal antibody titers using rabbit complement (rSBA) and NmA-specific immunoglobulin G (IgG) by enzyme-linked immunosorbent assay. The proportion of participants putatively protected and the age group- and sex-specific rSBA geometric mean titers (GMTs) and IgG geometric mean concentrations (GMCs) were determined. Results.?Two years postvaccination, nearly all of the 800 participants (99.0%; 95% confidence interval [CI], 98.3%–99.7%) maintained NmA-specific rSBA titers ?8, the accepted threshold for protection; 98.6% (95% CI, 97.8%–99.4%) had titers ?128, and 89.5% (95% CI, 87.4%–91.6%) had titers ?1024. The rSBA GMTs were significantly higher in females than in males aged <18 years at vaccination (P < .0001). NmA-specific IgG levels ?2 µg/mL were found in 88.5% (95% CI, 86.3%–90.7%) of participants. Conclusions.?Two years after PsA-TT introduction, a very high proportion of the population targeted for vaccination maintains high antibody titers against NmA. Assessing the duration of protection provided by PsA-TT is a priority for implementing evidence-based vaccination strategies. Representative, population-based seroprevalence studies complement clinical trials and provide this key evidence. PMID:26553687

  3. Identification of glycosylated regions in pneumococcal PspA conjugated to serotype 6B capsular polysaccharide.

    PubMed

    Barazzone, Giovana Cappio; Pinto, Vittoria; Donnarumma, Danilo; Tanizaki, Martha Massako; Norais, Nathalie; Berti, Francesco

    2014-04-01

    Conjugate vaccines are being widely used since their introduction. Nowadays the interest in these vaccines is still growing and new antigens and conjugate chemistry are being studied and developed. Pneumococcal surface protein A (PspA) is one of the most studied pneumococcal antigens and is an important vaccine candidate. One approach to broaden the conjugate vaccine coverage could be the conjugation of the polysaccharide to a pneumococcal protein such as PspA. Previous results have shown that conjugated recombinant fragment of PspA (rPspA) not only maintained but also in some conjugates improved the induction of protective antibodies raised against the protein carrier. We describe here a characterization study to identify the domains of Streptococcus pneumoniae recombinant PspA (rPspA), from family 1 clade 1 and family 2 clade 3, involved in the conjugation with serotype 6B capsular polysaccharide. PMID:24658681

  4. Evaluation of recombinant SEA-TSST fusion toxoid for protection against superantigen induced toxicity in mouse model.

    PubMed

    Reddy, Prakash Narayana; Paul, Soumya; Sripathy, Murali H; Batra, Harsh Vardhan

    2015-09-01

    Treatment of Staphylococcus aureus infections has become complicated owing to growing antibiotic resistance mechanisms and due to the multitude of virulence factors secreted by this organism. Failures with traditional monovalent vaccines or toxoids have brought a shift towards the use of multivalent formulas and neutralizing antibodies to combat and prevent range of staphylococcal infections. In this study, we evaluated the efficacy of a fusion protein (r-ET) comprising truncated regions of staphylococcal enterotoxin A (SEA) and toxic shock syndrome toxin (TSST-1) in generating neutralizing antibodies against superantigen induced toxicity in murine model. Serum antibodies showed specific reactivity to both SEA and TSST-1 native toxins. Hyperimmune serum from immunized animals protected cultured splenocytes from non-specific superantigen induced proliferation completely. Passive antibody administration prevented tissue damage from acute inflammation associated with superantigen challenge from S. aureus cell free culture supernatants. Approximately 80% and 50% of actively and passively immunized mice respectively were protected from lethal dose against S. aureus toxin challenge. This study revealed that r-ET protein is non-toxic and a strong immunogen which generated neutralizing antibodies and memory immune response against superantigen induced toxic effects in mice model. PMID:26091873

  5. Protection against avian necrotic enteritis after immunisation with NetB genetic or formaldehyde toxoids?

    PubMed Central

    Fernandes da Costa, Sérgio P.; Mot, Dorien; Bokori-Brown, Monika; Savva, Christos G.; Basak, Ajit K.; Van Immerseel, Filip; Titball, Richard W.

    2013-01-01

    NetB (necrotic enteritis toxin B) is a recently identified ?-pore-forming toxin produced by Clostridium perfringens. This toxin has been shown to play a major role in avian necrotic enteritis. In recent years, a dramatic increase in necrotic enteritis has been observed, especially in countries where the use of antimicrobial growth promoters in animal feedstuffs has been banned. The aim of this work was to determine whether immunisation with a NetB toxoid would provide protection against necrotic enteritis. The immunisation of poultry with a formaldehyde NetB toxoid or with a NetB genetic toxoid (W262A) resulted in the induction of antibody responses against NetB and provided partial protection against disease. PMID:23727000

  6. Rapid modification of retroviruses using lipid conjugates

    NASA Astrophysics Data System (ADS)

    Mukherjee, Nimisha G.; Lyon, L. Andrew; LeDoux, Joseph M.

    2009-02-01

    Methods are needed to manipulate natural nanoparticles. Viruses are particularly interesting because they can act as therapeutic cellular delivery agents. Here we examine a new method for rapidly modifying retroviruses that uses lipid conjugates composed of a lipid anchor (1,2-distearoyl-sn-glycero-3-phosphoethanolamine), a polyethylene glycol chain, and biotin. The conjugates rapidly and stably modified retroviruses and enabled them to bind streptavidin. The implication of this work for modifying viruses for gene therapy and vaccination protocols is discussed.

  7. An Age-Structured Model for Pneumococcal Infection with Vaccination

    E-print Network

    An Age-Structured Model for Pneumococcal Infection with Vaccination Karyn L. Sutton1,2,3 , H. T the young and the old. The development of an effective vaccine against these infections, especially the younger ages, has not been successful despite the licensing of the pneumococcal conjugate vaccine (PCV7

  8. Glycoprotein Vaccines DOI: 10.1002/anie.201006327

    E-print Network

    Davis, Ben G.

    Glycoprotein Vaccines DOI: 10.1002/anie.201006327 A Coordinated Synthesis and Conjugation Strategy for the Preparation of Homogeneous Glycoconjugate Vaccine Candidates** Elizabeth J. Grayson, Gonçalo J. L. Bernardes are the center of many therapeutic strat- egies[1­3] and carbohydrate-based vaccines in particular hold great

  9. New Meningococcal Vaccine Recommendations under Consideration

    ERIC Educational Resources Information Center

    Turner, James C.

    2004-01-01

    The Advisory Committee on Immunization Practices (ACIP) at the Center for Disease Control and Prevention (CDC) will be considering a new vaccination recommendation for the prevention of invasive "N. meningitidis" infection when meningococcal conjugate vaccines are licensed in the United States. The CDC has also updated the Working Group in the…

  10. Efficacy of a type C botulism vaccine in green-winged teal

    USGS Publications Warehouse

    Rocke, T.E.; Samuel, M.D.; Swift, P.K.; Yarris, G.S.

    2000-01-01

    We tested the efficacy of a single dose of Botumink toxoid for protecting wild green-winged teal (Anas crecca) during botulism epizootics caused by Clostridium botulinum type C. We challenged control and immunized ducks with four different doses of type C botulinum toxin to determine the LD50 for this species and to evaluate vaccine protection. Fewer immunized ducks were affected with botulism than control ducks, indicating that a single dose of Botumink toxoid could increase the survival of ducks during epizootics. However, the frequency of immunized ducks with signs of botulism increased with the challenge dose of botulinum toxin. Even at doses of botulinum toxin approximately 2 to 4 green-winged teal LD50, about 50% of the immunized ducks were affected. We believe an improved vaccine or a better delivery system is required to justify immunization of wild birds for experimental survival studies.

  11. Serotypes, antimicrobial susceptibility, and molecular epidemiology of invasive and non-invasive Streptococcus pneumoniae isolates in paediatric patients after the introduction of 13-valent conjugate vaccine in a nationwide surveillance study conducted in Japan in 2012-2014.

    PubMed

    Nakano, Satoshi; Fujisawa, Takao; Ito, Yutaka; Chang, Bin; Suga, Shigeru; Noguchi, Taro; Yamamoto, Masaki; Matsumura, Yasufumi; Nagao, Miki; Takakura, Shunji; Ohnishi, Makoto; Ihara, Toshiaki; Ichiyama, Satoshi

    2016-01-01

    Pneumococcal infection in children is a major public health problem worldwide, including in Japan. The pneumococcal conjugate vaccine 7 (PCV7) was licensed for use in Japan in 2010 followed by PCV13 in 2013. This report includes the results of a nationwide surveillance of invasive pneumococcal disease (IPD) and non-IPD in paediatric patients from January 2012 to December 2014. We collected 343 isolates from 337 IPD patients and 286 isolates from 278 non-IPD patients. Of the IPD isolates, the most identified serotypes included 19A, 24F, and 15A. The prevalence of non-PCV13 serotype isolates increased significantly from 2012 to 2014 (51.6-71.4%, p=0.004). Serotypes 19A, 15A and 35B were highly non-susceptible to penicillin, and the rates of non-susceptible isolates from IPD patients to penicillin and cefotaxime significantly declined during the study period (p=0.029 and p=0.013, respectively). The non-susceptible rate to meropenem increased, particularly for serotype 15A. The IPD isolates comprised clonal complex (CC) 3111 (93.8% was serotype 19A) followed by CC2572 (81.5% was serotype 24F) and CC63 (97.1% was serotype 15A). CC3111, CC63 and CC156 (33.3% was serotype 23A, 28.6% was serotype 6B, and 14.3% was serotype 19A) were highly non-susceptible to penicillin. Of the non-IPD isolates, the most identified serotypes included 19A, 15A, and 3. In conclusion, the introduction of PCV7 and PCV13 resulted in increasing non-PCV13 serotypes and clones, including antimicrobial resistant serotypes 15A and CC63 (Sweden(15A)-25 clone). PMID:26602268

  12. Pneumococcal Vaccination Recommendations for Children and Adults by Age and/or Risk Factor

    MedlinePLUS

    Pneumococcal Vaccination Recommendations for Children 1 and Adults by Age and/or Risk Factor Routine Recommendations for Pneumococcal Conjugate ... X X X X X 1 For PCV13 vaccination of healthy children, see “Recommen- dations for Pneumococcal ...

  13. CD4 T-helper cell cytokine phenotypes and antibody response following tetanus toxoid booster immunization

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Routine methods for enumerating antigen-specific T-helper cells may not identify low-frequency phenotypes such as Th2 cells. We compared methods of evaluating such responses to identify tetanus toxoid- (TT) specific Th1, Th2, Th17 and IL10+ cells. Eight healthy subjects were given a TT booster vacci...

  14. Typhoid Vaccine

    MedlinePLUS

    ... million people a year around the world and kills about 200,000. 2 Typhoid vaccines Typhoid vaccine can prevent typhoid. There are two vaccines to prevent typhoid. One is an inactivated (killed) vaccine gotten as a shot. The other is a live, attenuated (weakened) vaccine which is taken orally (by ...

  15. Controlled field trials and laboratory studies on the effectiveness of typhoid vaccines in Poland, 1961-64*

    PubMed Central

    1966-01-01

    In recent years studies of the effectiveness of different typhoid vaccines have been sponsored by the World Health Organization in British Guiana, the USSR, and Yugoslavia. A similarly sponsored study has been made in Poland under the auspices of the Polish Typhoid Committee. In the controlled field trial four types of vaccine were used: (1) bacterial acetone-killed and -dried (vaccines K and P), (2) bacterial formol-killed phenol-preserved (vaccine N), (3) Westphal's endotoxin adsorbed on aluminium hydroxide (vaccine S), and (4) Grasset's vaccine (autolysate of typhoid bacilli adsorbed on aluminium hydroxide; vaccine T). The control vaccine was tetanus toxoid (vaccine O). Laboratory tests were also carried out. In children aged 5-14 years who received two inoculations, vaccine N was the most effective, followed by K; vaccine T was distinctly less effective. In people aged 15-60 years the small number of typhoid cases made evaluation difficult; however, vaccines N and P inoculated once afforded protection, whereas vaccine S imparted none. Further studies are desirable on the laboratory testing of typhoid vaccines: at present the H and O agglutination tests with sera of immunized rabbits, combined with an active mouse-protection test, can be recommended, provided that a standard typhoid vaccine is used for comparison. PMID:5296128

  16. Synthesis and Activity of 6?-Deoxy-6?-thio-?-GalCer and Peptide Conjugates.

    PubMed

    Compton, Benjamin J; Tang, Ching-Wen; Johnston, Karen A; Osmond, Taryn L; Hayman, Colin M; Larsen, David S; Hermans, Ian F; Painter, Gavin F

    2015-12-18

    A major challenge in the development of highly defined synthetic vaccines is the codelivery of vaccine components (i.e., antigen and adjuvant) to secondary lymphoid tissue to induce optimal immune responses. This problem can be addressed by synthesizing vaccines that comprise peptide antigens covalently attached to glycolipid adjuvants through biologically cleavable linkers. Toward this, a strategy utilizing previously unreported 6?-deoxy-6?-thio analogues of ?-GalCer that can undergo chemoselective conjugation with peptide antigens is described. Administration of these conjugate vaccines leads to enhanced priming of antigen specific T cells. This simple vaccine design is broadly applicable to multiple disease indications such as cancer and infectious disease. PMID:26606283

  17. Booster vaccination: the role of reduced antigen content vaccines as a preschool booster.

    PubMed

    Gabutti, Giovanni; Trucchi, Cecilia; Conversano, Michele; Zivelonghi, Giambattista; Zoppi, Giorgio

    2014-01-01

    The need for boosters for tetanus, diphtheria, pertussis, and polio, starting from preschool age, is related to the waning immune protection conferred by vaccination, the elimination/reduction of natural boosters due to large-scale immunization programs, and the possibility of reintroduction of wild agents from endemic areas. Taking into account the relevance of safety/tolerability in the compliance with vaccination among the population, it have been assessed whether today enough scientific evidences are available to support the use of dTap-IPV booster in preschool age. The review of the literature was conducted using the PubMed search engine. A total of 41 works has been selected; besides, the documentation produced by the World Health Organization, the European Centre for Disease Control, and the Italian Ministry of Health has been consulted. Many recent papers confirm the opportunity to use a low antigenic dose vaccine starting from 4 to 6 years of age. There is also evidence that 10 years after immunization the rate of seroprotected subjects against diphtheria does not differ significantly between those vaccinated with paediatric dose (DTaP) or reduced dose (dTaP or dTap) product. The dTpa vaccine is highly immunogenic for diphtheria toxoids regardless of prior vaccination history (2 + 1 and 3 + 1 schedules). PMID:24678509

  18. Booster Vaccination: The Role of Reduced Antigen Content Vaccines as a Preschool Booster

    PubMed Central

    Conversano, Michele; Zivelonghi, Giambattista; Zoppi, Giorgio

    2014-01-01

    The need for boosters for tetanus, diphtheria, pertussis, and polio, starting from preschool age, is related to the waning immune protection conferred by vaccination, the elimination/reduction of natural boosters due to large-scale immunization programs, and the possibility of reintroduction of wild agents from endemic areas. Taking into account the relevance of safety/tolerability in the compliance with vaccination among the population, it have been assessed whether today enough scientific evidences are available to support the use of dTap-IPV booster in preschool age. The review of the literature was conducted using the PubMed search engine. A total of 41 works has been selected; besides, the documentation produced by the World Health Organization, the European Centre for Disease Control, and the Italian Ministry of Health has been consulted. Many recent papers confirm the opportunity to use a low antigenic dose vaccine starting from 4 to 6 years of age. There is also evidence that 10 years after immunization the rate of seroprotected subjects against diphtheria does not differ significantly between those vaccinated with paediatric dose (DTaP) or reduced dose (dTaP or dTap) product. The dTpa vaccine is highly immunogenic for diphtheria toxoids regardless of prior vaccination history (2 + 1 and 3 + 1 schedules). PMID:24678509

  19. The Evolution of the Meningitis Vaccine Project

    PubMed Central

    Tiffay, Kathleen; Jodar, Luis; Kieny, Marie-Paule; Socquet, Muriel; LaForce, F. Marc

    2015-01-01

    Background.?In 2001, the Meningitis Vaccine Project (MVP) was tasked to develop, test, license, and introduce a group A meningococcal (MenA) conjugate vaccine for sub-Saharan Africa. African public health officials emphasized that a vaccine price of less than US$0.50 per dose was necessary to ensure introduction and sustained use of this new vaccine. Methods.?Initially, MVP envisioned partnering with a multinational vaccine manufacturer, but the target price and opportunity costs were problematic and formal negotiations ended in 2002. MVP chose to become a “virtual vaccine company,” and over the next decade managed a network of public–private and public–public partnerships for pharmaceutical development, clinical development, and regulatory submission. MVP supported the transfer of key know-how for the production of group A polysaccharide and a new conjugation method to the Serum Institute of India, Ltd, based in Pune, India. A robust staff structure supported by technical consultants and overseen by advisory groups in Europe and Africa ensured that the MenA conjugate vaccine would meet all international standards. Results.?A robust project structure including a team of technical consultants and 3 advisory groups in Europe and Africa ensured that the MenA conjugate vaccine (PsA-TT, MenAfriVac) was licensed by the Drug Controller General of India and prequalified by the World Health Organization in June 2010. The vaccine was introduced in Burkina Faso, Mali, and Niger in December 2010. Conclusions.?The development, through a public–private partnership, of a safe, effective, and affordable vaccine for sub-Saharan Africa, PsA-TT, offers a new paradigm for the development of vaccines specifically targeting populations in resource-poor countries. PMID:26553666

  20. HPV vaccine

    MedlinePLUS

    Vaccine - HPV; Immunization - HPV; Gardasil; Cervarix; HPV2; HPV4; Vaccine to prevent cervical cancer ... of Obstetricians and Gynecologists. Committee Opinion No. 588: Human Papillomavirus Vaccination. Obstet Gynecol . 2014;123:712-8. American ...

  1. Polio Vaccination

    MedlinePLUS

    ... for Polio Vaccination for Travel to and from Countries Affected by Wild Poliovirus , MMWR, July 7, 2014 Polio Vaccine Timeline Source: History of Vaccines Top of Page Beliefs & Concerns Debunked: ...

  2. Vaccine acceptance

    PubMed Central

    Ford, John A; Mahgoub, Hamid; Shankar, Ananda Giri

    2013-01-01

    The United Kingdom has had a long history with vaccine acceptability dating back to Edward Jenner’s theory of small pox vaccination. More recently, the discredited, Wakefield study published in 1998 continues to cause MMR skepticism. In pregnant women pertussis vaccination has been considerably more successful than influenza vaccination. Influenza vaccine uptake in healthcare workers remains poor. The media, politicians, and health reforms have contributed to the mixed coverage for these vaccines. In this article we examine vaccine acceptability from a UK perspective, and consider the future impact this is likely to have on the introduction of rotavirus and shingles vaccine in the UK in 2013. PMID:24025731

  3. Vaccine Hesitancy.

    PubMed

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

    2015-11-01

    Vaccine refusal received a lot of press with the 2015 Disneyland measles outbreak, but vaccine refusal is only a fraction of a much larger problem of vaccine delay and hesitancy. Opposition to vaccination dates back to the 1800s, Edward Jenner, and the first vaccine ever. It has never gone away despite the public's growing scientific sophistication. A variety of factors contribute to modern vaccine hesitancy, including the layperson's heuristic thinking when it comes to balancing risks and benefits as well as a number of other features of vaccination, including falling victim to its own success. Vaccine hesitancy is pervasive, affecting a quarter to a third of US parents. Clinicians report that they routinely receive requests to delay vaccines and that they routinely acquiesce. Vaccine rates vary by state and locale and by specific vaccine, and vaccine hesitancy results in personal risk and in the failure to achieve or sustain herd immunity to protect others who have contraindications to the vaccine or fail to generate immunity to the vaccine. Clinicians should adopt a variety of practices to combat vaccine hesitancy, including a variety of population health management approaches that go beyond the usual call to educate patients, clinicians, and the public. Strategies include using every visit to vaccinate, the creation of standing orders or nursing protocols to provide vaccination without clinical encounters, and adopting the practice of stating clear recommendations. Up-to-date, trusted resources exist to support clinicians' efforts in adopting these approaches to reduce vaccine hesitancy and its impact. PMID:26541249

  4. Vaccines to prevent enteric infections.

    PubMed

    Levine, M M; Noriega, F

    1993-06-01

    Considerable progress has been made in the last decade in developing vaccines against the enteric infections of greatest public health importance. A quadrivalent rotavirus vaccine consisting of rhesus rotavirus vaccine (which contains serotype 3 neutralization antigen) and three reassortant viruses (rhesus virus expressing neutralization antigens of serotypes 1, 2 or 4) is undergoing placebo-controlled field trials of efficacy in the USA and in two developing countries. Two new vaccines against typhoid fever (oral Ty21a and parenteral Vi polysaccharide) have been licensed in many countries. Even newer generations of typhoid vaccines are undergoing clinical testing, including new attenuated S. typhi strains and Vi polysaccharide-carrier protein conjugate vaccines. Two inactivated oral cholera vaccines, consisting of inactivated V. cholerae O1 bacteria alone or in combination with purified B subunit of cholera toxin, each conferred 50-53% protection over 3 years in a field trial in Bangladesh where subjects were immunized with a three-dose regimen. In extensive clinical trials in adults and children in less-developed countries, an engineered live oral cholera vaccine, strain CVD 103-HgR, has been shown to be well tolerated and highly immunogenic following administration of just a single oral dose; a large-scale field trial in 70,000 subjects is underway to investigate the efficacy of this vaccine. Several candidate vaccines against Shigella and enterotoxigenic Escherichia coli are in clinical trials. Accumulating knowledge on pathogenesis of enteric infections and advances in mucosal and cellular immunology, coupled with the application of modern biotechnology, have resulted in a plethora of vaccine candidates. It is expected that in future years efforts will be directed to construct vaccines against other enteric pathogens. PMID:8364252

  5. Mucosal and systemic immune responses induced by a single time vaccination strategy in mice.

    PubMed

    González Aznar, Elizabeth; Romeu, Belkis; Lastre, Miriam; Zayas, Caridad; Cuello, Maribel; Cabrera, Osmir; Valdez, Yolanda; Fariñas, Mildrey; Pérez, Oliver

    2015-08-01

    Vaccination is considered by the World Health Organization as the most cost-effective strategy for controlling infectious diseases. In spite of great successes with vaccines, many infectious diseases are still leading killers, because of the inadequate coverage of many vaccines. Several factors have been responsible: number of doses, high vaccine reactogenicity, vaccine costs, vaccination policy, among others. Contradictorily, few vaccines are of single dose and even less of mucosal administration. However, more common infections occur via mucosa, where secretory immunoglobulin A plays an essential role. As an alternative, we proposed a novel protocol of vaccination called Single Time Vaccination Strategy (SinTimVaS) by immunizing 2 priming doses at the same time: one by mucosal route and the other by parenteral route. Here, the mucosal and systemic responses induced by Finlay adjuvants (AF Proteoliposome 1 and AF Cochleate 1) implementing SinTimVaS in BALB/c mice were evaluated. One intranasal dose of AF Cochleate 1 and an intramuscular dose of AF Proteoliposome 1 adsorbed onto aluminum hydroxide, with bovine serum albumin or tetanus toxoid as model antigens, administrated at the same time, induced potent specific mucosal and systemic immune responses. Also, we demonstrated that SinTimVaS using other mucosal routes like oral and sublingual, in combination with the subcutaneous route elicits immune responses. SinTimVaS, as a new immunization strategy, could increase vaccination coverage and reduce time-cost vaccines campaigns, adding the benefits of immune response in mucosa. PMID:26140382

  6. A nonadjuvanted transcutaneous tetanus patch is effective in boosting anti-tetanus toxoid immune responses.

    PubMed

    Seid, Robert C; Reinisch, Christoph; Schlegl, Robert; Moehlen, Michael; Meinke, Andreas; Lundberg, Urban

    2014-02-01

    Dry tetanus toxoid (TTx) patches were formulated without any adjuvant, with excipients to impart antigen stabilization and to enhance skin delivery. The booster effects of the TTx patches were assessed using a guinea pig model. The study revealed significant rises in TTx IgG titers induced by the TTx patches after a low-dose subcutaneous (s.c.) prime with TTx adsorbed to aluminum hydroxide. The TTx patch can therefore be considered an effective alternative to a subcutaneous booster. PMID:24334688

  7. Recent advances in polymer drug conjugates.

    PubMed

    Sharma, Rajiv; Singla, Nishu; Mehta, Sahil; Gaba, Tripti; Rawal, Ravinder K; Rao, H S; Bhardwaj, T R

    2015-01-01

    Polymer drug conjugates play an important role in the delivery of drugs. In the polymeric drug conjugates, the bioactive agent is combined covalently with polymer to achieve the efficient delivery of bioactive agents in the required or specific period of time along with the enhancement of permeability and retention time. A large number of biodegradable polymers have been widely used in the area of biomedical science. Among them, polyphosphazene, is a biodegradable polymer having versatile nature because of its two chlorine atoms attached on both sides of phosphorus atom of its polymeric backbone, it can be easily replaced by nucleophilic substitution reaction. A plenty of work has been explored for its biomedical applications such as tissue engineering, vaccine drug delivery, polyphosphazene- anticancer drug conjugates with doxorubicin, paclitaxel, platinum complexes, methotrexate and gemcitabine for the targeted drug delivery etc. This review is focused on the recent advances in the biomedical applications of polyphosphazene-drug conjugates. PMID:25985952

  8. Enhanced transdermal-immunization with diptheria-toxoid using local hyperthermia.

    PubMed

    Upadhyay, Pramod

    2006-07-01

    In this study we have investigated how mild local hyperthermia could be used for transdermal-immunization. Mild hyperthermia is found unique in many ways. It activates the immune system and it also results in higher mass transport of high molecular weight molecules and nanometer size quantum dots labeled antigens across the skin in experimental animals. Hyperthermia increases the expression of co-stimulatory molecules such as CD80 and CD86. Mice transdermally immunized with diphtheria toxoid, without any adjuvant or penetration enhancing reagent but under the conditions of local hyperthermia generate an antibody response. In the memory recall assay, the splenocytes of hyperthermia enhanced transdermal-immunized mice undergo proliferation, when exposed to diphtheria toxoid. Comparable response was generated when mice were immunized with diphtheria toxoid by hyperthermia enhanced transdermal route or by conventional inter-muscular injection. Hyperthermia enhanced transdermal-immunization procedure is likely to have higher compliance as it does not cause any pain or visible damage to the skin. PMID:16735086

  9. Genetic Fusions of a CFA/I/II/IV MEFA (Multiepitope Fusion Antigen) and a Toxoid Fusion of Heat-Stable Toxin (STa) and Heat-Labile Toxin (LT) of Enterotoxigenic Escherichia coli (ETEC) Retain Broad Anti-CFA and Antitoxin Antigenicity

    PubMed Central

    Ruan, Xiaosai; Sack, David A.; Zhang, Weiping

    2015-01-01

    Immunological heterogeneity has long been the major challenge in developing broadly effective vaccines to protect humans and animals against bacterial and viral infections. Enterotoxigenic Escherichia coli (ETEC) strains, the leading bacterial cause of diarrhea in humans, express at least 23 immunologically different colonization factor antigens (CFAs) and two distinct enterotoxins [heat-labile toxin (LT) and heat-stable toxin type Ib (STa or hSTa)]. ETEC strains expressing any one or two CFAs and either toxin cause diarrhea, therefore vaccines inducing broad immunity against a majority of CFAs, if not all, and both toxins are expected to be effective against ETEC. In this study, we applied the multiepitope fusion antigen (MEFA) strategy to construct ETEC antigens and examined antigens for broad anti-CFA and antitoxin immunogenicity. CFA MEFA CFA/I/II/IV [CVI 2014, 21(2):243-9], which carried epitopes of seven CFAs [CFA/I, CFA/II (CS1, CS2, CS3), CFA/IV (CS4, CS5, CS6)] expressed by the most prevalent and virulent ETEC strains, was genetically fused to LT-STa toxoid fusion monomer 3xSTaA14Q-dmLT or 3xSTaN12S-dmLT [IAI 2014, 82(5):1823-32] for CFA/I/II/IV-STaA14Q-dmLT and CFA/I/II/IV-STaN12S-dmLT MEFAs. Mice intraperitoneally immunized with either CFA/I/II/IV-STa-toxoid-dmLT MEFA developed antibodies specific to seven CFAs and both toxins, at levels equivalent or comparable to those induced from co-administration of the CFA/I/II/IV MEFA and toxoid fusion 3xSTaN12S-dmLT. Moreover, induced antibodies showed in vitro adherence inhibition activities against ETEC or E. coli strains expressing these seven CFAs and neutralization activities against both toxins. These results indicated CFA/I/II/IV-STa-toxoid-dmLT MEFA or CFA/I/II/IV MEFA combined with 3xSTaN12S-dmLT induced broadly protective anti-CFA and antitoxin immunity, and suggested their potential application in broadly effective ETEC vaccine development. This MEFA strategy may be generally used in multivalent vaccine development. PMID:25803825

  10. Medical Management of Acute Radiation Syndromes : Immunoprophylaxis by Antiradiation Vaccine

    NASA Astrophysics Data System (ADS)

    Popov, Dmitri; Maliev, Vecheslav; Jones, Jeffrey; Casey, Rachael; Kedar, Prasad

    Introduction: Traditionally, the treatment of Acute Radiation Syndrome (ARS) includes supportive therapy, cytokine therapy, blood component transfusions and even stem cell transplantation. Recommendations for ARS treatment are based on clinical symptoms, laboratory results, radiation exposure doses and information received from medical examinations. However, the current medical management of ARS does not include immune prophylaxis based on antiradiation vaccines or immune therapy with hyperimmune antiradiation serum. Immuneprophylaxis of ARS could result from stimulating the immune system via immunization with small doses of radiation toxins (Specific Radiation Determinants-SRD) that possess significant immuno-stimulatory properties. Methods: Principles of immuno-toxicology were used to derive this method of immune prophylaxis. An antiradiation vaccine containing a mixture of Hematotoxic, Neurotoxic and Non-bacterial (GI) radiation toxins, underwent modification into a toxoid forms of the original SRD radiation toxins. The vaccine was administered to animals at different times prior to irradiation. The animals were subjected to lethal doses of radiation that induced different forms of ARS at LD 100/30. Survival rates and clinical symptoms were observed in both control and vaccine-treated animals. Results: Vaccination with non-toxic doses of Radiation toxoids induced immunity from the elaborated Specific Radiation Determinant (SRD) toxins. Neutralization of radiation toxins by specific antiradiation antibodies resulted in significantly improved clinical symptoms in the severe forms of ARS and observed survival rates of 60-80% in animals subjected to lethal doses of radiation expected to induce different forms of ARS at LD 100/30. The most effective vaccination schedule for the antiradiation vaccine consisted of repeated injections 24 and 34 days before irradiation. The vaccine remained effective for the next two years, although the specific immune memory probably persists for a much longer time period. Conclusion: The medical management of ARS by the application of an ARS-specific antiradiation vaccine resulted in significant increases of post-radiation survival rates, even in the absence of traditional ARS therapeutic treatments. The decreased mortality and improved clinical symptoms observed in animals treated with the antiradiation vaccine may lessen the burden of medical therapy and pharmaceuticals required for treatment. However, we hypothesize that a combination of the traditional treatment methods and specific immune prophylaxis by an antiradiation vaccine will potentially be even more effective than either alone.

  11. Review of meningococcal vaccines with updates on immunization in adults.

    PubMed

    Zahlanie, Yorgo C; Hammadi, Moza M; Ghanem, Soha T; Dbaibo, Ghassan S

    2014-01-01

    Meningococcal disease is a serious and global life-threatening disease. Six serogroups (A, B, C, W-135, X, and Y) account for the majority of meningococcal disease worldwide. Meningococcal polysaccharide vaccines were introduced several decades ago and have led to the decline in the burden of disease. However, polysaccharide vaccines have several limitations, including poor immunogenicity in infants and toddlers, short-lived protection, lack of immunologic memory, negligible impact on nasopharyngeal carriage, and presence of hyporesponsiveness after repeated doses. The chemical conjugation of plain polysaccharide vaccines has the potential to overcome these drawbacks. Meningococcal conjugate vaccines include the quadrivalent vaccines (MenACWY-DT, MenACWY-CRM, and MenACWY-TT) as well as the monovalent A and C vaccines. These conjugate vaccines were shown to elicit strong immune response in adults. This review addresses the various aspects of meningococcal disease, the limitations posed by polysaccharide vaccines, the different conjugate vaccines with their immunogenicity and reactogenicity in adults, and the current recommendations in adults. PMID:24500529

  12. VACCINE INFORMATION STATEMENT Hepatitis B Vaccine

    E-print Network

    VACCINE INFORMATION STATEMENT Hepatitis B Vaccine What You Need to Know Many Vaccine Information stuck with a used needle. Hepatitis B vaccine: Why get 2 vaccinated? Hepatitis B vaccine can prevent. Hepatitis B vaccine may be given by itself or in the same shot with other vaccines. Routine hepatitis B

  13. Humoral responses to independent vaccinations are correlated in healthy boosted adults

    PubMed Central

    Garman, Lori; Vineyard, Amanda J.; Crowe, Sherry R.; Harley, John B.; Spooner, Christina E.; Collins, Limone C.; Nelson, Michael R.; Engler, Renata J.M.; James, Judith A.

    2015-01-01

    Background Roughly half of U.S. adults do not receive recommended booster vaccinations, but protective antibody levels are rarely measured in adults. Demographic factors, vaccination history, and responses to other vaccinations could help identify at-risk individuals. We sought to characterize rates of seroconversion and determine associations of humoral responses to multiple vaccinations in healthy adults. Methods Humoral responses toward measles, mumps, tetanus toxoid, pertussis, hepatitis B surface antigen, and anthrax protective antigen were measured by ELISA in post-immunization samples from 1,465 healthy U.S. military members. We examined the effects of demographic and clinical factors on immunization responses, as well as assessed correlations between vaccination responses. Results Subsets of boosted adults did not have seroprotective levels of antibodies toward measles (10.4%), mumps (9.4%), pertussis (4.7%), hepatitis B (8.6%) or protective antigen (14.4%) detected. Half-lives of antibody responses were generally long (>30 years). Measles and mumps antibody levels were correlated (r=0.31, p<0.001), but not associated with select demographic features or vaccination history. Measles and mumps antibody levels also correlated with tetanus antibody response (r=0.11, p<0.001). Conclusions Vaccination responses are predominantly robust and vaccine specific. However, a small but significant portion of the vaccinated adult population may not have quantitative seroprotective antibody to common vaccine-preventable infections. PMID:25140930

  14. Gold nanorod vaccine for respiratory syncytial virus

    NASA Astrophysics Data System (ADS)

    Stone, John W.; Thornburg, Natalie J.; Blum, David L.; Kuhn, Sam J.; Wright, David W.; Crowe, James E., Jr.

    2013-07-01

    Respiratory syncytial virus (RSV) is a major cause of pneumonia and wheezing in infants and the elderly, but to date there is no licensed vaccine. We developed a gold nanorod construct that displayed the major protective antigen of the virus, the fusion protein (F). Nanorods conjugated to RSV F were formulated as a candidate vaccine preparation by covalent attachment of viral protein using a layer-by-layer approach. In vitro studies using ELISA, electron microscopy and circular dichroism revealed that conformation-dependent epitopes were maintained during conjugation, and transmission electron microscopy studies showed that a dispersed population of particles could be achieved. Human dendritic cells treated with the vaccine induced immune responses in primary human T cells. These results suggest that this vaccine approach may be a potent method for immunizing against viruses such as RSV with surface glycoproteins that are targets for the human immune response.

  15. Vaccine Safety

    MedlinePLUS

    ... Search The CDC Cancel Submit Search The CDC Vaccine Safety Note: Javascript is disabled or is not ... on Facebook Tweet Share Compartir Back to School: Vaccines for Preteens Learn about the safety of Tdap, ...

  16. [Cholera update and vaccination problems].

    PubMed

    Fournier, J M; Villeneuve, S

    1998-01-01

    Cholera remains an important public health problem. The long-term control of cholera depends on good personal hygiene, uncontaminated water supply and appropriate sewage disposal. However, the improvement of hygiene is distant goal for many countries. Thus the availability of an effective cholera vaccine is important for the prevention of cholera in these countries. Research on new cholera vaccines has mainly focused on oral formulations that stimulate the mucosal secretory immune system. Two oral cholera vaccines were experimented on large scale in human. The first vaccine, containing inactivated bacterial cells and B-subunit of cholera toxin, has been tested in Bangladesh from 1985 to 1989. This vaccine, according to WHO, may prove useful in the stable phase of refugee/displaced person crises, especially when given preventively. The second vaccine is a live attenuated vaccine containing the genetically manipulated Vibrio cholerae O1 strain CVD 103-HgR. Despite its efficacy in adult volunteers, results of a large-scale field trial carried-out in Indonesia for 4 years have shown a surprisingly low protection. Moreover, one of the safety concerns associated with live cholera vaccine is a possible horizontal gene transfer and recombination event leading to reversion to virulence. A new vaccine development program for cholera is based upon the hypothesis that immunoglobulins G directed to the O-specific polysaccharide of Vibrio cholerae O1 could confer protective immunity to cholera by inactivating the inoculum on intestinal mucosal surface. This program may lead to the development of cholera conjugate vaccines to elicit protection in infants. PMID:9812307

  17. Enhanced mucosal immune responses against tetanus toxoid using novel delivery system comprised of chitosan-functionalized gold nanoparticles and botanical adjuvant: characterization, immunogenicity, and stability assessment.

    PubMed

    Barhate, Ganesh; Gautam, Manish; Gairola, Sunil; Jadhav, Suresh; Pokharkar, Varsha

    2014-11-01

    Approaches based on combined use of delivery systems and adjuvants are being favored to maximize efficient mucosal delivery of antigens. Here, we describe a novel delivery system comprised of chitosan-functionalized gold nanoparticles (CsAuNPs) and saponin-containing botanical adjuvant; Asparagus racemosus extract (ARE) for oral delivery of tetanus toxoid (TT). A significant increase in TT-specific IgG (34.53-fold) and IgA (43.75-fold) was observed when TT-CsAuNPs were formulated with ARE (TT-ARE-CsAuNPs). The local IgA immune responses for TT also showed a significant increase (106.5-fold in intestine washes and 99.74-fold in feces) with ARE-based formulations as compared with plain TT group. No effect of ARE was observed on size, charge, and loading properties of CsAuNPs. Additionally, no effect of ARE and CsAuNPs was observed on antigenicity and secondary structure of TT as determined by fluorescence, circular dichroism, and Fourier transform infrared spectroscopy. The stability studies demonstrated excellent stability profile of formulation at recommended storage conditions. The study establishes the possible role of immunomodulatory adjuvants in particulate delivery systems for mucosal delivery of vaccines. PMID:25219511

  18. Vaccination Mathematics

    E-print Network

    Meade, Douglas B.

    Vaccination Strategies for Epidemic Models Douglas B. Meade Department of Mathematics University://www.math.sc.edu/~meade/ 27 May 1999 #12; May 1999 IMA Mathematical Biology Seminar 0 Vaccination Strategies for Epidemic and natural death -- no death from infection -- no vaccination Ref: Shulgin, Stone, and Agur, Bull Math Bio

  19. [Salmonella typhi vaccination response study reveals defective antibody production selective IgA deficiency patient].

    PubMed

    Pleguezuelo, Daniel E; Gianelli, Carla

    2015-01-01

    Selective IgA deficiency (SIgAD) is the most prevalent immunodeficiency worldwide, progressing to common variable immunodeficiency only in few reported cases. We report the case of a Spanish female aged 22 and diagnosed of selective IgA deficiency, a long history of bronchitis, several episodes of pneumonia, bilateral bronchiectasis, normal IgG, IgM, IgG subclasses, and detectable pre-vaccination IgG antibodies against tetanus toxoid and Streptococcus pneumoniae. She was evaluated in our clinic in order to rule out common variable immunodeficiency. We observed good antibody response to tetanus toxoid, absence of circulating switched memory B cells, decreased response to pneumococcal polysaccharide antigens and a lack of response to Salmonella typhi vaccine. Most SIgAD patients presents with upper respiratory tract infections or mild diarrhea. Those with lower tract infections, pneumonia or untreatable diarrhea should follow B-cell subpopulations' study and antibody response to vaccines. Absence of response to Salmonella typhi vaccine allowed us to expose the defective antibody production. PMID:26556667

  20. Diversity of the Antibody Response to Tetanus Toxoid: Comparison of Hybridoma Library to Phage Display Library

    PubMed Central

    Sorouri, Mahsa; Fitzsimmons, Sean P.; Aydanian, Antonina G.; Bennett, Sonita; Shapiro, Marjorie A.

    2014-01-01

    Monoclonal antibodies are important tools in research and since the 1990s have been an important therapeutic class targeting a wide variety of diseases. Earlier methods of mAb production relied exclusively on the lengthy process of making hybridomas. The advent of phage display technology introduced an alternative approach for mAb production. A potential concern with this approach is its complete dependence on an in vitro selection process, which may result in selection of VH-VL pairs normally eliminated during the in vivo selection process. The diversity of VH-VL pairs selected from phage display libraries relative to an endogenous response is unknown. To address these questions, we constructed a panel of hybridomas and a phage display library using the spleen of a single tetanus toxoid-immunized mouse and compared the diversity of the immune response generated using each technique. Surprisingly, the tetanus toxoid-specific antibodies produced by the hybridoma library exhibited a higher degree of VH-VL genetic diversity than their phage display-derived counterparts. Furthermore, the overlap among the V-genes from each library was very limited. Consistent with the notion that accumulation of many small DNA changes lead to increased antigen specificity and affinity, the phage clones displayed substantial micro-heterogeneity. Contrary to previous reports, we found that antigen specificity against tetanus toxoid is encoded by both V? and VH genes. Finally, the phage-derived tetanus-specific clones had a lower binding affinity than the hybridomas, a phenomenon thought to be the result of random pairing of the V-genes. PMID:25268771

  1. VACCINE INFORMATION STATEMENT Hepatitis A Vaccine

    E-print Network

    Leistikow, Bruce N.

    VACCINE INFORMATION STATEMENT Hepatitis A Vaccine What You Need to Know Many Vaccine Information 1,000 cases). Hepatitis A vaccine can prevent hepatitis A. 2 Who should get hepatitis A vaccine and when? WHO? Some people should be routinely vaccinated with hepatitis A vaccine: · All children between

  2. DNA vaccines

    NASA Astrophysics Data System (ADS)

    Gregersen, Jens-Peter

    2001-12-01

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

  3. O:2-CRM(197) conjugates against Salmonella Paratyphi A.

    PubMed

    Micoli, Francesca; Rondini, Simona; Gavini, Massimiliano; Lanzilao, Luisa; Medaglini, Donata; Saul, Allan; Martin, Laura B

    2012-01-01

    Enteric fevers remain a common and serious disease, affecting mainly children and adolescents in developing countries. Salmonella enterica serovar Typhi was believed to cause most enteric fever episodes, but several recent reports have shown an increasing incidence of S. Paratyphi A, encouraging the development of a bivalent vaccine to protect against both serovars, especially considering that at present there is no vaccine against S. Paratyphi A. The O-specific polysaccharide (O:2) of S. Paratyphi A is a protective antigen and clinical data have previously demonstrated the potential of using O:2 conjugate vaccines. Here we describe a new conjugation chemistry to link O:2 and the carrier protein CRM(197), using the terminus 3-deoxy-D-manno-octulosonic acid (KDO), thus leaving the O:2 chain unmodified. The new conjugates were tested in mice and compared with other O:2-antigen conjugates, synthesized adopting previously described methods that use CRM(197) as carrier protein. The newly developed conjugation chemistry yielded immunogenic conjugates with strong serum bactericidal activity against S. Paratyphi A. PMID:23144798

  4. Enteric vaccines.

    PubMed

    Edelman, R; Levine, M M

    1991-03-01

    Considerable progress has been made in the past decade in developing vaccines against the most important bacterial and viral infections of the gastrointestinal tract. Members of the Division of Geographic Medicine in the Center for Vaccine Development have played a prominent role in the laboratory development and clinical testing of these vaccines. A new oral typhoid vaccine, Ty21a, has been licensed in the United States. A genetically engineered live oral cholera vaccine developed in the CVD is undergoing clinical trials in cholera-endemic areas. Multiple vaccine candidates against Shigella, enterotoxigenic E. coli, and rotavirus are in clinical trial in the United States or overseas. Rapid advances in molecular biology, together with new knowledge of mucosal and cellular immunity, will produce more vaccine candidates in the future. The CVD intends to be in the forefront of these developments. PMID:2008164

  5. Panel 6: Vaccines

    PubMed Central

    Pelton, Stephen I.; Pettigrew, Melinda M.; Barenkamp, Stephen J.; Godfroid, Fabrice; Grijalva, Carlos G.; Leach, Amanda; Patel, Janak; Murphy, Timothy F.; Selak, Sanja; Bakaletz, Lauren O.

    2014-01-01

    Objective To update progress on the effectiveness of vaccine for prevention of acute otitis media (AOM) and identification of promising candidate antigens against Streptococcus pneumoniae, nontypeable Haemophilus influenzae, and Moraxella catarrhalis. Review Methods Literature searches were performed in OvidSP and PubMed restricted to articles published between June 2007 and September 2011. Search terms included otitis media, vaccines, vaccine antigens, and each of the otitis pathogens and candidate antigens identified in the ninth conference report. Conclusions The current report provides further evidence for the effectiveness of pneumococcal conjugate vaccines (PCVs) in the prevention of otitis media. Observational studies demonstrate a greater decline in AOM episodes than reported in clinical efficacy trials. Unmet challenges include extending protection to additional serotypes and additional pathogens, the need to prevent early episodes, the development of correlates of protection for protein antigens, and the need to define where an otitis media vaccine strategy fits with priorities for child health. Implications for Practice Acute otitis media continues to be a burden on children and families, especially those who suffer from frequent recurrences. The 7-valent PCV (PCV7) has reduced the burden of disease as well as shifted the pneumococcal serotypes and the distribution of otopathogens currently reported in children with AOM. Antibiotic resistance remains an ongoing challenge. Multiple candidate antigens have demonstrated the necessary requirements of conservation, surface exposure, immunogenicity, and protection in animal models. Further research on the role of each antigen in pathogenesis, in the development of correlates of protection in animal models, and in new adjuvants to elicit responses in the youngest infants is likely to be productive and permit more antigens to move into human clinical trials. PMID:23536534

  6. Identification of human antibody fragment clones specific for tetanus toxoid in a bacteriophage. lambda. immunoexpression library

    SciTech Connect

    Mullinax, R.L.; Gross, E.A.; Amberg, J.R.; Hogrefe, H.H.; Kubitz, M.M.; Greener, A.; Alting-Mees, M.; Ardourel, D.; Short, J.M.; Sorge, J.A. ); Hay, B.N.; Shopes, B. )

    1990-10-01

    The authors have applied a molecular biology approach to the identification of human monoclonal antibodies. Human peripheral blood lymphocyte mRNA was converted to cDNA and a select subset was amplified by the polymerase chain reaction. These products, containing coding sequences for numerous immunoglobulin heavy- and {kappa} light-chain variable and constant region domains, were inserted into modified bacteriophase {lambda} expression vectors and introduced into Escherichia coli by infection to yield a combinatorial immunoexpression library. Clones with binding activity to tetanus toxoid were identified by filter hybridization with radiolabeled antigen and appeared at a frequency of 0.2{percent} in the library. These human antigen binding fragments, consisting of a heavy-chain fragment covalently linked to a light chain, displayed high affinity of binding to tetanus toxoid with equilibrium constants in the nanomolar range but did not cross-react with other proteins tested. They estimate that this human immunoexpression library contains 20,000 clones with high affinity and specificity to our chosen antigen.

  7. Meningococcal meningitis: vaccination outbreak response and epidemiological changes in the African meningitis belt.

    PubMed

    Carod Artal, Francisco Javier

    2015-07-01

    The main approach to controlling epidemics of meningococcal meningitis in the African meningitis belt has been reactive vaccination campaigns with serogroup A polysaccharide vaccine once the outbreak reached an incidence threshold. Early reactive vaccination is effective in reducing morbidity and mortality. A recent paper in International Health has shown that earlier reactive vaccination campaigns may be even more effective than increasing the coverage area of vaccination. Monovalent serogroup A conjugate vaccine programs have recently been launched to prevent transmission in endemic areas in the African meningitis belt. Conjugate vaccines can induce immunological memory and have impact on pharyngeal carriage. However, reactive vaccination still has a role to play taking into account the dynamic changes in the epidemiology of meningitis in this area. PMID:25878213

  8. Designer vaccines to prevent infections due to group B Streptococcus.

    PubMed

    Kasper, D L

    1995-10-01

    Group B streptococci (GBS) are the major cause of serious infections in neonates and an important cause of infection in adults, particularly peripartum women and patients with diabetes mellitus and malignancy. Immunity to GBS in neonates is associated with naturally acquired maternal antibodies to the type-specific capsular polysaccharides of these organisms. IgG class antibodies directed to these polysaccharides are passed transplacentally and protect the child from invasive GBS disease. Phase I and II clinical trials showed that the purified polysaccharides had limited immunogenicity. However, vaccine responders passed functional IgG class antibodies to their children. A glycoconjugate vaccine has been designed so that the type-specific polysaccharides are covalently linked to a carrier protein. This secondary amine linkage is between aldehyde groups created on the eighth carbon of a selected number of periodate-oxidized sialic acid residues of the polysaccharide and epsilon-amino groups on lysine residues of tetanus toxoid. Careful epitope mapping studies had demonstrated that modification by controlled periodate oxidation could be accomplished and that an important conformational epitope on the polysaccharide would be preserved. Preclinical testing of the glycoconjugate vaccines in animal models of GBS disease demonstrated the immunogenicity and protective efficacy of the vaccine-induced antibodies. Phase I clinical testing of the glycoconjugate vaccine is in progress, and the early results appear promising. PMID:8608425

  9. Vaccines.gov

    MedlinePLUS

    ... of Vaccines Features: News & Video Free Resources HPV Vaccine is Cancer Prevention HPV vaccination protects against several ... flu isn’t part of your travel plans. Vaccines: A Strong Record of Safety Vaccines to prevent ...

  10. Vaccine Adverse Events

    MedlinePLUS

    ... Vaccines, Blood & Biologics Animal & Veterinary Cosmetics Tobacco Products Vaccines, Blood & Biologics Home Vaccines, Blood & Biologics Safety & Availability ( ... Center for Biologics Evaluation & Research Vaccine Adverse Events Vaccine Adverse Events Share Tweet Linkedin Pin it More ...

  11. DNA conjugation andDNA conjugation and reversibility onreversibility on

    E-print Network

    Rubloff, Gary W.

    DNA conjugation andDNA conjugation and reversibility onreversibility on chitosan surfaceschitosan surfaceschitosan surfaceschitosan surfaces Rubloff Research Group Accomplishments #12;DNA conjugation and reversibility onDNA conjugation and reversibility on chitosan surfaceschitosan surfaces Accomplishment Single

  12. Vaccines Through Centuries: Major Cornerstones of Global Health.

    PubMed

    Hajj Hussein, Inaya; Chams, Nour; Chams, Sana; El Sayegh, Skye; Badran, Reina; Raad, Mohamad; Gerges-Geagea, Alice; Leone, Angelo; Jurjus, Abdo

    2015-01-01

    Multiple cornerstones have shaped the history of vaccines, which may contain live-attenuated viruses, inactivated organisms/viruses, inactivated toxins, or merely segments of the pathogen that could elicit an immune response. The story began with Hippocrates 400 B.C. with his description of mumps and diphtheria. No further discoveries were recorded until 1100 A.D. when the smallpox vaccine was described. During the eighteenth century, vaccines for cholera and yellow fever were reported and Edward Jenner, the father of vaccination and immunology, published his work on smallpox. The nineteenth century was a major landmark, with the "Germ Theory of disease" of Louis Pasteur, the discovery of the germ tubercle bacillus for tuberculosis by Robert Koch, and the isolation of pneumococcus organism by George Miller Sternberg. Another landmark was the discovery of diphtheria toxin by Emile Roux and its serological treatment by Emil Von Behring and Paul Ehrlih. In addition, Pasteur was able to generate the first live-attenuated viral vaccine against rabies. Typhoid vaccines were then developed, followed by the plague vaccine of Yersin. At the beginning of World War I, the tetanus toxoid was introduced, followed in 1915 by the pertussis vaccine. In 1974, The Expanded Program of Immunization was established within the WHO for bacille Calmette-Guerin, Polio, DTP, measles, yellow fever, and hepatitis B. The year 1996 witnessed the launching of the International AIDS Vaccine Initiative. In 1988, the WHO passed a resolution to eradicate polio by the year 2000 and in 2006; the first vaccine to prevent cervical cancer was developed. In 2010, "The Decade of vaccines" was launched, and on April 1st 2012, the United Nations launched the "shot@Life" campaign. In brief, the armamentarium of vaccines continues to grow with more emphasis on safety, availability, and accessibility. This mini review highlights the major historical events and pioneers in the course of development of vaccines, which have eradicated so many life-threatening diseases, despite the vaccination attitudes and waves appearing through history. PMID:26636066

  13. Vaccines Through Centuries: Major Cornerstones of Global Health

    PubMed Central

    Hajj Hussein, Inaya; Chams, Nour; Chams, Sana; El Sayegh, Skye; Badran, Reina; Raad, Mohamad; Gerges-Geagea, Alice; Leone, Angelo; Jurjus, Abdo

    2015-01-01

    Multiple cornerstones have shaped the history of vaccines, which may contain live-attenuated viruses, inactivated organisms/viruses, inactivated toxins, or merely segments of the pathogen that could elicit an immune response. The story began with Hippocrates 400 B.C. with his description of mumps and diphtheria. No further discoveries were recorded until 1100 A.D. when the smallpox vaccine was described. During the eighteenth century, vaccines for cholera and yellow fever were reported and Edward Jenner, the father of vaccination and immunology, published his work on smallpox. The nineteenth century was a major landmark, with the “Germ Theory of disease” of Louis Pasteur, the discovery of the germ tubercle bacillus for tuberculosis by Robert Koch, and the isolation of pneumococcus organism by George Miller Sternberg. Another landmark was the discovery of diphtheria toxin by Emile Roux and its serological treatment by Emil Von Behring and Paul Ehrlih. In addition, Pasteur was able to generate the first live-attenuated viral vaccine against rabies. Typhoid vaccines were then developed, followed by the plague vaccine of Yersin. At the beginning of World War I, the tetanus toxoid was introduced, followed in 1915 by the pertussis vaccine. In 1974, The Expanded Program of Immunization was established within the WHO for bacille Calmette–Guerin, Polio, DTP, measles, yellow fever, and hepatitis B. The year 1996 witnessed the launching of the International AIDS Vaccine Initiative. In 1988, the WHO passed a resolution to eradicate polio by the year 2000 and in 2006; the first vaccine to prevent cervical cancer was developed. In 2010, “The Decade of vaccines” was launched, and on April 1st 2012, the United Nations launched the “shot@Life” campaign. In brief, the armamentarium of vaccines continues to grow with more emphasis on safety, availability, and accessibility. This mini review highlights the major historical events and pioneers in the course of development of vaccines, which have eradicated so many life-threatening diseases, despite the vaccination attitudes and waves appearing through history. PMID:26636066

  14. VACCINE INFORMATION STATEMENT HPV Vaccine Cervarix

    E-print Network

    Pawlowski, Wojtek

    VACCINE INFORMATION STATEMENT HPV Vaccine Cervarix® What You Need to Know (Human Papillomavirus) Many Vaccine Information Statements are available in Spanish and other languages. See www, but some of the problems it causes can be treated. 2 HPV vaccine: Why get vaccinated? HPV vaccine

  15. [Towards a new vaccine economy?].

    PubMed

    Poirot, P; Martin, J F

    1994-01-01

    When Jonas Salk announced in the mid-50s the availability of a new vaccine against poliomyelitis, the world had the impression that it was now controlling infectious diseases. In fact, the success of this vaccine has been considerable and although some innovations lead to the launch of vaccines against flu, measles, rubella or mumps, the world vaccine market remained remarkably stable till the mid-80s. However, since 1984 (launch of the hepatitis B vaccine) there have been very substantial changes and further change is expected in the next ten years in the world market. Today, big companies are making a concentrated supply: Pasteur Mérieux with its subsidiary Connaught, SmithKline Beecham who acquired the Belgian company RIT, and Merck & Co. who is joining its forces with Pasteur Mérieux. Medium sized and small companies remain and reflect the situation of the past, but must work hard to secure their long term existence eventhough the world demand is going to double before the year 2000. Very substantial technological innovations explain to a large extent the development of the supply: progress in molecular biology, and particularly genetic engineering, lead to recombinant vaccines of which hepatitis B is the best example with worldwide sales in the range of $600 million a year. Similarly, conjugation technologies have allowed the development of new vaccines against meningitis, particularly Haemophilus influenzae type b. More recently, an efficacious vaccine against hepatitis A has been launched and many new products will be marketed in the next years against herpes, Lyme disease, and agents of other meningitis, etc.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:7921683

  16. Recent advances in the molecular design of synthetic vaccines.

    PubMed

    Jones, Lyn H

    2015-11-20

    Vaccines have typically been prepared using whole organisms. These are normally either attenuated bacteria or viruses that are live but have been altered to reduce their virulence, or pathogens that have been inactivated and effectively killed through exposure to heat or formaldehyde. However, using whole organisms to elicit an immune response introduces the potential for infections arising from a reversion to a virulent form in live pathogens, unproductive reactions to vaccine components or batch-to-batch variability. Synthetic vaccines, in which a molecular antigen is conjugated to a carrier protein, offer the opportunity to circumvent these problems. This Perspective will highlight the progress that has been achieved in developing synthetic vaccines using a variety of molecular antigens. In particular, the different approaches used to develop conjugate vaccines using peptide/proteins, carbohydrates and other small molecule haptens as antigens are compared. PMID:26587710

  17. Antibiotics Modulate Vaccine-Induced Humoral Immune Response

    PubMed Central

    Woo, Patrick C. Y.; Tsoi, Hoi-Wah; Wong, Lei-Po; Leung, Harry C. H.; Yuen, Kwok-Yung

    1999-01-01

    The effects of antibiotics on the antigen-specific humoral immune response are not known. Macrolides, tetracyclines, and beta-lactams are commonly prescribed antibiotics. The first two are known to have immunomodulatory activities. The effects of clarithromycin, doxycycline, and ampicillin on the primary and secondary antibody responses to tetanus toxoid, a pneumococcal polysaccharide vaccine, a hepatitis B virus surface antigen (HBsAg) vaccine, and live attenuated Salmonella typhi (Ty21a) were investigated using a mouse model. For the mice receiving the tetanus toxoid, the immunoglobulin M (IgM) level of the clarithromycin group at day 7 was significantly lower than the corresponding antibody level of the normal saline (NS) group. For the mice receiving the pneumococcal polysaccharide vaccine, the total antibody and IgM levels of the clarithromycin group and the IgM level of the doxycycline group at day 7 were significantly lower than the corresponding antibody levels of the ampicillin and NS groups. For the mice receiving the HBsAg vaccine, the IgM level of the doxycycline group at day 7 was significantly lower than the corresponding antibody levels of the clarithromycin and NS groups, while the IgM level of the clarithromycin group at day 28 was significantly lower than the corresponding antibody levels of the doxycycline, ampicillin, and NS groups. For the mice receiving all three vaccines, there were no statistically significant differences between any of the antibody levels of the ampicillin group and the corresponding antibody levels of the NS group. For the mice receiving Ty21a, the total antibody levels of the ampicillin group at days 7 and 21 were significantly higher than the corresponding antibody levels of the NS group. Moreover, the IgM levels of the clarithromycin, doxycycline, and ampicillin groups at days 7 and 21 were significantly higher than the corresponding antibody levels of the NS group. Furthermore, the total antibody level of the ampicillin group at day 21 was significantly higher than the corresponding antibody level of the doxycycline group. For all four vaccines, there were no statistically significant differences among the serum levels of interleukin-10 and gamma interferon for the mice treated with the various antibiotics. We conclude that clarithromycin and doxycycline, but not ampicillin, suppress the antibody responses of mice to T-cell-dependent and T-cell-independent antigens, whereas all three antibiotics enhance the antibody response to live attenuated mucosal bacterial vaccines. PMID:10548572

  18. Nanogel antigenic protein-delivery system for adjuvant-free intranasal vaccines

    NASA Astrophysics Data System (ADS)

    Nochi, Tomonori; Yuki, Yoshikazu; Takahashi, Haruko; Sawada, Shin-Ichi; Mejima, Mio; Kohda, Tomoko; Harada, Norihiro; Kong, Il Gyu; Sato, Ayuko; Kataoka, Nobuhiro; Tokuhara, Daisuke; Kurokawa, Shiho; Takahashi, Yuko; Tsukada, Hideo; Kozaki, Shunji; Akiyoshi, Kazunari; Kiyono, Hiroshi

    2010-07-01

    Nanotechnology is an innovative method of freely controlling nanometre-sized materials. Recent outbreaks of mucosal infectious diseases have increased the demands for development of mucosal vaccines because they induce both systemic and mucosal antigen-specific immune responses. Here we developed an intranasal vaccine-delivery system with a nanometre-sized hydrogel (`nanogel') consisting of a cationic type of cholesteryl-group-bearing pullulan (cCHP). A non-toxic subunit fragment of Clostridium botulinum type-A neurotoxin BoHc/A administered intranasally with cCHP nanogel (cCHP-BoHc/A) continuously adhered to the nasal epithelium and was effectively taken up by mucosal dendritic cells after its release from the cCHP nanogel. Vigorous botulinum-neurotoxin-A-neutralizing serum IgG and secretory IgA antibody responses were induced without co-administration of mucosal adjuvant. Importantly, intranasally administered cCHP-BoHc/A did not accumulate in the olfactory bulbs or brain. Moreover, intranasally immunized tetanus toxoid with cCHP nanogel induced strong tetanus-toxoid-specific systemic and mucosal immune responses. These results indicate that cCHP nanogel can be used as a universal protein-based antigen-delivery vehicle for adjuvant-free intranasal vaccination.

  19. Gender-specific effects of cytokine gene polymorphisms on childhood vaccine responses.

    PubMed

    Baynam, Gareth; Zhang, Guicheng; Khoo, Siew-Kim; Sly, Peter; Holt, Patrick; Goldblatt, Jack; Le Souëf, Peter N

    2008-07-01

    Cytokine gene polymorphisms affect vaccine responses and gender-specific effects are known for many phenotypes. Therefore, this study investigated gender-specific effects of cytokine gene polymorphisms on vaccine responses. In 263 2-year-old subjects selected for parental history of atopy, boys with IL-4 C-589T and IL-4Ralpha I50V genotypes associated with atopy had increased Diptheria Toxoid (DiphTox) and Tetanus Toxoid (TetTox) responses compared with the remaining alleles (IL-4 C-589T: DipTox p=0.01, TetTox p=0.04; IL-4Ralpha.I50V: DipTox p=0.04, TetTox p=0.08). Contrastingly, girls with IL-10 -592C genotypes associated with atopy had lower levels of DiphTox (p=0.03) and TetTox (p=0.02) responses compared with the remaining allele. Additionally, interaction effects were found for IL-4 C-589T (p=0.01) and IL-4Ralpha I50V (p=0.04) polymorphisms. In conclusion, these findings support the interaction of primary genetic and modifying factors on vaccine responses and the importance of atopic genetics to these responses. PMID:18547691

  20. Rotavirus Vaccine

    MedlinePLUS

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

  1. Haemophilus influenzae type b vaccination and risk of childhood leukemia in a vaccine trial in finland.

    PubMed

    Groves; Auvinen; Hakulinen

    2000-10-01

    PURPOSE: To compare the incidence of childhood leukemia among children who received multiple early vaccine doses versus a single late dose in the context of a clinical trial in Finland during 1986 and 1987.METHODS: The trial was offered to the parents of all 114,000 children born in Finland between October 1, 1985 and August 31, 1987; 98% of the eligible children were enrolled. The vaccine consisted of heat-sized capsular polysaccharide of Haemophilus influenzae type b (Hib) coupled to diptheria toxoid (PRP-D). Children with odd birth dates received four doses of the vaccine at the ages of 3, 4, 6, and 14 months; children with even birth dates received only one dose, at the age of 24 months. The numbers of boys and girls with even and odd birth dates during the window of eligibility who remained alive during the follow-up period were obtained from the Finnish Population Registry. Numbers of leukemia cases diagnosed through 1996 among children with even and odd birth dates during the window of eligibility were obtained from the Finnish Cancer Registry. Poisson regression analysis of leukaemia incidence rates was conducted using the number of cases as the outcome variable and the natural logarithm of number of children at risk as an offset term. For comparison of the early and late vaccination groups, a binary variable based on odd or even date of birth was used.RESULTS: Among the 114,000 subjects, a total of 77 cases of childhood leukaemia were diagnosed: 33 in the early-vaccination group and 44 in the late-vaccination group. The incidence of childhood leukaemia was lower in the early-vaccination group (relative risk 0.72, 95% confidence interval 0.46-1.13) than in the late-vaccination group, but the difference did not reach statistical significance.CONCLUSIONS: Our results suggest that early vaccination against Hib may reduce the incidence of childhood leukaemia, but confirmatory studies are needed. PMID:11018411

  2. From Epidemic Meningitis Vaccines for Africa to the Meningitis Vaccine Project

    PubMed Central

    Aguado, M. Teresa; Jodar, Luis; Granoff, Dan; Rabinovich, Regina; Ceccarini, Costante; Perkin, Gordon W.

    2015-01-01

    Background.?Polysaccharide vaccines had been used to control African meningitis epidemics for >30 years but with little or modest success, largely because of logistical problems in the implementation of reactive vaccination campaigns that are begun after epidemics are under way. After the major group A meningococcal meningitis epidemics in 1996–1997 (250 000 cases and 25 000 deaths), African ministers of health declared the prevention of meningitis a high priority and asked the World Health Organization (WHO) for help in developing better immunization strategies to eliminate meningitis epidemics in Africa. Methods.?WHO accepted the challenge and created a project called Epidemic Meningitis Vaccines for Africa (EVA) that served as an organizational framework for external consultants, PATH, the US Centers for Disease Control and Prevention (CDC), and the Bill & Melinda Gates Foundation (BMGF). Consultations were initiated with major vaccine manufacturers. EVA commissioned a costing study/business plan for the development of new group A or A/C conjugate vaccines and explored the feasibility of developing these products as a public–private partnership. Representatives from African countries were consulted. They confirmed that the development of conjugate vaccines was a priority and provided information on preferred product characteristics. In parallel, a strategy for successful introduction was also anticipated and discussed. Results.?The expert consultations recommended that a group A meningococcal conjugate vaccine be developed and introduced into the African meningitis belt. The results of the costing study indicated that the “cost of goods” to develop a group A – containing conjugate vaccine in the United States would be in the range of US$0.35–$1.35 per dose, depending on composition (A vs A/C), number of doses/vials, and presentation. Following an invitation from BMGF, a proposal was submitted in the spring of 2001. Conclusions.?In June 2001, BMGF awarded a grant of US$70 million to create the Meningitis Vaccine Project (MVP) as a partnership between PATH and WHO, with the specific goal of developing an affordable MenA conjugate vaccine to eliminate MenA meningitis epidemics in Africa. EVA is an example of the use of WHO as an important convening instrument to facilitate new approaches to address major public health problems. PMID:26553665

  3. A method of lyophilizing vaccines containing aluminum salts into a dry powder without causing particle aggregation or decreasing the immunogenicity following reconstitution.

    PubMed

    Li, Xinran; Thakkar, Sachin G; Ruwona, Tinashe B; Williams, Robert O; Cui, Zhengrong

    2015-04-28

    Many currently licensed and commercially available human vaccines contain aluminum salts as vaccine adjuvants. A major limitation with these vaccines is that they must not be exposed to freezing temperatures during transport or storage such that the liquid vaccine freezes, because freezing causes irreversible coagulation that damages the vaccines (e.g., loss of efficacy). Therefore, vaccines that contain aluminum salts as adjuvants are formulated as liquid suspensions and are required to be kept in cold chain (2-8°C) during transport and storage. Formulating vaccines adjuvanted with aluminum salts into dry powder that can be readily reconstituted before injection may address this limitation. Spray freeze-drying of vaccines with low concentrations of aluminum salts and high concentrations of trehalose alone, or a mixture of sugars and amino acids, as excipients can convert vaccines containing aluminum salts into dry powder, but fails to preserve the particle size and/or immunogenicity of the vaccines. In the present study, using ovalbumin as a model antigen adsorbed onto aluminum hydroxide or aluminum phosphate, a commercially available tetanus toxoid vaccine adjuvanted with potassium alum, a human hepatitis B vaccine adjuvanted with aluminum hydroxide, and a human papillomavirus vaccine adjuvanted with aluminum hydroxyphosphate sulfate, it was shown that vaccines containing a relatively high concentration of aluminum salts (i.e., up to ~1%, w/v, of aluminum hydroxide) can be converted into a dry powder by thin-film freezing followed by removal of the frozen solvent by lyophilization while using low levels of trehalose (i.e., as low as 2% w/v) as an excipient. Importantly, the thin-film freeze-drying process did not cause particle aggregation, nor decreased the immunogenicity of the vaccines. Moreover, repeated freezing-and-thawing of the dry vaccine powder did not cause aggregation. Thin-film freeze-drying is a viable platform technology to produce dry powders of vaccines that contain aluminum salts. PMID:25735896

  4. [The current status of research on a cholera vaccine].

    PubMed

    Fournier, J M

    1998-01-01

    Cholera remains today a major health problem in most developing countries. The long-term control of cholera depends on the improvement of hygiene but this is a distant goal for many countries. The availability of an effective cholera vaccine is thus important for the prevention of cholera in such countries. More than a century after the first attempt to vaccinate against cholera by Ferran in Spain, there is still no truly effective cholera vaccine. A bacterial fraction vaccine, referred to as CH1 +2 was prepared by Professor A. Dodin. A field trial of this vaccine was carried out in Zaire in 1983. Significant protection was observed but this vaccine was not evaluated in additional trials. Two other oral cholera vaccines, developed in Sweden and in the USA, were widely experimented on human beings: a combination of cholera toxin B-subunit and inactivated bacterial cells, and a live attenuated vaccine containing the genetically manipulated Vibrio cholerae O1 strain CVD 103-HgR. Despite their efficiency as evaluated in field trials (inactivated vaccine) or on volunteers (live vaccine), these vaccines have drawbacks that may limit their usefulness as practical vaccines. Protection induced by the inactivated vaccine was transient in young children, lasting only approximately for six months. One of the safety concerns associated with live vaccines is a possible reversion to virulence. Efforts should be continued to find a better cholera vaccine. A new vaccine development program based upon the hypothesis that immunoglobulin G directed to the O-specific polysaccharide of Vibrio cholerae O1 could confer protective immunity to cholera. This program may lead to the development of a cholera conjugate vaccine to elicit protection in infants. PMID:10078377

  5. Synthetic self-adjuvanting glycopeptide cancer vaccines

    PubMed Central

    McDonald, David M.; Byrne, Scott N.; Payne, Richard J.

    2015-01-01

    Due to changes in glycosyltransferase expression during oncogenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens (TACAs), and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system toward tumor-associated glycopeptide antigens via synthetic self-adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Many of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo. PMID:26557640

  6. Synthetic Self-Adjuvanting Glycopeptide Cancer Vaccines

    NASA Astrophysics Data System (ADS)

    Payne, Richard; McDonald, David; Byrne, Scott

    2015-10-01

    Due to changes in glycosyltransferase expression during tumorigenesis, the glycoproteins of cancer cells often carry highly truncated carbohydrate chains compared to those on healthy cells. These glycans are known as tumor-associated carbohydrate antigens, and are prime targets for use in vaccines for the prevention and treatment of cancer. Herein, we review the state-of-the-art in targeting the immune system towards tumor-associated glycopeptide antigens via synthetic self adjuvanting vaccines, in which the antigenic and adjuvanting moieties of the vaccines are present in the same molecule. The majority of the self-adjuvanting glycopeptide cancer vaccines reported to date employ antigens from mucin 1, a protein which is highly over-expressed and aberrantly glycosylated in many forms of cancer. The adjuvants used in these vaccines predominantly include lipopeptide- or lipoamino acid-based TLR2 agonists, although studies investigating stimulation of TLR9 and TLR4 are also discussed. Most of these adjuvants are highly lipophilic, and, upon conjugation to antigenic peptides, provide amphiphilic vaccine molecules. The amphiphilic nature of these vaccine constructs can lead to the formation of higher-order structures by vaccines in solution, which are likely to be important for their efficacy in vivo.

  7. Immunogenicity and reactogenicity of the Biken acellular pertussis vaccine in young adults.

    PubMed

    Schmitt, H J; Mohnike, K; Zepp, F; Herden, P; Hosbach, P

    2000-10-15

    To assess the reactogenicity and immunogenicity of the Biken acellular pertussis vaccine (Pa) following administration of a single vaccine dose to young adults with or without a history of prior pertussis immunization, 104 healthy, male and female adults without primary pertussis immunization were enrolled in Mainz (former West Germany; "not previously pertussis vaccinated", N-PPV-group); in parallel, 103 adults with a history of having received >/=four doses of a combined diphtheria-, tetanus-toxoid, whole-cell pertussis vaccine (DTwP) were enrolled in Magdeburg (former East Germany; "previously pertussis-vaccinated", PPV-group). Large areas of redness (>20 mm) were seen in 2.9%/1.0% of subjects in the N-PPV/PPV group, and a large swelling was seen in 6.8%/1.0%, respectively. As compared to baseline concentrations, antibody titers to PT and FHA were 77-(PT)/64-(FHA) (N-PPV group) and 94-(PT)/126-(FHA) fold (PPV group) higher. The study vaccine was safe and induced infrequent and mostly mild, local and general symptoms that all resolved spontaneously; it was highly immunogenic in adults, whether or not they had been previously vaccinated with DTwP. PMID:11027800

  8. Oral Vitamin A and Retinoic Acid Supplementation Stimulates Antibody Production and Splenic Stra6 Expression in Tetanus Toxoid–Immunized Mice12

    PubMed Central

    Tan, Libo; Wray, Amanda E.; Ross, A. Catharine

    2012-01-01

    Coadministration of retinoic acid (RA) and polyinosinic acid:polycytidylic acid (PIC) has been shown to cooperatively enhance the anti–tetanus toxoid (anti-TT) vaccine response in adult mice. Germinal center formation in the spleen is critical for a normal antibody response. Recent studies have identified Stimulated by Retinoic Acid-6 (Stra6) as the cell membrane receptor for retinol-binding protein (RBP) in many organs, including spleen. The objectives of the present studies were to test whether orally administered vitamin A (VA) itself, either alone or combined with RA, and/or treatment with PIC regulates Stra6 gene expression in mouse spleen and, concomitantly, antibody production. Eight-week-old C57BL/6 mice were immunized with TT. In an initial kinetic study, oral VA (6 mg/kg) increased anti-TT IgM and IgG production as well as splenic Stra6 mRNA expression. In treatment studies that were analyzed 9 d postimmunization, retinoids including VA, RA, VA and RA combined, and PIC significantly increased plasma anti-TT IgM and IgG (P < 0.05) and splenic Stra6 mRNA (P < 0.05). Treatments that included PIC elevated plasma anti-TT IgM and IgG concentrations >20-fold (P < 0.01). Immunohistochemistry of STRA6 protein in mouse spleen confirmed its increase after immunization and retinoid treatment. In conclusion, retinoid treatments that included VA, RA, VA and RA combined, and the combination of retinoid and PIC stimulated the expression of Stra6 in spleen, which potentially could increase the local uptake of retinol. Concomitantly, these treatments increased the systemic antigen-specific antibody response. The ability of oral retinoids to stimulate systemic immunity has implications for public health and therapeutic use of VA. PMID:22739370

  9. Cholera vaccines.

    PubMed

    Ryan, E T; Calderwood, S B

    2000-08-01

    Cholera causes significant morbidity and mortality worldwide. For travelers, the risk of developing cholera per month of stay in a developing country is approximately 0.001%-0.01%, and cholera may present as traveler's diarrhea. In the United States, only a poorly tolerated, marginally effective, parenterally administered, phenol-inactivated vaccine is available. Outside the United States, 2 additional vaccines are commercially available: an oral killed whole cell-cholera toxin recombinant B subunit vaccine (WC-rBS) and an oral live attenuated Vibrio cholerae vaccine (CVD 103-HgR). These oral vaccines are well tolerated. In field trials, WC-rBS provides 80%-85% protection from cholera caused by V. cholerae serogroup O1 for at least 6 months. In volunteer studies, CVD 103-HgR provides 62%-100% protection against cholera caused by V. cholerae for at least 6 months. No commercially available cholera vaccine protects against disease caused by V. cholerae serogroup O139. New cholera vaccines are being developed. PMID:10987721

  10. Rotavirus vaccines.

    PubMed

    Barnes, G

    1998-01-01

    Encouraging results have been reported from several large trials of tetravalent rhesus rotavirus vaccine, with efficacy of 70-80% against severe disease. A recent Venezuelan study showed similar results to trials in USA and Europe. The vaccine may soon be licensed in USA. It provides the exciting prospect of a strategy to prevent one of the world's major child killers. Other candidate vaccines are under development including human-bovine reassortants, neonatal strains, non-replicating rotaviruses, vector vaccines and other genetically engineered products. Second and third generation rotavirus vaccines are on the horizon. The need for a rotavirus vaccine is well accepted by paediatricians, but public health authorities need to be lobbied. Other issues which need to be addressed include relative importance of non-group A rotaviruses, possible administration with OPV, the influence of breast feeding, and most importantly, cost. It is essential that rotavirus vaccine is somehow made available to all of the world's children, not just those in developed countries. PMID:9553287

  11. A randomized, placebo-controlled trial of subcutaneous administration of GM-CSF as a vaccine adjuvant: effect on cellular and humoral immune responses.

    PubMed

    Somani, Jyoti; Lonial, Sagar; Rosenthal, Hilary; Resnick, Suzanne; Kakhniashvili, Irina; Waller, Edmund K

    2002-12-13

    Thirty healthy volunteers were randomly assigned to receive either a single subcutaneous injection of GM-CSF or placebo at the time of vaccination with tetanus and diptheria toxoid (Td), influenza and hepatitis A vaccines. Humoral response was measured by weekly serum samples assayed for antibodies to tetanus toxoid (TT), influenza and hepatitis A; while cellular response to TT was determined by measuring IL-2 expression in T-cells following in vitro exposure to TT antigen using a flow cytometric assay. It was hypothesized that (1). GM-CSF would augment immune response and (2). that the frequencies of TT responsive T-cells in the blood would predict humoral responses. The administration of subcutaneous GM-CSF as an adjuvant at the time of vaccination did not augment the antibody responses to influenza or hepatitis A in normal volunteers when compared to placebo. Subjects who received GM-CSF had statistically significant lower increases in anti-tetanus antibodies than placebo recipients. Immunization with TT resulted in an increase in the frequency of antigen responsive T-cells in the blood over time. The frequencies of TT responsive T-cells in baseline blood samples were correlated with baseline anti-tetanus antibody titers, but humoral and cellular responses were not correlated following vaccination. Recipients of GM-CSF did not develop significantly higher numbers of TT responsive T-cells after vaccination compared to recipients who received placebo. PMID:12450697

  12. Men with Low Vitamin A Stores Respond Adequately to Primary Yellow Fever and Secondary Tetanus Toxoid Vaccination

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Current recommendations for vitamin A intake and liver stores (20 mg/g) are based on maintaining normal vision. Higher levels may be required for maintaining normal immune function. To test this hypothesis, we conducted an 8 wk residential study among 36 healthy Bangladeshi men with low serum retino...

  13. Comparative assessment of immunization coverage of migrant children between national immunization program vaccines and non-national immunization program vaccines in East China.

    PubMed

    Hu, Yu; Luo, Shuying; Tang, Xuewen; Lou, Linqiao; Chen, Yaping; Guo, Jing

    2015-01-01

    This study aimed to describe the disparities in immunization coverage between National Immunization Program (NIP) vaccines and non-NIP vaccines in Yiwu and to identify potential determinants. A face-to-face interview-based questionnaire survey among 423 migrant children born from 1 June 2010 to 31 May 2013 was conducted. Immunization coverage was estimated according to the vaccines scheduled at different age, the birth cohorts, and socio- demographic characteristics. Single-level logistic regression analysis was applied to identify the determinants of coverage of non-NIP vaccines. We found that NIP vaccines recorded higher immunization coverage compared with non-NIP vaccines (87.9100%- vs 0%-74.8%). Among the non-NIP vaccines, varicella vaccine (VarV) recorded the highest coverage of 85.4%, which was introduced in 1998; while 7-valent pneumococcal conjugate vaccine(PCV7) recorded the lowest coverage of 0% for primary series, which was introduced recently. Lower coverage rate of non-NIP vaccines was significantly associated with more siblings in household, shorter duration of living in the surveyed areas, lower family income, mother with a job, mother with poor awareness of vaccination, and mother with lower education level. We found the immunization coverage rate of non-NIP vaccines was significant lower than that of NIP vaccines. Expansion of NIP to include non-NIP vaccines can provide better protection against the vaccine preventable diseases through increased immunization coverage. PMID:25760670

  14. M cell-targeted DNA vaccination

    NASA Astrophysics Data System (ADS)

    Wu, Yunpeng; Wang, Xinhai; Csencsits, Keri L.; Haddad, Asmahan; Walters, Nancy; Pascual, David W.

    2001-07-01

    DNA immunization, although attractive, is poor for inducing mucosal immunity, thus limiting its protective value against most infectious agents. To surmount this shortcoming, we devised a method for mucosal transgene vaccination by using an M cell ligand to direct the DNA vaccine to mucosal inductive tissues and the respiratory epithelium. This ligand, reovirus protein 1, when conjugated to polylysine (PL), can bind the apical surface of M cells from nasal-associated lymphoid tissues. Intranasal immunizations with protein 1-PL-DNA complexes produced antigen-specific serum IgG and prolonged mucosal IgA, as well as enhanced cell-mediated immunity, made evident by elevated pulmonary cytotoxic T lymphocyte responses. Therefore, targeted transgene vaccination represents an approach for enabling DNA vaccination of the mucosa.

  15. Anthrax Vaccine

    MedlinePLUS

    ... 1-800-822-7967. VAERS does not provide medical advice. ... Injury compensationA Federal program, the Countermeasures Injury Compensation ... who have a serious reaction to this vaccine.If you have a reaction ...

  16. Pertussis Vaccine

    Cancer.gov

    The National Institute of Child Health and Human Development (NICHD) is seeking statements of capability or interest from parties interested in collaborative research to further co-develop vaccines against pertussis.

  17. Typhoid Vaccine

    MedlinePLUS

    ... serious disease. It is caused by bacteria called Salmonella Typhi. Typhoid causes a high fever, fatigue, weakness, ... a typhoid carrier. Laboratory workers who work with Salmonella Typhi bacteria. Inactivated typhoid vaccine (shot)One dose ...

  18. Vaccination Records for Kids

    MedlinePLUS

    ... Vaccines Home For Parents: Vaccines for Your Children Vaccination Records for Kids On this Page Recording Immunizations ... for your college-age child. Many colleges provide vaccinations, especially those required for enrollment. Contact your college's ...

  19. Preteen and Teen Vaccines

    MedlinePLUS

    ... My Preteen or Teen Vaccinated? Which Vaccines Do Preteens and Teens Need, and When? All preteens (age ... Adult Vaccine Quiz . How Can I Get My Preteen or Teen Vaccinated? Preteens and teens typically see ...

  20. Live Virus Smallpox Vaccine

    MedlinePLUS

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

  1. 9 CFR 113.110 - Clostridium Botulinum Type C Bacterin-Toxoid.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    .... (2) The vaccinates and controls shall be observed for 7 days post-challenge and signs of botulism and deaths noted. For a valid test, the controls shall die of botulism. If the test is valid and 80 percent of the vaccinates do not remain free of botulism, the serial is unsatisfactory....

  2. 9 CFR 113.110 - Clostridium Botulinum Type C Bacterin-Toxoid.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    .... (2) The vaccinates and controls shall be observed for 7 days post-challenge and signs of botulism and deaths noted. For a valid test, the controls shall die of botulism. If the test is valid and 80 percent of the vaccinates do not remain free of botulism, the serial is unsatisfactory....

  3. 9 CFR 113.110 - Clostridium Botulinum Type C Bacterin-Toxoid.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    .... (2) The vaccinates and controls shall be observed for 7 days post-challenge and signs of botulism and deaths noted. For a valid test, the controls shall die of botulism. If the test is valid and 80 percent of the vaccinates do not remain free of botulism, the serial is unsatisfactory....

  4. 9 CFR 113.110 - Clostridium Botulinum Type C Bacterin-Toxoid.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    .... (2) The vaccinates and controls shall be observed for 7 days post-challenge and signs of botulism and deaths noted. For a valid test, the controls shall die of botulism. If the test is valid and 80 percent of the vaccinates do not remain free of botulism, the serial is unsatisfactory....

  5. 9 CFR 113.110 - Clostridium Botulinum Type C Bacterin-Toxoid.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    .... (2) The vaccinates and controls shall be observed for 7 days post-challenge and signs of botulism and deaths noted. For a valid test, the controls shall die of botulism. If the test is valid and 80 percent of the vaccinates do not remain free of botulism, the serial is unsatisfactory....

  6. [Vaccination schedule of the Spanish Association of Pediatrics: recommendations 2007].

    PubMed

    Bernaola Iturbe, E; Giménez Sánchez, F; Baca Cots, M; de Juan Martín, F; Díez Domingo, J; Garcés Sánchez, M; Gómez-Campderá, A; Martinón-Torres, F; Picazo, J J; Pineda Solás, V

    2007-01-01

    The Vaccine Advisory Committee of the Spanish Association of Pediatrics provides information on the new developments in vaccines that have taken place in 2006 and recommends certain modifications to the Immunization Schedule for 2007. To ensure early protection, the measles-mumps-rubella (MMR) vaccine booster dose should be administered when children start school (3-4 years). Based on existing scientific evidence, the importance of universal heptavalent conjugate pneumococcal vaccination, as occurs in most similar European countries and in the autonomous community of Madrid in Spain, is confirmed. The safety and efficacy of rotavirus and human papilloma virus vaccines, as well as their use in our environment, is discussed and the role of pediatricians in their implementation is stressed. The recommended immunization schedule for children and adolescents starting vaccination late is also discussed. PMID:17266854

  7. Vaccine development and deployment: opportunities and challenges in India.

    PubMed

    Gupta, Sanjukta Sen; Nair, G Balakrish; Arora, Narendra Kumar; Ganguly, Nirmal Kumar

    2013-04-18

    The Indian economy is among the fastest growing economies in the world. The country forayed into manufacturing vaccines starting with a few public-sector manufacturers in the late 1960s but has emerged as the major supplier of basic Expanded Programme on Immunization vaccines to the United Nations Children's Fund (UNICEF) because of substantial private-sector investment in the area. The Indian vaccine industry is now able to produce new and more complex vaccines such as the meningitis, Haemophilus influenzae type b, and pneumococcal conjugate vaccines, rotavirus vaccine and influenza A (H1N1) vaccines. This has been possible because of an attractive investment environment, effective and innovative governmental support, international partnerships and the growing in-country technical work force. A large number of vaccines, including those mentioned, is available and administered in the private sector within the country, but India has been slow in introducing new vaccines in its publically funded programs. Growth in the economy and technological accomplishments are not reflected in a reduction in health inequalities, and India continues to contribute significantly to global child mortality figures. This paper reviews the development of the Indian vaccine industry, policy support for it and its current status. It also highlights opportunities and challenges for the introduction of new and underutilized vaccines at home. PMID:23598492

  8. Enhancement of the Immunostimulatory Activity of a TLR7 Ligand by Conjugation to Polysaccharides.

    PubMed

    Shinchi, Hiroyuki; Crain, Brian; Yao, Shiyin; Chan, Michael; Zhang, Shannon S; Ahmadiiveli, Alast; Suda, Yasuo; Hayashi, Tomoko; Cottam, Howard B; Carson, Dennis A

    2015-08-19

    Toll-like receptors (TLRs) in the innate immune system recognize specific pathogen-associated molecular patterns derived from microbes. Synthetic small molecule TLR7 agonists have been extensively evaluated as topical agents for antiviral and anticancer therapy, and as adjuvants for vaccine. However, safe and reproducible administration of synthetic TLR7 ligands has been difficult to achieve due to undesirable pharmacokinetics and unacceptable side effects. Here, we conjugated a versatile low molecular weight TLR7 ligand to various polysaccharides in order to improve its water solubility, enhance its potency, and maintain low toxicity. The synthetic TLR7 ligand, 2-methoxyethoxy-8-oxo-9-(4-carboxy benzyl)adenine, designated 1V209, was stably conjugated to primary amine functionalized Ficoll or dextran using benzoic acid functional groups. The conjugation ratios using specified equivalents of TLR7 ligand were dose responsive and reproducible. The zeta potential value of the polysaccharides was decreased in inverse proportion to the ratio of conjugated TLR7 ligand. These conjugates were highly water-soluble, stable for at least 6 months at room temperature in aqueous solution, and easy to lyophilize and reconstitute without altering potency. In vitro studies with murine mononuclear leukocytes showed that the TLR7 agonist conjugated to polysaccharides had 10- to 1000-fold higher potencies than the unconjugated TLR7 ligand. In vivo pharmacodynamics studies after injection indicate that the conjugates induced systemic cytokine production. When the conjugates were used as vaccine adjuvants, they enhanced antigen specific humoral and cellular immune responses to a much greater extent than did unconjugated TLR7 ligands. These results indicated that small molecule TLR7 ligands conjugated to polysaccharides have improved immunostimulatory potency and pharmacodynamics. Polysaccharides can be conjugated to a variety of molecules such as antigens, peptides, and TLR ligands. Therefore, such conjugates could represent a versatile platform for the development of vaccines against cancer and infectious diseases. PMID:26193334

  9. In vivo efficacy and toxicity evaluation of polycaprolactone nanoparticles and aluminum based admixture formulation as vaccine delivery system.

    PubMed

    Bansal, Vivek; Kumar, Manoj; Bhardwaj, Arun; Brahmne, H G; Singh, Harpal

    2015-10-13

    Delivery of antigen through admixture formulation containing poly caprolactone (PCL) and aluminum phosphate was studied as a promising strategy to generate antigen specific immune response. The present study demonstrates the synergistic effect of admixture formulation of PCL with reduced aluminum (PCL-Al 0.2mg-TT and PCL-PEG-Al 0.2mg-TT) as a potential adjuvant system using tetanus toxoid (TT) as a model antigen. On evaluation of the magnitude of efficacy for the proposed formulation by ELISA as well as challenge method, persistent and strong antibody response was obtained throughout the 180 day study period on storage at 5±3°C. In comparison to the aluminum phosphate based conventional tetanus vaccine, higher levels of IFN-? and IL-4 were obtained with PCL-Al 0.2mg-TT and PCL-PEG-Al 0.2mg-TT, indicating the presence of cell mediated as well as humoral immune responses. Histopathology and serum biochemistry profile in mice further indicated the suitability of the proposed formulation. Percent adsorption/encapsulation of the antigen also increased to nearly 95% in the admixture formulation compared to 55% adsorption in the conventional tetanus vaccine. The present study established a useful baseline for designing biocompatible and effective delivery system for toxoid vaccines through judicious use of PCL based biodegradable nanoparticles in combination with aluminum phosphate. PMID:26343498

  10. A review of the current status of enteric vaccines.

    PubMed

    Levine, M M; Noriega, F

    1995-12-01

    Much progress has been made in developing vaccines against the most important enteric infections. Two new vaccines against typhoid fever (oral Ty21a and parenteral Vi polysaccharide) have been licensed in many countries. Newer, more sophisticated typhoid vaccines undergoing clinical testing include recombinant attenuated Salmonella typhi strains and Vi polysaccharide-carrier-protein conjugate vaccines. Two inactivated oral cholera vaccines, consisting of inactivated Vibrio cholerae O1 bacteria alone or in combination with B subunit of cholera toxin, each conferred 50-53% protection over three years in a field trial in Bangladesh where subjects were immunized with a three-dose regimen. An engineered live oral cholera vaccine, strain CVD 103-HgR, has been shown in extensive clinical trials to be well tolerated by children and adults in less developed countries and highly immunogenic following administration of just a single oral dose; a large-scale field trial of the efficacy of this vaccine is underway. In experimental challenge studies in volunteers, a single dose of CVD 103-HgR confers significant protection against challenge with wild-type V. cholerae O1 of either classical or El Tor biotype and either Inaba or Ogawa serotype. Several candidate vaccines against Shigella and enterotoxigenic Escherichia coli are in clinical trials. A multivalent rotavirus vaccine (rhesus reassortant vaccine) is undergoing extensive field testing in developed and less developed countries. PMID:9522876

  11. Vaccination Drives Changes in Metabolic and Virulence Profiles of Streptococcus pneumoniae

    PubMed Central

    Watkins, Eleanor R.; Penman, Bridget S.; Lourenço, José; Buckee, Caroline O.; Maiden, Martin C. J.; Gupta, Sunetra

    2015-01-01

    The bacterial pathogen, Streptococcus pneumoniae (the pneumococcus), is a leading cause of life-threatening illness and death worldwide. Available conjugate vaccines target only a small subset (up to 13) of >90 known capsular serotypes of S. pneumoniae and, since their introduction, increases in non-vaccine serotypes have been recorded in several countries: a phenomenon termed Vaccine Induced Serotype Replacement (VISR). Here, using a combination of mathematical modelling and whole genome analysis, we show that targeting particular serotypes through vaccination can also cause their metabolic and virulence-associated components to transfer through recombination to non-vaccine serotypes: a phenomenon we term Vaccine-Induced Metabolic Shift (VIMS). Our results provide a novel explanation for changes observed in the population structure of the pneumococcus following vaccination, and have important implications for strain-targeted vaccination in a range of infectious disease systems. PMID:26181911

  12. [Vaccination schedule of the Spanish association of pediatrics: recommendations 2009].

    PubMed

    Bernaola Iturbe, E; Giménez Sánchez, F; Baca Cots, M; De Juan Martín, F; Diez Domingo, J; Garcés Sánchez, M; Gómez-Campderá, A; Martinón-Torres, F; Picazo, J J; Pineda Solás, V

    2009-01-01

    Based on the available evidence, we, the Vaccine Advisory Committee (CAV) of the Spanish Association of Pediatrics (Asociación Española de Pediatría, AEP), provide information about and comments on vaccine-related innovation during 2008. Modifications to the Vaccine Schedule for 2009 are also discussed. The importance of the recommendation of administration of a varicella booster at start of school (3-4 years of age) is highlighted according to the technical specifications of one of the vaccines. The importance of making the heptavalent pneumococcal conjugate vaccine universally available is reiterated in accordance with the unquestionable results of scientific tests, WHO recommendations, the posture adopted by the majority of neighboring European countries, and the decision taken in 2006 by the autonomous community of Madrid (Spain). New scientific reasons are provided, corroborating the recommendation made by this committee in 2008, for the implementation by Spanish pediatricians of the vaccine against rotavirus and human papilloma virus. With regard to the latter, vaccination should be from 11 to 16 years of age, and then extended, in accordance with the technical specifications of the available vaccine preparations, to 26 years of age. As part of the recommendations, we insist that children in risk groups should be given flu vaccine and hepatitis A vaccine. The committee considers that these two vaccines must also be given, when pediatricians consider it appropriate, to children other than those in risk groups. This recommendation can be regarded as the first step towards a future recommendation of universal vaccination. Finally, this year we include an appendix with recommendations and vaccination strategies to be followed in children who have not previously received vaccines or who have not been completely immunized. PMID:19174124

  13. Replicating vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  14. AIDS Vaccines.

    ERIC Educational Resources Information Center

    Matthews, Thomas J.; Bolognesi, Dani P.

    1988-01-01

    Reveals that success of discovering vaccines is far from being assured although several candidates are being tested. States that the devious nature of the virus, the lack of a good animal model for the disease, and the difficulties of clinical trials inhibit the efforts of researchers. (RT)

  15. Vexing Vaccines

    ERIC Educational Resources Information Center

    Bowman, Darcia Harris

    2004-01-01

    Schools play a key role in ensuring that children are being immunized against diseases, but conflicting research is making enforcement difficult. This article discusses a growing trend of vaccine avoidance and the endless supply of conflicting information and research about immunization safety. Despite the controversy, many people appear to accept…

  16. Valuing vaccination

    PubMed Central

    Bärnighausen, Till; Bloom, David E.; Cafiero-Fonseca, Elizabeth T.; O’Brien, Jennifer Carroll

    2014-01-01

    Vaccination has led to remarkable health gains over the last century. However, large coverage gaps remain, which will require significant financial resources and political will to address. In recent years, a compelling line of inquiry has established the economic benefits of health, at both the individual and aggregate levels. Most existing economic evaluations of particular health interventions fail to account for this new research, leading to potentially sizable undervaluation of those interventions. In line with this new research, we set forth a framework for conceptualizing the full benefits of vaccination, including avoided medical care costs, outcome-related productivity gains, behavior-related productivity gains, community health externalities, community economic externalities, and the value of risk reduction and pure health gains. We also review literature highlighting the magnitude of these sources of benefit for different vaccinations. Finally, we outline the steps that need to be taken to implement a broad-approach economic evaluation and discuss the implications of this work for research, policy, and resource allocation for vaccine development and delivery. PMID:25136129

  17. Polio Vaccine

    MedlinePLUS

    ... of polio vaccination in the U.S. and other countries has sparked a world-wide effort to eliminate polio.Today: Polio has ... person infected with polio virus coming from another country to bring the disease ... the disease from the world is successful, some day we won't need ...

  18. Fish Vaccines in Aquaculture

    Technology Transfer Automated Retrieval System (TEKTRAN)

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

  19. VACCINE INFORMATION STATEMENT MMR Vaccine(Measles, Mumps,

    E-print Network

    Leistikow, Bruce N.

    VACCINE INFORMATION STATEMENT MMR Vaccine(Measles, Mumps, & Rubella) What You Need to Know Many Vaccine Information get vaccinated? Measles, mumps, and rubella are serious diseases. Before vaccines they were very

  20. Conjugate Gaze Palsies

    MedlinePLUS

    ... Consumer Version Brain, Spinal Cord, and Nerve Disorders Cranial Nerve Disorders Conjugate Gaze Palsies Horizontal gaze palsy Vertical ... to Consumer Version DOCTORS: Go to Professional Version Cranial Nerve Disorders Overview of the Cranial Nerves Internuclear Ophthalmoplegia ...

  1. Clinical manifestations of invasive pneumococcal disease by vaccine and non-vaccine types.

    PubMed

    Browall, Sarah; Backhaus, Erik; Naucler, Pontus; Galanis, Ilias; Sjöström, Karin; Karlsson, Diana; Berg, Stefan; Luthander, Joachim; Eriksson, Margareta; Spindler, Carl; Ejdebäck, Mikael; Trollfors, Birger; Darenberg, Jessica; Kalin, Mats; Örtqvist, Ake; Andersson, Rune; Henriques-Normark, Birgitta

    2014-12-01

    Pneumococcal conjugated vaccines (PCVs) have shown protection against invasive pneumococcal disease by vaccine serotypes, but an increase in non-vaccine serotype disease has been observed. Type-specific effects on clinical manifestation need to be explored. Clinical data from 2096 adults and 192 children with invasive pneumococcal disease were correlated to pneumococcal molecular serotypes. Invasive disease potential for pneumococcal serotypes were calculated using 165 invasive and 550 carriage isolates from children. The invasive disease potential was lower for non-PCV13 compared to vaccine-type strains. Patients infected with non-PCV13 strains had more underlying diseases, were less likely to have pneumonia and, in adults, tended to have a higher mortality. Furthermore, patients infected with pneumococci belonging to clonal serotypes only expressing non-PCV13 capsules had a higher risk for septicaemia and mortality. PCV vaccination will probably lead to a decrease in invasive pneumococcal disease but an alteration in the clinical manifestation of invasive pneumococcal disease. Genetic lineages causing invasive pneumococcal disease in adults often express non-vaccine serotypes, which can expand after vaccination with an increased risk of infection in patients with underlying diseases. PMID:25323223

  2. Immune Responses to HBsAg Conjugated to Protein D of Non-Typeable Haemophilus influenzae in Mice

    PubMed Central

    Su, Qiudong; Yi, Yao; Qiu, Feng; Lu, Xuexin; Ding, Junying; Jia, Zhiyuan; Tian, Ruiguang; Gao, Yan; Bi, Shengli

    2015-01-01

    Background Hepatitis B vaccine that contains an aluminum hydroxide adjuvant induces apoptotic death of Hepa 1–6 cells. Difficult-to-degrade chemical additives in vaccines effectively enhance vaccine immunogenicity, but also affect the host tissue. Identification of bio-molecules that are readily degraded and compatible in vivo as an adjuvant is important for vaccine research. The hapten–carrier effect suggests that stimulation of helper T (Th) cells by carrier adjuvants is feasible. Protein D (PD) of non-typeable Haemophilus influenzae covalently conjugated to some polysaccharide vaccines has been confirmed to convert T-cell independent (TI) antigens into T-cell dependent (TD) antigens, and elicit strong T-cell responses ultimately. Herein, we would substitube PD for aluminum hydroxide adjuvant in Hepatitis B vaccine. Methods and results Truncated PD (amino acids 20–364) was expressed in Escherichia coli and purified by (NH4)2SO4 precipitation and DEAE chromatography. After evaluation of antigenicity by western blotting, PD was covalently conjugated to yeast-derived recombinant HBsAg by cross-linking with glutaraldehyde. Intramuscular immunization with the conjugate induced higher level of HBsAg-specific antibody than did HBsAg alone (p < 0.05), and was comparable to commercial Hepatitis B vaccine. During the surveillance period (days 35–105), anti-HBs titers were hold high. Moreover, the conjugated vaccine enhanced Th1 immune responses, while Th2 responses were also activated and induced an antibody response, as determined by IFN-? ELISPOT and IgG1/IgG2a ratio assays. Conclusions Recombinant truncated PD covalently conjugated to HBsAg antigen enhanced the immunogenicity of the antigen in mice simultaneously by humoral and cellular immune response, which would facilitate therapeutic hepatitis B vaccines. PMID:25689855

  3. Immune interference after sequential alphavirus vaccine vaccinations.

    PubMed

    Pittman, Phillip R; Liu, Ching-Tong; Cannon, Timothy L; Mangiafico, Joseph A; Gibbs, Paul H

    2009-08-01

    We compared the effect of order of administration of investigational alphavirus vaccines on neutralizing antibody response. Volunteers who received the inactivated eastern and western equine encephalitis (EEE and WEE) vaccines before live attenuated Venezuelan (VEE) vaccine had significantly lower rates of antibody response than those receiving VEE vaccine before EEE and WEE vaccines (66.7% vs. 80.6%; p=0.026). The odds of having a VEE antibody non-response among those initially receiving EEE and WEE vaccines, adjusted for gender, were significant (odds ratio [OR]=2.20; 95% CI=1.2-4.1 [p=0.0145]) as were the odds of non-response among females adjusted for group (OR=1.81; 95% CI=1.2-2.7 [p=0.0037]). Antibody interference and gender effect have major implications for vaccine strategy among those receiving multiple alphavirus vaccines and those developing next generation vaccines for these threats. PMID:19576665

  4. Immunotherapy for Cancer: Synthetic Carbohydrate-based Vaccines

    PubMed Central

    Buskas, Therese; Thompson, Pamela

    2009-01-01

    Aberrant glycosylation of glycoproteins and glycolipids of cancer cells, which correlates with poor survival rates, is being exploited for the development of immunotherapies for cancer. In particular, advances in the knowledge of cooperation between the innate and adaptive system combined with the implementation of efficient synthetic methods for assembly of oligosaccharides and glycopeptides is providing avenues for the rationale design of vaccine candidates. In this respect, fully synthetic vaccine candidates show great promise because they incorporate only those elements requires for relevant immune responses, and hence do not suffer from immune suppression observed with classical carbohydrate-protein conjugate vaccines. Such vaccines are chemically well-defined and it is to be expected that they can be produced in a reproducible fashion. In this review article, recent advances in the development of fully synthetic sub-unit carbohydrate-based cancer vaccines will be discussed. PMID:19724783

  5. Activity of glycated chitosan and other adjuvants to PDT vaccines

    NASA Astrophysics Data System (ADS)

    Korbelik, Mladen; Banáth, Judit; ?iplys, Evaldas; Szulc, Zdzislaw; Bielawska, Alicja; Chen, Wei R.

    2015-03-01

    Glycated chitosan (GC), a water soluble galactose-conjugated natural polysaccharide, has proven to be an effective immunoadjuvant for treatment of tumors based on laser thermal therapy. It was also shown to act as adjuvant for tumor therapy with high-intensity ultrasound and in situ photodynamic therapy (PDT). In the present study, GC was examined as potential adjuvant to PDT-generated cancer vaccine. Two other agents, pure calreticulin protein and acid ceramidase inhibitor LCL521, were also tested as prospective adjuvants for use in conjunction with PDT vaccines. Single treatment with GC, included with PDT vaccine cells suspension, improved the therapeutic efficacy when compared to vaccine alone. This attractive prospect of GC application remains to be carefully optimized and mechanistically elucidated. Both calreticulin and LCL521 proved also effective adjuvants when combined with PDT vaccine tumor treatment.

  6. Who Needs Chickenpox Vaccine

    MedlinePLUS

    ... Vaccines and Immunizations Share Compartir Who Needs Chickenpox Vaccine For Public Children under age 13 years should ... who have never had chickenpox or received chickenpox vaccine should get two doses, at least 28 days ...

  7. Your Baby's First Vaccines

    MedlinePLUS

    ... Barcodes Related Link Vaccines & Immunizations Your Child's First Vaccines Format: Select one PDF [338 KB] RTF [260 ... child will get one or more of these vaccines today: DTaP Hib Hepatitis B Polio PCV13 Why ...

  8. Vaccines Stop Illness

    MedlinePLUS

    Skip Navigation Bar Home Current Issue Past Issues Vaccines Stop Illness Past Issues / Spring 2008 Table of ... meningitis won't infect, cripple, or kill children. Vaccine Safety In light of recent questions about vaccine ...

  9. Vaccinations and HIV

    MedlinePLUS

    ... Do not measure your viral load within 4 weeks of any vaccination. Flu shots have been studied ... live” vaccination in the past 2 or 3 weeks. Still, the “MMR” vaccine against measles, mumps and ...

  10. Vaccines and Pregnancy

    MedlinePLUS

    Vaccines and Pregnancy In every pregnancy, a woman starts out with a 3-5% chance of having ... advice from your health care provider. What are vaccines? Vaccines are given to help protect you from ...

  11. Novel Vaccine Adjuvants

    E-print Network

    Agrawal, Anshu; Owais, Mohammad; Singh, Udai P

    2013-01-01

    vaccines that nonspecifically stim- ulate the immune system,immune system cells, to enhance the immunogenicity of vaccines.vaccine may require a combination of adjuvants which can activate different parts of the immune system.

  12. Diphtheria Vaccination: Who Needs It?

    MedlinePLUS

    ... CDC.gov . Vaccines and Immunizations Share Compartir Diphtheria Vaccination: Who Needs It? On this Page Vaccine Who ... Vaccine Information Statement (VIS) See also: Healthcare Personnel Vaccination Recommendations [1 page] July 2008 Top of Page ...

  13. [Invasive pneumococcal disease in two non-vaccinated pediatric cases: pleural empyema and bacteremia].

    PubMed

    Kan?k Yüksek, Saliha; Gülhan, Belgin; Tezer, Hasan; Özkaya Parlakay, Asl?nur; Uzun Kenan, Bahriye; Sayed Oskovi, Hülya; Nar Ötgün, Selin

    2015-07-01

    Streptococcus pneumoniae, a gram-positive diplococcus, is the causative agent of invasive pneumococcal diseases (IPDs) characterized by severe infections such as bacteraemia, sepsis and meningitis. S.pneumoniae and IPDs are situated in the focus of the vaccine studies because of being encompassed of a significant burden of disease in the world, severe mortality and morbidities, and location in vaccine-preventable diseases group. Although S.pneumoniae has more than 90 defined serotypes, certain serotypes are often identified as the cause of IPDs. Individuals with comorbid and chronic diseases, primary or secondary immune deficiencies, and < 2 years or > 65 years of age are at increased risk for IPDs. Currently, a 23-valent polysaccharide vaccine and also 7, 10 and 13 valent pneumococcal conjugated vaccines (PCV) have been produced for pneumococci. Phase studies of protein based vaccines, which will provide protection independent of serotypes, and 15-valent pneumococcal conjugated vaccine are still ongoing. In Turkey, in November 2008 PCV7 and in April 2011 PCV13 have been implemented in the national immunization program. First case of the pneumococcal unvaccinated cases presented in this report was a 6-year-old girl patient with pneumonia and pleural empyema due to S.pneumoniae serotype 1, without any underlying risk factors. The other case is a 52-days-old male patient, who had a history of pneumococcal septicemia in the newborn period and was followed for bacteremia associated S.pneumoniae serotype 12B and diagnosed as complement deficiency on follow-up. S.pneumoniae serotype 1 is within serotypes covered by 10 and 13 valent pneumococcal conjugate vaccines and pneumococcal polysaccharide vaccine that are in use today, and is a highly invasive strain often isolated in pneumococcal lobar pneumonia and empyema. S.pneumoniae serotype 12B is a non-vaccine serotype not included in any of conjugate and polysaccharide vaccines, and usually obtained in respiratory infections and nasopharyngeal carriage studies. The first case of this report was presented because of an IPD with a serotype included in PCV13 implemented in the routine childhood vaccination schedule and to give an idea about pneumococcal strains circulating in the community. The second case was discussed to draw attention for the evaluation of immune deficiencies and other risk factors in recurrent infections with encapsulated bacteria such as pneumococci. Pneumococcal conjugate vaccines contribute the public immunity with the reduction of vaccine-type pneumococcal nasopharyngeal carriage, IPD incidence, and IPD associated morbidity and mortality especially in young children, at the same time cause a decrease in the prevalence of antibiotic-resistant infections. Application of the pneumococcal conjugate vaccines covering the whole society is important, according to all these important results. PMID:26313286

  14. Efficacy of a non-updated, Matrix-C-based equine influenza subunit-tetanus vaccine following Florida sublineage clade 2 challenge.

    PubMed

    Pouwels, H G W; Van de Zande, S M A; Horspool, L J I; Hoeijmakers, M J H

    2014-06-21

    Assessing the ability of current equine influenza vaccines to provide cross-protection against emerging strains is important. Horses not vaccinated previously and seronegative for equine influenza based on haemagglutination inhibition (HI) assay were assigned at random to vaccinated (n=7) or non-vaccinated (control, n=5) groups. Vaccination was performed twice four weeks apart with a 1?ml influenza subunit (A/eq/Prague/1/56, A/eq/Newmarket/1/93, A/eq/Newmarket/2/93), tetanus toxoid vaccine with Matrix-C adjuvant (EquilisPrequenza Te). All the horses were challenged individually by aerosol with A/eq/Richmond/1/07 three weeks after the second vaccination. Rectal temperature, clinical signs, serology and virus excretion were monitored for 14?days after challenge. There was no pain at the injection site or increases in rectal temperature following vaccination. Increases in rectal temperature and characteristic clinical signs were recorded in the control horses. Clinical signs were minimal in vaccinated horses. Clinical (P=0.0345) and total clinical scores (P=0.0180) were significantly lower in the vaccinated than in the control horses. Vaccination had a significant effect on indicators of viraemia - the extent (P=0.0006) and duration (P=<0.0001) of virus excretion and the total amount of virus excreted (AUC, P=0.0006). Vaccination also had a significant effect (P=0.0017) on whether a horse was positive or negative for virus excretion during the study. Further research is needed to fully understand the specific properties of this vaccine that may contribute to its cross-protective capacity. PMID:24795071

  15. Engineered human vaccines

    SciTech Connect

    Sandhu, J.S. . Div. of Immunology and Neurobiology)

    1994-01-01

    The limitations of human vaccines in use at present and the design requirements for a new generation of human vaccines are discussed. The progress in engineering of human vaccines for bacteria, viruses, parasites, and cancer is reviewed, and the data from human studies with the engineered vaccines are discussed, especially for cancer and AIDS vaccines. The final section of the review deals with the possible future developments in the field of engineered human vaccines and the requirement for effective new human adjuvants.

  16. [Poliovirus vaccine].

    PubMed

    Shimizu, Hiroyuki

    2012-06-01

    To avoid the risk of vaccine-associated paralytic poliomyelitis (VAPP) and polio outbreaks due to circulating vaccine-derived polioviruses, an inactivated poliovirus vaccine (IPV) was introduced for routine immunization in a number of countries with a low risk of polio outbreaks. Currently, production and marketing of a standalone conventional IPV and two diphtheria-pertussis-tetanus-IPV (Sabin-derived IPV; sIPV) products have been submitted, and it is expected that the IPV products will be introduced in Japan in the autumn of 2012. At the same time, a decline in the OPV immunization rate became apparent in Japan due to serious public concerns about a remaining risk of VAPP and introduction of IPV in the near future. Therefore, the recent development of polio immunity gaps should be carefully monitored, and surveillance of suspected polio cases and laboratory diagnosis of polioviruses have to be intensified for the transition period from OPV to IPV in Japan. The development of sIPV is one of the most realistic options to introduce affordable IPV to developing countries. In this regard, further clinical studies on its efficacy, safety, and interchangeability of sIPV will be needed after the introduction of the sIPV products, which will be licensed in Japan for the first time in the world. PMID:23189825

  17. An evaluation of emerging vaccines for childhood pneumococcal pneumonia

    PubMed Central

    2011-01-01

    Background Pneumonia is the leading cause of child mortality worldwide. Streptococcus pneumoniae (SP) or pneumococcus is estimated to cause 821,000 child deaths each year. It has over 90 serotypes, of which 7 to 13 serotypes are included in current formulations of pneumococcal conjugate vaccines that are efficacious in young children. To further reduce the burden from SP pneumonia, a vaccine is required that could protect children from a greater diversity of serotypes. Two different types of vaccines against pneumococcal pneumonia are currently at varying stages of development: a multivalent pneumococcal conjugate vaccine covering additional SP serotypes; and a conserved common pneumococcal protein antigen (PPA) vaccine offering protection for all serotypes. Methods We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In Stage I, we systematically reviewed the literature related to emerging SP vaccines relevant to several criteria of interest: answerability; efficacy and effectiveness; cost of development, production and implementation; deliverability, affordability and sustainability; maximum potential for disease burden reduction; acceptability to the end users and health workers; and effect on equity. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). The policy makers and industry representatives accepted our invitation on the condition of anonymity, due to sensitive nature of their involvement in such exercises. They answered questions from CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%. Results The experts expressed very high level of optimism (over 80%) that low-cost polysaccharide conjugate SP vaccines would satisfy each of the 9 relevant CHNRI criteria. The median potential effectiveness of conjugate SP vaccines in reduction of overall childhood pneumonia mortality was predicted to be about 25% (interquartile range 20-38%, min. 15%, max 45%). For low cost, cross-protective common protein vaccines for SP the experts expressed concerns over answerability (72%) and the level of development costs (50%), while the scores for all other criteria were over 80%. The median potential effectiveness of common protein vaccines in reduction of overall childhood pneumonia mortality was predicted to be about 30% (interquartile range 26-40%, min. 20%, max 45%). Conclusions Improved SP vaccines are a very promising investment that could substantially contribute to reduction of child mortality world-wide. PMID:21501444

  18. Vaccines for Farrowing Operations 

    E-print Network

    Lawhorn, D. Bruce

    1999-02-15

    Routine vaccination is necessary to control economically important swine diseases such as erysipelas, leptospirosis, parvovirus and colibacillosis. The symptoms and specific vaccines for these diseases are discussed....

  19. Recent developments for Staphylococcus aureus vaccines: clinical and basic science challenges.

    PubMed

    Proctor, R A

    2015-01-01

    Bacterial vaccines have made dramatic impacts upon morbidity and mortality caused by a number of common pathogens, but a vaccine to prevent Staphylococcus aureus infections has proven to be illusive. With successful bacterial vaccines, the organisms are all part of the transient flora, whereas, S. aureus is part of the normal human flora. This means that S. aureus has had a prolonged time to adapt to the host milieu and its defences. The failure of several staphylococcal antigens to protect humans from infection in vaccine clinical trials using active or passive immunisation has stimulated a re-examination of the fundamental assumptions about staphylococcal immunity in humans vs. animals, especially rodents. This has spurred an active debate about the appropriate models for vaccine development and an examination of our current understanding of the protective immunity in humans. A major factor in the development of previous bacterial vaccines was a biomarker that predicted human protection, e.g., antibodies to tetanus toxoid or to pneumococcal polysaccharide. While antibodies against a number of staphylococcal antigens have proven to be an excellent biomarker for protection in rodents, these have not been translated to human infections. Thus, while much work remains, there is a growing consensus that T-cell immunity plays an important role in protecting humans. Moreover, the presence of anti-staphylococcal toxin antibodies correlates with reduced disease severity in humans. The most important recent advances concerning potential biomarkers, and the role of pre-existing immune status of vaccines in vaccine-associated mortality are considered in this review. PMID:26629971

  20. Vaccination coverage of patients with inborn errors of metabolism and the attitudes of their parents towards vaccines.

    PubMed

    Cerutti, Marta; De Lonlay, Pascale; Menni, Francesca; Parini, Rossella; Principi, Nicola; Esposito, Susanna

    2015-11-27

    To evaluate vaccination coverage of children and adolescents with inborn errors of metabolism (IEMs) and the attitudes of their parents towards vaccination, the vaccination status of 128 patients with IEM and 128 age- and gender-matched healthy controls was established by consulting the official vaccination chart. In children with IEMs, compared with healthy controls, low vaccination rates and/or delays in administration were observed for pneumococcal conjugate, meningococcus C, measles, mumps, rubella, diphtheria-tetanus-pertussis-inactivated polio, Bacillus Calmette-Guerin, and influenza vaccines. Among the parents of IEM patients, vaccine schedule compliance was primarily driven by the doctors at the hospital's reference centres; among the parents of the healthy controls, compliance was driven by the primary care paediatricians. These results show that IEM patients demonstrate sub-optimal vaccination coverage. Further studies of the different vaccines in each IEM disorder and educational programmes aimed at physicians and parents to increase immunization coverage in these patients are urgently needed. PMID:26514424

  1. 9 CFR 113.110 - Clostridium Botulinum Type C Bacterin-Toxoid.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...7 days post-challenge and signs of botulism and deaths noted. For a valid test, the controls shall die of botulism. If the test is valid and 80 percent of the vaccinates do not remain free of botulism, the serial is unsatisfactory....

  2. Molecular signatures of antibody responses derived from a systems biological study of 5 human vaccines

    PubMed Central

    Li, Shuzhao; Rouphael, Nadine; Duraisingham, Sai; Romero-Steiner, Sandra; Presnell, Scott; Davis, Carl; Schmidt, Daniel S; Johnson, Scott E; Milton, Andrea; Rajam, Gowrisankar; Kasturi, Sudhir; Carlone, George M; Quinn, Charlie; Chaussabel, Damien; Palucka, A Karolina; Mulligan, Mark J; Ahmed, Rafi; Stephens, David S; Nakaya, Helder I; Pulendran, Bali

    2013-01-01

    Many vaccines induce protective immunity via antibodies. Recent studies have used systems biological approaches to determine signatures that predict vaccine immunity in humans, but whether there is a ‘universal signature’ that can predict antibody responses to any vaccine, is unknown. Here we performed systems analyses of immune responses to the meningococcal polysaccharide and conjugate vaccines in healthy adults, in the broader context of our previous studies with the yellow fever and two influenza vaccines. To achieve this, we performed a large-scale network integration of public human blood transcriptomes, and systems-scale databases in specific biological contexts, and deduced a set of blood transcription modules. These modules revealed distinct transcriptional signatures of antibody responses to different classes of vaccines providing key insights into primary viral, protein recall and anti-polysaccharide responses. These results illuminate the early transcriptional programs orchestrating vaccine immunity in humans, and demonstrate the power of integrative network modeling. PMID:24336226

  3. Avian influenza vaccines and vaccination for poultry

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Vaccines against avian influenza (AI) have had more limited use in poultry than vaccines against other poultry diseases such as Newcastle disease (ND) and infectious bronchitis, and have been used more commonly in the developing world. Over the past 40 years, AI vaccines have been primarily based o...

  4. History of vaccination

    PubMed Central

    Plotkin, Stanley

    2014-01-01

    Vaccines have a history that started late in the 18th century. From the late 19th century, vaccines could be developed in the laboratory. However, in the 20th century, it became possible to develop vaccines based on immunologic markers. In the 21st century, molecular biology permits vaccine development that was not possible before. PMID:25136134

  5. Understanding How Vaccines Work

    E-print Network

    Noble, William Stafford

    Understanding How Vaccines Work Last reviewed February 2013 Diseases that vaccines prevent can be dangerous, or even deadly. Vaccines greatly reduce the risk of infection by working with the body's natural and how vaccines work to protect people by producing immunity. The Immune System-- The Body's Defense

  6. A century of pneumococcal vaccination research in humans.

    PubMed

    Grabenstein, J D; Klugman, K P

    2012-10-01

    Sir Almroth Wright coordinated the first trial of a whole-cell pneumococcal vaccine in South Africa from 1911 to 1912. Wright started a chain of events that delivered pneumococcal vaccines of increasing clinical and public-health value, as medicine advanced from a vague understanding of the germ theory of disease to today's rational vaccine design. Early whole-cell pneumococcal vaccines mimicked early typhoid vaccines, as early pneumococcal antisera mimicked the first diphtheria antitoxins. Pneumococcal typing systems developed by Franz Neufeld and others led to serotype-specific whole-cell vaccines. Pivotally, Alphonse Dochez and Oswald Avery isolated pneumococcal capsular polysaccharides in 1916-17. Serial refinements permitted Colin MacLeod and Michael Heidelberger to conduct a 1944-45 clinical trial of quadrivalent pneumococcal polysaccharide vaccine (PPV), demonstrating a high degree of efficacy in soldiers against pneumococcal pneumonia. Two hexavalent PPVs were licensed in 1947, but were little used as clinicians preferred therapy with new antibiotics, rather than pneumococcal disease prevention. Robert Austrian's recognition of high pneumococcal case-fatality rates, even with antibiotic therapy, led to additional trials in South Africa, the USA and Papua New Guinea, with 14-valent and 23-valent PPVs licensed in 1977 and 1983 for adults and older children. Conjugation of polysaccharides to proteins led to several pneumococcal conjugate vaccines licensed since 2000, enabling immunization of infants and young children and resultant herd protection for all ages. Today, emergence of disease caused by pneumococcal serotypes not included in various vaccine formulations fuels research into conserved proteins or other means to maximize protection against more than 90 known pneumococcal serotypes. PMID:22882735

  7. Stabilized polyacrylic saccharide protein conjugates

    DOEpatents

    Callstrom, Matthew R. (Columbus, OH); Bednarski, Mark D. (Berkeley, CA); Gruber, Patrick R. (St. Paul, MN)

    1996-01-01

    This invention is directed to water soluble protein polymer conjugates which are stabile in hostile environments. The conjugate comprises a protein which is linked to an acrylic polymer at multiple points through saccharide linker groups.

  8. Stabilized polyacrylic saccharide protein conjugates

    DOEpatents

    Callstrom, M.R.; Bednarski, M.D.; Gruber, P.R.

    1996-02-20

    This invention is directed to water soluble protein polymer conjugates which are stable in hostile environments. The conjugate comprises a protein which is linked to an acrylic polymer at multiple points through saccharide linker groups. 16 figs.

  9. Different Immune Response of Mice Immunized with Conjugates Containing Multiple Copies of Either Consensus or Mixotope

    E-print Network

    Pompeu Fabra, Universitat

    rates and resulting polymorphism, its different mechanisms of evading the immune system, and the absenceDifferent Immune Response of Mice Immunized with Conjugates Containing Multiple Copies of Either (HIV-1) neutralization has caused this peptide to be used in many HIV-1 vaccine candidates. To enhance

  10. Roadmap for the international collaborative epidemiologic monitoring of safety and effectiveness of new high priority vaccines.

    PubMed

    Izurieta, Hector S; Zuber, Patrick; Bonhoeffer, Jan; Chen, Robert T; Sankohg, Osman; Laserson, Kayla F; Sturkenboom, Miriam; Loucq, Christian; Weibel, Daniel; Dodd, Caitlin; Black, Steve

    2013-08-01

    With the advent of new vaccines targeted to highly endemic diseases in low- and middle-income countries (LMIC) and with the expansion of vaccine manufacturing globally, there is an urgent need to establish an infrastructure to evaluate the benefit-risk profiles of vaccines in LMIC. Fortunately the usual decade(s)-long time gap between introduction of new vaccines in high and low income countries is being significantly reduced or eliminated due to initiatives such as the Global Alliance for Vaccines and Immunizations (GAVI) and the Decade of Vaccines for the implementation of the Global Vaccine Action Plan. While hoping for more rapid disease control, this time shift may potentially add risk, unless appropriate capacity for reliable and timely evaluation of vaccine benefit-risk profiles in some LMIC's are developed with external assistance from regional or global level. An ideal vaccine safety and effectiveness monitoring system should be flexible and sustainable, able to quickly detect possible vaccine-associated events, distinguish them from programmatic errors, reliably and quickly evaluate the suspected event and its association with vaccination and, if associated, determine the benefit-risk of vaccines to inform appropriate action. Based upon the demonstrated feasibility of active surveillance in LMIC as shown by the Burkina Faso assessment of meningococcal A conjugate vaccine or that of rotavirus vaccine in Mexico and Brazil, and upon the proof of concept international GBS study, we suggest a sustainable, flexible, affordable and timely international collaborative vaccine safety monitoring approach for vaccines being newly introduced. While this paper discusses only the vaccine component, the same system could also be eventually used for monitoring drug effectiveness (including the use of substandard drugs) and drug safety. PMID:23707171

  11. The ABC of pneumococcal infections and vaccination in patients with chronic kidney disease

    PubMed Central

    Vandecasteele, Stefaan J.; Ombelet, Sara; Blumental, Sophie; Peetermans, Willy E.

    2015-01-01

    Background In the general population, pneumococcal polysaccharide vaccines (PPV) decrease the incidence of invasive pneumococcal disease (IPD) whereas the impact on the prevention of noninvasive pneumococcal disease is less clear. As compared with PPV, pneumococcal conjugate vaccines (PCV) provoke a higher, longer-lasting immune response resulting in a 45% decreased incidence in vaccine-type pneumonia, and a 75% decrease in vaccine-type IPD. Methods Literature review on pneumococcal vaccination in end-stage renal disease. Results As compared with the general population, patients with chronic kidney disease (CKD) suffer increased mortality and morbidity from pneumococcal disease (PD), being up to 10-fold for those treated with dialysis. Numerous, usually small and methodological heterogeneous studies demonstrate that PPV provokes a serological response in dialysis patients, kidney transplant recipients, children with nephrotic syndrome and CKD patients receiving immunosuppressive medication. This response is of less intensity and duration than in healthy controls. Similar observations were made for the PCV. The protective value of these vaccine-elicited anti-pneumococcal antibodies in the CKD population remains to be substantiated. For patients treated with dialysis, epidemiological data demonstrate a correlation—which does not equal causality—between pneumococcal vaccination status and a slightly decreased total mortality. Clinical outcome data on the effectiveness of pneumococcal vaccination in the prevention of morbidity and mortality in the CKD population are lacking. Conclusions Awaiting better evidence, pneumococcal vaccination should be advocated in all patients with CKD, as early in their disease course as possible. The ACIP schedule recommends a PCV-13 prime vaccination followed by a PPV-23 repeated vaccine at least 8 weeks later in pneumococcal non-vaccinated patients, and a PCV-13 vaccine at least 1 year after the latest PPV vaccine in previously vaccinated patients. In the UK, vaccination with PPV-23 only is recommended. There exist no good data supporting re-vaccination after 5 years in the dialysis population. PMID:26034594

  12. Vaccines today, vaccines tomorrow: a perspective

    PubMed Central

    2013-01-01

    Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts. PMID:23596584

  13. Vaccines today, vaccines tomorrow: a perspective.

    PubMed

    Loucq, Christian

    2013-01-01

    Vaccines are considered as one of the major contributions of the 20th century and one of the most cost effective public health interventions. The International Vaccine Institute has as a mission to discover, develop and deliver new and improved vaccines against infectious diseases that affects developing nations. If Louis Pasteur is known across the globe, vaccinologists like Maurice Hilleman, Jonas Salk and Charles Mérieux are known among experts only despite their contribution to global health. Thanks to a vaccine, smallpox has been eradicated, polio has nearly disappeared, Haemophilus influenzae B, measles and more recently meningitis A are controlled in many countries. While a malaria vaccine is undergoing phase 3, International Vaccine Institute, in collaboration with an Indian manufacturer has brought an oral inactivated cholera vaccine to pre-qualification. The field of vaccinology has undergone major changes thanks to philanthropists such as Bill and Melinda Gates, initiatives like the Decade of Vaccines and public private partnerships. Current researches on vaccines have more challenging targets like the dengue viruses, malaria, human immunodeficiency virus, the respiratory syncytial virus and nosocomial diseases. Exciting research is taking place on new adjuvants, nanoparticles, virus like particles and new route of administration. An overcrowded infant immunization program, anti-vaccine groups, immunizing a growing number of elderlies and delivering vaccines to difficult places are among challenges faced by vaccinologists and global health experts. PMID:23596584

  14. Impact of Introducing the Pneumococcal and Rotavirus Vaccines Into the Routine Immunization Program in Niger

    PubMed Central

    Assi, Tina-Marie; Rajgopal, Jayant; Norman, Bryan A.; Chen, Sheng-I; Brown, Shawn T.; Slayton, Rachel B.; Kone, Souleymane; Kenea, Hailu; Welling, Joel S.; Connor, Diana L.; Wateska, Angela R.; Jana, Anirban; Wiringa, Ann E.; Van Panhuis, Willem G.; Burke, Donald S.

    2012-01-01

    Objectives. We investigated whether introducing the rotavirus and pneumococcal vaccines, which are greatly needed in West Africa, would overwhelm existing supply chains (i.e., the series of steps required to get a vaccine from the manufacturers to the target population) in Niger. Methods. As part of the Bill and Melinda Gates Foundation–funded Vaccine Modeling Initiative, we developed a computational model to determine the impact of introducing these new vaccines to Niger's Expanded Program on Immunization vaccine supply chain. Results. Introducing either the rotavirus vaccine or the 7-valent pneumococcal conjugate vaccine could overwhelm available storage and transport refrigerator space, creating bottlenecks that would prevent the flow of vaccines down to the clinics. As a result, the availability of all World Health Organization Expanded Program on Immunization vaccines to patients might decrease from an average of 69% to 28.2% (range = 10%–51%). Addition of refrigerator and transport capacity could alleviate this bottleneck. Conclusions. Our results suggest that the effects on the vaccine supply chain should be considered when introducing a new vaccine and that computational models can help assess evolving needs and prevent problems with vaccine delivery. PMID:21940923

  15. Modelling the impact of vaccination on curtailing Haemophilus influenzae serotype 'a'.

    PubMed

    Konini, Angjelina; Moghadas, Seyed M

    2015-12-21

    Haemophilus influenzae serotype a (Hia) is a human-restricted bacterial pathogen transmitted via direct contacts with an infectious individual. Currently, there is no vaccine available for prevention of Hia, and the disease is treated with antibiotics upon diagnosis. With ongoing efforts for the development of an anti-Hia protein-polysaccharide conjugated vaccine, we sought to investigate the effect of vaccination on curtailing Hia infection. We present the first stochastic model of Hia transmission and control dynamics, and parameterize it using available estimates in the literature. Since both naturally acquired and vaccine-induced immunity wane with time, model simulations show three important results. First, vaccination of only newborns cannot eliminate the pathogen from the population, even when a booster program is implemented with a high coverage. Second, achieving and maintaining a sufficiently high level of herd immunity for pathogen elimination requires vaccination of susceptible individuals in addition to a high vaccination coverage of newborns. Third, for a low vaccination rate of susceptible individuals, a high coverage of booster dose may be needed to raise the level of herd immunity for Hia eradication. Our findings highlight the importance of vaccination and timely boosting of the individual?s immunity within the expected duration of vaccine-induced protection against Hia. When an anti-Hia vaccine becomes available, enhanced surveillance of Hia incidence and herd immunity could help determine vaccination rates and timelines for booster doses necessary to eliminate Hia from affected populations. PMID:26453974

  16. Vaccines to prevent bacterial enteric infections in children.

    PubMed

    Levine, M M; Noriega, F

    1993-12-01

    Considerable progress has been made in the last decade in developing vaccines against the most important bacterial enteric infections. Two new vaccines against typhoid fever (oral Ty21a and parenteral Vi polysaccharide) have been licensed in many countries. Newer generations of more sophisticated typhoid vaccines are undergoing clinical testing including recombinant attenuated S typhi strains and Vi polysaccharide-carrier protein conjugate vaccines. Two inactivated oral cholera vaccines, consisting of inactivated V cholerae 01 bacteria alone or in combination with the B subunit of cholera toxin, each conferred 50% to 53% protection over 3 years in a field trial in Bangladesh where subjects were immunized with a three-dose regimen. An engineered live oral cholera vaccine, strain CVD 103-HgR, has been shown in extensive clinical trials to be well tolerated by children and adults in developing countries and highly immunogenic following administration of just a single oral dose; a large-scale field trial of the efficacy of this vaccine is underway. Several candidate vaccines against Shigella and enterotoxigenic E coli are in clinical trials. PMID:8139873

  17. Production of inflammatory cytokines in response to diphtheria-pertussis-tetanus (DPT), haemophilus influenzae type b (Hib), and 7-valent pneumococcal (PCV7) vaccines

    PubMed Central

    Kashiwagi, Yasuyo; Miyata, Akiko; Kumagai, Takuji; Maehara, Kouji; Suzuki, Eitarou; Nagai, Takao; Ozaki, Takao; Nishimura, Naoko; Okada, Kenji; Kawashima, Hisashi; Nakayama, Tetsuo

    2014-01-01

    Haemophilus influenzae type b (Hib) and 7-valent pneumococcal (PCV7) vaccines both became recommended in Japan in 2010. In this study, cytokine production was investigated in peripheral blood mononuclear cells (PBMCs) cultures stimulated with diphtheria and tetanus toxoids combined with acellular pertussis vaccine (DPT), Hib, and PCV7 separately or concurrent different combinations, all as final off-the-shelf vaccines without the individual vaccine components as controls. Higher IL-1? levels were produced when cultures were stimulated with PCV than with DPT or Hib, and the concurrent stimulation including PCV7 enhanced the production of IL-1?. Although Hib induced higher levels of IL-6, no significant difference was observed in IL-6 production with the concurrent stimulation. The concurrent stimulation with Hib/PCV7 and DPT/Hib/PCV7 produced higher levels of TNF-? and human G-CSF. Cytokine profiles were examined in serum samples obtained from 61 vaccine recipients with febrile reactions and 18 recipients without febrile illness within 24 h of vaccination. No significant difference was observed in cytokine levels of IL-1?, IL-4, IL-6, IL-10, IL-12, IFN-?, MIP-1, TNF-?, and prostaglandin E2 (PGE2) in sera between the two groups. However, significantly higher levels of human G-CSF were observed in recipients with febrile illness than in those without febrile reactions. Further investigations of the significance of elevated serum G-CSF levels are required in vaccine recipients with febrile illness. PMID:24589970

  18. Existing antiviral vaccines.

    PubMed

    Ravanfar, Parisa; Satyaprakash, Anita; Creed, Rosella; Mendoza, Natalia

    2009-01-01

    The innovation of vaccines has allowed for one of the greatest advancements in the history of public health. The first of the vaccines have been the antiviral vaccines, in particular the smallpox vaccine that was first developed by Edward Jenner in 1796. This article will review vaccination for the following viral diseases: measles, mumps, rubella, polio, hepatitis A, hepatitis B, influenza, rotavirus, rabies, monkeypox, smallpox, Japanese encephalitis, and yellow fever. PMID:19335723

  19. Conjugation in "Escherichia coli"

    ERIC Educational Resources Information Center

    Phornphisutthimas, Somkiat; Thamchaipenet, Arinthip; Panijpan, Bhinyo

    2007-01-01

    Bacterial conjugation is a genetic transfer that involves cell-to-cell between donor and recipient cells. With the current method used to teach students in genetic courses at the undergraduate level, the transconjugants are identified using bacterial physiology and/or antibiotic resistance. Using physiology, however, is difficult for both…

  20. Vaccines against malaria

    PubMed Central

    Hill, Adrian V. S.

    2011-01-01

    There is no licenced vaccine against any human parasitic disease and Plasmodium falciparum malaria, a major cause of infectious mortality, presents a great challenge to vaccine developers. This has led to the assessment of a wide variety of approaches to malaria vaccine design and development, assisted by the availability of a safe challenge model for small-scale efficacy testing of vaccine candidates. Malaria vaccine development has been at the forefront of assessing many new vaccine technologies including novel adjuvants, vectored prime-boost regimes and the concept of community vaccination to block malaria transmission. Most current vaccine candidates target a single stage of the parasite's life cycle and vaccines against the early pre-erythrocytic stages have shown most success. A protein in adjuvant vaccine, working through antibodies against sporozoites, and viral vector vaccines targeting the intracellular liver-stage parasite with cellular immunity show partial efficacy in humans, and the anti-sporozoite vaccine is currently in phase III trials. However, a more effective malaria vaccine suitable for widespread cost-effective deployment is likely to require a multi-component vaccine targeting more than one life cycle stage. The most attractive near-term approach to develop such a product is to combine existing partially effective pre-erythrocytic vaccine candidates. PMID:21893544

  1. Who Should Not Get Vaccinated with These Vaccines?

    MedlinePLUS

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

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

    MedlinePLUS

    ... Vaccine Effectiveness - How Well Does the Flu Vaccine Work? Questions & Answers Language: English Español Recommend on ... are factors that influenza how well the vaccine works? How well the flu vaccine works (or its ...

  3. Research Article Theme: Emerging Concepts for Vaccine Development and Vaccination

    E-print Network

    Feng, Zhilan

    Research Article Theme: Emerging Concepts for Vaccine Development and Vaccination Guest Editors: Stanley Hem, Craig Svensson, and Harm Hogenesch Modeling the Effects of Vaccination and Treatment the effectiveness of various control programs via vaccination and antiviral treatment. We use susceptible

  4. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ...2013-10-01 2013-10-01 false Pneumococcal vaccine and flu vaccine. 410.57 Section 410.57 Public Health ...Other Health Services § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays...

  5. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ...2012-10-01 2012-10-01 false Pneumococcal vaccine and flu vaccine. 410.57 Section 410.57 Public Health ...Other Health Services § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays...

  6. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ...2014-10-01 2014-10-01 false Pneumococcal vaccine and flu vaccine. 410.57 Section 410.57 Public Health ...Other Health Services § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays...

  7. Single-dose monomeric HA subunit vaccine generates full protection from influenza challenge

    PubMed Central

    Mallajosyula, Jyothi K; Hiatt, Ernie; Hume, Steve; Johnson, Ashley; Jeevan, Trushar; Chikwamba, Rachel; Pogue, Gregory P; Bratcher, Barry; Haydon, Hugh; Webby, Richard J; McCormick, Alison A

    2014-01-01

    Recombinant subunit vaccines are an efficient strategy to meet the demands of a possible influenza pandemic, because of rapid and scalable production. However, vaccines made from recombinant hemagglutinin (HA) subunit protein are often of low potency, requiring high dose or boosting to generate a sustained immune response. We have improved the immunogenicity of a plant-made HA vaccine by chemical conjugation to the surface of the Tobacco mosaic virus (TMV) which is non infectious in mammals. We have previously shown that TMV is taken up by mammalian dendritic cells and is a highly effective antigen carrier. In this work, we tested several TMV-HA conjugation chemistries, and compared immunogenicity in mice as measured by anti-HA IgG titers and hemagglutination inhibition (HAI). Importantly, pre-existing immunity to TMV did not reduce initial or boosted titers. Further optimization included dosing with and without alum or oil-in water adjuvants. Surprisingly, we were able to stimulate potent immunogenicity and HAI titers with a single 15µg dose of HA as a TMV conjugate. We then evaluated the efficacy of the TMV-HA vaccine in a lethal virus challenge in mice. Our results show that a single dose of the TMV-HA conjugate vaccine is sufficient to generate 50% survival, or 100% survival with adjuvant, compared with 10% survival after vaccination with a commercially available H1N1 vaccine. TMV-HA is an effective dose-sparing influenza vaccine, using a single-step process to rapidly generate large quantities of highly effective flu vaccine from an otherwise low potency HA subunit protein. PMID:24378714

  8. Rotavirus vaccine: a review.

    PubMed

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

    2012-12-01

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

  9. Vaccination: An Act of Love

    MedlinePLUS

    ... benefits of vaccines. For this reason, we created Vaccination Week in the Americas to get vaccines to ... and no one gets left behind. Help the vaccination teams when they come to your town, your ...

  10. HIV Infection and Adult Vaccination

    MedlinePLUS

    ... against seasonal flu Tdap vaccine to protect against whooping cough and tetanus Pneumococcal vaccine to protect against pneumonia ... against seasonal flu Tdap vaccine to protect against whooping cough and tetanus Pneumococcal vaccine to protect against pneumonia ...

  11. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 42 Public Health 2 2012-10-01 2012-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  12. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 42 Public Health 2 2011-10-01 2011-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  13. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 42 Public Health 2 2014-10-01 2014-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  14. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 42 Public Health 2 2013-10-01 2013-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  15. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 42 Public Health 2 2010-10-01 2010-10-01 false Pneumococcal vaccine and flu vaccine. 410.57... § 410.57 Pneumococcal vaccine and flu vaccine. (a) Medicare Part B pays for pneumococcal vaccine and its administration when reasonable and necessary for the prevention of disease, if the vaccine is ordered by a...

  16. Vaccines against poverty

    PubMed Central

    MacLennan, Calman A.; Saul, Allan

    2014-01-01

    With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vaccines for neglected infectious diseases. However, the majority of this went to three diseases: HIV/AIDS, malaria, and tuberculosis, and not neglected diseases. Much of it went to basic research rather than development, with an ongoing decline in funding for product development partnerships. Further investment in vaccines against diarrheal diseases, hepatitis C, and group A Streptococcus could lead to a major health impact in LMICs, along with vaccines to prevent sepsis, particularly among mothers and neonates. The Advanced Market Commitment strategy of the Global Alliance for Vaccines and Immunisation (GAVI) Alliance is helping to implement vaccines against rotavirus and pneumococcus in LMICs, and the roll out of the MenAfriVac meningococcal A vaccine in the African Meningitis Belt represents a paradigm shift in vaccines against poverty: the development of a vaccine primarily targeted at LMICs. Global health vaccine institutes and increasing capacity of vaccine manufacturers in emerging economies are helping drive forward new vaccines for LMICs. Above all, partnership is needed between those developing and manufacturing LMIC vaccines and the scientists, health care professionals, and policy makers in LMICs where such vaccines will be implemented. PMID:25136089

  17. Vaccines against poverty.

    PubMed

    MacLennan, Calman A; Saul, Allan

    2014-08-26

    With the 2010s declared the Decade of Vaccines, and Millennium Development Goals 4 and 5 focused on reducing diseases that are potentially vaccine preventable, now is an exciting time for vaccines against poverty, that is, vaccines against diseases that disproportionately affect low- and middle-income countries (LMICs). The Global Burden of Disease Study 2010 has helped better understand which vaccines are most needed. In 2012, US$1.3 billion was spent on research and development for new vaccines for neglected infectious diseases. However, the majority of this went to three diseases: HIV/AIDS, malaria, and tuberculosis, and not neglected diseases. Much of it went to basic research rather than development, with an ongoing decline in funding for product development partnerships. Further investment in vaccines against diarrheal diseases, hepatitis C, and group A Streptococcus could lead to a major health impact in LMICs, along with vaccines to prevent sepsis, particularly among mothers and neonates. The Advanced Market Commitment strategy of the Global Alliance for Vaccines and Immunisation (GAVI) Alliance is helping to implement vaccines against rotavirus and pneumococcus in LMICs, and the roll out of the MenAfriVac meningococcal A vaccine in the African Meningitis Belt represents a paradigm shift in vaccines against poverty: the development of a vaccine primarily targeted at LMICs. Global health vaccine institutes and increasing capacity of vaccine manufacturers in emerging economies are helping drive forward new vaccines for LMICs. Above all, partnership is needed between those developing and manufacturing LMIC vaccines and the scientists, health care professionals, and policy makers in LMICs where such vaccines will be implemented. PMID:25136089

  18. The preteen visit: an opportunity for prevention.

    PubMed

    Campos-Outcalt, Doug

    2006-12-01

    All early adolescents should visit a physician at age 11 or 12 years to receive a set of recommended vaccines. Two vaccines are recommended for boys in this age group-quadrivalent meningococcal conjugate vaccine (MCV4) and tetanus toxoid, reduced diphtheria, and acellular pertussis vaccine (Tdap). Three vaccines are recommended for girls--MCV4, Tdap, and human papilloma virus (HPV) vaccine. In addition, 2 doses of varicella vaccine are now recommended before age 5 years; both boys and girls at age 11 or 12 who have received only 1 dose should be given a second. PMID:17137541

  19. Intellectual property rights and challenges for development of affordable human papillomavirus, rotavirus and pneumococcal vaccines: Patent landscaping and perspectives of developing country vaccine manufacturers.

    PubMed

    Chandrasekharan, Subhashini; Amin, Tahir; Kim, Joyce; Furrer, Eliane; Matterson, Anna-Carin; Schwalbe, Nina; Nguyen, Aurélia

    2015-11-17

    The success of Gavi, the Vaccine Alliance depends on the vaccine markets providing appropriate, affordable vaccines at sufficient and reliable quantities. Gavi's current supplier base for new and underutilized vaccines, such as the human papillomavirus (HPV), rotavirus, and the pneumococcal conjugate vaccine is very small. There is growing concern that following globalization of laws on intellectual property rights (IPRs) through trade agreements, IPRs are impeding new manufacturers from entering the market with competing vaccines. This article examines the extent to which IPRs, specifically patents, can create such obstacles, in particular for developing country vaccine manufacturers (DCVMs). Through building patent landscapes in Brazil, China, and India and interviews with manufacturers and experts in the field, we found intense patenting activity for the HPV and pneumococcal vaccines that could potentially delay the entry of new manufacturers. Increased transparency around patenting of vaccine technologies, stricter patentability criteria suited for local development needs and strengthening of IPRs management capabilities where relevant, may help reduce impediments to market entry for new manufacturers and ensure a competitive supplier base for quality vaccines at sustainably low prices. PMID:26368398

  20. Conjugate flow action functionals

    SciTech Connect

    Venturi, Daniele

    2013-11-15

    We present a new general framework to construct an action functional for a non-potential field theory. The key idea relies on representing the governing equations relative to a diffeomorphic flow of curvilinear coordinates which is assumed to be functionally dependent on the solution field. Such flow, which will be called the conjugate flow, evolves in space and time similarly to a physical fluid flow of classical mechanics and it can be selected in order to symmetrize the Gâteaux derivative of the field equations with respect to suitable local bilinear forms. This is equivalent to requiring that the governing equations of the field theory can be derived from a principle of stationary action on a Lie group manifold. By using a general operator framework, we obtain the determining equations of such manifold and the corresponding conjugate flow action functional. In particular, we study scalar and vector field theories governed by second-order nonlinear partial differential equations. The identification of transformation groups leaving the conjugate flow action functional invariant could lead to the discovery of new conservation laws in fluid dynamics and other disciplines.

  1. Strain Selection for Generation of O-Antigen-Based Glycoconjugate Vaccines against Invasive Nontyphoidal Salmonella Disease.

    PubMed

    Lanzilao, Luisa; Stefanetti, Giuseppe; Saul, Allan; MacLennan, Calman A; Micoli, Francesca; Rondini, Simona

    2015-01-01

    Nontyphoidal Salmonellae, principally S. Typhimurium and S. Enteritidis, are a major cause of invasive bloodstream infections in sub-Saharan Africa with no vaccine currently available. Conjugation of lipopolysaccharide O-antigen to a carrier protein constitutes a promising vaccination strategy. Here we describe a rational process to select the most appropriate isolates of Salmonella as source of O-antigen for developing a bivalent glycoconjugate vaccine. We screened a library of 30 S. Typhimurium and 21 S. Enteritidis in order to identify the most suitable strains for large scale O-antigen production and generation of conjugate vaccines. Initial screening was based on growth characteristics, safety profile of the isolates, O-antigen production, and O-antigen characteristics in terms of molecular size, O-acetylation and glucosylation level and position, as determined by phenol sulfuric assay, NMR, HPLC-SEC and HPAEC-PAD. Three animal isolates for each serovar were identified and used to synthesize candidate glycoconjugate vaccines, using CRM197 as carrier protein. The immunogenicity of these conjugates and the functional activity of the induced antibodies was investigated by ELISA, serum bactericidal assay and flow cytometry. S. Typhimurium O-antigen showed high structural diversity, including O-acetylation of rhamnose in a Malawian invasive strain generating a specific immunodominant epitope. S. Typhimurium conjugates provoked an anti-O-antigen response primarily against the O:5 determinant. O-antigen from S. Enteritidis was structurally more homogeneous than from S. Typhimurium, and no idiosyncratic antibody responses were detected for the S. Enteritidis conjugates. Of the three initially selected isolates, two S. Typhimurium (1418 and 2189) and two S. Enteritidis (502 and 618) strains generated glycoconjugates able to induce high specific antibody levels with high breadth of serovar-specific strain coverage, and were selected for use in vaccine production. The strain selection approach described is potentially applicable to the development of glycoconjugate vaccines against other bacterial pathogens. PMID:26445460

  2. Strain Selection for Generation of O-Antigen-Based Glycoconjugate Vaccines against Invasive Nontyphoidal Salmonella Disease

    PubMed Central

    Saul, Allan; MacLennan, Calman A.; Micoli, Francesca; Rondini, Simona

    2015-01-01

    Nontyphoidal Salmonellae, principally S. Typhimurium and S. Enteritidis, are a major cause of invasive bloodstream infections in sub-Saharan Africa with no vaccine currently available. Conjugation of lipopolysaccharide O-antigen to a carrier protein constitutes a promising vaccination strategy. Here we describe a rational process to select the most appropriate isolates of Salmonella as source of O-antigen for developing a bivalent glycoconjugate vaccine. We screened a library of 30 S. Typhimurium and 21 S. Enteritidis in order to identify the most suitable strains for large scale O-antigen production and generation of conjugate vaccines. Initial screening was based on growth characteristics, safety profile of the isolates, O-antigen production, and O-antigen characteristics in terms of molecular size, O-acetylation and glucosylation level and position, as determined by phenol sulfuric assay, NMR, HPLC-SEC and HPAEC-PAD. Three animal isolates for each serovar were identified and used to synthesize candidate glycoconjugate vaccines, using CRM197 as carrier protein. The immunogenicity of these conjugates and the functional activity of the induced antibodies was investigated by ELISA, serum bactericidal assay and flow cytometry. S. Typhimurium O-antigen showed high structural diversity, including O-acetylation of rhamnose in a Malawian invasive strain generating a specific immunodominant epitope. S. Typhimurium conjugates provoked an anti-O-antigen response primarily against the O:5 determinant. O-antigen from S. Enteritidis was structurally more homogeneous than from S. Typhimurium, and no idiosyncratic antibody responses were detected for the S. Enteritidis conjugates. Of the three initially selected isolates, two S. Typhimurium (1418 and 2189) and two S. Enteritidis (502 and 618) strains generated glycoconjugates able to induce high specific antibody levels with high breadth of serovar-specific strain coverage, and were selected for use in vaccine production. The strain selection approach described is potentially applicable to the development of glycoconjugate vaccines against other bacterial pathogens. PMID:26445460

  3. Active self-healing encapsulation of vaccine antigens in PLGA microspheres

    PubMed Central

    Desai, Kashappa-Goud H.; Schwendeman, Steven P.

    2013-01-01

    Herein, we describe the detailed development of a simple and effective method to microencapsulate vaccine antigens in poly(lactic-co-glycolic acid) (PLGA) by simple mixing of preformed active self-microencapsulating (SM) PLGA microspheres in a low concentration aqueous antigen solution at modest temperature (10-38 °C). Co-encapsulating protein-sorbing vaccine adjuvants and polymer plasticizers were used to “actively” load the protein in the polymer pores and facilitate polymer self-healing at temperature > hydrated polymer glass transition temperature, respectively. The microsphere formulation parameters and loading conditions to provide optimal active self-healing microencapsulation of vaccine antigen in PLGA was investigated. Active self-healing encapsulation of two vaccine antigens, ovalbumin and tetanus toxoid (TT), in PLGA microspheres was adjusted by preparing blank microspheres containing different vaccine adjuvant (aluminum hydroxide (Al(OH)3) or calcium phosphate). Active loading of vaccine antigen in Al(OH)3-PLGA microspheres was found to: a) increase proportionally with an increasing loading of Al(OH)3 (0.88-3 wt%) and addition of porosigen, b) decrease when the inner Al(OH)3/trehalose phase to 1 mL outer oil phase and size of microspheres was respectively > 0.2 mL and 63 ?m, and c) change negligibly by PLGA concentration and initial incubation (loading) temperature. Encapsulation of protein sorbing Al(OH)3 in PLGA microspheres resulted in suppression of self-healing of PLGA pores, which was then overcome by improving polymer chain mobility, which in turn was accomplished by coincorporating hydrophobic plasticizers in PLGA. Active self-healing microencapsulation of manufacturing process-labile TT in PLGA was found to: a) obviate micronization- and organic solvent-induced TT degradation, b) improve antigen loading (1.4-1.8 wt% TT) and encapsulation efficiency (~ 97%), c) provide nearly homogeneous distribution and stabilization of antigen in polymer, and d) provide improved in vitro controlled release of antigenic TT. PMID:23103983

  4. Safety of engineered allergen-specific immunotherapy vaccines

    PubMed Central

    Focke-Tejkl, Margarete; Valenta, Rudolf

    2015-01-01

    Purpose of review The purpose of the review is to summarize and comment on recent developments regarding the safety of engineered immunotherapy vaccines. Recent findings In the last 2 years, several studies were published in which allergy vaccines were developed on the basis of chemical modification of natural allergen extracts, the engineering of allergen molecules by recombinant DNA technology and synthetic peptide chemistry, allergen genes, new application routes and conjugation with immune modulatory molecules. Several studies exemplified the general applicability of hypoallergenic vaccines on the basis of recombinant fusion proteins consisting of nonallergenic allergen-derived peptides fused to allergen-unrelated carrier molecules. These vaccines are engineered to reduce both, immunoglobulin E (IgE) as well as allergen-specific T cell epitopes in the vaccines, and thus should provoke less IgE and T-cell-mediated side-effects. They are made to induce allergen-specific IgG antibodies against the IgE-binding sites of allergens with the T-cell help of the carrier molecule. Summary Several interesting examples of allergy vaccines with potentially increased safety profiles have been published. The concept of fusion proteins consisting of allergen-derived hypoallergenic peptides fused to allergen-unrelated proteins that seems to be broadly applicable for a variety of allergens appears to be of particular interest because it promises not only to reduce side-effects but also to increase efficacy and convenience of allergy vaccines. PMID:22885888

  5. Vaccine Safety Datalink

    Cancer.gov

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

  6. Clinical vaccine development

    PubMed Central

    2015-01-01

    Vaccination is regarded as one of the biggest triumphs in the history of medicine. We are living in the most successful period of vaccine development. The accumulation of multidisciplinary knowledge and the investment of massive funding have enabled the development of vaccines against many infectious diseases as well as other diseases including malignant tumors. The paradigm of clinical vaccine evaluation and licensure has also been modernized based on scientific improvements and historical experience. However, there remain a number of hurdles to overcome. Continuous efforts are focused on increasing the efficacy and reducing the risks related to vaccine use. Cutting-edge knowledge about immunology and microbiology is being rapidly translated to vaccine development. Thus, physicians and others involved in the clinical development of vaccines should have sufficient understanding of the recent developmental trends in vaccination and the diseases of interest. PMID:25648742

  7. Vaccinations during Pregnancy

    MedlinePLUS

    ... other vaccinations during pregnancy. These include: Anthrax Japanese encephalitis Polio Rabies Vaccinia (for smallpox) Yellow fever What ... other vaccinations during pregnancy. These include: Anthrax Japanese encephalitis Polio Rabies Vaccinia (for smallpox) Yellow fever What ...

  8. Anthrax Vaccine Approval Expanded

    MedlinePLUS

    ... nih.gov/medlineplus/news/fullstory_155893.html Anthrax Vaccine Approval Expanded Now sanctioned for adults 18 to ... and Drug Administration approval for the BioThrax anthrax vaccine has been expanded to include adults aged 18 ...

  9. Vaccine Working Group

    Cancer.gov

    Brainstorming, cross-fertilization, and idea sharing within the NCI vaccine community. Consensus on issues, such as identification of tumor antigens and determination of relevant and effective assays for evaluating immunologic responses to cancer vaccines

  10. Vaccine Working Group

    Cancer.gov

    Mission The Vaccine Working Group enhances the research efforts within the NCI intramural program toward developing novel vaccines for cancer immunotherapy and human immunodeficiency virus (HIV). The group brings together members from throughout the Insti

  11. Hepatitis B Vaccination Protection

    MedlinePLUS

    ... the time the procedure takes place. To ensure immunity, it is important for individuals to complete the ... great majority of those vaccinated will devel- op immunity to the hepatitis B virus. The vaccine causes ...

  12. The Economics of Vaccination

    E-print Network

    Chen, Frederick; Toxvaerd, Flavio

    2014-08-09

    The market for vaccinations is widely believed to be characterized by market failures, because individuals do not internalize the positive externalities that their vaccination decisions may confer on other individuals. Francis (1997) provided a set...

  13. Hepatitis B Vaccine

    MedlinePLUS

    ... as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... What is hepatitis B?Hepatitis B is a serious infection that affects the liver. It is caused by the hepatitis B virus. ...

  14. Tetanus, Diphtheria (Td) Vaccine

    MedlinePLUS

    ... Tetanus-causing bacteria enter the body through cuts, scratches, or wounds.TETANUS (Lockjaw) causes painful muscle tightening ... Vaccine Injury Compensation ProgramThe National Vaccine Injury Compensation Program (VICP) is a federal program that was created ...

  15. National Vaccine Program Office

    MedlinePLUS

    ... Plan Resources Text Size: A A A National Vaccine Program Office (NVPO) NVPO provides leadership and coordination ... to carry out the goals of the National Vaccine Plan. Follow our roadmap for the 21 st ...

  16. Ear Infection and Vaccines

    MedlinePLUS

    ... Meeting Calendar Find an ENT Doctor Near You Ear Infection and Vaccines Ear Infection and Vaccines Patient Health Information News media ... who suffer from the most common type of ear infection, called middle ear infection or otitis media ( ...

  17. Hepatitis A Vaccine

    MedlinePLUS

    Twinrix® (as a combination product containing Hepatitis A Vaccine, Hepatitis B Vaccine) ... What is hepatitis A?Hepatitis A is a serious liver disease caused by the hepatitis A virus (HAV). HAV is found in ...

  18. Your baby's first vaccines

    MedlinePLUS

    ... substance. Some of these vaccines contain neomycin, streptomycin, yeast, lactose, sucrose, or latex. Tell your doctor if ... if your child has a severe allergy to yeast. PCV13 vaccine , if your child has a severe ...

  19. Childhood Vaccine Schedule

    MedlinePLUS

    ... vaccine (three doses)— Hib Protects against illnesses like meningitis, pneumonia, and infections of the blood, bones, and ... infections such as pneumonia, blood infections, and bacterial meningitis Rotavirus vaccine (three doses)— RV Protects against severe ...

  20. Human Papillomavirus (HPV) Vaccines

    MedlinePLUS

    ... been vaccinated still need to be screened for cervical cancer? How much do these vaccines cost, and will ... High-risk HPVs cause several types of cancer. Cervical cancer : Virtually all cases of cervical cancer are caused ...

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

    PubMed

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

    2015-12-01

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

  2. Methods and challenges for the health impact assessment of vaccination programs in Latin America

    PubMed Central

    Sartori, Ana Marli Christovam; Nascimento, Andréia de Fátima; Yuba, Tânia Yuka; de Soárez, Patrícia Coelho; Novaes, Hillegonda Maria Dutilh

    2015-01-01

    ABSTRACT OBJECTIVE To describe methods and challenges faced in the health impact assessment of vaccination programs, focusing on the pneumococcal conjugate and rotavirus vaccines in Latin America and the Caribbean. METHODS For this narrative review, we searched for the terms “rotavirus”, “pneumococcal”, “conjugate vaccine”, “vaccination”, “program”, and “impact” in the databases Medline and LILACS. The search was extended to the grey literature in Google Scholar. No limits were defined for publication year. Original articles on the health impact assessment of pneumococcal and rotavirus vaccination programs in Latin America and the Caribbean in English, Spanish or Portuguese were included. RESULTS We identified 207 articles. After removing duplicates and assessing eligibility, we reviewed 33 studies, 25 focusing on rotavirus and eight on pneumococcal vaccination programs. The most frequent studies were ecological, with time series analysis or comparing pre- and post-vaccination periods. The main data sources were: health information systems; population-, sentinel- or laboratory-based surveillance systems; statistics reports; and medical records from one or few health care services. Few studies used primary data. Hospitalization and death were the main outcomes assessed. CONCLUSIONS Over the last years, a significant number of health impact assessments of pneumococcal and rotavirus vaccination programs have been conducted in Latin America and the Caribbean. These studies were carried out few years after the programs were implemented, meet the basic methodological requirements and suggest positive health impact. Future assessments should consider methodological issues and challenges arisen in these first studies conducted in the region.

  3. Smallpox Vaccine Overview

    MedlinePLUS

    ... every 1 million people vaccinated for the first time experienced reactions that, while not life-threatening, were serious. These ... every 1 million people vaccinated for the first time experienced potentially life-threatening reactions to the vaccine. Based on past experience, it ...

  4. Vaccines in dermatological diseases.

    PubMed

    Magel, G D; Mendoza, N; Digiorgio, C M; Haitz, K A; Lapolla, W J; Tyring, S K

    2011-06-01

    Vaccines have been a cornerstone in medicine and public health since their inception in the 18th century by Edward Jenner. Today, greater than 20 vaccines are used worldwide for the prevention of both viral and bacterial diseases. This article will review the vaccines used for the following dermatological diseases: smallpox, measles, mumps, rubella, chickenpox, shingles, and human papillomavirus. PMID:21566552

  5. Vaccines in Dermatology.

    PubMed

    Shah, Mitali M; Shah, Aishani C; Mahajan, Rashmi S; Bilimoria, Freny E

    2015-01-01

    A vaccine is a biological preparation that improves immunity to a specific disease. More than two centuries have passed since the first successful vaccine for smallpox was developed. We've come a long way since. Today's vaccines are among the 21(st) century's most successful and cost-effective public health tools for preventing diseases. PMID:26120155

  6. Update on Routine Childhood and Adolescent Immunizations.

    PubMed

    Ackerman, Lani K; Serrano, Jacquelyn L

    2015-09-15

    Recommendations for routine vaccinations in children and adolescents have changed multiple times in recent years, based on findings in clinical trials, licensure of new vaccines, and evidence of waning immunity. Despite the overwhelming success of vaccinations, vaccine delay and refusal are leading to pockets of vaccine-preventable diseases. Schedules for diphtheria and tetanus toxoids, and acellular pertussis (DTaP); hepatitis A and B; Haemophilus influenzae type b (Hib); inactivated poliovirus; varicella; and measles, mumps, and rubella are unchanged. However, since 2008, 13-valent pneumococcal conjugate vaccine has replaced the 7-valent vaccine; a new two-dose oral rotavirus vaccine has been approved; use of the tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap) vaccine has been expanded to children seven to 10 years of age who received fewer than five doses of DTaP, as well as during each pregnancy; a booster dose of meningococcal vaccine is recommended in adolescents 16 to 18 years of age (unless the first dose was given after 16 years of age); new meningococcal vaccines have been approved for use in infants at high risk of meningococcal disease; influenza vaccine has been expanded to routine use in all children six months and older; and the human papillomavirus vaccine has been approved for routine immunization of adolescent boys and girls. For the 2015-2016 influenza season, either live attenuated or inactivated vaccine can be administered to healthy children two to eight years of age. PMID:26371731

  7. Improving newcastle disease vaccination with homologous vaccines

    Technology Transfer Automated Retrieval System (TEKTRAN)

    All Newcastle disease viruses (NDVs) belong to a single serotype; however, current vaccine strains display important amino acid differences at the F and HN protein compared with virulent outbreak strains (vNDV). Previous studies have shown decreased viral shedding after challenge when vaccines were...

  8. Conjugation of a peptide to mannan and its confirmation by tricine sodium dodecyl sulfate-polyacrylamide gel electrophoresis.

    PubMed

    Tapeinou, Anthi; Androutsou, Maria-Eleni; Kyrtata, Konstantina; Vlamis-Gardikas, Alexios; Apostolopoulos, Vasso; Matsoukas, John; Tselios, Theodore

    2015-09-15

    The conjugation of polysaccharides to peptides is essential for antigen delivery and vaccine development. Herein, we show that tricine SDS-PAGE in combination with Coomassie Blue staining was adequate to determine the conjugation efficacy of a peptide (epitope 35-55 of myelin oligodendrocyte glycoprotein) to mannan. In addition, tricine SDS-PAGE and periodic acid-Schiff stains were able to monitor the redox state of mannan. Using the described protocol, more than 99.9% of a peptide containing five lysines at its N-terminus was confirmed conjugated to mannan. PMID:26079707

  9. Conjugate Sporadic-E measurements

    NASA Astrophysics Data System (ADS)

    MacDougall, John; Abdu, M. A.; Batista, I.

    2009-08-01

    During an equatorial campaign called COPEX (Conjugate Point Equatorial Experiment) ionosondes at a pair of conjugate stations in Brazil were operated for 2 months in 2002. One expected the sporadic-E (Es) layers to be rather similar at the conjugate locations. However, there were significant differences in the Es, particularly in the part of the Es trace that extends above the blanketing frequency. Considerations of the ambient conditions at the conjugate locations indicate that relatively small differences in parameters such as the tidal winds, electric fields, and background density gradients can significantly affect the structuring of the Es layer.

  10. Pneumococcal vaccination among HIV-infected adult patients in the era of combination antiretroviral therapy

    PubMed Central

    Lee, Kuan-Yeh; Tsai, Mao-Song; Kuo, Kuang-Che; Tsai, Jen-Chih; Sun, Hsin-Yun; Cheng, Aristine C; Chang, Sui-Yuan; Lee, Chen-Hsiang; Hung, Chien-Ching

    2014-01-01

    HIV-infected patients remain at higher risk for pneumococcal disease than the general population despite immune reconstitution and suppression of HIV replication with combination antiretroviral therapy. Vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV23) composed of T-cell-independent antigens has been recommended to reduce the risk of pneumococcal disease in HIV-infected adults. However, given the heterogeneity of study design, execution and subjects enrolled, studies examining serological responses to PPV23 yielded conflicting results and observational studies of clinical effectiveness only provided moderate evidence to support the routine use of PPV23 in HIV-infected adults. Pneumococcal conjugate vaccine (PCV), with conjugation of the capsular polysaccharide to a protein carrier, is more immunogenic than PPV23 and has been demonstrated to protect against pneumococcal disease in HIV-infected children and recurrent invasive pneumococcal disease in HIV-infected adolescents and adults. Guidelines have recently been revised to recommend that HIV-infected patients aged 19 y or older receive one dose of 13-valent pneumococcal conjugate vaccine (PCV13) followed by a booster vaccination with PPV23. In this paper, we review the studies using different vaccination strategies to improve immunogenicity among HIV-infected adult patients. PMID:25483681

  11. Human Vaccines and Immunotherapeutics: News

    PubMed Central

    Riedmann, Eva M

    2013-01-01

    Agenus brain cancer vaccine improves survival in phase 2 trial Meningococcal meningitis cases fall 94% following vaccine introduction Most vaccines are safe during breastfeeding Promising phase 1 results for Genocea’s herpes simplex virus vaccine Delayed vaccinations clearly increase risk of whooping cough Positive news from early-stage HIV vaccines Sanofi’s H7N9 vaccine trial with MF59 and AS03 PMID:24192581

  12. Conjugate and method for forming aminomethyl phosphorus conjugates

    DOEpatents

    Katti, Kattesh V. (Columbia, MO); Berning, Douglas E. (Columbia, MO); Volkert, Wynn A. (Columbia, MO); Ketring, Alan R. (Columbia, MO); Churchill, Robert (Columbia, MO)

    1999-01-01

    A method of forming phosphine-amine conjugates includes reacting a hydroxymethyl phosphine group of an amine-free first molecule with at least one free amine group of a second molecule to covalently bond the first molecule with the second molecule through an aminomethyl phosphorus linkage and the conjugates formed thereby.

  13. Emerging Vaccine Informatics

    PubMed Central

    He, Yongqun; Rappuoli, Rino; De Groot, Anne S.; Chen, Robert T.

    2010-01-01

    Vaccine informatics is an emerging research area that focuses on development and applications of bioinformatics methods that can be used to facilitate every aspect of the preclinical, clinical, and postlicensure vaccine enterprises. Many immunoinformatics algorithms and resources have been developed to predict T- and B-cell immune epitopes for epitope vaccine development and protective immunity analysis. Vaccine protein candidates are predictable in silico from genome sequences using reverse vaccinology. Systematic transcriptomics and proteomics gene expression analyses facilitate rational vaccine design and identification of gene responses that are correlates of protection in vivo. Mathematical simulations have been used to model host-pathogen interactions and improve vaccine production and vaccination protocols. Computational methods have also been used for development of immunization registries or immunization information systems, assessment of vaccine safety and efficacy, and immunization modeling. Computational literature mining and databases effectively process, mine, and store large amounts of vaccine literature and data. Vaccine Ontology (VO) has been initiated to integrate various vaccine data and support automated reasoning. PMID:21772787

  14. [New human vaccines].

    PubMed

    Grimprel, Emmanuel

    2012-03-01

    Proteinaceous meningococcal B vaccines are under development, and the most advanced, Bexsero, is currently being evaluated by the European Medicines Agency. Approval, if granted, will be based on safety, immunogenicity, and theoretical strain coverage established in vitro. Clinical effectiveness will only be determined after market release. New, more effective influenza vaccines are also being developed. A trivalent attenuated nasal influenza vaccine (Fluenz) shows better efficacy in children than the classic trivalent seasonal inactivated vaccine, but its use is restricted to children over 2 years of age because of safety and efficacy considerations. The more potent trivalent (MF59) adjuvated inactivated influenza vaccine (Fluad), licensed for adults over 65 years of age, is being evaluated through a pediatric investigation plan. This vaccine could be useful for infants in whom unadjuvated inactivated vaccines are poorly protective, but its safety must first be fully established. PMID:23472347

  15. Immunology of vaccination.

    PubMed

    Beverley, P C L

    2002-01-01

    An ideal vaccine is relatively easy to define, but few real vaccines approach the ideal and no vaccines exist for many organisms, for which a vaccine is the only realistic protective strategy in the foreseeable future. Many difficulties account for the failure to produce these vaccines. All micro-organisms deploy evasion mechanisms that interfere with effective immune responses and, for many organisms, it is not clear which immune responses provide effective protection. However, recent advances in methods for studying immune response to pathogens have provided a better understanding of immune mechanisms, including immunological memory, and led to the realisation that the initiation of immune responses is a key event requiring triggering through 'danger' signals. Based on these findings, the development of novel adjuvants, vectors and vaccine formulations allowing stimulation of optimal and prolonged protective immunity should lead to the introduction of vaccines for previously resistant organisms. PMID:12176847

  16. Vaccine 21 (2003) 10441047 MMR vaccination advice over the Internet

    E-print Network

    Colquhoun, David

    2003-01-01

    Vaccine 21 (2003) 1044­1047 MMR vaccination advice over the Internet Katja Schmidt, Edzard Ernst vaccination programme (MMR) vaccination via the Internet. Online referral directories listing e-mail addresses vaccination. After sending a follow-up letter explaining the nature and aim of this project and offering

  17. Vaccinations Etes-vous jour dans vos vaccinations ?

    E-print Network

    Di Girolami, Cristina

    Vaccinations Etes-vous à jour dans vos vaccinations ? * Nous réalisons gratuitement les vaccins suivants : DT Polio, Hépatite B, DTP +Coqueluche Les autres vaccins peuvent être prescrits par les médecins'infirmière. * Venez vous informer sur les vaccins : hépatite B, papillomavirus (prévention du cancer du col de l

  18. Chiral Conjugated Corrals.

    PubMed

    Ball, Melissa; Fowler, Brandon; Li, Panpan; Joyce, Leo A; Li, Fang; Liu, Taifeng; Paley, Daniel; Zhong, Yu; Li, Hexing; Xiao, Shengxiong; Ng, Fay; Steigerwald, Michael L; Nuckolls, Colin

    2015-08-12

    We present here a new design motif for strained, conjugated macrocycles that incorporates two different aromatics into the cycle with an -A-B-A-B- pattern. In this study, we demonstrate the concept by alternating electron donors and acceptors in a conjugated cycle. The donor is a bithiophene, and the acceptor is a perylene diimide derivative. The macrocycle formed has a persistent elliptiform cavity that is lined with the sulfur atoms of the thiophenes and the ?-faces of the perylene diimide. Due to the linkage of the perylene diimide subunits, the macrocycles exist in both chiral and achiral forms. We separate the three stereoisomers using chiral high-performance liquid chromatography and study their interconversion. The mechanism for interconversion involves an "intramolecular somersault" in which one of the PDIs rotates around its transverse axis, thereby moving one of its diimide heads through the plane of the cavity. These unusual macrocycles are black in color with an absorption spectrum that spans the visible range. Density functional theory calculations reveal a photoinduced electron transfer from the bithiophene to the perylene diimide. PMID:26225639

  19. Vaccination Expands Antigen-Specific CD4+ Memory T Cells and Mobilizes Bystander Central Memory T Cells

    PubMed Central

    Li Causi, Eleonora; Parikh, Suraj C.; Chudley, Lindsey; Layfield, David M.; Ottensmeier, Christian H.; Stevenson, Freda K.; Di Genova, Gianfranco

    2015-01-01

    CD4+ T helper memory (Thmem) cells influence both natural and vaccine-boosted immunity, but mechanisms for their maintenance remain unclear. Pro-survival signals from the common gamma-chain cytokines, in particular IL-7, appear important. Previously we showed in healthy volunteers that a booster vaccination with tetanus toxoid (TT) expanded peripheral blood TT-specific Thmem cells as expected, but was accompanied by parallel increase of Thmem cells specific for two unrelated and non cross-reactive common recall antigens. Here, in a new cohort of healthy human subjects, we compare blood vaccine-specific and bystander Thmem cells in terms of differentiation stage, function, activation and proliferative status. Both responses peaked 1 week post-vaccination. Vaccine-specific cytokine-producing Thmem cells were predominantly effector memory, whereas bystander cells were mainly of central memory phenotype. Importantly, TT-specific Thmem cells were activated (CD38High HLA-DR+), cycling or recently divided (Ki-67+), and apparently vulnerable to death (IL-7R?Low and Bcl-2 Low). In contrast, bystander Thmem cells were resting (CD38Low HLA-DR- Ki-67-) with high expression of IL-7R? and Bcl-2. These findings allow a clear distinction between vaccine-specific and bystander Thmem cells, suggesting the latter do not derive from recent proliferation but from cells mobilized from as yet undefined reservoirs. Furthermore, they reveal the interdependent dynamics of specific and bystander T-cell responses which will inform assessments of responses to vaccines. PMID:26332995

  20. Cancer vaccine THERATOPE- Biomira.

    PubMed

    2003-01-01

    Biomira is developing a therapeutic cancer vaccine [THERATOPE] for treatment of breast and other cancers. This profile has been selected from R&D Insight, a pharmaceutical intelligence database produced by Adis International Ltd. THERATOPE consists of the mucin antigen, sialyl-Tn (STn), a carbohydrate located on the surface of breast, colorectal and ovarian cancer cells, conjugated to keyhole limpet haemocyanin (KLH). Merck KGaA has acquired a worldwide licence to THERATOPE for treatment of breast cancer. Under the terms of the licence, Biomira and Merck KGaA, via its US affiliate, EMD Pharmaceuticals, will jointly market the vaccine in the US. Merck KGaA holds exclusive marketing rights for the rest of the world, except in Canada (where Biomira retains rights), Israel and the Palestine Autonomy Area. Merck KGaA is now collaborating on phase III development for breast cancer. Biomira stands to receive $US150 million in licence, milestone payments and equity investments. The development costs will be shared between the two companies in North America but Merck KGaA will be solely responsible for these costs in countries outside the US. Previously, Chiron Corporation had purchased a licence to THERATOPE in 1997; however, Chiron terminated this agreement in June 2000. Under the terms of the termination, Biomira paid Chiron $US2.25 million to compensate the company for its investment in the development of THERATOPE. In addition, Biomira will make another payment of $US3.25 million to Chiron upon FDA approval of the vaccine. No further payments or royalties will be made. In the third quarter of 2002, an independent review of interim data from the trial was conducted. This was the fifth scheduled review of the data by the Independent Data Safety Monitoring Board (DSMB), all of which produced a positive response. Following the completion of the review, the DSMB stated that the trial should continue and that it had no safety concerns regarding this trial. Although the data, to which Biomira and Merck KgaA are blinded, did not meet the predetermined statistical significance for either endpoint at the time of the review, both companies have chosen to continue with the trial. Biomira has since announced that the p-value for the interim survival analysis was set at 0.01, while it is set at 0.03 for final survival analysis. The tighter criteria was set for the interim analysis to potentially give the companies the opportunity of applying for marketing approval earlier than expected. Final analysis of the trial will take place in mid-2003. If these analyses indicate therapeutic efficacy, Biomira will meet the FDA and Canadian regulatory officials to obtain marketing approval for the vaccine for breast cancer under the accelerated review guidelines. Assuming a best-case scenario, the vaccine could be filed for approval in 2004. The phase III trial was initiated following positive preliminary results achieved in a bridging study in patients with metastatic breast cancer in the US and UK. Biomira announced final results of the bridging study in May 1999. The results confirmed that antibody titres against the STn antigen were significantly higher in patients treated with the improved formulation of THERATOPE, compared with the corresponding titres of patients in the phase II trials of the old formulation of THERATOPE. In September 2002, the first patient was enrolled in a phase II THERATOPE trial, which is enrolling patients with metastatic breast cancer who are taking either an aromatase inhibitor or fulvestrant. Approximately 95 patients will be enrolled in the trial at up to 12 US sites. The study is primarily designed to evaluate THERATOPE's ability to induce an immune response in these patients. However, the safety and tolerability of the aromatase inhibitor plus THERATOPE, and the fulvestrant plus THERATOPE combinations will also be evaluated. The trial has not been designed to evaluate the efficacy of the two combinations. The US FDA has granted fast-track status tranted fast-track status to THERATOPE for development as an adjunct t

  1. Determinants of childhood vaccination completion at a peri-urban hospital in Kenya, December 2013 -January 2014: a case control study

    PubMed Central

    Emmanuel, Okunga Wandera; Samuel, Amwayi Anyangu; Helen, Kutima Lydia

    2015-01-01

    Introduction Vaccine preventable diseases account for about 17% of deaths among children below five years in Kenya. Immunization is one the most cost-effective ways of reducing child mortality and morbidity worldwide. In Kenya, national full vaccination coverage today stands at above 80%. However there continue to be pockets of low full vaccination coverage like the catchment area of Alupe Sub-District Hospital which pose a threat to the rest of the country. Methods This was a case-control study at Alupe Sub-District Hospital, Western Kenya. Sixty one (61) cases and 122 controls were sampled from the facility maternal and child health register by systematic random sampling and traced to their households. Cases were defined as children 12-23 months resident in Kenya who received at least one infant vaccine at the facility but were not fully vaccinated at the time of the study, while controls were children 12-23 months who were fully vaccinated by the time of the study. Pretested structured questionnaires were used for data collection. Data entry and analysis was done using Epi-Info 3.5.4 statistical software. Results Independent determinants of infant vaccination completion were the child's age < 18 months (AOR 4.2(1.8-9.6), p < 0.01), maternal age < 25 years (AOR 2.5(1.1-5.0), p = 0.03), maternal tetanus toxoid vaccination status < 2 TT doses (AOR 2.5(1.2-5.4), p < 0.02) and late receipt of BCG [AOR 3.2(1.4-7.3), p = 0.005). Conclusion Strategies to increase full vaccination should target young mothers especially during antenatal period. PMID:26161200

  2. Antibody-gold cluster conjugates

    DOEpatents

    Hainfeld, J.F.

    1988-06-28

    Antibody- or antibody fragment-gold cluster conjugates are shown wherein the conjugate size can be about 5.0 nm. Methods and reagents are disclosed in which antibodies or Fab' fragments thereof are covalently bound to a stable cluster of gold atoms. 2 figs.

  3. An evaluation of emerging vaccines for childhood meningococcal disease

    PubMed Central

    2011-01-01

    Background Meningococcal meningitis is a major cause of disease worldwide, with frequent epidemics particularly affecting an area of sub-Saharan Africa known as the “meningitis belt”. Neisseria meningitidis group A (MenA) is responsible for major epidemics in Africa. Recently W-135 has emerged as an important pathogen. Currently, the strategy for control of such outbreaks is emergency use of meningococcal (MC) polysaccharide vaccines, but these have a limited ability to induce herd immunity and elicit an adequate immune response in infant and young children. In recent times initiatives have been taken to introduce meningococcal conjugate vaccine in these African countries. Currently there are two different types of MC conjugate vaccines at late stages of development covering serogroup A and W-135: a multivalent MC conjugate vaccine against serogroup A,C,Y and W-135; and a monovalent conjugate vaccine against serogroup A. We aimed to perform a structured assessment of these emerging meningococcal vaccines as a means of reducing global meningococal disease burden among children under 5 years of age. Methods We used a modified CHNRI methodology for setting priorities in health research investments. This was done in two stages. In the first stage we systematically reviewed the literature related to emerging MC vaccines relevant to 12 criteria of interest. In Stage II, we conducted an expert opinion exercise by inviting 20 experts (leading basic scientists, international public health researchers, international policy makers and representatives of pharmaceutical companies). They answered questions from CHNRI framework and their “collective optimism” towards each criterion was documented on a scale from 0 to 100%. Results For MenA conjugate vaccine the experts showed very high level of optimism (~ 90% or more) for 7 out of the 12 criteria. The experts felt that the likelihood of efficacy on meningitis was very high (~ 90%). Deliverability, acceptability to health workers, end users and the effect on equity were all seen as highly likely (~ 90%). In terms of the maximum potential impact on meningitis disease burden, the median potential effectiveness of the vaccines in reduction of overall meningitis mortality was estimated to be 20%; (interquartile range 20-40% and min. 8%, max 50 %). For the multivalent meningococcal vaccines the experts had similar optimism for most of the 12 CHNRI criteria with slightly lower optimism in answerability and low development cost criteria. The main concern was expressed over the cost of product, its affordability and cost of implementation. Conclusions With increasing recognition of the burden of meningococcal meningitis, especially during epidemics in Africa, it is vitally important that strategies are taken to reduce the morbidity and mortality attributable to this disease. Improved MC vaccines are a promising investment that could substantially contribute to reduction of child meningitis mortality world-wide. PMID:21501447

  4. Hacking into the granuloma: could antibody antibiotic conjugates be developed for TB?

    PubMed

    Ekins, Sean

    2014-12-01

    Alternatives to small molecule or vaccine approaches to treating tuberculosis are rarely discussed. Attacking Mycobacterium tuberculosis in the granuloma represents a challenge. It is proposed that the conjugation of small molecules onto a monoclonal antibody that recognizes macrophage or lymphocytes cell surface receptors, might be a way to target the bacteria in the granuloma. This antibody drug conjugate approach is currently being used in 2 FDA approved targeted cancer therapies. The pros and cons of this proposal for further research are discussed. PMID:25287628

  5. Protective T cell immunity in mice following protein-TLR7/8 agonist-conjugate immunization requires aggregation, type I IFN, and multiple DC subsets

    PubMed Central

    Kastenmüller, Kathrin; Wille-Reece, Ulrike; Lindsay, Ross W.B.; Trager, Lauren R.; Darrah, Patricia A.; Flynn, Barbara J.; Becker, Maria R.; Udey, Mark C.; Clausen, Björn E.; Igyarto, Botond Z.; Kaplan, Daniel H.; Kastenmüller, Wolfgang; Germain, Ronald N.; Seder, Robert A.

    2011-01-01

    The success of a non-live vaccine requires improved formulation and adjuvant selection to generate robust T cell immunity following immunization. Here, using protein linked to a TLR7/8 agonist (conjugate vaccine), we investigated the functional properties of vaccine formulation, the cytokines, and the DC subsets required to induce protective multifunctional T cell immunity in vivo. The conjugate vaccine required aggregation of the protein to elicit potent Th1 CD4+ and CD8+ T cell responses. Remarkably, the conjugate vaccine, through aggregation of the protein and activation of TLR7 in vivo, led to an influx of migratory DCs to the LN and increased antigen uptake by several resident and migratory DC subsets, with the latter effect strongly influenced by vaccine-induced type I IFN. Ex vivo migratory CD8–DEC205+CD103–CD326– langerin-negative dermal DCs were as potent in cross-presenting antigen to naive CD8+ T cells as CD11c+CD8+ DCs. Moreover, these cells also influenced Th1 CD4+ T cell priming. In summary, we propose a model in which broad-based T cell–mediated responses upon vaccination can be maximized by codelivery of aggregated protein and TLR7/8 agonist, which together promote optimal antigen acquisition and presentation by multiple DC subsets in the context of critical proinflammatory cytokines. PMID:21540549

  6. Vaccination against helminth parasite infections

    E-print Network

    Vaccination against helminth parasite infections Expert Rev. Vaccines Early online, 1­15 (2014, but the immune system can be driven to expel them by prior vaccination. However, no vaccines are currently available for human use. Recent advances in vaccination with recombinant helminth antigens have been

  7. Development of a Vaccine for Bacterial Kidney Disease in Salmon, 1988 Final Report.

    SciTech Connect

    Kaattari, Stephen L.

    1989-08-01

    Bacterial kidney disease of salmonids is a very complex disease which appears to exploit a variety of pathogenic mechanisms. An understanding of these mechanisms is essential to the development of efficacious vaccines. It has become well established from the studies published .in this report and those of others that soluble antigens which are secreted by Renibacterium salmoninarum have toxigenic potential. If they are found to be responsible for mortality, the development of toxoid(s) could be paramount to the production of a vaccine. One must, however, be circumspect in producing a vaccine. A thorough knowledge, not only of the pathogen, but also of the immune system of the host is an absolute requirement. This becomes of particular importance when dealing with fish diseases, since the field of fish immunology is still within its infancy. This lack of knowledge is particularly felt when the induction of a prophylactic immune response concomitantly leads to pathological side effects which may be as destructive as the original infection. Indeed, it appears that some aspects of BKD may be due to the induction of hypersensitivity reactions. If such immunopathologies are expressed, it is prudent to thoroughly evaluate the nature of the immunoprophylaxis to insure that these harmful sequelae do not occur. Evaluation of a variety of antigens, adjuvants, immune responses, and survival data leads us to recommend that attempts at prophylaxis against BKD should center upon the elicitation of cellular immunity utilizing preparations of Mycobacterium chelonii. The choice of this species of mycobacteria was made because of its effectiveness, ease of maintenance and production, and the lack of need for its propagation within containment facilities. These assets are important to consider if large scale vaccine production is to be profitable. As can be seen from the data provided, M. chelonii alone is capable of producing prophylaxis to BKD, however, this is likely due to the induction of non-specific immunity and not to the existence of crossreactive antigens. Therefore, future studies should be devoted to further work on the induction of specific immunoprophylaxis incorporating this agent.

  8. Spotlight on Tdap? vaccine (Covaxis®) as a single-booster immunization for the prevention of tetanus, diphtheria, and pertussis: in children (aged ?4 years), adolescents, and adults.

    PubMed

    Scott, Lesley J

    2011-04-01

    Covaxis® (also licensed as Triaxis® or Adacel® in individual countries) is a Tdap? (i.e. combined tetanus toxoid, reduced diphtheria toxoid, five component acellular pertussis [namely detoxified pertussis toxin, filamentous hemagglutinin, pertactin, and fimbriae types 2 and 3]) vaccine for the prevention of diphtheria, tetanus, and pertussis. It is approved for use in Europe as a single intramuscular booster dose in children (aged ?4 years), adolescents, and adults, and in the US it is approved for use in individuals aged 11-64 years. In large, randomized, controlled clinical trials conducted in the UK and North America, a single intramuscular booster dose of Covaxis® induced robust immune responses for all of its component antigens when given to children (aged ?4 years), adolescents, and adults. In addition, Covaxis® vaccine was safe and generally well tolerated in terms of solicited and unsolicited local injection-site and systemic adverse events, most of which were of mild intensity and resolved without sequelae. Furthermore, the immunogenicity of each individual component and the reactogenicity of Covaxis® vaccine in children, adolescents, and adults was generally similar to that of comparator vaccines. Despite being a vaccine-preventable disease and having >90% primary vaccination coverage worldwide, pertussis remains uncontrolled, particularly amongst adolescents and adults. Given the changing epidemiology of pertussis and the requirement to reduce infection in adolescents and adults (including healthcare workers) and thereby prevent transmission of the disease from these individuals to very young infants, the new 'cocoon strategy' recommended in current vaccination guidelines has become a key strategy in the management of morbidity and mortality associated with pertussis. This strategy focuses on the immunization of healthcare workers, and the parents and family members of infants who are too young to have undergone primary immunization, so as to prevent the transmission of pertussis to these young at-risk infants. The implementation of the 'cocoon strategy' may finally give countries the ability to control pertussis infections in these at-risk infants and ultimately provide the desired herd immunity against pertussis. In line with this strategy, a booster dose of Covaxis® vaccine provides a valuable option to reduce pertussis morbidity and mortality, and to maintain seroprotection against diphtheria and tetanus in children (aged ?4 years), adolescents, and adults. PMID:21351814

  9. The Danish vaccination register.

    PubMed

    Grove Krause, T; Jakobsen, S; Haarh, M; Mølbak, K

    2012-01-01

    Immunisation information systems (IIS) are valuable tools for monitoring vaccination coverage and for estimating vaccine effectiveness and safety. Since 2009, an advanced IIS has been developed in Denmark and will be implemented during 2012–14. This IIS is based on a database existing since 2000. The reporting of all administered vaccinations including vaccinations outside the national programme will become mandatory. Citizens will get access to data about their own vaccinations and healthcare personnel will get access to information on the vaccinations of their patients. A national concept of identification, a national solution combining a personal code and a card with codes, ensures easy and secure access to the register. From the outset, the IIS will include data on childhood vaccinations administered from 1996 and onwards. All Danish citizens have a unique identifier, a so called civil registration number, which allows the linking of information on vaccinations coming from different electronic data sources. The main challenge will be to integrate the IIS with the different electronic patient record systems currently existing at general practitioner, vaccination clinic and hospital level thereby avoiding double-entry. A need has been identified for an updated international classification of vaccine products on the market. Such a classification would also be useful for the future exchange of data on immunisations from IIS between countries. PMID:22551494

  10. Current Ebola vaccines

    PubMed Central

    Hoenen, Thomas; Groseth, Allison; Feldmann, Heinz

    2012-01-01

    Introduction Ebolaviruses cause severe viral hemorrhagic fever in humans and non-human primates, with case fatality rates of up to 90%. Currently, neither a specific treatment nor a vaccine licensed for use in humans is available. However, a number of vaccine candidates have been developed in the last decade that are highly protective in non-human primates, the gold standard animal model for Ebola hemorrhagic fever. Areas covered This review analyzes a number of scenarios for the use of ebolavirus vaccines, discusses the requirements for ebolavirus vaccines in these scenarios, and describes current ebolavirus vaccines. Among these vaccines are recombinant Adenoviruses, recombinant Vesicular Stomatitis viruses, recombinant Human Parainfluenza viruses and virus-like particles. Interestingly, one of these vaccine platforms, based on recombinant Vesicular Stomatitis viruses, has also demonstrated post-exposure protection in non-human primates. Expert opinion The most pressing remaining challenge is now to move these vaccine candidates forward into human trials and towards licensure. In order to achieve this, it will be necessary to establish the mechanisms and correlates of protection for these vaccines, and to continue to demonstrate their safety, particularly in potentially immunocompromised populations. However, already now there is sufficient evidence that, from a scientific perspective, a vaccine protective against ebolaviruses is possible. PMID:22559078

  11. The post-vaccine microevolution of invasive Streptococcus pneumoniae

    PubMed Central

    Cremers, Amelieke J. H.; Mobegi, Fredrick M.; de Jonge, Marien I.; van Hijum, Sacha A. F. T.; Meis, Jacques F.; Hermans, Peter W. M.; Ferwerda, Gerben; Bentley, Stephen D.; Zomer, Aldert L.

    2015-01-01

    The 7-valent pneumococcal conjugated vaccine (PCV7) has affected the genetic population of Streptococcus pneumoniae in pediatric carriage. Little is known however about pneumococcal population genomics in adult invasive pneumococcal disease (IPD) under vaccine pressure. We sequenced and serotyped 349 strains of S. pneumoniae isolated from IPD patients in Nijmegen between 2001 and 2011. Introduction of PCV7 in the Dutch National Immunization Program in 2006 preluded substantial alterations in the IPD population structure caused by serotype replacement. No evidence could be found for vaccine induced capsular switches. We observed that after a temporary bottleneck in gene diversity after the introduction of PCV7, the accessory gene pool re-expanded mainly by genes already circulating pre-PCV7. In the post-vaccine genomic population a number of genes changed frequency, certain genes became overrepresented in vaccine serotypes, while others shifted towards non-vaccine serotypes. Whether these dynamics in the invasive pneumococcal population have truly contributed to invasiveness and manifestations of disease remains to be further elucidated. We suggest the use of whole genome sequencing for surveillance of pneumococcal population dynamics that could give a prospect on the course of disease, facilitating effective prevention and management of IPD. PMID:26492862

  12. Cutaneous reactions to vaccinations.

    PubMed

    Rosenblatt, Adena E; Stein, Sarah L

    2015-01-01

    Vaccinations are important for infectious disease prevention; however, there are adverse effects of vaccines, many of which are cutaneous. Some of these reactions are due to nonspecific inflammation and irritation at the injection site, whereas other reactions are directly related to the live attenuated virus. Rarely, vaccinations have been associated with generalized hypersensitivity reactions, such as erythema multiforme, Stevens-Johnson syndrome, urticaria, acute generalized exanthematous pustulosis, and drug hypersensitivity syndrome. The onset of certain inflammatory dermatologic conditions, such as lichen planus, granuloma annulare, and pemphigoid, were reported to occur shortly after vaccine administration. Allergic contact dermatitis can develop at the injection site, typically due to adjuvant ingredients in the vaccine, such as thimerosal and aluminum. Vaccinations are important to promote development of both individual and herd immunity. Although most vaccinations are considered relatively safe, there may be adverse effects associated with any vaccine. Cutaneous manifestations make up a large portion of the types of reactions associated with vaccines. There are many different reasons for the development of a cutaneous reaction to a vaccination. Some are directly related to the injection of a live attenuated virus, such as varicella or vaccinia (for immunity to smallpox), whereas others cause more nonspecific erythema and swelling at the injection site, as a result of local inflammation or irritation. Vaccinations have also been associated in rare reports with generalized hypersensitivity reactions, such as erythema multiforme, Stevens-Johnson syndrome, urticaria, acute generalized exanthematous pustulosis, and drug hypersensitivity syndrome. There have been case reports associating the administration of a vaccine with the new onset of a dermatologic condition, such as lichen planus, granuloma annulare, and Sweet syndrome. Finally, allergic contact dermatitis can develop at the injection site, typically due to adjuvant ingredients in the vaccine, such as thimerosal and aluminum. PMID:25889134

  13. Varicella vaccination in children.

    PubMed

    Clements, D A

    2000-07-01

    Varicella vaccines have been developed, studied, tested and used since the early 1970s, first in Japan and subsequently in Europe, the US, Asia and South and Central America. Varicella vaccination was first used to immunise Japanese children in cancer remission, as wild-type varicella disease is often fatal in immunocompromised individuals. Since then, it has been licensed for use in healthy children as well. There are 3 manufacturers of the vaccine: Biken (Japan), Merck and Co. (US) and SmithKline Beecham (Belgium). The Biken vaccine has been approved for use in Japan since 1986 (although it was developed and used for research purposes from 1974). The Merck and Co. vaccine was approved in the US in March 1995 and the SmithKline Beecham vaccine was first licensed for use in immunocompromised children in 1984 and for healthy children in Sweden in October 1994. All 3 vaccines are derived from the Oka (Japanese) strain obtained from an immunologically normal 3-year-old Japanese boy named Oka with wild-type disease. Aventis-Pasteur has also purchased the rights to the Oka strain but no published literature is available for review. Use of the varicella vaccine has been controversial because many argue that: (i) the disease is mild and not worth preventing; (ii) the long term immunity provided by the vaccine is unknown; and (iii) the average age of those with the disease will increase if the vaccine is used and hence there will be more complications in older patients and, therefore, more costs. Because of some outbreaks of secondary bacterial infections after varicella in children in US day care centres, vaccination of healthy children is required in some states. It will be interesting to see whether other countries adopt a similar recommendation as more families have 2 working parents. The financial benefit of the vaccine (keeping parents at work) may encourage more use of the vaccine and a subsequent recommendation for immunisation schedules. PMID:18034555

  14. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ...Medicare Part B pays for pneumococcal vaccine and its administration when reasonable...the prevention of disease, if the vaccine is ordered by a doctor of medicine...Medicare Part B pays for the influenza virus vaccine and its administration....

  15. 42 CFR 410.57 - Pneumococcal vaccine and flu vaccine.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ...Medicare Part B pays for pneumococcal vaccine and its administration when reasonable...the prevention of disease, if the vaccine is ordered by a doctor of medicine...Medicare Part B pays for the influenza virus vaccine and its administration....

  16. 75 FR 48712 - Proposed Vaccine Information Materials for Influenza Vaccine

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-11

    ...as interim influenza Vaccine Information Statements...2010-11 influenza vaccine until final materials are effective and available for distribution...Interim) Influenza Vaccine Information Statements...caused by the influenza virus, which can be...

  17. Vaccination uptake by vaccine-hesitant parents attending a specialist immunization clinic in Australia.

    PubMed

    Forbes, Thomas A; McMinn, Alissa; Crawford, Nigel; Leask, Julie; Danchin, Margie

    2015-12-01

    Vaccine hesitancy (VH) is an issue of global concern. The quality of communication between healthcare providers and parents can influence parental immunization acceptance. We aimed to describe immunization uptake following specialist immunization clinic (SIC) consultation for Australian children of VH parents as a cohort, and according to pre-clinic parental position on immunization. At a single tertiary pediatric SIC (RCH, Melbourne) a retrospective descriptive study classified VH families according to 3 proposed parental positions on immunization at initial clinic attendance. Immunization status at follow up was ascertained via the Australian Children's Immunization Register and National HPV Program Register and compared between groups. Of the VH cohort, 13/38 (34%) families were classified as hesitant, 21 (55%) as late/selective vaccinators and 4 (11%) as vaccine refusers. Mean follow up post-SIC attendance was 14.5 months. For the overall VH cohort, the majority chose selective immunization (42%) following SIC consultation. When analyzed by pre-clinic parental position on immunization, there was a trend for hesitant families to proceed with full immunization, selective families to continue selective immunization and refusing families to remain unimmunised (p < 0.0001). The most commonly omitted vaccines were hepatitis B (66%) and Haemophilus influenzae type B (55%), followed by the meningococcal C conjugate vaccine (53%) and measles, mumps and rubella vaccine (53%). Immunization outcome appears to correlate with pre-clinic parental position on immunization for the majority of families attending a SIC in Australia, with selective immunization the most common outcome. Tailored communication approaches based on parental position on immunization may optimise clinic resources and engagement of families, but require prospective research evaluation. PMID:26366978

  18. Tetanus toxoid-loaded layer-by-layer nanoassemblies for efficient systemic, mucosal, and cellular immunostimulatory response following oral administration.

    PubMed

    Harde, Harshad; Agrawal, Ashish Kumar; Jain, Sanyog

    2015-10-01

    The present study reports the tetanus toxoid (TT)-loaded layer-by-layer nanoassemblies (layersomes) with enhanced protection, permeation, and presentation for comprehensive oral immunization. The stable and lyophilized TT-loaded layersomes were prepared by a thin-film hydration method followed by alternate layer-by-layer coating of an electrolyte. The developed system was assessed for in vitro stability of antigen and formulation, cellular uptake, ex vivo intestinal uptake, and immunostimulatory response using a suitable experimental protocol. Layersomes improved the stability in simulated biological media as well as protected the integrity/conformation and native 3D structure of TT as confirmed by sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE), circular dichroism (CD), and fluorescence spectroscopy, respectively. The cell culture studies demonstrated a 3.8-fold higher permeation of layersomes in Caco-2 cells and an 8.5-fold higher uptake by antigen-presenting cells (RAW 264.7). The TT-loaded layersomes elicited a complete immunostimulatory profile consisting of higher systemic (serum IgG titer), mucosal (sIgA titer), and cellular (interleukin-2 (IL-2) and interferon-? (IFN-?) levels) immune response after peroral administration in mice. The modified TT inhibition assay further confirmed the elicitation of complete protective levels of anti-TT antibody (>0.1 IU/mL) by layersomes. In conclusion, the proposed strategy is expected to contribute significantly in the field of stable liposome technology for mass immunization through the oral route. PMID:26195222

  19. [Vaccines and preventive activities in patients with inflammatory arthritis].

    PubMed

    Casals-Sánchez, J L; Casals Vázquez, C; Vázquez Sánchez, M Á; Giménez Basallote, S

    2013-10-01

    Patients with inflammatory arthritis and eligible for immunosuppressive therapy account for more than 1% of general population, and represents a significant workload on family doctors. They are prone to other comorbidities, with an increased cardiovascular risk and a higher incidence of infections than the general population, especially skin infections and pneumonitis. This comorbidity can be considered vulnerable to a prevention program-prevention of cardiovascular risk, cancer screening, vaccination schedule for adults. As for prevention through vaccination, importance should be given to pneumococcal infection - significant in adults aged 50 or over, especially amongst immunosuppressed patients. The 13-valent conjugate vaccine, which has been recently approved for adults, must be considered. An attempt has been made to write a simple, applicable document on preventive measures that should be implemented both at primary and secondary care level for those adults. PMID:24095166

  20. The costs and effectiveness of large Phase III pre-licensure vaccine clinical trials.

    PubMed

    Black, Steven

    2015-12-01

    Prior to the 1980s, most vaccines were licensed based upon safety and effectiveness studies in several hundred individuals. Beginning with the evaluation of Haemophilus influenzae type b conjugate vaccines, much larger pre-licensure trials became common. The pre-licensure trial for Haemophilus influenzae oligosaccharide conjugate vaccine had more than 60,000 children and that of the seven-valent pneumococcal conjugate vaccine included almost 38,000 children. Although trial sizes for both of these studies were driven by the sample size required to demonstrate efficacy, the sample size requirements for safety evaluations of other vaccines have subsequently increased. With the demonstration of an increased risk of intussusception following the Rotashield brand rotavirus vaccine, this trend has continued. However, routinely requiring safety studies of 20,000-50,000 or more participants has two major downsides. First, the cost of performing large safety trials routinely prior to licensure of a vaccine is very large, with some estimates as high at US$200 million euros for one vaccine. This high financial cost engenders an opportunity cost whereby the number of vaccines that a company is willing or able to develop to meet public health needs becomes limited by this financial barrier. The second downside is that in the pre-licensure setting, such studies are very time consuming and delay the availability of a beneficial vaccine substantially. One might argue that in some situations, this financial commitment is warranted such as for evaluations of the risk of intussusception following newer rotavirus vaccines. However, it must be noted that while an increased risk of intussusception was not identified in large pre-licensure studies, in post marketing evaluations an increased risk of this outcome has been identified. Thus, even the extensive pre-licensure evaluations conducted did not identify an associated risk. The limitations of large Phase III trials have also been demonstrated in efficacy trials. Notably, pre-licensure trials of pneumococcal conjugate severely underestimated their true effect and cost-effectiveness. In fact, in discussions prior to vaccine introduction in the USA for PCV7, the vaccine was said to be not cost-effective and some counseled against its introduction. In reality, following introduction, PCV7 has been shown to be highly cost-effective. In the last decade, new methods have been identified using large linked databases such as the Vaccine Safety Datalink in the USA that allow identification of an increased risk of an event within a few months of vaccine introduction and that can screen for unanticipated very rare events as well. In addition, the availability of electronic medical records and hospital discharge data in many settings allows for accurate assessment of vaccine effectiveness. Given the high financial and opportunity cost of requiring large pre-licensure safety studies, consideration could be given to 'conditional licensure' of vaccines whose delivery system is well characterized in a setting where sophisticated pharmacovigilance systems exist on the condition that such licensure would incorporate a requirement for rapid cycle and other real-time evaluations of safety and effectiveness following introduction. This would actually allow for a more complete and timely evaluation of vaccines, lower the financial barrier to development of new vaccines and thus allow a broader portfolio of vaccines to be developed and successfully introduced. PMID:26414015

  1. Human prophylactic vaccine adjuvants and their determinant role in new vaccine formulations

    PubMed Central

    Pérez, O.; Batista-Duharte, A.; González, E.; Zayas, C.; Balboa, J.; Cuello, M.; Cabrera, O.; Lastre, M.; Schijns, V.E.J.C.

    2012-01-01

    Adjuvants have been considered for a long time to be an accessory and empirical component of vaccine formulations. However, accumulating evidence of their crucial role in initiating and directing the immune response has increased our awareness of the importance of adjuvant research in the past decade. Nevertheless, the importance of adjuvants still is not fully realized by many researchers working in the vaccine field, who are involved mostly in the search for better target antigens. The choice of a proper adjuvant can be determinant for obtaining the best results for a given vaccine candidate, but it is restricted due to intellectual property and know-how issues. Consequently, in most cases the selected adjuvant continues to be the aluminum salt, which has a record of safety, but predominantly constitutes a delivery system (DS). Ideally, new strategies should combine immune potentiators (IP) and DS by mixing both compounds or by obtaining structures that contain both IP and DS. In addition, the term immune polarizer has been introduced as an essential concept in the vaccine design strategies. Here, we review the theme, with emphasis on the discussion of the few licensed new adjuvants, the need for safe mucosal adjuvants and the adjuvant/immunopotentiating activity of conjugation. A summary of toxicology and regulatory issues will also be discussed, and the Finlay Adjuvant Platform is briefly summarized. PMID:22527130

  2. Liver Disease and Adult Vaccination

    MedlinePLUS

    ... Resources for Healthcare Professionals Liver Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  3. What Vaccinations Do You Need?

    MedlinePLUS

    ... Newsroom Contact Us You are here Home » What Vaccinations Do You Need? A Guide for Adults with ... a Kidney Transplant Why do I need a vaccination? Vaccinations, usually given as a shot, protect you ...

  4. Renal Disease and Adult Vaccination

    MedlinePLUS

    ... Resources for Healthcare Professionals Renal Disease and Adult Vaccination Recommend on Facebook Tweet Share Compartir Vaccines are ... have immunity to this disease Learn about adult vaccination and other health conditions Asplenia Diabetes Type 1 ...

  5. Pneumococcal Vaccination: Who Needs It?

    MedlinePLUS

    ... CDC.gov . Vaccines and Immunizations Share Compartir Pneumococcal Vaccination: Who Needs It? There are currently 2 types ... doses will depend on the child's age when vaccination begins. Ask your healthcare provider for details. Children ...

  6. Vaccinations for Adults with Diabetes

    MedlinePLUS

    ... t had this vaccine previously. Tetanus, diphtheria, and whooping cough (pertussis) (Tdap, Td) Yes! All adults need to get Tdap vaccine (the adult whooping cough vaccine) and women need to get a dose ...

  7. Tetanus, Diphtheria, Pertussis (Tdap) Vaccine

    MedlinePLUS

    ... or sneezing. Tetanus enters the body through cuts, scratches, or wounds. Before vaccines, the United States saw ... Vaccine Injury Compensation ProgramThe National Vaccine Injury Compensation Program (VICP) is a federal program that was created ...

  8. Vaccine Treatment for Prostate Cancer

    MedlinePLUS

    ... Preventing and treating prostate cancer spread to bones Vaccine treatment for prostate cancer Sipuleucel-T (Provenge ® ) is ... less advanced prostate cancer. Possible side effects of vaccine treatment Side effects from the vaccine tend to ...

  9. List of Vaccine-Preventable Diseases

    MedlinePLUS

    ... gov . Vaccines and Immunizations Share Compartir List of Vaccine-Preventable Diseases The following links will lead you ... page that describes both the disease and the vaccine(s). Vaccines are available for all of the following ...

  10. Response to the Critique of "New Meningococcal Vaccine Recommendations under Consideration"

    ERIC Educational Resources Information Center

    Turner, James C.

    2005-01-01

    The CDC recently published the ACIP recommendations regarding the use of meningococcal conjugate vaccine. The report includes detailed epidemiologic and cost analysis information. At the conclusion of lengthy discussions, the ACIP voted unanimously to approve the recommendation as written. In this article, the author provides his counterreaction…

  11. Vaccination against pneumococcus in West Africa: perspectives and prospects

    PubMed Central

    Donkor, Eric S; Dayie, Nicholas TKD; Badoe, Ebenezer V

    2013-01-01

    Background Pneumococcal vaccination has become obligatory due to the enormous burden of pneumococcal diseases. Quite recently, pneumococcal conjugate vaccines have been developed, and have been shown to be superior to the previous polyvalent polysaccharide vaccine of the organism. Pneumococcal conjugate vaccines (PCVs) are being introduced in many West African countries and it is important to understand the expected performance, relevance, and limitations of these vaccines in the subregion. Aim The objective of the study presented here was to provide epidemiological insights into PCVs in West Africa based on the prevailing pneumococcal serotypes in the subregion. Methods A systematic review was carried out on pneumococcal serotypes causing invasive and noninvasive diseases in West Africa. Studies included in the review were those that reported at least 20 serotyped pneumococcal isolates and which were conducted prior to the introduction of PCVs in the region in 2009. The proportion of pneumococcal disease associated with each serotype as well as the serotype coverage of various PCVs (PCV7, PCV10, and PCV13) were calculated. Results The data covered 718 serotyped pneumococcal isolates from six West African countries: Burkina Faso, Ghana, Nigeria, Mali, Senegal, and The Gambia. The 718 isolates covered more than 20 serotypes. Serotype 1 was the most prevalent serotype (32%), followed by serotype 5 (15%), serotype 6 (7%), serotype 2 (6%), serotype 3 (6%), and serotype 12 (5%). The estimated serotype coverage of PCVs among the West African countries was 2%–36% for PCV7, 39%–80% for PCV10, and 65%–87% for PCV13. Conclusion A pneumococcal capsular vaccine