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

    PubMed Central

    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

  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. Enhanced immunogenicity of a tricomponent mannan tetanus toxoid conjugate vaccine targeted to dendritic cells via Dectin-1 by incorporating ?-glucan.

    PubMed

    Lipinski, Tomasz; Fitieh, Amira; St Pierre, Joëlle; Ostergaard, Hanne L; Bundle, David R; Touret, Nicolas

    2013-04-15

    In a previous attempt to generate a protective vaccine against Candida albicans, a ?-mannan tetanus toxoid conjugate showed poor immunogenicity in mice. To improve the specific activation toward the fungal pathogen, we aimed to target Dectin-1, a pattern-recognition receptor expressed on monocytes, macrophages, and dendritic cells. Laminarin, a ?-glucan ligand of Dectin-1, was incorporated into the original ?-mannan tetanus toxoid conjugate providing a tricomponent conjugate vaccine. A macrophage cell line expressing Dectin-1 was employed to show binding and activation of Dectin-1 signal transduction pathway by the ?-glucan-containing vaccine. Ligand binding to Dectin-1 resulted in the following: 1) activation of Src family kinases and Syk revealed by their recruitment and phosphorylation in the vicinity of bound conjugate and 2) translocation of NF-?B to the nucleus. Treatment of immature bone marrow-derived dendritic cells (BMDCs) with tricomponent or control vaccine confirmed that the ?-glucan-containing vaccine exerted its enhanced activity by virtue of dendritic cell targeting and uptake. Immature primary cells stimulated by the tricomponent vaccine, but not the ?-mannan tetanus toxoid vaccine, showed activation of BMDCs. Moreover, treated BMDCs secreted increased levels of several cytokines, including TGF-? and IL-6, which are known activators of Th17 cells. Immunization of mice with the novel type of vaccine resulted in improved immune response manifested by high titers of Ab recognizing C. albicans ?-mannan Ag. Vaccine containing laminarin also affected distribution of IgG subclasses, showing that vaccine targeting to Dectin-1 receptor can benefit from augmentation and immunomodulation of the immune response. PMID:23514738

  5. Comparison of the Safety and Immunogenicity of a Novel Quadrivalent Meningococcal ACWY-Tetanus Toxoid Conjugate Vaccine and a Marketed Quadrivalent Meningococcal ACWY-Diphtheria Toxoid Conjugate Vaccine in Healthy Individuals 10–25 Years of Age

    PubMed Central

    Halperin, Scott A.; Baine, Yaela; Domachowske, Joseph B.; Aggarwal, Naresh; Simon, Michael; Langley, Joanne M.; McNeil, Shelly A.; Friedland, Leonard R.; Bianco, Veronique; Baccarini, Carmen I.; Miller, Jacqueline M.

    2014-01-01

    Background Universal immunization of adolescents against meningococcal disease with a quadrivalent meningococcal ACWY (MenACWY) conjugate vaccine is recommended in a number of countries. Methods In a randomized, controlled, observer-blinded, multicenter trial, 1016 participants, 10–25 years of age, were randomly allocated 1:1:1 to receive a single dose of 1 of 2 lots of an investigational tetanus toxoid?conjugated MenACWY vaccine (MenACWY?TT) or a marketed diphtheria toxoid?conjugated MenACWY vaccine (MenACWY?DT). The primary outcome was the noninferiority of the vaccine response after MenACWY?TT (lot A) compared with MenACWY?DT for all 4 serogroups. Vaccine response was defined as a postvaccination human serum bactericidal antibody (hSBA) titer against each of the serogroups of at least 1:8 in persons initially seronegative (<1:4) or as a 4?fold increase in titer pre? to postvaccination in persons initially seropositive (?1:4). Adverse events (AEs) after immunization were measured 4 and 31 days postvaccination. Results The mean age of participants was 16.3 years; 977 (96.6%) completed the study. The noninferiority of MenACWY?TT (lot A) to the control vaccine in terms of the percentage of participants with hSBA vaccine response was demonstrated for each serogroup. Vaccine response rates ranged from 51.0% to 82.5% for the 4 serogroups after MenACWY?TT (both lots) compared with 39.0%–76.3% for the 4 serogroups after MenACWY?DT. Pain was the most common injection?site reaction reported by 50.8%–55.4% across the 3 groups. Fatigue and headache were the most common systemic solicited AEs, reported by 27.3%–29.2% and 25.5%–26.4%, respectively. Conclusions Tetanus toxoid?conjugated MenACWY vaccine was well tolerated and elicited an immune response that was noninferior to that of a marketed MenACWY?DT (www.clinicaltrials.gov NCT01165242). PMID:24567843

  6. Murine Immune Responses to Neisseria meningitidis Group C Capsular Polysaccharide and a Thymus-Dependent Toxoid Conjugate Vaccine

    PubMed Central

    Rubinstein, Leonard J.; García-Ojeda, Pablo A.; Michon, Francis; Jennings, Harold J.; Stein, Kathryn E.

    1998-01-01

    The polysaccharide (PS) capsules of many pathogenic bacteria are poor immunogens in infants and young children as a result of the delayed response to PS antigens during ontogeny. The development of polysaccharide-protein conjugate vaccines for Haemophilus influenzae type b, which have proven to be efficacious in this age group, has led to active development by a number of investigators of conjugate vaccines for other diseases. We describe here the response of several mouse strains to the capsular PS of Neisseria meningitidis group C (MCPS) conjugated to tetanus toxoid (MCPS-TT) and the same response in BALB/c mice as a model of the immune consequences of conjugate vaccine immunization. The use of a conjugate vaccine results in a shift in the isotype elicited in response to the MCPS, from immunoglobulin M (IgM) and IgG3 to primarily IgG1. A response to MCPS-TT is seen even among mouse strains which respond poorly to MCPS itself, emphasizing the importance of a strain survey when choosing a mouse model for a vaccine. The marked increase in IgG1 antibody titer was accompanied by a large increase in bactericidal activity of sera from these animals. Animals primed with the conjugate vaccine demonstrated a booster response after secondary immunization with either the MCPS or the conjugate. The ability to produce a boosted IgG1 anti-MCPS response to the MCPS can be transferred to adoptive recipients by B cells alone from mice primed with MCPS-TT but not mice primed with MCPS alone. These data indicate that in BALB/c mice a single immunization with MCPS-TT is sufficient to induce a shift to IgG1 and generate a memory B-cell population that does not require T cells for boosting. PMID:9784556

  7. Meningococcal groups C and Y and haemophilus B tetanus toxoid conjugate vaccine (HibMenCY-TT; MenHibrix(®)): a review.

    PubMed

    Perry, Caroline M

    2013-05-01

    The meningococcal groups C and Y and Haemophilus b (Hib) tetanus toxoid conjugate vaccine (HibMenCY-TT) contains Neisseria meningitidis serogroup C and Y capsular polysaccharide antigens, and Hib capsular polysaccharide [polyribosyl-ribitol-phosphate (PRP)]. The HibMenCY-TT vaccine is available in the USA for use as active immunization to prevent invasive disease caused by N. meningitidis serogroups C (MenC) and Y (MenY), and Hib in children 6 weeks-18 months of age. HibMenCY-TT is the first meningococcal vaccine available for use in the USA that can be administered to infants as young as 6 weeks of age. In a randomized, controlled, phase III clinical trial, the HibMenCY-TT vaccine, administered to infants at 2, 4, 6 and 12-15 months of age, was immunogenic against MenC and MenY, and met the prespecified criteria for immunogenicity. Anti-PRP antibodies, which have been shown to correlate with protection against Hib invasive disease, were also induced in the infants who received the HibMenCY-TT vaccine, with induced levels of this antibody noninferior to those occurring in the control group of infants who received a Hib tetanus toxoid conjugate vaccine at 2, 4, and 6 months and a single dose of Hib conjugated to N. meningitidis outer membrane protein at 12-15 months. In several randomized, controlled clinical trials, HibMenCY-TT was coadministered with vaccines that are routinely administered to infants and toddlers in the USA. These vaccines included: diphtheria and tetanus toxoids and acellular pertussis adsorbed, hepatitis B (recombinant) and inactivated poliovirus vaccine combined; 7-valent Streptococcus pneumoniae polysaccharide conjugate vaccine; measles, mumps and rubella vaccine; and varicella vaccine. Coadministration of these vaccines did not interfere with the immunogenicity of the HibMenCY-TT vaccine. Similarly, immune responses to the coadministered vaccines were not affected by the HibMenCY-TT vaccine. The tolerability profile of the HibMenCY-TT vaccine in infants and toddlers in the phase III trial was considered to be clinically acceptable and comparable to that of the Hib conjugate vaccines received by the control group. PMID:23649970

  8. Immunogenicity of meningococcal quadrivalent (serogroup A, C, W135 and Y) tetanus toxoid conjugate vaccine: systematic review and meta-analysis.

    PubMed

    Pellegrino, Paolo; Perrone, Valentina; Radice, Sonia; Capuano, Annalisa; Clementi, Emilio

    2015-02-01

    Meningococcal meningitis represents one of the leading cause of bacterial meningitis in developed countries. Among the thirteen described serogroups, only five are usually responsible of invasive infections making immunisation against multiple serogroups the best strategy to protect individuals from this disease. Herein we carried out a systematic review and meta-analysis, in accordance with the PRISMA statement, of the recently EU-licensed meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT). We included 15 randomised clinical trials, comparing MenACWY-TT and Men-PS (ten studies), MenACWY-TT and MenC-CRM197 (four studies) and MenACWY-TT and MenACWY-DT (one study). All studies included in the meta-analysis showed high immunogenicity for MenACWY-TT vaccines in all tested serogroups. Our results suggest that the MenACWY-TT vaccine is as immunogenic as the other commercial available meningococcal vaccines. PMID:25447792

  9. Comparison of CRM197, diphtheria toxoid and tetanus toxoid as protein carriers for meningococcal glycoconjugate vaccines.

    PubMed

    Tontini, M; Berti, F; Romano, M R; Proietti, D; Zambonelli, C; Bottomley, M J; De Gregorio, E; Del Giudice, G; Rappuoli, R; Costantino, P; Brogioni, G; Balocchi, C; Biancucci, M; Malito, E

    2013-10-01

    Glycoconjugate vaccines are among the most effective and safest vaccines ever developed. Diphtheria toxoid (DT), tetanus toxoid (TT) and CRM197 have been mostly used as protein carriers in licensed vaccines. We evaluated the immunogenicity of serogroup A, C, W-135 and Y meningococcal oligosaccharides conjugated to CRM197, DT and TT in naïve mice. The three carriers were equally efficient in inducing an immune response against the carbohydrate moiety in immunologically naïve mice. The effect of previous exposure to different dosages of the carrier protein on the anti-carbohydrate response was studied using serogroup A meningococcal (MenA) saccharide conjugates as a model. CRM197 showed a strong propensity to positively prime the anti-carbohydrate response elicited by its conjugates or those with the antigenically related carrier DT. Conversely in any of the tested conditions TT priming did not result in enhancement of the anti-carbohydrate response elicited by the corresponding conjugates. Repeated exposure of mice to TT or to CRM197 before immunization with the respective MenA conjugates resulted in a drastic suppression of the anti-carbohydrate response in the case of TT conjugate and only in a slight reduction in the case of CRM197. The effect of carrier priming on the anti-MenA response of DT-based conjugates varied depending on their carbohydrate to protein ratio. These data may have implications for human vaccination since conjugate vaccines are widely used in individuals previously immunized with DT and TT carrier proteins. PMID:23965218

  10. 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

  11. Efficacy, but Not Antibody Titer or Affinity, of a Heroin Hapten Conjugate Vaccine Correlates with Increasing Hapten Densities on Tetanus Toxoid, but Not on CRM197 Carriers.

    PubMed

    Jalah, Rashmi; Torres, Oscar B; Mayorov, Alexander V; Li, Fuying; Antoline, Joshua F G; Jacobson, Arthur E; Rice, Kenner C; Deschamps, Jeffrey R; Beck, Zoltan; Alving, Carl R; Matyas, Gary R

    2015-06-17

    Vaccines against drugs of abuse have induced antibodies in animals that blocked the biological effects of the drug by sequestering the drug in the blood and preventing it from crossing the blood-brain barrier. Drugs of abuse are too small to induce antibodies and, therefore, require conjugation of drug hapten analogs to a carrier protein. The efficacy of these conjugate vaccines depends on several factors including hapten design, coupling strategy, hapten density, carrier protein selection, and vaccine adjuvant. Previously, we have shown that 1 (MorHap), a heroin/morphine hapten, conjugated to tetanus toxoid (TT) and mixed with liposomes containing monophosphoryl lipid A [L(MPLA)] as adjuvant, partially blocked the antinociceptive effects of heroin in mice. Herein, we extended those findings, demonstrating greatly improved vaccine induced antinociceptive effects up to 3% mean maximal potential effect (%MPE). This was obtained by evaluating the effects of vaccine efficacy of hapten 1 vaccine conjugates with varying hapten densities using two different commonly used carrier proteins, TT and cross-reactive material 197 (CRM197). Immunization of mice with these conjugates mixed with L(MPLA) induced very high anti-1 IgG peak levels of 400-1500 ?g/mL that bound to both heroin and its metabolites, 6-acetylmorphine and morphine. Except for the lowest hapten density for each carrier, the antibody titers and affinity were independent of hapten density. The TT carrier based vaccines induced long-lived inhibition of heroin-induced antinociception that correlated with increasing hapten density. The best formulation contained TT with the highest hapten density of ?30 haptens/TT molecule and induced %MPE of approximately 3% after heroin challenge. In contrast, the best formulation using CRM197 was with intermediate 1 densities (10-15 haptens/CRM197 molecule), but the %MPE was approximately 13%. In addition, the chemical synthesis of 1, the optimization of the conjugation method, and the methods for the accurate quantification of hapten density are described. PMID:25970207

  12. Immunological evaluation of meningococcal group C polysaccharide-tetanus toxoid conjugate in mice.

    PubMed Central

    Beuvery, E C; van Delft, R W; Miedema, F; Kanhai, V; Nagel, J

    1983-01-01

    Neisseria meningitidis group C polysaccharide-tetanus toxoid conjugate was prepared to obtain the polysaccharide component in a thymus-dependent form and to preserve the immunogenic properties of the tetanus toxoid component. Biochemical and immunochemical analyses of this conjugate revealed that (i) it was composed of equal amounts of polysaccharide and protein; (ii) the antigenic activity of the polysaccharide component was greatly reduced; (iii) it contained about 10% free polysaccharide; (iv) the composition was not homogeneous; and (v) only 5% of the tetanus toxoid component was present at the surface of the conjugate molecules. In this study, the influence of these characteristics on the antibody response to both components in mice was investigated. The dose-response relationship, the persistence of antibodies, a possible antigenic competition, and the specificities of the antibodies induced were also studied. Our data suggest that the conjugate behaves as a pronounced thymus-dependent antigen, that the tetanus toxoid component is more immunogenic at lower dosages (0.8 and 20 ng) than equivalent doses of tetanus vaccine, that the presence of free polysaccharide does not influence the induction of antibodies to polysaccharide by the conjugate, and that no antibodies to new structures in the conjugate are induced. These characteristics favor the application of this conjugate as a vaccine for human use. PMID:6409811

  13. Safety and immunogenocity of a novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine in healthy Chinese children aged 6 months to 5 years old.

    PubMed

    Hu, Jian-Li; Tao, Hong; Li, Jing-Xin; Dai, Wei-Ming; Song, Bin; Sun, Jin-Fang; Liu, Pei; Tang, Jie; Liu, Wen-Yu; Wang, Shi-Yuan; Zhu, Feng-Cai

    2015-05-01

    A novel combined Haemophilus influenzae type b-Neisseria meningitidis serogroups A and C-tetanus-toxoid conjugate vaccine (Hib-MenAC vaccine) has been developed to protect children against diseases caused by Hib, MenA, and MenC. This study investigated the safety and immunogenicity of the Hib-MenAC vaccine administered in 2-dose series to children aged 6-23 months and in a single dose to children aged 2-5 y. A randomized, positive-controlled, non-inferiority clinical trial was conducted for 1200 healthy participants in each age group. Within each age group, participants were randomly allocated to the Hib-MenAC group or the control group at a ratio of 1:1. Adverse reactions were recorded within 28 d after each dose. Blood samples were obtained to assess immunogenicity on day 0 and at 28 d after a complete vaccination course. For the investigational vaccine, the incidence of total adverse reactions in vaccinees aged 6-23 months was 46.8% and that in vaccinees aged 2-5 y was 29.8%. Most adverse reactions were mild or moderate. One non-fatal serious adverse event occurred in the Hib-MenAC group, but was unrelated to vaccination. The seroconversion rate to the 3 components reached 94.0%, and the proportion of vaccinees with rSBA titers ? 1:8 and PRP ? 0.15 g/mL reached 97.0% in both age groups. The safety and immunogenicity of the Hib-MenAC vaccine were non-inferior when compared to the licensed vaccines. It was concluded that the novel vaccine would be expected to protect children against all of the targeted diseases. PMID:25833163

  14. Immunogenicity and safety of four different doses of Haemophilus influenzae type b-tetanus toxoid conjugated vaccine, combined with diphtheria–tetanus–pertussis vaccine (DTP-Hib), in Indonesian infants

    Microsoft Academic Search

    Narain H. Punjabi; Emily L. Richie; Cyrus H. Simanjuntak; Sri Juliani Harjanto; Ferry Wangsasaputra; Sumarjati Arjoso; Ainur Rofiq; Mulyati Prijanto; Julitasari; Ursula Yela; Christian Herzog

    2006-01-01

    Widespread use of Haemophilus influenzae type b (Hib) conjugated vaccine in industrialized countries has resulted in a dramatic decline in the incidence of invasive Hib diseases, but the vaccine's cost has prevented its inclusion in basic immunization programs in developing countries. To overcome this problem, combination with diphtheria–tetanus–pertussis (DTP) vaccine or reduction in the dose of Hib vaccine has been

  15. Murine Immune Response to Neisseria meningitidis Group C Capsular Polysaccharide: Analysis of Monoclonal Antibodies Generated in Response to a Thymus-Independent Antigen and a Thymus-Dependent Toxoid Conjugate Vaccine

    PubMed Central

    García-Ojeda, Pablo A.; Monser, Martha E.; Rubinstein, Leonard J.; Jennings, Harold J.; Stein, Kathryn E.

    2000-01-01

    Antibody (Ab) responses to polysaccharides (PSs) such as Neisseria meningitidis group C PS (MCPS) are characterized as being thymus independent (TI) and are restricted with regard to clonotype and isotype expression. PS conjugated to proteins, e.g., MCPS coupled to tetanus toxoid (MCPS-TT), elicits a thymus-dependent (TD) response. In order to understand the influence of the form of a vaccine (TI versus TD) on the Ab repertoire, we generated monoclonal antibody (MAb) panels from mice immunized and boosted with MCPS or MCPS-TT in different ways. The panels of MAbs were examined for isotype, fine specificity, affinity, and VH gene family usage. The use of MCPS-TT resulted in a shift in the isotype from immunoglobulin M (IgM) and IgG3 elicited in response to the MCPS to primarily IgG1. This isotype shift was accompanied by a change in the fine specificity of the response to the conjugate compared to that of PS. New fine specificities and increased affinity were observed in response to the TD antigen (Ag). Dot blot and Northern analyses of MCPS MAbs revealed that VH gene family usage is dominated by VHJ558, used by 23 of 39 MAbs. VH3609 was seen in three MAbs of restricted fine specificity. VHQ52, VH7183, and VHVGAM3-8 were seen in more than one MAb across these panels, while VH10 and VHX24 were detected only once in response to the TI-2 Ag. All MAbs in the panels utilized kappa light chains, and all functional J? genes were expressed. PMID:10603394

  16. A clinical trial examining the effect of increased total CRM 197 carrier protein dose on the antibody response to Haemophilus influenzae type b CRM 197 conjugate vaccine

    Microsoft Academic Search

    Vytautas Usonis; Vytautas Bakasenas; Stephen Lockhart; Sherryl Baker; William Gruber

    2008-01-01

    CRM197 is a carrier protein in certain conjugate vaccines. When multiple conjugate vaccines with the same carrier protein are administered simultaneously, reduced response to vaccines and\\/or antigens related to the carrier protein may occur. This study examined responses of infants who, in addition to diphtheria toxoid\\/tetanus toxoid\\/acellular pertussis vaccine (DTaP) received either diphtheria CRM197-based Haemophilus influenzae type b conjugate vaccine

  17. 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

  18. Beta-glucan-CRM197 conjugates as candidates antifungal vaccines

    Microsoft Academic Search

    Carla Bromuro; Maria Romano; Paola Chiani; Francesco Berti; Marta Tontini; Daniela Proietti; Elena Mori; Antonella Torosantucci; Paolo Costantino; Rino Rappuoli; Antonio Cassone

    2010-01-01

    A laminarin-diphtheria toxoid (CRM197) conjugate vaccine conferred protection against fungal infections in mice. We have now generated novel ?-glucan-CRM197 vaccines, with either natural (Curd-CRM197) or synthetic linear (15mer-CRM197), or ?-(1,6)-branched (17mer-CRM197) ?-(1,3)-oligosaccharides, formulated with the human-acceptable adjuvant MF59. Curd-CRM197 and 15mer-CRM197 conjugates, which induced high titers of anti-?-(1,3)-glucan IgG, but no antibodies against ?-(1,6)-glucan, conferred protection to mice lethally challenged

  19. Immunogenicity and reactogenicity of a Haemophilus influenzae type b tetanus conjugate vaccine when administered separately or mixed with concomitant diphtheria-tetanus-toxoid and acellular pertussis vaccine for primary and for booster immunizations

    Microsoft Academic Search

    H. J. Schmitt; F. Zepp; S. Müschenborn; G. Sümenicht; A. Schuind; K. Beutel; M. Knuf; H. L. Bock; H. Bogaerts; R. Clemens

    1998-01-01

    With an increasing number of new vaccines available for routine childhood immunization, combination vaccines are needed in\\u000a order to maintain or achieve a high compliance with recommended immunization programmes. In a prospective, randomized, comparative,\\u000a multi-centre study, 822 healthy infants were enrolled to receive three doses of either a candidate or a commercially available\\u000a Haemophilus influenzae type b (Hib) vaccine concomitantly

  20. Effect of Vaccination with Carrier Protein on Response to Meningococcal C Conjugate Vaccines and Value of Different Immunoassays as Predictors of Protection

    Microsoft Academic Search

    Moya Burrage; Andrew Robinson; Ray Borrow; Nick Andrews; Jamie Findlow; Sarah Martin; Carol Thornton; David Goldblatt; Michael Corbel; Dorothea Sesardic; Keith Cartwight; Peter Richmond; Elizabeth Miller

    2002-01-01

    In order to plan for the wide-scale introduction of meningococcal C conjugate (MCC) vaccine for United Kingdom children up to 18 years old, phase II trials were undertaken to investigate whether there was any interaction between MCC vaccines conjugated to tetanus toxoid (TT) or a derivative of diphtheria toxin (CRM197) and diphtheria-tetanus vaccines given for boosting at school entry or

  1. Development of Vi conjugate - a new generation of typhoid vaccine.

    PubMed

    Szu, Shousun Chen

    2013-11-01

    Typhoid fever remains to be a serious disease burden worldwide with an estimated annual incidence about 20 million. The licensed vaccines showed moderate protections and have multiple deficiencies. Most important of all, none of the licensed typhoid vaccines demonstrated protection for children under 5 years old. These limitations impeded successful implementation of typhoid vaccination programs. To improve immunogenicity Vi was conjugated to rEPA, a recombinant exoprotein A from Pseudomonas aeruginosa. Vi-rEPA showed higher and longer lasting anti-Vi IgG in adults and children than Vi alone in high endemic areas. In school-age children and adults, the immunity persisted more than 8 years. In a double-blind, placebo-controlled and randomized efficacy trial in 2- to 5-year-old children, Vi-rEPA conferred 89% protective efficacy against typhoid fever and the protection lasted at least 4 years. When given concomitantly with infant routine vaccines, Vi-rEPA was safe, immunogenic and showed no interference with the routine vaccines. Vi conjugate vaccine was also attempted and successfully demonstrated by several other laboratories and manufactures. Using either rEPA or different carrier proteins, such as diphtheria or tetanus toxoid, recombinant diphtheria toxin (CRM197), the Vi conjugates synthesized was significantly more immunogenic than Vi alone. Recently, two Vi-tetanus toxoid conjugates were licensed in India for all ages, starts as young as 3 month old. This new generation of typhoid vaccine opens up a new era for typhoid prevention and elimination. PMID:24156285

  2. Safety and immunogenicity of two inactivated poliovirus vaccines in combination with an acellular pertussis vaccine and diphtheria and tetanus toxoids in seventeen- to nineteen-month-old infants

    Microsoft Academic Search

    Scott A. Halperin; H. Dele Davies; Luis Barreto; Roland Guasparini; William Meekison; Garry Humphreys; Brian J. Eastwood

    1997-01-01

    Objectives: To compare the safety and immunity of an acellular pertussis vaccine containing pertussis toxoid, filamentous hemagglutinin, 69 kd protein, fimbriae 2 and 3 combined with diphtheria and tetanus toxoids given as single or separate injection with inactivated poliovirus vaccine (MRC-5– or Vero cell–derived) or live attenuated polio vaccine.Methods: A total of 425 healthy children between 17 and 19 months

  3. Adverse event reporting rates following tetanus–diphtheria and tetanus toxoid vaccinations: data from the Vaccine Adverse Event Reporting System (VAERS), 1991–1997

    Microsoft Academic Search

    Jenifer C. Lloyd; Penina Haber; Gina T. Mootrey; M. Miles Braun; Philip H. Rhodes; Robert T. Chen

    2003-01-01

    Since 1966, the Advisory Committee on Immunization Practices (ACIP) has recommended tetanus–diphtheria toxoid (Td) be used instead of single antigen tetanus toxoid (TT) because, while both vaccines protect against tetanus, only Td protects against diphtheria. Despite this recommendation, approximately 2.5 million doses of TT were distributed annually from 1991 to 1997. One possible explanation for the continued use of TT

  4. A novel glyco-conjugate vaccine against fungal pathogens

    PubMed Central

    Torosantucci, Antonella; Bromuro, Carla; Chiani, Paola; De Bernardis, Flavia; Berti, Francesco; Galli, Chiara; Norelli, Francesco; Bellucci, Cinzia; Polonelli, Luciano; Costantino, Paolo; Rappuoli, Rino; Cassone, Antonio

    2005-01-01

    To generate a vaccine to protect against a variety of human pathogenic fungi, we conjugated laminarin (Lam), a well-characterized but poorly immunogenic ?-glucan preparation from the brown alga Laminaria digitata, with the diphtheria toxoid CRM197, a carrier protein used in some glyco-conjugate bacterial vaccines. This Lam-CRM conjugate proved to be immunogenic and protective as immunoprophylactic vaccine against both systemic and mucosal (vaginal) infections by Candida albicans. Protection probably was mediated by anti-?-glucan antibodies as demonstrated by passive transfer of protection to naive mice by the whole immune serum, the immune vaginal fluid, and the affinity-purified anti-?-glucan IgG fractions, as well as by administration of a ?-glucan–directed IgG2b mAb. Passive protection was prevented by adsorption of antibodies on Candida cells or ?-glucan particles before transfer. Anti-?-glucan antibodies bound to C. albicans hyphae and inhibited their growth in vitro in the absence of immune-effector cells. Remarkably, Lam-CRM–vaccinated mice also were protected from a lethal challenge with conidia of Aspergillus fumigatus, and their serum also bound to and markedly inhibited the growth of A. fumigatus hyphae. Thus, this novel conjugate vaccine can efficiently immunize and protect against two major fungal pathogens by mechanisms that may include direct antifungal properties of anti-?-glucan antibodies. PMID:16147975

  5. 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

  6. Antibody responses to natural rattlesnake envenomation and a rattlesnake toxoid vaccine in horses.

    PubMed

    Gilliam, Lyndi L; Carmichael, Robert C; Holbrook, Todd C; Taylor, Jennifer M; Ownby, Charlotte L; McFarlane, Dianne; Payton, Mark E

    2013-05-01

    Antivenom antibody titers following administration of rattlesnake venom for antivenom production in horses are well documented; however, antivenom antibody titers following natural rattlesnake envenomation in horses are not. Antibody titers produced in response to the commercially available rattlesnake venom vaccine are also not published. Our study objectives were to measure antivenom antibody titers in rattlesnake-bitten horses and compare them to titers in horses vaccinated with the rattlesnake venom vaccine. Additionally, titers were compared in pregnant versus nonpregnant horses to assess the affect of pregnancy on vaccine response and were measured pre- and postsuckle in foals of vaccinated mares to detect passive transfer of vaccine immunoglobulins. Blood samples were collected from 16 rattlesnake-bitten horses. Thirty-six horses (11 pregnant mares, 12 nonpregnant mares, 13 geldings) were vaccinated using a Crotalus atrox venom toxoid vaccine. Blood was collected before administering each vaccination and 30 days following the third vaccination. Blood was collected from foals of vaccinated mares pre- and postsuckle. All serum was assayed for anti-Crotalus atrox venom antibodies using an enzyme-linked immunosorbent assay (ELISA). Rattlesnake-bitten horses had higher (P = 0.001) titers than vaccinated horses. There was no significant difference between titers in vaccinated pregnant versus nonpregnant horses. One mare had a positive titer at foaling, and the foals had positive postsuckle titers. Antivenom antibody titer development was variable following natural envenomation and vaccination, and vaccine-induced titers were lower than natural envenomation titers. Further studies are required to determine if natural or vaccine antivenom antibody titers reduce the effects of envenomation. PMID:23515015

  7. The influence of carrier protein on the immunogenicity of simultaneously administered conjugate vaccines in infants.

    PubMed

    Pöllabauer, Eva Maria; Petermann, Robert; Ehrlich, Hartmut J

    2009-03-10

    Continuing additions of new vaccines to routine infant vaccination schedules have prompted concerns about potential interactions between vaccine components reducing desired protective effects. One hypothesis is that increasing loads of carrier protein may interfere with immune responses to polysaccharide components of co-administered glycoconjugate vaccines. Based upon a critical appraisal of existing evidence, however, neither carrier protein type nor dose adequately explains observed interference. Moreover, in five clinical trials, enhancement of anti-polyribosylribitol phosphate Haemophilus influenzae type b antibody has been demonstrated after co-administration of monovalent meningococcal C conjugate vaccine with tetanus toxoid carrier. Empirical observations do not fit well with carrier-induced epitope suppression as an underlying mechanism of interference. Thus, co-administration of conjugate vaccines can have positive as well as negative effects, and predictors of vaccine interactions are still lacking. PMID:19168106

  8. 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

  9. Immunogenicity of meningococcal B polysaccharide conjugated to tetanus toxoid or CRM197 via adipic acid dihydrazide

    Microsoft Academic Search

    Antonella Bartoloni; Francesco Norelli; Costante Ceccarini; Rino Rappuoli; Paolo Costantino

    1995-01-01

    Vaccine development against Group B Neisseria meningitidis is complicated by the nature of the capsular polysaccharide, which is ? 2-8-linked poly-sialic acid, identical in structure to the poly-sialic acid found in many mammalian tissues during development. To test the feasibility of a vaccine based on this polysaccharide, we synthesized several conjugates of meningococcal B polysaccharide linked to a carrier protein

  10. Self-adjuvanting glycopeptide conjugate vaccine against disseminated candidiasis.

    PubMed

    Xin, Hong; Cartmell, Jonathan; Bailey, Justin J; Dziadek, Sebastian; Bundle, David R; Cutler, Jim E

    2012-01-01

    Our research on pathogenesis of disseminated candidiasis led to the discovery that antibodies specific for Candida albicans cell surface ?-1, 2-mannotriose [?-(Man)(3)] protect mice. A 14 mer peptide Fba, which derived from the N-terminal portion of the C. albicans cytosolic/cell surface protein fructose-bisphosphate aldolase, was used as the glycan carrier and resulted in a novel synthetic glycopeptide vaccine ?-(Man)(3)-Fba. By a dendritic cell-based immunization approach, this conjugate induced protective antibody responses against both the glycan and peptide parts of the vaccine. In this report, we modified the ?-(Man)(3)-Fba conjugate by coupling it to tetanus toxoid (TT) in order to improve immunogenicity and allow for use of an adjuvant suitable for human use. By new immunization procedures entirely compatible with human use, the modified ?-(Man)(3)-Fba-TT was administered either alone or as a mixture made with alum or monophosphoryl lipid A (MPL) adjuvants and given to mice by a subcutaneous (s.c.) route. Mice vaccinated with or, surprisingly, without adjuvant responded well by making robust antibody responses. The immunized groups showed a high degree of protection against a lethal challenge with C. albicans as evidenced by increased survival times and reduced kidney fungal burden as compared to control groups that received only adjuvant or DPBS buffer prior to challenge. To confirm that induced antibodies were protective, sera from mice immunized against the ?-(Man)(3)-Fba-TT conjugate transferred protection against disseminated candidiasis to naïve mice, whereas C. albicans-absorbed immune sera did not. Similar antibody responses and protection induced by the ?-(Man)(3)-Fba-TT vaccine was observed in inbred BALB/c and outbred Swiss Webster mice. We conclude that addition of TT to the glycopeptide conjugate results in a self-adjuvanting vaccine that promotes robust antibody responses without the need for additional adjuvant, which is novel and represents a major step forward in vaccine design against disseminated candidiasis. PMID:22563378

  11. 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.

  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 [Institute of Immunology, Centre de Recherche Public de la Santé/Laboratoire National de Santé, 20A rue Auguste Lumière, L-1950 Luxembourg, Grand-Duchy of Luxembourg (Luxembourg); Schroeder, Henri [University of Nancy, URAFPA, INRA UC340, F-54500 Vandoeuvre-lès-Nancy (France); Muller, Claude P., E-mail: claude.muller@crp-sante.lu [Institute of Immunology, Centre de Recherche Public de la Santé/Laboratoire National de Santé, 20A rue Auguste Lumière, L-1950 Luxembourg, Grand-Duchy of Luxembourg (Luxembourg)

    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. Tetanus toxoid vaccine: Elimination of neonatal tetanus in selected states of India

    PubMed Central

    Verma, Ramesh; Khanna, Pardeep

    2012-01-01

    Tetanus is caused by a neurotoxin produced by Clostridium tetani (C. tetani), a spore-forming bacterium. Infection begins when tetanus spores are introduced into damaged tissue. Tetanus is characterized by muscle rigidity and painful muscle spasms caused by tetanus toxin’s blockade of inhibitory neurons that normally oppose and modulate the action of excitatory motor neurons. Maternal and neonatal tetanus (MNT) are caused by unhygienic methods of delivery, abortion, or umbilical-cord care. Maternal and neonatal tetanus are both forms of generalized tetanus and have similar clinical courses. About 90% of neonates with tetanus develop symptoms in the first 3–14 d of life, mostly on days 6–8, distinguishing neonatal tetanus from other causes of neonatal mortality which typically occur during the first two days of life. Overall case fatality rates for patients admitted to the hospital with neonatal tetanus in developing countries are 8–50%, while the fatality rate can be as high as 100% without hospital care. Tetanus toxoid (TT) vaccination of pregnant women to prevent neonatal tetanus was included in WHO’s Expanded Program on Immunization (EPI) a few years after its inception in 1974. In 2000, WHO, UNICEF, and UNFPA formed a partnership to relaunch efforts toward this goal, adding the elimination of maternal tetanus as a program objective, and setting a new target date of 2005. By February 2007, 40 countries had implemented tetanus vaccination campaigns in high-risk areas, targeting more than 94 million women, and protecting more than 70 million subjects with at least two doses of TT. In 2011, 653 NT cases were reported in India compared with 9313 in 1990. As of February 2012, 25 countries and 15 States and Union Territories of India, all of Ethiopia except Somaliland, and almost 29 of 34 provinces in Indonesia have been validated to have eliminated MNT. PMID:22894950

  14. Safety and immunogenicity of two doses of quadrivalent meningococcal conjugate vaccine or one dose of meningococcal group C conjugate vaccine, both administered concomitantly with routine immunization to 12- to 18-month-old children

    PubMed Central

    Noya, Francisco; McCormack, Deirdre; Reynolds, Donna L; Neame, Dion; Oster, Philipp

    2014-01-01

    OBJECTIVES: To describe the immunogenicity and safety of a two-dose series of a quadrivalent meningococcal (serogroups A, C, Y and W) polysaccharide diphtheria toxoid conjugate vaccine (MenACYW-D) administered to toddlers. METHODS: Children were randomly assigned (1:1) at study entry to receive MenACYW-D at 12 and 18 months of age (group 1; n=61) or meningococcal serogroup C conjugate vaccine (MCC) at 12 months of age (group 2; n=62). All received routine childhood immunizations. A, C, Y and W antibody titres were measured in group 1 before and one month after the 18-month MenACYW-D vaccination and were measured in group 2 at one and seven months post-MCC vaccination. Antibodies elicited by diphtheria and tetanus toxoids, and acellular pertussis vaccine adsorbed combined with inactivated poliomyelitis vaccine and Haemophilus influenzae b conjugate (DTaP-IPV-Hib) vaccine coadministered at the 18-month vaccination were measured one month later. Safety data were collected. RESULTS: At 19 months of age, ?96% in group 1 achieved protective titres for the four meningococcal serogroups after dose 2; 67% in group 2 exhibited protective titres against serogroup C 28 days after MCC vaccination at 12 months of age, declining to 27% seven months later. DTaP-IPV-Hib elicited high antibody concentrations/titres in groups 1 and 2, consistent with historical values. The safety profiles after each dose generated no unexpected safety signals; no serious adverse events were related to vaccination. DISCUSSION: A two-dose series of MenACYW-D given concomitantly with a DTaP-IPV-Hib booster dose at 18 months of age demonstrated a good immunogenicity and safety profile. A two-dose series of MenACYW-D can be used as an alternative to one dose of MCC and provides protection against additional serogroups (NCT ID: NCT01359449). PMID:25285126

  15. Biochemical and biological characteristics of cross-reacting material 197 (CRM 197), a non-toxic mutant of diphtheria toxin: Use as a conjugation protein in vaccines and other potential clinical applications

    Microsoft Academic Search

    Michael Bröker; Paolo Costantino; Lisa DeTora; E. David McIntosh; Rino Rappuoli

    2011-01-01

    The biochemical and biological characteristics of CRM197 are reviewed. Polysaccharide protein conjugate vaccines represent an important technological advancement that allowed for protection against dangerous diseases in vulnerable populations such as infants. The first carrier proteins, diphtheria and tetanus toxoids, were chosen in the context of an extensive body of information describing their immunogenicity and safety profiles in clinical use. These

  16. 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

  17. Protection of mice against Salmonella typhimurium with an O-specific polysaccharide-protein conjugate vaccine.

    PubMed Central

    Watson, D C; Robbins, J B; Szu, S C

    1992-01-01

    Serious infections with salmonellae remain a threat in many human populations. Despite extensive study of salmonella infections in animals and clinical experience with killed cellular vaccines, there are no vaccines against serotypes other than Salmonella typhi licensed for human use. Serum antibodies to the O-specific polysaccharide (O-SP) of salmonellae protect mice against invasive infection. In order to render it immunogenic, we have conjugated the O-SP of Salmonella typhimurium to carrier proteins by various schemes. O-SP conjugated to tetanus toxoid (O-SP-TT) elicited antibodies in outbred mice after three subcutaneous injections without adjuvant. The O-SP alone elicited no detectable antibody. The antibody response to O-SP-TT was boosted by successive doses and consisted of immunoglobulin G (IgG) and IgM. Most mice only produced antibodies specific for the abequose (O:4 factor) region of the O-SP. Occasional animals also produced antibodies to the core oligosaccharide. Immunized mice were protected against intraperitoneal challenge with S. typhimurium, demonstrating a 160-fold increase in the 50% lethal dose. Passive immunization with conjugate-induced IgM or IgG also protected against challenge. These results indicate that an O-SP-TT conjugate, when given by a route and formulation acceptable for human use, protects mice against challenge with S. typhimurium. Images PMID:1383154

  18. Pertussis toxin-induced alterations of murine hepatic drug metabolism following administration of diphtheria and tetanus toxoids and pertussis vaccine adsorbed.

    PubMed Central

    Ansher, S; Thompson, W; Bridgewater, J; Snoy, P

    1993-01-01

    Administration of pertussis toxin (PT) in combination with diphtheria and tetanus toxoids adsorbed (DT vaccine) or with acellular pertussis vaccine adsorbed and diphtheria and tetanus toxoids (APDT) elicits dose- and time-dependent alterations in hepatic drug metabolism in mice. Cytochrome P-450 (P-450) levels were inhibited more than 50% at 7 days following a single injection of PT mixed with either vaccine. When combined with DT vaccine, 125 ng of PT was required to produce this effect, while as little as 16 ng of PT combined with APDT vaccine inhibited P-450 levels. The inhibition of P-450 levels is similar to that observed after a single injection of diphtheria and tetanus toxoids and pertussis vaccine adsorbed (DTP). Alterations of P-450 levels were accompanied by increased activities of quinone reductase but not with changes in plasma interleukin-6 or tumor necrosis factor levels. Other Bordetella pertussis virulence factors, such as filamentous hemagglutinin, fimbriae and pertactin, were also tested but had no significant effect on hepatic drug metabolism. Endotoxin or preparations containing endotoxin caused alterations in hepatic drug metabolism within 24 h, concomitant with increased interleukin-6 and tumor necrosis factor levels, but these effects had resolved by 1 week. DTP vaccine and preparations containing PT caused a marked induction of gamma interferon coincident with the maximal inhibition of P-450 levels. This effect was not present with DT or APDT vaccine alone, nor with endotoxin or any combination of factors that did not contain PT. These results demonstrate that PT is a necessary component for the sustained effects of DTP vaccine on hepatic drug metabolism and suggest a role for gamma interferon in this process. PMID:8406812

  19. Continuing effectiveness of serogroup A meningococcal conjugate vaccine, Chad, 2013.

    PubMed

    Gamougam, Kadidja; Daugla, Doumagoum M; Toralta, Jacques; Ngadoua, Cyriaque; Fermon, Florence; Page, Anne-Laure; Djingarey, Mamoudou H; Caugant, Dominique A; Manigart, Olivier; Trotter, Caroline L; Stuart, James M; Greenwood, Brian M

    2015-01-01

    In 2011, vaccination with a serogroup A meningococcal polysaccharide conjugate vaccine was implemented in 3 of 23 regions in Chad. Cases of meningitis declined dramatically in vaccinated areas, but an epidemic continued in the rest of Chad. In 2012, the remaining Chad population was vaccinated, and the epidemic was halted. PMID:25536336

  20. Continuing Effectiveness of Serogroup A Meningococcal Conjugate Vaccine, Chad, 2013

    PubMed Central

    Gamougam, Kadidja; Daugla, Doumagoum M.; Toralta, Jacques; Ngadoua, Cyriaque; Fermon, Florence; Page, Anne-Laure; Djingarey, Mamoudou H.; Caugant, Dominique A.; Manigart, Olivier; Trotter, Caroline L.; Greenwood, Brian M.

    2015-01-01

    In 2011, vaccination with a serogroup A meningococcal polysaccharide conjugate vaccine was implemented in 3 of 23 regions in Chad. Cases of meningitis declined dramatically in vaccinated areas, but an epidemic continued in the rest of Chad. In 2012, the remaining Chad population was vaccinated, and the epidemic was halted. PMID:25536336

  1. Bystander stimulation of activated CD4+ T cells of unrelated specificity following a booster vaccination with tetanus toxoid.

    PubMed

    Di Genova, Gianfranco; Savelyeva, Natalia; Suchacki, Amy; Thirdborough, Stephen M; Stevenson, Freda K

    2010-04-01

    Antigen-specific CD4(+) T cells are central to natural and vaccine-induced immunity. An ongoing antigen-specific T-cell response can, however, influence surrounding T cells with unrelated antigen specificities. We previously observed this bystander effect in healthy human subjects following recall vaccination with tetanus toxoid (TT). Since this interplay could be important for maintenance of memory, we have moved to a mouse model for further analysis. We investigated whether boosting memory CD4(+) T cells against TT in vivo would influence injected CD4(+) TCR transgenic T cells (OT-II) specific for an unrelated OVA peptide. If OT-II cells were pre-activated with OVA peptide in vitro, these cells showed a bystander proliferative response during the ongoing parallel TT-specific response. Bystander proliferation was dependent on boosting of the TT-specific memory response in the recipients, with no effect in naive mice. Bystander stimulation was also proportional to the strength of the TT-specific memory T-cell response. T cells activated in vitro displayed functional receptors for IL-2 and IL-7, suggesting these as potential mediators. This crosstalk between a stimulated CD4(+) memory T-cell response and CD4(+) T cells activated by an unrelated antigen could be important in human subjects continually buffeted by environmental antigens. PMID:20104490

  2. Immunogenicity, reactogenicity, and immune memory after primary vaccination with a novel Haemophilus influenzae-Neisseria meningitidis serogroup C conjugate vaccine.

    PubMed

    Schmitt, Heinz-J; Maechler, Gudrun; Habermehl, Pirmin; Knuf, Markus; Saenger, Roland; Begg, Norman; Boutriau, Dominique

    2007-04-01

    We evaluated two formulations of a new combined Haemophilus influenzae type b (Hib)-meningococcal serogroup C (MenC)-tetanus toxoid (TT) conjugated vaccine and two formulations of a new MenC-TT vaccine (trials 711202/001 and 711202/008; clinical trial register numbers NCT00135486 and NCT00135564 [www.ClinicalTrials.gov]). A total of 520 healthy infants were randomized to receive primary vaccination (at 2, 3, and 4 months) with either MenC-TT plus diphtheria-tetanus-acellular pertussis (DTPa)-hepatitis B virus (HBV)-inactivated poliovirus (IPV)/Hib, Hib-MenC-TT plus DTPa-HBV-IPV, or MenC-CRM(197) plus DTPa-HBV-IPV/Hib (control). At 12 to 15 months, subjects received a polysaccharide challenge with meningococcal polysaccharide C plus a DTPa-HBV-IPV/Hib booster. Immune responses were assessed 1 month after dose 2, 1 month after dose 3, and prior to and 1 month after the booster. After primary vaccination, there was no difference between groups in seroprotection rates as measured by titers of serum bactericidal antibody (SBA) to MenC (> or = 1:8) or concentrations of anti-polyribosyl ribitol phosphate (PRP) antibody (> or = 0.15 microg/ml). Prior to the booster, there was no difference between groups in SBA seroprotection rates, whereas anti-PRP seroprotection rates were significantly higher after priming with Hib-MenC-TT. Booster doses induced large increases in SBA and anti-PRP antibodies in primed groups, indicating successful priming with induction of immune memory. Reactogenicity and safety were similar in all groups during the primary and booster phases. A novel combined Hib-MenC-TT conjugate vaccine induced MenC and Hib responses comparable to those induced by licensed monovalent vaccines. A Hib-MenC-TT conjugate vaccine provides vaccination against two major pathogens in a single injection and is a suitable candidate for use in primary or booster vaccination schedules. PMID:17287313

  3. A Licensed Combined Haemophilus influenzae Type b-Serogroups C and Y Meningococcal Conjugate Vaccine.

    PubMed

    Perrett, Kirsten P; Nolan, Terry M; McVernon, Jodie

    2013-06-01

    The highest incidence of meningococcal disease occurs in infants younger than 1 year of age. However, in the US, prior to June 2012, there was no meningococcal vaccine licensed for use in this age group. In the US, where both serogroups C and Y contribute substantially to the overall epidemiology of invasive meningococcal disease, a vaccine combining these capsular polysaccharides was developed. We review the newly licensed HibMenCY-TT (MenHibrix™, GlaxoSmithKline Biologicals, Rixensart, Belgium), a novel vaccine containing Haemophilus influenzae type b (Hib) and serogroups C and Y Neisseria meningitidis conjugated to tetanus toxoid. We describe the vaccine, summarize the clinical trial data, and describe the patient populations recommended to receive HibMenCY-TT as their primary vaccination against Hib. Phase II and III clinical trials found HibMenCY-TT to be well tolerated, safe, and immunogenic when administered at 2, 4, 6, and 12-15 months of age for primary vaccination against both Hib and serogroups C and Y meningococcal disease. In October 2012, the Advisory Committee on Immunisation Practice in the US recommended HibMenCY-TT vaccination for infants at increased risk of meningococcal disease. HibMenCY-TT may be given concomitantly with other routine infant vaccines. It induces antibodies against Hib as well as bactericidal activity against meningococcal serogroup C and Y without increasing the number of injections required. As meningococcal disease epidemiology is dynamic, global surveillance remains essential. In the future, other countries may also benefit from the addition of HibMenCY-TT into their vaccine armamentarium against meningococcal disease. PMID:25135819

  4. Conjugate vaccines and the carriage of Haemophilus influenzae type b.

    PubMed Central

    Barbour, M. L.

    1996-01-01

    Pharyngeal carriage of Haemophilus influenzae type b (Hib) is important in the transmission of Hib organisms, the pathogenesis of Hib disease, and the development of immunity to the bacterium. The remarkable success of current vaccination programs against Hib has been due in part to the effect of conjugate Hib vaccines in decreasing carriage of Hib. This review explores evidence for this effect, and discusses the possible mechanisms of the mucosal influence of Hib conjugate vaccines. PMID:8903227

  5. Tetanus Toxoid?Pulsed Monocyte Vaccination for Augmentation of Collateral Vessel Growth

    PubMed Central

    Herold, Joerg; Francke, Alexander; Weinert, Soenke; Schmeisser, Alexander; Hebel, Katrin; Schraven, Burkhart; Roehl, Friedich?Wilhelm; Strasser, Ruth H.; Braun?Dullaeus, Ruediger C.

    2014-01-01

    Background The pathogenesis of collateral growth (arteriogenesis) has been linked to both the innate and adaptive immune systems. While therapeutic approaches for the augmentation of arteriogenesis have focused on innate immunity, exploiting both innate and adaptive immune responses has not been examined. We hypothesized that tetanus toxoid (tt) immunization of mice followed by transplantation of monocytes (Mo) exposed ex vivo to tt augments arteriogenesis after ligation of the hind limb. Methods and Results Mo were generated from nonimmunized BALB/c mice, exposed ex vivo to tt for 24 hours and intravenously injected (ttMo, 2.5×106) into the tail veins of tt?immunized syngeneic mice whose hind limbs had been ligated 24 hours prior to transplantation. Laser Doppler perfusion imaging was applied, and a perfusion index (PI) was calculated (ratio ligated/unligated). Twenty?one days after ligation, the arteriogenesis of untreated BALB/c mice was limited (PI=0.49±0.09). Hind limb function was impaired in 80% of animals. Injection of non?engineered Mo insignificantly increased the PI to 0.56±0.07. However, ttMo transplantation resulted in a strong increase of the PI to 0.82±0.08 (n=7; P<0.001), with no (0%) detectable functional impairment. ttMo injected into nonimmunized mice had no effect. The strong arteriogenic response of ttMo transplantation into immunized mice was prevented when mice had been depleted of T?helper cells by CD4?antibody pretreatment (PI=0.50±0.08; n=17; P<0.001), supporting the hypothesis that transplanted cells interact with recipient lymphocytes. Conclusions Transplantation of ttMo into pre?immunized mice strongly promotes arteriogenesis. This therapeutic approach is feasible and highly attractive for the alleviation of morbidity associated with vascular occlusive disease. PMID:24732919

  6. Investigation of Different Group A Immunoassays following One Dose of Meningococcal Group A Conjugate Vaccine or A/C Polysaccharide Vaccine in Adults?

    PubMed Central

    Findlow, H.; Plikaytis, B. D.; Aase, A.; Bash, M. C.; Chadha, H.; Elie, C.; Laher, G.; Martinez, J.; Herstad, T.; Newton, E.; Viviani, S.; Papaspyridis, C.; Kulkarni, P.; Wilding, M.; Preziosi, M. P.; Marchetti, E.; Hassan-King, M.; La Force, F. M.; Carlone, G.; Borrow, R.

    2009-01-01

    A double-blind, randomized, controlled phase I study to assess the safety, immunogenicity, and antibody persistence of a new group A conjugate vaccine (PsA-TT) in volunteers aged 18 to 35 years was previously performed. Subjects received one dose of either the PsA-TT conjugate vaccine, meningococcal A/C polysaccharide vaccine (PsA/C), or tetanus toxoid vaccine. The conjugate vaccine was shown to be safe and immunogenic as demonstrated by a standardized group A-specific immunoglobulin G (IgG) enzyme-linked immunosorbent assay (ELISA) and by a serum bactericidal antibody (SBA) assay using rabbit complement (rSBA). This report details further analysis of the sera using four additional immunologic assays to investigate the relationship between the different immunoassays. The immunoassays used were an SBA assay that used human complement (hSBA), a group A-specific IgG multiplexed bead assay, and two opsonophagocytic antibody (OPA) assays which used two different methodologies. For each vaccine group, geometric mean concentrations or geometric mean titers were determined for all assays before and 4, 24, and 48 weeks after vaccination. Pearson's correlation coefficients were used to assess the relationship between the six assays using data from all available visits. An excellent correlation was observed between the group A-specific IgG concentrations obtained by ELISA and those obtained by the multiplexed bead assay. hSBA and rSBA titers correlated moderately, although proportions of subjects with putatively protective titers and those demonstrating a ?4-fold rise were similar. The two OPA methods correlated weakly and achieved only a low correlation with the other immunoassays. The correlation between hSBA and group A-specific IgG was higher for the PsA-TT group than for the PsA/C group. PMID:19474264

  7. Glycoconjugate vaccines and immune interactions, and implications for vaccination schedules.

    PubMed

    Borrow, Ray; Dagan, Ron; Zepp, Fred; Hallander, Hans; Poolman, Jan

    2011-11-01

    Conjugate vaccines using diphtheria toxoid variant (CRM(197)), diphtheria toxoid and tetanus toxoid (TT) as carrier protein may induce immune interactions (interference or impairment as measured by lower antibody levels, or enhancement [higher antibody levels]) when coadministered with other vaccines. Immune enhancement occurs when two TT conjugates are coadministered. CRM(197) conjugate vaccines induce immune bystander interference when given with diphtheria-tetanus-acellular pertussis vaccines, which reduces responses to coadministered Haemophilus influenzae type b vaccine conjugated to TT. These bystander effects are greater as the amount of CRM(197) administered increases. When large amounts of either TT or CRM(197) are coadministered, dose-related carrier-induced epitopic suppression may occur, affecting immune responses to meningococcal or pneumococcal polysaccharides. These observations have implications for vaccine scheduling. The range of available alternative vaccines means that specific vaccine coadministrations can avoid or reduce CRM(197)-induced interference. Potential interactions arising from new CRM(197) or TT conjugates will need to be thoroughly examined. PMID:22043960

  8. 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

  9. Experience with pneumococcal polysaccharide conjugate vaccine (conjugated to CRM197 carrier protein) in children and adults.

    PubMed

    Durando, P; Faust, S N; Fletcher, M; Krizova, P; Torres, A; Welte, T

    2013-10-01

    Streptococcus pneumoniae-related infections are a major cause of morbidity and mortality in people of all ages worldwide. Pneumococcal vaccine development started in 1911 with a whole cell vaccine and more recently multivalent plain polysaccharide and polysaccharide conjugate vaccines have been developed. The recent vaccines rely on capsular polysaccharide antigens to induce serotype-specific immune responses. We summarize here the presentations on pneumococcal polysaccharide conjugate vaccine (conjugated to CRM197 carrier protein) given during the integrated symposium organized and funded by Pfizer International Operations during the 22nd European Congress of Clinical Microbiology and Infectious Diseases (ECCMID) 31 March to 3 April 2012, London, UK. A dramatic reduction in the incidence of invasive pneumococcal diseases (IPD) due to vaccine serotypes (VST-IPD) has been reported since the introduction of a hepta-valent pneumococcal conjugate vaccine (PCV7). An indirect (herd) effect has been demonstrated to be associated with PCV7 infant vaccination programmes, with many studies reporting reductions in VST-IPD in populations that are not eligible for PCV7 vaccination. Since 2010, a 13-valent pneumococcal conjugate vaccine (PCV13) has been introduced into national immunization programmes and results from early surveillance suggest that this vaccine also has an impact on the serotypes unique to PCV13, as well as continuing to protect against the PCV7 serotypes. Data from a passive surveillance system in Europe in 2009, for instance, showed that the highest incidence of IPD remains in those aged >65 years and in children <5 years. PCV13 has now been licensed for vaccination of adults >50 years based on safety and immunogenicity data; an efficacy trial is being conducted. Regardless of previous pneumococcal vaccination status, if the use of 23-valent polysaccharide is considered appropriate, it is recommended to give PCV13 first. Novel immunization strategies remain the only practical means to reduce significantly the remaining global mortality and morbidity due to S. pneumoniae in adults. PMID:24083785

  10. Moderate PEGylation of the carrier protein improves the polysaccharide-specific immunogenicity of meningococcal group A polysaccharide conjugate vaccine.

    PubMed

    Zhang, Tingting; Yu, Weili; Wang, Yanfei; Hu, Tao

    2015-06-22

    Neisseria meningitidis can cause severe and fulminant diseases such as meningitis. Meningococcal capsular polysaccharide (PS) is a key virulence determinant that is not able to induce immunological memory. Conjugation of PS to a carrier protein can significantly increase the immunogenicity of PS and induce immunological memory. Due to the classically described carrier-induced epitopic suppression (CIES) mechanisms, a strong immune response against the carrier protein could suppress the immune response to PS after coadministration of free carrier protein with the conjugate vaccine. However, it was not clear whether suppressing or enhancing the protein-specific immunogenicity could improve the PS-specific immunogenicity of the conjugate vaccine. Thus, moderate PEGylation, extensive PEGylation and oligomerization were used to regulate the immunogenicity of tetanus toxoid (TT) in the conjugate vaccine (PS-TT). Moderate PEGylation led to a 2.7-fold increase in the PS-specific IgG titers elicited by PS-TT. In contrast, extensive PEGylation and oligomerization of TT led to 1.4-fold and 1.6-fold decrease in the PS-specific IgG titers elicited by PS-TT, respectively. The PS-specific immunogenicity of PS-TT can be increased by moderate PEGylation through mild suppression of the TT-specific immunogenicity. The PS-specific immunogenicity of PS-TT was decreased through significant suppression or enhancement of the TT-specific immunogenicity. Thus, our study contributes to understand the CIES mechanisms and improve the PS-specific immunogenicity of a meningococcal PS conjugate vaccine. PMID:25964170

  11. Evaluation of biological safety in vitro and immunogenicity in vivo of recombinant Escherichia coli Shiga toxoids as candidate vaccines in cattle.

    PubMed

    Kerner, Katharina; Bridger, Philip S; Köpf, Gabriele; Fröhlich, Julia; Barth, Stefanie; Willems, Hermann; Bauerfeind, Rolf; Baljer, Georg; Menge, Christian

    2015-01-01

    Cattle are the most important reservoir for enterohemorrhagic Escherichia coli (EHEC), a subset of shigatoxigenic E. coli (STEC) capable of causing life-threatening infectious diseases in humans. In cattle, Shiga toxins (Stx) suppress the immune system thereby promoting long-term STEC shedding. First infections of animals at calves' age coincide with the lack of Stx-specific antibodies. We hypothesize that vaccination of calves against Shiga toxins prior to STEC infection may help to prevent the establishment of a persistent type of infection. The objectives of this study were to generate recombinant Shiga toxoids (rStx1mut & rStx2mut) by site-directed mutagenesis and to assess their immunomodulatory, antigenic, and immunogenic properties. Cultures of bovine primary immune cells were used as test systems. In ileal intraepithelial lymphocytes both, recombinant wild type Stx1 (rStx1WT) and rStx2WT significantly induced transcription of IL-4 mRNA. rStx1WT and rStx2WT reduced the expression of Stx-receptor CD77 (syn. Globotriaosylceramide, Gb3) on B and T cells from peripheral blood and of CD14 on monocyte-derived macrophages. At the same concentrations, rStx1mut and rStx2mut exhibited neither of these effects. Antibodies in sera of cattle naturally infected with STEC recognized the rStxmut toxoids equally well as the recombinant wild type toxins. Immunization of calves with rStx1mut plus rStx2mut led to induction of antibodies neutralizing Stx1 and Stx2. While keeping their antigenicity and immunogenicity recombinant Shiga toxoids are devoid of the immunosuppressive properties of the corresponding wild type toxins in cattle and candidate vaccines to mitigate long-term STEC shedding by the reservoir host. PMID:25889651

  12. Invasive pneumococcal infection despite 7-valent conjugated vaccine

    PubMed Central

    Joye, Sebastien; Gao, Anja; Kayemba-Kay’s, Simon; Cotting, Jacques; Perez, Marie-Hélène

    2013-01-01

    Despite good cover with 7-valent vaccination, invasive pneumococcal infections may still be misdiagnosed and may lead to lifethreatening situations or death in young children. New serotypes are emerging and, therefore, clinicians must keep a high level of suspicion in young children regardless of their vaccination status. We report three cases of invasive pneumococcal infection due to new serotypes not covered by the 7-valent conjugated vaccine, two of which led children to death. PMID:24765491

  13. Hypothesis: conjugate vaccines may predispose children to autism spectrum disorders.

    PubMed

    Richmand, Brian J

    2011-12-01

    The first conjugate vaccine was approved for use in the US in 1988 to protect infants and young children against the capsular bacteria Haemophilus influenzae type b (Hib). Since its introduction in the US, this vaccine has been approved in most developed countries, including Denmark and Israel where the vaccine was added to their national vaccine programs in 1993 and 1994, respectively. There have been marked increases in the reported prevalence of autism spectrum disorders (ASDs) among children in the US beginning with birth cohorts in the late 1980s and in Denmark and Israel starting approximately 4-5 years later. Although these increases may partly reflect ascertainment biases, an exogenous trigger could explain a significant portion of the reported increases in ASDs. It is hypothesized here that the introduction of the Hib conjugate vaccine in the US in 1988 and its subsequent introduction in Denmark and Israel could explain a substantial portion of the initial increases in ASDs in those countries. The continuation of the trend toward increased rates of ASDs could be further explained by increased usage of the vaccine, a change in 1990 in the recommended age of vaccination in the US from 15 to 2 months, increased immunogenicity of the vaccine through changes in its carrier protein, and the subsequent introduction of the conjugate vaccine for Streptococcus pneumoniae. Although conjugate vaccines have been highly effective in protecting infants and young children from the significant morbidity and mortality caused by Hib and S. pneumoniae, the potential effects of conjugate vaccines on neural development merit close examination. Conjugate vaccines fundamentally change the manner in which the immune systems of infants and young children function by deviating their immune responses to the targeted carbohydrate antigens from a state of hypo-responsiveness to a robust B2 B cell mediated response. This period of hypo-responsiveness to carbohydrate antigens coincides with the intense myelination process in infants and young children, and conjugate vaccines may have disrupted evolutionary forces that favored early brain development over the need to protect infants and young children from capsular bacteria. PMID:21993250

  14. Optimal Serotype Compositions for Pneumococcal Conjugate Vaccination under Serotype Replacement

    PubMed Central

    Nurhonen, Markku; Auranen, Kari

    2014-01-01

    Pneumococcal conjugate vaccination has proved highly effective in eliminating vaccine-type pneumococcal carriage and disease. However, the potential adverse effects of serotype replacement remain a major concern when implementing routine childhood pneumococcal conjugate vaccination programmes. Applying a concise predictive model, we present a ready-to-use quantitative tool to investigate the implications of serotype replacement on the net effectiveness of vaccination against invasive pneumococcal disease (IPD) and to guide in the selection of optimal vaccine serotype compositions. We utilise pre-vaccination data on pneumococcal carriage and IPD and assume partial or complete elimination of vaccine-type carriage, its replacement by non-vaccine-type carriage, and stable case-to-carrier ratios (probability of IPD per carriage episode). The model predicts that the post-vaccination IPD incidences in Finland for currently available vaccine serotype compositions can eventually decrease among the target age group of children <5 years of age by 75%. However, due to replacement through herd effects, the decrease among the older population is predicted to be much less (20–40%). We introduce a sequential algorithm for the search of optimal serotype compositions and assess the robustness of inferences to uncertainties in data and assumptions about carriage and IPD. The optimal serotype composition depends on the age group of interest and some serotypes may be highly beneficial vaccine types in one age category (e.g. 6B in children), while being disadvantageous in another. The net effectiveness will be improved only if the added serotype has a higher case-to-carrier ratio than the average case-to-carrier ratio of the current non-vaccine types and the degree of improvement in effectiveness depends on the carriage incidence of the serotype. The serotype compositions of currently available pneumococcal vaccines are not optimal and the effectiveness of vaccination in the population at large could be improved by including new serotypes in the vaccine (e.g. 22 and 9N). PMID:24550722

  15. Immune response to a diphtheria and tetanus toxoid administration in a three-dose diphtheria tetanus whole-cell pertussis\\/enhanced inactivated poliovirus vaccination schedule: A 7-year follow up

    Microsoft Academic Search

    T. A. Swartz; P. Saliou; E. Catznelson; C. Blondeau; I. Gil; T. Peled; O. Havkin; M. Fletcher

    2003-01-01

    The immune response to diphtheria and tetanus toxoid components of a combined diphtheria tetanus whole-cell pertussis\\/enhanced inactivated poliovirus (DTwP\\/eIPV) vaccine, administered in a three-dose schedule to infants at 2, 3\\u000a$${\\\\raise0.7ex\\\\hbox{$1$} \\\\!\\\\mathord{\\\\left\\/ {\\\\vphantom {1 2}}\\\\right.\\\\kern-\\\

  16. Efficacy and effectiveness of extended-valency pneumococcal conjugate vaccines

    PubMed Central

    Lee, Hyunju; Choi, Eun Hwa

    2014-01-01

    The 7-valent pneumococcal protein conjugate vaccine (PCV7) has been shown to be highly efficacious against invasive pneumococcal diseases and effective against pneumonia and in reducing otitis media. The introduction of PCV7 has resulted in major changes in the epidemiology of pneumococcal diseases. However, pneumococcal vaccines induce serotype-specific immunity, and a relative increase in non-vaccine serotypes has been reported following the widespread use of PCV7, leading to a need for extended serotype coverage for protection. PCV10 and PCV13 have been licensed on the basis of noninferiority of immunogenicity compared to a licensed conjugate vaccine. In this article, we aimed to review important data regarding the efficacy and effectiveness of the extended-coverage PCVs published or reported thus far and to discuss future implications for pneumococcal vaccines in Korea. After the introduction of PCV10 and PCV13, within a short period of time, evidence of protection conferred by these vaccines against invasive and mucosal infections caused by most of the serotypes included in the vaccines is accumulating. The choice of vaccine should be based on the changes in the dynamics of pneumococcal serotype distribution and diseases in the region where the vaccines are to be used. Continuous surveillance is essential for the appropriate use of pneumococcal vaccines and evaluation of the impact of PCVs on pneumococcal diseases. PMID:24678328

  17. 10-Valent pneumococcal non-typeable haemophilus influenzae protein D-conjugate vaccine: a review in infants and children.

    PubMed

    Plosker, Greg L

    2014-10-01

    The 10-valent pneumococcal non-typeable Haemophilus influenzae protein D-conjugate vaccine (PHiD-CV) (Synflorix™) includes ten serotype-specific polysaccharides of Streptococcus pneumoniae, eight of which are conjugated individually to a nonlipidated cell-surface lipoprotein (protein D) of non-typeable H. influenzae and two of which are conjugated to nontoxic tetanus or diphtheria toxoid carrier proteins. This article provides an overview of the well-established immunogenicity of PHiD-CV, including functional immune responses and immunologic memory, as well as immune responses in preterm infants and HIV-infected children. It also includes a brief discussion of cross-protection against vaccine-related serotypes (6A and 19A) and focuses on labelling in the EU, where PHiD-CV is approved for active immunization against invasive disease, pneumonia, and acute otitis media (AOM) caused by S. pneumoniae in infants and young children up to 5 years of age. Evidence of the protective efficacy and effectiveness of PHiD-CV against pneumococcal diseases is available from several studies, including the randomized, double-blind trials COMPAS (Clinical Otitis Media and Pneumonia Study) and FinIP (Finnish Invasive Pneumococcal disease), as well as postmarketing studies from various countries. As would be expected, protection against pneumonia or AOM is substantially lower than that against invasive pneumococcal disease, as many micro-organisms other than pneumococcal vaccine serotypes can cause pneumonia and AOM, thereby limiting the overall protection of PHiD-CV against these diseases. PHiD-CV has a safety and reactogenicity profile similar to that of other pneumococcal conjugate vaccines. PMID:25192686

  18. Biochemical and biological characteristics of cross-reacting material 197 CRM197, a non-toxic mutant of diphtheria toxin: use as a conjugation protein in vaccines and other potential clinical applications.

    PubMed

    Bröker, Michael; Costantino, Paolo; DeTora, Lisa; McIntosh, E David; Rappuoli, Rino

    2011-07-01

    The biochemical and biological characteristics of CRM(197) are reviewed. Polysaccharide protein conjugate vaccines represent an important technological advancement that allowed for protection against dangerous diseases in vulnerable populations such as infants. The first carrier proteins, diphtheria and tetanus toxoids, were chosen in the context of an extensive body of information describing their immunogenicity and safety profiles in clinical use. These carriers perform well, and they require detoxification. A non-toxic mutant of diphtheria toxin, cross-reacting material 197 (CRM(197)), is a useful carrier protein with several manufacturing and other potential advantages over toxoids. For over a decade, several important and widely used routine childhood glycoconjugate vaccines against serious illnesses, including Haemophilus influenzae type b and pneumococcal disease, have employed CRM(197) as carrier protein. Additional clinical applications of CRM(197), as in chemotherapy, also exist. PMID:21715186

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

    PubMed

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

    2015-03-10

    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

  20. Effect of currently approved carriers and adjuvants on the pre-clinical efficacy of a conjugate vaccine against oxycodone in mice and rats.

    PubMed

    Pravetoni, Marco; Vervacke, Jeffrey S; Distefano, Mark D; Tucker, Ashli M; Laudenbach, Megan; Pentel, Paul R

    2014-01-01

    Vaccination against the highly abused prescription opioid oxycodone has shown pre-clinical efficacy for blocking oxycodone effects. The current study further evaluated a candidate vaccine composed of oxycodone derivatized at the C6 position (6OXY) conjugated to the native keyhole limpet hemocyanin (nKLH) carrier protein. To provide an oxycodone vaccine formulation suitable for human studies, we studied the effect of alternative carriers and adjuvants on the generation of oxycodone-specific serum antibody and B cell responses, and the effect of immunization on oxycodone distribution and oxycodone-induced antinociception in mice and rats. 6OXY conjugated to tetanus toxoid (TT) or a GMP grade KLH dimer (dKLH) was as effective as 6OXY conjugated to the nKLH decamer in mice and rats, while the 6OXY hapten conjugated to a TT-derived peptide was not effective in preventing oxycodone-induced antinociception in mice. Immunization with 6OXY-TT s.c. absorbed on alum adjuvant provided similar protection to 6OXY-TT administered i.p. with Freund's adjuvant in rats. The toll-like receptor 4 (TLR4) agonist monophosphoryl lipid A (MPLA) adjuvant, alone or in combination with alum, offered no advantage over alum alone for generating oxycodone-specific serum antibodies or 6OXY-specific antibody secreting B cells in mice vaccinated with 6OXY-nKLH or 6OXY-TT. The immunogenicity of oxycodone vaccines may be modulated by TLR4 signaling since responses to 6OXY-nKLH in alum were decreased in TLR4-deficient mice. These data suggest that TT, nKLH and dKLH carriers provide consistent 6OXY conjugate vaccine immunogenicity across species, strains and via different routes of administration, while adjuvant formulations may need to be tailored to individual immunogens or patient populations. PMID:24797666

  1. Effect of Vaccine Shortages on Timeliness of Pneumococcal Conjugate Vaccination: Results From the 2001-2005 National Immunization Survey

    Microsoft Academic Search

    Philip J. Smith; J. Pekka Nuorti; James A. Singleton; Zhen Zhao; Kirk M. Wolter

    BACKGROUND. In September 2001 and again in February 2004, the Centers for Disease Control and Prevention announced shortages in the supply of the pneumococcal conjugate vaccine. We describe the effects of the pneumococcal conjugate vaccine shortages in 2001-2003 and 2004 on the timeliness of vaccination uptake for quarterly birth cohorts affected by the shortages. METHODS. A total of 102 478

  2. Impact of conjugation chemistry on the immunogenicity of S. Typhimurium conjugate vaccines.

    PubMed

    Stefanetti, G; Rondini, S; Lanzilao, L; Saul, A; MacLennan, C A; Micoli, F

    2014-10-21

    Salmonella Typhimurium is major cause of invasive nontyphoidal Salmonella disease in Africa. Conjugation of S. Typhimurium O-antigen to an appropriate carrier protein constitutes a possible strategy for the development of a vaccine against this disease, for which no vaccines are currently available. The conjugation chemistry used is one of the parameters that can affect the immunogenicity of glycoconjugate vaccines. Herein different glycoconjugates were synthesized to investigate the impact of this variable on the immunogenicity of S. Typhimurium conjugate vaccines in mice, all with CRM??? as carrier protein. Random derivatization along the O-antigen chain was compared with site-directed activation of the terminal KDO sugar residue of the core oligosaccharide. In particular, two different random approaches were used, based on the oxidation of the polysaccharide, which differently impact the structure and conformation of the O-antigen chain. For the selective conjugation methods, linkers of two different lengths were compared. When tested in mice, all conjugates induced anti-O-antigen IgG antibodies with serum bactericidal activity. Similar anti-O-antigen antibody levels were elicited independent of the chemistry used and a higher degree of saccharide derivatization did not impact negatively on the anti-O-antigen IgG response. Bactericidal activity of serum antibodies induced by selective conjugates was similar independent of the length of the spacer used. Random conjugates elicited antibodies with greater bactericidal activity than selective ones, and an inverse correlation was found between degree of O-antigen modification and antibody functional activity. PMID:25192974

  3. Effectiveness of pneumococcal conjugate vaccine and rotavirus vaccine introduction into the South African public immunisation programme.

    PubMed

    Madhi, S A; Bamford, L; Ngcobo, N

    2014-03-01

    Immunisation has contributed greatly to the control of vaccine-preventable diseases and therefore to improvements in health and survival, especially among young children, and remains one of the most successful and cost-effective public health interventions. This remains true for many of the newer, more expensive vaccines. Vaccines against invasive pneumococcal disease and rotavirus infection were introduced into the South African Expanded Programme on Immunization in April 2009. This article describes the rationale for and process of the introduction of these two vaccines, pneumococcal conjugate vaccine and rotavirus vaccine. It also aims to evaluate the success of and challenges related to their introduction, in terms of both achieving universal coverage and improving survival and health in South African children. PMID:24893498

  4. Pneumococcal conjugate vaccines for preventing otitis media

    Microsoft Academic Search

    A. G. S. C. Jansen; E. Hak; R. H. Veenhoven; R. A. M. J. Damoiseaux; A. G. M. Schilder; E. A. M. Sanders

    2009-01-01

    Background\\u000aAcute otitis media (AOM) is a very common early infancy and childhood disease. The marginal benefits of antibiotics on AOM, the\\u000aincreasing problem of bacterial resistance to antibiotics, and the huge estimated direct and indirect annual costs associated with otitis\\u000amedia (OM) have prompted a search for effective vaccines to prevent AOM.\\u000aObjectives\\u000aTo assess the effect of pneumococcal

  5. 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

  6. Management of Febrile Children in the Conjugate Pneumococcal Vaccine Era

    Microsoft Academic Search

    Michael E. Gabriel; Leslie Aiuto; Nina Kohn; Stephen R. Barone

    2004-01-01

    The objective of this study was to evaluate physician attitudes toward the management of young febrile children since the introduction of the conjugate heptavalent pneumococcal vaccine (PCV 7). Seven thousand five hundred pediatricians and 7,500 emergency department (ED) physicians were surveyed with regard to their management of a febrile 7-month-old child and 20-month-old child without an apparent fever focus. Specifically,

  7. Acute mastoiditis in the pneumococcal conjugate vaccine era.

    PubMed

    Tamir, Sharon Ovnat; Roth, Yehudah; Dalal, Ilan; Goldfarb, Abraham; Marom, Tal

    2014-08-01

    Following the introduction of the 7- and 13-valent pneumococcal conjugate vaccines, we observed an inverse relationship between the increasing rate of immunized children and the proportion of middle ear fluid cultures collected during acute mastoiditis episodes that tested positive for Streptococcus pneumoniae among a subset of children 0 to 6 years old who had initially presented with severe acute otitis media and had bacterial cultures collected during tympanocentesis or from spontaneous otorrhea. PMID:24920600

  8. Acute Mastoiditis in the Pneumococcal Conjugate Vaccine Era

    PubMed Central

    Tamir, Sharon Ovnat; Roth, Yehudah; Dalal, Ilan; Goldfarb, Abraham

    2014-01-01

    Following the introduction of the 7- and 13-valent pneumococcal conjugate vaccines, we observed an inverse relationship between the increasing rate of immunized children and the proportion of middle ear fluid cultures collected during acute mastoiditis episodes that tested positive for Streptococcus pneumoniae among a subset of children 0 to 6 years old who had initially presented with severe acute otitis media and had bacterial cultures collected during tympanocentesis or from spontaneous otorrhea. PMID:24920600

  9. Impact of the Conjugation Method on the Immunogenicity of Streptococcus pneumoniae Serotype 19F Polysaccharide in Conjugate Vaccines ?

    PubMed Central

    Poolman, Jan; Frasch, Carl; Nurkka, Anu; Käyhty, Helena; Biemans, Ralph; Schuerman, Lode

    2011-01-01

    7vCRM (Pfizer, Inc.) and PHiD-CV (GlaxoSmithKline Biologicals) are two pneumococcal conjugate vaccines licensed for the prevention of invasive pneumococcal disease and acute otitis media caused by the vaccine serotypes of Streptococcus pneumoniae. Neither vaccine contains serotype 19A, but both contain the closely related serotype 19F. No decrease in the incidence of serotype 19A disease has been observed following the introduction of 7vCRM, suggesting that this serotype 19F-containing vaccine provides limited cross-protection against serotype 19A. To investigate the impact that conjugation methods may have on antipolysaccharide immune responses and to determine whether this limited cross-protection is characteristic of the serotype 19F polysaccharide or rather of the 19F-CRM (cross-reacting material) conjugate, we compared naturally induced antibodies against serotypes 19F and 19A with antibodies induced after vaccination with different pneumococcal conjugate vaccines. We found that conjugation of the serotype 19F polysaccharide using reductive amination (as in 7vCRM) resulted in the formation of at least one additional epitope that is not present in the native form of the 19F polysaccharide or following 19F conjugation using a bifunctional spacer (as in the prototype vaccine 7vOMPC) or cyanylation (as in PHiD-CV). We also found that pneumococcal vaccines conjugated using cyanylation induce more opsonophagocytic antibodies against serotype 19F and a considerably higher level of cross-opsonophagocytic antibodies against serotype 19A than vaccines conjugated using reductive amination. In conclusion, these results suggest that the conjugation method can influence the functionality of the antibodies induced against the homologous serotype 19F and the cross-reactive serotype 19A of S. pneumoniae. PMID:21123523

  10. 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

  11. Cost effectiveness of child pneumococcal conjugate vaccination in middle-income countries

    Microsoft Academic Search

    Mari M. Nakamura; Azadeh Tasslimi; Tracy A. Lieu; Orin Levine; Maria Deloria Knoll; Louise B. Russell; Anushua Sinha

    Policy-makers require information on the potential benefits of and economic case for pneumococcal conjugate vaccination in middle-income countries. We built decision analysis models to evaluate a three-dose infant series of the 7-, 10- or 13-valent pneumococcal conjugate vaccines in 77 middle-income countries compared with no vaccination, accounting for direct protection of vaccinated children as well as herd protection and serotype

  12. Influence of preimmunization with tetanus toxoid on immune responses to tetanus toxin fragment C-guest antigen fusions in a Salmonella vaccine carrier.

    PubMed

    Chabalgoity, J A; Villareal-Ramos, B; Khan, C M; Chatfield, S N; de Hormaeche, R D; Hormaeche, C E

    1995-07-01

    We have previously described a new system for the delivery of recombinant antigens in live Salmonella vaccines as genetic fusions to the C terminus of fragment C of tetanus toxin (TetC) driven by the anaerobically inducible nirB promoter. It has been reported that preimmunization with tetanus toxoid (TT) can suppress the antibody response to peptides chemically coupled to TT (epitope-specific suppression) in both animals and humans, which could interfere with efficacy of the Salmonella-TetC delivery system. We report that preimmunization of BALB/c mice with TT in alum did not suppress the response to either of two protective antigens of Schistosoma mansoni, the full-length S. mansoni P28 glutathione S-transferase (P28) and a construct consisting of eight tandem copies of the protective peptide comprising amino acids 115 to 131 of P28. The guest antigens were expressed in the aroA Salmonella typhimurium SL3261 vaccine strain as fusions to TetC. Preimmunization with TT 10 weeks before administration of the recombinant salmonellae did not alter the antibody response to the full-length P28, whereas the response to the peptide comprising amino acids 115 to 131 was increased by preimmunization with TT, with the increase seen mainly in the immunoglobulin G1 isotype. The antitetanus response was increased by preimmunization with TT in all groups receiving salmonellae expressing TetC. The results could be important when one is considering the use of the Salmonella-TetC delivery system in populations preimmunized with TT. PMID:7790070

  13. Mycobacterium tuberculosis arabinomannan–protein conjugates protect against tuberculosis

    Microsoft Academic Search

    Beston Hamasur; Melles Haile; Andrzej Pawlowski; Ulf Schröder; Ann Williams; Graham Hatch; Graham Hall; Philip Marsh; Gunilla Källenius; Stefan B. Svenson

    2003-01-01

    Lipoarabinomannan (LAM) is a major structural surface component of mycobacteria. Arabinomannan (AM) oligosaccharides derived from LAM of Mycobacterium tuberculosis H37Rv were isolated and covalently conjugated to tetanus toxoid (TT) or to short-term culture filtrate proteins (antigen 85B (Ag85B) or a 75kDa protein) from M. tuberculosis strain Harlingen. The different AM oligosaccharide (AMOs)–protein conjugate vaccine candidates proved to be highly immunogenic,

  14. Investigation in a murine model of possible mechanisms of enhanced local reactions to post-primary diphtheria-tetanus toxoid boosters in recipients of acellular pertussis-diphtheria-tetanus vaccine

    PubMed Central

    Ochiai, Masaki; Horiuchi, Yoshinobu; Yuen, Chun-Ting; Asokanathan, Catpagavalli; Yamamoto, Akihiko; Okada, Kenji; Kataoka, Michiyo; Markey, Kevin; Corbel, Michael; Xing, Dorothy

    2014-01-01

    In recipients primed with acellular pertussis diphtheria-tetanus combined vaccine (DTaP) an increased incidence of severe local reactions with extensive redness/swelling has been reported for each subsequent dose of diphtheria-tetanus based combination vaccine given as a booster. This has been attributed to residual active pertussis toxin (PT) in the primary vaccine. In this study, we investigated the possible contribution of the A-subunit enzymatic activity and the B-oligomer carbohydrate binding activity of residual PT in DTaP to local reactions in a murine model using Japanese DTaP batches produced before and after the introduction of a test for reversion of pertussis toxoid to toxin. Residual PT activity was correlated with the B-oligomer carbohydrate binding activity. The in vivo mouse footpad swelling model assay indicated that the B-oligomer carbohydrate binding activity and possibly other factors were associated with intensified sensitization to local reaction following diphtheria toxoid booster. PMID:25424818

  15. Otitis media in children vaccinated during consecutive 7-valent or 10-valent pneumococcal conjugate vaccination schedules

    PubMed Central

    2014-01-01

    Background In 2001 when 7-valent pneumococcal conjugate vaccine (PCV7) was introduced, almost all (90%) young Australian Indigenous children living in remote communities had some form of otitis media (OM), including 24% with tympanic membrane perforation (TMP). In late 2009, the Northern Territory childhood vaccination schedule replaced PCV7 with 10-valent pneumococcal Haemophilus influenzae protein D conjugate vaccine (PHiD-CV10). Methods We conducted regular surveillance of all forms of OM in children in remote Indigenous communities between September 2008 and December 2012. This analysis compares children less than 36 months of age who received a primary course of at least two doses of PCV7 or PHiD-CV10, and not more than one dose of another pneumococcal vaccine. Results Mean ages of 444 PCV7- and 451 PHiD-CV10-vaccinated children were 20 and 18 months, respectively. Bilaterally normal middle ears were detected in 7% and 9% respectively. OM with effusion was diagnosed in 41% and 51% (Risk Difference 10% [95% Confidence Interval 3 to 17] p?=?0.002), any suppurative OM (acute OM or any TMP) in 51% versus 39% (RD ?12% [95% CI ?19 to ?5] p?=?0.0004], and TMP in 17% versus 14% (RD ?3% [95% CI ?8 to 2] p?=?0.2), respectively. Multivariate analyses described a similar independent negative association between suppurative OM and PHiD-CV10 compared to PCV7 (Odds Ratio?=?0.6 [95% CI 0.4 to 0.8] p?=?0.001). Additional children in the household were a risk factor for OM (OR?=?2.4 [95% CI 2 to 4] p?=?0.001 for the third additional child), and older age and male gender were associated with less disease. Other measured risk factors were non-significant. Similar clinical results were found for children who had received non-mixed PCV schedules. Conclusions Otitis media remains a significant health and social issue for Australian Indigenous children despite PCV vaccination. Around 90% of young children have some form of OM. Children vaccinated in with PHiD-CV10 had less suppurative OM than children vaccinated with PCV7. Ongoing surveillance during the PCV13 era, and trials of early intervention including earlier and mixed vaccine schedules are warranted. PMID:25109288

  16. Cost effectiveness of child pneumococcal conjugate vaccination in GAVI-eligible countries

    Microsoft Academic Search

    Azadeh Tasslimi; Mari M. Nakamura; Orin Levine; Maria D. Knoll; Louise B. Russell; Anushua Sinha

    Policy-makers increasingly rely on cost-effectiveness analysis, in addition to clinical effectiveness, when considering the introduction of new childhood vaccines. A previous analysis determined vaccination of infants with 7-valent pneumococcal conjugate vaccine (PCV) to be highly cost effective in preventing child mortality in countries eligible for financial support from the Global Alliance for Vaccines and Immunization (GAVI). We aimed to update

  17. Immunogenicity and safety of heptavalent conjugate vaccine against Streptococcus pneumoniae in pre-term Polish infants

    Microsoft Academic Search

    Ewa Szynczewska; Danuta Chlebna-Sokó?

    2011-01-01

    The purpose of the study was to assess post-vaccination immune response and occurrence of adverse events in the group of prematurely born infants. The study included 40 pre-term infants. Each child was vaccined four times (2, 4, 6 and 16 months) with the heptavalent conjugated pneumococcal vaccine (PCV7). Assessing of the level of antibodies was performed before vaccination, 4 weeks

  18. 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

  19. The Differential Impact of Coadministered Vaccines, Geographic Region, Vaccine Product and Other Covariates on Pneumococcal Conjugate Vaccine Immunogenicity

    PubMed Central

    2014-01-01

    Background: Antipneumococcal capsular polysaccharide antibody concentrations are used as predictors of vaccine efficacy against vaccine serotype (ST) pneumococcal disease among infants. While pneumococcal conjugate vaccines (PCV) are recommended globally, factors associated with optimal PCV immune response are not well described. We aimed to systematically assess local setting factors, beyond dosing schedule, which may affect PCV antibody levels. Methods: We conducted a literature review of PCV immunogenicity, abstracting data from published reports, unpublished sources, and conference abstracts from 1994 to 2010 (and ad hoc 2011 reports). Studies included in this analysis evaluated ? 2 primary doses of PCV before 6 months of age in non–high-risk populations, used 7-valent or higher PCV products (excluding Aventis-Pasteur and Merck products) and provided information on geometric mean concentration (GMC) for STs 1, 5, 6B, 14, 19F or 23F. Using random effects meta-regression, we assessed the impact of geographic region, coadministered vaccines and PCV product on postprimary GMC, adjusting for dosing schedule and ELISA laboratory method. Results: Of 12,980 citations reviewed, we identified 103 vaccine study arms for this analysis. Children in studies from Asia, Africa and Latin America had significantly higher GMC responses compared with those in studies from Europe and North America. Coadministration with acellular pertussis DTP compared with whole-cell DTP had no effect on PCV immunogenicity except for ST14, where GMCs were higher when coadministered with acellular pertussis DTP. Vaccine product, number of PCV doses, dosing interval, age at first dose and ELISA laboratory method also affected the GMC. Conclusions: PCV immunogenicity is associated with geographic region and vaccine product; however, the associations and magnitude varied by ST. Consideration of these factors is essential when comparing PCV immunogenicity results between groups and should be included in the evidence base when selecting optimal PCV vaccine schedules in specific settings. PMID:24336055

  20. A Study on Longevity of Immune Response after Vaccination with Salmonella Typhi Vi Conjugate Vaccine (Pedatyph™) in Children

    PubMed Central

    Sadasivam, Kanimozhi; Vivekanandhan, Aravindhan; Arunachalam, Prema; Pasupathy, Sekar

    2015-01-01

    Background and Objectives Owing to the limitations of the conventional polysaccharide vaccines, global efforts have been made to develop conjugated polysaccharide vaccines for typhoid. Duration of immune response induced by these vaccines is critical to define the efficacy and frequency of required booster dose. This study was done to determine the duration of immune response following vaccination with Salmonella Typhi Vi conjugate vaccine (Pedatyph™) in children and to assess the booster effect of second dose of conjugate typhoid vaccine. Materials and Methods Forty children were recalled from a cohort of 400 children, who received one dose or two doses of PedaTyph™, 30 months after vaccination. Ten non-vaccinated children were also recalled. Their serum samples were assessed by ELISA for anti Vi antibody. Results Significantly high titers of anti-Vi polysaccharide IgG antibodies were present in vaccinated children even after 30 months of vaccination as compared to non-vaccinated children. Geometric mean titers (GMT) with 95% confidence intervals were 14 (4.8-29.8), 17 (7.4-33) and 6.4 (0.8-12) ?g/ml for single dose, two doses and control group respectively. The children in two doses group had higher antibody titers as compared to single dose group. However, the difference was not significant. Interpretation and Conclusion PedaTyph™ was found to induce long term immune response as evidenced by presence of significant anti-Vi polysaccharide antibodies after 30 months of vaccination. No significant advantage of two doses regimen over one dose was found. Hence one dose vaccination with PedaTyph™ is suggested.

  1. Making new vaccines affordable: a comparison of financing processes used to develop and deploy new meningococcal and pneumococcal conjugate vaccines.

    PubMed

    Hargreaves, James R; Greenwood, Brian; Clift, Charles; Goel, Akshay; Roemer-Mahler, Anne; Smith, Richard; Heymann, David L

    2011-11-26

    Mechanisms to increase access to health products are varied and controversial. Two innovative mechanisms have been used to accelerate the development of low-price supply lines for conjugate vaccines. The Meningitis Vaccine Project is a so-called push mechanism that facilitated technology transfer to an Indian company to establish capacity to manufacture a vaccine. The Advanced Market Commitment for pneumococcal vaccines is a so-called pull mechanism that guarantees companies a supplement paid in addition to the purchase price for vaccines for a specific period. We compare these approaches, identifying key dimensions of each and considering their potential for replication. We also discuss issues that the Global Alliance for Vaccines and Immunisation (GAVI) face now that these new vaccines are available. Progress towards GAVI's strategic aims is needed and funding is crucial. Approaches that decrease the financial pressure on GAVI and greatly increase political and financial engagement by low-income countries should also be considered. PMID:21664678

  2. Impact of conjugate 7-valent vaccination in Belgium: addressing methodological challenges.

    PubMed

    Hanquet, Germaine; Lernout, Tinne; Vergison, Anne; Verhaegen, Jan; Kissling, Esther; Tuerlinckx, David; Malfroot, Anne; Swennen, Béatrice; Sabbe, Martine

    2011-04-01

    In Belgium, the 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the national schedule in 2007. The early impact of PCV7 vaccination on paediatric invasive disease was estimated by comparing pre- and post-vaccination incidence from national surveillance. In children <2 year-olds, vaccine-serotype incidence declined by 96% but non-vaccine-types increased 2-3-fold. Overall invasive disease decreased by 23-46%, depending on adjustment for under-reporting and pre-vaccine trends. Non-vaccine-types 1 and 19A had increased before PCV7 use, suggesting the contribution of other factors. Estimation of PCV7 impact comparing pre- and post-vaccination data should adjust for pre-vaccine trends, and serotype dynamics need further exploration. PMID:21342667

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

    Microsoft Academic Search

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

    2009-01-01

    Although the currently available 7-valent pneumococcal conjugate vaccine (PCV7-CRM197) 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

  4. Transferrin conjugation confers mucosal molecular targeting to a model HIV-1 trimeric gp140 vaccine antigen?

    PubMed Central

    Mann, J.F.S.; Stieh, D.; Klein, K.; de Stegmann, D.S. Miranda; Cranage, M.P.; Shattock, R.J.; McKay, P.F.

    2012-01-01

    The generation of effective immune responses by mucosal vaccination without the use of inflammatory adjuvants, that compromise the epithelial barrier and recruit new cellular targets, is a key goal of vaccines designed to protect against sexually acquired pathogens. In the present study we use a model HIV antigen (CN54gp140) conjugated to transferrin (Tf) and evaluate the ability of the natural transferrin receptor CD71 to modulate immunity. We show that the conjugated transferrin retained high affinity for its receptor and that the conjugate was specifically transported across an epithelial barrier, co-localizing with MHC Class II+ cells in the sub-mucosal stroma. Vaccination studies in mice revealed that the Tf-gp140 conjugate elicited high titres of CN54gp140-specific serum antibodies, equivalent to a systemic vaccination, when conjugate was applied topically to the nasal mucosae whereas gp140 alone was poorly immunogenic. Moreover, the Tf-gp140 conjugate elicited both IgG and IgA responses and significantly higher gp140-specific IgA titre in the female genital tract than unconjugated antigen. These responses were achieved after mucosal application of the conjugated protein alone, in the absence of any pro-inflammatory adjuvant and suggest a potentially useful and novel molecular targeting approach, delivering a vaccine cargo to directly elicit or enhance pathogen-specific mucosal immunity. PMID:22119743

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

    Microsoft Academic Search

    Mei M Ho; Barbara Bolgiano; Michael J Corbel

    2000-01-01

    In this stability study, meningococcal C-CRM197 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°C for 5 weeks or subjected to ten cycles of freeze-thawing. The structural stability,

  6. Pneumococcal vaccination strategies in adult population: perspectives with the pneumococcal 13 - valent polysaccharide conjugate vaccine.

    PubMed

    Alicino, C; Barberis, I; Orsi, A; Durando, P

    2014-02-01

    Streptococcus pneumoniae (Sp) is a leading cause of infection in people of all ages worldwide, determining a significant impact because of its relatively high incidence rate, the associated economic costs, and the high case-fatality rates. More attention has to be paid for elderly and people with one or more risk factors, in order to reduce health costs and pneumococcal hospital admissions. Moreover, the increasing incidence of antibiotic-resistant Sp strains is a source of concern for its relevant clinical importance in health-care settings. At present, the 23-valent polysaccharide (PPV23) vaccine has shown some limits in terms of protection in the elderly population and against invasive diseases, among adults affected with chronic diseases, non-bacteriemic pneumonias and with immune suppression, in particular in adults with HIV. In December 2011, FDA licensed the 13-valent pneumococcal conjugate vaccine (PCV13) for prevention of pneumonia and invasive diseases (IPDs) in adults aged ?50 years. The same decision was concomitantly assumed in Europe by EMA. PCV13 has shown superior results both in terms of immunogenicity and of adequate stimulation of a stable and long-lasting immunological memory. European recommendations for PCV13 vaccination in adults are still heterogeneous between Countries. The availability of PCV13 for adults offer a new and promising tool against Sp IPDs and non-IPDs, especially in elderly and at risk populations. PMID:24572454

  7. Pneumococcal antibodies in a child with type 14 pneumococcal conjugate vaccine failure

    Microsoft Academic Search

    Katherine L. O’Brien; Jennifer Moïsi; Sandra Romero-Steiner; Patricia Holder; George M. Carlone; Raymond Reid; Mathuram Santosham

    2009-01-01

    We measured the concentration, opsonic activity, and avidity of serotype-specific serum antibodies in a pneumococcal conjugate vaccine (PnCRM7) efficacy trial participant who contracted serotype 14 pneumococcal bacteremia following dose 3 of PnCRM7. Controls included 18 PnCRM7- and 10 MnCC-vaccinated children without invasive pneumococcal disease (IPD). The child with vaccine failure had 4.98mcg\\/mL of serotype 14 antibodies 10 days before disease

  8. Randomized Clinical Trial To Evaluate the Immunogenicity of Quadrivalent Meningococcal Conjugate and Polysaccharide Vaccines in Adults in the United Kingdom

    PubMed Central

    Clutterbuck, Elizabeth A.; Haworth, Kathryn; Bowman, Jaclyn; Omar, Omar; Thompson, Amber J.; Blanchard-Rohner, Geraldine; Yu, Ly-Mee; Snape, Matthew D.; Pollard, Andrew J.

    2014-01-01

    Meningococcal conjugate vaccines are today successfully deployed in universal programs for children and adolescents in different geographic regions to control meningitis and septicemia. However, in adults, the advantages of these conjugates over the older polysaccharide vaccines are less clear. In this randomized clinical trial, we demonstrated that both conjugate and polysaccharide quadrivalent meningococcal vaccines elicit protective antibody responses in adults aged 18 to 70. (This study has been registered at www.clinicaltrials.gov under registration no. NCT00901940.) PMID:24964805

  9. Booster Effect of Low Doses of Tetanus Toxoid in Elderly Vaccinees

    Microsoft Academic Search

    B. Björkholm; L. Hagberg; G. Sundbeck; M. Granström

    2000-01-01

    In order to improve the immunity to diphtheria, the recommended booster dose of diphtheria\\/tetanus vaccine for adults in\\u000a Sweden was changed in 1986 from 0.5?ml of tetanus vaccine with a small diphtheria dose to 0.25?ml of a diphtheria\\/tetanus\\u000a vaccine containing 7.5?Lf tetanus toxoid and 30?Lf diphtheria toxoid\\/ml. This change resulted in an increase in the dose of\\u000a diphtheria toxoid from

  10. Safety and immunogenicity of a booster dose of the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine coadministered with DTPw-HBV/Hib and poliovirus vaccines.

    PubMed

    Bermal, Nancy; Szenborn, Leszek; Edison, Alberto; Hernandez, Marina; Pejcz, Jerzy; Majda-Stanislawska, Ewa; Gatchalian, Salvacion; Fanic, Aurélie; Dieussaert, Ilse; Schuerman, Lode

    2011-01-01

    The safety and reactogenicity profiles of the 10-valent pneumococcal conjugate vaccine, PHiD-CV, and 7vCRM were comparable within the Philippines and Poland when coadministered as a booster dose with DTPw-HBV/Hib and poliovirus vaccines to toddlers primed with the same vaccines. Robust immune responses for all 10 vaccine pneumococcal serotypes and protein D following PHiD-CV booster vaccination were indicative of effective priming. PMID:20980933

  11. [Introduction of a conjugate vaccine against Hib in Chile and Uruguay].

    PubMed

    Landaverde, M; Di Fabio, J L; Ruocco, G; Leal, I; de Quadros, C

    1999-03-01

    In some countries, the invasive disease caused by Haemophilus influenzae type b (Hib) has been practically eliminated thanks to vaccination. However, in much of the developing world, meningitides and pneumonias caused by these bacteria continue to be a major cause of childhood morbidity and mortality, as well as high hospitalization costs. Because safe and effective conjugate vaccines are now available, the Special Program for Vaccines and Immunization of the Pan American Health Organization has recommended introducing them into the regular vaccination regimen of as many countries as possible. This has been done in Chile and Uruguay, where the Hib vaccine now forms part of the regular vaccination routine. When the vaccine was being introduced, both countries had difficulties they could have avoided if they had known of the experiences of other nations. Therefore, these two countries now offer the lessons they learned to other nations considering introducing the vaccine into their immunization programs. The most important lessons were to: strengthen the epidemiological surveillance system sufficiently in advance of introducing the vaccine; with the support of scientific societies, present the technical information that justifies introducing the vaccine; seek community backing and acceptance; precisely establish in advance the presentation and dosage of the vaccine that is most appropriate for the country; and be certain to have the political and legal decisions needed to ensure the continuity of Hib vaccination in the future. PMID:10355317

  12. Spotlight on DTPa-HBV-IPV/Hib Vaccine (Infanrix hexa).

    PubMed

    Dhillon, Sohita

    2010-10-01

    Infanrix hexa, administered intramuscularly, is a diphtheria, tetanus, acellular pertussis, hepatitis B (HBV), inactivated poliomyelitis and Haemophilus influenzae type b (Hib) conjugate vaccine, indicated for primary and booster vaccination of infants. Infanrix hexa should be administered as a two- or three-dose primary vaccination course in infants aged < or =6 months, followed by booster vaccination between 11 and 18 months of age, with an interval of at least 6 months between the last dose of primary vaccination and the booster dose. This spotlight reviews the immunogenicity and protective effectiveness, as well as the reactogenicity and safety of Infanrix hexa. Infanrix hexa as primary and booster vaccination was safe and highly immunogenic for all its component toxoids/antigens in infants aged <2 years, regardless of vaccination schedules. Its immunogenicity and safety profiles were generally similar to those of currently available vaccines, the diphtheria, tetanus and acellular pertussis-based pentavalent vaccines plus monovalent HBV or Hib vaccines. In large clinical studies, Infanrix hexa elicited a strong immune response against vaccine toxoids/antigens, as indicated by high seroprotection/seropositivity/vaccine response rates and geometric mean titers. Moreover, antibodies against vaccine toxoids/antigens persisted for up to a mean of approximately 6 years after booster vaccination, and the vaccine induced long-term immune memory against hepatitis B surface antigen and Hib antigen. A strong immune response against Infanrix hexa toxoids/antigens after primary vaccination was also induced in infants who had received a dose of HBV vaccine at birth and in pre-term infants, although the response in the latter group was somewhat lower than that in full-term infants. In addition, when coadministered with other childhood vaccines, the immunogenicity of Infanrix hexa or that of the concomitantly administered vaccine was generally not altered. Hexavalent vaccines, including Infanrix hexa, were protective against invasive Hib disease; Infanrix hexa is also expected to be protective against pertussis. Most solicited local and general symptoms with Infanrix hexa were mild to moderate in intensity and the vaccine was associated with few unsolicited adverse events. Available clinical data from more than 10 years' experience with the vaccine suggest that Infanrix hexa as primary and booster vaccination is a safe and useful option for providing protection against the common childhood diseases of diphtheria, tetanus, poliomyelitis, pertussis, hepatitis B and invasive Hib disease. PMID:20795752

  13. Scientific challenges for the quality control and production of group C meningococcal conjugate vaccines.

    PubMed

    Jódar, Luis; Griffiths, Elwyn; Feavers, Ian

    2004-02-25

    Recommendations (formerly known as requirements) for meningococcal polysaccharide vaccines were adopted by the World Health Organisation (WHO) Expert Committee on Biological Standardisation in 1976 and amended in 1978 and 1981. In clinical studies, these vaccines have been shown to have efficacy of at least 90% and have proved to be highly effective in vaccination programmes. Nevertheless, their inability to elicit protective responses in young infants or to induce good immunological memory has prevented their implementation in national infant immunisation schedules. Following the successful introduction of the Haemophilus influenzae type b conjugate (Hib) vaccines, considerable progress has been made in the development of similar conjugate vaccines based on meningococcal group C capsular polysaccharide. Controlled clinical trials have demonstrated that they induce protective levels of antibodies to group C polysaccharide in all age groups and, as T-cell dependent antigens, induce immunological memory and affinity maturation of anti-capsular antibodies. Such vaccines have been shown to offer protective immunity following the introduction of group C conjugates in the UK. The World Health Organisation has produced recommendations for the production and control of these new vaccines. PMID:15161082

  14. DTPa-HBV-IPV/Hib Vaccine (Infanrix hexa): A Review of its Use as Primary and Booster Vaccination.

    PubMed

    Dhillon, Sohita

    2010-05-28

    Infanrix hexa, administered intramuscularly, is a diphtheria, tetanus, acellular pertussis, hepatitis B (HBV), inactivated poliomyelitis and Haemophilus influenzae type b (Hib) conjugate vaccine, indicated for primary and booster vaccination of infants. Infanrix hexa should be administered as a two- or three-dose primary vaccination course in infants aged vaccination between 11 and 18 months of age, with an interval of at least 6 months between the last dose of primary vaccination and the booster dose. This article reviews the immunogenicity and protective effectiveness, as well as the reactogenicity and safety of Infanrix hexa. Infanrix hexa as primary and booster vaccination was safe and highly immunogenic for all its component toxoids/antigens in infants aged <2 years, regardless of vaccination schedules. Its immunogenicity and safety profiles were generally similar to those of currently available vaccines, the diphtheria, tetanus and acellular pertussis-based pentavalent vaccines plus monovalent HBV or Hib vaccines. In large clinical studies, Infanrix hexa elicited a strong immune response against vaccine toxoids/antigens, as indicated by high seroprotection/seropositivity/vaccine response rates and geometric mean titres. Moreover, antibodies against vaccine toxoids/antigens persisted for up to a mean of approximately 6 years after booster vaccination, and the vaccine induced long-term immune memory against hepatitis B surface antigen and Hib antigen. A strong immune response against Infanrix hexa toxoids/antigens after primary vaccination was also induced in infants who had received a dose of HBV vaccine at birth and in pre-term infants, although the response in the latter group was somewhat lower than that in full-term infants. In addition, when coadministered with other childhood vaccines, the immunogenicity of Infanrix hexa or that of the concomitantly administered vaccine was generally not altered. Hexavalent vaccines, including Infanrix hexa, were protective against invasive Hib disease; Infanrix hexa is also expected to be protective against pertussis. Most solicited local and general symptoms with Infanrix hexa were mild to moderate in intensity and the vaccine was associated with few unsolicited adverse events. Available clinical data from more than 10 years' experience with the vaccine suggest that Infanrix hexa as primary and booster vaccination is a safe and useful option for providing protection against the common childhood diseases of diphtheria, tetanus, poliomyelitis, pertussis, hepatitis B and invasive Hib disease. PMID:20481658

  15. Predicting the impact of new pneumococcal conjugate vaccines: serotype composition is not enough.

    PubMed

    Hausdorff, William P; Hoet, Bernard; Adegbola, Richard A

    2015-03-01

    Streptococcus pneumoniae is a major cause of childhood morbidity and mortality worldwide. A heptavalent polysaccharide-protein conjugate vaccine (PCV) has proven highly effective in preventing pneumococcal disease in industrialized countries. Two higher-valent pneumococcal conjugate vaccines are now widely available, even in the poorest countries. These differ from each other in the number of serotypes and carrier proteins used for their conjugation. Some have assumed that the only meaningful clinical difference between PCV formulations is a function of the number of serotypes each contains. A careful review of recent clinical data with these and several unlicensed PCV formulations points to important similarities but also that some key properties of each vaccine likely differ from one another. PMID:25266168

  16. Donor immunization with pneumococcal conjugate vaccine and early protective antibody responses following allogeneic hematopoietic cell transplantation

    Microsoft Academic Search

    Deborah C. Molrine; Joseph H. Antin; Eva C. Guinan; Robert J. Soiffer; Kristin MacDonald; Richard Malley; Frank Malinoski; Susan Trocciola; Marjorie Wilson; Donna M. Ambrosino

    2002-01-01

    Patients undergoing hematopoietic cell transplantation (HCT) are at increased risk for infections with Streptococcus pneumoniae and have long-lasting, im- paired antibody responses to pneumococ- cal polysaccharide vaccines. We exam- ined whether donor immunization with a heptavalent pneumococcal conjugate vac- cine (PCV7) would elicit protective anti- body responses to additional doses of vaccine administered early after trans- plantation. Ninety-six patients scheduled

  17. Preparation and Evaluation of a New Lipopolysaccharide-based Conjugate as a Vaccine Candidate for Brucellosis

    PubMed Central

    Siadat, Seyed Davar; Vaziri, Farzam; Eftekhary, Mamak; Karbasian, Maryam; Moshiri, Arfa; Aghasadeghi, Mohammad R.; Ardestani, Mehdi S.; Alitappeh, Meghdad Abdollahpour; Arsang, Amin; Fateh, Abolfazl; Peerayeh, Shahin Najar; Bahrmand, Ahmad R.

    2014-01-01

    Objectives Development of an efficacious vaccine against brucellosis has been a challenge for scientists for many years. At present, there is no licensed vaccine against human brucellosis. To overcome this problem, currently, antigenic determinants of Brucella cell wall such as Lipopolysaccharide (LPS) are considered as potential candidates to develop subunit vaccines. Methods In this study, Brucella abortus LPS was used for conjugation to Neisseria meningitidis serogroup B outer membrane vesicle (OMV) as carrier protein using carbodiimide and adipic acid–mediated coupling and linking, respectively. Groups of eight BALB/c mice were injected subcutaneously with 10 ?g LPS alone, combined LPS + OMV and conjugated LPS–OMV on 0 days, 14 days, 28 days and 42 days. Anti-LPS IgG was measured in serum. Results The yield of LPS to OMV in LPS–OMV conjugate was 46.55%, on the basis of carbohydrate content. The ratio for LPS to OMV was 4.07. The LPS–OMV conjugate was the most immunogenic compound that stimulated following the first injection with increased IgG titer of ?5-fold and ?1.3-fold higher than that produced against LPS and LPS in noncovalent complex to OMV (LPS + OMV), respectively. The highest anti-LPS IgG titer was detected 2 weeks after the third injection (Day 42) of LPS–OMV conjugate. The conjugated compound elicited higher titers of IgG than LPS + OMV, that showed a 100–120-fold rise of anti-LPS IgG in mice. Conclusion These results indicate that our conjugated LPS–OMV can be used as a brucellosis vaccine, but further investigation is required. PMID:25737825

  18. Distance to health services affects local-level vaccine efficacy for pneumococcal conjugate vaccine (PCV) among rural Filipino children

    PubMed Central

    Root, Elisabeth Dowling; Lucero, Marilla; Nohynek, Hanna; Anthamatten, Peter; Thomas, Deborah S. K.; Tallo, Veronica; Tanskanen, Antti; Quiambao, Beatriz P.; Puumalainen, Taneli; Lupisan, Socorro P.; Ruutu, Petri; Ladesma, Erma; Williams, Gail M.; Riley, Ian; Simões, Eric A. F.

    2014-01-01

    Pneumococcal conjugate vaccines (PCVs) have demonstrated efficacy against childhood pneumococcal disease in several regions globally. We demonstrate how spatial epidemiological analysis of a PCV trial can assist in developing vaccination strategies that target specific geographic subpopulations at greater risk for pneumococcal pneumonia. We conducted a secondary analysis of a randomized, placebo-controlled, double-blind vaccine trial that examined the efficacy of an 11-valent PCV among children less than 2 y of age in Bohol, Philippines. Trial data were linked to the residential location of each participant using a geographic information system. We use spatial interpolation methods to create smoothed surface maps of vaccination rates and local-level vaccine efficacy across the study area. We then measure the relationship between distance to the main study hospital and local-level vaccine efficacy, controlling for ecological factors, using spatial autoregressive models with spatial autoregressive disturbances. We find a significant amount of spatial variation in vaccination rates across the study area. For the primary study endpoint vaccine efficacy increased with distance from the main study hospital from ?14% for children living less than 1.5 km from Bohol Regional Hospital (BRH) to 55% for children living greater than 8.5 km from BRH. Spatial regression models indicated that after adjustment for ecological factors, distance to the main study hospital was positively related to vaccine efficacy, increasing at a rate of 4.5% per kilometer distance. Because areas with poor access to care have significantly higher VE, targeted vaccination of children in these areas might allow for a more effective implementation of global programs. PMID:24550454

  19. Possibility of application of new pneumococcal conjugate vaccines in children in Slovenia.

    PubMed

    Paragi, Metka; Kolman, Jana; Kraigher, Alenka; Cizman, Milan; Gubina, Marija; Ribic, Helena

    2003-12-01

    The emergence of pneumococcal strains resistant to penicillin caused a lot of problems in the therapy of invasive diseases, and added new dimensions to the role of immunisation. In addition to the currently available 23-valent pneumococcal polysaccharide vaccine (PPV) and a new 7-valent conjugate vaccine (PCV) (Prevnar, Wyeth Lederle), two new conjugate vaccines-a 9- and a 11-valent-are being developed. So far, the choice of most appropriate vaccines has depended on the established prevalence of serotypes causing invasive diseases and their antibiotic resistance in the Slovene children population. Between 1993 and 2001, 263 invasive pneumococcal strains isolated from children with invasive diseases were typed. During the period 1998-2001, the same 161 invasive strains were tested for their antibiotic sensitivity. Streptococcus pneumoniae was identified as the major cause of invasive bacterial diseases in the Slovene children population, especially in children under 4 years of age. Distribution by age groups showed the highest incidence in children aged 0-1 years. The predominant serotypes in all age groups were serotypes 14, 1, 19F, 23F, 6B, 18C and 6A. The distribution of penicillin-intermediate and penicillin-resistant strains showed the predominance of serotypes 23F, 14 and 19F. As concerns infection with S. pneumoniae serotypes, we have proved that children aged less than 5 years are more likely to be infected with penicillin-nonsusceptible or intermediate susceptible strains than older children. The 7-valent conjugate vaccine covers 74% of invasive strains in toddlers, but is less effective in older children. We can conclude that the 9-valent vaccine formulation is optimal for our country, but further cost-effectiveness analysis must be done for recommendation of wide use. At that moment it is reasonable to use the 7-valent conjugate vaccine for children with chronic cardiovascular, pulmonary, urinary and liver diseases, with asplenia, neoplasmia, diabetes, meningomyelocoele, before or after bone marrow transplantation and in cases of immunodeficiency. PMID:14585680

  20. Immunization with the 7-valent conjugate pneumococcal vaccine: impact evaluation, continuing surveillance and future perspectives.

    PubMed

    Bechini, Angela; Boccalini, Sara; Bonanni, Paolo

    2009-05-26

    The 7-valent Pneumococcal Conjugate Vaccine (PCV) showed high efficacy against invasive pneumococcal diseases caused by vaccine serotypes in children less than 2 years-old. Its effectiveness was confirmed under routine use in the US, Canada and several European countries. Disease surveillance and several studies showed that population indirect protection outweighs direct protection of immunized subjects. A substantial impact was also confirmed on pneumonia and acute otitis media. A limited increase in IPD caused by non-vaccine serotypes was registered to date, but far below the magnitude of the beneficial reduction in IPD due to vaccine serotypes. This fact underpins the need for ongoing improved surveillance. New tests based on PCR for the identification and typing of pneumococci represent a very interesting alternative to traditional cultural tests that should be evaluated in the near future. The World Health Organization has recognized the priority to introduce PCV into the routine infant immunization schedule in all countries, due to the extremely high yearly mortality toll for pneumococcal diseases in the world (1.6 million deaths estimated). Conjugate vaccines with additional serotypes are in advanced stage of development or under evaluation. These new products need to be compared with the existing vaccine, following WHO recommendations regarding correlates of protection, in order to show their possibility to substitute the current vaccine obtaining the same impressive level of efficacy and effectiveness. PMID:19200829

  1. Safety and immunogenicity of three lots of meningococcal serogroup C conjugate vaccine administered at 2, 3 and 4 months of age

    Microsoft Academic Search

    J. Claire Bramley; Timothy Hall; Adam Finn; Roger B Buttery; David Elliman; Stephen Lockhart; Raymond Borrow; Ian G Jones

    2001-01-01

    The reactogenicity and immunogenicity of meningococcal serogroup C conjugate (MenC) vaccine was assessed in 322 infants vaccinated at 2, 3, and 4 months of age, with concomitant administration of mixed diphtheria–tetanus-whole-cell pertussis vaccine and Haemophilus influenzae type b conjugate vaccine (DTwP-Hib) and oral polio vaccine. All infants in whom post-vaccination meningococcal C anticapsular IgG levels were assayed (n=265) attained ?2

  2. 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

  3. Effectiveness of Meningococcal C Conjugate Vaccine in Salvador, Brazil: A Case-Control Study

    PubMed Central

    Cardoso, Cristiane Wanderley; Ribeiro, Guilherme Sousa; Reis, Mitermayer Galvão; Flannery, Brendan; Reis, Joice Neves

    2015-01-01

    Background During a citywide epidemic of serogroup C meningococcal disease in Salvador in 2010, Brazil, the state government initiated mass vaccination targeting two age groups with high attack rates: individuals aged <5 years and 10–24 years. More than 600,000 doses of meningococcal serogroup C conjugate vaccines were administered. We performed a case-control study to evaluate vaccine uptake, document vaccine effectiveness and identify reasons for non-vaccination. Methods and Findings Population-based surveillance identified patients with laboratory-confirmed invasive meningococcal C (MenC) disease during 2010. Information on MenC vaccination was obtained from case patients and age-matched individuals from the same neighborhoods. MenC vaccine effectiveness was estimated based on the exact odds ratios obtained by conditional logistic regression analysis. Of 51 laboratory-confirmed cases of serogroup C meningococcal disease among patients <5 and 10–24 years of age 50 were included in the study and matched with 240 controls. Overall case-fatality was 25%. MenC vaccine coverage among controls increased from 7.1% to 70.2% after initiation of the vaccination campaign. None of the 50 case patients but 70 (29.2%) of the 240 control individuals, including 59 (70.2%) of 84 matched with cases from the period after MenC vaccination, had received at least one MenC vaccine dose. Overall effectiveness of MenC was 98% with a lower 95% exact confidence limit of 89%. Conclusions MenC vaccines administered during the meningococcal epidemic were highly effective, suggesting that rapid vaccine uptake through campaigns contributed to control of meningococcal disease. PMID:25874777

  4. 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

  5. Pneumococcal conjugate vaccines and otitis media: an appraisal of the clinical trials.

    PubMed

    Fletcher, Mark A; Fritzell, Bernard

    2012-01-01

    Streptococcus pneumoniae is the predominant otitis media pathogen and its prevention through effective vaccination could diminish childhood illness and antibiotic use. This paper reviews 5 pneumococcal conjugate vaccine (PCV) trials that used otitis media as an endpoint: Northern California Kaiser Permanente (NCKP; vaccine, 7-valent PCV [PCV7]-CRM); Finnish Otitis Media (FinOM; vaccines, PCV7-CRM or PCV7-OMPC); Native American Trial (vaccine, PCV7-CRM); Pneumococcal Otitis Efficacy Trial (POET; vaccine, 11-valent PCV [PCV11]-PD). For the microbiological endpoint, vaccine efficacy against vaccine-serotype pneumococcal otitis media was about 60% across trials. Against the clinical endpoint of all episodes, vaccine efficacy was 7% (PCV7-CRM/NCKP), 6% (PCV7-CRM/FinOM), -1% (PCV7-OMPC/FinOM), and -0.4% (PCV7-CRM/Native American Trial); 34% against first episodes of ear, nose, and throat specialist-referral cases (PCV11-PD/POET). Both follow-up through 2 years of age, for the 5 trials, and long-term follow-up, for PCV7-CRM/NCKP and PCV7-CRM/FinOM, demonstrated greater vaccine efficacy against recurrent AOM and tympanostomy-tube placement, suggesting that vaccination against early episodes of AOM may prevent subsequent episodes of complicated otitis media. Although study designs varied by primary endpoint measured, age at follow-up, source of middle-ear fluid for culture, case ascertainment, and type of randomization, each clinical trial demonstrated vaccine efficacy against microbiological and/or clinical otitis media. PMID:22701486

  6. Epidemiology of vaccine-preventable invasive diseases in Catalonia in the era of conjugate vaccines

    PubMed Central

    Ciruela, Pilar; Martínez, Ana; Izquierdo, Conchita; Hernández, Sergi; Broner, Sonia; Muñoz-Almagro, Carmen; Domínguez, Àngela; of Catalonia Study Group, the Microbiological Reporting System

    2013-01-01

    We investigated the incidence and distribution of cases of invasive pneumococcal disease (IPD), invasive meningococcal disease (IMD) and invasive Hemophilus influenzae disease (IHiD) notified by hospital laboratories to the Microbiological Reporting System of Catalonia between 2005 and 2009. Incidence rates were compared using the rate ratio (RR) and 95% CI were calculated. A value of p < 0.05 was considered statistically significant. Of the 6,661 cases, 6,012 were IPD, 436 IMD and 213 IHiD. The global annual incidence per 105 inhabitants was 16.62 (95% CI 16.20–17.04) for IPD, 1.21 (95% CI 1.09–1.32) for IMD and 0.59 (95% CI 0.51–0.67) for IHiD. IPD increased in 2009 compared with 2005 (RR:1.55, 95%CI: 1.43–1.70) and IMD and IHiD remained stable. Pneumonia was the most-frequent clinical manifestation of IPD (75.6%) and IHiD (44.1%) and meningoencephalitis with or without sepsis for IMD (70.6%). The male:female ratio was 1.37 for IPD, 1.0 for IMD and 1.15 for IHiD. The age groups with the highest incidence were the ? 2 y and 2–4 y groups for IPD (66.40 and 50.66/100,000 persons-year) and IMD (14.88 and 7.26/100,000 persons-year) and the ? 2 y and ? 65 y groups for IHiD (1.88 and 1.89/100,000 persons-year). The most-frequent serotypes were serotype 1 (19.0%) in IPD and untypeable serotypes (60.8%) in IHiD. Serogroup B (78.3%) was the most frequent in IMD. S. pneumoniae is the most-frequent agent causing invasive disease in Catalonia. The main clinical manifestations were pneumonia in IPD and IHiD and meningitis in IMD. The main causative agent of meningitis was N. meningitidis in people aged < 20 y and S. pneumoniae in people aged ? 20 y. Vaccination with conjugate vaccines may reduce the risk of infectious disease in our setting. PMID:23303166

  7. Meningococcal serogroup C serum and salivary antibody responses to meningococcal quadrivalent conjugate vaccine in Saudi Arabian adolescents previously vaccinated with bivalent and quadrivalent meningococcal polysaccharide vaccine.

    PubMed

    Khalil, Mohamed; Al-Mazrou, Yagob; Findlow, Helen; Chadha, Helen; Bosch Castells, Valerie; Oster, Philipp; Borrow, Ray

    2014-09-29

    Following repeated polysaccharide vaccination, reduced immune responses have been reported, but there are limited data on the mucosal response of meningococcal polysaccharide vaccine (PSV) or meningococcal conjugate vaccination. Saudi Arabian adolescents (aged 16-19 years) who had previously been vaccinated with ?1 dose of bivalent meningococcal polysaccharide vaccine and 1 dose of quadrivalent meningococcal polysaccharide (MPSV4) were enrolled in a controlled, randomised, and modified observer-blind study (collectively termed the PSV-exposed group). The PSV-exposed group was randomised to receive either quadrivalent meningococcal conjugate vaccine (MCV4) (PSV-exposed/MCV4 group) or MPSV4 (PSV-exposed/MPSV4 group), and a PSV-naïve group received MCV4. Serum and saliva samples were collected pre-vaccination and 28 days post-vaccination. Serum serogroup-specific A, C, W and Y IgG were quantified as were salivary serogroup-specific C IgG and IgA together with total salivary IgG and IgA. For each serogroup, the post-vaccination serum geometric mean concentrations (GMCs) were significantly higher in the PSV-naïve and the PSV-exposed/MCV4 group than in the PSV-exposed/PSV4 group. For serogroup C, serum serogroup-specific IgG for the PSV-naïve group was significantly higher than both the PSV exposed groups. Higher levels of salivary serogroup C-specific IgG were found in the PSV-naïve group than those who had received two doses of polysaccharide but no significant differences were noted with regards to serogroup-specific IgA. PMID:25151042

  8. Polyspecific human and murine antibodies to diphtheria and tetanus toxoids and phospholipids.

    PubMed Central

    Sutjita, M; Hohmann, A; Comacchio, R; Bradley, J

    1988-01-01

    Human-human hybridomas produced from lymphocytes of normal individuals yielded seven clones producing monoclonal antibody reacting with tetanus toxoid. Three of these antibodies cross-reacted with diphtheria toxoid. These three and two others also reacted with cardiolipin and two with other phospholipids. One of the seven antibodies reacted with tetanus and diphtheria toxoids, cardiolipin and single-stranded DNA. All seven antibodies were IgM. To examine further this unusual cross-reactivity serum antibodies from patients with SLE and healthy individuals were affinity-purified to yield diphtheria toxoid antibodies. Six out of nine of these anti-diphtheria preparations contained IgG antibodies which cross-reacted with tetanus toxoid and two of these also reacted with cardiolipin; four preparations cross-reacted with DNA. Anti-cardiolipin and anti-DNA cross-reactivity were found in preparations from both normal and SLE sera. Similar cross-reactivities were demonstrated using four mouse monoclonal IgM antibodies raised against phospholipids. All four of these antibodies reacted with both cardiolipin and tetanus toxoid and two also reacted with diphtheria toxoid and DNA. Using a thiocyanate elution procedure, it was shown that the cross-reactivity of the monoclonal antibodies was not related to their relative affinities. The results clearly indicate that cross-reactive epitopes occur on routinely used toxoid vaccines and self antigens. Antibodies which bind to these cross-reactive epitopes are common and are not restricted in isotype, affinity or species of origin. PMID:3263226

  9. Monitoring the Introduction of Pneumococcal Conjugate Vaccines into West Africa: Design and Implementation of a Population-Based Surveillance System

    Microsoft Academic Search

    Grant A. Mackenzie; Ian D. Plumb; Sana Sambou; Debasish Saha; Uchendu Uchendu; Bolanle Akinsola; Usman N. Ikumapayi; Ignatius Baldeh; Effua Usuf; Kebba Touray; Momodou Jasseh; Stephen R. C. Howie; Andre Wattiaux; Ellen Lee; Maria Deloria Knoll; Orin S. Levine; Brian M. Greenwood; Richard A. Adegbola; Philip C. Hill

    2012-01-01

    Philip Campbell Hill and colleagues describe how they set up a population-based surveillance system to assess the impact of pneumococcal conjugate vaccines on invasive pneumococcal disease (IPD) and radiological pneumonia in children in The Gambia.

  10. Post-marketing effectiveness of Prevnar [pneumococcal 7-valent conjugate vaccine (diphtheria CRM197 protein)] and implications for adult immunization

    Microsoft Academic Search

    Betsy Abraham-Van Parijs; Frank J Malinoski

    2004-01-01

    Pneumococcal pneumonia is a significant health concern for pediatric, healthy adult, and elderly populations. The newly licensed pneumococcal 7-valent conjugate (diphtheria CRM197 protein) vaccine, Prevnar, and a second generation experimental 9-valent product have demonstrated, for the first time, a clear and significant impact on pneumococcal pneumonia in children. The potential for saccharide-conjugate vaccines to help prevent pneumococcal pneumonia in adult

  11. A preclinical study comparing approaches for augmenting the immunogenicity of a heptavalent KLH-conjugate vaccine against epithelial cancers

    Microsoft Academic Search

    Govind Ragupathi; Fusataka Koide; Natarajan Sathyan; Ella Kagan; Maria Spassova; William Bornmann; Polly Gregor; Celso A. Reis; Henrik Clausen; Samuel J. Danishefsky; Philip O. Livingston

    2003-01-01

    Previously using a series of monovalent vaccines, we demonstrated that the optimal method for inducing an antibody response against cancer cell-surface antigens is covalent conjugation of the antigens to keyhole limpet hemocyanin (KLH) and the use of a saponin adjuvant. We have prepared a heptavalent-KLH conjugate vaccine containing the seven epithelial cancer antigens GM2, Globo H, Lewis y, TF(c), Tn(c),

  12. Production of a conjugate vaccine for Salmonella enterica serovar Typhi from Citrobacter Vi.

    PubMed

    Micoli, F; Rondini, S; Pisoni, I; Giannelli, C; Di Cioccio, V; Costantino, P; Saul, A; Martin, L B

    2012-01-20

    A conjugate vaccine for Salmonella enterica serovar Typhi was produced by chemically linking Vi, purified from Citrobacter, to the non-toxic mutant diphtheria toxin CRM(197) via an adipic dihydrazide spacer using N-(3-Dimethylaminopropyl)-N'-ethylcarbodiimide coupling chemistry. The polysaccharide purification process was developed based on Vi precipitation from culture supernatant with cetyl trimethylammonium bromide (CTAB), solubilization of the CTA-polysaccharide salt with ethanol followed by exchange of the CTA(+) counter ion with Na(+). The purified Vi polysaccharide was fully O-acetylated and with high purity. The conjugation process was optimized to obtain a scalable process that has been used for GMP production at pilot scale of vaccine currently in clinical trials. PMID:22172503

  13. 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

  14. Saccharide/protein conjugate vaccines for Bordetella species: preparation of saccharide, development of new conjugation procedures, and physico-chemical and immunological characterization of the conjugates

    PubMed Central

    Kubler-Kielb, Joanna; Vinogradov, Evgeny; Ben-Menachem, Gil; Pozsgay, Vince; Robbins, John B.; Schneerson, Rachel

    2008-01-01

    Bordetellae are Gram-negative bacilli causing respiratory tract infections of mammals and birds. Clinically important are B. pertussis, B. parapertussis and B. bronchiseptica. B. pertussis vaccines have been successful in preventing pertussis in infants and children. Veterinary vaccines against B. bronchiseptica are available, but their efficacy and mode of action are not established. There is no vaccine against B. parapertussis. Based on the concept that immunity to non-capsulated Gram-negative bacteria may be conferred by serum IgG anti-LPS we studied chemical, serological and immunological properties of the O-specific polysaccharides (O-SP) of B. bronchiseptica and B. parapertussis obtained by different degradation procedures. One type of the B. parapertussis and two types of B. bronchiseptica O-SP were recognized based on the structure of their non-reducing end saccharide; no cross-reaction between the two B. bronchiseptica types was observed. Competitive inhibition assays showed the immunodominance of the non-reducing end of these O-SP. Conjugates of B. bronchiseptica and B. parapertussis O-SP were prepared by two methods: using the Kdo residue exposed by mild acid hydrolysis of the LPS or the core glucosamine residue exposed by deamination of the LPS, for binding to an aminooxylated protein. Both coupling methods were carried out at a neutral pH, room temperature, and in a short time. All conjugates, injected as saline solutions at a fraction of an estimated human dose, induced antibodies in mice to the homologous O-SP. These methodologies can be applied to prepare O-SP-based vaccines against other Gram-negative bacteria. PMID:18539367

  15. 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

  16. Impact of Pneumococcal Conjugate Vaccination on Otitis Media: A Systematic Review

    PubMed Central

    Taylor, Sylvia; Marchisio, Paola; Vergison, Anne; Harriague, Julie; Hausdorff, William P.; Haggard, Mark

    2012-01-01

    Acute otitis media (AOM) is a leading cause of visits to physicians and of antibiotic prescriptions for young children. We systematically reviewed studies on all-cause AOM episodes and physician visits in which impact was attributed to pneumococcal conjugate vaccines, either as efficacy or effectiveness. Of 18 relevant publications found, most used the 7-valent pneumococcal conjugate vaccine (7vCRM). The efficacy of 7vCRM against all-cause AOM episodes or visits was 0%–9% in randomized trials and 17%–23% in nonrandomized trials. In observational database studies, physician visits for AOM were already declining in the 3–5 years before 7vCRM introduction (mean change, ?15%; range, +14% to ?24%) and continued to decline afterward (mean, ?19%; range, +7% to ?48%). This vaccine provides some protection against OM, but other factors have also contributed to the recent decline in OM incidence. Future effectiveness studies should thus use better-controlled methods to estimate the true impact of vaccination on AOM. PMID:22423134

  17. Effectiveness of a 2+1 dose schedule pneumococcal conjugate vaccination programme on invasive pneumococcal disease among children in Norway

    Microsoft Academic Search

    Didrik F. Vestrheim; Øistein Løvoll; Ingeborg S. Aaberge; Dominique A. Caugant; E. Arne Høiby; Hilde Bakke; Marianne R. Bergsaker

    2008-01-01

    The 7-valent pneumococcal conjugate vaccine (PCV-7) was licensed in Norway in 2001. In July 2006, PCV-7 was introduced in the Norwegian Childhood Vaccination Programme in a 2+1 dose schedule, with immunizations administered at 3, 5 and 12 months of age. PCV-7 was offered through the vaccination programme to all children born from January 2006, i.e. a catch-up for children aged

  18. Introduction of Hib conjugate vaccines in the non-industrialized world: experience in four 'newly adopting' countries.

    PubMed

    Wenger, J D; DiFabio, J; Landaverde, J M; Levine, O S; Gaafar, T

    1999-11-12

    Hib conjugate vaccines are widely used in the industrialized world, but are just now beginning to be introduced into other countries. To identify factors facilitating rapid global introduction, we evaluated the decision-making process, mode of introduction, effectiveness, and impact on the immunization program of Hib conjugate vaccine introduction in four non- industrialized countries through site visits and use of a standardized questionnaire. The key promoters of Hib introduction were the pediatric community and ministries of health. Local surveillance and severity data were critical in the decision to adopt Hib vaccine. Assistance with surveillance, introduction guidelines, educational material, tenders, and funding is needed to accelerate wider adoption. PMID:10547434

  19. Anti-Group B Streptococcus Glycan-Conjugate Vaccines Using Pilus Protein GBS80 As Carrier and Antigen: Comparing Lysine and Tyrosine-directed Conjugation.

    PubMed

    Nilo, Alberto; Morelli, Laura; Passalacqua, Irene; Brogioni, Barbara; Allan, Martin; Carboni, Filippo; Pezzicoli, Alfredo; Zerbini, Francesca; Maione, Domenico; Fabbrini, Monica; Romano, Maria Rosaria; Hu, Qi-Ying; Margarit, Immaculada; Berti, Francesco; Adamo, Roberto

    2015-07-17

    Gram-positive Streptococcus agalactiae or group B Streptococcus (GBS) is a leading cause of invasive infections in pregnant women, newborns, and elderly people. Vaccination of pregnant women represents the best strategy for prevention of neonatal disease, and GBS polysaccharide-based conjugate vaccines are currently under clinical testing. The potential of GBS pilus proteins selected by genome-based reverse vaccinology as protective antigens for anti-streptococcal vaccines has also been demonstrated. Dressing pilus proteins with surface glycan antigens could be an attractive approach to extend vaccine coverage. We have recently developed an efficient method for tyrosine-directed ligation of large glycans to proteins via copper-free azide-alkyne [3 + 2] cycloaddition. This method enables targeting of predetermined sites of the protein, ensuring that protein epitopes are preserved prior to glycan coupling and a higher consistency in glycoconjugate batches. Herein, we compared conjugates of the GBS type II polysaccharide (PSII) and the GBS80 pilus protein obtained by classic lysine random conjugation and by the recently developed tyrosine-directed ligation. PSII conjugated to CRM197, a carrier protein used for vaccines in the market, was used as a control. We found that the constructs made from PSII and GBS80 were able to elicit murine antibodies recognizing individually the glycan and protein epitopes on the bacterial surface. The generated antibodies were efficacious in mediating opsonophagocytic killing of strains expressing exclusively PSII or GBS80 proteins. The two glycoconjugates were also effective in protecting newborn mice against GBS infection following vaccination of the dams. Altogether, these results demonstrated that polysaccharide-conjugated GBS80 pilus protein functions as a carrier comparably to CRM197, while maintaining its properties of protective protein antigen. Glycoconjugation and reverse vaccinology can, therefore, be combined to design vaccines with broad coverage. This approach opens a path to a new generation of vaccines. Tyrosine-ligation allows creation of more homogeneous vaccines, correlation of the immune response to defined connectivity points, and fine-tuning of the conjugation site in glycan-protein conjugates. PMID:25906283

  20. 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

  1. 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

  2. Development of a Pfs25-EPA malaria transmission blocking vaccine as a chemically conjugated nanoparticle

    PubMed Central

    Shimp, Richard L.; Rowe, Christopher; Reiter, Karine; Chen, Beth; Nguyen, Vu; Aebig, Joan; Rausch, Kelly M.; Kumar, Krishan; Wu, Yimin; Jin, Albert J.; Jones, David S.; Narum, David L.

    2013-01-01

    Successful efforts to control infectious diseases have often required the use of effective vaccines. The current global strategy for control of malaria, including elimination and eradication will also benefit from the development of an effective vaccine that interrupts malaria transmission. To this end, a vaccine that disrupts malaria transmission within the mosquito host has been investigated for several decades targeting a 25 kDa ookinete specific surface protein, identified as Pfs25. Phase 1 human trial results using a recombinant Pfs25H/Montanide ISA51 formulation demonstrated that human Pfs25 specific antibodies block parasite infectivity to mosquitoes; however, the extent of blocking was likely insufficient for an effective transmission blocking vaccine. To overcome the poor immunogenicity, processes to produce and characterize recombinant Pfs25H conjugated to a detoxified form of Pseudomonas aeruginosa exoprotein A (EPA) have been developed and used to manufacture a cGMP pilot lot for use in human clinical trials. The Pfs25-EPA conjugate appears as a nanoparticle with an average molar mass in solution of approximately 600 kDa by static light scattering with an average diameter 20 nm (range 10 to 40 nm) by dynamic light scattering. The molar ratio of Pfs25H to EPA is about 3 to 1 by amino acid analysis, respectively. Outbred mice immunized with the Pfs25-EPA conjugated nanoparticle formulated on Alhydrogel® had a 75 to 110 fold increase in Pfs25H specific antibodies when compared to an unconjugated Pfs25H/Alhydrogel® formulation. A phase 1 human trial using the Pfs25-EPA/Alhydrogel® formulation is ongoing in the United States. PMID:23623858

  3. 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

  4. 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

  5. 75 FR 48707 - Proposed Vaccine Information Materials for Pneumococcal Conjugate Vaccine and Human...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2010-08-11

    ...Children who are known to have a severe allergy to any component of PCV7 or PCV13 should...provider if your child has any severe allergies. Children with minor illnesses, such...person getting vaccinated has any severe allergies, including an allergy to yeast....

  6. Synthesis of a glycopeptide vaccine conjugate for induction of antibodies recognizing O-mannosyl glycopeptides.

    PubMed

    Yu, Jin; Westerlind, Ulrika

    2014-05-01

    In spite of the clear importance of protein O-mannosylation in brain glycobiology, tools are lacking for specific detection, enrichment, and identification of proteins containing these modifycations. We envisioned inducing antibodies that specifically recognize O-mannose glycans on proteins and peptides. With this in mind, we prepared a glycopeptide vaccine construct containing the N-acetyllactosamine-extended mannose motif Gal?1-4GlcNAc?1-2Man?Thr, found as a common core structure on almost all mammalian O-mannosyl glycoproteins identified. O-mannose glycosylated amino acid building blocks and the corresponding glycopeptides were prepared by chemical synthesis and then conjugated to an immune carrier protein. After administration of the synthetic vaccine into rabbits, strong immune responses were obtained. Further evaluation by ELISA neutralization experiments and glycopeptide microarrays showed that the induced antibodies were highly specific to the glycopeptide antigen. PMID:24753400

  7. 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

  8. Preparation, Characterization, andImmunogenicity of Conjugate Vaccines Directed against Actinobacillus pleuropneumoniae Virulence Determinants

    Microsoft Academic Search

    SOLOMON KADISt

    1992-01-01

    reaction. TheCPandtheLPSwere found tobecovalently coupled totheHPinthe conjugates as determined bysodiumdodecyl sulfate-polyacrylamide gelelectrophoresis anddetergent gel chromatography analyses. Following a booster vaccination, pigsexhibited significantly high(P< 0.05) immunoglobulin G antibodies against CP,LPS,andHP.Theanti-CP andanti-LPS immunoglobulin G antibodies were found tofunction asopsonins inthephagocytosis ofA.pleuropneumoniae bypolymorphonu- clear leukocytes, whereas antibodies totheHPneutralized thecytotoxic effect oftheHPonpolymorphonuclear leukocytes. Nokilling ofA.pleuropneumoniae wasobserved whentheeffects oftheantibodies weretested inthe presenceofcomplement. Thus,polysaccharide-protein A.pleuropneumoniaeconjugates elicit

  9. Evolving role of 13-valent pneumococcal conjugate vaccine in clinical practice.

    PubMed

    Azzari, Chiara; Martinón-Torres, Federico; Schmitt, Heinz-Josef; Dagan, Ron

    2014-08-01

    Since the introduction of 7-valent pneumococcal conjugate vaccine (PCV7), PCVs with extended coverage have become available, and there is emerging global evidence that these vaccines, in particular PCV13, have further reduced rates of invasive pneumococcal disease compared with PCV7. The present article aims to address emerging topics related to PCV13 use in routine clinical practice; specifically: (1) the potential role of high-valent PCVs in reducing pneumococcal disease burden; (2) the impact of PCVs on nasopharyngeal carriage and how this may contribute to reductions in otitis media and pneumonia, as well as the prevalence of resistant pneumococcal strains; (3) new PCV13 indications and (4) importance of schedule adherence for PCV in the prevention of cases of vaccine serotype-specific invasive pneumococcal disease. The beneficial effects of PCVs in protecting individuals from a wide spectrum of pneumococcal diseases can be increased by improving the vaccine coverage and adhering to the recommended vaccination schedules. There is increasing evidence that PCV13 has reduced much of the post-PCV7 burden of pneumococcal diseases in the pediatric community, including reducing pneumococcal colonization and the incidence of invasive pneumococcal disease and mucosal diseases. This has also led to a reduction in antibiotic-resistant pneumococcal diseases. The role of PCV13 in clinical practice is evolving, with PCV13 now available for children and adolescents between the ages of 6 weeks and 17 years, thus ensuring that children in all age groups can be protected against vaccine-serotype pneumococcal diseases. Continued surveillance is warranted to monitor the impact of PCV13 on disease burden. PMID:24618937

  10. Impact of Pneumococcal Conjugate Vaccine on Pediatric Tympanostomy Tube Insertion in Partial Immunized Population

    PubMed Central

    Wang, Mao-Che; Wang, Ying-Piao; Chu, Chia-Huei; Shiao, An-Suey; Chou, Pesus

    2015-01-01

    Objective. To investigate the impact of seven-valent pneumococcal conjugate vaccine on tube insertions in a partial immunized pediatric population. Study Design. Retrospective ecological study. Methods. This study used Taiwan National Health Insurance Research Database for the period 2000–2009. Every child under 17 years old who received tubes during this 10-year period was identified and analyzed. The tube insertion rates in different age groups and the risk to receive tubes in different birth cohorts before and after the release of the vaccine in 2005 were compared. Results. The tube insertion rates for children under 17 years of age ranged from 21.6 to 31.9 for 100,000 persons/year. The tube insertion rate of children under 2 years old decreased significantly after 2005 in period effect analysis (? = ?0.074, P < 0.05, and the negative ? value means a downward trend) and increased in children 2 to 9 years old throughout the study period (positive ? values which mean upward trends, P < 0.05). The rate of tube insertion was lower in 2004-2005 and 2006-2007 birth cohorts than that of 2002-2003 birth cohort (RR = 0.90 and 0.21, 95% CI 0.83–0.97 and 0.19–0.23, resp.). Conclusion. The seven-valent pneumococcal conjugate vaccine may reduce the risk of tube insertion for children of later birth cohorts. The vaccine may have the protective effect on tube insertions in a partial immunized pediatric population. PMID:25839052

  11. Sustained high-titer antibody responses induced by conjugating a malarial vaccine candidate to outer-membrane protein complex

    PubMed Central

    Wu, Yimin; Przysiecki, Craig; Flanagan, Elizabeth; Bello-Irizarry, Sheila N.; Ionescu, Roxana; Muratova, Olga; Dobrescu, Gelu; Lambert, Lynn; Keister, David; Rippeon, Yvette; Long, Carole A.; Shi, Li; Caulfield, Michael; Shaw, Alan; Saul, Allan; Shiver, John; Miller, Louis H.

    2006-01-01

    The development of protein subunit vaccines to combat some of the world's deadliest pathogens such as a malaria parasite, Plasmodium falciparum, is stalled, due in part to the inability to induce and sustain high-titer antibody responses. Here, we show the induction of persistent, high-titer antibody responses to recombinant Pfs25H, a human malarial transmission-blocking protein vaccine candidate, after chemical conjugation to the outer-membrane protein complex (OMPC) of Neisseria meningitidis serogroup B and adsorption to aluminum hydroxyphosphate. In mice, the Pfs25H-OMPC conjugate vaccine was >1,000 times more potent in generating anti-Pfs25H ELISA reactivity than a similar 0.5-?g dose of Pfs25H alone in Montanide ISA720, a water-in-oil adjuvant. The immune enhancement requires covalent conjugation between Pfs25H and the OMPC, given that physically mixed Pfs25H and OMPC on aluminum hydroxyphosphate failed to induce greater activity than the nonconjugated Pfs25H on aluminum hydroxyphosphate. The conjugate vaccine Pfs25H-OMPC also was highly immunogenic in rabbits and rhesus monkeys. In rhesus monkeys, the antibody responses were sustained over 18 months, at which time another vaccination with nonconjugated Pfs25H induced strong anamnestic responses. The vaccine-induced anti-Pfs25-specific antibodies in all animal species blocked the transmission of parasites to mosquitoes. Protein antigen conjugation to OMPC or other protein carrier may have general application to a spectrum of protein subunit vaccines to increase immunogenicity without the need for potentially reactogenic adjuvants. PMID:17110440

  12. Investigation of the factors affecting catabolism of antibodies raised against a vaccine candidate based on the conserved region of the M-protein

    Microsoft Academic Search

    Manisha Pandey; Michael F. Good; Michael R. Batzloff

    2006-01-01

    A non-host reactive, conformationally constrained, minimal B-cell epitope from the conserved region of M-protein has been identified as a GAS vaccine candidate. The immunogenic potential of this chimeric peptide J8 conjugated to diphtheria toxoid (DT) has been demonstrated previously and the protection is believed to be mediated by J8-specific IgG. To expand further on these studies, we are interested in

  13. 7Valent Pneumococcal Conjugate Vaccination in England and Wales: Is It Still Beneficial Despite High Levels of Serotype Replacement?

    Microsoft Academic Search

    Yoon Hong Choi; Mark Jit; Nigel Gay; Nick Andrews; Pauline A. Waight; Alessia Melegaro; Robert George; Elizabeth Miller; Ray Borrow

    2011-01-01

    BackgroundThe UK introduced the 7-valent pneumococcal conjugate vaccine (PCV7) into the national vaccination program in September 2006. Previous modelling assumed that the likely impact of PCV7 on invasive pneumococcal disease (IPD) would be similar to the US experience with PCV7. However, recent surveillance data show a more rapid replacement of PCV7 IPD cases by non-PCV7 IPD cases than was seen

  14. Humoral immune response of a pneumococcal conjugate vaccine: Capsular polysaccharide serotype 14—Lysine modified PspA

    Microsoft Academic Search

    Raquel Santamaria; Cibelly Goulart; Catia T. Perciani; Giovana C. Barazzone; Rimenys Jr. Carvalho; Viviane M. Gonçalves; Luciana C. C. Leite; Martha M. Tanizaki

    2011-01-01

    Polysaccharide–protein conjugates are so far the current antigens used for pneumococcal vaccines for children under 2 years of age. In this study, pneumococcal surface protein A (PspA) was used as a carrier protein for pneumococcal capsular polysaccharide serotype 14 as an alternative to broaden the vaccine coverage. PspA was modified by reductive amination with formaldehyde in order to improve the

  15. Induction of opsonophagocytic killing activity with pneumococcal conjugate vaccine in human immunodeficiency virus-infected Ugandan adults

    Microsoft Academic Search

    Meng Chen; Francis Ssali; Maureen Mulungi; Peter Awio; Hiroyuki Yoshimine; Reiki Kuroki; Akitsugu Furumoto; Susumu Tanimura; Cissy Kityo; Tsuyoshi Nagatake; Peter Mugyenyi; Kazunori Oishi

    2008-01-01

    The levels of IgG determined by ELISA may have limited relevance in human immunodeficiency virus (HIV)-infected adults because of non-functional antibodies. 58 HIV-1-infected and 29 HIV-uninfected Ugandan adults were immunized with conjugate vaccine (CV) followed by polysaccharide vaccine (PV) after a 2-month interval, and the opsonophagocytic killing (OPK) titers against serotype 4 or 14 pneumococcal strains as well as the

  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. 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

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

    PubMed

    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

  19. 13-valent pneumococcal conjugate vaccine: a review of its use in infants, children, and adolescents.

    PubMed

    Plosker, Greg L

    2013-10-01

    The 13-valent pneumococcal conjugate vaccine (Prevenar 13(®); Prevnar 13(®)) [PCV13] includes 13 serotype-specific polysaccharides of Streptococcus pneumoniae conjugated individually to non-toxic diphtheria CRM197 protein, thus providing wider coverage of pneumococcal serotypes than its 7-valent predecessor (PCV7). For pediatric populations, PCV13 was initially approved for use in infants and children up to 5 years of age, but recently received approval for expanded use (ages 6 weeks to 17 years) in the EU and the USA. This change in labeling was made primarily on the basis of results of Study 3011, which demonstrated the serotype-specific immunogenicity of a single dose of PCV13 in children ?5 to <10 years of age who had previously received PCV7. Study 3011 also demonstrated functional immune responses after a single dose of PCV13 in a cohort ?10 to <18 years of age who had not previously received PCV7. Importantly, prior to Study 3011, several randomized studies comparing PCV13 and PCV7 in infants and younger children demonstrated noninferiority of immune responses to the seven serotypes common to both vaccines after a two- or three-dose primary infant series and after the toddler booster dose; immunogenicity and functional immune responses were also demonstrated for the six additional serotypes. The safety and reactogenicity of PCV13 was generally similar to that of PCV7, and PCV13 did not interfere with the immune responses to coadministered routine pediatric vaccines. PCV13 is expected to substantially reduce the incidence of invasive pneumococcal diseases in a manner similar to that which occurred after PCV7 was introduced, and evidence of the protective effectiveness of PCV13 against pneumococcal diseases is emerging. PMID:24030738

  20. 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

  1. A strategy for rational design of fully synthetic glycopeptide conjugate vaccines.

    PubMed Central

    Chong, P; Chan, N; Kandil, A; Tripet, B; James, O; Yang, Y P; Shi, S P; Klein, M

    1997-01-01

    The present study describes a strategy to rationally design fully synthetic glycopeptide conjugate vaccines. Glycopeptide immunogens were constructed by coupling synthetic oligosaccharides comprising repeating units of synthetic 3-beta-D-ribose-(1-1)-D-ribitol-5-phosphate (sPRP) to synthetic peptides containing potent T-helper cell determinants and B-cell epitopes of the Haemophilus influenzae type b (Hib) outer membrane proteins (OMPs) P1, P2, and P6. Rabbit immunogenicity studies revealed that some of these fully synthetic glycoconjugates were capable of eliciting high titers of both anti-PRP and anti-OMP immunoglobulin G antibodies. In addition, we systematically investigated the factors which could influence their immunogenicity. We observed that the magnitude of the anti-PRP antibody response markedly depended on the relative spatial orientation of sPRP and T-cell epitopes, the anti-PRP antibody response was enhanced when a multiple antigenic peptide was used as a carrier, the anti-PRP antibody response was optimal for three PRP repeating units, and lipidation of peptide-PRP conjugates had a minimal effect on the magnitude of the anti-PRP antibody response. The results of this study clearly demonstrate that coupling a carbohydrate hapten to a peptide can provide T-cell help and convert it into a T-cell-dependent antigen. The antisera raised against these conjugates were also found to be protective against Hib infection in the infant rat model of bacteremia. PMID:9393776

  2. Development and clinical evaluation of Prevnar 13, a 13-valent pneumocococcal CRM197 conjugate vaccine.

    PubMed

    Gruber, William C; Scott, Daniel A; Emini, Emilio A

    2012-08-01

    Pneumococcus is the leading cause of bacterial illness in children worldwide. The development, clinical evaluation, and postlicensure impact of the pneumococcal CRM(197) protein conjugate vaccine, PCV13, (Prevnar 13®) builds upon the excellent safety and substantial effectiveness of PCV7 (Prevnar®) in preventing pneumococcal disease in children. PCV13 adds pneumococcal serotypes 1, 3, 5, 6A, 7F, and 19A to serotypes 4, 6B, 9V, 14, 18C, 19F, 23F in PCV7 to provide comprehensive coverage for over 85% of epidemiologically important pneumococcal serotypes in the United States and throughout the world. PCV13 development required demonstration of immunologic responses to the 13 serotypes contained in the vaccine that were noninferior to the responses elicited by PCV7, and demonstration of a satisfactory safety profile. Studies were also performed to demonstrate compatibility with other childhood vaccines. Now licensed in many countries worldwide, PCV13 shows significant promise for expanded protection against pneumococcal disease in children. PMID:22830997

  3. Piliation of Invasive Streptococcus pneumoniae Isolates in the Era before Pneumococcal Conjugate Vaccine Introduction in Malawi

    PubMed Central

    Gray, Katherine; Kamng'ona, Arox; Cornick, Jennifer; Bentley, Stephen D.; Heyderman, Robert S.; Everett, Dean B.

    2013-01-01

    The pneumococcal pilus has been shown to be an important determinant of adhesion and virulence in mouse models of colonization, pneumonia, and bacteremia. A pilus is capable of inducing protective immunity, supporting its inclusion in next-generation pneumococcal protein vaccine formulations. Whether this vaccine target is common among pneumococci in sub-Saharan Africa is uncertain. To define the prevalence and genetic diversity of type I and II pili among invasive pneumococci in Malawi prior to the introduction of the 13-valent pneumococcal conjugate vaccine (PCV13) into routine childhood immunization, we examined 188 Streptococcus pneumoniae isolates collected between 2002 and 2008 (17% serotype 1). In this region of high disease burden, we found a low frequency of invasive piliated pneumococci (14%) and pilus gene sequence diversity similar to that seen previously in multiple global pneumococcal lineages. All common serotypes with pilus were covered by PCV13 and so we predict that pilus prevalence will be reduced in the Malawian pneumococcal population after PCV13 introduction. PMID:24027261

  4. Modeling the impact of the 13-valent pneumococcal conjugate vaccine serotype catch-up program using United States claims data

    PubMed Central

    2012-01-01

    Background Analysis of US claims data from April 2010 to June 2011 estimated that 39% of the 13-valent pneumococcal conjugate vaccine (PCV13) catch-up eligible cohort would ever receive the catch-up vaccination; a previous analysis assumed 87%. Methods This updated figure was applied to a previously published 10-year Markov model while holding all other inputs constant. Results Our model estimated that the catch-up program as currently implemented is estimated to prevent an additional 1.7 million cases of disease in children aged ?59?months over a 10-year period, compared with routine PCV13 vaccination with no catch-up program. Conclusions Because 39% catch-up uptake is less than the level of completion of the 4-dose primary PCV13 series, vaccine-preventable cases of pneumococcal disease and related deaths could be decreased further with additional uptake of catch-up vaccination in the catch-up eligible cohort. PMID:22863074

  5. Synthesis and immunological study of ?-2,9-oligosialic acid conjugates as anti-group C meningitis vaccines.

    PubMed

    Liao, Guochao; Zhou, Zhifang; Guo, Zhongwu

    2015-05-28

    ?-2,9-Di-, tri-, tetra-, and pentasialic acids were prepared and conjugated with a carrier protein. The resultant glycoconjugates elicited robust T cell-mediated immunity in mice. ?-2,9-Trisialic acid was identified as a promising antigen for developing glycoconjugate vaccines against group C Neisseria meningitidis. PMID:25973942

  6. Characterization of a recombinant pneumolysin and its use as a protein carrier for pneumococcal type 18C conjugate vaccines.

    PubMed Central

    Kuo, J; Douglas, M; Ree, H K; Lindberg, A A

    1995-01-01

    Pneumolysin from Streptococcus pneumoniae was expressed in Escherichia coli as a glutathione S-transferase fusion protein and purified by affinity and hydroxylapatite chromatography. The purified recombinant pneumolysin (rPL), with a molecular mass of 53 kDa, had a specific activity of 3 x 10(5) hemolytic units per mg of protein on rabbit erythrocytes and reacted identically in immunodiffusion with the antisera against native pneumolysin. The rPL was used as a protein carrier to prepare conjugate vaccine with pneumococcal type 18C polysaccharide (PS18C). The PS18C was directly coupled to rPL by reductive animation or was indirectly coupled to rPL via a spacer molecule, adipic acid dihydrazide. The conjugates were nontoxic for mice and guinea pigs at 100 micrograms per dose. The immunogenicity and protective efficacy of both conjugates were tested in mice. A single dose of either of the vaccines elicited a rise in immunoglobulin G antibody production; after two booster injections of the vaccines, statistically significant booster responses (P < 0.001) to both rPL and PS18C were produced. The sera containing the antibodies to rPL were capable of neutralizing the hemolytic activity of rPL to rabbit erythrocytes and the cytotoxicity of rPL to bovine pulmonary endothelial cells. Immunization with the conjugate vaccines conferred statistically significant protection in mice against lethal challenge with type 18C pneumococci. PMID:7790088

  7. Effectiveness of a 2+1 dose schedule pneumococcal conjugate vaccination programme on invasive pneumococcal disease among children in Norway.

    PubMed

    Vestrheim, Didrik F; Løvoll, Oistein; Aaberge, Ingeborg S; Caugant, Dominique A; Høiby, E Arne; Bakke, Hilde; Bergsaker, Marianne R

    2008-06-19

    The 7-valent pneumococcal conjugate vaccine (PCV-7) was licensed in Norway in 2001. In July 2006, PCV-7 was introduced in the Norwegian Childhood Vaccination Programme in a 2+1 dose schedule, with immunizations administered at 3, 5 and 12 months of age. PCV-7 was offered through the vaccination programme to all children born from January 2006, i.e. a catch-up for children aged 3-6 months. Prior to 2006 the use of PCV-7 was negligible. The effectiveness of the PCV-7 vaccination programme was assessed using data on invasive pneumococcal disease (IPD) incidence obtained from the Norwegian Surveillance System for Communicable Diseases, serotype distribution from the National Reference Laboratory for Pneumococci, and vaccine coverage and vaccination status from the Norwegian National Vaccination Register. Vaccine coverage quickly reached high levels; 95% of children >3 months born from January 2006 had received at least one immunization with PCV-7. The incidence rate of IPD among children <2 years rapidly declined; the rate of vaccine serotype IPD in this age group fell from an average of 47.1 cases/100,000 population in the 2 years prior to PCV-7 introduction to 13.7 cases/100,000 population in 2007. The incidence rate of nonvaccine serotype IPD remained stable. The vaccine programme effectiveness was estimated to be 74% (95% CI 57-85%). No vaccine failure was seen after complete primary immunization with two vaccine doses. Our findings indicate that PCV-7 provides highly effective protection against vaccine serotype IPD when administered in a 2+1 dose schedule. PMID:18456376

  8. 9 CFR 113.115 - Staphylococcus Aureus Bacterin-Toxoid.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...2012-01-01 2012-01-01 false Staphylococcus Aureus Bacterin-Toxoid. 113.115...Inactivated Bacterial Products § 113.115 Staphylococcus Aureus Bacterin-Toxoid. Staphylococcus Aureus Bacterin-Toxoid shall...

  9. 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...Inactivated Bacterial Products § 113.115 Staphylococcus Aureus Bacterin-Toxoid. Staphylococcus Aureus Bacterin-Toxoid shall...

  10. 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...Inactivated Bacterial Products § 113.115 Staphylococcus Aureus Bacterin-Toxoid. Staphylococcus Aureus Bacterin-Toxoid shall...

  11. Evaluation of meningitis surveillance before introduction of serogroup a meningococcal conjugate vaccine - Burkina Faso and Mali.

    PubMed

    2012-12-21

    Each year, 450 million persons in a region of sub-Saharan Africa known as the "meningitis belt" are at risk for death and disability from epidemic meningitis caused by serogroup A Neisseria meningitidis. In 2009, the first serogroup A meningococcal conjugate vaccine (PsA-TT) developed solely for Africa (MenAfriVac, Serum Institute of India, Ltd.), was licensed for persons aged 1-29 years. During 2010-2011, the vaccine was introduced in the hyperendemic countries of Burkina Faso, Mali, and Niger through mass campaigns. Strong meningitis surveillance is critical for evaluating the impact of PsA-TT because it was licensed based on safety and immunogenicity data without field effectiveness trials. Case-based surveillance, which includes the collection of epidemiologic and laboratory data on individual cases year-round, is recommended for countries that aim to evaluate the vaccine's impact. A key component of case-based surveillance is expansion of laboratory confirmation to include every case of bacterial meningitis because multiple meningococcal serogroups and different pathogens such as Haemophilus influenzae type b and Streptococcus pneumoniae cause meningitis that is clinically indistinguishable from that caused by serogroup A Neisseria meningitidis. Before the introduction of PsA-TT, evaluations of the existing meningitis surveillance in Burkina Faso and Mali were conducted to assess the capacity for case-based surveillance. This report describes the results of those evaluations, which found that surveillance infrastructures were strong but opportunities existed for improving data management, handling of specimens shipped to reference laboratories, and laboratory capacity for confirming cases. These findings underscore the need to evaluate surveillance before vaccine introduction so that activities to strengthen surveillance are tailored to a country's needs and capacities. PMID:23254257

  12. The effect of Haemophilus influenzae type B and pneumococcal conjugate vaccines on childhood meningitis mortality: a systematic review

    PubMed Central

    2013-01-01

    Background Two of the most prevalent causes of severe bacterial meningitis in children, Haemophilus influenzae type B (Hib) and Streptococcus pneumoniae, are preventable by existing vaccines increasingly available in developing countries. Our objective was to estimate the dose-specific effect of Hib and pneumococcal conjugate vaccines (PCV) on childhood meningitis mortality in low-income countries for use in the Lives Saved Tool (LiST). Methods We systematically searched and reviewed published vaccine efficacy trials and observational studies reporting the effect of Hib or PCV vaccines on organism-specific meningitis, bacterial meningitis and all-cause meningitis incidence and mortality among children less than five years old in low- and middle-income countries. Data collection and quality assessments were performed using standardized guidelines. For outcomes available across multiple studies (?2) and approximating meningitis mortality, we pooled estimates reporting dose-specific effects using random effects meta-analytic methods, then combined these with meningitis etiology data to determine the preventable fraction of childhood meningitis mortality for inclusion in LiST. Results We identified 18 studies of Hib conjugate vaccines reporting relevant meningitis morbidity and mortality outcomes (2 randomized controlled trials [RCTs], 16 observational studies) but few provided dose-specific effects. A meta-analysis of four case-control studies examined the dose-specific effect of Hib conjugate vaccines on Hib meningitis morbidity (1 dose: RR=0.64, 95% CI 0.38-1.06; 2 doses: RR=0.09, 95% CI 0.03-0.27; 3 doses: RR=0.06, 95% CI 0.02-0.22), consistent with results from single RCTs. Pooled estimates of two RCTs provided evidence for the effect of three doses of PCV on vaccine-serotype meningitis morbidity (RR=0.16, 95% CI 0.02-1.20). We considered these outcomes of severe disease as proxy estimates for meningitis mortality and combined the estimates of protective effects with meningitis etiology data to provide an estimate of the preventable fraction of childhood meningitis mortality with three doses of Hib (38-43%) and pneumococcal conjugate vaccines (28-35%) for use in LiST. Conclusions Few RCTs or vaccine effectiveness studies evaluated the dose-specific impact of Hib and PCV vaccines on childhood meningitis mortality, necessitating use of proxy measures to estimate population impact in LiST. Our analysis indicates that approximately three-quarters of meningitis deaths are preventable with existing Hib and PCV vaccines. PMID:24564188

  13. Concentration and high avidity of pneumococcal antibodies persist at least 4 years after immunization with pneumococcal conjugate vaccine in infancy.

    PubMed

    Ekström, Nina; Ahman, Heidi; Palmu, Arto; Grönholm, Sinikka; Kilpi, Terhi; Käyhty, Helena

    2013-07-01

    To provide more extensive evidence of long-term effects of vaccination on immunity against Streptococcus pneumoniae, a follow-up study of the Finnish Otitis Media (FinOM) Vaccine Trial was conducted. One of the objectives was to assess the persistence and avidity of pneumococcal antibodies 4 years after pneumococcal vaccination given in infancy. Children with complete follow-up in the FinOM trial up to 24 months of age were invited to a single visit in their fifth year of life. A blood sample was taken from all children for determination of anticapsular antibody concentrations to vaccine serotypes and avidity of antibodies to three serotypes. Children had been vaccinated at 2, 4, 6, and 12 months of age with 7-valent pneumococcal capsular polysaccharide, CRM197 conjugate vaccine (PCV7), or a control vaccine. Serum IgG antibody concentrations to vaccine serotypes remained significantly higher in children who had received PCV7 than in control children for 4 years after the fourth PCV7 dose. Concentrations of antibodies to frequently carried serotypes (6B and 19F) declined less than those of antibodies to a rarely carried serotype (4), suggesting that natural boosting contributed to antibody persistence. Furthermore, antibody avidity was significantly higher in PCV7 than control vaccine recipients. Four doses of PCV7 given in infancy elicit long-lasting antibody responses with high avidity. (This study has been registered at ClinicalTrials.gov under registration no. NCT00378417.). PMID:23658394

  14. [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

  15. 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

  16. 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

  17. 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

  18. 66 FR 13540 - Proposed Vaccine Information Materials for Pneumococcal Conjugate, Diphtheria, Tetanus, Acellular...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2001-03-06

    ...Acellular Pertussis (DTaP/DT) and Hepatitis B Vaccines AGENCY: Centers for Disease...pertussis (DTaP/DT) vaccines and hepatitis B vaccine. DATES: Written comments...Vaccine Injury Compensation Program: hepatitis B, haemophilus influenzae type b...

  19. 67 FR 61110 - Vaccine Information Materials for Pneumococcal Conjugate, Diphtheria, Tetanus, acellular...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2002-09-27

    ...Diphtheria, Tetanus, acellular Pertussis and Hepatitis B Vaccines AGENCY: Centers for Disease...pertussis (DTaP/DT) vaccines and hepatitis B vaccine. Following review of the comments...diphtheria, tetanus, acellular pertussis or hepatitis B vaccine shall, prior to...

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

    PubMed

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

    2015-06-01

    Infant 13-valent pneumococcal conjugate vaccination (PCV13) was introduced to the UK in 2010. Its impact on serotypes implicated in adult non-bacteraemic pneumococcal pneumonia is not known. Beginning in 2008, a 5-year prospective cohort study of adults admitted to hospital with community-acquired pneumonia (CAP) was conducted. Pneumococcal serotype was established using a validated multiplex immunoassay (Bio-Plex; Bio-Rad, Hercules, CA, USA). The overall incidence for hospitalised CAP and pneumococcal CAP was 79.9 (95% CI 76.6-83.3) and 23.4 (95% CI 21.6-25.3) per 100?000 population, respectively. A decline in CAP (incidence rate ratio (IRR) per year 0.96, 95% CI 0.94-0.99; p=0.016) and pneumococcal CAP (IRR per year 0.84, 95% CI 0.80-0.89; p<0.001) was observed over the 5-year period of the study. Between the pre- and post-PCV13 periods of the study, the incidence of CAP due to serotypes included in the PCV7 declined by 88% (IRR 0.12, 95% CI 0.08-0.20; p<0.001), and CAP due to the additional 6 serotypes in PCV13 declined by 30% (IRR 0.70, 95% CI 0.51-0.96; p=0.024). Incidence of adult pneumococcal pneumonia declined over the last 5?years, with serotypes included in PCV13 declining post-PCV13 introduction, indicating early herd protection effects from PCV13 infant vaccination on adult non-bacteraemic disease. These effects may accrue over the coming years with implications for national pneumococcal vaccination policies in adults. PMID:25792633

  1. Polysaccharide-specific memory B cells generated by conjugate vaccines in humans conform to the CD27+IgG+ isotype-switched memory B Cell phenotype and require contact-dependent signals from bystander T cells activated by bacterial proteins to differentiate into plasma cells.

    PubMed

    Clarke, Edward T; Williams, Neil A; Findlow, Jamie; Borrow, Ray; Heyderman, Robert S; Finn, Adam

    2013-12-15

    The polysaccharides (PS) surrounding encapsulated bacteria are generally unable to activate T cells and hence do not induce B cell memory (BMEM). PS conjugate vaccines recruit CD4(+) T cells via a carrier protein, such as tetanus toxoid (TT), resulting in the induction of PS-specific BMEM. However, the requirement for T cells in the subsequent activation of the BMEM at the time of bacterial encounter is poorly understood, despite having critical implications for protection. We demonstrate that the PS-specific BMEM induced in humans by a meningococcal serogroup C PS (Men C)-TT conjugate vaccine conform to the isotype-switched (IgG(+)CD27(+)) rather than the IgM memory (IgM(+)CD27(+)) phenotype. Both Men C and TT-specific BMEM require CD4(+) T cells to differentiate into plasma cells. However, noncognate bystander T cells provide such signals to PS-specific BMEM with comparable effect to the cognate T cells available to TT-specific BMEM. The interaction between the two populations is contact-dependent and is mediated in part through CD40. Meningococci drive the differentiation of the Men C-specific BMEM through the activation of bystander T cells by bacterial proteins, although these signals are enhanced by T cell-independent innate signals. An effect of the TT-specific T cells activated by the vaccine on unrelated BMEM in vivo is also demonstrated. These data highlight that any protection conferred by PS-specific BMEM at the time of bacterial encounter will depend on the effectiveness with which bacterial proteins are able to activate bystander T cells. Priming for T cell memory against bacterial proteins through their inclusion in vaccine preparations must continue to be pursued. PMID:24227777

  2. 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

  3. Protein antigens increase the protective efficacy of a capsule-based vaccine against Staphylococcus aureus in a rat model of osteomyelitis.

    PubMed

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

    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

  4. Safety and immunogenicity of CRM197-conjugated pneumococcal–meningococcal C combination vaccine (9vPnC–MnCC) whether given in two or three primary doses

    Microsoft Academic Search

    Sigurveig Th. Sigurdardottir; Katrin Davidsdottir; Vilhjalmur A. Arason; Olof Jonsdottir; William C. Gruber; Ingileif Jonsdottir

    2008-01-01

    This randomized trial compares safety and immunogenicity when vaccinating infants with a pneumococcal–meningococcal conjugate vaccine in two doses vs. three doses. Infants (N=223) received 9vPnC–MnCC (CRM197-conjugated pneumococcal serotypes 1, 4, 5, 6B, 9V, 14, 18C, 19F, 23F and meningococcal C polysaccharides) either at 3 and 5 or 3, 4 and 5 months and a booster with either 9vPnC–MnCC or 23-valent

  5. A Poly-N-acetylglucosamine-Shiga toxin broad-spectrum conjugate vaccine for Shiga toxin-producing Escherichia coli.

    PubMed

    Lu, Xi; Skurnik, David; Pozzi, Clarissa; Roux, Damien; Cywes-Bentley, Colette; Ritchie, Jennifer M; Munera, Diana; Gening, Marina L; Tsvetkov, Yury E; Nifantiev, Nikolay E; Waldor, Matthew K; Pier, Gerald B

    2014-01-01

    Many pathogens produce the ?-(1-6)-linked poly-N-acetylglucosamine (PNAG) surface polysaccharide that is being developed as a broadly protective antimicrobial vaccine. However, it is unknown whether systemically injected PNAG vaccines or antibodies would provide protective immunity against pathogens confined to the gastrointestinal tract such as Shiga toxin (Stx)-producing Escherichia coli (STEC), an important group of gastrointestinal (GI) pathogens for which effective immunotherapeutics are lacking. To ascertain whether systemic IgG antibody to PNAG impacts this infectious situation, a vaccine consisting of a synthetic nonamer of nonacetylated PNAG, 9GlcNH2, conjugated to the Shiga toxin 1b subunit (9GlcNH2-Stx1b) was produced. Rabbit antibodies raised to the conjugate vaccine were tested for bacterial killing and toxin neutralization in vitro and protection against infection in infant mice. Cell surface PNAG was detected on all 9 STEC isolates tested, representing 6 STEC serogroups, including E. coli O157:H7. Antibody to the 9GlcNH2-Stx1b conjugate neutralized Stx1 potently and Stx2 modestly. For O157:H7 and O104:H4 STEC strains, antibodies elicited by the 9GlcNH2-Stx1b conjugate possessed opsonic killing and bactericidal activity. Following intraperitoneal injection, antibodies to both PNAG and Stx were needed for infant mouse protection against O157 STEC. These antibodies also mediated protection against the Stx2-producing O104:H4 strain that was the cause of a recent outbreak in Germany, although sufficient doses of antibody to PNAG alone were protective against this strain in infant mice. Our observations suggest that vaccination against both PNAG and Stx, using a construct such as the 9GlcNH2-Stx1b conjugate vaccine, would be protective against a broad range of STEC serogroups. IMPORTANCE The presence of poly-N-acetylglucosamine (PNAG) on many pathogens presents an opportunity to target this one structure with a multispecies vaccine. Whether antibodies to PNAG can protect against pathogens confined to the gastrointestinal tract is not known. As Shiga toxin (Stx)-producing Escherichia coli (STEC) bacteria are serious causes of infection whose virulence is dependent on elaboration of Stx, we prepared a vaccine containing a synthetic nonamer of PNAG (9GlcNH2) conjugated to Shiga toxin 1b subunit (9GlcNH2-Stx1b) to evaluate bacterial killing, toxin neutralization, and protective efficacy in infant mice. All nine (100%) clinical strains of STEC from different serogroups expressed PNAG. Vaccine-induced antibody mediated in vitro killing of STEC and neutralization of both Stx1 and Stx2. Passive administration of antibody to the conjugate showed protection requiring immunity to both PNAG and Stx for O157 strains, although for an O104 strain, antibody to PNAG alone was protective. Immunity to PNAG may contribute to protection against STEC infections. PMID:24667709

  6. Prompt effect of replacing the 7-valent pneumococcal conjugate vaccine with the 13-valent vaccine on the epidemiology of invasive pneumococcal disease in Norway.

    PubMed

    Steens, Anneke; Bergsaker, Marianne A Riise; Aaberge, Ingeborg S; Rønning, Karin; Vestrheim, Didrik F

    2013-12-16

    The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in the childhood immunisation programme in Norway in 2006 substantially decreased the incidence of vaccine-type (VT) invasive pneumococcal disease (IPD) in all age groups. Additionally, a slight increase in the non-vaccine (NVT) serotype IPD incidence (serotype replacement) was observed. After replacing PCV7 with PCV13 in 2011, a further decrease in IPD incidence is expected. However, the protection by the six additional serotypes opens new nasopharyngeal niches for colonisation, which favours conditions for serotype replacement. Close monitoring of IPD therefore remains important in order to quickly detect changes. In this observational retrospective population-based cohort study we used data notified nationally between 1 January 2004 and 31 December 2012 to determine the VT- and NVT-IPD incidences. The diversity in serotype distribution per year was analysed using the Simpson's index of diversity. Immunisation history of young children was obtained from the Norwegian Vaccination Registry to determine vaccine failure. The incidence of VT-IPD decreased in the targeted (<5 years) and non-targeted (?5) age groups since PCV7 introduction and further decreased after the replacement with PCV13. Only two cases of vaccine failure were identified. This indicates very high effectiveness of the 2+1 schedules with PCV7 or PCV13 and suggests that non-vaccinated individuals profit through indirect protection. The decrease in incidence of PCV7-IPD in non-targeted age groups became larger in later years, indicating a lag phase for the indirect effects, and suggests that the indirect protection of PCV13 will increase in coming years. The incidence of some NVT, specifically serotypes 23B and 15A, increased after PCV13 introduction. This coincided with an increased Simpson's index of diversity in the targeted age group. As this suggests that serotype replacement is again occurring, continues monitoring of IPD is important so that adaptations to vaccine recommendations can be promptly issued. PMID:24176490

  7. Effect of physico-chemical modification on the immunogenicity of Haemophilus influenzae type b oligosaccharide–CRM 197 conjugate vaccines

    Microsoft Academic Search

    Barbara Bolgiano; Fatme Mawas; Susan E. Yost; Dennis T. Crane; Xavier Lemercinier; Michael J. Corbel

    2001-01-01

    Haemophilus influenzae type b (Hib) poly-ribosyl-ribityl phosphate (PRP) oligosaccharide–CRM197 conjugate vaccines from two different manufacturers (Hib A and Hib B) were subjected to adverse storage conditions and used to establish correlates between physico-chemical characteristics and immunogenicity. There were manufacturer-specific differences in the effect of freezing or freeze-thawing on the carrier protein conformation and the anti-CRM197 or anti-PRP IgG response in

  8. Immunogenicity and immunological memory induced by a 7-valent pneumococcal CRM197 conjugate vaccine in symptomatic HIV1 infected children

    Microsoft Academic Search

    Vana I. Spoulou; Dimitris L. Tsoumas; Vana G. Papaevangelou; Glykeria I. Mostrou; Maria C. Theodoridou

    2005-01-01

    A 7-valent CRM197 conjugate pneumococcal vaccine (PCV)-induced immune response were evaluated in all Greek symptomatic HIV-1 infected children and 21 age-matched controls. PCV immunogenicity was inferior in HIV patients compared with the controls although differences in geometric mean concentrations (GMC) were not significant (P>.05). Immune responses were strikingly different after anamnestic immunization, given in all study subjects, 12 months later.

  9. Humoral immune response of a pneumococcal conjugate vaccine: capsular polysaccharide serotype 14-Lysine modified PspA.

    PubMed

    Santamaria, Raquel; Goulart, Cibelly; Perciani, Catia T; Barazzone, Giovana C; Carvalho, Rimenys; Gonçalves, Viviane M; Leite, Luciana C C; Tanizaki, Martha M

    2011-11-01

    Polysaccharide-protein conjugates are so far the current antigens used for pneumococcal vaccines for children under 2 years of age. In this study, pneumococcal surface protein A (PspA) was used as a carrier protein for pneumococcal capsular polysaccharide serotype 14 as an alternative to broaden the vaccine coverage. PspA was modified by reductive amination with formaldehyde in order to improve the specificity of the reaction between protein and polysaccharide, inhibiting polymerization and the gel formation reaction. In the synthesis process, the currently used activator, 1-[3-(dimethylamine)propyl]-3-ethylcarbodiimide hydrochloride (EDAC) was substituted for 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM). BALB/c mice were immunized with either the PS14-mPspA conjugate or the co-administered components in a three dose regimen and sera from the immunized animals were assayed for immunity induced against both antigens: PS14 and mPspA. Modification of more than 70% of lysine residues from PspA (mPspA) did not interfere in the immune response as evaluated by the anti-PspA titer and C3 complement deposition assay. Sera of mice immunized with conjugated PS14-mPspA showed similar IgG titers, avidity and isotype profile as compared to controls immunized with PspA or mPspA alone. The complement deposition was higher in the sera of mice immunized with the conjugate vaccine and the opsonophagocytic activity was similar for both sera. Conjugation improved the immune response against PS14. The anti PS14 IgG titer was higher in sera of mice immunized with the conjugate than with co-administered antigens and presented an increased avidity index, induction of a predominant IgG1 isotype and increased complement deposition on a bacteria with a surface serotype 14. These results strongly support the use of PspA as carrier in a conjugate vaccine where both components act as antigens. PMID:21906649

  10. Economic evaluation of meningococcal serogroup C conjugate vaccination programmes in The Netherlands and its impact on decision-making.

    PubMed

    Welte, R; van den Dobbelsteen, G; Bos, J M; de Melker, H; van Alphen, L; Spanjaard, L; Rümke, H C; Postma, M J

    2004-12-01

    The cost-effectiveness of one time vaccination of all persons aged 14 months to 18 years (catch-up programme) and of routine childhood immunisation at either ages 2 + 3 + 4 months, 5 + 6 months, or 14 months with a meningococcal C conjugate vaccine was estimated for The Netherlands, from a societal and a health care payer perspective. A decision analysis cohort model was employed (time horizon 77 years), direct and indirect costs (friction cost method) were considered and future costs and effects were discounted at 4%. The results showed that all vaccination options yield a substantial health gain and that the catch-up programme and routine vaccination at 14 months render favourable cost-effectiveness ratios: between about 13,200 and 17,700 per life year gained for the catch-up programme and between about 2200 and 2400 per life year gained for routine childhood vaccination at 14 months, depending on the perspective. In comparison to vaccination at 14 months, routine childhood vaccination during the first year of life is much less cost-effective: each additional life year gained costs approximately 147,000 (2 + 3 + 4 months) or 102,000 (5 + 6 months), from both perspectives. Additionally, inclusion of the likely herd immunity effect of the catch-up programme increases these incremental cost-effectiveness ratios. These results played a major role in the decision to add meningococcal C vaccination to the routine childhood immunisation schedule at 14 months and to implement a catch-up vaccination programme in The Netherlands in 2002. PMID:15530695

  11. PspA Family Distribution, unlike Capsular Serotype, Remains Unaltered following Introduction of the Heptavalent Pneumococcal Conjugate Vaccine

    PubMed Central

    Croney, Christina M.; Coats, Mamie T.; Nahm, Moon H.; Briles, David E.

    2012-01-01

    Pneumococcal conjugate vaccines (PCVs) are recommended for the prevention of invasive pneumococcal disease (IPD) in young children. Since the introduction of the heptavalent pneumococcal vaccine (PCV7) in 2000, IPD caused by serotypes in the vaccine has almost been eliminated, and previously uncommon capsular serotypes now cause most cases of pediatric IPD in the United States. One way to protect against these strains would be to add cross-reactive protein antigens to new vaccines. One such protein is pneumococcal surface protein A (PspA). Prior to 2000, PspA families 1 and 2 were expressed by 94% of isolates. Because PCV7 vaccine pressure has resulted in IPD caused by capsular serotypes that were previously uncommon and unstudied for PspA expression, it was possible that many of the new strains expressed different PspA antigens or even lacked PspA. Of 157 pediatric invasive pneumococcal isolates collected at a large pediatric hospital in Alabama between 2002 and 2010, only 60.5% had capsular serotypes included in PCV13, which came into general use in Alabama after our strains were collected. These isolates included 17 serotypes that were not covered by PCV13. Nonetheless, pneumococcal capsular serotype replacement was not associated with changes in PspA expression; 96% of strains in this collection expressed PspA family 1 or 2. Continued surveillance will be critical to vaccine strategies to further reduce IPD. PMID:22539473

  12. Monitoring the introduction of pneumococcal conjugate vaccines into West Africa: design and implementation of a population-based surveillance system.

    PubMed

    Mackenzie, Grant A; Plumb, Ian D; Sambou, Sana; Saha, Debasish; Uchendu, Uchendu; Akinsola, Bolanle; Ikumapayi, Usman N; Baldeh, Ignatius; Usuf, Effua; Touray, Kebba; Jasseh, Momodou; Howie, Stephen R C; Wattiaux, Andre; Lee, Ellen; Knoll, Maria Deloria; Levine, Orin S; Greenwood, Brian M; Adegbola, Richard A; Hill, Philip C

    2012-01-01

    Routine use of pneumococcal conjugate vaccines (PCVs) in developing countries is expected to lead to a significant reduction in childhood deaths. However, PCVs have been associated with replacement disease with non-vaccine serotypes. We established a population-based surveillance system to document the direct and indirect impact of PCVs on the incidence of invasive pneumococcal disease (IPD) and radiological pneumonia in those aged 2 months and older in The Gambia, and to monitor changes in serotype-specific IPD. Here we describe how this surveillance system was set up and is being operated as a partnership between the Medical Research Council Unit and the Gambian Government. This surveillance system is expected to provide crucial information for immunisation policy and serves as a potential model for those introducing routine PCV vaccination in diverse settings. PMID:22272192

  13. Effect of monophosphoryl lipid A (MPL ®) on T-helper cells when administered as an adjuvant with pneumocococcal–CRM 197 conjugate vaccine in healthy toddlers

    Microsoft Academic Search

    Louis Vernacchio; Henry Bernstein; Steve Pelton; Carole Allen; Kristin MacDonald; Jessica Dunn; David D. Duncan; Grace Tsao; Vincent LaPosta; John Eldridge; Suzanne Laussucq; Donna M. Ambrosino; Deborah C. Molrine

    2002-01-01

    As new vaccines are developed, novel adjuvants may play an important role in eliciting an effective immune response. We evaluated the safety and adjuvant properties of monophosphoryl lipid A (MPL®) in 129 healthy toddlers immunized with two doses of nine-valent pneumococcal–CRM197 protein conjugate vaccine (PCV9) combined with 10, 25, or 50?g of MPL® with or without alum (AlPO4). Vaccine-specific humoral

  14. Impact of heptavalent pneumococcal conjugate vaccine on invasive disease, antimicrobial resistance and colonization in Alaska Natives: progress towards elimination of a health disparity

    Microsoft Academic Search

    Thomas W. Hennessy; Rosalyn J. Singleton; Lisa R. Bulkow; Dana L. Bruden; Debby A. Hurlburt; Debra Parks; Matthew Moore; Alan J. Parkinson; Anne Schuchat; Jay C. Butler

    2005-01-01

    We evaluated invasive pneumococcal disease (IPD), antimicrobial resistance and nasopharyngeal colonization before and after introduction of pneumococcal conjugate vaccine (PCV7) in Alaska Natives (AN), a population with high IPD rates. We obtained IPD rates from population-based surveillance. Colonization was determined from annual surveys among rural AN of all ages and from urban children. After vaccine introduction, vaccine-type IPD rates declined

  15. Safety and immunogenicity of oligosaccharide conjugate Haemophilus influenzae type b (HbOC) vaccine in infancy. The Northern California Kaiser Permanente Vaccine Study Center Pediatrics Group.

    PubMed

    Black, S B; Shinefield, H R; Lampert, D; Fireman, B; Hiatt, R A; Polen, M; Vittinghoff, E

    1991-02-01

    The safety and immunogenicity of the HbOC conjugate vaccine have been evaluated in a study population of 61,080 children in the Kaiser Permanente Medical Care Program of Northern California. Half of the population served as controls. The vaccine was given as part of a three-dose regimen in the first year of life with the first dose given between 6 weeks and 6 months of age, a minimum interval of 1 month between doses and with the third dose given by 1 year of age. The vaccine was highly immunogenic with 97% of infants developing 1 microgram/ml or more of anti-polyribosyl phosphate antibody as measured by Farr assay 1 month after completion of the three-dose series and with 71% maintaining this concentration until a booster dose was given at approximately 18 months of age. There were three cases of Haemophilus influenzae type b disease after the first dose of vaccine and two of these children died. However, there was no statistically significant difference between either the incidence of H. influenzae type b disease or the mortality rate in infants after one dose of HbOC vaccine when compared with H. influenzae type b disease incidence and mortality in unvaccinated children of the same age. The rate of sudden infant death syndrome following HbOC vaccine was lower than that observed within the Kaiser Permanente Medical Care Program as a whole or in the three counties in which sudden infant death syndrome surveillance was tabulated. Immediate local and systemic reactions were evaluated by telephone interviews of 6887 infants within 72 hours of vaccine.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2062620

  16. Cost-benefit analysis for the use of Haemophilus influenzae type b conjugate vaccine in Santiago, Chile.

    PubMed

    Levine, O S; Ortiz, E; Contreras, R; Lagos, R; Vial, P; Misraji, A; Ferreccio, C; Espinoza, C; Adlerstein, L; Herrera, P

    1993-06-01

    Cost-benefit analyses can be integral to the evaluation of interventions in developing countries. The authors compare the potential benefits to the Chilean Ministry of Health, in terms of treatment costs averted, by prevention of Haemophilus influenzae type b (HIB) invasive disease, with the costs of adding HIB conjugate vaccine to the diphtheria-tetanus-pertussis (DTP) immunization routinely administered to infants. In their basecase model, over a 10-year period (1991-2000), vaccination against HIB will prevent 1,229 cases of HIB invasive disease, including 713 cases of meningitis, 107 of whom would suffer severe, long-term sequelae, and between 29 and 116 deaths. Assuming a cost of US$1 for a full three-dose regimen of vaccine, the benefit/cost ratio of 1.66, with a net discounted savings of over $403,225, illustrates that HIB vaccine can be cost-beneficial. Sensitivity analyses which alter each of the variables in the analysis indicate that if the true incidence of HIB disease is twice the published rate, then three doses of vaccine remains cost-beneficial at US#3. PMID:8322763

  17. Differential B-Cell Memory Around the 11-Month Booster in Children Vaccinated With a 10- or 13-Valent Pneumococcal Conjugate Vaccine

    PubMed Central

    van Westen, Els; Wijmenga-Monsuur, Alienke J.; van Dijken, Harry H.; van Gaans-van den Brink, Jacqueline A. M.; Kuipers, Betsy; Knol, Mirjam J.; Berbers, Guy A. M.; Sanders, Elisabeth A. M.; Rots, Nynke Y.; van Els, Cécile A. C. M.

    2015-01-01

    Background.?Both the 10- and 13-valent pneumococcal conjugate vaccines (PCV10 and PCV13) induce immunological memory against Streptococcus pneumoniae infections caused by vaccine serotypes. In addition to comparing serum antibody levels, we investigated frequencies of serotype-specific plasma cells (PCs) and memory B-cells (Bmems) as potential predictors of long-term immunity around the booster vaccination at 11 months of age. Methods.?Infants were immunized with PCV10 or PCV13 at 2, 3, 4, and 11 months of age. Blood was collected before the 11-month booster or 7–9 days afterward. Serotype-specific immunoglobulin G (IgG) levels were determined in serum samples by multiplex immunoassay. Circulating specific PCs and Bmems against shared serotypes 1, 6B, 7F, and 19F and against PCV13 serotypes 6A and 19A were measured in peripheral blood mononuclear cells by enzyme-linked immunospot assay. Results.?No major differences in IgG levels and PC frequencies between groups were found for the 4 shared serotypes. Notably, PCV13 vaccination resulted in higher frequencies of Bmems than PCV10 vaccination, both before and after the booster dose, for all 4 shared serotypes except for serotype 1 postbooster. For PCV13-specific serotypes 6A and 19A, the IgG levels and frequencies of PCs and Bmems were higher in the PCV13 group, pre- and postbooster, except for PC frequencies prebooster. Conclusions.?Both PCVs are immunogenic and induce measurable IgG, PC, and Bmem booster responses at 11 months. Compared to PCV10, vaccination with PCV13 was associated with overall similar IgG levels and PC frequencies but with higher Bmem frequencies before and after the 11-month booster. The clinical implications of these results need further follow-up. Clinical Trials Registration.?NTR3069. PMID:25838290

  18. 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

  19. 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

  20. Immunogenicity and Efficacy of Cryptococcus neoformans Capsular Polysaccharide Glucuronoxylomannan Peptide Mimotope-Protein Conjugates in Human Immunoglobulin Transgenic Mice

    PubMed Central

    Maitta, Robert W.; Datta, Kausik; Lees, Andrew; Belouski, Shelley Sims; Pirofski, Liise-anne

    2004-01-01

    Peptide mimotopes of capsular polysaccharides have been proposed as antigens for vaccines against encapsulated pathogens. In this study, we determined the antibody response to and efficacy of P13, a peptide mimetic of the Cryptococcus neoformans capsular polysaccharide glucuronoxylomannan (GXM), in mice that produce human antibodies. P13 was conjugated to tetanus toxoid (TT) or diphtheria toxoid (DT) and administered subcutaneously in Alhydrogel with or without CpG to mice transgenic for human immunoglobulin loci (XenoMouse mice) and expressing either immunoglobulin G2 (IgG2) (G2 mice) or IgG4 (G4 mice). Mice were vaccinated and revaccinated two or three times. The serum antibody responses of the mice to GXM and P13 and antibody idiotype expression were analyzed by an enzyme-linked immunosorbent assay. The results showed that both P13-TT and P13-DT were antigenic, inducing a mimetic response to P13 in both G2 and G4 mice, and immunogenic, inducing a mimotope response including VH3 (idiotype)-positive antibodies to GXM in G2 but not G4 mice. CpG led to higher titers of IgG to P13 and GXM in P13-TT-vaccinated G2 mice. C. neoformans challenge of P13-protein conjugate-vaccinated and control G2 mice induced anamnestic IgG- and VH3-positive responses to GXM and was associated with a significantly decreased risk of death and a prolongation of survival in P13-DT-vaccinated mice compared to phosphate-buffered saline-treated or protein carrier-vaccinated mice. These findings reveal that P13 elicited a human antibody response with VH3 expression in human immunoglobulin transgenic mice that has been observed for human antibodies to GXM and support the concept that peptide mimotope-based vaccines may hold promise for the treatment of C. neoformans infections. PMID:14688097

  1. DNA Vaccination against Tuberculosis: Expression of a Ubiquitin-Conjugated Tuberculosis Protein Enhances Antimycobacterial Immunity

    Microsoft Academic Search

    GIOVANNI DELOGU; ANGELA HOWARD; FRANK M. COLLINS; SHELDON L. MORRIS

    2000-01-01

    Genetic immunization is a promising new technology for developing vaccines against tuberculosis that are more effective. In the present study, we evaluated the effects of intracellular turnover of antigens expressed by DNA vaccines on the immune response induced by these vaccines in a mouse model of pulmonary tuberculosis. The mycobacterial culture filtrate protein MPT64 was expressed as a chimeric protein

  2. Vaccination Coverage and Compliance with Three Recommended Schedules of 10-Valent Pneumococcal Conjugate Vaccine during the First Year of Its Introduction in Brazil: A Cross-Sectional Study

    PubMed Central

    2015-01-01

    Pneumococcal 10-valent conjugate vaccine (PCV10) was introduced to Brazil’s National Immunization Program (NIP) in 2010. During the first year of vaccine introduction three schedules were used to deal with age at initiation of PCV for catch-up purposes: 3 primary doses + 1 booster (for children aged ?6 months), a catch-up schedule of 2 doses + 1 booster (7-11 months), and a catch-up schedule of a single dose (12-15 months). The purpose of this study was to assess the magnitude and associated risk factors for under-vaccination or lack of on time vaccination six to eight months after PCV10 introduction. A household survey was conducted in the municipality of Goiania with 1,237 children, who were retroactively classified into one of three age groups, as a factor of the child’s age relatively to 30 days after PCV10 introduction. Socioeconomic characteristics and vaccination dates were obtained during home interviews. Vaccination coverage was defined as the percentage of children who completed the recommended number of doses. Compliance with recommended schedules was defined as the percentage of children who received all valid doses at the NIP recommended time interval. Adjusted prevalence ratios (PR) of variables independently associated with coverage and compliance were estimated by log binomial regression. Coverage of DTP-Hib was used for comparison purposes. Overall, vaccination coverage was 54.6% (95% CI 52.1-57.7%), lower than DTP-Hib coverage (93.0%; 95% CI 91.5-94.3%). Compliance with recommended schedules was 16.8% (95% CI: 14.7-18.6%). Children 7-11 months old had lower coverage (40.7%) and compliance (6.3%) compared to children aged 12-15 months (coverage: 88.8%; compliance: 35.6%) and ?6 months old (coverage: 54%; compliance: 18.8%). Having private health insurance was associated with higher PCV10 coverage (PR=1.25; 95% CI: 1.06-1.47, p=0.007), and compliance (PR=1.09; 95% CI: 1.02-1.16, p=0.015). Although PCV10 coverage rapidly increased shortly after vaccination introduction, it was not matched by compliance with recommended schedules. Public initiatives should target compliance of PCV10 because of the burden of pneumococcal diseases on childhood morbidity and mortality. PMID:26061276

  3. Immunogenicity of conjugate vaccines consisting of pneumococcal capsular polysaccharide types 6B, 14, 19F, and 23F and a meningococcal outer membrane protein complex.

    PubMed Central

    Vella, P P; Marburg, S; Staub, J M; Kniskern, P J; Miller, W; Hagopian, A; Ip, C; Tolman, R L; Rusk, C M; Chupak, L S

    1992-01-01

    In an effort to prepare pneumococcal (Pn) capsular polysaccharide (Ps) vaccines that would be immunogenic in infants, covalent conjugates were prepared for Pn types 6B, 14, 19F, and 23F. Each Ps type was covalently bound to an outer membrane protein complex from Neisseria meningitidis serogroup B and evaluated for immunogenicity in mice and infant monkeys. The conjugates induced specific anti-Ps antibody responses in mice and in infant rhesus and African green monkeys; a conjugate of 6B and outer membrane protein complex was immunogenic at Ps doses as low as 20 ng. Although low levels of the Pn group-common cell wall polysaccharide were present in all type-specific Ps preparations, anti-cell wall polysaccharide responses induced by covalent conjugates were < 1% of the total anti-Ps response after two doses of vaccine. In contrast, the anti-cell wall polysaccharide response of a noncovalent conjugate represented 41% of the anti-Ps response after two doses. Relative T-cell dependence, a requirement for the human target population of infants less than 18 months old, was demonstrated for all four Pn Ps conjugates in an athymic mouse model. Therefore, these Pn Ps-outer membrane protein complex conjugate vaccines are excellent candidates for evaluation in human infants. PMID:1452327

  4. Double-blind study comparing the immunogenicity of a licensed DTwPHib-CRM197 conjugate vaccine (Quattvaxem™) with three investigational, liquid formulations using lower doses of Hib-CRM197 conjugate

    Microsoft Academic Search

    Eda Tamm; Alessandra Veronese; Mario Contorni; Sirli Meriste; Pantaleo Nacci; Simonetta Viviani

    2005-01-01

    We performed a double-blind clinical study to evaluate the safety and immunogenicity of four formulations of a DTwPHib full liquid vaccine, three of which contained fractional doses of the 10?g-dose of CRM197-Hib conjugate vaccine.A total of 261 infants were enrolled and randomised to receive at 3, 4 and 5 months of age, in a double-blind fashion, one of the four

  5. Functional activity of antibodies to the group B polysaccharide of group B streptococci elicited by a polysaccharide-protein conjugate vaccine.

    PubMed Central

    Marques, M B; Kasper, D L; Shroff, A; Michon, F; Jennings, H J; Wessels, M R

    1994-01-01

    Group B streptococci (GBS) are a major cause of sepsis and meningitis in infants. While antibodies directed to the type-specific GBS capsule have been shown to be protective, it is less clear whether antibodies to the group B polysaccharide, a noncapsular, cell wall-associated antigen, may play a role in immunity. To investigate the functional activity of group B polysaccharide-specific antibodies, we tested sera from rabbits vaccinated with group B polysaccharide coupled to tetanus toxoid (B-TT). Anti-B-TT was weakly opsonic in vitro for a highly encapsulated type III strain, while antiserum elicited by vaccination with type III capsular polysaccharide linked to tetanus toxoid (III-TT) was a very effective opsonin. In contrast to anti-III-TT, anti-B-TT given before or after bacterial challenge was only marginally effective in protecting newborn mice against lethal infection with type III GBS. The number of C3 molecules bound to type III GBS was augmented by anti-III-TT but not by high antibody concentrations of anti-B-TT. These results suggest that the difference in opsonic activity between anti-B-TT and anti-III-TT may be due to a difference in their ability to deposit C3. In addition, the maximum number of antibody molecules bound to the bacterial surface was greater for anti-III-TT than for anti-B-TT. That anti-B-TT binds to fewer sites than anti-III-TT may explain the differences in complement activation and in opsonic and protective efficacy of antibodies to group B polysaccharide compared with antibodies to the type-specific capsular polysaccharide. Images PMID:8168919

  6. Immunological evaluation of a synthetic Clostridium difficile oligosaccharide conjugate vaccine candidate and identification of a minimal epitope.

    PubMed

    Martin, Christopher E; Broecker, Felix; Oberli, Matthias A; Komor, Julia; Mattner, Jochen; Anish, Chakkumkal; Seeberger, Peter H

    2013-07-01

    Clostridium difficile is the cause of emerging nosocomial infections that result in abundant morbidity and mortality worldwide. Thus, the development of a vaccine to kill the bacteria to prevent this disease is highly desirable. Several recently identified bacterial surface glycans, such as PS-I and PS-II, are promising vaccine candidates to preclude C. difficile infection. To circumvent difficulties with the generation of natural PS-I due to its low expression levels in bacterial cultures, improved chemical synthesis protocols for the pentasaccharide repeating unit of PS-I and oligosaccharide substructures were utilized to produce large quantities of well-defined PS-I related glycans. The analysis of stool and serum samples obtained from C. difficile patients using glycan microarrays of synthetic oligosaccharide epitopes revealed humoral immune responses to the PS-I related glycan epitopes. Two different vaccine candidates were evaluated in the mouse model. A synthetic PS-I repeating unit CRM197 conjugate was immunogenic in mice and induced immunoglobulin class switching as well as affinity maturation. Microarray screening employing PS-I repeating unit substructures revealed the disaccharide Rha-(1?3)-Glc as a minimal epitope. A CRM197-Rha-(1?3)-Glc disaccharide conjugate was able to elicit antibodies recognizing the C. difficile PS-I pentasaccharide. We herein demonstrate that glycan microarrays exposing defined oligosaccharide epitopes help to determine the minimal immunogenic epitopes of complex oligosaccharide antigens. The synthetic PS-I pentasaccharide repeating unit as well as the Rha-(1?3)-Glc disaccharide are promising novel vaccine candidates against C. difficile that are currently in preclinical evaluation. PMID:23795894

  7. 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

  8. Serologic response to primary vaccination with 7-valent pneumococcal conjugate vaccine is better than with 23-valent pneumococcal polysaccharide vaccine in HIV-infected patients in the era of combination antiretroviral therapy

    PubMed Central

    Lu, Ching-Lan; Hung, Chien-Ching; Chuang, Yu-Chung; Liu, Wen-Chun; Su, Chin-Ting; Su, Yi-Ching; Chang, Shu-Fang; Chang, Sui-Yuan; Chang, Shan-Chwen

    2013-01-01

    Objectives: The objectives of this study were to compare the serologic responses at week 48 to primary vaccination with 23-valent pneumococcal polysaccharide vaccine (PPV) vs. 7-valent pneumococcal conjugate vaccine (PCV); and to identify factors associated with serologic response in HIV-infected adult patients with access to combination antiretroviral therapy (cART). Methods: One hundred and four CD4-matched pairs of HIV-infected patients who underwent primary pneumococcal vaccination with 23-valent PPV or 7-valent PCV were enrolled for determinations of anti-capsular antibody responses against four serotypes (6B, 14, 19F and 23F) at baseline, 24 weeks and 48 weeks following vaccination. Significant antibody responses were defined as 2-fold or greater increase of antibody levels at week 48 compared with baseline. The logistic regression model was used to determine the factors associated with serologic response to at least one and two serotypes. Results: At week 48, patients who received PCV demonstrated a statistically significantly higher response rate to at least 2 serotypes than those who received PPV (37.5% vs. 20.2%, p = 0.006). In multivariate analysis, factors associated with significant antibody responses to at least one or two serotypes included receipt of PCV (adjusted odds ratio [AOR], 2.42 [95% CI, 1.23–4.78] and 3.58 [95% CI. 1.76–7.28], respectively), and undetectable plasma HIV RNA load (< 400 copies/ml) at vaccination (AOR, 1.47 [95% CI, 0.60–3.64] and 3.62 [95% CI, 1.11–11.81], respectively). Conclusions: Primary vaccination with 7-valent PCV achieved a significantly better serologic responses to one or two out of the four serotypes studied at week 48 than with 23-valent PPV in HIV-infected patients in the cART era. Suppression of HIV replication when primary vaccination was administered was associated with better serologic responses. PMID:23291936

  9. 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

  10. Synthesis of Mercapto (+) methamphetamine Haptens and Their Use for Obtaining Improved Epitope Density on (+) Methamphetamine Conjugate Vaccines

    PubMed Central

    Carroll, F. Ivy; Blough, Bruce E.; Pidaparthi, Ramakrishna R.; Abraham, Philip; Gong, Paul K.; Deng, Liu; Huang, Xiaodong; Gunnell, Melinda; Lay, Jackson O.; Peterson, Eric C.; Owens, S. Michael

    2011-01-01

    This study reports the synthesis of the mercapto hapten (S)-N-(2-(mercaptoethyl)-6-(3-(2-(methylamino)propyl)phenoxy)hexanamide [3, (+)-METH HSMO9] and its use to prepare METH-conjugated vaccines (MCV) from maleimide activated proteins. MALDI-TOF mass spectrometry analysis of the MCV synthesized using 3 showed there was a high and controllable epitope density on two different carrier proteins. In addition, the MCV produced a substantially greater immunological response in mice than previous METH haptens, and a monoclonal antibody generated from this MCV in mice showed a very high affinity for (+)-METH (KD = 6.8 nM). The efficient covalent coupling of (+)-METH HSMO9 to the activated carrier proteins suggests this approach could be cost effective for large-scale production of MCV. In addition, the general methods described for the synthesis of (+) METH HSMO9 (3) and its use to synthesize MCV will be applicable for conjugated vaccines of small molecules and other substances of abuse such as morphine, nicotine, and cocaine. PMID:21682289

  11. Economic and clinical evaluation of a catch-up dose of 13-valent pneumococcal conjugate vaccine in children already immunized with three doses of the 7-valent vaccine in Italy

    Microsoft Academic Search

    Sara Boccalini; Chiara Azzari; Massimo Resti; Claudia Valleriani; Martina Cortimiglia; Emilia Tiscione; Angela Bechini; Paolo Bonanni

    A new 13-valent conjugated polysaccharide vaccine (PCV13) against Streptococcus pneumoniae infections, which replaced the 7-valent vaccine (PCV7) in the regional immunization programmes for newborns and children who started but not completed the 3 doses schedule of PCV7, is available in Italy since 2010. The opportunity of administering a further dose of PCV13 to children under 5 years of age who

  12. CpG Oligodeoxynucleotides Act as Adjuvants for Pneumococcal Polysaccharide-Protein Conjugate Vaccines and Enhance Antipolysaccharide Immunoglobulin G2a (IgG2a) and IgG3 Antibodies

    Microsoft Academic Search

    ROSE S. CHU; TERA MCCOOL; NEIL S. GREENSPAN; JOHN R. SCHREIBER; CLIFFORD V. HARDING

    2000-01-01

    Pneumococcal polysaccharide-protein conjugate vaccines elicit antipolysaccharide antibodies, but multiple doses are required to achieve protective antibody levels in children. In addition, the immunogenicity of experimental multivalent pneumococcal conjugate vaccines varies with different polysaccharide serotypes. One strategy to improve these vaccines is to incorporate an adjuvant to enhance their immunogenicity. Synthetic oligodeoxynucleotides containing unmethylated CpG motifs (CpG ODN) are adjuvants that

  13. Pre-clinical evaluation of a 15-valent pneumococcal conjugate vaccine (PCV15-CRM197) in an infant-rhesus monkey immunogenicity model.

    PubMed

    Skinner, Julie M; Indrawati, Lani; Cannon, Jayme; Blue, Jeffrey; Winters, Michael; Macnair, John; Pujar, Narahari; Manger, Walter; Zhang, Yuhua; Antonello, Joseph; Shiver, John; Caulfield, Michael; Heinrichs, Jon H

    2011-11-01

    The incidence of invasive pneumococcal disease (IPD), caused by the approximately 91 serotypes of Streptococcus pneumoniae (PN), varies geographically and temporally as a result of changing epidemiology and vaccination patterns as well as due to regional measurement differences. Prevnar(®) (Pfizer), the first licensed pneumococcal conjugate vaccine (PCV), comprises polysaccharides (PS) from 7 serotypes conjugated to the mutant diphtheria toxin carrier protein, CRM197. In the United States and elsewhere, this vaccine has been highly efficacious in reducing the incidence of IPD caused by vaccine serotypes, however, the incidence of non-vaccine serotypes (e.g., 19A, 22F, and 33F) has increased, resulting in the need for vaccines with higher valencies. In response, 10- and 13-valent PCVs have recently been licensed. To further increase serotype coverage, we have developed a 15-valent PCV containing PS from serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, 22F, 23F and 33F conjugated to CRM197 and formulated on aluminum phosphate adjuvant. Vaccine immunogenicity was evaluated in infant rhesus monkeys since they, like human infants, respond poorly to unconjugated PN PS. Infant (2-3 month old) rhesus monkeys were vaccinated three times with PCV-15 or Prevnar(®) at 2 month intervals, and serotype-specific IgG antibodies were measured using a multiarray electrochemiluminescence (ECL) assay. The results indicate that antibody responses to PCV-15 and Prevnar(®) were comparable for the 7 common serotypes and that post-vaccination responses to PCV-15 were >10-fold higher than baseline for the 8 additional serotypes. PMID:21964055

  14. Public health and economic impact of the 13-valent pneumococcal conjugate vaccine (PCV13) in the United States.

    PubMed

    Rubin, Jaime L; McGarry, Lisa J; Strutton, David R; Klugman, Keith P; Pelton, Stephen I; Gilmore, Kristen E; Weinstein, Milton C

    2010-11-10

    The 7-valent pneumococcal conjugate vaccine (PCV7) has dramatically decreased pneumococcal disease incidence, and the 13-valent vaccine (PCV13) protects against 6 additional Streptococcus pneumoniae serotypes. A decision-analytic model was constructed to evaluate the impact of infant vaccination with PCV13 versus PCV7 on pneumococcal disease incidence and mortality as well as the incremental benefit of a serotype catch-up program. PCV13 effectiveness was extrapolated from observed PCV7 data, using assumptions regarding serotype prevalence and PCV13 protection against additional serotypes. The model predicts that PCV13 is more effective and cost saving compared with PCV7, preventing 106,000 invasive pneumococcal disease (IPD) cases and 2.9 million pneumonia cases, and saving $11.6 billion over a 10-year period. The serotype catch-up program would prevent an additional 12,600 IPD cases and 404,000 pneumonia cases, and save an additional $737 million compared with no catch-up program. PMID:20883739

  15. Efficacy of Haemophilus influenzae type b conjugate vaccines and persistence of disease in disadvantaged populations. The Haemophilus Influenzae Study Group.

    PubMed Central

    Jafari, H S; Adams, W G; Robinson, K A; Plikaytis, B D; Wenger, J D

    1999-01-01

    OBJECTIVES: The purpose of this study was to evaluate the effectiveness of Haemophilus influenzae type b (Hib) conjugate vaccines among children aged 2 to 18 months and to determine risk factors for invasive Hib disease during a period of declining incidence (1991-1994). METHODS: A prospective population-based case-control study was conducted in a multistate US population of 15.5 million. A laboratory-based active surveillance system was used for case detection. RESULTS: In a multivariate analysis, having a single-parent mother (odds ratio [OR] = 4.3, 95% confidence interval [CI] = 1.2, 14.8) and household crowding (OR = 3.5, 95% CI = 1.03, 11.7) were risk factors for Hib disease independent of vaccination status. After adjustment for these risk factors, the protective efficacy of 2 or more Hib vaccine doses was 86% (95% CI = 16%, 98%). Among undervaccinated subjects, living with a smoker (P = .02) and several indicators of lower socioeconomic status were risk factors for Hib disease. CONCLUSIONS: Hib disease still occurs at low levels in the United States, predominantly in socioeconomically disadvantaged populations. Low immunization coverage may facilitate continuing transmission of Hib. Special efforts to achieve complete and timely immunization in disadvantaged populations are needed. PMID:10076486

  16. Immunogenicity and safety of 13-valent pneumococcal conjugate vaccine when administered to healthy Japanese adults aged ?50 years

    PubMed Central

    Shiramoto, Masanari; Irie, Shin; Juergens, Christine; Yamaji, Masako; Tamai, Satoshi; Aizawa, Masakazu; Belanger, Todd; Gruber, William C; Scott, Daniel A; Schmoele-Thoma, Beate

    2014-01-01

    This open-label study was designed to assess immunogenicity and safety of 13-valent pneumococcal conjugate vaccine (PCV13) when administered to Japanese adults aged ?50 years not previously vaccinated with 23-valent pneumococcal polysaccharide vaccine and to compare this Japanese study population with similar study populations in the United States (US; 50–64 years age group) and European Union (EU; ?65 years age group). Functional antibody immune responses were measured by opsonophagocytic activity assays. Immune responses in both Japanese age groups showed significant pre/postvaccination fold rises for each serotype. In the Japanese 50–64 years age group, immune responses for the majority of serotypes were significantly lower than in the ?65 years Japanese age group and generally lower than in the 50–64 years age group in the US study. Immune responses in the Japanese ?65 years age group were significantly higher for the majority of serotypes compared with the ?65 years age group in the EU study. The safety profiles across age groups and studies were generally similar. In conclusion, PCV13 elicited robust immune responses in the Japanese study population. The unanticipated higher immune responses observed in the older age group in the Japanese study are of interest and of potential benefit given the higher incidence of pneumococcal disease in older adults. PCV13 was well tolerated and safe. PMID:25424792

  17. 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

  18. Effect of zinc and vitamin A supplementation on antibody responses to a pneumococcal conjugate vaccine in HIV-positive injection drug users: a randomized trial.

    PubMed

    Deloria-Knoll, Maria; Steinhoff, Mark; Semba, Richard D; Nelson, Kenrad; Vlahov, David; Meinert, Curtis L

    2006-03-01

    HIV-infected individuals have impaired immune responses to vaccines and high rates of pneumococcal disease. The effect of vitamin A and zinc supplementation on the immunogenicity of a 7-valent pneumococcal CRM-197 conjugate vaccine (PC-7) was evaluated in 118 HIV+ injection drug users. Subjects were randomized to oral 400,000 IU vitamin A, 300 mg zinc, vitamin A + zinc, or placebo, then immunized. Geometric mean titer increased 1.3-3.3-fold for all pneumococcal serotypes. PC-7 elicited an immune response in HIV-infected adults but neither vitamin A nor zinc altered the immunogenicity of the evaluated vaccines. PMID:16256250

  19. Overcoming the need for a cold chain with conjugated meningococcal Group C vaccine: A controlled, randomized, double-blind study in toddlers on the safety and immunogenicity of Menjugate ®, stored at room temperature for 6 months

    Microsoft Academic Search

    Ines Schöndorf; Angelika Banzhoff; Uwe Nicolay; Francisco Diaz-Mitoma

    2007-01-01

    Millions of vaccine doses are wasted each year due to a lapse in recommended storage conditions. Maintaining the cold chain for vaccines is both expensive and difficult, especially in developing countries. The present study investigated the safety and immunogenicity of a single dose of the conjugated meningococcal Group C vaccine, Menjugate®, stored for 6 months at room temperature (25±2°C, N=250)

  20. 9 CFR 113.112 - Clostridium Perfringens Type D Toxoid and Bacterin-Toxoid.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Inactivated Bacterial Products § 113.112 Clostridium Perfringens Type D Toxoid and...

  1. 9 CFR 113.111 - Clostridium Perfringens Type C Toxoid and Bacterin-Toxoid.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...PLANT HEALTH INSPECTION SERVICE, DEPARTMENT OF AGRICULTURE VIRUSES, SERUMS, TOXINS, AND ANALOGOUS PRODUCTS; ORGANISMS AND VECTORS STANDARD REQUIREMENTS Inactivated Bacterial Products § 113.111 Clostridium Perfringens Type C Toxoid and...

  2. Prevention of adult pneumococcal pneumonia with the 13-valent pneumococcal conjugate vaccine: CAPiTA, the community-acquired pneumonia immunization trial in adults.

    PubMed

    Isturiz, Raul; Webber, Chris

    2015-07-01

    The aging of the world population is expected to be accompanied by increased pneumococcal pneumonia in older adults. To address this, the Community-Acquired Pneumonia immunization Trial in Adults (CAPiTA), a large, randomized, placebo-controlled trial conducted to assess the 13-valent pneumococcal conjugate vaccine (PCV13) in adults ?65 years, found statistically significant vaccine efficacy for first episodes of vaccine-type community-acquired pneumonia (VT-CAP; 46%), nonbacteremic/noninvasive VT-CAP (45%), and VT invasive pneumococcal disease (75%), along with an acceptable safety profile. Study results were presented to the US Advisory Committee on Immunization Practices in June 2014, which subsequently recommended sequential PCV13 and 23-valent pneumococcal polysaccharide vaccination for adults ?65 years. Thus, appropriate protection of adults at risk for pneumococcal CAP will include vaccination with PCV13. PMID:26076136

  3. Levels and functionality of antibodies after pneumococcal conjugate vaccine in schedules with different timing of the booster dose.

    PubMed

    van Westen, Els; Rodenburg, Gerwin D; van Gils, Elske J M; Tcherniaeva, Irina; Berbers, Guy A M; Cowell, Lucy; Goldblatt, David; Rots, Nynke Y; van den Dobbelsteen, Germie P J M; Sanders, Elisabeth A M

    2013-12-01

    The seven-valent pneumococcal conjugate vaccine (PCV7) has been introduced in most high-income countries, although with differences in age, timing and number of primary doses before 6 months of age and presence and timing of a booster vaccination. The objective was to determine and compare the IgG antibody levels and functionality of IgG responses (avidity and opsonophagocytoses) at 1 and 2 years of age following 2 primary doses with a booster at 11 or 24 months of age. Children received PCV7 at 2 and 4 months (2-dose group), or at 2, 4 and 11 months (2+1-dose group), or no PCV7 (controls) before 1 year of age. All children received a PCV7 dose at 24 months of age. At the age of 12 months, the 2+1-dose group had higher IgG levels and functional antibody levels, compared to the 2-dose group for all serotypes, but at 25 months the difference between the 2-dose and 2+1-dose groups had disappeared for most serotypes. The kinetics of opsonophagocytic antibodies were in line with the specific IgG antibody levels for most serotypes, although differences between the 2-dose and the 2+1-dose group were more pronounced in OPA activity as compared to the IgG levels especially at the age of 24 months. Delaying the booster dose from 11 months to 24 months after 2 primary doses resulted in significantly higher OPA GMTs one month after the booster dose. This must, however, be balanced against the risk of leaving children unboosted between the age of 11 and 24 months at a time when disease risk is still high. Local decisions about the timing of a booster dose should also take into account vaccine coverage and the indirect herd effect in a well vaccinated population. Trial registration clinicaltrials.gov Identifier: NCT00189020. PMID:24120678

  4. Understanding the impact of Hib conjugate vaccine on transmission, immunity and disease in the United Kingdom.

    PubMed

    McVernon, J; Ramsay, M E; McLean, A R

    2008-06-01

    A rise in invasive Haemophilus influenzae type b (Hib) infections occurred 8 years after vaccine introduction in the United Kingdom. Aspects of Hib vaccine delivery unique to the United Kingdom have been implicated. The authors developed a fully age-structured deterministic susceptible-infected-resistant-susceptible mathematical model, expressed as a set of partial differential equations, to better understand the causes of declining vaccine effectiveness. We also investigated the consequences of the vaccine's impact on reducing Hib transmission for maintenance of immunity. Our findings emphasized the importance of maintaining high post-immunization antibody titres among age groups at greatest risk of invasive infections. In keeping with UK population-based estimates, low direct efficacy of immunological memory against disease was found, cautioning against over-reliance on evidence of priming alone as a correlate of population protection. The contribution of herd immunity to disease control was reinforced. Possible intervention strategies will be explored in subsequent work. PMID:17678559

  5. Increase in the nasopharyngeal carriage of non-vaccine serogroup 15 Streptococcus pneumoniae after introduction of children pneumococcal conjugate vaccination in Hong Kong.

    PubMed

    Ho, Pak-Leung; Chiu, Susan S; Law, Pierra Y; Chan, Eunice L; Lai, Eileen L; Chow, Kin-Hung

    2015-02-01

    This study assessed pneumococcal carriage in the early periods after routine use of 13-valent pneumococcal conjugate vaccine (PCV13) in Hong Kong. Nasopharyngeal swabs were obtained from 1110 children (<5 years) admitted with acute illness during September 2010-August 2013. Pneumococcal carriage rate was 13.5% in unvaccinated children, 14.1% in children who had ?1 PCV dose and 15.3% in children who had ?3 PCV doses. Nonv-PCV13 serotypes comprised 56.4% of all isolates. The most common serogroup/types were 15 (15A, 5.1%; 15B, 10.3%; 15C, 9.6%; 15F, 0.6%), 19F (17.9%), 6A (7.1%) and 6C (7.1%). Carriage of serogroup 15 was more common among vaccinated children (4.1% versus 0.6%, P = 0.033). Molecular typing revealed that expansion of several clones (clonal complex, CC63, CC199, CC1262, CC3397) was responsible for the increase in serogroup 15. Almost all CC63 and CC3397 isolates were nonsusceptible to both penicillin and erythromycin. The finding highlights the emergence of serogroup 15 following PCV13 use. PMID:25483278

  6. Bacterial Meningitis after Cochlear Implantation among Children without Polyvalent Conjugate Vaccine: A Brief Report of an Iranian Cohort Study on 371 Cases

    PubMed Central

    Afsharpaiman, Shahla; Amirsalari, Susan; Ajalloueyan, Mohammad; Saburi, Amin

    2014-01-01

    Background: Regarding risk of bacterial meningitis (BM) after Cochlear implantation (CI), it was suggested to receive polyvalent conjugate vaccine. We aimed to estimate the prevalence of BM post CI in child recipients who do not receive polyvalent vaccine. Methods: We enrolled 371 children who had received cochlear implants from 2007 to 2010. None of them received pre or post implantation polyvalent conjugate vaccine for BM. We followed all of them for BM for 2 years after implantation. Results: We detected only one female case of BM (0.3% of patients) with the age of 24 months. The mean age of noninfected children was 36.7 ± 23.2 months. The education level of parents was “college level or higher” in less than half of them, and about 65% of patients were products of consanguineous marriage. Conclusions: Our findings indicated that the incidence of BM was not higher in our cochlear implanted children who did not receive immunization than patients from countries in which routine vaccination is done. We suggest that although proper immunization is recommended before surgery, this procedure could be performed without vaccination, especially in developing countries that face financial problems for preparing vaccines. PMID:25489459

  7. Optimising assessments of the epidemiological impact in The Netherlands of paediatric immunisation with 13-valent pneumococcal conjugate vaccine using dynamic transmission modelling.

    PubMed

    De Cao, Elisabetta; Melegaro, Alessia; Klok, Rogier; Postma, Maarten

    2014-01-01

    This work is the first attempt to quantify the overall effects of a 13-valent pneumococcal conjugate vaccine (PCV13) vaccination programme in the Dutch population taking into account all the direct and indirect effects of the vaccine on invasive pneumococcal disease. Using available Dutch data, a dynamic transmission model for the spread of pneumococci and potential subsequent invasive pneumococcal disease has been adapted to the Dutch setting. Overall, invasive pneumococcal disease cases in the Netherlands are predicted to decrease from a pre-vaccination level of 2623 cases annually to 2475, 2289, 2185, 2179, and 2178 cases annually 5-, 10-, 20-, 30-, and 40-years, respectively, post-vaccination. Therefore, vaccination with PCV13 in the Netherlands is predicted to lower invasive pneumococcal disease cases per year by up to 445 cases in the medium- to long-term. The results are quite robust for the sensitivity analyses performed on the parameters that regulate herd immunity and competition between vaccine and non-vaccine types. PMID:24694656

  8. Blood stream infection is associated with altered heptavalent pneumococcal conjugate vaccine immune responses in very low birth weight infants

    PubMed Central

    Wynn, James L.; Li, Lei; Cotten, C. Michael; Phelps, Dale L.; Shankaran, Seetha; Goldberg, Ronald N; Carlo, Waldemar A.; Van Meurs, Krisa; Das, Abhik; Vohr, Betty R.; Higgins, Rosemary D.; Stoll, Barbara J; D’Angio, Carl T

    2013-01-01

    Objective Sepsis in older children and adults modifies immune system function. We compared serotype-specific antibody responses to heptavalent pneumococcal conjugate vaccine (PCV7) in very low birth weight infants (<1500g,VLBW) with and without blood stream infection (BSI) during their birth hospitalization. Patients and Methods Retrospective analysis of prospectively collected data for the Neonatal Research Network study of PCV7 responses among VLBWs. Infants received PCV7 at 2, 4, and 6 months after birth with blood drawn 4–6 weeks after 3rd dose. Serotype antibodies were compared between infants with or without a history of BSI. Regression models were constructed with birth-weight groups and other confounding factors identified in the primary study. Results 244 infants completed the vaccine series and had serum antibody available; 82 had BSI. After adjustment, BSI was not associated with reduced odds of serum antibody ?0.35?g/mL. Conclusions BSI was not associated with reduced odds of WHO-defined protective PCV7 responses in VLBWs. PMID:23370608

  9. Is a single infant priming dose of meningococcal serogroup C conjugate vaccine in the United Kingdom sufficient?

    PubMed

    Findlow, Helen; Borrow, Ray

    2015-06-01

    In 1999, the UK introduced meningococcal serogroup C conjugate (MCC) vaccination at 2, 3, 4 months of age with a single dose for children 1-18 y In 2006, the schedule was refined to a 2 dose priming schedule with a booster in the second year of life. In 2013, the number of priming doses was reduced to a single priming dose, the booster maintained at 12 months of age and an adolescent booster dose introduced. The paper presents the evidence supporting the reduction in the number of priming doses. A UK study provided evidence for reducing the priming doses of MCC-TT together with the positive correlation of lower quantity of antigen and serum bactericidal antibody (SBA) levels post-primary but a higher magnitude of the booster response. Another UK study, demonstrated one dose of MCC-TT or MCC-CRM197 at 3 months gave comparable responses to 2 doses (SBA titres ?8) both post-primary vaccination and post-booster Hib/MCC-TT at 12 months. However, the magnitude of the SBA GMT was higher in the MCC-TT primed post-booster. A single priming dose of MCC-TT (at 4 or 6 months) compared to 2 doses (2 and 4 months) gave higher SBA titres in all groups, post-primary and post-booster at 12-13 months, with the highest SBA responses observed in the 4 month single dose group. A study in Malta, comparing one dose of MCC-TT or MCC-CRM197 at (3 months) versus 2 doses of MCC-CRM197 (3 and 4 months), showed a high proportion (>84.72%) of subjects achieving SBA titres ?8 following a single dose. These studies show that a single-dose priming MCC vaccination in infancy is sufficient. PMID:25912095

  10. Invasive and Noninvasive Streptococcus pneumoniae Capsule and Surface Protein Diversity following the Use of a Conjugate Vaccine

    PubMed Central

    Croney, Christina M.; Nahm, Moon H.; Juhn, Steven K.; Briles, David E.

    2013-01-01

    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

  11. Non-invasive pneumococcal serotypes and antimicrobial susceptibilities in a paediatric hospital in the era of conjugate vaccines.

    PubMed

    McElligott, Martha; Vickers, Imelda; Cafferkey, Mary; Cunney, Robert; Humphreys, Hilary

    2014-06-12

    To evaluate the effects of 7-valent pneumococcal conjugate vaccine (PCV7) introduction to the routine childhood immunisation schedule in 2008 and its replacement by PCV13 in 2010 in Ireland, we surveyed the serotypes and antimicrobial susceptibilities of 339 pneumococci associated with carriage and non-invasive infection (NII) in a Dublin paediatric hospital from 2009 to 2012. Furthermore, we compared the distribution of pneumococcal serotypes collected from 2009 to 2012 to 105 NII pneumococci isolated in 2007, the year before conjugate vaccine introduction. PCV7 serotypes declined from 2007 to 2012 as follows: carriage, 67-23% (p=0.0004); conjunctivitis, 58-0% (p<0.0001); non-bacteraemic lower respiratory tract infection, 50-19% (p=0.0363) and otitis media 54-27%. Notably, antimicrobial resistant (AMR) PCV7 serotypes showed a significant decrease by the end of the study period (i.e. 2012) (p<0.0001). Compared with 2007 the overall occurrence of serotype 19A increased from 1.9 to 10% in 2010 (p=0.0132) and to 15% in 2011 (p=0.0005). Importantly, serotype 19A declined significantly from 2011 levels to an overall prevalence of 4.8% in 2012 (p=0.0243). Most striking was the significant reduction of AMR 19A (p=0.0195). Conversely, increases were observed in non-vaccine type (NVT) pneumococci in 2009-2012, of which serotypes 11A (n=30), 15B/C (n=17), 22F (n=14), 35Bn=13), non-typeable pneumococci (n=13) and 23A (n=12) were the most prevalent. Moreover, an increase in NVT non-susceptible to at least one antimicrobial in 2009-2012 was noted, attributable to serotypes 35B (n=10) and 15A (n=7). In summary, this study has shown that PCV7 and PCV13 introduction has had a positive impact on their target serotypes and antimicrobial resistance amongst pneumococci within a paediatric hospital within a short time period. However, the increase in NVT prevalence highlights the need for continued surveillance. PMID:24795223

  12. Impact of meningococcal C conjugate vaccination campaign in Emilia-Romagna, Italy

    PubMed Central

    Pascucci, Maria Grazia; Di Gregori, Valentina; Frasca, Gabriella; Rucci, Paola; Finarelli, Alba Carola; Moschella, Laura; Borrini, Bianca Maria; Cavrini, Francesca; Liguori, Giovanna; Sambri, Vittorio; Bonanni, Paolo; Fantini, Maria Pia

    2014-01-01

    The incidence of reported meningococcal disease in Italy is among the lowest in Europe. The trend of the disease was increasing up to 2005 and then declined after the gradual introduction of a universal Men C vaccination program in 17/21 Italian regions. Since 2006, in Emilia-Romagna region vaccination against Neisseria meningitidis serogroup C was actively offered free of charge in a single dose to the age groups 12–15 months and 14–15 years, in addition to people with defined epidemiological risk. Our aim was to measure the impact of vaccination on the incidence of meningococcal disease caused by different serogroups among the population of Emilia Romagna Region, Northern Italy (approximately 4.5 million inhabitants) subdivided by age. Using surveillance data, we computed the incidence rates of Neisseria meninigitidis related invasive disease per 100.000 inhabitants for the years 2000 to 2012. In addition, the percentage change in incidence and the mortality rates were calculated. Results indicate a 70.1% decrease in the incidence of meningococcus C-related invasive disease after the introduction of MenC universal vaccination. No case of serogroup C related infection was observed since 2006 in children aged 1–4 years. These findings suggest that the single-dose vaccination strategy against serogroup C N.meningitidis targeted to the age groups 12–15 months and 14–15 years was effective in the Emilia-Romagna population. However, the occurrence of two cases of meningiditis in a 5-month child and in a 9-years child suggests caution and careful consideration in surveillance for the next years. PMID:24384537

  13. Duration of protective immunity conferred by maternal tetanus toxoid immunization: further evidence from Matlab, Bangladesh.

    PubMed Central

    Koenig, M A; Roy, N C; McElrath, T; Shahidullah, M; Wojtyniak, B

    1998-01-01

    OBJECTIVES: Although maternal tetanus immunization has been shown to be highly effective in the prevention of neonatal tetanus, unresolved questions remain concerning the required minimum number of doses and the resulting duration of effective immunity. This study examined the duration of effective immunity against neonatal tetanus provided by maternal tetanus immunization. METHODS: A randomized, double-blind cholera vaccine trial of 41,571 children and nonpregnant adult women carried out in 1974 in the Matlab comparison area of rural Bangladesh provided a unique opportunity to address dose and immunity issues. RESULTS: Children of women who received either 1 or 2 injections of tetanus toxoid experienced 4- to 14-day mortality levels consistently lower than those of children of unimmunized mothers. Analysis of neonatal-tetanus-related mortality showed that 2 injections of tetanus toxoid provided significant protection for subsequent durations of up to 12 or 13 years. CONCLUSIONS: The data demonstrate that a limited-dose regimen of maternal tetanus toxoid provides significant and extended protection against the risk of neonatal tetanus death. PMID:9618617

  14. A Randomized Controlled Trial of Oral Administration of Tetanus Toxoid (TT) Versus Tetanus and Reduced Diphtheria (Td) in Pregnant Women

    Microsoft Academic Search

    Maha M. Salama; Osama A. W. Hady; Wael Ashour; Amal Mostafa; Sahar El Alkamy; Nehad El Sayed; Remon Abu El Yazeed

    2009-01-01

    Introduction  The present study was designed as a randomized clinical trial to compare the immunogenicity, reactogenicity, and efficacy\\u000a of tetanus toxoid (TT) and the combined tetanus and reduced diphtheria (Td) in pregnant women in four rural communities in\\u000a Egypt. The pregnant women in each four villages received either TT or Td randomly. Both TT and Td vaccines are manufactured\\u000a by the

  15. 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

  16. 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

  17. Immunochemical studies of Shigella flexneri 2a and 6, and Shigella dysenteriae type 1 O-specific polysaccharide-core fragments and their protein conjugates as vaccine candidates

    PubMed Central

    Kubler-Kielb, Joanna; Vinogradov, Evgeny; Mocca, Christopher; Pozsgay, Vince; Coxon, Bruce; Robbins, John B.; Schneerson, Rachel

    2010-01-01

    There is no licensed vaccine for the prevention of shigellosis. Our approach to the development of Shigella vaccine is based on inducing serum IgG antibodies to the O-specific polysaccharide (O-SP) domain of their lipopolysaccharides (LPS). We have shown that low molecular mass O-SP-core (O-SPC) fragments isolated from Shigella sonnei LPS conjugated to proteins induced significantly higher antibody levels in mice than the full length O-SP conjugates. This finding is now extended to the O-SPC of S. flexneri 2a and 6, and S. dysenteriae type 1. The structures of O-SPC, containing core plus 1–4 O-SP repeat units (RU), were analyzed by NMR and mass spectroscopy. The first RUs attached to the cores of S. flexneri 2a and 6 LPS were different from the following RUs in their O-acetylation and/or glucosylation. Conjugates of core plus more than 1 RUs were necessary to induce LPS antibodies in mice. The resulting antibody levels were comparable to those induced by the full length O-SP conjugates. In S. dysenteriae type 1, the first RU was identical to the following RUs, with the exception that the GlcNAc was bound to the core in the ?-configuration, while in all other RUs the GlcNAc was present in the ?-configuration. In spite of this difference, conjugates of S. dysenteriae type 1 core with 1, 2, or 3 RUs induced LPS antibodies in mice with levels statistically higher than those of the full size O-SP conjugates. O-SPC conjugates are easy to prepare, characterize, and standardize, and their clinical evaluation is planned. PMID:20542498

  18. The impact of pre-existing antibody on subsequent immune responses to meningococcal A-containing vaccines.

    PubMed

    Idoko, Olubukola T; Okolo, Seline N; Plikaytis, Brian; Akinsola, Adebayo; Viviani, Simonetta; Borrow, Ray; Carlone, George; Findlow, Helen; Elie, Cheryl; Kulkarni, Prasad S; Preziosi, Marie-Pierre; Ota, Martin; Kampmann, Beate

    2014-07-16

    Major epidemics of serogroup A meningococcal meningitis continue to affect the African meningitis belt. The development of an affordable conjugate vaccine against the disease became a priority for World Health Organization (WHO) in the late 1990s. Licensing of meningococcal vaccines has been based on serological correlates of protection alone, but such correlates might differ in different geographical regions. If high pre-vaccination antibody concentrations/titers impacts on the response to vaccination and possibly vaccine efficacy, is not clearly understood. We set out to define the pre-vaccination Meningococcal group A (Men A) antibody concentrations/titers in The Gambia and study their impact on the immunogenicity of Men A containing vaccines. Data from subjects originally enrolled in studies to test the safety and immunogenicity of the MenA vaccine recently developed for Africa meningococcal A polysaccharide conjugated to tetanus toxoid, MenAfriVac(®) (PsA-TT) were analyzed. Participants had been randomized to receive either the study vaccine PsA-TT or the reference quadrivalent plain polysaccharide vaccine containing meningococcal groups A, C, W, and Y, Mencevax(®) ACWY, GlaxoSmithKline (PsACWY) in a 2:1 ratio. Venous blood samples were collected before and 28 days after vaccination. Antibodies were assayed by enzyme-linked immunosorbent assay (ELISA) for geometric mean concentrations and serum bactericidal antibody (SBA) for functional antibody. The inter age group differences were compared using ANOVA and the pre and post-vaccination differences by t test. Over 80% of the ?19 year olds had pre-vaccination antibody concentrations above putatively protective concentrations as compared to only 10% of 1-2 year olds. Ninety-five percent of those who received the study vaccine had ?4-fold antibody responses if they had low pre-vaccination concentrations compared to 76% of those with high pre-vaccination concentrations. All subjects with low pre-vaccination titers attained ?4-fold responses as compared to 76% with high titers where study vaccine was received. Our data confirm the presence of high pre-vaccination Men A antibody concentrations/titers within the African meningitis belt, with significantly higher concentrations in older individuals. Although all participants had significant increase in antibody levels following vaccination, the four-fold or greater response in antibody titers were significantly higher in individuals with lower pre-existing antibody titers, especially after receiving PsA-TT. This finding may have some implications for vaccination strategies adopted in the future. PMID:24863486

  19. Efficacy in infancy of oligosaccharide conjugate Haemophilus influenzae type b (HbOC) vaccine in a United States population of 61,080 children. The Northern California Kaiser Permanente Vaccine Study Center Pediatrics Group.

    PubMed

    Black, S B; Shinefield, H R; Fireman, B; Hiatt, R; Polen, M; Vittinghoff, E

    1991-02-01

    The efficacy of the HbOC conjugate Haemophilus influenzae type b vaccine was evaluated in a study population of 61,080 infants in the Northern California Kaiser Permanente Medical Care Program. Between February, 1988, and June, 1990, the HbOC vaccine was given as part of a three-dose series at 2, 4, and 6 months of age to 20,800 infants. The study population included children with a well-care visit at a study center during the first 6 months of life. There were 25 cases of Haemophilus influenzae type b disease in the study population: 22 in unvaccinated children and 3 in children who received only one dose of HbOC vaccine. The efficacy of the full three-dose series was evaluated by several methods: a primary analysis comparing fully vaccinated children with unvaccinated children from 7 to 18 months of age; a stratified exact analysis adjusted for age and seasonality; and a case-control analysis which further adjusted for known risk factors. The efficacy of three doses of vaccine was 100% with the lower bound of the 95% confidence interval for the three analyses at 68, 71, and 64%, respectively. There were no cases of disease resulting from two doses of HbOC vaccine yielding an estimate of 100% efficacy (95% confidence interval, 47 to 100) for two doses of HbOC vaccine. However, for children who had received only one dose of HbOC vaccine, vaccine efficacy was estimated to be 26% and the possibility that one dose of HbOC vaccine had no efficacy could not be excluded.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2062621

  20. Working Group on quality, safety and efficacy of typhoid Vi capsular polysaccharide conjugate, vaccines, Jeju, Republic of Korea, 5-7 September 2012.

    PubMed

    Jones, Chris; Lee, Chung Keel; Ahn, Chiyoung; Shin, Jinho; Knezevic, Ivana

    2013-09-23

    Typhoid fever is a gastrointestinal disease transmitted through the ingestion of contaminated water or food. The bacterium, Salmonella enterica subspecies enterica serovar Typhi is an important cause of illness and death in many poor countries where access to safe water and basic sanitation is limited. Humans are the only natural host and reservoir of S. Typhi. Typhoid fever causes around 21 million cases and at least 200,000 deaths per year. Currently, several groups are developing typhoid conjugate vaccines that are expected to be safe and effective in infancy or early childhood. The World Health Organization convened a meeting, in collaboration with the Korea Food and Drug Administration, with experts group in September 2012 to develop guidelines for regulatory evaluation of the quality, safety and efficacy of typhoid conjugate vaccines. This report summarizes collective views on scientific and technical issues that need to be considered in the guidelines. PMID:23933367

  1. Neonatal immune response and serum bactericidal activity induced by a meningococcal conjugate vaccine is enhanced by LT-K63 and CpG2006

    Microsoft Academic Search

    Siggeir F. Brynjolfsson; Stefania P. Bjarnarson; Elena Mori; Giuseppe Del Giudice; Ingileif Jonsdottir

    2008-01-01

    Neonates have a poorly developed immune system. Therefore it is important to develop vaccination strategies that induce protective immunity and immunological memory against pathogens early in life. The immunogenicity of a meningococcal serogroup C polysaccharide conjugate (MenC-CRM197) was assessed in neonatal mice, and effects of LT-K63 and CpG2006 and immunisation routes were compared.Neonatal mice were primed subcutaneously (s.c.) or intranasally

  2. Efficacy of nine-valent pneumococcal conjugate vaccine against pneumonia and invasive pneumococcal disease in The Gambia: randomised, double-blind, placebo-controlled trial

    Microsoft Academic Search

    FT Cutts; SMA Zaman; G Enwere; S Jaffar; OS Levine; JB Okoko; C Oluwalana; A Vaughan; SK Obaro; A Leach; KP McAdam; E Biney; M Saaka; U Onwuchekwa; F Yallop; NF Pierce; BM Greenwood; RA Adegbola

    2005-01-01

    Methods We undertook a randomised, placebo-controlled, double-blind trial in eastern Gambia. Children age 6-51 weeks were randomly allocated three doses of either pneumococcal conjugate vaccine (n=8718) or placebo (8719), with intervals of at least 25 days between doses. Our primary outcome was first episode of radiological pneumonia. Secondary endpoints were clinical or severe clinical pneumonia, invasive pneumococcal disease, and all-cause

  3. Molecular epidemiology of pneumococci obtained from Gambian children aged 2–29 months with invasive pneumococcal disease during a trial of a 9-valent pneumococcal conjugate vaccine

    Microsoft Academic Search

    Martin Antonio; Hannah Dada-Adegbola; Ekow Biney; Tim Awine; John O'Callaghan; Valentin Pfluger; Godwin Enwere; Brown Okoko; Claire Oluwalana; Adeola Vaughan; Syed MA Zaman; Gerd Pluschke; Brian M Greenwood; Felicity Cutts; Richard A Adegbola

    2008-01-01

    BACKGROUND: The study describes the molecular epidemiology of Streptococcus pneumoniae causing invasive disease in Gambian children METHODS: One hundred and thirty-two S. pneumoniae isolates were recovered from children aged 2–29 months during the course of a pneumococcal conjugate vaccine trial conducted in The Gambia of which 131 were characterized by serotyping, antibiotic susceptibility, BOX-PCR and MLST. RESULTS: Twenty-nine different serotypes

  4. Effectiveness of 7-Valent Pneumococcal Conjugate Vaccine Against Invasive Pneumococcal Disease in HIV-Infected and -Uninfected Children in South Africa: A Matched Case-Control Study

    PubMed Central

    Cohen, Cheryl; von Mollendorf, Claire; de Gouveia, Linda; Naidoo, Nireshni; Meiring, Susan; Quan, Vanessa; Nokeri, Vusi; Fortuin-de Smit, Melony; Malope-Kgokong, Babatyi; Moore, David; Reubenson, Gary; Moshe, Mamokgethi; Madhi, Shabir A.; Eley, Brian; Hallbauer, Ute; Kularatne, Ranmini; Conklin, Laura; O'Brien, Katherine L.; Zell, Elizabeth R.; Klugman, Keith; Whitney, Cynthia G.; von Gottberg, Anne; Moore, David; Verwey, Charl; Varughese, Sheeba; Archary, Moherndran; Naby, Fathima; Dawood, Khathija; Naidoo, Ramola; Elliott, Gene; Hallbauer, Ute; Eley, Brian; Nuttall, James; Cooke, Louise; Finlayson, Heather; Rabie, Helena; Whitelaw, Andrew; Perez, Dania; Jooste, Pieter; Naidoo, Dhamiran; Kularatne, Ranmini; Reubenson, Gary; Cohen, Cheryl; de Gouveia, Linda; du Plessis, Mignon; Govender, Nevashan; Meiring, Susan; Quan, Vanessa; von Mollendorf, Claire; Fortuin-de Smidt, Melony; Naidoo, Nireshni; Malope-Kgokong, Babatyi; Nokeri, Vusi; Ncha, Relebohile; Lindani, Sonwabo; von Gottberg, Anne; Spies, Barry; Sono, Lino; Maredi, Phasweni; Hamese, Ken; Moshe, Mamokgethi; Nchabeleng, Maphosane; Ngcobo, Ntombenhle; van den Heever, Johann; Madhi, Shabir; Conklin, Laura; Verani, Jennifer; Whitney, Cynthia; Zell, Elizabeth; Loo, Jennifer; Nelson, George; Klugman, Keith; O'Brien, Katherine

    2014-01-01

    Background.?South Africa introduced 7-valent pneumococcal conjugate vaccine (PCV7) in April 2009 using a 2 + 1 schedule (6 and 14 weeks and 9 months). We estimated the effectiveness of ?2 PCV7 doses against invasive pneumococcal disease (IPD) in human immunodeficiency virus (HIV)–infected and -uninfected children. Methods.?IPD (pneumococcus identified from a normally sterile site) cases were identified through national laboratory-based surveillance. Specimens were serotyped by Quellung or polymerase chain reaction. Four controls, matched for age, HIV status, and hospital were sought for each case. Using conditional logistic regression, we calculated vaccine effectiveness (VE) as 1 minus the adjusted odds ratio for vaccination. Results.?From March 2010 through November 2012, we enrolled 187 HIV-uninfected (48 [26%] vaccine serotype) and 109 HIV-infected (43 [39%] vaccine serotype) cases and 752 HIV-uninfected and 347 HIV-infected controls aged ?16 weeks. Effectiveness of ?2 PCV7 doses against vaccine-serotype IPD was 74% (95% confidence interval [CI], 25%–91%) among HIV-uninfected and ?12% (95% CI, ?449% to 77%) among HIV-infected children. Effectiveness of ?3 doses against vaccine-serotype IPD was 90% (95% CI, 14%–99%) among HIV-uninfected and 57% (95% CI, ?371% to 96%) among HIV-infected children. Among HIV-exposed but -uninfected children, effectiveness of ?2 doses was 92% (95% CI, 47%–99%) against vaccine-serotype IPD. Effectiveness of ?2 doses against all-serotype multidrug-resistant IPD was 96% (95% CI, 62%–100%) among HIV-uninfected children. Conclusions.?A 2 + 1 PCV7 schedule was effective in preventing vaccine-serotype IPD in HIV-uninfected and HIV-exposed, uninfected children. This finding supports the World Health Organization recommendation for this schedule as an alternative to a 3-dose primary series among HIV-uninfected individuals. PMID:24917657

  5. 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

  6. Safety and immunogenicity of a four-component meningococcal group B vaccine (4CMenB) and a quadrivalent meningococcal group ACWY conjugate vaccine administered concomitantly in healthy laboratory workers.

    PubMed

    Findlow, Jamie; Bai, Xilian; Findlow, Helen; Newton, Emma; Kaczmarski, Ed; Miller, Elizabeth; Borrow, Ray

    2015-06-26

    Safety precautions for laboratory staff working with meningococci should primarily rely on laboratory procedures preventing exposure to aerosols containing viable meningococci. Despite this, vaccination is a key component of protection in the occupational setting. In the UK in 2009, there were no licensed vaccines for meningococcal capsular group B or conjugate vaccines for capsular groups A, C, W and Y. We therefore undertook a Phase II trial in laboratory workers to investigate the safety and immunogenicity of a four component group B vaccine (4CMenB) and a quadrivalent group A, C, W and Y conjugate vaccine (ACWY-CRM). Enrolment was open to staff aged 18-65 years at the Public Health Laboratory, Manchester who may have had a potential occupational exposure risk to meningococci. 4CMenB was administered at 0, 2 and 6 months in the non-dominant arm and ACWY-CRM concomitantly at 0 months in the dominant arm. Pre- and post-vaccination blood samples were taken and analysed by the serum bactericidal antibody (SBA) assay against A, C, W and Y strains and a panel of seven diverse group B strains. Diary cards were used to record any local and systemic reactions following each vaccination. In total, 38 staff were enrolled and received initial vaccinations with 31 completing the trial per protocol. Both vaccines were proven safe, with local reactogenicity being more commonly reported following 4CMenB than ACWY-CRM. High proportions of subjects had putative protective SBA titres pre-vaccination, with 61-84 and 61-87% protected against A, C, W and Y strains and diverse MenB strains, respectively. Post-vaccination, SBA titres increased with 95-100 and 90-100% of subjects with protective SBA titres against A, C, W and Y strains and diverse MenB strains, respectively. These data suggest that 4CMenB and ACWY-CRM are safe when administered concomitantly and have the potential to enhance protection for laboratory workers. www.clinicaltrials.gov identifier: NCT00962624. PMID:26025807

  7. Serotype of Streptococcus pneumoniae capsular polysaccharide can modify the Th1\\/Th2 cytokine profile and IgG subclass response to pneumococal-CRM 197 conjugate vaccines in a murine model

    Microsoft Academic Search

    F. Mawas; I. M. Feavers; M. J. Corbel

    2000-01-01

    The cellular and antibody responses to type 14 and type 19F Streptococcus pneumoniae capsular polysaccharides (PS) conjugated to CRM197 were investigated in a mouse model developed for pre-clinical evaluation and quality control of pneumococcal conjugate vaccines. Total IgG antibody and IgG subclasses against PS and the carrier protein for both conjugates were measured in addition to the T cell proliferation

  8. B cell memory to a serogroup C meningococcal conjugate vaccine in childhood and response to booster: little association with serum IgG antibody.

    PubMed

    Perrett, Kirsten P; Jin, Celina; Clutterbuck, Elizabeth; John, Tessa M; Winter, Amy P; Kibwana, Elizabeth; Yu, Ly-Mee; Curtis, Nigel; Pollard, Andrew J

    2012-09-01

    The maintenance of adequate serum Ab levels following immunization has been identified as the most important mechanism for individual long-term protection against rapidly invading encapsulated bacteria. The mechanisms for maintaining adequate serum Ab levels and the relationship between Ag-specific memory B cells and Ab at steady state are poorly understood. We measured the frequency of circulating serogroup C meningococcal (MenC)-specific memory B cells in 250 healthy 6- to 12-y-old children 6 y following MenC conjugate vaccine priming, before a booster of a combined Haemophilus influenzae type b-MenC conjugate vaccine and then 1 wk, 1 mo, and 1 y after the booster. We investigated the relationship between circulating MenC-specific memory B cell frequencies and Ab at baseline and following the booster vaccine. We found very low frequencies of circulating MenC-specific memory B cells at steady state in primary school-aged children and little association with MenC IgG Ab levels. Following vaccination, there were robust memory B cell booster responses that, unlike Ab levels, were not dependent on age at priming with MenC. Measurement of B cell memory in peripheral blood does not predict steady state Ab levels nor the capacity to respond to a booster dose of MenC Ag. PMID:22855707

  9. 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

  10. 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

  11. The Development of an Experimental Multiple Serogroups Vaccine for Neisseria meningitidis

    PubMed Central

    Pinto, Valerian B.; Burden, Robert; Wagner, Allyn; Moran, Elizabeth E.; Lee, Che-Hung

    2013-01-01

    A native outer membrane vesicles (NOMV) vaccine was developed from three antigenically diverse strains of Neisseria meningitidis that express the L1,8, L2, and L3,7 lipooligosaccharide (LOS) immunotypes, and whose synX, and lpxL1 genes were deleted.. Immunogenicity studies in mice showed that the vaccine induced bactericidal antibody against serogroups B, C, W, Y and X N. meningitidis strains. However, this experimental NOMV vaccine was not effective against serogroup A N. meningitidis strains. N. meningitidis capsular polysaccharide (PS) from serogroups A, C, W and Y were effective at inducing bactericidal antibody when conjugated to either tetanus toxoid or the fHbp1-fHbp2 fusion protein fHbp(1+2). The combination of the NOMV vaccine and the N. meningitidis serogroup A capsular polysaccharide (MAPS) protein conjugate was capable of inducing bactericidal antibodies against a limited number of N. meningitidis strains from serogroups A, B, C, W, Y and X tested in this study. PMID:24244473

  12. Divalent toxoids loaded stable chitosan-glucomannan nanoassemblies for efficient systemic, mucosal and cellular immunostimulatory response following oral administration.

    PubMed

    Harde, Harshad; Siddhapura, Krupa; Agrawal, Ashish Kumar; Jain, Sanyog

    2015-06-20

    The present study reports dual tetanus and diphtheria toxoids loaded stable chitosan-glucomannan nanoassemblies (sCh-GM-NAs) formulated using tandem ionic gelation technique for oral mucosal immunization. The stable, lyophilized sCh-GM-NAs exhibited ~152nm particle size and ~85% EE of both the toxoids. The lyophilized sCh-GM-NAs displayed excellent stability in biomimetic media and preserved chemical, conformation and biological stability of encapsulated toxoids. The higher intracellular APCs uptake of sCh-GM-NAs was concentration and time dependent which may be attributed to the receptor mediated endocytosis via mannose and glucose receptor. The higher Caco-2 uptake of sCh-GM-NAs was further confirmed by ex vivo intestinal uptake studies. The in vivo evaluation revealed that sCh-GM-NAs posed significantly (p<0.001) higher humoral, mucosal and cellular immune response than other counterparts by eliciting complete protective levels of anti-TT and anti-DT (~0.1IU/mL) antibodies. Importantly, commercial 'Dual antigen' vaccine administered through oral or intramuscular route was unable to elicit all type of immune response. Conclusively, sCh-GM-NAs could be considered as promising vaccine adjuvant for oral mucosal immunization. PMID:25895719

  13. Antibody- and cell-mediated immune responses to a synthetic oligosaccharide conjugate vaccine after booster immunization.

    PubMed

    Safari, Dodi; Dekker, Huberta A Th; de Jong, Ben; Rijkers, Ger T; Kamerling, Johannis P; Snippe, Harm

    2011-09-01

    Memory formation to CRM-neoglycoconjugate, a synthetic branched tetrasaccharide of Streptococcus pneumoniae type 14 polysaccharide (Pn14PS) that is conjugated to a CRM197 protein, was investigated using mice models. Mice were first immunized with the CRM-neoglycoconjugate and then boosted with either the same neoglycoconjugate or a native Pn14PS in order to investigate the effect of booster immunization. Boosting with the CRM-neoglycoconjugate resulted in increased levels of interleukin 5 (IL-5) in the serum on Day 1, followed by the appearance of high levels of specific anti-Pn14PS IgG antibodies on Day 7. Boosting with native Pn14PS resulted in neither IL-5 induction nor the generation of anti-Pn14PS IgG antibodies. In vitro (re)stimulation of spleen cells after booster injection with the neoglycoconjugate revealed the presence of IL-4 and IL-5. This was not seen in spleen cells obtained from mice boosted with the polysaccharide. When stimulated with heat-inactivated bacteria, however, the polysaccharide-boosted mice did have higher levels of IFN-? and lower levels of IL-17 than both the CRM-neoglycoconjugate-boosted mice and the mock-immunized mice. In conclusion, neoglycoconjugate boosting is responsible for the activation of memory cells and the establishment of sustained immunity. Not only is a booster with native polysaccharide ineffective in inducing opsonic antibodies, but it also interferes with several immunoregulatory mechanisms. PMID:21767596

  14. Age-Dependent Prevalence of Nasopharyngeal Carriage of Streptococcus pneumoniae before Conjugate Vaccine Introduction: A Prediction Model Based on a Meta-Analysis

    PubMed Central

    Le Polain de Waroux, Olivier; Flasche, Stefan; Prieto-Merino, David; Edmunds, W. John

    2014-01-01

    Introduction Data on the prevalence of nasopharyngeal carriage of S.pneumoniae in all age groups are important to help predict the impact of introducing pneumococcal conjugate vaccines (PCV) into routine infant immunization, given the important indirect effect of the vaccine. Yet most carriage studies are limited to children under five years of age. We here explore the association between carriage prevalence and serotype distribution in children aged ?5 years and in adults compared to children. Methods We conducted a systematic review of studies providing carriage estimates across age groups in healthy populations not previously exposed to PCV, using MEDLINE and Embase. We used Bayesian linear meta-regression models to predict the overall carriage prevalence as well as the prevalence and distribution of vaccine and nonvaccine type (VT and NVT) serotypes in older age groups as a function of that in <5 y olds. Results Twenty-nine studies compromising of 20,391 individuals were included in the analysis. In all studies nasopharyngeal carriage decreased with increasing age. We found a strong positive linear association between the carriage prevalence in pre-school childen (<5 y) and both that in school aged children (5–17 y olds) and in adults. The proportion of VT serotypes isolated from carriers was consistently lower in older age groups and on average about 73% that of children <5 y among 5–17 y olds and adults respectively. We provide a prediction model to infer the carriage prevalence and serotype distribution in 5–17 y olds and adults as a function of that in children <5 years of age. Conclusion Such predictions are helpful for assessing the potential population-wide effects of vaccination programmes, e.g. via transmission models, and thus assist in the design of future pneumococcal conjugate vaccination strategies. PMID:24465920

  15. Effect of 7-valent pneumococcal conjugate vaccine on nasopharyngeal carriage with Haemophilus influenzae and Moraxella catarrhalis in a randomized controlled trial.

    PubMed

    van Gils, Elske J M; Veenhoven, Reinier H; Rodenburg, Gerwin D; Hak, Eelko; Sanders, Elisabeth A M

    2011-10-13

    Seven-valent CRM197-conjugated pneumococcal conjugate vaccine (PCV7(CRM197)) reduces both vaccine serotype nasopharyngeal colonization and vaccine serotype acute otitis media by 50-60%. However, overall pneumococcal carriage and impact on otitis media are partly offset by concomitant increase of nonvaccine serotypes. We investigated in a randomized controlled trial the impact of 2-doses and 2+1-doses of PCV7(CRM197) on carriage of Streptococcus pneumoniae and of other nasopharyngeal commensals and well-known otitis media pathogens, Haemophilus influenzae and Moraxella catarrhalis, in children. Nasopharyngeal swabs were collected at the age of 6 weeks and at 6, 12, 18 and 24 months. We observed high carriage rates up to 68% for S. pneumoniae, 71% for H. influenzae and 68% for M. catarrhalis at the age of 18 months. Reduced dose (CRM197) schedules induced a slight reduction in overall pneumococcal carriage but no increases in the presence of H. influenzae and M. catarrhalis. PMID:21893151

  16. 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

  17. Immunological responses to nasal delivery of free and encapsulated tetanus toxoid: studies on the effect of vehicle volume.

    PubMed

    Eyles, J E; Williamson, E D; Alpar, H O

    1999-10-28

    In light of growing interest in the intranasal route as a non-invasive mode of immunisation, we have investigated the relationship between the volume of liquid instilled into the nasal passages and the development of subsequent immunological responses. Groups of six mice were intranasally immunised with soluble or microsphere encapsulated tetanus toxoid on days 1, 14 and 28 of the experiment. Microsphere suspensions and tetanus toxoid solutions were nasally instilled in two different volumes of buffer (10 or 50 microl). Nasal instillation of microspheres in 10 microl of buffer generated statistically depressed (P<0.001) tertiary serum anti-toxoid IgG responses in comparison to animals immunised with 10 or 50 microl of soluble vaccine, or 50 microl of microsphere suspension. Relative to other treatments, nasal inoculation of encapsulated toxoid suspended in 50 microl generated statistically (P<0.05) superior levels of specific IgG and IgA antibodies in day 49 lung wash samples. When radiolabelled microspheres were nasally instilled into mouse nares in 50-microl volumes of buffer, a significant portion of the dose (48%) entered the lungs (P<0.001), whereas more particles remained in the nasal passages when a smaller (10 microl) volume of suspension was given (P<0.001). These biodistribution and immunological data indicate that to generate optimal bronchopulmonary and systemic responses in concert following nasal administration, microparticulated vaccines should be administered with a delivery device that targets the formulation to distal regions of the nasal passages and the lower respiratory tract. PMID:10518687

  18. Comparative Immunogenicity of 7 and 13-Valent Pneumococcal Conjugate Vaccines and the Development of Functional Antibodies to Cross-Reactive Serotypes

    PubMed Central

    Grant, Lindsay R.; O’Brien, Sarah E.; Burbidge, Polly; Haston, Mitch; Zancolli, Marta; Cowell, Lucy; Johnson, Marina; Weatherholtz, Robert C.; Reid, Raymond; Santosham, Mathuram; O’Brien, Katherine L.; Goldblatt, David

    2013-01-01

    Background Protection against disease or colonization from serotypes related to those in pneumococcal conjugate vaccines (i.e. cross-protection) vary by serotype; the basis for this variation is not understood. The 13-valent pneumococcal conjugate vaccine (PCV13) replaced 7-valent conjugate (PCV7) in the USA in 2010 allowing assessment of PCV7 and PCV13 immunogenicity and functional cross-protection in vitro. Methods Post-primary, pre-booster and post-booster sera from American Indian children receiving exclusively PCV7 or PCV13 were collected. IgG was measured by ELISA for 13 vaccine serotypes; functional antibody was assessed by opsonophagocytic killing assays for serotypes 6A/B/C and 19A/F. Results Post-primary IgG geometric mean concentrations (GMC) for serotypes 4 and 9V were lower in PCV13 recipients while 19F GMCs were higher. Only 19F differences persisted after receipt of the booster dose. Functional antibody activity was higher among PCV13 recipients for 6A, 6C, 19A and 19F (p<0.04), and among PCV7 recipients for 6B (p?=?0.01). Following PCV7, functional antibodies to 6A but not 19A were observed. High levels of 6C functional activity were seen after PCV13 but not PCV7. Conclusions Functional antibody activity against 6A/B/C and 19A/F suggest that PCV13 is likely to control the 19A disease and 6C disease remaining despite widespread use of PCV7. PMID:24086394

  19. 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

  20. Vibrio cholerae O139 Conjugate Vaccines: Synthesis and Immunogenicity of V. cholerae O139 Capsular Polysaccharide Conjugates with Recombinant Diphtheria Toxin Mutant in Mice

    PubMed Central

    Kossaczka, Zuzana; Shiloach, Joseph; Johnson, Virginia; Taylor, David N.; Finkelstein, Richard A.; Robbins, John B.; Szu, Shousun C.

    2000-01-01

    Epidemiologic and experimental data provide evidence that a critical level of serum immunoglobulin G (IgG) antibodies to the surface polysaccharide of Vibrio cholerae O1 (lipopolysaccharide) and of Vibrio cholerae O139 (capsular polysaccharide [CPS]) is associated with immunity to the homologous pathogen. The immunogenicity of polysaccharides, especially in infants, may be enhanced by their covalent attachment to proteins (conjugates). Two synthetic schemes, involving 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) as activating agents, were adapted to prepare four conjugates of V. cholerae O139 CPS with the recombinant diphtheria toxin mutant, CRMH21G. Adipic acid dihydrazide was used as a linker. When injected subcutaneously into young outbred mice by a clinically relevant dose and schedule, these conjugates elicited serum CPS antibodies of the IgG and IgM classes with vibriocidal activity to strains of capsulated V. cholerae O139. Treatment of these sera with 2-mercaptoethanol (2-ME) reduced, but did not eliminate, their vibriocidal activity. These results indicate that the conjugates elicited IgG with vibriocidal activity. Conjugates also elicited high levels of serum diphtheria toxin IgG. Convalescent sera from 20 cholera patients infected with V. cholerae O139 had vibriocidal titers ranging from 100 to 3,200: absorption with the CPS reduced the vibriocidal titer of all sera to ?50. Treatment with 2-ME reduced the titers of 17 of 20 patients to ?50. These data show that, like infection with V. cholerae O1, infection with V. cholerae O139 induces vibriocidal antibodies specific to the surface polysaccharide of this bacterium (CPS) that are mostly of IgM class. Based on these data, clinical trials with the V. cholerae O139 CPS conjugates with recombinant diphtheria toxin are planned. PMID:10948122

  1. 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

    Microsoft Academic Search

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

    2005-01-01

    Thirty-six healthy volunteers received either a single intramuscular injection of Neisseria meningitidis sero- group 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

  2. Salmonella enterica Serovar Enteritidis Core O Polysaccharide Conjugated to H:g,m Flagellin as a Candidate Vaccine for Protection against Invasive Infection with S. Enteritidis?†

    PubMed Central

    Simon, Raphael; Tennant, Sharon M.; Wang, Jin Y.; Schmidlein, Patrick J.; Lees, Andrew; Ernst, Robert K.; Pasetti, Marcela F.; Galen, James E.; Levine, Myron M.

    2011-01-01

    Nontyphoidal Salmonella enterica serovars Enteritidis and Typhimurium are a common cause of gastroenteritis but also cause invasive infections and enteric fever in certain hosts (young children in sub-Saharan Africa, the elderly, and immunocompromised individuals). Salmonella O polysaccharides (OPS) and flagellar proteins are virulence factors and protective antigens. The surface polysaccharides of Salmonella are poorly immunogenic and do not confer immunologic memory, limitations overcome by covalently attaching them to carrier proteins. We conjugated core polysaccharide-OPS (COPS) of Salmonella Enteritidis lipopolysaccharide (LPS) to flagellin protein from the homologous strain. COPS and flagellin were purified from a genetically attenuated (?guaBA) “reagent strain” (derived from an isolate from a patient with clinical bacteremia) engineered for increased flagellin production (?clpPX). Conjugates were constructed by linking flagellin monomers or polymers at random COPS hydroxyls with various polysaccharide/protein ratios by 1-cyano-4-dimethylaminopyridinium tetrafluoroborate (CDAP) or at the 3-deoxy-d-manno-octulosonic acid (KDO) terminus by thioether chemistry. Mice immunized on days 0, 28, and 56 with COPS-flagellin conjugates mounted higher anti-LPS IgG levels than mice receiving unconjugated COPS and exhibited high antiflagellin IgG; anti-LPS and antiflagellin IgG levels increased following booster doses. Antibodies generated by COPS-flagellin conjugates mediated opsonophagocytosis of S. Enteritidis cells into mouse macrophages. Mice immunized with flagellin alone, COPS-CRM197, or COPS-flagellin conjugates were significantly protected from lethal challenge with wild-type S. Enteritidis (80 to 100% vaccine efficacy). PMID:21807909

  3. Serotype distribution and antimicrobial susceptibility of USA Streptococcus pneumoniae isolates collected prior to and post introduction of 13-valent pneumococcal conjugate vaccine.

    PubMed

    Mendes, Rodrigo E; Costello, Andrew J; Jacobs, Michael R; Biek, Donald; Critchley, Ian A; Jones, Ronald N

    2014-09-01

    This study evaluated pneumococci cultured from blood or lower respiratory tract specimens from hospitalized patients in the USA (all age groups) during 2011-2012 (N = 1190) and compared findings with those from a similar study performed in 2008 (N = 694). Isolates were tested for susceptibility by broth microdilution and serotypes determined by cpsB sequencing, supplemented with multiplex PCR and capsular swelling assays. Relative percentages of 7-valent pneumococcal conjugate vaccine (PCV7) types were 6.3 and 4.9% in 2008 and 2011-2012, respectively, and the most common PCV7 serotypes (19F and 6B) comprised only 3.7% and 4.0% of all isolates from both periods, respectively. Thirteen-valent pneumococcal conjugate vaccine (PCV13) serotypes represented 42.9% of isolates in 2008 and 30.1% in the second period, and this decrease was driven by 19A and 7F. Non-PCV13 serogroups/serotypes 23A, 15B/15C, 7C, 8, and 31 increased. Penicillin non-susceptibility rates were 9.6-10.0% and 38.9-42.7% when applying the parenteral (i.e. ? 4 ?g/mL) and oral breakpoints (i.e. ? 0.12 ?g/mL), respectively. Ceftaroline was the most potent agent tested based on MIC50 and MIC90 values (? 0.015 and 0.12 ?g/mL, respectively) for both time periods. PMID:24974272

  4. Maternal vaccination against subclinical necrotic enteritis in broilers

    Microsoft Academic Search

    Atle Lovland; Magne Kaldhusdal; Keith Redhead; Eystein Skjerve; Atle Lillehaug

    2004-01-01

    The inclusion of antibacterial feed additives has until now been the major strategy for controlling Clostridium perfringens-associated necrotic enteritis in broilers. In the present study, the effect of maternal immunization against the disease was examined. Broiler breeder hens were injected intramuscularly with candidate vaccines based on C. perfringens type A and type C toxoids adjuvanted with aluminium hydroxide. Vaccination resulted

  5. Antigen processing of glycoconjugate vaccines; the polysaccharide portion of the pneumococcal CRM 197 conjugate vaccine co-localizes with MHC II on the antigen processing cell surface

    Microsoft Academic Search

    Zengzu Lai; John R. Schreiber

    2009-01-01

    Pneumococcal (Pn) polysaccharides (PS) are T-independent (TI) antigens and do not induce immunological memory or antibodies in infants. Conjugation of PnPS to the carrier protein CRM197 induces PS-specific antibody in infants, and memory similar to T-dependent (Td) antigens. Conjugates have improved immunogenicity via antigen processing and presentation of carrier protein with MHC II and recruitment of T cell help, but

  6. Performance and potency of tetanus toxoid: implications for eliminating neonatal tetanus.

    PubMed Central

    Dietz, V.; Milstien, J. B.; van Loon, F.; Cochi, S.; Bennett, J.

    1996-01-01

    Neonatal tetanus (NT) is a major cause of mortality in developing countries, with over 400,000 deaths estimated to occur annually. WHO has adopted the goal of eliminating NT worldwide, and a major strategy for its prevention is the administration of at least two properly spaced doses of tetanus toxoid (TT) to women of childbearing age in high-risk areas to protect passively their newborns at birth. In certain countries the locally produced TT vaccine has been shown to be subpotent, while other countries have reported NT among infants born to vaccinated women. An extensive review of production and quality control procedures was carried out between 1993 and 1995 in 8 of 22 TT-producing countries that also report NT cases, with a more superficial assessment being carried out in the remaining 14 countries. Only 4 of the 22 countries have a functioning national control authority to monitor TT production and vaccine quality. A total of 80 TT lots from 21 manufacturers in 14 of the 22 NT-reporting countries were tested for potency. Of these, 15 lots from eight manufacturers in seven countries had potency values below WHO requirements. TT potency can also be compromised by improper vaccine handling. To eliminate neonatal tetanus worldwide requires assurance that all doses of TT meet WHO production and quality requirements and that the field effectiveness of TT is monitored through systematic NT case investigations and assessment of coverage. PMID:9060223

  7. Immunogenicity in mice and non-human primates of the Group A Streptococcal J8 peptide vaccine candidate conjugated to CRM197.

    PubMed

    Caro-Aguilar, Ivette; Ottinger, Elizabeth; Hepler, Robert W; Nahas, Deborah D; Wu, Chengwei; Good, Michael F; Batzloff, Michael; Joyce, Joseph G; Heinrichs, Jon H; Skinner, Julie M

    2013-03-01

    Vaccine development for Group A streptococcal (GAS) infection has been extensively focused on the N-terminal hypervariable or the C-terminal conserved regions of the M protein, a major virulence factor of GAS. We evaluated the immunogenicity and functional activity of the conserved C-terminal peptide vaccine candidate, J8, conjugated to CRM197, in two mouse strains: C3H (H2(k)) and Balb/c (H2(d)), and in rhesus macaques. Mice were immunized with J8-CRM197 formulated with Amorphous Aluminum Hydroxyphosphate Sulfate Adjuvant (AAHSA), and non-human primates were immunized with J8-CRM197 formulated with AAHSA, ISCOMATRIX (TM) adjuvant, or AAHSA/ISCOMATRIX adjuvant. J8-CRM197 was immunogenic in mice from both H2(k) and H2(d) backgrounds, and the antibodies generated bound to the surface of four different GAS serotypes and had functional bacterial opsonic activity. Mice immunized with J8-CRM197/AAHSA demonstrated varying degrees of protection from lethal challenge. We also demonstrated that J8-CRM197 is immunogenic in non-human primates. Our data confirm the utility of J8 as a potential GAS vaccine candidate and demonstrate that CRM197 is an acceptable protein carrier for this peptide. PMID:23249976

  8. 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

  9. B and T-Cell Immune Responses to Pneumococcal Conjugate Vaccines: Divergence between Carrier and Polysaccharide-Specific Immunogenicity

    Microsoft Academic Search

    TERA L. MCCOOL; CLIFFORD V. HARDING; NEIL S. GREENSPAN; JOHN R. SCHREIBER

    1999-01-01

    Conjugation of various serotypes of pneumococcal polysaccharide (PnPS) to carrier protein enhances the magnitude of the polysaccharide-specific antibody response, presumably by eliciting T-cell help. However, variability in PnPS serotype-specific immunogenicity has been observed. CBA\\/J mice immunized with either 6B or 19F PnPS conjugated to the protein carrier Cross Reactive Material197 (CRM197) produce a strong anti-PnPS antibody response; however, when mice

  10. Development and Use of a Serum Bactericidal Assay Using Pooled Human Complement To Assess Responses to a Meningococcal Group A Conjugate Vaccine in African Toddlers

    PubMed Central

    Lynn, Freyja; Mocca, Brian; Borrow, Ray; Findlow, Helen; Hassan-King, Musa; Preziosi, Marie-Pierre; Idoko, Olubukola; Sow, Samba; Kulkarni, Prasad; LaForce, F. Marc

    2014-01-01

    A meningococcal group A polysaccharide (PS) conjugate vaccine (PsA-TT) has been developed for African countries affected by epidemic meningitis caused by Neisseria meningitidis. Complement-mediated serum bactericidal antibody (SBA) assays are used to assess protective immune responses to meningococcal vaccination. Human complement (hC?) was used in early studies demonstrating antibody-mediated protection against disease, but it is difficult to obtain and standardize. We developed and evaluated a method for sourcing hC? and then used the SBA assay with hC? (hSBA) to measure bactericidal responses to PsA-TT vaccination in 12- to 23-month-old African children. Sera with active complement from 100 unvaccinated blood donors were tested for intrinsic bactericidal activity, SBA titer using rabbit complement (rSBA), and anti-group A PS antibody concentration. Performance criteria and pooling strategies were examined and then verified by comparisons of three independently prepared hC? lots in two laboratories. hSBA titers of clinical trial sera were then determined using this complement sourcing method. Two different functional antibody tests were necessary for screening hC?. hSBA titers determined using three independent lots of pooled hC? were within expected assay variation among lots and between laboratories. In African toddlers, PsA-TT elicited higher hSBA titers than meningococcal polysaccharide or Hib vaccines. PsA-TT immunization or PS challenge of PsA-TT-primed subjects resulted in vigorous hSBA memory responses, and titers persisted in boosted groups for over a year. Quantifying SBA using pooled hC? is feasible and showed that PsA-TT was highly immunogenic in African toddlers. PMID:24671551

  11. Tetanus toxoid coverage as an indicator of serological protection against neonatal tetanus.

    PubMed Central

    Deming, Michael S.; Roungou, Jean-Baptiste; Kristiansen, Max; Heron, Iver; Yango, Alphonse; Guenengafo, Alexis; Ndamobissi, Robert

    2002-01-01

    OBJECTIVE: A Multiple-Indicator Cluster Survey (MICS) was conducted at mid-decade in more than 60 developing countries to measure progress towards the year 2000 World Summit for Children goals. These goals included the protection of at least 90% of children against neonatal tetanus through the immunization of their mothers, as measured by tetanus toxoid (TT) coverage. In the Central African Republic (CAR), serological testing was added to the MICS to understand better the relationship between survey estimates of TT coverage and the prevalence of serological protection. METHODS: In the CAR MICS, mothers of children younger than one year of age gave verbal histories of the TT vaccinations they had received, using the MICS TT questionnaire. A subsample of mothers was tested for tetanus antitoxin, using a double-antigen enzyme-linked immunoadsorbent assay (ELISA). Seropositivity was defined as a titre of > or =0.01 IU/ml, and TT coverage was defined as the proportion of mothers protected at delivery, according to their history of TT vaccinations. FINDINGS: Among the 222 mothers in the subsample, weighted TT coverage was 74.4% (95% Confidence Interval (CI); 67.0% - 81.7%) and tetanus antitoxin seroprevalence was 88.7% (95% CI; 83.2% - 94.2%). The weighted median antitoxin titre was 0.35 IU/ml. CONCLUSIONS: Tetanus toxoid coverage in the CAR was lower than the prevalence of serological protection against neonatal tetanus. If this relationship holds for other countries, TT coverage estimates from the MICS may underestimate the extent to which the year 2000 goal for protecting children against neonatal tetanus was reached. We also showed that a high level of serological protection had been achieved in a country facing major public health challenges and resource constraints. PMID:12378286

  12. Surveillance of adverse events following the introduction of 13-valent pneumococcal conjugate vaccine in infants, and comparison with adverse events following 7-valent pneumococcal conjugate vaccine, in Victoria, Australia.

    PubMed

    Littlejohn, E S; Clothier, H J; Perrett, K P; Danchin, M

    2015-07-01

    The 13-valent pneumococcal vaccine (PCV13) replaced the 7-valent vaccine (PCV7) on the Australian National Immunization Program (NIP) in 2011. Post-marketing surveillance of adverse events following immunization (AEFI) is crucial for detecting potential safety signals and maintaining confidence in the NIP. This study describes all AEFI reported to Surveillance of Adverse Events following Vaccination in the Community (SAEFVIC), Melbourne, Australia, following both the primary series of PCV13 (children <7 months) and the catch-up dose (12 months-35months) in its first year of inclusion on the NIP. AEFI reporting rates per 100,000 doses of vaccine administered were compared for the PCV13 primary series and PCV7 primary series in the previous year. SAEFVIC received 229 reports describing 406 AEFI following PCV13 vaccine in the 12 months post introduction. There was no difference in the total number of AEFI cases reported between the vaccines but 7 AEFI categories were reported at a significantly higher rate following PCV13 compared with PCV7. No difference in reporting rate was observed for serious AEFI (p = 0.25). Post-hoc analysis of a further 12 months of PCV13 data revealed that all 7 AEFI categories that were initially reported at a significantly higher rate following PCV13 compared to PCV7 in the first 12 months post introduction, were no longer significantly increased in the 13-24 month period. The initial high reporting rate for several common AEFI post PCV13 compared to PCV7 may be explained by heightened awareness of the new vaccine. There were no safety signals detected for rare or serious AEFI that would require further investigation at this time. PMID:26075435

  13. All-Cause Pneumonia Hospitalizations in Children <2 Years Old in Sweden, 1998 to 2012: Impact of Pneumococcal Conjugate Vaccine Introduction

    PubMed Central

    Berglund, Anders; Ekelund, Mats; Fletcher, Mark A.; Nyman, Lars

    2014-01-01

    Background In late 2007, some Swedish County Councils started 7-valent pneumococcal conjugate vaccine (PCV7) implementation for children, and PCV7 was included in the national immunization program in 2009. By 2010, both PCV10 and PCV13 were licensed, and the selection of vaccine was subject to County Councils tenders. This study investigated the impact of the order of PCV introduction into vaccination programs on the incidence of all-cause pneumonia hospitalizations in children <2 years-old. Methods Using population-based data from the publicly available National Inpatient Registry, the incidence of inpatient pneumonia (ICD-10 J12-J18) hospitalizations by County Councils among children <2 years old was identified between 1998 and 2012. Incidence rate ratios (IRR; 95% CI) were calculated during the nationwide implementation of PCV7 and then between County Councils, as based on the higher-valent vaccine chosen for a program. Results There was a lower risk of all-cause pneumonia hospitalization among <2 year-old children following the introduction of PCV7, as compared to the pre-PCV7 period (0.77; 0.63–0.93). A decreased risk of all-cause pneumonia was also observed in the County Councils that followed the order PCV7 then PCV13 (0.82; 0.66–1.01), while no trend was observed in County Councils with a program in the order PCV7 then PCV10 (1.03; 0.82–1.30). When comparing the higher-valent vaccines, there was a 21% (0.79; 0.66–0.96) lower risk for childhood pneumonia hospitalization in County Councils finally using PCV13 as compared to the experience in County Councils that ultimately adopted PCV10. Conclusions Among children <2 years-old, all-cause pneumonia hospitalizations were significantly reduced by 23% one to two years after introduction of PCV7 vaccination in Sweden. In those County Councils that next introduced PCV13, a further decline in all-cause pneumonia hospitalization was observed, in contrast to those County Councils that followed with PCV10; this 21% lower risk for childhood pneumonia hospitalization was statistically significant. PMID:25379659

  14. 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

  15. Does a 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine prevent respiratory exacerbations in children with recurrent protracted bacterial bronchitis, chronic suppurative lung disease and bronchiectasis: protocol for a randomised controlled trial

    PubMed Central

    2013-01-01

    Background Recurrent protracted bacterial bronchitis (PBB), chronic suppurative lung disease (CSLD) and bronchiectasis are characterised by a chronic wet cough and are important causes of childhood respiratory morbidity globally. Haemophilus influenzae and Streptococcus pneumoniae are the most commonly associated pathogens. As respiratory exacerbations impair quality of life and may be associated with disease progression, we will determine if the novel 10-valent pneumococcal-Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) reduces exacerbations in these children. Methods A multi-centre, parallel group, double-blind, randomised controlled trial in tertiary paediatric centres from three Australian cities is planned. Two hundred six children aged 18 months to 14 years with recurrent PBB, CSLD or bronchiectasis will be randomised to receive either two doses of PHiD-CV or control meningococcal (ACYW135) conjugate vaccine 2 months apart and followed for 12 months after the second vaccine dose. Randomisation will be stratified by site, age (<6 years and ?6 years) and aetiology (recurrent PBB or CSLD/bronchiectasis). Clinical histories, respiratory status (including spirometry in children aged ?6 years), nasopharyngeal and saliva swabs, and serum will be collected at baseline and at 2, 3, 8 and 14 months post-enrolment. Local and systemic reactions will be recorded on daily diaries for 7 and 30 days, respectively, following each vaccine dose and serious adverse events monitored throughout the trial. Fortnightly, parental contact will help record respiratory exacerbations. The primary outcome is the incidence of respiratory exacerbations in the 12 months following the second vaccine dose. Secondary outcomes include: nasopharyngeal carriage of H. influenzae and S. pneumoniae vaccine and vaccine- related serotypes; systemic and mucosal immune responses to H. influenzae proteins and S. pneumoniae vaccine and vaccine-related serotypes; impact upon lung function in children aged ?6 years; and vaccine safety. Discussion As H. influenzae is the most common bacterial pathogen associated with these chronic respiratory diseases in children, a novel pneumococcal conjugate vaccine that also impacts upon H. influenzae and helps prevent respiratory exacerbations would assist clinical management with potential short- and long-term health benefits. Our study will be the first to assess vaccine efficacy targeting H. influenzae in children with recurrent PBB, CSLD and bronchiectasis. Trial registration Australia and New Zealand Clinical Trials Registry (ANZCTR) number: ACTRN12612000034831. PMID:24010917

  16. Economic and clinical evaluation of a catch-up dose of 13-valent pneumococcal conjugate vaccine in children already immunized with three doses of the 7-valent vaccine in Italy.

    PubMed

    Boccalini, Sara; Azzari, Chiara; Resti, Massimo; Valleriani, Claudia; Cortimiglia, Martina; Tiscione, Emilia; Bechini, Angela; Bonanni, Paolo

    2011-11-28

    A new 13-valent conjugated polysaccharide vaccine (PCV13) against Streptococcus pneumoniae infections, which replaced the 7-valent vaccine (PCV7) in the regional immunization programmes for newborns and children who started but not completed the 3 doses schedule of PCV7, is available in Italy since 2010. The opportunity of administering a further dose of PCV13 to children under 5 years of age who had already completed their vaccination with PCV7, with the aim of extending the serotype coverage, triggered an animated scientific debate. The purpose of this study was to perform a clinical/economic evaluation of the administration of a dose of PCV13, in a catch-up programme, for children under 5 years of age, who had already received 3 doses of PCV7. A mathematical model of the clinical/economic impact of the adoption of 4 catch-up strategies with PCV13 (children up to 24, 36, 48 and 60 months old) was set up, with a vaccination coverage of 80%, versus immunization with 3 doses of PCV7 without the catch-up programme. The time span covered by the simulation was 5.5 years. The following clinical outcomes of infection were evaluated: hospitalised meningitis/sepsis, hospitalised bacteraemic pneumonias (complicated and uncomplicated), hospitalised non-bacteraemic pneumonias, and non-hospitalised pneumonias. The administration of one dose of PCV13 to children up to 60 months of age significantly reduces the number of cases of pneumococcal diseases (especially, non-hospitalised pneumonias, 80% of all events prevented, and hospitalised cases of non-bacteraemic pneumococcal pneumonias, 15% of all events prevented) and, subsequently, the relative cost for medical treatment. This results in savings for medical costs amounting to more than 1,000,000 Euros when vaccinating children under 24 months of age (up to almost 3 million Euros for children up to 60 months). More than half of those savings are attributable to avoided hospitalised cases of non-bacteraemic pneumococcal pneumonias. Increasing the number of cohorts involved in the vaccination programme, the impact of immunization increases. The average cost per event avoided is 1674 Euros vaccinating children up to 24 months, and increases to 2522 Euros by vaccinating up to 60 months of age. The cost per year of life saved for different vaccination strategies is always acceptable (from 12,250 Euros to 22,093 Euros). The results of this study justify, even from the economic point of view, the recommendation of the Italian Ministry of Health to vaccinate children up to 24 months of life in a catch-up programme, as well as the administration of PCV13 children up to 36 months of age, already used in some Italian regions. Furthermore, a catch-up programme that provides the immunization of children under 60 months of age, is also justified from both the economic and clinical point of view. PMID:22008820

  17. 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

  18. A Phase II, Randomized Study on an Investigational DTPw-HBV/Hib-MenAC Conjugate Vaccine Administered to Infants in Northern Ghana

    PubMed Central

    Hodgson, Abraham; Forgor, Abudulai Adams; Chandramohan, Daniel; Reed, Zarifah; Binka, Fred; Bevilacqua, Cornelia; Boutriau, Dominique; Greenwood, Brian

    2008-01-01

    Background Combining meningococcal vaccination with routine immunization in infancy may reduce the burden of meningococcal meningitis, especially in the meningitis belt of Africa. We have evaluated the immunogenicity, persistence of immune response, immune memory and safety of an investigational DTPw-HBV/Hib-MenAC conjugate vaccine given to infants in Northern Ghana. Methods and Findings In this phase II, double blind, randomized, controlled study, 280 infants were primed with DTPw-HBV/Hib-MenAC or DTPw-HBV/Hib vaccines at 6, 10 and 14 weeks of age. At 12 months of age, children in each group received a challenge dose of serogroup A+C polysaccharides. Antibody responses were assessed pre, and one month-post dose 3 of the priming schedule and pre and 1 month after administration of the challenge dose. One month post-dose 3, 87.8% and 88.2% of subjects in the study group had bactericidal meningococcal serogroup A (SBA-MenA) and meningococcal serogroup C (SBA-MenC) antibody titres ?1?8 respectively. Seroprotection/seropositivity rates to the 5 antigens administered in the routine EPI schedule were non-inferior in children in the study group compared to those in the control group. The percentages of subjects in the study group with persisting SBA-MenA titres ? 1?8 or SBA-MenC titres ?1?8 at the age of 12 months prior to challenge were significantly higher than in control group (47.7% vs 25.7% and 56.4% vs 5.1% respectively). The administration of 10 ?g of serogroup A polysaccharide increased the SBA-MenA GMT by 14.0-fold in the DTPW-HBV/HibMenAC-group compared to a 3.8 fold increase in the control-group. Corresponding fold-increases in SBA-MenC titres following challenge with 10 ?g of group C polysaccharide were 18.8 and 1.9 respectively. Reactogenicity following primary vaccination or the administration of the challenge dose was similar in both groups, except for swelling (Grade 3) after primary vaccination which was more frequent in children in the vaccine than in the control group (23.7%; 95%CI [19.6–28.1] of doses vs 14.1%; 95% CI [10.9–17.8] of doses). Fifty-nine SAEs (including 8 deaths), none of them related to vaccination, were reported during the entire study. Conclusions Three dose primary vaccination with DTPw-HBV/Hib-MenAC was non-inferior to DTPw-HBV/Hib for the 5 common antigens used in the routine EPI schedule and induced bactericidal antibodies against Neisseria meningitidis of serogroups A and C in the majority of infants. Serogroup A and C bactericidal antibody levels had fallen below titres associated with protection in nearly half of the infants by the age of 12 months confirming that a booster dose is required at about that age. An enhanced memory response was shown after polysaccharide challenge. This vaccine could provide protection against 7 important childhood diseases (including meningococcal A and C) and be of particular value in countries of the African meningitis belt. Trial Registration Controlled-Trials.com ISRCTN35754083 PMID:18478093

  19. 10-valent pneumococcal non-typeable Haemophilus influenzae protein-D conjugate vaccine (PHiD-CV) induces memory B cell responses in healthy Kenyan toddlers.

    PubMed

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

    2015-08-01

    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?

  20. Analysis of Invasiveness of Pneumococcal Serotypes and Clones Circulating in Portugal before Widespread Use of Conjugate Vaccines Reveals Heterogeneous Behavior of Clones Expressing the Same Serotype?†

    PubMed Central

    Sá-Leão, Raquel; Pinto, Francisco; Aguiar, Sandra; Nunes, Sónia; Carriço, João A.; Frazão, Nelson; Gonçalves-Sousa, Natacha; Melo-Cristino, José; de Lencastre, Hermínia; Ramirez, Mário

    2011-01-01

    To estimate the invasive disease potential of serotypes and clones circulating in Portugal before extensive use of the seven-valent pneumococcal conjugate vaccine, we analyzed 475 invasive isolates recovered from children and adults and 769 carriage isolates recovered from children between 2001 and 2003. Isolates were serotyped and genotyped by pulsed-field gel electrophoresis, and a selection of isolates were also characterized by multilocus sequence typing. We found that the diversities of serotypes and genotypes of pneumococci responsible for invasive infections and carriage were identical and that most carried clones could also be detected as causes of invasive disease. Their ability to do so, however, varied substantially. Serotypes 1, 3, 4, 5, 7F, 8, 9N, 9L, 12B, 14, 18C, and 20 were found to have an enhanced propensity to cause invasive disease, while serotypes 6A, 6B, 11A, 15B/C, 16F, 19F, 23F, 34, 35F, and 37 were associated with carriage. In addition, significant differences in invasive disease potential between clones sharing the same serotype were found among several serotypes, namely, 3, 6A, 6B, 11A, 14, 19A, 19F, 22F, 23F, 34, and NT. This heterogeneous behavior of the clones was found irrespective of the serotype's overall invasive disease potential. Our results highlight the importance of the genetic background when analyzing the invasive disease potential of certain serotypes and provide an important baseline for its monitoring following conjugate vaccine use. Continuous surveillance should be maintained, and current research should focus on uncovering the genetic determinants that contribute to the heterogeneity of invasive disease potential of clones sharing the same serotype. PMID:21270219

  1. Vaccination during pregnancy

    PubMed Central

    Bozzo, Pina; Narducci, Andrea; Einarson, Adrienne

    2011-01-01

    Abstract Question One of my patients is studying to become a dental hygienist. Owing to the program requirements, she received several vaccinations last week, including measles-mumps-rubella, varicella, and hepatitis B (HB) vaccines, as well as a tetanus booster. However, today a blood test confirmed that she is currently 6 weeks pregnant. What is known about the safety of these vaccines during pregnancy, and are there any general recommendations for vaccines for women who are planning to become pregnant or who are currently pregnant? Answer The combination measles-mumps-rubella vaccine and the varicella vaccine are live attenuated vaccines, and are contraindicated during pregnancy owing to theoretical concerns. However, there is no evidence that there are increased risks of malformations, congenital rubella syndrome, or varicella syndrome attributable to these vaccines. The HB and tetanus vaccines are composed of noninfectious particles or toxoids, and theoretically should cause no increased risk to the developing fetus. In addition, limited observational data also support no increased risk of any adverse pregnancy outcomes; consequently, administration of the HB and tetanus vaccines might be, if indicated, considered during pregnancy. PMID:21571717

  2. 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

    The MenAfriCar consortium

    2015-04-09

    ]. In high-income countries, meningococcal carriage occurs most frequently in older children and young adults and is linked to smoking, nightclub attendance, and intimate kissing [4]. Less is known about the epide- miology and risks factors of meningococcal... a 50% reduction in serogroup A carriage following vaccination. Isolation and Characterization of Meningococci Swabbing Technique Pilot studies established that swabbing both the posterior phar- ynx and the tonsils or just the posterior of the pharynx...

  3. Temporal analysis of invasive pneumococcal clones from Scotland illustrates fluctuations in diversity of serotype and genotype in the absence of pneumococcal conjugate vaccine.

    PubMed

    Jefferies, J M; Smith, A J; Edwards, G F S; McMenamin, J; Mitchell, T J; Clarke, S C

    2010-01-01

    In September 2006, the seven-valent pneumococcal conjugate vaccine (PCV7; Prevenar) was introduced into the childhood vaccination schedule in the United Kingdom. We monitored the population of invasive pneumococci in Scotland in the 5 years preceding the introduction of PCV7 by using serogrouping, multilocus sequence typing (MLST), and eBURST analysis. Here, we present a unique analysis of a complete national data set of invasive pneumococci over this time. We observed an increase in invasive pneumococcal disease (IPD) caused by serotypes 1, 4, and 6 and a decrease in serogroup 14-, 19-, and 23-associated disease. Analysis of sequence type (ST) data shows a significant increase in ST306, associated with serotype 1, and a decrease in ST124, associated with serotype 14. There have also been increases in the amounts of IPD caused by ST227 (serotype 1) and ST53 (serotype 8), although these increases were not found to reach significance (P = 0.08 and 0.06, respectively). In the course of the study period preceding the introduction of PCV7, we observed considerable and significant changes in serogroup and clonal distribution over time. PMID:19923488

  4. Tetanus toxoid immunization to reduce mortality from neonatal tetanus

    PubMed Central

    Blencowe, Hannah; Lawn, Joy; Vandelaer, Jos; Roper, Martha

    2010-01-01

    Background Neonatal tetanus remains an important and preventable cause of neonatal mortality globally. Large reductions in neonatal tetanus deaths have been reported following major increases in the coverage of tetanus toxoid immunization, yet the level of evidence for the mortality effect of tetanus toxoid immunization is surprisingly weak with only two trials considered in a Cochrane review. Objective To review the evidence for and estimate the effect on neonatal tetanus mortality of immunization with tetanus toxoid of pregnant women, or women of childbearing age. Methods We conducted a systematic review of multiple databases. Standardized abstraction forms were used. Individual study quality and the overall quality of evidence were assessed using an adaptation of the GRADE approach. Meta-analyses were performed. Results Only one randomised controlled trial (RCT) and one well-controlled cohort study were identified, which met inclusion criteria for meta-analysis. Immunization of pregnant women or women of childbearing age with at least two doses of tetanus toxoid is estimated to reduce mortality from neonatal tetanus by 94% [95% confidence interval (CI) 80–98%]. Additionally, another RCT with a case definition based on day of death, 3 case–control studies and 1 before-and-after study gave consistent results. Based on the consistency of the mortality data, the very large effect size and that the data are all from low/middle-income countries, the overall quality of the evidence was judged to be moderate. Conclusion This review uses a standard approach to provide a transparent estimate of the high impact of tetanus toxoid immunization on neonatal tetanus. PMID:20348112

  5. Immunogenicity and safety of a multicomponent meningococcal serogroup B vaccine and a quadrivalent meningococcal CRM197 conjugate vaccine against serogroups A, C, W-135, and Y in adults who are at increased risk for occupational exposure to meningococcal isolates.

    PubMed

    Kimura, Alan; Toneatto, Daniela; Kleinschmidt, Annett; Wang, Huajun; Dull, Peter

    2011-03-01

    Laboratory staff who work with meningococcal isolates are at increased risk for developing invasive disease relative to the general population. This was the first study of laboratory workers who received both a conjugate vaccine against meningococcal serogroups A, C, W-135, and Y (Men ACWY-CRM, Menveo) and an investigational multicomponent vaccine against serogroup B containing factor H binding protein, neisserial adhesin A, Neisseria heparin binding antigen, and New Zealand strain outer membrane vesicles (4CMenB). Healthy adults (18 to 50 years of age) received three doses of 4CMenB at baseline, 2 months, and 6 months followed by a single dose of MenACWY-CRM 1 month later. Immunogenicity was assessed via serum bactericidal assay using human complement (hSBA) at 1 month postvaccination; solicited reactogenicity and adverse events were monitored. Fifty-four participants enrolled. Bactericidal immune responses were evident after each dose of 4CMenB, as assessed by hSBA geometric mean titers and percentages of subjects with hSBA titers of ?4 against the test strains or a 4-fold rise in titer over baseline. At 1 month postvaccination, most MenACWY-CRM recipients had hSBA titers of ?8 against serogroups A, C, W-135, and Y. Few participants discontinued due to an adverse event or vaccine reaction. Rates of solicited reactions were lower after MenACWY-CRM than after 4CMenB administration. Sequential administration of 4CMenB and MenACWY-CRM provided robust evidence of an immune response against serogroups A, B, C, W-135, and Y in laboratory workers routinely exposed to meningococcal isolates. PMID:21177912

  6. Vaccination coverage among children in kindergarten--United States, 2006-07 school year.

    PubMed

    2007-08-17

    Healthy People 2010 objectives include increasing vaccination coverage among children in kindergarten and first grade (objective 14-23). For these children, the target is >/=95% vaccination coverage for the following: hepatitis B vaccine; diphtheria and tetanus toxoids and pertussis vaccine, diphtheria and tetanus toxoids and acellular pertussis vaccine, or diphtheria and tetanus toxoids vaccine (DTP/DTaP/DT); poliovirus vaccine; measles, mumps, and rubella (MMR) vaccine; and varicella vaccine. To assess progress toward national goals and determine vaccination coverage among children in kindergarten, data were analyzed from reports submitted to CDC by 49 states and the District of Columbia (DC) for the 2006-07 school year. This report summarizes findings from that analysis, which indicated that approximately 75% of states have reached the 2010 objective of at least 95% coverage for all of the vaccines recommended by the Advisory Committee on Immunization Practices (ACIP) for children in kindergarten. These results underscore the effectiveness of school-entry requirements in increasing vaccination coverage but highlight a need for more standardized vaccination reporting among states. PMID:17703172

  7. Critical appraisal of a quadrivalent CRM197 conjugate vaccine against meningococcal serogroups A, C W-135 and Y (Menveo®) in the context of treatment and prevention of invasive disease

    PubMed Central

    Bröker, Michael; Cooper, Brian; DeTora, Lisa M; Stoddard, Jeffrey J

    2011-01-01

    Worldwide, invasive meningococcal disease affects about 500,000 people annually. Case fatality in developed countries averages 10%, and higher rates are reported in less prosperous regions. According to the World Health Organization, the most important pathogenic serogroups are A, B, C, W-135, X, and Y. Clinical features of invasive meningococcal disease make diagnosis and management difficult. Antibiotic measures are recommended for prophylaxis after exposure and for treatment of invasive meningococcal disease cases; however, resistant strains may be emerging. Vaccines are generally regarded as the best preventative measure for invasive meningococcal disease. Polysaccharide vaccines against serogroups A, C, W-135, and Y using protein conjugation technology have clear advantages over older plain polysaccharide formulations without a protein component. The first quadrivalent meningococcal conjugate vaccine (MenACWY-D) was licensed in the US in 2005. More recently, MenACWY-CRM (Menveo®) was licensed in Europe, the US, the Middle East, and Latin America. MenACWY-CRM uses cross-reactive material 197, a nontoxic mutant of diphtheria toxin, as the carrier protein. MenACWY-CRM offers robust immunogenicity in all age groups, with a tolerability profile similar to that of a plain polysaccharide vaccine. Given its potential for protecting persons from infancy to old age, MenACWY-CRM offers the opportunity to protect broad populations against invasive meningococcal disease. The most optimal strategy for use of the vaccine has to be assessed country by country on the basis of local epidemiology, individual health care systems, and need. PMID:21904459

  8. Safety and immunogenicity of 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) in Nigerian children: Booster dose and 2-dose catch-up regimens in the second year of life.

    PubMed

    Odusanya, Olumuyiwa O; Kuyinu, Yetunde A; Kehinde, Omolara A; Shafi, Fakrudeen; François, Nancy; Yarzabal, Juan Pablo; Dobbelaere, Kurt; Rüggeberg, Jens U; Borys, Dorota; Schuerman, Lode

    2014-01-01

    In a previous study, 3-dose primary vaccination of Nigerian infants with the 10-valent pneumococcal nontypeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) was immunogenic for vaccine pneumococcal serotypes, with comparable tolerability between PHiD-CV and control groups. In an open-label study (ClinicalTrials.gov, NCT01153893), 68 primed children received a PHiD-CV booster dose co-administered with a diphtheria-tetanus-acellular pertussis (DTPa) booster dose at 15-21 months and 36 children unprimed for pneumococcal vaccination received two PHiD-CV catch-up doses (first dose co-administered with DTPa booster dose) at 15-21 and 17-23 months. Adverse events were recorded and immune responses were measured before and one month after vaccination. In both groups, pain was the most frequent solicited local symptom and fever was the most frequent solicited general symptom after the booster dose and each catch-up dose. Few grade 3 solicited symptoms and no vaccine-related serious adverse events were reported. After booster vaccination, for each vaccine serotype, at least 98.5% of children had an antibody concentration ? 0.2 µg/ml and at least 94.0% had an opsonophagocytic activity (OPA) titer ? 8. After 2-dose catch-up, for each vaccine serotype, at least 97.1% had an antibody concentration ? 0.2 µg/ml, except for serotypes 6B (82.9%) and 23F (88.6%), and at least 91.4% had an OPA titer ?8, except for serotypes 6B (77.4%) and 19F (85.3%). PHiD-CV induced antibody responses against protein D in both groups. In conclusion, PHiD-CV administered to Nigerian toddlers as a booster dose or 2-dose catch-up was well tolerated and immunogenic for vaccine pneumococcal serotypes and protein D. PMID:24356787

  9. Meningococcal vaccines.

    PubMed

    Rüggeberg, Jens U; Pollard, Andrew J

    2004-01-01

    Meningococcal disease is one of the most feared and serious infections in the young and its prevention by vaccination is an important goal. The high degree of antigenic variability of the organism makes the meningococcus a challenging target for vaccine prevention. Meningococcal polysaccharide vaccines against serogroup A and C are efficacious and have been widely used, often in combination with serogroup Y and W135 components. Their relative lack of immunogenicity in young children and infants can be overcome by conjugation to a protein carrier. The effectiveness of serogroup C glycoconjugate vaccines in children of all ages has been demonstrated and they have now been introduced into routine vaccination schedules. Conjugate vaccines against other serogroups, including A, Y, and W135 will soon be available and it is hoped they may emulate this success. Prevention of serogroup B disease has proven more elusive. Several serogroup B vaccines based on outer membrane vesicles have been shown to be immunogenic and reasonably effective in adults and older children, but the protection offered by them is chiefly strain-specific. Multivalent recombinant PorA vaccines have been developed to broaden the protective effect, but no efficacy data are available as yet. Intensive efforts have been directed at other outer membrane protein vaccine candidates and lipopolysaccharide, and some of these have been shown to offer protection in experimental animal models. Nonpathogenic Neisseriae spp. such as Neisseria lactamica are also possible vaccine candidates. Previously unknown proteins have been identified from in silico analysis of the meningococcal genome and their vaccine potential explored. However, none of these has yet been presented as the 'universal' protective antigen and work in this field continues to be held back by our limited knowledge concerning the mechanisms of natural protection against serogroup B meningococci. PMID:15339202

  10. 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

  11. The adjuvant effect of synthetic oligodeoxynucleotide containing CpG motif converts the anti- Haemophilus influenzae type b glycoconjugates into efficient anti-polysaccharide and anti-carrier polyvalent vaccines

    Microsoft Academic Search

    Christina von Hunolstein; Sabrina Mariotti; Raffaela Teloni; Giovanna Alfarone; Giulia Romagnoli; Graziella Orefici; Roberto Nisini

    2001-01-01

    Synthetic oligodeoxynucleotides containing CpG immunostimulatory sequences (ISS) have been shown to act as potent adjuvants of type 1 immune responses when co-administered with protein or peptide vaccines. We have recently shown that ISS can increase the anti-polysaccharide (CHO) and anti-tetanus toxoid (TT) or anti-diphtheria (CRM) toxoid antibody levels if used as adjuvant of anti-Haemophilus influenzae type b (Hib) CHO vaccine

  12. Impact of 13-valent pneumococcal conjugate vaccine (PCV13) in a pandemic similar to the 2009 H1N1 in the United States

    PubMed Central

    2013-01-01

    Background High rates of bacterial coinfection in autopsy data from the 2009 H1N1 influenza (“flu”) pandemic suggest synergies between flu and pneumococcal disease (PD) during pandemic conditions, and highlight the importance of interventions like the 13-valent pneumococcal conjugate vaccine (PCV13) that may mitigate the impact of a pandemic. Methods We used a decision-analytic model, estimated from published sources, to assess the impact of pediatric vaccination with PCV13 versus the 7-valent vaccine (PCV7) on PD incidence and mortality in a normal flu season (10% flu incidence) and in a pandemic similar to 2009-2010 H1N1 (20% flu incidence, mild virulence, high impact in children). Both direct and indirect (herd) effects against PD were considered. Effectiveness of PCV13 was extrapolated from observed PCV7 data, using assumptions of serotype prevalence and PCV13 protection against the 6 serotypes not in PCV7. To simulate 2009–2010 H1N1, autopsy data were used to estimate the overall proportion of flu deaths with bacterial coinfections. By assuming that increased risk of death during the pandemic occurred among those with comorbidity (using obesity as proxy) and bacterial coinfections primarily due to S. pneumoniae or S. aureus, we estimated the proportion co-infected among all (fatal and non-fatal) flu cases (7.6% co-infected with any organism; 2.2% with S. pneumoniae). PD incidence, mortality, and total healthcare costs were evaluated over a 1-year horizon. Results In a normal flu season, compared to PCV7, PCV13 is expected to prevent an additional 13,400 invasive PD (IPD) cases, 399,000 pneumonia cases, and 2,900 deaths, leading to cost savings of $472 M. In a pandemic similar to 2009–2010 H1N1, PCV13 would prevent 22,800 IPD cases, 872,000 pneumonia cases, and 3,700 deaths, resulting in cost savings of $1.0 B compared to PCV7. Conclusions In a flu pandemic similar to the 2009–2010 H1N1, protection against the 6 additional serotypes in PCV13 would likely be effective in preventing pandemic-related PD cases, mortality, and associated costs. PMID:23687999

  13. A mucosal vaccine against diphtheria: formulation of cross reacting material (CRM 197) of diphtheria toxin with chitosan enhances local and systemic antibody and Th2 responses following nasal delivery

    Microsoft Academic Search

    Edel A McNeela; David O'Connor; Inderjit Jabbal-Gill; Lisbeth Illum; Stanley S Davis; Mariagrazia Pizza; Samuele Peppoloni; Rino Rappuoli; Kingston H. G Mills

    2000-01-01

    The development of new generation vaccines against diphtheria is dependent on the identification of antigens and routes of immunization that are capable of stimulating immune responses similar to, or greater than, those obtained with the parenterally-delivered toxoid vaccine, while reducing the adverse effects that have been associated with the traditional vaccine. In this study, we examined the cellular and humoral

  14. 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

  15. The Impact of Making Vaccines Thermostable in Niger’s Vaccine Supply Chain

    PubMed Central

    Lee, Bruce Y.; Cakouros, Brigid E.; Assi, Tina-Marie; Connor, Diana L.; Welling, Joel; Kone, Souleymane; Djibo, Ali; Wateska, Angela R.; Pierre, Lionel; Brown, Shawn T.

    2012-01-01

    Objective Determine the effects on the vaccine cold chain of making different types of World Health Organization (WHO) Expanded Program on Immunizations (EPI) vaccines thermostable. Methods Utilizing a detailed computational, discrete-event simulation model of the Niger vaccine supply chain, we simulated the impact of making different combinations of the six current EPI vaccines thermostable. Findings Making any EPI vaccine thermostable relieved existing supply chain bottlenecks (especially at the lowest levels), increased vaccine availability of all EPI vaccines, and decreased cold storage and transport capacity utilization. By far, the most substantial impact came from making the pentavalent vaccine thermostable, increasing its own vaccine availability from 87% to 97% and the vaccine availabilities of all other remaining non-thermostable EPI vaccines to over 93%. By contrast, making each of the other vaccines thermostable had considerably less effect on the remaining vaccines, failing to increase the vaccine availabilities of other vaccines to more than 89%. Making tetanus toxoid vaccine along with the pentavalent thermostable further increased the vaccine availability of all EPI vaccines by at least 1–2%. Conclusion Our study shows the potential benefits of making any of Niger’s EPI vaccines thermostable and therefore supports further development of thermostable vaccines. Eliminating the need for refrigerators and freezers should not necessarily be the only benefit and goal of vaccine thermostability. Rather, making even a single vaccine (or some subset of the vaccines) thermostable could free up significant cold storage space for other vaccines, and thereby help alleviate supply chain bottlenecks that occur throughout the world. PMID:22789507

  16. Meningococcal vaccines.

    PubMed

    Bethell, Delia; Pollard, Andrew J

    2002-06-01

    The successful introduction of a protein-polysaccharide conjugate vaccine against serogroup C meningococci into the UK infant immunization schedule, in combination with a catch-up campaign for individuals less than 18 years of age, has seen virtually all group C disease eliminated in childhood. From being a devastating disease with a very high mortality, the possibility of eradicating invasive meningococcal disease now seems eminently feasible. Since similar technology is likely to facilitate prevention of disease caused be serogroup A, Y and W135 meningococci, the major hurdle in achieving the goal of eradication is development of a safe and immunogenic vaccine against serogroup B infections. Outer membrane vesicle vaccines remain in development and further trials are anticipated. Through the recent availability of the meningococcal genome sequence, many new vaccine candidates are being identified and there is increasing optimism that a solution to the problem can be found. PMID:12908514

  17. 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

  18. Enhanced immune response against pertussis toxoid by IgA-loaded chitosan-dextran sulfate nanoparticles.

    PubMed

    Sharma, Sameer; Mukkur, Trilochan Ks; Benson, Heather Ae; Chen, Yan

    2012-01-01

    The objective of the present study was to evaluate immunological activities of chitosan-dextran sulfate (CS-DS) nanoparticle formulation of pertussis toxoid (PTXd) and its combination with a potential immunological adjuvant, immunoglobulin A (IgA). CS-DS nanoparticles were prepared using a complex coacervation (polyelectrolyte complexation) technique. CS-DS nanoparticle formulations with size and zeta potential in a range of 300-350 nm and +40-+55 mV, respectively, were obtained. An entrapment efficiency of more than 90% was obtained for pertussis toxin and IgA in CS-DS nanoparticles. All loaded nanoparticle formulations showed less than 20% of release within 24 h in in vitro release studies. The immunological evaluation of developed formulations in female Balb/c mice groups showed that the CS-DS nanoparticles formulations induced significantly higher serum IgG and IgG1 titers (p < 0.05) as compared with conventional alum-adjuvanted PTXd formulation administered by subcutaneous route. This study indicated the potential of CS-DS nanoparticles to be a simple and effective particulate delivery system with in-built immunological adjuvant property for acellular protein antigens. The study also revealed the potential important role of IgA-loaded CS-DS nanoparticles as a novel immunological adjuvant for vaccine delivery. PMID:21953499

  19. 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.

  20. 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

  1. Changes in nasopharyngeal carriage of Streptococcus pneumoniae, Haemophilus influenzae and Moraxella catarrhalis among healthy children attending a day-care centre before and after official financial support for the 7-valent pneumococcal conjugate vaccine and H. influenzae type b vaccine in Japan.

    PubMed

    Oikawa, Junko; Ishiwada, Naruhiko; Takahashi, Yoshiko; Hishiki, Haruka; Nagasawa, Koo; Takahashi, Sachiko; Watanabe, Masaharu; Chang, Bin; Kohno, Yoichi

    2014-02-01

    The 7-valent pneumococcal conjugate vaccine (PCV7) and Haemophilus influenzae type b (Hib) vaccine reduce nasopharyngeal carriage of vaccine-type bacteria, which may in turn influence the presence of other nasopharyngeal bacterial pathogens. To investigate this possibility, nasopharyngeal carriage of potential pathogens was examined before and after official financial support was provided to offer the PCV7 and Hib vaccines in healthy children attending a day care centre in Japan during 2011-2012. Despite a virtual disappearance of PCV7 serotypes over time, the overall pneumococcal carriage rate remained unchanged. Although others have reported an increase in PCV13 serotypes following PCV7 vaccination, only non-PCV13 serotypes were observed to have increased in this study. The majority of H. influenzae isolates were non-typeable and Hib was not found. Our data identified an unexpected pattern of pneumococcal serotype replacement following PCV7. Continuous monitoring of pneumococcal carriage is important for decisions regarding the future of national vaccination policy in Japan. PMID:24582389

  2. Significant decline in pneumonia admission rate after the introduction of routine 2+1 dose schedule heptavalent pneumococcal conjugate vaccine (PCV7) in children under 5 years of age in Kielce, Poland.

    PubMed

    Patrza?ek, M; Albrecht, P; Sobczynski, M

    2010-07-01

    This study was performed to estimate the effect of heptavalent pneumococcal conjugate vaccine (PCV7) on the pneumonia admission rate in children younger than 5 years of age, after the introduction of routine 2+1 dose schedule immunization. We compared the pneumonia admission rate (number of cases per 1,000 population) 2 years before and 2 years after the introduction of PCV7 in 2006. Only children with radiologically confirmed pneumonia were analyzed. The vaccination rate in the analyzed periods was around 99%. In the period preceding the implementation of PCV7, the average pneumonia admission rate was 41.48/1,000 and 6.15/1,000 for 1-year-old and 2-4-year-old children, respectively. Statistical analysis showed a significant fall in this rate in two consecutive years after PCV7 implementation (p < 0.0000001 for 1-year-old and p = 0.011 for 2-4-year-old children, respectively). In the first year of vaccination, the admission number decreased in these two groups by about 65 and 23%, respectively. In the second year, only a few percent fall in the admission rate was noted. In children younger than 2 years of age, the age group targeted for vaccination, pneumonia-related healthcare utilization declined substantially following PCV7 introduction. These results suggest that PCV7 may play an important role in reducing the burden of pneumonia in Poland. PMID:20437068

  3. Complete List of Vaccines Licensed for Immunization and Distributed in the U.S.

    MedlinePLUS

    ... A. Haemophilus b Conjugate Vaccine (Meningococcal Protein Conjugate) & Hepatitis B Vaccine (Recombinant) Comvax Merck & Co, Inc Hepatitis A Vaccine, ... and Hepatitis B (Recombinant) Vaccine Twinrix GlaxoSmithKline Biologicals Hepatitis B Vaccine (Recombinant) Recombivax HB Merck & Co, Inc Hepatitis B ...

  4. [Influenza vaccine and adjuvant].

    PubMed

    Nakayama, Tetsuo

    2011-01-01

    Adjuvant is originated from the Latin word "adjuvare" which means "help" in English to enhance the immunological responses when given together with antigens. The beginning of adjuvant was mineral oil which enhanced the immune response when it was given with inactivated Salmonella typhimurium. Aluminium salt was used to precipitate diphtheria toxoid and increased level of antibody response was demonstrated when administered with alum-precipitated antigens. Since 1930, aluminium salt has been used as DTaP (diphtheria-tetanus-acellular pertussis vaccine) adjuvant. Many candidates were tested for adjuvant activity but only aluminum salt is allowed to use for human vaccines. New adjuvant MF59, oil-in-water emulsion type, was developed for influenza vaccine for elderly (Fluad) and series of AS adjuvant are used for hepatitis B, pandemic flue, and human papiloma virus vaccines. Oil-adjuvanted influenza pandemic vaccines induced higher antibody response than alum-adjuvanted vaccine with higher incidence of adverse events, especially for local reactions. Alum-adjuvanted whole virion inactivated H5N1 vaccine was developed in Japan, and it induced relatively well immune responses in adults. When it applied for children, febrile reaction was noted in approximately 60% of the subjects, with higher antibodies. Recent investigation on innate immunity demonstrates that adjuvant activity is initiated from the stimulation on innate immunity and/or inflammasome, resulting in cytokine induction and antigen uptake by monocytes and macrophages. The probable reason for high incidence of febrile reaction should be investigated to develop a safe and effective influenza vaccine. PMID:22129866

  5. Preparation and in vitro/in vivo evaluation of mucosal adjuvant in situ forming gels with diphtheria toxoid.

    PubMed

    Ozb?lg?n, Nalan Deniz; Saka, Ongun Mehmet; Bozk?r, Asuman

    2014-03-01

    Studies on preparation of in situ gel formulations containing diphtheria toxoid as the model active substance and their intranasal administration have been conducted in this study. The objective of mucosal vaccination is to stimulate both systemic and mucosal immune responses. In situ gel formulations were prepared by using, in different ratios, mixtures of Poloxamer 407 and Poloxamer 188 polymers, which gelate in a temperature-dependent manner, and mucoadhesive polymers carbopol 934, hydroxypropyl methyl cellulose, hydroxypropyl cellulose or chitosan. Following pre-formulation studies, F1, F2, F3, F4, F5, F6 and F7 formulations, which gelate at intervals and temperatures in accordance with nasal temperatures, were subjected to more comprehensive studies. For this purpose, organoleptic characteristics of the formulations were identified, their pH and mucoadhesive potencies were measured and rheological behaviors were characterized. Calculated amounts of diphtheria toxoid were added to formulations after optimization of formulations was achieved, and assay and in vitro release studies were carried out. Formulations coded F3 and F7 were considered to be superior to other formulations given the in vitro test results. Therefore, these formulations were tested in guinea pigs to determine immune responses, which they would produce following intranasal and subcutaneous administration. Absorbance values of ELISA tests and antibody neutralization test showed that formulations coded F3 and F7 were unable to stimulate adequate systemic immune response when either of the formulations was administered alone intranasally, whereas F7 resulted in significantly increased neutralizing antibody titers with intranasal administration as a booster dose following subcutaneous administration. PMID:24559517

  6. Safety, Immunogenicity and Dose Ranging of a New Vi-CRM197 Conjugate Vaccine against Typhoid Fever: Randomized Clinical Testing in Healthy Adults

    Microsoft Academic Search

    Pierre van Damme; Froukje Kafeja; Alessandra Anemona; Venere Basile; Anne Katrin Hilbert; Ilse de Coster; Simona Rondini; Francesca Micoli; Rana M. Qasim Khan; Elisa Marchetti; Vito di Cioccio; Allan Saul; Laura B. Martin; Audino Podda; Ray Borrow

    2011-01-01

    BackgroundTyphoid fever causes more than 21 million cases of disease and 200,000 deaths yearly worldwide, with more than 90% of the disease burden being reported from Asia. Epidemiological data show high disease incidence in young children and suggest that immunization programs should target children below two years of age: this is not possible with available vaccines. The Novartis Vaccines Institute

  7. Apnoea and bradycardia in preterm infants following immunisation with pentavalent or hexavalent vaccines

    Microsoft Academic Search

    Sven Schulzke; Ulrich Heininger; Michael Lücking-Famira; Hubert Fahnenstich

    2005-01-01

    There is a lack of data regarding the incidence and clinical significance of apnoea or bradycardia (AB) following immunisation with combination vaccines containing an acellular pertussis (Pa) component in respiratory stable preterm infants. Medical records of respiratory stable preterm infants who received a first dose of a combined diphtheria (D) and tetanus (T) toxoids, Pa, Haemophilus influenzae type b (Hib),

  8. Supplementation with Natural Forms of Vitamin E Augments Antigen-Specific TH1-Type Immune Response to Tetanus Toxoid

    PubMed Central

    Radhakrishnan, Ammu Kutty; Mahalingam, Dashayini; Selvaduray, Kanga Rani; Nesaretnam, Kalanithi

    2013-01-01

    This study compared the ability of three forms of vitamin E [tocotrienol-rich fraction (TRF), alpha-tocopherol (?-T), and delta-tocotrienol (?-T3)] to enhance immune response to tetanus toxoid (TT) immunisation in a mouse model. Twenty BALB/c mice were divided into four groups of five mice each. The mice were fed with the different forms of vitamin E (1?mg) or vehicle daily for two weeks before they were given the TT vaccine [4 Lf] intramuscularly (i.m.). Booster vaccinations were given on days 28 and 42. Serum was collected (days 0, 28, and 56) to quantify anti-TT levels. At autopsy, splenocytes harvested were cultured with TT or mitogens. The production of anti-TT antibodies was augmented (P < 0.05) in mice that were fed with ?-T3 or TRF compared to controls. The production of IFN-? and IL-4 by splenocytes from the vitamin E treated mice was significantly (P < 0.05) higher than that from controls. The IFN-? production was the highest in animals supplemented with ?-T3 followed by TRF and finally ?-T. Production of TNF-? was suppressed in the vitamin E treated group compared to vehicle-supplemented controls. Supplementation with ?-T3 or TRF can enhance immune response to TT immunisation and production of cytokines that promote cell-mediated (TH1) immune response. PMID:23936847

  9. Pneumococcal Conjugate Vaccine (PCV7)

    MedlinePLUS

    ... completed the PCV series should get 1 dose. Children with medical conditions such as sickle cell disease, a damaged spleen or no spleen, cochlear implants, HIV/AIDS or other diseases that affect the ...

  10. Immunoregulation in humans: control of antitetanus toxoid antibody production after booster immunization.

    PubMed Central

    Stevens, R H; Saxon, A

    1978-01-01

    Booster immunization of normal individuals with soluble tetanus toxoid resulted in the ability of the individuals' peripheral blood lymphocytes to synthesize immunoglobulin (Ig)G antitetanus toxoid antibody in vitro when stimulated by pokeweed mitogen. The capacity for this in vitro antitetanus toxoid antibody response developed within 14 days after booster immunization, reached a peak between days 36--50, and disappeared by day 60. The inability of pokeweed mitogen to stimulate antitetanus toxoid antibody synthesis in vitro before booster immunization was not due to excess suppression by thymus-derived (T) lymphocytes but reflected insufficient numbers of functionally specific helper T lymphocytes and bone marrow-derived (B) lymphocytes. Antigen-specific T-lymphocyte suppression and decreased B-lymphocyte function were associated with the observed reduction of in vitro synthesis of antitetanus toxoid antibody from 20--60 days post-immunization. The in vitro kinetics of antitetanus toxoid antibody synthesis paralleled the synthesis of total IgG in that stimulation by pokeweed mitogen was required and that antibody secretion into the medium initiated by day 4 and increased through day 9. PMID:311781

  11. Immunogenicity, safety, and reactogenicity of the 10-valent pneumococcal non-typeable Hemophilus influenzae protein D conjugate vaccine (PHiD-CV) when co-administered with the DTPw-HBV/Hib vaccine in Indian infants: a single-blind, randomized, controlled study.

    PubMed

    Lalwani, Sanjay; Chatterjee, Sukanta; Chhatwal, Jugesh; Verghese, Valsan P; Mehta, Shailesh; Shafi, Fakrudeen; Borys, Dorota; Moreira, Marta; Schuerman, Lode

    2012-05-01

    In India, pneumococcal diseases are major causes of child mortality, and effective vaccines against Streptococcus pneumoniae are needed. This single-blind, randomized study assessed the immunogenicity, reactogenicity, and safety of the 10-valent pneumococcal non-typeable Hemophilus influenzae (NTHi) protein D conjugate vaccine (PHiD-CV) co-administered with DTPw-HBV/Hib in Indian infants as 3-dose primary vaccination course. A total of 360 infants were randomized (2:1) to receive either PHiD-CV co-administered with DTPw-HBV/Hib (PHiD-CV group) or a Hib vaccine co-administered with DTPw-HBV (control group) at 6, 10, and 14 weeks of age. For each vaccine pneumococcal serotype, the percentage of infants in the PHiD-CV group with antibody concentrations ? 0.2 µg/mL one month after the third vaccine dose was at least 98.3%, except for serotypes 6B (77.7%) and 23F (89.5%), and opsonophagocytic activity titers ? 8 were measured in at least 95.7% of infants, except for serotypes 1 (90.5%) and 6B (84.5%). In addition, all the infants in the PHiD-CV group were seroprotected against diphtheria, tetanus, Hib, and hepatitis B or seropositive for antibodies against pertussis and NTHi protein D (except one infant). Incidences of solicited local and general symptoms were comparable between groups, except for fever (axillary temperature ? 37.5°C), which seemed to occur more frequently in the PHiD-CV group. In conclusion, PHiD-CV was shown to be immunogenic and well-tolerated when co-administered with DTPw-HBV/Hib in Indian infants. PMID:22634448

  12. Meningococcal vaccine evolution.

    PubMed

    Bona, G; Guidi, C

    2012-09-01

    Neisseria meningitidis is a leading cause of bacterial sepsis and meningitis worldwide. Invasive meningococcal disease (IMD) can develop rapidly and is associated with high mortality and morbidity. Case fatality in developed countries averages 10% and higher rates are reported in less prosperous regions. The incidence of invasive disease due to Neisseria meningitidis is highly variable according to geographical area and serogroup distribution. The major disease burden is in developing countries; in industrialized countries meningococcal disease occurs sporadically and most IMD is caused by serogroups B and C. In the US serogroup Y is a major cause of meningococcal disease, accounting for more than one third of cases. Polysaccharide vaccines against serogroups A, C, W-135, and Y were developed but they were not so effective in protecting infants, who are at particularly high risk from invasive meningococcal infections. Conjugation of bacterial capsular polysaccharide to a carrier protein generates a T cell dependent immune response and immunological memory from infancy. After the introduction of serogroup C meningococcal conjugate vaccines since 1999, the incidence of serogroup C disease fell dramatically in countries in which they have been used. The first quadrivalent meningococcal conjugate vaccine (MenACWY-D) was licensed in the US in 2005. More recently, another tetravalent meningococcal conjugate vaccine (MenACWY-CRM, Menveo) was licensed in Europe and the US. Although polysaccharide and glycoconjugate vaccines have been developed for serogroups A, C, Y and W-135, currently there are no broadly effective vaccines available for the prevention of meningococcal B disease. PMID:23362617

  13. A serogroup A meningococcal polysaccharide vaccine

    PubMed Central

    Erwa, H. H.; Haseeb, M. A.; Idris, A. A.; Lapeyssonnie, L.; Sanborn, W. R.; Sippel, J. E.

    1973-01-01

    Vaccination against cerebrospinal meningitis (CSM) has regained interest with the use of capsular polysaccharides (or polyosides) of the meningococcus as specific immunizing agents. These compounds proved to be effective in the USA against meningitis caused by Neisseria meningitidis serotype C. This study considers whether the polysaccharides of the serotype A meningococcus, which is prevalent in the African CSM belt, could be protective in epidemic conditions. Taking advantage of the usual seasonal peak of CSM cases, controlled field trials were undertaken in the Sudan early in 1973. 21 640 persons were vaccinated, half of them with a meningococcal polyoside A vaccine and the other half with tetanus toxoid as a placebo. In the former group there were no cases of meningitis, whereas in the latter 10 cases were reported, of which 7 were confirmed by laboratory tests. These studies indicate that the meningococcal polyoside A vaccine is efficient in epidemic conditions and could be used to control outbreaks of meningococcal meningitis. PMID:4211056

  14. 21 CFR 522.1083 - Gonadotropin releasing factor analog-diphtheria toxoid conjugate.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ...should be administered at least 4 weeks after the first dose. (2) Indications for use. For the temporary immunological castration (suppression of testicular function) and reduction of boar taint in intact male pigs intended for slaughter. (3)...

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

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ...should be administered at least 4 weeks after the first dose. (2) Indications for use. For the temporary immunological castration (suppression of testicular function) and reduction of boar taint in intact male pigs intended for slaughter. (3)...

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

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ...should be administered at least 4 weeks after the first dose. (2) Indications for use. For the temporary immunological castration (suppression of testicular function) and reduction of boar taint in intact male pigs intended for slaughter. (3)...

  17. Temporal changes in nasopharyngeal carriage of Streptococcus pneumoniae serotype 1 genotypes in healthy Gambians before and after the 7-valent pneumococcal conjugate vaccine.

    PubMed

    Ebruke, Chinelo; Roca, Anna; Egere, Uzochukwu; Darboe, Ousainou; Hill, Philip C; Greenwood, Brian; Wren, Brendan W; Adegbola, Richard A; Antonio, Martin

    2015-01-01

    Streptococcus pneumoniae serotype 1 is one of the leading causes of invasive pneumococcal disease. However, this invasive serotype is hardly found in nasopharyngeal asymptomatic carriage and therefore large epidemiological studies are needed to assess the dynamics of serotype 1 infection. Within the context of a large cluster randomized trial conducted in rural Gambia to assess the impact of PCV-7 vaccination on nasopharyngeal carriage, we present an ancillary analysis describing the prevalence of nasopharyngeal carriage of pneumococcal serotype 1 and temporal changes of its more frequent genotypes. Nasopharyngeal swabs (NPS) were collected before PCV-7 vaccination (December 2003-May 2004) and up to 30 months after PCV-7 vaccination. The post-vaccination time was divided in three periods to ensure an equal distribution of the number of samples: (1) July 2006-March 2007, (2) April 2007-March 2008 and (3) April 2008-Feb 2009. S. pneumoniae serotype 1 were genotyped by MLST. Serotype 1 was recovered from 87 (0.71%) of 12,319 NPS samples collected. In the pre-vaccination period, prevalence of serotype 1 was 0.47% in both study arms. In the post-vaccination periods, prevalence in the fully vaccinated villages ranged between 0.08% in period 1 and 0.165% in period 2, while prevalence in partly vaccinated villages was between 0.17% in period 3 and 1.34% in period 2. Overall, four different genotypes were obtained, with ST3081 the most prevalent (60.71%), followed by ST618 (29.76%). ST3081 was found only in post-vaccination period 2 and 3, while ST618 had disappeared in post-vaccination period 3. Distribution of these major genotypes was similar in both study arms. Emergence of ST3081 and concomitant disappearance of ST618 may suggest a change in the molecular epidemiology of pneumococcal serotype 1 in this region. This change is not likely to be associated with the introduction of PCV-7 which lacks serotype 1, as it was observed simultaneously in both study arms. Future population-based epidemiological studies will provide further evidence of substantive changes in the pneumococcal serotype 1 epidemiology and the likely mechanisms. PMID:25945306

  18. [Vaccination strategies for anthrax prevention].

    PubMed

    Beyer, Wolfgang

    2004-01-01

    Apart from live spore vaccines with a certain amount of residual virulence for various animal species, there are two acellular protein vaccines for immunoprophylaxis against anthrax in humans. For ethical reasons there are no experimental data available on the efficacy and duration of the immunity they induce in men. Their efficacy was evaluated in laboratory animals, mainly rabbits and rhesus monkeys. Furthermore, it is well known that these vaccines elicit only partial protection in guinea pigs and almost no protection in mice against a challenge with fully virulent spores of Bacillus (B.) anthracis. Other disadvantages are the high amount of boosters necessary to elicit and to maintain a protective immune response, the variability in the composition of bacterial culture supernatants used for production, and the appearance of clinically relevant side effects. Therefore, there is ongoing work worldwide to improve the existing vaccines by substitution with recombinant antigens and to develop new vaccines on the basis of recombinant bacterial or viral live vectors, DNA-vectors, and by addition of new adjuvants. Special attention is given to supplementing the existing toxoid-vaccines with an anti-bacterial component. PMID:15584433

  19. 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...

  20. Levels of diphtheria and tetanus specific IgG of Portuguese adult women, before and after vaccination with adult type Td. Duration of immunity following vaccination

    PubMed Central

    Gonçalves, Guilherme; Santos, Maria Augusta; Frade, João Graça; Cunha, José Saraiva

    2007-01-01

    Background The need for tetanus toxoid decennial booster doses has been questioned by some experts. Several counter arguments have been presented, supporting the maintenance of decennial adult booster doses with tetanus and diphtheria toxoids (adult formulation of the vaccine: Td). This study aimed to evaluate the use of Td in Portuguese adult women under routine conditions. For that purpose we selected a group of women 30+ years of age to which vaccination was recommended. We intended to know if pre-vaccination antibody concentrations were associated with factors as age at first and last vaccination, number of doses and time since last revaccination. We also intended to assess the serological efficacy of Td booster. Methods Following the Portuguese guidelines 100 women were vaccinated with Td. Antitetanus toxin IgG (ATT IgG) and antidiphtheria toxin IgG (ADT IgG) levels were measured (mIU/ml) in 100 pre-vaccination and 91 post-vaccination sera. Detailed vaccination records were available from 88 participants. Results Twenty-two women (Group A) began vaccination with DPT/DT in their early childhood and their pre-vaccination ATT IgG levels increased with the number of doses received (p = 0.022) and decreased with time since last vaccination (p = 0.016). Among the 66 women who began vaccination in adolescence and adulthood (Group B), with monovalent TT, ATT IgG levels decreased with age at first dose (p < 0.001) and with time since last vaccination (p = 0.041). In Group A, antidiphtheria toxin IgG kinetics was very similar to that observed for ATT IgG. Among women not vaccinated with diphtheria toxoid, ADT IgG levels decreased with age. Serological response to both components of Td was good but more pronounced for ATT IgG. Conclusion Our study suggests that, to protect against tetanus, there is no need to administer decennial boosters to the Portuguese adults who have complied with the childhood/adolescent schedule (6 doses of tetanus toxoid). The adult booster intervals could be wider, probably of 20 years. This also seems to apply to protection against diphtheria, but issues on the herd immunity and on the circulation of toxigenic strains need to be better understood. PMID:17565697

  1. 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

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

    PubMed

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

    2013-08-20

    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

  3. Immunogenicity in a mouse model of a conjugate vaccine made with a synthetic single repeating unit of type 14 peumococcal polysaccharide coupled to CRM197

    Microsoft Academic Search

    Fatme Mawas; J. Niggeman; Christopher Jones; Michael J. Corbel; Johannis P. Kamerling; Johannes F. G. Vliegenthart

    2002-01-01

    Oligosaccharides (OSs) related to the pneumococcal type 14 capsular polysaccharide (Pn14PS) were studied for their ability to inhibit the binding between anti-PS14 antisera and native PS14. A synthetic tetrasaccharide corresponding to the repeating unit of the Pn14PS, a hexasaccharide mimic, and an octasaccharide fragment obtained by Pn14PS depolymerization were good inhibitors. CRM197 conjugates of the tetrasaccharide and an octasaccharide mimic

  4. The efficacy and safety of a nicotine conjugate vaccine (NicVAX®) or placebo co-administered with varenicline (Champix®) for smoking cessation: study protocol of a phase IIb, double blind, randomized, placebo controlled trial

    PubMed Central

    2012-01-01

    Background A potential new treatment in smoking cessation and relapse prevention is nicotine vaccination which is based on active immunization against the nicotine molecule. This immunization will elicit the immune system to produce nicotine-specific antibodies that sequester nicotine in the blood stream, after inhaling tobacco products. The resulting antibody-antigen is too large to cross the blood–brain barrier and is therefore postulated to attenuate the rewarding effect of nicotine by preventing the latter from reaching its receptors in the brain and causing the release of dopamine. The aim of this paper is to describe the design of a phase IIb, multi-center, double blind, randomized, placebo controlled trial to assess the efficacy of the nicotine vaccine NicVAX® co-administered with varenicline (Champix®) and intensive counseling as an aid in smoking cessation and relapse prevention. Methods/design Two centers will include a total of 600 smokers who are motivated to quit smoking. At week ?2 these smokers will be randomized, in a 1:1 ratio, to either 6 injections of NicVAX® or placebo, both co-administered with 12-weeks of varenicline treatment, starting at week 0. The target quit day will be set after 7?days of varenicline treatment at week 1. Smokers will be followed up for 54?weeks. The primary outcome is defined as biochemically validated prolonged smoking abstinence from week 9 to 52. Secondary outcomes include safety, immunogenicity, smoking abstinence from week 37 to 52, abstinence from week 9 to 24, abstinence in the subset of subjects with the highest antibody response, and lapse/relapse rate. Discussion This is the first study to assess the efficacy of a nicotine conjugate vaccine in combination with an evidence-based smoking cessation pharmacotherapy (varenicline) to quit smoking. Although NicVAX® is primarily designed as an aid to smoking cessation, our study is designed to explore its potential to maintain abstinence and prevent relapse. The results of this trial will give a unique insight in the potential of nicotine vaccination for relapse prevention. Trial registration ClinicalTrials.gov: (NCT00995033) PMID:23216646

  5. Vaccination against nicotine during continued nicotine administration in rats: immunogenicity of the vaccine and effects on nicotine distribution to brain

    Microsoft Academic Search

    Y Hieda; D. E Keyler; S Ennifar; A Fattom; P. R Pentel

    2000-01-01

    Vaccination against nicotine has been proposed as a potential treatment for nicotine dependence. Because vaccination may take months to elicit satisfactory antibody levels, the clinical usefulness of this approach will be enhanced if vaccination can be accomplished during continued nicotine intake (e.g., before a smoker quits). The current study examined the immunogenicity of a nicotine conjugate vaccine during continued nicotine

  6. Neisseria meningitidis B vaccines.

    PubMed

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

    2011-09-01

    Invasive infections caused by Neisseria meningitidis are a serious public health problem worldwide and have a heavy economic impact. The incidence of invasive disease due to Neisseria meningitidis is highly variable according to geographical area and serogroup distribution. Since the introduction of vaccination programs with conjugated vaccine C in children and adolescents, most cases of invasive meningococcal disease in developed countries have been caused by meningococcus B. It is important to underline that invasive meningococcal disease will not be controlled until safe and effective vaccines for meningococcal B are available and widely used. The aims of this article are to describe the most recent developments in meningococcal B vaccines and to discuss how these vaccines can contribute to containing meningococcal disease. PMID:21919622

  7. Ear Infection and Vaccines

    MedlinePLUS

    ... more information. Conjugate vaccines are effective against otitis media in children under the age of five because they have ... that an infant?s immature defense system can recognize. Children older than five, ... Here are issues to consider. Streptococcus pneumoniae bacteria ( ...

  8. Adequate immune response to tetanus toxoid and failure of vitamin A and E supplementation to enhance antibody response in healthy children.

    PubMed

    Kutukculer, N; Akil, T; Egemen, A; Kurugöl, Z; Ak?it, S; Ozmen, D; Turgan, N; Bayindir, O; Ca?layan, S

    2000-07-01

    The effects of vitamin A and vitamin E supplementation on the IgG response to tetanus toxoid after primary immunization were evaluated in a prospective, randomized controlled clinical trial involving 89 healthy infants with normal serum vitamin A and E levels at 2 months of age. Before the first dose of DPT vaccine, the infants were randomly enrolled into four different study groups [Group I (n=24): 30,000 IU vitamin A for 3 days just after each three doses of primary vaccination, Group II (n=21): 150 mg oral vitamin E for only 1 day after the injections for primary immunization, Group III (n=21): vitamins A and E together in the same order, Group IV (n=23) no vitamin after DPT vaccines]. Serum tetanus antitoxin (IgG) titres were measured three times; initially at 2 months of age before the first dose of DPT, secondly at 5 months of age 1 month after primary immunization and thirdly at 16-18 months of age before the booster dose of DPT. Before the first dose of the DPT vaccine, 1 month after the third DPT injection and at 16-18 months before the booster dose of DPT, there was no significant difference in serum tetanus antitoxin levels between these four groups. A significant increase was observed in all the groups when serum tetanus antitoxin levels before (2 months) and after (5 months) primary immunization were compared. In addition, serum antibody levels against tetanus significantly decreased in the four groups before booster vaccination. Before the beginning of primary immunization, 15 infants (16.8%) had serum tetanus antitoxins (IgG) below protective level. After three doses of DPT, all the infants had protective antitoxin levels. At 16-18 months of age before booster dose, four infants (10%) also had serum tetanus antitoxins (IgG) below the protective level. No side-effects were observed except bulging fontanelle in two infants in Group I. PMID:10825599

  9. 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...

  10. Tetanus toxoid coverage as an indicator of serological protection against neonatal tetanus

    Microsoft Academic Search

    Michael S. Deming; Jean-Baptiste Roungou; Max Kristiansen; Iver Heron; Alphonse Yango; Alexis Guenengafo; Robert Ndamobissi

    2002-01-01

    Objective A Multiple-Indicator Cluster Survey (MICS) was conducted at mid-decade in more than 60 developing countries to measure progress towards the year 2000 World Summit for Children goals. These goals included the protection of at least 90% of children against neonatal tetanus through the immunization of their mothers, as measured by tetanus toxoid (TT) coverage. In the Central African Republic

  11. Clinical trial of concentrated inactivated polio vaccine in a simplified immunization program.

    PubMed

    Fillastre, C; Emmou, C; Meyran, M; Schlumberger, M; Guérin, N

    1981-01-01

    The aims of the trial were: 1) to verify the effectiveness of injectable polio vaccine (inactivated) combined with concentrated diphtheria and tetanus toxoid, in one or two injections given at an interval of 6 months; 2) to compare the killed polio vaccine with the oral vaccine which is recommended in the Ivory Coast program: 4 doses in 15 months. The effectiveness of the immunizations is judged by the serum antibody levels 8 to 12 weeks following immunization. The comparative study of 2 inactivated polio vaccines A and C with live oral vaccine showed the superiority of inactivated vaccine, which resulted in good seroconversion after a single dose. The increase in the serologic response is proportional to the antigenic mass since it appears that the concentration of vaccine C is double that of A. PMID:6262148

  12. [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

  13. Evaluation of two GnRH-I based vaccine formulations on the testes function of entire Suffolk cross ram lambs.

    PubMed

    Earl, Elizabeth R; Waterston, Mary M; Aughey, Elizabeth; Harvey, Michael J A; Matschke, Christian; Colston, Angela; Ferro, Valerie A

    2006-04-12

    A modified GnRH peptide (CHWSYGLRPG-NH(2)) was conjugated to tetanus toxoid (TT) or diphtheria toxoid (DT) and formulated with Quil A saponin or a sustained release injectible PLGA (poly(lactide-co-glycolide)/triacetin). For the Quil A formulations, two administrations of TT conjugate at 3-weekly intervals were followed by two booster injections with the DT conjugate in entire ram lambs. With the PLGA formulations, only two injections were administered; the first containing TT and the second DT at 6-weekly intervals. Evaluation was carried out by comparing the specific antibody levels produced in relationship to hormone profiles and testicular changes. The Quil A formulation was considered the most effective, as it caused significant reduction in testosterone and follicle stimulating hormone levels, resulting in marked suppression of spermatogenesis. PMID:16483697

  14. Immunogenicity and safety of 23-valent pneumococcal polysaccharide vaccine as a booster dose in 12- to 18-month-old children primed with 3 doses of 7-valent pneumococcal conjugate vaccine

    PubMed Central

    Thisyakorn, Usa; Chokephaibulkit, Kulkanya; Kosalaraksa, Pope; Benjaponpitak, Suwat; Pancharoen, Chitsanu; Chuenkitmongkol, Sunate

    2014-01-01

    The current study examined the safety and immunogenicity of 23-valent pneumococcal capsular polysaccharide vaccine (Pneumo23® [PPV23], Sanofi Pasteur) as a booster dose in 12- to 18-month-old children primed with heptavalent pneumococcal vaccine (PCV7; Prevnar®, Pfizer). This was a randomized, observer-blinded, 2-arm, controlled, multicenter phase III study performed in Thailand to assess and describe the immunogenicity and safety of PPV23 as a booster dose in children who had received the 3 primary doses of PCV7, the pneumococcal vaccine available during the study period. Children primed with 3 doses of PCV7 were randomized 1:1 to receive a booster immunization with PPV23 or PCV7. Pneumococcal antibody concentrations were measured by enzyme-linked immunosorbent assay and functional antibody levels by multiplex opsonophagocytosis assay on day 30. A total of 339 children were enrolled. Geometric mean serum antibody concentrations against serotypes common to PCV7 and PPV23 (4, 6B, 9V, 14, 18C, 19F, and 23F) increased in both groups but they were higher for serotypes 4, 9V, 18C, and 19F in the PPV23 group. Opsonization indices increased in both groups for all measured serotypes (1, 6B, 14, 19A, and 23F) and were higher for serotypes 6B, 14, and 23F in the PCV7 group and for serotypes 1 and 19A in PPV23 group. Solicited reactions and unsolicited adverse events were similar in the 2 groups and generally mild and transient. No treatment-related serious adverse events were reported. These results confirm that boosting with PPV23 is immunogenic and well tolerated in healthy toddlers primed with PCV7. PMID:25424793

  15. Vaccine process technology.

    PubMed

    Josefsberg, Jessica O; Buckland, Barry

    2012-06-01

    The evolution of vaccines (e.g., live attenuated, recombinant) and vaccine production methods (e.g., in ovo, cell culture) are intimately tied to each other. As vaccine technology has advanced, the methods to produce the vaccine have advanced and new vaccine opportunities have been created. These technologies will continue to evolve as we strive for safer and more immunogenic vaccines and as our understanding of biology improves. The evolution of vaccine process technology has occurred in parallel to the remarkable growth in the development of therapeutic proteins as products; therefore, recent vaccine innovations can leverage the progress made in the broader biotechnology industry. Numerous important legacy vaccines are still in use today despite their traditional manufacturing processes, with further development focusing on improving stability (e.g., novel excipients) and updating formulation (e.g., combination vaccines) and delivery methods (e.g., skin patches). Modern vaccine development is currently exploiting a wide array of novel technologies to create safer and more efficacious vaccines including: viral vectors produced in animal cells, virus-like particles produced in yeast or insect cells, polysaccharide conjugation to carrier proteins, DNA plasmids produced in E. coli, and therapeutic cancer vaccines created by in vitro activation of patient leukocytes. Purification advances (e.g., membrane adsorption, precipitation) are increasing efficiency, while innovative analytical methods (e.g., microsphere-based multiplex assays, RNA microarrays) are improving process understanding. Novel adjuvants such as monophosphoryl lipid A, which acts on antigen presenting cell toll-like receptors, are expanding the previously conservative list of widely accepted vaccine adjuvants. As in other areas of biotechnology, process characterization by sophisticated analysis is critical not only to improve yields, but also to determine the final product quality. From a regulatory perspective, Quality by Design (QbD) and Process Analytical Technology (PAT) are important initiatives that can be applied effectively to many types of vaccine processes. Universal demand for vaccines requires that a manufacturer plan to supply tens and sometimes hundreds of millions of doses per year at low cost. To enable broader use, there is intense interest in improving temperature stability to allow for excursions from a rigid cold chain supply, especially at the point of vaccination. Finally, there is progress in novel routes of delivery to move away from the traditional intramuscular injection by syringe approach. PMID:22407777

  16. Effect of schedule on reactogenicity and antibody persistence of acellular and whole-cell pertussis vaccines: value of laboratory tests as predictors of clinical performance

    Microsoft Academic Search

    E. Miller; L. A. E. Ashworth; K. Redhead; C. Thornton; P. A. Waight; T. Coleman

    1997-01-01

    The performance of four acellular pertussis vaccines containing between two and five pertussis antigens combined with diphtheria and tetanus toxoids was compared with that of British whole-cell diphtheria\\/tetanus\\/pertussis (DTP) vaccine both in laboratory assays for potency, toxicity and immunogenicity, and for reactogenicity and immunogenicity in infants. Clinical responses were evaluated in double blind randomized Phase II trials using 3\\/5\\/9 month

  17. Natural autoantibodies, IgG antibodies to tetanus toxoid and CD5+ B cells in patients with Mediterranean visceral leishmaniasis. The Leishmania Study Group.

    PubMed Central

    Louzir, H; Belal-Kacemi, L; Sassi, A; Laouini, D; Ben Ismail, R; Dellagi, K

    1994-01-01

    Natural autoantibodies (NaAb) and IgG antibodies to tetanus toxoid (TT) were analysed in the sera of 38 children with active visceral leishmaniasis (VL) previously vaccinated with TT and in 30 healthy controls matched for sex and age. Patients exhibited high levels of NaAb to a panel of self antigens (tubulin, myosin, myoglobin, actin) contrasting to a low level of IgG to TT. Analysis of the circulating B cells in 26 untreated patients showed a low percentage of CD5+ per total B cells (3-66%, mean 36.6%) compared with 14 normal controls (17.8-66.6%, mean 52.7%) (P < 0.001). Evaluation of these parameters after antimonial therapy showed a significant decrease of the level of the NaAb (P < 0.0005), and a spontaneous increase of the level of the IgG to TT without any vaccine boosting (P < 0.01). In contrast, there was a significant increase in CD5+ B cells (P < 0.0005). This result suggests that CD5+ B cells may be sequestrated in parasitized lymphoid organs and may be released after remission. These findings show that the polyclonal B cell activation that occurs during active VL involves mainly B cells bearing NaAb and are in favour of a functional dichotomy of B cells. PMID:7511080

  18. Comparative Estimation of Coverage between National Immunization Program Vaccines and Non-NIP Vaccines in Korea

    PubMed Central

    Choe, Young June; Yang, Jae Jeong; Park, Sue K.; Lee, Hoan Jong

    2013-01-01

    This study aimed to describe the differences in vaccination coverage between National Immunization Program (NIP) vaccines and non-NIP vaccines in Korea and to identify factors affecting the difference. Nationwide face-to-face interview-based questionnaire survey among randomly selected 4,374 participants aged 7-83 months was conducted. Vaccination coverage analyzed according to the birth cohorts, geographic areas, and socio-demographic characteristics. We found that NIP vaccines recorded higher primary vaccination coverage compared to non-NIP vaccines (95.9%-100% vs 30.7%-85.4%). The highest rate was Haemophilus influenzae type b (Hib) vaccine (85.4%), which was introduced in 1996, and the lowest rate was rotavirus vaccine (30.7%), which was introduced recently. On multivariate analysis, having a sibling were significantly associated with lower uptake of Hib vaccine, pneumococcal conjugate vaccine (PCV), and rotavirus vaccine; while, older mother's age and attendance to daycare center were significantly associated with lower uptake of PCV and rotavirus vaccine (P < 0.001). We found differences in the vaccine coverage rate between NIP vaccines and non-NIP vaccines; and the data suggests potential disparity in accessing non-NIP vaccines in Korea. Expansion of NIP to include non-NIP vaccines can provide better protection against the diseases through increased coverage. PMID:24015031

  19. Effectiveness of a seventh grade school entry vaccination requirement--statewide and Orange County, Florida, 1997-1998.

    PubMed

    1998-09-01

    Vaccine-preventable diseases continue to occur among adolescents (i.e., persons aged 11-21 years). In 1996, the Advisory Committee on Immunization Practices (ACIP), the American Academy of Pediatrics, the American Academy of Family Physicians, and the American Medical Association published joint recommendations emphasizing appropriate vaccination of adolescents aged 11-12 years who have not been vaccinated with hepatitis B vaccine, a second dose of measles, mumps, and rubella vaccine (MMR), varicella vaccine (if indicated), a booster dose of tetanus and diphtheria toxoids (Td), and other vaccines that may be indicated for certain adolescents. School entry requirements are an effective mechanism for ensuring high vaccination coverage among children. At the start of the 1997-98 school year, an amendment to the Florida Administrative Code (64D-3.011, F.A.C.) was instituted that requires all persons entering seventh grade to be vaccinated with three doses of hepatitis B vaccine, a second dose of MMR, and a Td booster, or to be on schedule for vaccination (i.e., having received at least one dose of hepatitis B vaccine, one dose of MMR, and a Td booster). To determine vaccination coverage among students entering seventh grade in Florida and in Orange County in 1997, CDC, in collaboration with the Florida Department of Health, analyzed state vaccination coverage data. This report summarizes the results of the analysis and indicates that a vaccination requirement for middle school entry can be effective in ensuring vaccination of adolescents. PMID:9746399

  20. Seroprevalence of Tetanus Antibody in Turkish Population and Effectiveness of Single-Dose Tetanus Toxoid

    Microsoft Academic Search

    S. Cavuslu; O. Oncul; H. Altunay; M. F. Ozsoy; N. Kocak

    2003-01-01

    The study presented here was performed to determine the rates of immunity to tetanus in a cross section of the Turkish population and to assess the impact of a single-dose tetanus toxoid in previously unvaccinated individuals. Among 18-year-old participants who received their last tetanus booster 4 years prior to the study and 22-year-old participants who received the booster 8 years

  1. A Nonadjuvanted Transcutaneous Tetanus Patch Is Effective in Boosting Anti-Tetanus Toxoid Immune Responses

    PubMed Central

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

    2014-01-01

    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

  2. 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

  3. Impact of Pneumococcal Conjugate Vaccines on the Incidence of Pneumonia in Hospitalized Children after Five Years of Its Introduction in Uruguay

    PubMed Central

    Hortal, María; Estevan, Miguel; Meny, Miguel; Iraola, Inés; Laurani, Hilda

    2014-01-01

    Background Data on the burden of pneumococcal disease and the most frequent serotypes demonstrated that invasive disease and pneumonia were important manifestations affecting children under 5 years of age. Therefore, pneumococcal diseases prevention became a public health priority. Uruguay was the first Latin American country to incorporate PCV7 into its National Immunization Program. The aim of this study is to compare the incidence rates for hospitalized pneumonia in children from the pre PCV introduction period and the following five years of PCVs application in Uruguay. Methods and Findings Population-based surveillance of pneumonia hospitalization rates, in children, less than 14 years of age, had been performed prior pneumococcal vaccination, and continued following PCV7 introduction and PCV13 replacement, using the same methodology. Hospitalized children with pneumonia were enrolled from January 1, 2009 through December 31st, 2012. The study was carried out in an area with a population of 238,002 inhabitants of whom 18, 055 were under five years of age. Patients with acute lower respiratory infections for whom a chest radiograph was performed on admission were eligible. Digitalized radiographs were interpreted by a reference radiologist, using WHO criteria. Pneumonia was confirmed in 2,697 patients, 1,267 with consolidated and 1,430 with non consolidated pneumonia of which incidence decrease, between 2009 and 2012, was 27.3% and 46.4% respectively. 2001–2004 and 2009–2012 comparison showed a significant difference of 20.4% for consolidated pneumonia hospitalizations. A significant incidence decline was recorded among children 6 to 35 months of age. Conclusions An overall significant reduction in pneumonia hospitalizations was observed following the introduction of PCV7 and furthermore following the change to PCV13. PMID:24905093

  4. 76 FR 13646 - Vaccines and Related Biological Products Advisory Committee; Notice of Meeting

    Federal Register 2010, 2011, 2012, 2013, 2014

    2011-03-14

    ...demonstration of effectiveness of meningococcal serogroups A, C, Y, and W-135 conjugate vaccines administered to children less...approaches to licensure of meningococcal serogroup B vaccines. FDA intends to make...

  5. Translational research on vaccines: influenza as an example.

    PubMed

    Belshe, R B

    2007-12-01

    Influenza vaccine development is reviewed as an example of ongoing translational research, which is moving fundamental advances in biology into useful products. The types of new influenza vaccines span the gamut of modern biology research and include new methods of vaccine production (tissue culture compared with egg-produced vaccine). New vaccines being studied include recombinant proteins, polynucleotide vaccines, conjugate vaccines, peptides, expression vectors, and live attenuated vaccines; new adjuvants are being explored to reduce the quantity of antigen needed. The benefits of using reverse genetics are explored. The limits of translational research for predicting clinical results after wide use of vaccines are discussed, including one example of "overinterpretation" of data; some questions should be left to phase IV experience to answer. The pipeline for new influenza vaccines is robust, and recent investment by government and industry in newer vaccines will bring several new products to clinical use. PMID:17971813

  6. A comparative study of PENTA™ vaccine booster doses given at 12, 15 or 18 months of age

    Microsoft Academic Search

    David W Scheifele; Roland Guasparini; Pierre Lavigne

    1999-01-01

    For infants immunized with Haemophilus influenzae type b conjugate vaccines, booster immunization is usually recommended in the second year of life, typically between 12 and 18 months. This study assessed the effect of age at booster immunization on pre-immunization antibody trough levels and on subsequent responses, for a PRP-T conjugate vaccine. Subjects were healthy children who had received PENTA™ vaccine

  7. Immunological Links to Nonspecific Effects of DTwP and BCG Vaccines on Infant Mortality

    PubMed Central

    Claesson, Mogens Helweg

    2011-01-01

    A number of mainly observational studies suggest that many African females below the age of one year die each year from the nonspecific effects of vaccination with diphtheria-tetanus toxoids and killed (whole-cell) Bordetella pertussis (DTwP). In contrast, similar studies suggest that many African females and males may have their lives saved each year by the nonspecific immunological benefits of Bacillus Calmette-Guerin (BCG) vaccination. From an immunological point of view, we hypothesise that the adverse effects of DTwP vaccine may occur because of the Th2-polarising effect of the aluminium phosphate adjuvant in the vaccine and because intramuscular administration of the vaccine may cause chronic inflammation at the site of injection. However, the Th1-polarising effect of BCG is likely to be beneficial. Sexual dimorphism affecting immune functions and vitamin A supplementation may influence both the deleterious and beneficial nonspecific effects of immunisation. PMID:21760811

  8. Neonatal BCG vaccination is associated with enhanced T-helper 1 immune responses to heterologous infant vaccines.

    PubMed

    Libraty, Daniel H; Zhang, Lei; Woda, Marcia; Acosta, Luz P; Obcena, Anamae; Brion, Job D; Capeding, Rosario Z

    2014-01-01

    Neonatal Bacille Calmette Guérin (BCG) vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1) immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2-3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-? (IFN-?) producing spot-forming cells (SFC) to tetanus toxoid 2-3 months later. The frequency of IFN-? producing SFC to polioviruses 1-3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-?+/tumor necrosis factor-? (TNF-?)+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA)/Ionomycin was higher in 2-3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3)+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2-3 months later. PMID:24611083

  9. Neonatal BCG vaccination is associated with enhanced T-helper 1 immune responses to heterologous infant vaccines

    PubMed Central

    Libraty, Daniel H.; Zhang, Lei; Woda, Marcia; Acosta, Luz P.; Obcena, AnaMae; Brion, Job D.; Capeding, Rosario Z.

    2014-01-01

    Neonatal Bacille Calmette Guérin (BCG) vaccination has been reported to have beneficial effects beyond preventing infantile tuberculous meningitis and miliary disease. We hypothesized that BCG vaccine given at birth would enhance T-helper 1 (Th1) immune responses to the first vaccines given later in infancy. We conducted a nested case-control study of neonatal BCG vaccination and its heterologous Th1 immune effects in 2–3 months old infants. BCG vaccination at birth was associated with an increased frequency of interferon-? (IFN-?) producing spot-forming cells (SFC) to tetanus toxoid 2–3 months later. The frequency of IFN-? producing SFC to polioviruses 1–3 also trended higher among infants who received BCG vaccination at birth. The frequency of IFN-?+/tumor necrosis factor-? (TNF-?)+CD45RO+CD4+ T-cells upon stimulation with phorbol myristate acetate (PMA)/Ionomycin was higher in 2–3 months old infants who received BCG vaccination at birth compared to those who did not. The circulating frequency of forkhead box P3 (FoxP3)+ CD45RO+ regulatory CD4+ T-cells also trended lower in these infants. Neonatal BCG vaccination is associated with heterologous Th1 immune effects 2–3 months later. PMID:24611083

  10. Botulism and vaccines for its prevention.

    PubMed

    Smith, Leonard A

    2009-11-01

    Botulism is a severe neuroparalytic disease caused by toxins produced by several Clostridium species. Botulinum toxin has been of concern to the US military and its allies as a biowarfare weapon since World War II and, in more recent times, by the Centers for Disease Control and Prevention (CDC) as a potential bioterrorist threat to the public. The most effective means of defending against the toxin is by inducing a protective immune response through vaccination. Vaccination with an appropriate antigen will produce neutralizing antibodies that will bind to and clear toxin from the circulation before it can enter nerve cells and block neurotransmission. Immunity from botulism, however, has the disadvantage of precluding an individual from realizing the potential benefits of therapeutic botulinum toxin, if such a need were to arise. Botulinum toxin has been used in the treatment of numerous neuromuscular, autonomic, and sensory disorders since it was first approved for the management of strabismus and blepharospasm by the Food and Drug Administration (FDA) in 1989. Notwithstanding the value of the neurotoxin as a therapeutic drug, vaccines have been and will continue to be an important line of defense for those who work with the toxin (at-risk workers) and a select population of the military, law enforcement, and first responders. The first vaccine used to protect against botulinum neurotoxin was a chemically detoxified extract from Clostridium botulinum. A Pentavalent botulinum toxoid (PBT) vaccine in service today is administered under an Investigational New Drug (IND) application held by the CDC. Recombinant subunit vaccines are in development and a bivalent H(c) vaccine (rBV A/B (Pichia pastoris)) is presently being evaluated in a phase II clinical trial. This review focuses on botulism and the development of vaccines for its prevention. PMID:19837283

  11. Vaccination coverage among children in kindergarten - United States, 2012-13 school year.

    PubMed

    2013-08-01

    State and local school vaccination requirements are implemented to maintain high vaccination coverage and minimize the risk from vaccine preventable diseases. To assess school vaccination coverage and exemptions, CDC annually analyzes school vaccination coverage data from federally funded immunization programs. These awardees include 50 states and the District of Columbia (DC), five cities, and eight U.S.-affiliated jurisdictions. This report summarizes vaccination coverage from 48 states and DC and exemption rates from 49 states and DC for children entering kindergarten for the 2012-13 school year. Forty-eight states and DC reported vaccination coverage, with medians of 94.5% for 2 doses of measles, mumps, and rubella (MMR) vaccine; 95.1% for local requirements for diphtheria, tetanus toxoid, and acellular pertussis (DTaP) vaccination; and 93.8% for 2 doses of varicella vaccine among awardees with a 2-dose requirement. Forty-nine states and DC reported exemption rates, with the median total of 1.8%. Although school entry coverage for most awardees was at or near national Healthy People 2020 targets of maintaining 95% vaccination coverage levels for 2 doses of MMR vaccine, 4 doses of DTaP† vaccine, and 2 doses of varicella vaccine, low vaccination and high exemption levels can cluster within communities, increasing the risk for disease. Reports to CDC are aggregated at the state level; however, local reporting of school vaccination coverage might be accessible by awardees. These local-level data can be used to create evidence-based health communication strategies to help parents understand the risks for vaccine-preventable diseases and the benefits of vaccinations to the health of their children and other kindergarteners. PMID:23903595

  12. Efficacy of an anti-fertility vaccine based on mammalian gonadotrophin releasing hormone (GnRH-I)--a histological comparison in male animals.

    PubMed

    Ferro, V A; Khan, M A H; McAdam, D; Colston, A; Aughey, E; Mullen, A B; Waterston, M M; Harvey, M J A

    2004-09-01

    A N-terminal modified gonadotrophin releasing hormone (GnRH-I, tetanus toxoid-CHWSYGLRPG-NH2) conjugate was evaluated histologically in a number of male animal species (mice, dogs and sheep). The immunogen has previously been shown to be highly effective in rats, by suppressing both steroidogenesis and spermatogenesis. However, cross-species efficacy of peptide vaccines is known to be highly variable. Therefore, a comparative evaluation of reproductive tissues from animals immunized against this immunogen adsorbed onto an alum-based adjuvant was made. The sheep and dogs were chosen, as use of anti-fertility vaccines in these species is important in farming and veterinary practice. Changes in testicular size were measured during the immunization period and the greatest alteration (attributed to gonadal atrophy) was observed in the rat. Following euthanasia, the testicular tissue was evaluated for spermatogenesis. The most susceptible species to GnRH-I ablation was the rat, which showed significant (P < 0.0001) arrest in spermatogenesis compared with untreated controls. Testicular sections taken from treated animals were completely devoid of spermatozoa or spermatids, in comparison with 94% of the untreated controls showing evidence of spermatogenesis. The immunized mice and rams also showed significant arrest (P < 0.0001). There was a 30-45% decrease in spermatogenesis and total azoospermia was not apparent. However, the least responsive were the dogs, which showed little significant variation compared to untreated animals and only a 5% decrease in activity. A comparison of the specific IgG response to GnRH-I indicated that in sheep and dogs the response was not maintained, unlike in rodents, suggesting that suppression of fertility may be due to differences in immune responses in different animal species. PMID:15261694

  13. Typhoid Vaccine

    MedlinePLUS

    ... risks from typhoid vaccine?Like any medicine, a vaccine could cause a serious problem, such as a severe allergic reaction. The risk of typhoid vaccine causing serious harm, or death, is extremely small. ...

  14. Vaccine Shortages

    MedlinePLUS

    ... part of their regular immunizations) and others. What causes vaccine shortages? A vaccine shortage can occur for many ... quickly enough. Often, a combination of these factors causes a vaccine shortage in one or more areas of the ...

  15. Treatment with staphylococcus toxoid in fibromyalgia/chronic fatigue syndrome--a randomised controlled trial.

    PubMed

    Zachrisson, Olof; Regland, Björn; Jahreskog, Marianne; Jonsson, Michael; Kron, Margareta; Gottfries, Carl-Gerhard

    2002-01-01

    We have previously conducted a small treatment study on staphylococcus toxoid in fibromyalgia (FM) and chronic fatigue syndrome (CFS). The aim of the present study was to further assess the efficacy of the staphylococcus toxoid preparation Staphypan Berna (SB) during 6 months in FM/CFS patients. One hundred consecutively referred patients fulfilling the ACR criteria for FM and the 1994 CDC criteria for CFS were randomised to receive active drug or placebo. Treatment included weekly injections containing 0.1 ml, 0.2 ml, 0.3 ml, 0.4 ml, 0.6 ml, 0.8 ml, 0.9 ml, and 1.0 ml SB or coloured sterile water, followed by booster doses given 4-weekly until endpoint. Main outcome measures were the proportion of responders according to global ratings and the proportion of patients with a symptom reduction of > or =50% on a 15-item subscale derived from the comprehensive psychopathological rating scale (CPRS). The treatment was well tolerated. Intention-to-treat analysis showed 32/49 (65%) responders in the SB group compared to 9/49 (18%) in the placebo group (P<0.001). Sixteen patients (33%) in the SB group reduced their CPRS scores by at least 50% compared to five patients (10%) in the placebo group (P< 0.01). Mean change score on the CPRS (95% confidence interval) was 10.0 (6.7-13.3) in the SB group and 3.9 (1.1-6.6) in the placebo group (P<0.01). An increase in CPRS symptoms at withdrawal was noted in the SB group. In conclusion, treatment with staphylococcus toxoid injections over 6 months led to significant improvement in patients with FM and CFS. Maintenance treatment is required to prevent relapse. PMID:12413434

  16. 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

  17. The Impact of Vaccination on Rhinosinusitis and Otitis Media

    Microsoft Academic Search

    Michael S. Benninger; Ryan Manz

    2010-01-01

    Routine childhood vaccination has affected frequency and bacteriology of acute otitis media (AOM) and acute bacterial rhinosinusitis\\u000a (ABRS). Routine influenza vaccination moderately reduces AOM, and the Haemophilus influenzae type b vaccine likely had a minor role in AOM and ABRS. The conjugated pneumococcal vaccine has drastically reduced invasive\\u000a pneumococcal disease and caused a moderate decrease in AOM and, likely, ABRS.

  18. 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

  19. Evaluation of synergistic effect of biodegradable polymeric nanoparticles and aluminum based adjuvant for improving vaccine efficacy.

    PubMed

    Bansal, Vivek; Kumar, Manoj; Dalela, Manu; Brahmne, H G; Singh, Harpal

    2014-08-25

    Aluminum based adjuvants have been used widely to induce long lasting protective immunity through vaccination. But reported incidences of toxicity and side effects of aluminum have raised concerns regarding their safety in childhood vaccines. The present study demonstrates the synergistic effect of admixture of polylactic acid-polyethylene glycol (PLA-PEG) based biodegradable nanoparticles (NPs) and aluminum phosphate as a potential adjuvant system using tetanus toxoid (TT) as a model antigen. The immunological activity of the admixture formulation was maintained up to 180 days of storage at 5 °C±3 °C. Percent adsorption/encapsulation of tetanus toxoid increased to nearly 90% in admixture formulation as compared to 55% in conventional vaccine. Admixture preparation (PLA-PEG-Al 0.2 mg-TT and PLA-Al 0.2 mg-TT) showed 80% and 50% survival respectively, even at 180 days as compared to 30% survival observed in the conventional tetanus vaccine. The present study established the feasibility to formulate a dosage form with improved efficacy and reduced aluminum concentration for vaccination. PMID:24939616

  20. Anthrax vaccines.

    PubMed

    Splino, Miroslav; Patocka, Jiri; Prymula, Roman; Chlibek, Roman

    2005-01-01

    Anthrax, an uncommon disease in humans, is caused by a large bacterium, Bacillus anthracis. The risk of inhalation infection is the main indication for anthrax vaccination. Pre-exposure vaccination is provided by an acellular vaccine (anthrax vaccine adsorbed or AVA), which contains anthrax toxin elements and results in protective immunity after 3 to 6 doses. Anthrax vaccine precipitated (AVP) is administered at primovaccination in 3 doses with a booster dose after 6 months. To evoke and maintain protective immunity, it is necessary to administer a booster dose once at 12 months. In Russia, live spore vaccine (STI) has been used in a two-dose schedule. Current anthrax vaccines show considerable local and general reactogenicity (erythema, induration, soreness, fever). Serious adverse reactions occur in about 1% of vaccinations. New second-generation vaccines in current research programs include recombinant live vaccines and recombinant sub-unit vaccines. PMID:15977694

  1. 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.

  2. Vaccines for low-income countries.

    PubMed

    MacLennan, Calman A

    2013-04-01

    Low-income countries typically lag behind industrialised nations, where the introduction of new vaccines is commonly tailored to the pressures of the commercial market. Happily in recent years this paradigm has started to change with the introduction of a univalent meningococcal A conjugate vaccine that is specifically targeted for the prevention of epidemic meningitis in Africa. The declaration of the 2010s as a New Decade of Vaccines, together with Millennium Development Goals 4 and 5, provide a strong mandate for a new approach to the development of vaccines for low-income countries, so that there has never been a more exciting time to work in this field. This review considers the opportunities and challenges of developing these new vaccines in the context of innovations in vaccinology, the need to induce protective immunity in the populations at risk and the requirement for strong partnership between the countries that will use these vaccines and different elements of the vaccine industry. PMID:23757292

  3. Development of Streptococcus pneumoniae Vaccines Using Live Vectors

    PubMed Central

    Wang, Shifeng; Curtiss, Roy

    2014-01-01

    Streptococcus pneumoniae still causes severe morbidity and mortality worldwide, especially in young children and the elderly. Much effort has been dedicated to developing protein-based universal vaccines to conquer the current shortcomings of capsular vaccines and capsular conjugate vaccines, such as serotype replacement, limited coverage and high costs. A recombinant live vector vaccine delivering protective antigens is a promising way to achieve this goal. In this review, we discuss the researches using live recombinant vaccines, mainly live attenuated Salmonella and lactic acid bacteria, to deliver pneumococcal antigens. We also discuss both the limitations and the future of these vaccines. PMID:25309747

  4. A PHASE IV OPEN LABEL STUDY TO ASSESS THE SAFETY, TOLERABILITY AND IMMUNOGENICITY OF A HAEMOPHILUS INFLUENZAE TYPE B (HIB) CRM197 CONJUGATED VACCINE ADMINISTERED TO HEALTHY INFANTS AT 2, 4, AND 6 MONTHS OF AGE

    Microsoft Academic Search

    Chitsanu Pancharoen; Jutarat Mekmullica; Massimo Bianchini

    The objective of this prospective clinical study was to evaluate the safety, tolerability and immunogenicity of Chiron Hib vaccine (Vaxem Hib ® ) in Thai infants. This trial was conducted at Bhumibol Adulyadej Hospital, Bangkok, Thailand from June to November 1999. Three intramuscu- lar injections of the vaccine were given to 119 infants at 2, 4 and 6 months of

  5. Microneedle patches for vaccine delivery

    PubMed Central

    Suh, Hyemee; Shin, Juhyung

    2014-01-01

    In today's medical industry, the range of vaccines that exist for administration in humans represents an eclectic variety of forms and immunologic mechanisms. Namely, these are the live attenuated viruses, inactivated viruses, subunit proteins, and virus-like particles for treating virus-caused diseases, as well as the bacterial-based polysaccharide, protein, and conjugated vaccines. Currently, a new approach to vaccination is being investigated with the concept of DNA vaccines. As an alternative delivery route to enhance the vaccination efficacy, microneedles have been devised to target the rich network of immunologic antigen-presenting cells in the dermis and epidermis layers under the skin. Numerous studies have outlined the parameters of microneedle delivery of a wide range of vaccines, revealing comparable or higher immunogenicity to conventional intramuscular routes, overall level of stability, and dose-sparing advantages. Furthermore, recent mechanism studies have begun to successfully elucidate the biological mechanisms behind microneedle vaccination. This paper describes the current status of microneedle vaccine research. PMID:24427762

  6. Impaired human responses to tetanus toxoid in vitamin A-deficient SCID mice reconstituted with human peripheral blood lymphocytes.

    PubMed Central

    Molrine, D C; Polk, D B; Ciamarra, A; Phillips, N; Ambrosino, D M

    1995-01-01

    Vitamin A deficiency is associated with increased childhood morbidity and mortality from respiratory and diarrheal diseases. In order to evaluate the effect of vitamin A on human antibody responses, we developed a vitamin A-deficient severe combined immunodeficient (SCID) mouse model. Vitamin A-deficient mice were produced by depriving them of vitamin A at day 7 of gestation. Mice were reconstituted with human peripheral blood lymphocytes (huPBL) from tetanus toxoid immune donors at 6 weeks of age and immunized with tetanus toxoid at 6 and 8 weeks of age. Secondary human antibody responses were determined 10 days later. The geometric mean human anti-tetanus toxoid immunoglobulin G concentrations were 3.75 micrograms/ml for the deficient mice and 148 micrograms/ml for controls (P = 0.0005). Vitamin A-deficient mice had only a 2.9-fold increase in human anti-tetanus toxoid antibody compared with a 74-fold increase in controls (P < 0.01). Supplementation with vitamin A prior to reconstitution restored human antibody responses to normal. These data suggest that vitamin A deficiency impairs human antibody responses. We speculate that impaired responses could increase susceptibility to certain infections. Furthermore, we propose that effects of other nutritional deficiencies on the human immune system could be evaluated in the SCID-huPBL model. PMID:7622207

  7. Development of a freeze-stable formulation for vaccines containing aluminum salt adjuvants.

    PubMed

    Braun, LaToya Jones; Tyagi, Anil; Perkins, Shalimar; Carpenter, John; Sylvester, David; Guy, Mark; Kristensen, Debra; Chen, Dexiang

    2009-01-01

    Vaccines containing aluminum salt adjuvants are prone to inactivation following exposure to freeze-thaw stress. Many are also prone to inactivation by heat. Thus, for maximum potency, these vaccines must be maintained at temperatures between 2 degrees C and 8 degrees C which requires the use of the cold chain. Nevertheless, the cold chain is not infallible. Vaccines are subject to freezing during both transport and storage, and frozen vaccines are discarded (under the best circumstances) or inadvertently administered despite potentially reduced potency. Here we describe an approach to minimize our reliance on the proper implementation of the cold chain to protect vaccines from freeze-thaw inactivation. By including PEG 300, propylene glycol, or glycerol in a hepatitis B vaccine, particle agglomeration, changes in the fluorescence emission spectrum--indicative of antigen tertiary structural changes--and losses of in vitro and in vivo indicators of potency were prevented following multiple exposures to -20 degrees C. The effect of propylene glycol was examined in more detail and revealed that even at concentrations too low to prevent freezing at -10 degrees C, -20 degrees C, and -80 degrees C, damage to the vaccine could be prevented. A pilot study using two commercially available diphtheria, tetanus toxoid, and acellular pertussis (DTaP) vaccines suggested that the same stabilizers might protect these vaccines from freeze-thaw agglomeration as well. It remains to be determined if preventing agglomeration of DTaP vaccines preserves their antigenic activity following freeze-thaw events. PMID:18973782

  8. VACCINE INFORMATION STATEMENT Influenza Vaccine

    E-print Network

    Oklahoma, University of

    VACCINE INFORMATION STATEMENT Influenza Vaccine What You Need to Know (Flu Vaccine, Live idiomas. Visite www.immunize.org/vis 1 Why get vaccinated? Influenza ("flu") is a contagious disease by the influenza virus, and can be spread by coughing, sneezing, and close contact. Anyone can get flu

  9. VACCINE INFORMATION STATEMENT Influenza Vaccine

    E-print Network

    Oklahoma, University of

    VACCINE INFORMATION STATEMENT Influenza Vaccine What You Need to Know (Flu Vaccine, Inactivated.immunize.org/vis 1 Why get vaccinated? Influenza ("flu") is a contagious disease that spreads around the United States every winter, usually between October and May. Flu is caused by the influenza virus, and can

  10. VACCINE INFORMATION STATEMENT Influenza Vaccine

    E-print Network

    Lien, Jyh-Ming

    VACCINE INFORMATION STATEMENT Influenza Vaccine What You Need to Know (Flu Vaccine, Inactivated idiomas. Visite www.immunize.org/vis 1 Why get vaccinated? Influenza ("flu") is a contagious disease that spreads around the United States every winter, usually between October and May. Flu is caused by influenza

  11. Safety and immunogenicity of a combined five-component pertussis-diphtheria-tetanus-inactivated poliomyelitis- Haemophilus b conjugate vaccine administered to infants at two, four and six months of age

    Microsoft Academic Search

    Elaine Mills; Ronald Gold; John Thipphawong; Luis Barreto; Roland Guasparini; William Meekison; Les Cunning; Margaret Russell; Dana Harrison; Melody Boyd; Fang Xie

    1998-01-01

    Safety, immunogenicity and lot consistency of five-component pertussis combination vaccine (CPDT-IPV\\/PRP-T) in infants were compared to that of whole cell pertussis combination vaccine (DPT-IPV\\/\\/PRP-T), as were separate and combined injections of CPDT-IPV and PRP-T. No significant differences in adverse event rates were observed between lots of CPDT-IPV\\/\\/PRP-T or between separate or combined injections of CPDT-IPV and PRP-T. Minor differences in

  12. [Vaccines, immunization and technological innovation: an update].

    PubMed

    Homma, Akira; Martins, Reinaldo de Menezes; Leal, Maria da Luz Fernandes; Freire, Marcos da Silva; Couto, Artur Roberto

    2011-02-01

    The smallpox worldwide eradication was the major world public health achievement. The binomial - vaccines and immunization - continues to demonstrate very high performance in the prevention and control of other diseases preventable by vaccination. The new global initiatives on vaccination, such as GAVI, have made possible the introduction of new and important vaccines preventing million of children deaths in the poorest countries in the world. The National Immunization Program of Brazil is also being strengthened, with the introduction of several new vaccines into the basic calendar as rotavirus, pneumococcal and meningococcal conjugated and H1N1 in national campaign, covering the population at risk. With the discovery of high valued vaccines, the big pharmaceutical companies became interested in this area, investing heavily in technological innovation, making fusions, acquisitions and technological partnerships. Brazil has also established a new innovation policy, creating new laws as well as subsidizing projects in technological innovation and modernization of production infra-structure. PMID:21340320

  13. 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.

  14. Protective vaccination with a recombinant fragment of Clostridium botulinum neurotoxin serotype A expressed from a synthetic gene in Escherichia coli.

    PubMed Central

    Clayton, M A; Clayton, J M; Brown, D R; Middlebrook, J L

    1995-01-01

    A completely synthetic gene encoding fragment C, a approximately 50-kDa fragment, of botulinum neurotoxin serotype A was constructed from oligonucleotides. The gene was expressed in Escherichia coli, and full-sized product was produced as judged by Western blot (immunoblot) analysis. Crude extracts of E. coli expressing the gene were used to vaccinate mice and evaluate their survival against challenge with active toxin. Mice given three subcutaneous vaccinations were protected against an intraperitoneal administration of 10(6) 50% lethal doses (ID50) of serotype A toxin. The same mice survived when challenged with 3 LD50 of botulinum toxin serotype E but died when challenged with 10 LD50 of serotype E or 3 LD50 of serotype B. Purified fragment C was compared with the botulinum toxoid vaccine in a vaccination and challenge study. Fragment C was as efficacious in protecting against challenge with active botulinum neurotoxin serotype A as the toxoid vaccine. This recombinant protein product has many properties that make it a good candidate for human use to protect against botulinum toxin. PMID:7790092

  15. Vaccine Finder

    MedlinePLUS

    ... Vaccine Information Statement for Shingles . Tetanus, Diphtheria, Whooping Cough (Tdap) Protects against whooping cough (pertussis), a very ... Vaccine Information Statement for Td . Tetanus, Diphtheria, Whooping Cough Tetanus, Diphtheria, Whooping Cough (Tdap) Protects against whooping ...

  16. The monoclonal antibody 26 raised against tetanus toxoid also recognizes tetanus toxin and ?2-glycoprotein I - its binding properties in vitro and potential applications

    Microsoft Academic Search

    ALEKSANDRA B. INI?-KANADA; MARIJANA M. STOJANOVI?; Irena Zivkovic; Vladimir Petrusic; Ljiljana Dimitrijevic

    2009-01-01

    A murine monoclonal IgG1 antibody, marked as MAb26, specific for tetanus toxoid has been immunochemically characterized. By performing en- zyme-linked immunosorbent assays (ELISAs) and western blot analyses, it was demonstrated that MAb26 reacted with tetanus toxoid, tetanus toxin and ?2-gly- coprotein I (?2GPI). According to the results, MAb26 recognized the sequential epitope on the tetanus heavy chain. The affinity constant,

  17. Pneumococcal vaccine and opsonic pneumococcal antibody.

    PubMed

    Song, Joon Young; Moseley, M Allen; Burton, Robert L; Nahm, Moon H

    2013-06-01

    Streptococcus pneumoniae is a major human pathogen responsible for the majority of bacterial pneumonia cases as well as invasive pneumococcal diseases with high mortality and morbidity. Use of conjugate vaccines targeting the pneumococcal capsule has dramatically reduced the incidence of invasive diseases, and there are active efforts to further improve the conjugate vaccines. However, in children new pneumococcal vaccines can no longer be tested with placebo-based clinical trials because effective vaccines are currently available. Thus, vaccine studies must depend on surrogate markers of vaccine efficacy. Although traditional antibody levels (e.g., ELISA) are useful as a surrogate marker of protection, they have limitations, and a bioassay measuring the capacity of antibodies to opsonize pneumococci has been developed. This opsonophagocytosis assay (OPA) replicates the in vivo mechanism of antibody protection and should therefore better reflect protection by vaccine-induced antibodies. Technical improvements of OPA have made this bioassay rapid, multiplexed, and practical for analyzing small samples including those from children. Strong correlations between ELISA and OPA have been observed in many studies of young children. However, poor correlations have been found in some important clinical situations (such as determination of protection by cross-reactive antibodies) and populations (such as elderly adults and immunodeficient patients). In these settings, OPA has become a useful supplementary measure of pneumococcal vaccine immunogenicity. Current efforts to standardize OPA will further expand its uses. PMID:23657429

  18. Recent developments in vaccines to prevent meningococcal serogroup B infections.

    PubMed

    Vermont, Clementien L; van den Dobbelsteen, Germie P J M; de Groot, Ronald

    2003-02-01

    Meningococcal disease in most western countries is mainly caused by serogroup B. Despite the availability of successful meningococcal serogroup C conjugate vaccines, there is no effective vaccine against serogroup B. Efficacy trials with outer membrane vesicle (OMV) vaccines were ineffective and are complicated by the high variability of its main component, porin A. Several new approaches to either optimizing these OMV vaccines or searching for new, highly conserved antigens are therefore being investigated. The completion of the meningococcal genome sequence has provided new challenges. This review summarizes recent developments in the search for a broadly protective meningococcal serogroup B vaccine. PMID:12669468

  19. Recombinant cholera toxin B subunit (rCTB) as a mucosal adjuvant enhances induction of diphtheria and tetanus antitoxin antibodies in mice by intranasal administration with diphtheria-pertussis-tetanus (DPT) combination vaccine.

    PubMed

    Isaka, Masanori; Komiya, Takako; Takahashi, Motohide; Yasuda, Yoko; Taniguchi, Tooru; Zhao, Yanqiu; Matano, Keiko; Matsui, Hideyuki; Maeyama, Jun-Ichi; Morokuma, Kazunori; Ohkuma, Kunio; Goto, Norihisa; Tochikubo, Kunio

    2004-08-13

    Recombinant cholera toxin B subunit (rCTB) which is produced by Bacillus brevis carrying pNU212-CTB acts as a mucosal adjuvant capable of enhancing host immune responses specific to unrelated, mucosally co-administered vaccine antigens. When mice were administered intranasally with diphtheria-pertussis-tetanus (DPT) combination vaccine consisting of diphtheria toxoid (DTd), tetanus toxoid (TTd), pertussis toxoid (PTd), and formalin-treated filamentous hemagglutinin (fFHA), the presence of rCTB elevated constantly high values of DTd- and TTd-specific serum ELISA IgG antibody titres, and protective levels of diphtheria and tetanus toxin-neutralizing antibodies but the absence of rCTB did not. Moreover, the addition of rCTB protected all mice against tetanic symptoms and deaths. DPT combination vaccine raised high levels of serum anti-PT IgG antibody titres regardless of rCTB and protected mice from Bordetella pertussis challenge. These results suggest that co-administration of rCTB as an adjuvant is necessary for induction of diphtheria and tetanus antitoxin antibodies on the occasion of intranasal administration of DPT combination vaccine. PMID:15297056

  20. Smallpox Vaccine

    MedlinePLUS

    ... outbreak of the disease. In most cases, the vaccine causes mild side effects, such as soreness around the vaccination site, fever, and body aches. A very small percentage of people will suffer serious side effects and may even die. Thus the vaccine is only necessary when there has been an ...

  1. 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

  2. Oral vitamin A and retinoic acid supplementation stimulates antibody production and splenic Stra6 expression in tetanus toxoid-immunized mice.

    PubMed

    Tan, Libo; Wray, Amanda E; Ross, A Catharine

    2012-08-01

    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

  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. 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.

  5. Safety and immunogenicity of fully liquid DTaP?-IPV-Hib pediatric combination vaccine (Pediacel®) compared to DTaP?-HBV-IPV/Hib (Infanrix® Hexa) when coadministered with heptavalent pneumococcal conjugate vaccine (PCV7) as a booster at 11-18 months of age: a phase III, modified double-blind, randomized, controlled, multicenter study.

    PubMed

    Berner, Reinhard; Boisnard, Florence; Thomas, Stéphane; Mwawasi, Grace; Reynolds, Donna

    2012-07-27

    This study compared the safety and immunogenicity of DTaP?-IPV-Hib vaccine (followed by monovalent hepatitis B vaccine [HBV]) and DTaP?-HBV-IPV/Hib vaccines, both coadministered with PCV7, as a fourth-dose booster in toddlers 11-18 months who had a hexavalent vaccine primary series. The fever rate within 4 days of DTaP?-IPV-Hib was noninferior to DTaP?-HBV-IPV/Hib. DTaP?-IPV-Hib induced a marked immune response and had a similar safety and immunogenicity profile compared with DTaP?-HBV-IPV/Hib. Fully liquid DTaP?-IPV-Hib can be used as a booster after a hexavalent vaccine primary series; where required, a fourth dose of monovalent HBV can be administered after DTaP?-IPV-Hib (NCT ID: NCT00355654). PMID:22691430

  6. Anti-Tetanus Toxoid Antibody Production and Protection against Lethal Doses of Tetanus Toxin in hu-PBL-SCID Mice

    Microsoft Academic Search

    Seishiro Naito; Yoshiaki Okada; Motohide Takahashi; Hiroshi Kato; Maiko Taneichi; Yasushi Ami; Yuriko Suzaki; Tetsuya Oka; Kunio Okuma; Kazunori Morokuma; Hideki Onodera; Masayoshi Inoue; Yoshiharu Takahashi; Setuko Yamazaki; Hitoshi Kimura; Katsutoshi Komuro; Tetsuya Uchida

    2000-01-01

    Background: In this study, severe combined immunodeficiency (SCID) mice, which permit the survival of lymphoid cells of human origin, were used to study the human anti-tetanus immune response. Methods: Human peripheral blood lymphocytes (hu-PBL) obtained from 88 healthy donors (aged from 18 to 62) were transplanted into SCID mice, and anti-tetanus toxoid (Ttd) antibody production and protection against lethal doses

  7. A serogroup A meningococcal polysaccharide vaccine: studies in the Sudan to combat cerebrospinal meningitis caused by Neisseria meningitidis group A.

    PubMed

    Erwa, H H; Haseeb, M A; Idris, A A; Lapeyssonnie, L; Sanborn, W R; Sippel, J E

    1973-01-01

    Vaccination against cerebrospinal meningitis (CSM) has regained interest with the use of capsular polysaccharides (or polyosides) of the meningococcus as specific immunizing agents. These compounds proved to be effective in the USA against meningitis caused by Neisseria meningitidis serotype C. This study considers whether the polysaccharides of the serotype A meningococcus, which is prevalent in the African CSM belt, could be protective in epidemic conditions. Taking advantage of the usual seasonal peak of CSM cases, controlled field trials were undertaken in the Sudan early in 1973. 21 640 persons were vaccinated, half of them with a meningococcal polyoside A vaccine and the other half with tetanus toxoid as a placebo. In the former group there were no cases of meningitis, whereas in the latter 10 cases were reported, of which 7 were confirmed by laboratory tests. These studies indicate that the meningococcal polyoside A vaccine is efficient in epidemic conditions and could be used to control outbreaks of meningococcal meningitis. PMID:4211056

  8. 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...

  9. Vaccine allergies

    PubMed Central

    2014-01-01

    Currently, the increasing numbers of vaccine administrations are associated with increased reports of adverse vaccine reactions. Whilst the general adverse reactions including allergic reactions caused by the vaccine itself or the vaccine components, are rare, they can in some circumstances be serious and even fatal. In accordance with many IgE-mediated reactions and immediate-type allergic reactions, the primary allergens are proteins. The proteins most often implicated in vaccine allergies are egg and gelatin, with perhaps rare reactions to yeast or latex. Numerous studies have demonstrated that the injectable influenza vaccine can be safely administered, although with appropriate precautions, to patients with severe egg allergy, as the current influenza vaccines contain small trace amounts of egg protein. If an allergy is suspected, an accurate examination followed by algorithms is vital for correct diagnosis, treatment and decision regarding re-vaccination in patients with immediate-type reactions to vaccines. Facilities and health care professionals should be available to treat immediate hypersensitivity reactions (anaphylaxis) in all settings where vaccines are administered. PMID:24427763

  10. Immunogenicity of Well-Characterized Synthetic Plasmodium falciparum Multiple Antigen Peptide Conjugates

    Microsoft Academic Search

    MANJU B. JOSHI; ALBERT A. GAM; ROBERT A. BOYKINS; SANJAI KUMAR; JOHN SACCI; STEPHEN L. HOFFMAN; HIRA L. NAKHASI; RICHARD T. KENNEY

    2001-01-01

    Given the emerging difficulties with malaria drug resistance and vector control, as well as the persistent lack of an effective vaccine, new malaria vaccine development strategies are needed. We used a novel methodology to synthesize and fully characterize multiple antigen peptide (MAP) conjugates containing protective epitopes from Plasmodium falciparum and evaluated their immunogenicity in four different strains of mice. A

  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. Hepatitis B Vaccine

    MedlinePLUS

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

  13. Vaccine Production

    Microsoft Academic Search

    Jack Melling

    \\u000a The biotechnology revolution which began in the 1970s with the advent of genetic engineering, coupled with major developments\\u000a in fermentation and downstream processing technology, has had major impacts on research, development and production of vaccines.\\u000a In the case of vaccine production, the effect of recombinant DNA techniques has been to make vaccines available against agents\\u000a where previously production and isolation

  14. Conjugate Gaze Palsies

    MedlinePLUS

    ... Nerve Disorders Overview of the Cranial Nerves Internuclear Ophthalmoplegia Conjugate Gaze Palsies Palsies of Cranial Nerves That ... Nerve Disorders Overview of the Cranial Nerves Internuclear Ophthalmoplegia Conjugate Gaze Palsies Palsies of Cranial Nerves That ...

  15. DTPa-HBV-IPV/Hib vaccine (Infanrix hexa™): a guide to its use in infants.

    PubMed

    Lyseng-Williamson, Katherine A; Dhillon, Sohita

    2012-10-01

    Infanrix hexa™, a diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated poliomyelitis, and Haemophilus influenzae type b (Hib) conjugate vaccine, is indicated for primary and booster vaccination of infants. Available clinical data from more than a decade of experience with the vaccine indicate that primary and booster vaccination with Infanrix hexa™ is a safe and useful option for providing protection against the common childhood diseases of diphtheria, tetanus, poliomyelitis, pertussis, hepatitis B, and disease caused by Hib. PMID:22873778

  16. EVALUATION OF GNRH CONTRACEPTIVE VACCINE USING DOMESTIC SWINE AS A MODEL FOR FERAL HOGS

    Microsoft Academic Search

    LOWELL MILLER; JACK RHYAN; GARY KILLIAN

    We determined the effect of a GnRH vaccine on reproductive function of sexually mature 5-month female and male domestic swine. The vaccine, GonaConTM, developed at NWRC contains a GnRH peptide conjugated to KLH, combined with AdjuVacTM adjuvant also developed at NWRC. Four groups of ten females were given single IM immunizations either of 800µg GnRH vaccine, 1600µg GnRH vaccine, a

  17. BCG vaccination.

    PubMed

    Guerin, N; Bregere, P

    1992-01-01

    The practical elements of BCG vaccination in neonates are used in most developing countries are outlined. The World Health Organization that all neonates be vaccinated, as well as all unvaccinated children when they present for health care, without prior PPD testing. BCG vaccine is a live attenuated TB vaccine in lyophilized state, so it must be kept cold and away from light. After redissolving, the vaccine is given intradermally with a 0.45% 10 mm needle either on the volar left forearm or the posterior left arm, at a consistent site in each country. The dose must be 0.05 ml for babies 1 year old, and 0.1 ml for older children. A wheal is formed that disappears in 30 minutes, followed by a red nodule in 3-4 weeks. The depressed scar is evidence of vaccination. In rare cases, lymphadenitis may appear, sometimes with a fistula. This is more likely when 0,1 ml is given to infants, the vaccine is not diluted properly, or the injection is given too deeply. While immunodeficiency is considered a contraindication for BCG vaccination, infants born to HIV-positive mothers have received it without adverse effects. Other immunizations such as oral polio may be given concomitantly. Verification of BCG vaccination is by presence of the scar or PPD testing. About 30-50% of children entering school are still positive; negative children may be revaccinated. PMID:12345145

  18. [Vaccines pharmacovigilance].

    PubMed

    Autret-Leca, Elisabeth; Jonville-Béra, Annie-Pierre; Beau-Salinas, Frédérique

    2004-03-15

    The pharmacovigilance of vaccines has the particularity of concerning medications with a preventative target, used in healthy subjects, who are often young. Their individual benefit is deferred and unknown, whereas their risk is immediate. Certain undesirable effects are linked to the antigen of live attenuated vaccines (post-MMR lymphocytic meningitis). Other non-specific effects are linked to other different components of the vaccines (macrophage and aluminium myofasciitis). Undesirable events susceptible to being due to the vaccination are identified and managed according to standardised procedures of pharmacovigilance, that is to say, based on "spontaneous notification", generation of an alert, confirmed or not by studies of pharmaco-epidemiology. The studies of pharmaco-epidemiology: have made evident oedematous reactions with cyanosis or purpura, with the vaccines containing the Haemophilus b valence, and the absence of an association with sudden death of the newborn; have excluded the existence of an elevated risk of demyelinisation or auto-immune disease associated with vaccination against hepatitis B, without being able to exclude a slight risk; go against the finding of an association between Crohn's disease and/or autisim and the MMR vaccination. Only their frequently encountered undesirable effects are well identified at the moment of commercialisation. Post-marketing surveillance of vaccines (declaration to the regional pharmacovigilance centres) allow the detection of possible rare and serious effects and the evaluation of the real vaccination risk. Thus it must be intensive and systematic. PMID:15176512

  19. Etiology and antimicrobial susceptibility of middle ear fluid pathogens in Costa Rican children with otitis media before and after the introduction of the 7-valent pneumococcal conjugate vaccine in the National Immunization Program: acute otitis media microbiology in Costa Rican children.

    PubMed

    Abdelnour, Arturo; Arguedas, Adriano; Dagan, Ron; Soley, Carolina; Porat, Nurith; Castrejon, Maria Mercedes; Ortega-Barria, Eduardo; Colindres, Romulo; Pirçon, Jean-Yves; DeAntonio, Rodrigo; Van Dyke, Melissa K

    2015-01-01

    Acute otitis media (AOM) microbiology was evaluated in children after 7-valent pneumococcal conjugate vaccine (PCV7) introduction in Costa Rica (private sector, 2004; National Immunization Program, 2009). This was a combined prospective and retrospective study conducted in a routine clinical setting in San José, Costa Rica. In the prospective part of the study, which was conducted post-PCV7 introduction (2010-2012), standard bacteriological procedures were used to evaluate the etiology and serotype distribution of middle ear fluid samples collected by tympanocentesis or otorrhea from children aged 3-59 months diagnosed with AOM. E-tests were used to evaluate antimicrobial susceptibility in culture-positive samples. Retrospective data recorded between 1999 and 2004 were used for comparison of bacterial etiology and serotype distribution before and after PCV7 introduction. Statistical significance was evaluated in bivariate analyses at the P-value < 0.05 level (without multiplicity correction). Post-PCV7 introduction, Haemophilus influenzae was detected in 118/456 and Streptococcus pneumoniae in 87/456 AOM episodes. Most H. influenzae isolates (113/118) were non-typeable. H. influenzae was more (27.4% vs 20.8%) and S. pneumoniae less (17.1% vs 25.5%) frequently observed in vaccinated (? 2 PCV7 doses or ? 1 PCV7 dose at >1 year of age) versus unvaccinated children. S. pneumoniae non-susceptibility rates were 1.1%, 34.5%, 31.7%, and 50.6% for penicillin, erythromycin, azithromycin, and trimethoprim/sulfamethoxazole (TMP-SMX), respectively. H. influenzae non-susceptibility rate was 66.9% for TMP-SMX. Between pre- and post-PCV7 introduction, H. influenzae became more (20.5% vs 25.9%; P-value < 0.001) and S. pneumoniae less (27.7% vs 19.1%; P-value = 0.002) prevalent, and PCV7 serotype proportions decreased among pneumococcal isolates (65.8% vs 43.7%; P-value = 0.0005). Frequently identified pneumococcal serotypes were 19F (34.2%), 3 (9.7%), 6B (9.7%), and 14 (9.7%) pre-PCV7 introduction, and 19F (27.6%), 14 (8.0%), and 35B (8.0%) post-PCV7 introduction. Following PCV7 introduction, a change in the distribution of AOM episodes caused by H. influenzae and pneumococcal serotypes included in PCV7 was observed in Costa Rican children. Pneumococcal vaccines impact should be further evaluated following broader vaccination coverage. PMID:25590837

  20. Irradiation of the Crude Venom of Bothrops jararacussu to Obtain Toxoid

    NASA Astrophysics Data System (ADS)

    Ferreira, Camila G.; Avalloni, Tânia M.; Oshima-Franco, Yoko; de J. Oliveira, Sara; de Oliveira, José M.; Cogo, José C.

    2011-08-01

    The aim of this work was to reduce the toxicity of Bothrops jararacussu venom using gamma-rays of low-energy coming from a source of Americium-241 (E = 59.6 keV and 3.7×109 Bq of activity) in order to obtain a toxoid. The radiation dose that each sample received was controlled by exposure time of the venom to the radiation beam. Mouse nerve phrenic-diaphragm preparation was used for testing the loss of venom toxicity, since the venom causes an irreversible neuromuscular blockade. In this condition, the several samples of irradiated venom, when assayed in neuromuscular preparation showed that with a dose of 0.051 Gy the paralysis caused by the irradiated venom was of 91%, at 0.360 Gy was of 79%, at 1.662 Gy was of 50% and at 2.448 Gy was of 42%. Therefore, it can be concluded that the irradiation model was able to induce a progressive loss of the venom toxicity.

  1. [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

  2. Additional conjugation methods and immunogenicity of Bacillus anthracis poly-gamma-D-glutamic acid-protein conjugates.

    PubMed

    Kubler-Kielb, Joanna; Liu, Teh-Yung; Mocca, Christopher; Majadly, Fathy; Robbins, John B; Schneerson, Rachel

    2006-08-01

    The capsule of Bacillus anthracis, composed of poly-gamma-d-glutamic acid (gammaDPGA), is an essential virulence factor of B. anthracis. The capsule inhibits innate host defense through its antiphagocytic action. gammaDPGA is a poor immunogen, but when covalently bound to a carrier protein, it elicits serum antibodies. To identify the optimal construct for clinical use, synthetic gammaDPGAs of different lengths were bound to carrier proteins at different densities. The advantages of the synthetic over the natural polypeptide are the homogeneous chain length and end groups, allowing conjugates to be accurately characterized and standardized and their chemical compositions to be related to their immunogenicities. In the present study, we evaluated, in addition to methods reported by us, hydrazone, oxime, and thioether linkages between gammaDPGA and several proteins, including bovine serum albumin, recombinant Pseudomonas aeruginosa exotoxin A, recombinant B. anthracis protective antigen (rPA), and tetanus toxoid (TT). The effects of the dosage and formulation on the immunogenicities of the conjugates were evaluated in mice. All conjugates were immunogenic. The optimal gammaDPGA chain length of 10 to 15 amino acids and the density, an average of 15 mol gammaDPGA per mol of protein, were confirmed. The thioether bond was the optimal linkage type, and TT and rPA were the best carriers. The optimal dosage was 1.2 to 2.5 microg of gammaDPGA per mouse, and adsorption of the conjugates onto aluminum hydroxide significantly increased the antibody response to the protein with a lesser effect on anti-gammaDPGA levels. PMID:16861662

  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. 9 CFR 113.110 - Clostridium Botulinum Type C Bacterin-Toxoid.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...intraperitoneally with botulinum Type C toxin which has been titrated in mice to provide for a 104.0 mouse MLD dose. The titration technique shall include inoculation of the mice intraperitoneally. (2) The vaccinates and controls shall be...

  5. 9 CFR 113.110 - Clostridium Botulinum Type C Bacterin-Toxoid.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...intraperitoneally with botulinum Type C toxin which has been titrated in mice to provide for a 104.0 mouse MLD dose. The titration technique shall include inoculation of the mice intraperitoneally. (2) The vaccinates and controls shall be...

  6. 9 CFR 113.110 - Clostridium Botulinum Type C Bacterin-Toxoid.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...intraperitoneally with botulinum Type C toxin which has been titrated in mice to provide for a 104.0 mouse MLD dose. The titration technique shall include inoculation of the mice intraperitoneally. (2) The vaccinates and controls shall be...

  7. Adult vaccination.

    PubMed

    Swanson, Kena A; Schmitt, H Josef; Jansen, Kathrin U; Anderson, Annaliesa S

    2015-01-01

    Vaccination of children has had a major impact on the morbidity and mortality of many infectious diseases globally. However, with age, immune responses to vaccines can be less robust, which can be further enhanced by underlying diseases that are common in the older adult. In many countries around the globe booster vaccinations against diphtheria, tetanus, and pertussis are recommended for adults. For the older adult, vaccination against pneumococcal diseases, influenza and herpes zoster are also recommended. Despite these recommendations, the widespread use of these vaccines in the adult population clearly lags behind the vaccine uptake and successes documented for pediatric vaccination programs. Furthermore, extensive and sometimes inappropriate use of antibiotics have fostered the emergence of antibiotic-resistant bacteria (e.g., methicillin resistant Staphylococcus aureus (MRSA)) as well as increased susceptibility in the elderly to bacterial species such as Clostridium difficile. Infectious diseases remain an important unmet medical need and new concepts to successfully implement vaccination of adults are urgently needed. PMID:25483533

  8. Vi capsular polysaccharide-protein conjugates for prevention of typhoid fever. Preparation, characterization, and immunogenicity in laboratory animals

    PubMed Central

    1987-01-01

    The Vi has proven to be a protective antigen in two double masked, controlled clinical trials in areas with high rates of typhoid fever (approximately 1% per annum). In both studies the protective efficacy of the Vi was approximately 70%. Approximately 75% of subjects in these areas responded with a fourfold or greater rise of serum Vi antibodies. In contrast, the Vi elicited a fourfold or greater rise in 95-100% of young adults in France and the United States. Methods were devised, therefore, to synthesize Vi-protein conjugates in order to both enhance the antibody response and confer T-dependent properties to the Vi (and theoretically increase its protective action in populations at high risk for typhoid fever). We settled on a method that used the heterobifunctional crosslinking reagent, N-succinimidyl-3-(2- pyridyldithio)-propionate (SPDP), to bind thiol derivatives of the Vi to proteins. This synthetic scheme was reproducible, provided high yields of Vi-protein conjugates, and was applicable to several medically relevant proteins such as diphtheria and tetanus toxoids. The resultant conjugates were more immunogenic in mice and juvenile Rhesus monkeys than the Vi alone. In contrast to the T-independent properties of the Vi, conjugates of this polysaccharide with several medically relevant proteins induced booster responses in mice and in juvenile Rhesus monkeys. Clinical studies with Vi-protein conjugates are planned. This scheme is also applicable to synthesize protein conjugates with other polysaccharides that have carboxyl functions. PMID:3681191

  9. Revisiting conjugate schedules.

    PubMed

    MacAleese, Kenneth R; Ghezzi, Patrick M; Rapp, John T

    2015-07-01

    The effects of conjugate reinforcement on the responding of 13 college students were examined in three experiments. Conjugate reinforcement was provided via key presses that changed the clarity of pictures displayed on a computer monitor in a manner proportional to the rate of responding. Experiment 1, which included seven parameters of clarity change per response, revealed that responding decreased as the percentage clarity per response increased for all five participants. These results indicate that each participant's responding was sensitive to intensity change, which is a parameter of conjugate reinforcement schedules. Experiment 2 showed that responding increased during conjugate reinforcement phases and decreased during extinction phases for all four participants. Experiment 3 also showed that responding increased during conjugate reinforcement and further showed that responding decreased during a conjugate negative punishment condition for another four participants. Directions for future research with conjugate schedules are briefly discussed. PMID:26150349

  10. Suppression of the immune response to diphtheria toxoid in murine schistosomiasis.

    PubMed

    Haseeb, M A; Craig, J P

    1997-01-01

    Studies in humans and experimental animals indicate that infection with schistosomes results in impaired immune response to a variety of antigens. Since artificial immunization against a number of infections is frequently attempted in populations in which schistosomiasis is endemic, we have attempted to determine whether this impairment could be demonstrated in response to a commonly used immunogen. We have compared the serum antitoxin response to diphtheria toxoid (DTd) in normal, uninfected mice with that in mice bearing schistosome infections of different duration. Animals were infected with 100 Schistosoma mansoni cercariae 16, 12, 8, 4 and 2 weeks prior to, on the same day as, and 4 weeks after the first of three 1 microgram doses of DTd given at 3 week intervals. The antitoxin level of each mouse was taken as the mean of two sera obtained 1 and 2 weeks after the 3rd dose of DTd. The mean antitoxin level in uninfected-immunized control mice was 0.0457 Antitoxin Units (AU) ml-1. 71% of mice in this group developed antitoxin levels > or = 0.01 AU ml-1. Only 28% of the infected-immunized mice achieved antitoxin levels > or = 0.01 AU ml-1. In infected-immunized mice with infections of all durations, both the percentage of mice with > or = 0.01 AU ml-1 (0 to 50%) and mean antitoxin levels (0.003 to 0.016 AU ml-1) were lower than in uninfected-immunized mice. Antitoxin levels in animals infected 16, 12, 8 and 2 weeks prior to, simultaneously with, and 4 weeks after the first dose of DTd were significantly lower (P = < 0.05) than those of controls. Mice infected 4 weeks prior to the first dose of DTd had antitoxin levels 64% below controls but this difference was not significant. If similar immunosuppression occurs in human schistosomiasis, these findings may have implications for childhood immunization programs in areas where schistosomiasis is endemic. PMID:9041665

  11. Failure of a large dose of vitamin A to enhance the antibody response to tetanus toxoid in children.

    PubMed

    Brown, K H; Rajan, M M; Chakraborty, J; Aziz, K M

    1980-02-01

    Field studies to determine the effects of a large dose of water miscible vitamin A on selected parameters of children's immunological function were completed in rural Bangladesh. There was no difference between vitamin A treated or control groups in tetanus antitoxin responses after tetanus toxoid immunization or in skin test reactivity to common antigens. Subsequent studies with mice demonstrated vitamin A dose-related antitoxin responses, but the animals required amounts of vitamin that would be likely cause undesirable side effects if administered in similar doses to children. PMID:7355795

  12. Vaccine legislation.

    PubMed

    1999-07-23

    Rep. Nancy Pelosi (D-Calif.) has introduced the Lifesaving Vaccine Technology Act of 1999, designed to provide biotechnology and pharmaceutical companies with a 30 percent tax credit for costs associated with vaccine development. Sen. John Kerry (D-Mass.) is drafting similar legislation in the Senate. The tax credits would apply to vaccines for HIV, tuberculosis and malaria, which together kill more than 7 million people worldwide each year. The bill has not made it out of the House Ways and Means Committee; Pelosi hopes to attach the bill to one of several tax-cutting measures scheduled for a vote before the summer congressional recess. PMID:11366597

  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. 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 ...

  15. Oral vaccines

    PubMed Central

    Zhu, Qing; Berzofsky, Jay A.

    2013-01-01

    Oral vaccines are safe and easy to administer and convenient for all ages. They have been successfully developed to protect from many infectious diseases acquired through oral transmission. We recently found in animal models that formulation of oral vaccines in a nanoparticle-releasing microparticle delivery system is a viable approach for selectively inducing large intestinal protective immunity against infections at rectal and genital mucosae. These large-intestine targeted oral vaccines are a potential substitute for the intracolorectal immunization, which has been found to be effective against rectogenital infections but is not feasible for mass vaccination. Moreover, the newly developed delivery system can be modified to selectively target either the small or large intestine for immunization and accordingly revealed a regionalized immune system in the gut. Future applications and research endeavors suggested by the findings are discussed. PMID:23493163

  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. HPV Vaccine

    MedlinePLUS

    ... for Parents for Kids for Teens Teens Home Body Mind Sexual Health Food & Fitness Diseases & Conditions Infections Q&A School & Jobs Drugs & Alcohol Staying Safe Recipes En Español ... Body Image HPV Vaccine KidsHealth > Teens > Sexual Health > STDs & ...

  18. Helper T cell subsets for immunoglobulin A responses: oral immunization with tetanus toxoid and cholera toxin as adjuvant selectively induces Th2 cells in mucosa associated tissues

    PubMed Central

    1993-01-01

    Antigen-specific B cell responses to mucosally delivered proteins are dependent upon CD4-positive T helper (Th) cells, and the frequency of Th1 and Th2 cell responses after oral immunization may determine the level and isotype of mucosal antibody responses. We have used a protein- based vaccine, tetanus toxoid (TT), together with the mucosal adjuvant cholera toxin (CT), for oral immunization of mice to study the nature of antigen-specific Th cell subsets induced in Peyer's patches (PP) of the gastrointestinal (GI) tract and in the spleen (SP) during peak antibody responses. Mice orally immunized with TT and CT responded with antigen-specific secretory immunoglobulin A (S-IgA) antibodies in the GI tract, and with both IgG and IgA antibody responses in serum. PP and SP CD4+ T cells from mice orally immunized with TT plus CT were cultured with antigen-coated latex microspheres for induction of proliferative responses and for enumeration of cytokine producing CD4+ T cells. Interestingly, both PP and SP CD4+ T cell cultures showed increased numbers of IL-4- and IL-5 (Th2-type)-producing, spot-forming cells (SFCs) after 21 d of immunization, while essentially no interferon-gamma (IFN-gamma) or IL-2 (Th1-type) SFCs were noted. Cytokine-specific Northern blots and RT-PCR also revealed that significant IL-4 and IL-5 mRNA levels, but not IFN-gamma or IL-2 mRNA, were present in CD4+ T cells isolated from antigen-stimulated cultures. However, systemic immunization with TT and CT induced antigen-specific IgG and IgM but not IgA antibodies in serum. Further, both IL-2 and IFN- gamma-producing Th1-type cells as well as IL-4- and IL-5-secreting Th2- type cells were generated in SP. Our results show that oral immunization with TT and the mucosal adjuvant CT selectively induced antigen-specific Th2-type responses which may represent the major helper cell phenotype involved in mucosal IgA responses in the GI tract. PMID:8376936

  19. Polymeric penetration enhancers promote humoral immune responses to mucosal vaccines.

    PubMed

    Klein, Katja; Mann, Jamie F S; Rogers, Paul; Shattock, Robin J

    2014-06-10

    Protective mucosal immune responses are thought best induced by trans-mucosal vaccination, providing greater potential to generate potent local immune responses than conventional parenteral vaccination. However, poor trans-mucosal permeability of large macromolecular antigens limits bioavailability to local inductive immune cells. This study explores the utility of polymeric penetration enhancers to promote trans-mucosal bioavailability of insulin, as a biomarker of mucosal absorption, and two vaccine candidates: recombinant HIV-1 envelope glycoprotein (CN54gp140) and tetanus toxoid (TT). Responses to vaccinating antigens were assessed by measurement of serum and the vaginal humoral responses. Polyethyleneimine (PEI), Dimethyl-?-cyclodextrin (DM-?-CD) and Chitosan enhanced the bioavailability of insulin following intranasal (IN), sublingual (SL), intravaginal (I.Vag) and intrarectal (IR) administration. The same penetration enhancers also increased antigen-specific IgG and IgA antibody responses to the model vaccine antigens in serum and vaginal secretions following IN and SL application. Co-delivery of both antigens with PEI or Chitosan showed the highest increase in systemic IgG and IgA responses following IN or SL administration. However the highest IgA titres in vaginal secretions were achieved after IN immunisations with PEI and Chitosan. None of the penetration enhancers were able to increase antibody responses to gp140 after I.Vag immunisations, while in contrast PEI and Chitosan were able to induce TT-specific systemic IgG levels following I.Vag administration. In summary, we present supporting data that suggest appropriate co-formulation of vaccine antigens with excipients known to influence mucosal barrier functions can increase the bioavailability of mucosally applied antigens promoting the induction of mucosal and systemic antibody responses. PMID:24657807

  20. Your baby's first vaccines

    MedlinePLUS

    ... to the antibiotics neomycin, streptomycin or polymyxin B. Hepatitis B vaccine , if your child has a severe allergy to ... half of vaccinations, depending on the vaccine. Polio, Hepatitis B and Hib vaccines have been associated only with these kinds of ...

  1. Your Baby's First Vaccines

    MedlinePLUS

    ... to the antibiotics neomycin, streptomycin or polymyxin B. Hepatitis B vaccine , if your child has a severe allergy to ... half of vaccinations, depending on the vaccine. Polio, Hepatitis B and Hib Vaccines have been associated only with these kinds of ...

  2. Detection of Clostridium perfringens type C in pig herds following disease outbreak and subsequent vaccination.

    PubMed

    Schäfer, K; Wyder, M; Gobeli, S; Candi, A; Doherr, M G; Zehnder, B; Zimmermann, W; Posthaus, H

    2012-11-17

    Immunisation of sows using Clostridium perfringens type C toxoid vaccines is recommended to prevent necrotising enteritis (NE) on pig breeding farms. Absence of disease, however, oftentimes leads to the false assumption of pathogens being eradicated. The prevalence of C perfringens type C was determined by PCR in faecal samples of piglets and sows in three Swiss pig breeding farms two to four years after implementation of a vaccination programme following disease outbreaks. C perfringens type C could still be detected several years after an outbreak despite absence of NE. In-herd prevalence of the pathogens varied significantly between the farms and was also lower compared with a farm which experienced a recent outbreak. In conclusion, C perfringens type C can be detected on once-affected farms, even in the absence of NE for several years. PMID:23100304

  3. Long-Term Effects of Tetanus Toxoid Inoculation on the Demography and Life Expectancy of the Cayo Santiago Rhesus Macaques

    PubMed Central

    KESSLER, MATTHEW J.; PACHECO, RAISA HERNÁNDEZ; RAWLINS, RICHARD G.; RUIZ-LAMBRIDES, ANGELINA; DELGADO, DIANA L.; SABAT, ALBERTO M.

    2014-01-01

    Tetanus was a major cause of mortality in the free-ranging population of rhesus monkeys on Cayo Santiago prior to 1985 when the entire colony was given its first dose of tetanus toxoid. The immediate reduction in mortality that followed tetanus toxoid inoculation (TTI) has been documented, but the long-term demographic effects of eliminating tetanus infections have not. This study uses the Cayo Santiago demographic database to construct comparative life tables 12 years before, and 12 years after, TTI. Life tables and matrix projection models are used to test for differences in: (i) survival among all individuals as well as among social groups, (ii) long-term fitness of the population, (iii) age distribution, (iv) reproductive value, and (v) life expectancy. A retrospective life table response experiment (LTRE) was performed to determine which life cycle transition contributed most to observed changes in long-term fitness of the population post-TTI. Elimination of clinical tetanus infections through mass inoculation improved the health and well-being of the monkeys. It also profoundly affected the population by increasing survivorship and long-term fitness, decreasing the differences in survival rates among social groups, shifting the population’s age distribution towards older individuals, and increasing reproductive value and life expectancy. These findings are significant because they demonstrate the long-term effects of eradicating a major cause of mortality at a single point in time on survival, reproduction, and overall demography of a naturalistic population of primates. PMID:25230585

  4. 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....

  5. Overview of vaccines and vaccination

    Microsoft Academic Search

    Gordon Ada

    2005-01-01

    Of the 80-plus known infectious agents pathogenic for humans, there are now more than 30 vaccines against 26 mainly viral\\u000a and bacterial infections and these greatly minimize subsequent disease and prevent death after exposure to those agents. This\\u000a article describes the nature of the vaccines, from live attenuated agents to subunits, their efficacy and safety, and the\\u000a kind of the

  6. Meningococcal disease: risk for international travellers and vaccine strategies.

    PubMed

    Wilder-Smith, Annelies

    2008-07-01

    International travel and migration facilitate the rapid intercontinental spread of meningococcal disease. Serogroup A and, less so serogroup C, have been responsible for epidemics in the past (mainly in Africa). In recent years, W135 has emerged (first in Saudi Arabia, then in West Africa) as a serogroup that requires attention. Serogroups X and Y are infrequent, but associated with slowly rising trends. There are significant variations in the incidence of meningococcal disease and the distribution of serogroups responsible for meningococcal disease, both geographically and with time. Vaccine strategies need to address this variation, and broad coverage against all serogroups for which vaccines are currently available should be offered to travellers. Tetravalent polysaccharide meningococcal vaccines are limited by their poor immunogenicity in small infants and by the lack of long-term protection. In contrast, the novel tetravalent conjugate vaccine that is currently only available in North America is immunogenic in young infants, induces long-term protection and reduces nasopharyngeal carriage. The tetravalent conjugate meningococcal vaccine will be a leap forward in the control of meningococcal epidemics in affected countries. It will also boost the uptake of meningococcal vaccines in travellers because the duration of protection is longer and it eliminates the problem of immune hyporesponsiveness of serogroup C with repeated dosing. Current vaccine recommendations are to vaccinate all Hajj pilgrims, all travellers to areas with current outbreaks, travellers to the SubSaharan meningitis belt, and individuals with certain medical conditions. PMID:18571105

  7. 70 FR 43694 - Proposed Vaccine Information Materials for Hepatitis A and Influenza Vaccines; Interim Vaccine...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2005-07-28

    ...Proposed Vaccine Information Materials for Hepatitis A and Influenza Vaccines; Interim Vaccine...new vaccine information materials for hepatitis A and trivalent influenza vaccines...Vaccine Injury Compensation Program: hepatitis B, haemophilus influenzae type b...

  8. The effect of vaccination on Streptococcus pneumoniae resistance

    Microsoft Academic Search

    Eugene Leibovitz; Pediatric Infectious

    2008-01-01

    Following the introduction of the 7-valent pneumococcal conjugate vaccine (PCV-7) in the routine immunization schedule of\\u000a US children, the morbidity and mortality associated with Streptococcus pneumoniae infections have changed considerably. Post-licensure data from the United States have confirmed that PCV-7 has significantly\\u000a decreased the incidence of vaccine-type susceptible and antibiotic-resistant invasive pneumococcal diseases, community-acquired\\u000a respiratory infections, and nasopharyngeal colonization in

  9. Vaccination priorities.

    PubMed

    Steffen, Robert; Baños, Ana; deBernardis, Chiara

    2003-02-01

    Selection of immunizations should be based on requirements and on risk of infection. According to the International Health Regulations, many countries require yellow fever vaccination and proof thereof as the International Certificate of vaccination. Additionally selected countries require proof of vaccination against cholera and meningococcal disease. A consultation for travel health advice is always an opportunity to ascertain that routine immunizations have been performed. Recommended immunizations often are more important for traveller's health than the required or routine ones. The most frequent vaccine preventable infection in non-immune travellers to developing countries is hepatitis A with an average incidence rate of 0.3% per month; in high risk backpackers or foreign-aid-volunteers this rate is 2.0%. Many immunizations are recommended for special risk groups only: there is a growing tendency in many countries to immunize all young travellers to developing countries against hepatitis B, as it is uncertain who will voluntarily or involuntarily get exposed. The attack rate of influenza in intercontinental travel is estimated to be 1%. Immunity against poliomyelitis remains essential for travel to Africa and parts of Asia. Many of the 0.2-0.4% who experience an animal bite are at risk of rabies. Typhoid fever is diagnosed with an incidence rate of 0.03% per month among travellers to the Indian subcontinent, North and West Africa (except Tunisia), and Peru, elsewhere this rate is 10-fold lower. Meningococcal disease, Japanese encephalitis, cholera and tuberculosis have been reported in travellers, but these infections are rare in this population. Although no travel health vaccine is cost beneficial, most professionals will offer protection against the frequent risks, while most would find it ridiculous to use all available vaccines in every traveller. It is essentially an arbitrary decision made on the risk level one wishes to recommend protection--but the priorities need to be set correctly. PMID:12615383

  10. Cytomegalovirus Vaccines

    PubMed Central

    McVoy, Michael A.

    2013-01-01

    An effective cytomegalovirus (CMV) vaccine could prevent the majority of birth defects caused by congenital CMV infections. Candidate vaccines in clinical evaluation include live attenuated, protein subunit, DNA, and viral-vectored approaches. Subunit approaches have focused on the CMV proteins pp65 and IE1 as important inducers of cytotoxic T cells and glycoprotein B (gB) as an important inducer of neutralizing antibodies. A vaccine comprised of recombinant gB protein with MF59 adjuvant reduced the incidence of primary infection by 50%. Recent revelations regarding CMV entry pathways into different cell types suggest a possible course for improvement. A 5-subunit pentameric complex is uniquely required for endothelial and epithelial cell entry. Sera from naturally infected subjects contain high-potency neutralizing activities specific for this complex, whereas the gB/MF59 vaccine fails to induce comparable neutralizing activities. A vaccine's ability to induce salivary antibodies that neutralize epithelial cell entry may be especially important for preventing oral transmission as the first cells infected are presumably epithelial cells of the oral mucosa. In addition, recent evidence suggests that antibodies can inhibit postentry CMV spread between endothelial and epithelial cells. Such activities may serve to limit viral replication in tissues or impair dissemination to the placenta and fetus. Thus, inclusion of epitopes derived from the pentameric complex may provide enhanced efficacy by inducing potent neutralizing/spread-inhibiting antibodies that target virus replication in a broad spectrum of cell types. Next-generation vaccine candidates in preclinical development incorporate peptides, subunits, or multisubunit complexes representing parts or all of the pentameric complex. Approaches include peptides, recombinant proteins, DNA, replication-defective viral vectors, genetically disabled CMV, and inactivated CMV virions. The diversity of novel strategies under development engenders optimism that a successful candidate will emerge. PMID:24257427

  11. Human Vaccines & Immunotherapeutics: News

    PubMed Central

    Riedmann, Eva M.

    2013-01-01

    Oncolytic vaccinia virus vaccine: Promising in liver cancer patients FDA panel endorses quadrivalent influenza vaccines Approval for the first meningitis B vaccine Stallergenes seeks FDA approval for sublingual grass-pollen allergy tablet Live-attenuated dengue vaccine promising in Phase 1 GAVI funds HPV vaccines for girls in developing countries First human trials for new superantigen bioterrorism vaccine Hexyon hexavalent pediatric vaccine recommended for approval

  12. killed-virus influenza vaccine Polio vaccine

    E-print Network

    Shyy, Wei

    killed-virus influenza vaccine Polio vaccine FluMist Thomas Francis, Jr. National Institutes of Health live-virus influenza vaccine Hunein Maassab Jonas Salk Type-A virus trivalent cold that Maassab's innovative, trivalent, cold- adapted influenza vaccine, FluMist, which uses live but weakened

  13. 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

  14. New Directions in Nicotine Vaccine Design and Use

    PubMed Central

    Pentel, Paul R.; LeSage, Mark G.

    2014-01-01

    Clinical trials of nicotine vaccines suggest that they can enhance smoking cessation rates but do not reliably produce the consistently high serum antibody concentrations required. A wide array of next-generation strategies are being evaluated to enhance vaccine efficacy or provide antibody through other mechanisms. Protein conjugate vaccines may be improved by modifications of hapten or linker design or by optimizing hapten density. Conjugating hapten to viruslike particles or disrupted virus may allow exploitation of naturally occurring viral features associated with high immunogenicity. Conjugates that utilize different linker positions on nicotine can function as independent immunogens, so that using them in combination generates higher antibody concentrations than can be produced by a single immunogen. Nanoparticle vaccines, consisting of hapten, T cell help peptides, and adjuvants attached to a liposome or synthetic scaffold, are in the early stages of development. Nanoparticle vaccines offer the possibility of obtaining precise and consistent control of vaccine component stoichiometry and spacing and immunogen size and shape. Passive transfer of nicotine-specific monoclonal antibodies offers a greater control of antibody dose, the ability to give very high doses, and an immediate onset of action but is expensive and has a shorter duration of action than vaccines. Viral vector-mediated transfer of genes for antibody production can elicit high levels of antibody expression in animals and may present an alternative to vaccination or passive immunization if the long-term safety of this approach is confirmed. Next-generation immunotherapies are likely to be substantially more effective than first-generation vaccines. PMID:24484987

  15. Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments.

    PubMed

    Morelli, Laura; Cancogni, Damiano; Tontini, Marta; Nilo, Alberto; Filippini, Sara; Costantino, Paolo; Romano, Maria Rosaria; Berti, Francesco; Adamo, Roberto; Lay, Luigi

    2014-01-01

    A vaccine to prevent infections from the emerging Neisseria meningitidis X (MenX) is becoming an urgent issue. Recently MenX capsular polysaccharide (CPS) fragments conjugated to CRM197 as carrier protein have been confirmed at preclinical stage as promising candidates for vaccine development. However, more insights about the minimal epitope required for the immunological activity of MenX CPS are needed. We report herein the chemical conjugation of fully synthetic MenX CPS oligomers (monomer, dimer, and trimer) to CRM197. Moreover, improvements in some crucial steps leading to the synthesis of MenX CPS fragments are described. Following immunization with the obtained neoglycoconjugates, the conjugated trimer was demonstrated as the minimal fragment possessing immunogenic activity, even though significantly lower than a pentadecamer obtained from the native polymer and conjugated to the same protein. This finding suggests that oligomers longer than three repeating units are possibly needed to mimic the activity of the native polysaccharide. PMID:25383107

  16. 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...

  17. 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)

  18. [Preparation of cationic dextran microspheres loaded with tetanus toxoid and study on the mechanism of protein loading].

    PubMed

    Zheng, Chun-li; Liu, Xiao-qing; Zhu, Jia-bi; Zhao, Yu-na

    2010-09-01

    The aim of this study is to prepare cationic biodegradable dextran microspheres loaded with tetanus toxoid (TT) and to investigate the mechanism of protein loading. Positively charged microspheres were prepared by polymerization of hydroxylethyl methacrylate derivatized dextran (dex-HEMA) and dimethyl aminoethyl methacrylate (DMAEMA) in an aqueous two-phase system. The loading of the microspheres with TT was based on electrostatic attraction. The net positive surface charge increased with increasing amounts of DMAEMA. Confocal images showed fluorescein isothiocyanate labeled bovine serum albumin (FITC-BSA) could penetrate into cationic dextran microspheres but not natural dextran microspheres. TT loading efficiency by post-loading was higher compared with by pre-loading. Even though TT is incorporated in the hydrogel network based on electrostatic interaction, still a controlled release can be achieved by varying the initial network density of the microspheres. PMID:21351577

  19. Hidden efficiencies: making completion of the pediatric vaccine schedule more efficient for physicians.

    PubMed

    Ciarametaro, Mike; Bradshaw, Steven E; Guiglotto, Jillian; Hahn, Beth; Meier, Genevieve

    2015-01-01

    The objective of this work is to demonstrate the potential time and labor savings that may result from increased use of combination vaccinations. The study (GSK study identifier: HO-12-4735) was a model developed to evaluate the efficiency of the pediatric vaccine schedule, using time and motion studies. The model considered vaccination time and the associated labor costs, but vaccination acquisition costs were not considered. We also did not consider any efficacy or safety differences between formulations. The model inputs were supported by a targeted literature review. The reference year for the model was 2012. The most efficient vaccination program using currently available vaccines was predicted to reduce costs through a combination of fewer injections (62%) and less time per vaccination (38%). The most versus the least efficient vaccine program was predicted to result in a 47% reduction in vaccination time and a 42% reduction in labor and supply costs. The estimated administration cost saving with the most versus the least efficient program was estimated to be nearly US $45 million. If hypothetical 6- or 7-valent vaccines are developed using the already most efficient schedule by adding additional antigens (pneumococcal conjugate vaccine and Haemophilus influenzae type b) to the most efficient 5-valent vaccine, the savings are predicted to be even greater. Combination vaccinations reduce the time burden of the childhood immunization schedule and could create the potential to improve vaccination uptake and compliance as a result of fewer required injections. PMID:25634165

  20. Immunology of Vaccine Adjuvants

    Microsoft Academic Search

    C. M. S. Ribeiro; V. E. J. C. Schijns

    2010-01-01

    In recent times vaccine adjuvants, or immunopotentiators, received abundant attention in the media as critical ingredients of current and future vaccines. Indeed, vaccine adjuvants are recognized to make the difference between competing vaccines based on identical antigens. Moreover, it is recognized that vaccines designed for certain indications require a matching combination of selected antigen(s) together with a critical immunopotentiator that

  1. Human Vaccines & Immunotherapeutics

    PubMed Central

    Riedmann, Eva M

    2013-01-01

    DNA vaccine for T1D promising in the clinic HPV vaccines halved infections in US teenage girls Modified DC immunotherapy against melanoma New study looks at clinical severity of human H7N9 infections Prevnar vaccines are valuable for healthcare systems GAPVAC: New consortium in the fight of brain cancer Cytomegalovirus vaccine to enter phase 3 Malaria vaccination using chemically attenuated parasites

  2. Long-lasting hyporesponsivenss induced by the 23-valent pneumococcal polysaccharide vaccine (PPV23) in asplenic patients with ?-thalassemia major.

    PubMed

    Papadatou, I; Orthopoulos, G; Theodoridou, M; Spoulou, V

    2015-07-31

    We have previously shown that multiple vaccinations with 23-valent pneumococcal polysaccharide vaccine (PPV23s) resulted in attenuated antibody responses to subsequent 7-valent conjugate vaccine (PCV7) in asplenic adults with ?-thalassemia major (Orthopoulos et al. Vaccine 2009; 27:350). However, there is evidence that PPV23-induced immune hyporesponsiveness could be overcome with time (Papadatou et al. Clin Infect Dis 2014; 59:862). In the current study we investigate the duration of hyporesponsiveness in the same cohort seven years after the original study vaccinations. Patients received one dose of 13-valent conjugate vaccine (PCV13) and antibody levels were measured before and one month after vaccination. Antibodies increased significantly after vaccination with PCV13, but were lower than post-PCV7 seven years earlier. Lower pre-vaccination antibody levels were associated with more robust response to PCV13. Our findings suggest that PPV23 should be used cautiously in asplenic adults vaccinated with multiple PPV23s in the past. Measurement of anti-pneumococcal antibodies before and after vaccination could be used to optimise timing of vaccinations and certify vaccine immunogenicity in such individuals. PMID:26144903

  3. Review: current and new generation pneumococcal vaccines.

    PubMed

    Feldman, Charles; Anderson, Ronald

    2014-10-01

    Pneumococcal polysaccharide vaccines (PPVs) and conjugate vaccines (PCVs), of which PPV23 and PCV13 are the current front runners, have had a significant, beneficial impact on public health. With regard to PPV23, there has been some debate, however, about its protective efficacy against all-cause pneumonia, as opposed to invasive pneumococcal disease, in high-risk cases. PCVs, on the other hand, have been included in many national immunisation programmes for prevention of severe pneumococcal disease in infants and young children, as well as for adults in various high-risk categories. Although innovative and effective, the protective efficacy of PCVs, the composition of which is based on the geographic prevalence and virulence of pneumococcal serotypes, is limited due to colonisation of the nasopharynx with non-vaccine serotypes. This phenomenon of serotype replacement has provided the impetus for development of new generation recombinant protein and whole cell pneumococcal vaccines with the potential to provide serotype-independent protection. In addition to an overview of the successes and limitations of PPVs and PCVs, this review is focused on emerging and pipeline protein-based and whole cell vaccines, preceded by a consideration of conserved pneumococcal virulence factors which are potential vaccine candidates. PMID:24968238

  4. Routine vaccination against MenB

    PubMed Central

    Kaaijk, Patricia; van der Ende, Arie; Luytjes, Willem

    2014-01-01

    Effective polysaccharide(conjugate) vaccines against Neisseria meningitidis serogroups A, C, W, and Y have been widely used, but serogroup B meningococci remain a major cause of severe invasive meningococcal disease (IMD) worldwide, especially in infants. Recently, a vaccine, 4CMenB (Bexsero®), containing three recombinant proteins, and outer membrane vesicles (OMV) derived from a serogroup B meningococcal strain (MenB) has been licensed in Europe and Australia and is indicated for persons aged 2 mo or older. This article discusses what should be considered to enable a successful implementation of a broad coverage MenB vaccine in national immunization programs. Epidemiology data, vaccine characteristics including vaccine coverage, immunogenicity, post-implementation surveillance and costs are relevant aspects that should be taken into account when selecting an appropriate immunization strategy. The potential impact on strain variation and carriage, as well as monitoring vaccine effectiveness, and rare but potentially serious adverse events are points that need to be included in a post-implementation surveillance plan. PMID:24141209

  5. Exploiting fungal cell wall components in vaccines.

    PubMed

    Levitz, Stuart M; Huang, Haibin; Ostroff, Gary R; Specht, Charles A

    2015-03-01

    Innate recognition of fungi leads to strong adaptive immunity. Investigators are trying to exploit this observation in vaccine development by combining antigens with evolutionarily conserved fungal cell wall carbohydrates to induce protective responses. Best studied is ?-1,3-glucan, a glycan that activates complement and is recognized by dectin-1. Administration of antigens in association with ?-1,3-glucan, either by direct conjugation or complexed in glucan particles, results in robust humoral and cellular immune responses. While the host has a host of mannose receptors, responses to fungal mannoproteins generally are amplified if cells are cooperatively stimulated with an additional danger signal such as a toll-like receptor agonist. Chitosan, a polycationic homopolymer of glucosamine manufactured by the deacetylation of chitin, is being studied as an adjuvant in DNA and protein-based vaccines. It appears particularly promising in mucosal vaccines. Finally, universal and organism-specific fungal vaccines have been formulated by conjugating fungal cell wall glycans to carrier proteins. A major challenge will be to advance these experimental findings so that at risk patients can be protected. PMID:25404118

  6. Pneumococcal vaccination in Europe: schedule adherence.

    PubMed

    Gervaix, Alain; Ansaldi, Filippo; Brito-Avô, António; Azzari, Chiara; Knuf, Markus; Martinón-Torres, Federico; Tuerlinckx, David; Tin Htar, Myint Tin; Syrogiannopoulos, George A

    2014-05-01

    Nonadherence to recommended pneumococcal conjugate vaccine (PCV) schedules may have implications for protection against pneumococcal disease. In this commentary, we have assessed adherence to the recommended dosing schedules (the completion of the primary PCV and booster series) in different European countries. We found that adherence with the PCV schedule was lower than that for diphtheria-tetanus-acellular pertussis (DTaP) and that higher adherence was observed in countries where PCV vaccination is recommended and funded. Adherence with the booster dose is often lower than that with the primary series completion, and it is often given after the recommended age. These data highlight the need to encourage timely vaccination of children with PCV, in line with local immunization schedules. There is no single solution to improve adherence; actions need to be tailored to the context of individual countries through initiatives at the national, regional, and local levels and should target different stakeholders. PMID:24746990

  7. 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.

  8. Vaccines for Pregnant Women

    MedlinePLUS

    ... lifestyle, medical conditions you may have, such as asthma or diabetes, type and locations of travel, and previous vaccinations. See the Immunization and Pregnancy Vaccines Flyer [1 page] , which shows the vaccines ...

  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. RESPONSE TO CONJUGATEHAEMOPHILUS INFLUENZAEB VACCINE AMONG INFANTS IN NIAMEY, NIGER

    Microsoft Academic Search

    GERARD CAMPAGNE; AMADOU GARBA; ANNE SCHUCHAT; DENIS BOULANGER; BRIAN D. PLIKAYTIS; MARIAMA OUSSEINI; JEAN-PHILIPPE CHIPPAUX

    1998-01-01

    Despite near elimination of Haemophilus influenzae b (Hib) meningitis from several industrialized coun- tries following introduction of conjugate Hib vaccines into infant immunization schedules, Hib remains a major cause of meningitis and pneumonia in resource-poor countries. In Niger, Hib causes nearly 200 cases of meningitis per 100,000 children , one year of age, and . 40% of cases are fatal.

  11. Can optical phase conjugators produce a very short conjugate pulse

    SciTech Connect

    Suydam, B.R.

    1980-01-01

    In studying the transient behavior of phase conjugation via four wave mixing, it has been noted that very short probe pulses invariably produce considerably broadened conjugate pulses unless the conjugator is inordinately short. The present investigation was therefore undertaken to determine whether a short conjugate pulse might be produced by judicious programming of the probe. It was found that the probe can indeed be tailored to produce an arbitrarily short conjugate signal and, if the conjugating medium exhibits linear absorption, then the total energy in the probe signal is finite. The required probe programming can be determined by numerical evaluation of a Fourier transform.

  12. Subviral Particle as Vaccine and Vaccine Platform

    PubMed Central

    Tan, Ming; Jiang, Xi

    2014-01-01

    Recombinant subvirual particles retain similar antigenic features of their authentic viral capsids and thus have been applied as nonreplicating subunit vaccines against viral infection and illness. Additionally, the self-assembled, polyvalent subviral particles are excellent platforms to display foreign antigens for immune enhancement for vaccine development. These subviral particle-based vaccines are noninfectious and thus safer than the conventional live attenuated and inactivated vaccines. While several VLP vaccines are available in the markets, numerous others, including dual vaccines against more than one pathogen, are under clinical or preclinical development. This article provides an update of these efforts. PMID:24662314

  13. Engineered human vaccines

    SciTech Connect

    Sandhu, J.S. (Mount Sinai Hospital, Toronto, Ontario (Canada). Div. of Immunology and Neurobiology)

    1994-01-01

    The limitations of human vaccines in use at present and the design requirements for a new generation of human vaccines are discussed. The progress in engineering of human vaccines for bacteria, viruses, parasites, and cancer is reviewed, and the data from human studies with the engineered vaccines are discussed, especially for cancer and AIDS vaccines. The final section of the review deals with the possible future developments in the field of engineered human vaccines and the requirement for effective new human adjuvants.

  14. Human Vaccines & Immunotherapeutics: News

    PubMed Central

    Riedmann, Eva M.

    2013-01-01

    Therapeutic HIV vaccine promising in the clinic GAVI aims to immunize 30 million against HPV by 2020 Self-destructing Salmonella to deliver oral DNA vaccines Novel strategy for vaccine design: Enzymatically modified antibodies GSK’s four-strain seasonal influenza vaccine approved in the US MVA85A TB vaccine tested in newborns of HIV-positive mothers Use of oral cholera vaccines promoted GSK partners with Vodafone to increase childhood vaccinatin in Mozambique PMID:23449312

  15. 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....

  16. 71 FR 30938 - Vaccine Information Statement for Hepatitis A Vaccine; Revised Instructions for Use of Vaccine...

    Federal Register 2010, 2011, 2012, 2013, 2014

    2006-05-31

    ...Prevention Vaccine Information Statement for Hepatitis A Vaccine; Revised Instructions for...new vaccine information materials for hepatitis A vaccine. Following review of the comments...under the law, CDC has finalized the hepatitis A vaccine information materials....

  17. Double conjugate laser amplifier

    SciTech Connect

    Chandra, S.; Daunt, G.H.

    1991-01-29

    This paper describes a double conjugate laser amplifier system for producing a stable output laser beam in line with a laser oscillator input beam. It comprises: a laser oscillator which produces a low energy oscillator laser beam therefrom directly along a laser beam axis of the system; an amplification means comprised of double conjugate laser amplifiers further comprised of a first and a second singly phase conjugate amplifiers laterally opposite each other about the laser beam axis; polarizers with one of the polarizers positioned between each of the first and second singly phase conjugate amplifiers on the laser beam axis; Pockels cells with on of the Pockels cells positioned on the laser beam axis immediately prior to one of the polarizers; and a means for selectively switching the amplifier means comprised of applying a half-wave voltage at each of the Pockels cells to provide a polarization rotation of the input beam through 90{degrees} for routing of the oscillator laser beam directly through or reflected off the polarizes as an input beam to the amplification means wherein the amplification means amplifies the input beam twice in each of the first and second singly phase conjugate amplifiers and reflects the amplified laser beam off the polarizers as an amplified laser output beam in exactly the same direction as the input laser beam.

  18. Global practices of meningococcal vaccine use and impact on invasive disease

    PubMed Central

    Ali, Asad; Jafri, Rabab Zehra; Messonnier, Nancy; Tevi-Benissan, Carol; Durrheim, David; Eskola, Juhani; Fermon, Florence; Klugman, Keith P; Ramsay, Mary; Sow, Samba; Zhujun, Shao; Bhutta, Zulfiqar; Abramson, Jon

    2014-01-01

    A number of countries now include meningococcal vaccines in their routine immunization programs. This review focuses on different approaches to including meningococcal vaccines in country programs across the world and their effect on the burden of invasive meningococcal disease (IMD) as reflected by pre and post-vaccine incidence rates in the last 20 years. Mass campaigns using conjugated meningococcal vaccines have lead to control of serogroup C meningococcal disease in the UK, Canada, Australia, Spain, Belgium, Ireland, and Iceland. Serogroup B disease, predominant in New Zealand, has been dramatically decreased, partly due to the introduction of an outer membrane vesicle (OMV) vaccine. Polysaccharide vaccines were used in high risk people in Saudi Arabia and Syria and in routine immunization in China and Egypt. The highest incidence region of the meningitis belt initiated vaccination with the serogroup A conjugate vaccine in 2010 and catch-up vaccination is ongoing. Overall results of this vaccine introduction are encouraging especially in countries with a moderate to high level of endemic disease. Continued surveillance is required to monitor effectiveness in countries that recently implemented these programs. PMID:24548156

  19. Antigen-specific lymphoproliferative responses to tetanus toxoid: a means for the evaluation of Marek's disease virus-induced immunosuppression in chickens

    Microsoft Academic Search

    S. K. Reddy; M. Suresh; K. Karaca; J. M. Sharma; J. McMillen; R. D. Schwartz

    1996-01-01

    Antigen-specific lymphoproliferative responses were examined in chickens following immunization with tetanus toxoid (Ttx). The immune competence of chickens was assessed by mitogen assay utilizing phytohemagglutinin (PHA)-stimulation and Ttx-specific antigen proliferation assay (Ttx-APA). Immune spleen cells but not peripheral blood leucocytes demonstrated specific proliferation following stimulation in vitro in a Ttx-APA. In this study, we examined firstly the effects of Marek's

  20. School-Located Vaccination Clinics for Adolescents: Correlates of Acceptance Among Parents.

    PubMed

    Gargano, Lisa M; Weiss, Paul; Underwood, Natasha L; Seib, Katherine; Sales, Jessica M; Vogt, Tara M; Rask, Kimberly; Morfaw, Christopher; Murray, Dennis L; DiClemente, Ralph J; Hughes, James M

    2015-08-01

    Four vaccines are recommended by The Advisory Committee for Immunization Practices for adolescents: tetanus, diphtheria, acellular pertussis vaccine (Tdap), meningococcal conjugate vaccine (MCV4), human papillomavirus vaccine (HPV), and annual seasonal influenza vaccine. However, coverage among adolescents is suboptimal. School-located vaccination clinics (SLVCs) offer vaccines to students at school, increasing access. This study seeks to determine the relationship between attitudes of parents of middle- and high-school students and acceptance of SLVCs for all four adolescent recommended vaccines. We conducted a telephone and web-based survey among parents of students enrolled in six middle and five high schools in Georgia. Analyses were conducted to examine associations between parental attitudes and willingness to allow their child to be vaccinated at school. Tdap and influenza vaccine had the highest rates of parental SLVC acceptance while HPV vaccine had the lowest. Parents who accepted SLVCs had higher perceived severity of influenza, meningococcal, and HPV illnesses compared to parents who did not accept SLVC. Intention to vaccinate was associated with SLVC acceptance for Tdap [Adjusted OR (AOR) 7.38; 95 % confidence interval (CI) 2.44-22.31], MCV4 (AOR 2.97; 95 % CI 1.67-5.28), and HPV vaccines (AOR 7.61; 95 % CI 3.43-16.89). Social norms were associated with acceptance of SLVCs for influenza vaccine (AOR 1.44; 95 % CI 1.12-1.84). These findings suggest parents of adolescents are generally supportive of SLVCs for recommended adolescent vaccines. Perceived severity of illness and intention to get their adolescent vaccinated were the most consistent correlates of parental SLVC acceptance for all vaccines. Future SLVC planning should focus on perceptions of disease severity and benefits of vaccination. PMID:25528325

  1. [Vaccination and pregnancy].

    PubMed

    Anselem, Olivia; Parat, Sophie; Théau, Anne; Floret, Daniel; Tsatsaris, Vassilis; Goffinet, François; Launay, Odile

    2014-06-01

    Vaccination against influenza is recommended during the vaccination period in pregnant women regardless of trimester. In contrast, administration of live vaccines, such as the vaccine against varicella, MMR (measles-mumps-rubella) is contraindicated in pregnant women. Vaccinations against hepatitis B, diphtheria, tetanus, poliomyelitis, hepatitis A can be made as indicated. Vaccination against yellow fever may be considered in pregnant women travelling to endemic countries. In post-partum period, live vaccines may be administered if necessary, especially vaccination against whooping cough for women not to date with their vaccinations. Vaccination against yellow fever is contraindicated in case of breast feeding. Prevention of pertussis in newborns is based in France on vaccination of the mothers in the post-partum period, and the close contacts of the newborn during the pregnancy ("cocooning"). PMID:24863661

  2. 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

  3. Identification and characterization of the constituent human serum antibodies elicited by vaccination

    PubMed Central

    Lavinder, Jason J.; Wine, Yariv; Giesecke, Claudia; Ippolito, Gregory C.; Horton, Andrew P.; Lungu, Oana I.; Hoi, Kam Hon; DeKosky, Brandon J.; Murrin, Ellen M.; Wirth, Megan M.; Ellington, Andrew D.; Dörner, Thomas; Marcotte, Edward M.; Boutz, Daniel R.; Georgiou, George

    2014-01-01

    Most vaccines confer protection via the elicitation of serum antibodies, yet more than 100 y after the discovery of antibodies, the molecular composition of the human serum antibody repertoire to an antigen remains unknown. Using high-resolution liquid chromatography tandem MS proteomic analyses of serum antibodies coupled with next-generation sequencing of the V gene repertoire in peripheral B cells, we have delineated the human serum IgG and B-cell receptor repertoires following tetanus toxoid (TT) booster vaccination. We show that the TT+ serum IgG repertoire comprises ?100 antibody clonotypes, with three clonotypes accounting for >40% of the response. All 13 recombinant IgGs examined bound to vaccine antigen with Kd ? 10?8–10?10 M. Five of 13 IgGs recognized the same linear epitope on TT, occluding the binding site used by the toxin for cell entry, suggesting a possible explanation for the mechanism of protection conferred by the vaccine. Importantly, only a small fraction (<5%) of peripheral blood plasmablast clonotypes (CD3?CD14?CD19+CD27++CD38++CD20?TT+) at the peak of the response (day 7), and an even smaller fraction of memory B cells, were found to encode antibodies that could be detected in the serological memory response 9 mo postvaccination. This suggests that only a small fraction of responding peripheral B cells give rise to the bone marrow long-lived plasma cells responsible for the production of biologically relevant amounts of vaccine-specific antibodies (near or above the Kd). Collectively, our results reveal the nature and dynamics of the serological response to vaccination with direct implications for vaccine design and evaluation. PMID:24469811

  4. 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.

  5. 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.

  6. 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

  7. A novel chemistry for conjugating pneumococcal polysaccharides to Luminex microspheres.

    PubMed

    Schlottmann, Sonela A; Jain, Neil; Chirmule, Narendra; Esser, Mark T

    2006-02-20

    Here we describe a novel method to conjugate pneumococcal polysaccharides (PnPS) to Luminex microspheres for use in serological assays. 4-(4,6-dimethoxy[1,3,5]triazin-2-yl)-4-methyl-morpholinium (DMTMM) modification of PnPS and conjugation to carboxyl functional groups on Luminex microspheres (COOH-DMTMM method) was shown to be a reproducible chemistry that efficiently conjugated PnPS to Luminex microspheres without affecting the antigenicity of a broad set of PnPS. The COOH-DMTMM method was compared to three other methods for robustness, reproducibility and effect on PnPS antigenicity in a multiplexed assay format. The other methods examined included adsorption of the unmodified PnPS to Luminex microspheres, oxidation of the PnPS to conjugate them to amino-modified microspheres using carbodiimide chemistry and poly-l-lysine modification of the PnPS before conjugating to carboxy Luminex microspheres using carbodiimide chemistry. Of the four methods, the COOH-DMTMM chemistry was shown to be a robust methodology, producing stable PnPS coupled microspheres with a 4-log dynamic range and low cross-reactivity when used in a PnPS-specific IgG serology assay. This novel chemistry should be useful for developing serological assays to measure antibodies to polysaccharides for use in vaccine and epidemiology studies. PMID:16448665

  8. Influence of Two Vaccination Campaigns on Genetic Diversity of Invasive Neisseria meningitidis Isolates in Northern Spain (1997-2008)

    Microsoft Academic Search

    Diego Vicente; Olatz Esnal; M. José López de Goicoechea; Ramón Cisterna; Emilio Pérez-Trallero; Shabir Ahmed Madhi

    2009-01-01

    BackgroundNeisseria meningitidis diversifies rapidly, due to its high recombination rates. The aim of this study was to analyze the possible impact of two vaccination campaigns (a once-off A\\/C polysaccharide vaccination campaign in people aged 18 months to 20 years old in 1997, and a meningococcal C conjugate vaccination campaign in children aged ?6 years old from 2000 to 2008) on

  9. 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

  10. Conjugated Antisense Oligonucleotides

    Microsoft Academic Search

    Muthiah Manoharan; Kathleen L. Tivel; Thomas P. Condon; Laura K. Andrade; Isabelle Barber-Peoch; Gopal Inamati; Shefali Shah; Venkatraman Mohan; Mark J. Graham; C. Frank Bennett; Stanley T. Crooke; P. Dan Cook

    1997-01-01

    We have employed chemical modification strategies to improve cellular ahsorption of oligonucleotides. These include the conjugation of various pendant moieties to the oligonucleotide to affect its overall physical properties such as hydrophobicity, charge, and amphipathicity as well as pendants that may mediate absorption by binding to certain cellular receptors which internalize specific ligands. Our laboratory has prepared polyamines, polyethylene glycols

  11. LOWANDHIGHFREQUENCYOCEANACOUSTICPHASE CONJUGATION EXPERIMENTS

    E-print Network

    Buckingham, Michael

    conjugation (PC), focuses sound from a source-receive array (SRA) back to the probe source (PS) which ensoni ed the SRA. The SRA receives the probe source pulse eld, time-reverses it and then retransmits Rider R/V Alliance Vertical Source/ Receive Array (SRA) 78 m (VRA) Probe Source (PS) R/V Manning 1500

  12. 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.

  13. 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

  14. A Bivalent Vaccine to Protect against Streptococcus pneumoniae and Salmonella typhi

    PubMed Central

    Lu, Ying-Jie; Zhang, Fan; Sayeed, Sabina; Thompson, Claudette; Szu, Shousun; Anderson, Porter W.; Malley, Richard

    2012-01-01

    Pneumococcal and Salmonella typhi infections are two major diseases for children in developing countries. For typhoid fever, licensed Vi polysaccharide vaccines are ineffective in children <2 year-old. While investigational Vi conjugate vaccines have been shown effective in clinical trials, they are currently only available to restricted areas. Pneumococcal capsular polysaccharide conjugate vaccines are highly effective in children, but suffer from some limitations including cost and limited serotype coverage. We have previously shown that a fusion conjugate vaccine, consisting of pneumococcal fusion protein PsaA and pneumolysoid (PdT) conjugated to a polysaccharide, results in enhanced antibody and CD4+ Th17 cell responses as well as protection against pneumococcal colonization and disease in mice. Here we applied this approach to develop a bivalent vaccine against pneumococcus and S. typhi. Two species-conserved pneumococcal antigens (SP1572 or SP2070) were fused to the nonhemolytic pneumolysoid PdT. SP1572-PdT was then conjugated to Vi polysaccharide and SP2070-PdT was conjugated to the pneumococcal cell wall polysaccharide (CWPS; also conserved). Mice immunized with this bivalent conjugate were protected against pneumococcal colonization and sepsis challenges, and made anti-Vi antibody concentrations higher by 40 fold compared to mice that received equimolar mixtures of the antigens. An enhanced killing of Vi-bearing Salmonellae in vitro was demonstrated from plasma of mice that received the fusion conjugate but not the mixture of antigens. Our results support further evaluation of this bivalent immunogen for the prevention of pneumococcal colonization and disease, and of typhoid fever. PMID:22465750

  15. 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

  16. 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

  17. Human papillomavirus vaccine update.

    PubMed

    Gilmer, Lisa S

    2015-03-01

    This article provides an overview of human papillomavirus (HPV) infection and the burden of HPV-related diseases, including cervical cancer, in the United States. The article presents an overview of HPV vaccination, including the efficacy and safety of the HPV vaccine, recommendations for vaccination in the adolescent population, as well as points to counter several of the common barriers to vaccination. This information is valuable to providers in their efforts to consistently and strongly recommend HPV vaccination. PMID:25634702

  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. Birth Control Vaccine Targeting Leukemia Inhibitory Factor

    PubMed Central

    LEMONS, ANGELA R.; NAZ, RAJESH K.

    2011-01-01

    SUMMARY The population explosion and unintended pregnancies resulting in elective abortions continue to impose major public health issues. This calls for a better method of contraception. Immunocontraception has been proposed as a valuable alternative that can fulfill most, if not all, of the properties of an ideal contraceptive. There are several targets that are being explored for contraceptive vaccine development. Leukemia inhibitory factor (LIF), a member of interleukin-6 family, is required for embryo development and successful blastocyst implantation in several mammalian species. The present study was conducted to examine if LIF can be a target for the development of a birth control vaccine. Three sequences from LIF and two sequences from LIF-receptor (LIF-R) that span the regions involved in ligand-receptor binding were delineated, and peptides were synthesized based upon these sequences. Antibodies raised against these five peptides reduced LIF bioactivity in the in vitro culture assay using BA/F3 mLIF-R-mpg130 cells. Vaccines were prepared by conjugating these peptides to various carrier proteins. Immunization of female mice with these peptide vaccines induced a long-lasting, circulating as well as local antibody response in various parts of the genital tract, and resulted in a significant (p?0.05) inhibition in fertility in all the three trials; the LIF-R peptide vaccines proved to be a better vaccine target. The data indicate that LIF/LIF-R is an excellent target for the development of a birth control vaccine. This is the first study, to our knowledge, that examined LIF/LIF-R as a target for immunocontraception. The findings of this study can be easily translated to humans since LIF/LIF-R is also important for implantation and pregnancy in women. PMID:22139866

  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. The 1996 Albert Lasker Medical Research Awards. Prevention of systemic infections, especially meningitis, caused by Haemophilus influenzae type b. Impact on public health and implications for other polysaccharide-based vaccines.

    PubMed

    Robbins, J B; Schneerson, R; Anderson, P; Smith, D H

    1996-10-01

    The development of Haemophilus influenzae type b (Hib) conjugate vaccines has led to the virtual elimination of systemic infections caused by that pathogen, has provided insights into the pathogenesis of and immunity to other capsulated bacteria, and has contributed to the development of new vaccines. Meningitis, a common and serious infection of children, and other infections caused by Hib have been virtually eliminated in countries that have achieved widespread vaccination with Hib conjugates, including the United States, Canada, the United Kingdom, Iceland, Scandinavia, France, and Germany. Hib conjugates have also been shown to be highly effective in developing countries. The principles derived from the use of these vaccines, along with studies of other capsulated pathogens, should allow the rapid inclusion of new polysaccharide-based conjugates into routine vaccination schedules of infants, and should help to realize further reductions in serious systemic infectious diseases. PMID:8827975

  2. Tresyl-Based Conjugation of Protein Antigen to Lipid Nanoparticles Increases Antigen Immunogencity

    PubMed Central

    Jain, Anekant; Yan, Weili; Miller, Keith R.; O'Carra, Ronan; Woodward, Jerold G.; Mumper, Russell J.

    2010-01-01

    The present studies were aimed at investigating the engineering of NPs with protein-conjugated-surfactant at their surface. In order to increase the immunogenicity of a protein antigen, Brij 78 was functionalized by tresyl chloride and then further reacted with the primary amine of the model proteins ovalbumin (OVA) or horseradish peroxide (HRP). The reaction yielded Brij 78-OVA and Brij 78-HRP conjugates which were then used directly to form NP-OVA or NP-HRP using a one-step warm oil-in-water microemulsion precursor method with emulsifying wax as the oil phase, and Brij 78 and the Brij 78-OVA or Brij 78-HRP conjugate as surfactants. Similarly, Brij 700 was conjugated to HIV p24 antigen to yield Brij 700-p24 conjugate. The utility of these NPs for enhancing the immune responses to protein-based vaccines was evaluated in vivo using ovalbumin (OVA) as model protein and p24 as a relevant HIV antigen. In separate in vivo studies, female BALB/c mice were immunized by subcutaneous (s.c.) injection with NP-OVA and NP-p24 formulations along with several control formulations. These results suggested that with multiple antigens, covalent attachment of the antigen to the NP significantly enhanced antigen-specific immune responses. This facile covalent conjugation and incorporation method may be utilized to further incorporate other protein antigens, even multiple antigens, into an enhanced vaccine delivery system. PMID:20837122

  3. Tresyl-based conjugation of protein antigen to lipid nanoparticles increases antigen immunogenicity.

    PubMed

    Jain, Anekant; Yan, Weili; Miller, Keith R; O'Carra, Ronan; Woodward, Jerold G; Mumper, Russell J

    2010-11-30

    The present studies were aimed at investigating the engineering of NPs with protein-conjugated-surfactant at their surface. In order to increase the immunogenicity of a protein antigen, Brij 78 was functionalized by tresyl chloride and then further reacted with the primary amine of the model proteins ovalbumin (OVA) or horseradish peroxide (HRP). The reaction yielded Brij 78-OVA and Brij 78-HRP conjugates which were then used directly to form NP-OVA or NP-HRP using a one-step warm oil-in-water microemulsion precursor method with emulsifying wax as the oil phase, and Brij 78 and the Brij 78-OVA or Brij 78-HRP conjugate as surfactants. Similarly, Brij 700 was conjugated to HIV p24 antigen to yield Brij 700-p24 conjugate. The utility of these NPs for enhancing the immune responses to protein-based vaccines was evaluated in vivo using ovalbumin (OVA) as model protein and p24 as a relevant HIV antigen. In separate in vivo studies, female BALB/c mice were immunized by subcutaneous (s.c.) injection with NP-OVA and NP-p24 formulations along with several control formulations. These results suggested that with multiple antigens, covalent attachment of the antigen to the NP significantly enhanced antigen-specific immune responses. This facile covalent conjugation and incorporation method may be utilized to further incorporate other protein antigens, even multiple antigens, into an enhanced vaccine delivery system. PMID:20837122

  4. 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

  5. HIV Infection and Adult Vaccination

    MedlinePLUS

    ... to protect against pneumonia and other pneumococcal diseases Hepatitis B vaccine series to protect against hepatitis B HPV vaccine ... to protect against pneumonia and other pneumococcal diseases Hepatitis B vaccine series to protect against hepatitis B HPV vaccine ...

  6. Pneumococcal Conjugate Vaccine: What You Need to Know

    MedlinePLUS

    ... www.immunize.org/vis Hojas de información sobre vacunas están disponibles en español y en muchos otros ... severe health problems, including pneumonia, blood infections, and meningitis. Meningitis is an infection of the covering of ...

  7. 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

  8. Immunogenicity and safety results from a randomized multicenter trial comparing a Tdap-IPV vaccine (REPEVAX®) and a tetanus monovalent vaccine in healthy adults

    PubMed Central

    Laurichesse, Henri; Zimmermann, Ulrich; Galtier, Florence; Launay, Odile; Duval, Xavier; Richard, Patrick; Sadorge, Christine; Soubeyrand, Benoit

    2012-01-01

    In adults with a tetanus-prone injury, combined vaccines such as Tdap-IPV (REPEVAX®) can boost immunity against several diseases simultaneously. This Phase IIIb, parallel-group, open-label trial compared antibody responses to Tdap-IPV and tetanus monovalent vaccine (TMV; Vaccin Tétanique Pasteur® or Tetavax®) against tetanus toxoid 10 and 28 d post-vaccination. Between July and December 2009, four centers in France and five in Germany recruited healthy adults who had received a tetanus-containing vaccine 5?10 y previously. Participants were randomized 1:1 to receive at the first visit a single dose (0.5 mL) of Tdap-IPV or TMV, with follow-up visits at Day 10 and Day 28. Outcomes: per protocol (PP) population immunogenicity at Day 10 (primary) and at Day 28 (secondary); safety throughout the study. Of 456 adults randomized, 223 received Tdap-IPV and 233 received TMV (PP population: 183 and 199 participants, respectively). All participants receiving Tdap-IPV and 99.0% receiving TMV had an anti-tetanus antibody concentration ? 0.1 IU/mL, confirming non-inferiority of Tdap-IPV to TMV (95% confidence interval of the difference: –1.2, 3.6). Number of adverse events reported was comparable in each group. Injection-site reactions were reported by 76.6% participants receiving Tdap-IPV and 74.6% receiving TMV. Systemic events (e.g., malaise, myalgia and headache) were reported in 47.7% and 39.7% of the Tdap-IPV and the TMV groups, respectively. Tdap-IPV is effective and well-tolerated for use in the management of tetanus-prone injuries in emergency settings in persons for whom a booster against diphtheria, pertussis and poliomyelitis is also needed. ClinicalTrials.gov identifier: NCT00928785. Research sponsored by Sanofi Pasteur MSD. PMID:23032160

  9. DNA vaccines against anthrax.

    PubMed

    Galloway, Darrell R; Baillie, Les

    2004-10-01

    DNA vaccination is vaccination at its simplest. Due to renewed interest in vaccination against anthrax and other biothreat agents, a genetic immunisation approach offers attractive possibilities for rapid, responsive vaccine development. DNA vaccination against anthrax is an active area of research showing promising results at present, which in the short-term and in the future could form the basis for new advances in multi-agent vaccine development. The anthrax 'model' constitutes an important experimental system for genetic immunisation technology development. PMID:15461577

  10. Preclinical evaluation of MenB vaccines: prerequisites for clinical development.

    PubMed

    Sanders, Holly; Kaaijk, Patricia; van den Dobbelsteen, Germie Pjm

    2013-01-01

    Despite the widespread use of polysaccharide and conjugate vaccines against disease caused by several serogroups of Neisseria meningitidis, vaccines targeting meningococci expressing the serogroup B capsule (MenB) have focused on subcapsular antigens, due to crossreactivity of the polysaccharide with human glycoproteins. Protein vaccines composed of outer membrane vesicles have been used successfully to control epidemics of MenB disease in several countries; however, these are specific for epidemic strains. Currently, a single serogroup B vaccine, aiming to provide comprehensive coverage, has been approved for use, and several others are undergoing clinical trials. Data on potential new vaccine candidates, from discovery to initial preclinical evaluation, are regularly published. In this review, the data required to progress from preclinical to clinical development of MenB vaccines are outlined, with reference to relevant regulatory guidelines. The issues caused by a lack of reliable animal models, particularly with respect to determination of protective efficacy, are also discussed. PMID:23256737

  11. Universal fungal vaccines

    PubMed Central

    Hamad, Mawieh

    2012-01-01

    The complex nature of fungal pathogens, the intricate host-pathogen relationship and the health status of subjects in need of antifungal vaccination continue to hamper efforts to develop fungal vaccines for clinical use. That said, the rise of the universal vaccine concept is hoped to revive fungal vaccine research by expanding the pool of vaccine candidates worthy of clinical evaluation. It can do so through antigenic commonality-based screening for vaccine candidates from a wide range of pathogens and by reassessing the sizable collection of already available experimental and approved vaccines. Development of experimental vaccines protective against multiple fungal pathogens is evidence of the utility of this concept in fungal vaccine research. However, universal fungal vaccines are not without difficulties; for instance, development of vaccines with differential effectiveness is an issue that should be addressed. Additionally, rationalizing the development of universal fungal vaccines on health or economic basis could be contentious. Herein, universal fungal vaccines are discussed in terms of their potential usefulness and possible drawbacks. PMID:22922769

  12. Thimerosal in Vaccines

    MedlinePLUS

    ... most sensitive to damage by methyl mercury. Ethyl Mercury Prior to the removal of thimerosal from childhood recommended vaccines, infants were exposed to ethyl mercury by intramuscular injection during vaccination, not by ingestion. ...

  13. Adoption and Vaccines

    MedlinePLUS

    ... receives under your care. See more information about recording vaccinations . Learn about the vaccines that your foster ... permission from the trademark/copyright holder... more This graphic notice means that you are leaving an HHS ...

  14. Seasonal Influenza Vaccines

    Microsoft Academic Search

    Anthony E. Fiore; Carolyn B. Bridges; Nancy J. Cox

    \\u000a Influenza vaccines are the mainstay of efforts to reduce the substantial health burden from seasonal influenza. Inactivated\\u000a influenza vaccines have been available since the 1940s and are administered via intramuscular injection. Inactivated vaccines\\u000a can be given to anyone six months of age or older. Live attenuated, cold-adapted influenza vaccines (LAIV) were developed\\u000a in the 1960s but were not licensed in

  15. Vaccines against Coccidioides

    PubMed Central

    Clemons, Karl V.

    2013-01-01

    Vaccines against fungal diseases are gaining attention because of their growing impact on modern medicine. Development of these vaccines should incorporate immunological tools that integrate with or replace chemotherapy to minimize antibiotic use and consequent resistance. In this review, we evaluate the current developmental status of fungal vaccines against coccidioidomycosis. There is a need for a vaccine that sufficiently prevents disease, without eradicating the fungus, by neutralizing adhesions and enzymes or other low penetrance virulence tr