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1

Haemophilus b Conjugate Vaccine (Tetanus Toxoid ...  

Center for Biologics Evaluation and Research (CBER)

Text Version... Store at 2° - 8°C (35°- 46°F); a caution stating to SHAKE WELL after reconstitution; space for adding lot number and expiration date at the time ... More results from www.fda.gov/downloads/biologicsbloodvaccines/vaccines

2

Comparison of five different vaccination schedules with Haemophilus influenzae type b-tetanus toxoid conjugate vaccine  

Microsoft Academic Search

OBJECTIVE: To compare seroresponses to five different vaccination schedules for Haemophilus influenzae type b (Hib)-tetanus toxoid conjugate (PRP-T) vaccine in infants. DESIGN: Four different two-dose schedules were compared, with doses given at 1 and 3 months, 2 and 4 months, 2 and 6 months, or 4 and 6 months of age. One group received three doses at 2, 4, and

Sari Kurikka; Helena Käyhty; Leena Saarinen; Pirjo-Riitta Rönnberg; Juhani Eskola; P. Helena Mäkelä

1996-01-01

3

Functional Antibody Activity Elicited by Fractional Doses of Haemophilus influenzae Type b Conjugate Vaccine (Polyribosylribitol Phosphate-Tetanus Toxoid Conjugate)  

Microsoft Academic Search

We evaluated the functional activities of antibodies, serum bactericidal activity (SBA), and immunoglobulin G (IgG) antibody avidity indices, using sodium thiocyanate (NaSCN) elution, elicited after vaccination with fractional doses of the Haemophilus influenzae type b conjugate (polyribosylribitol phosphate (PRP) conjugated to tetanus toxoid (PRP-T)) vaccine. A cohort of 600 infants from the Dominican Republic were randomized to receive one of

SANDRA ROMERO-STEINER; JOSEFINA FERNANDEZ; CHRISTEL BILTOFT; MELISSA E. WOHL; JACQUELINE SANCHEZ; JESUS FERIS; SHARON BALTER; ORIN S. LEVINE; GEORGE M. CARLONE

2001-01-01

4

Immunoglobulin G Subclass Response to a Meningococcal Quadrivalent Polysaccharide-Diphtheria Toxoid Conjugate Vaccine  

Microsoft Academic Search

Changes in the immunoglobulin G1 (IgG1)\\/IgG2 ratio following vaccination can indicate the activation of cellular control mechanisms typical of a T-cell-dependent response. We examined IgG subclass ratios in 17 healthy adults (26 to 55 years of age) before and 4 to 6 weeks following immunization with a quadrivalent meningococcal- polysaccharide diphtheria toxoid conjugate vaccine against serogroups A, C, Y, and

Helen Findlow; Lesley Mabey; Paul Balmer; Robert S. Heyderman; Cressida Auckland; Rhonwen Morris; Elizabeth Miller; Ray Borrow

2006-01-01

5

Comparison of multiple immunization schedules for Haemophilus influenzae type b-conjugate and tetanus toxoid vaccines following bone marrow transplantation  

Microsoft Academic Search

Antibody concentrations to vaccine-preventable diseases decline following BMT and an optimal schedule for vaccination after transplant has not been established. We examined antibody responses to tetanus toxoid (TT) and Haemophilus influenzae type b-conjugate (HIB) vaccines of BMT patients immunized at 6, 12 and 24 months (6 month group, n = 21) and compared them to those previously reported for patients

E Vance; S George; EC Guinan; C Wheeler; JH Antin; DM Ambrosino; DC Molrine

1998-01-01

6

Safety and immunogenicity of a new Neisseria meningitidis serogroup C-tetanus toxoid conjugate vaccine in healthy adults  

Microsoft Academic Search

We evaluated the safety and immunogenicity of a single dose of a new serogroup C O-deacetylated meningococcal polysaccharide–tetanus toxoid conjugate vaccine in 30 healthy adult volunteers. The vaccine was well tolerated with no serious adverse events and minimal local reactions and systemic symptoms. All subjects developed a fourfold or greater increase in serum bactericidal antibody (SBA) to serogroup C meningococcus.

Peter Richmond; David Goldblatt; Peter C Fusco; Joan D. S Fusco; Iver Heron; Sarah Clark; Ray Borrow; Francis Michon

1999-01-01

7

Preclinical efficacy of a glucuronoxylomannan-tetanus toxoid conjugate vaccine of Cryptococcus neoformans in a murine model  

Microsoft Academic Search

The encapsulated yeast, Cryptococcus neoformans, causes life-threatening meningoencephalitis in immunocompromised humans, especially in AIDS patients. Fatality and relapse rates remain quite high despite aggressive therapy. A conjugate vaccine composed of the cryptococcal capsular glucuronoxylomannan covalently coupled to tetanus toxoid (GXM-TT) was constructed and evaluated. The vaccine elicited high levels of capsular antibodies in mice by active and passive immunizations and

Sarvamangala J. N. Devi

1996-01-01

8

Group B Streptococcus type II polysaccharide-tetanus toxoid conjugate vaccine.  

PubMed Central

Group B streptococci (GBS) are the most common cause of bacterial sepsis and meningitis in neonates in the United States. Although the capsular polysaccharide of GBS is an important virulence factor, it is variably immunogenic in humans. In this report, we have increased the immunogenicity of GBS type II polysaccharide by coupling it to tetanus toxoid (TT). Like other GBS capsular polysaccharides, the type II polysaccharide has side chains terminating in sialic acid. Controlled periodate oxidation of native II polysaccharide resulted in the conversion of 7% of sialic acid residues to an analog of sialic acid, 5-acetamido-3,5-dideoxy-D-galactosyloctulosonic acid. TT was conjugated to free aldehyde groups created on the oxidized sialic acid residues by reductive amination. Serum from rabbits vaccinated with type II-TT conjugate (II-TT) vaccine contained antibodies specific to type II polysaccharide as well as to TT, whereas rabbits vaccinated with uncoupled native type II polysaccharide failed to produce a type-specific antibody response. Antibodies elicited by II-TT vaccine were serotype specific and mediated phagocytosis and killing in vitro of type II GBS by human peripheral blood leukocytes. Serum from rabbits vaccinated with II-TT vaccine provided 100% protection in a mouse model of GBS type II infection. Antibodies induced by II-TT vaccine were specific for the native but not desialylated type II polysaccharide, suggesting that an important antigenic epitope of II-TT vaccine was dependent on the presence of sialic acid. Therefore, the coupling strategy which selectively modified a portion of the sialic acid residues of types II polysaccharide before coupling the polysaccharide to TT preserved the epitope essential to protective immunity and enhanced the immunogenicity of the polysaccharide.

Paoletti, L C; Wessels, M R; Michon, F; DiFabio, J; Jennings, H J; Kasper, D L

1992-01-01

9

Meningococcal quadrivalent (serogroups A, C, W135 and Y) tetanus toxoid conjugate vaccine (Nimenrix™).  

PubMed

Nimenrix™ (MenACWY-TT) is a quadrivalent meningococcal conjugate vaccine, comprising the polysaccharide serogroups A, C, W135 and Y, and tetanus toxoid (TT) as carrier protein. It is the first quadrivalent vaccine (administered as a single dose) to be approved in Europe for active immunization of individuals aged ? 12 months against invasive meningococcal disease caused by Neisseria meningitidis serogroups A, C, W135 and Y. Administration of a single dose of Nimenrix™ elicited a strong immune response against all four vaccine serogroups in healthy toddlers aged 12-23 months, children and adolescents aged 2-17 years and adults aged 18-55 years in randomized, multicentre, phase III trials. In toddlers, Nimenrix™ was noninferior to Meningitec® in terms of seroresponse rates against meningococcal serogroup C 42 days post-vaccination. In children, adolescents and adults, Nimenrix™ was noninferior to Mencevax™ in terms of vaccination response rates against all four serogroups 1 month post-vaccination. Furthermore, several phase II studies and a phase III trial showed that the immune response elicited by Nimenrix™ in all age groups persisted for 7-42 months after the primary vaccination (when evaluated by rabbit serum bactericidal activity), with the vaccine also inducing immune memory in toddlers. In addition, several randomized, multicentre, phase III, noninferiority trials showed that when coadministered with other childhood vaccines or a seasonal flu vaccine, the immunogenicity of Nimenrix™ or that of the coadministered vaccine was generally not altered. Nimenrix® was generally well tolerated in all age groups whether administered as a single vaccine or coadministered with other routine vaccines. The incidence of grade 3 local or systemic solicited adverse events during the first 4 days following vaccination and of serious adverse events over an extended follow-up period of up to 6 months was low (<4.5%). Although protective effectiveness and longer-term persistence studies are required, current evidence suggests that Nimenrix™, administered as a single dose, provides a valuable vaccination option for the prevention of meningococcal disease across a broad age group, including children as young as 12 months. PMID:23231026

Croxtall, Jamie D; Dhillon, Sohita

2012-12-24

10

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

PubMed

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

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

2013-03-20

11

Immunogenicity of, and Immunologic Memory to, a Reduced Primary Schedule of Meningococcal C-Tetanus Toxoid Conjugate Vaccine in Infants in the United Kingdom  

Microsoft Academic Search

It has been previously shown that one of the three meningococcal C conjugate (MCC) vaccines introduced in the United Kingdom proved highly immunogenic after the first dose of a three-dose schedule, with evidence of immune memory after dose 3. Thus, in infants a one- or two-dose schedule of this MCC vaccine, conjugated to tetanus toxoid (TT), may suffice. Healthy infants

Ray Borrow; David Goldblatt; Adam Finn; Lindsey Ashton; Nick Andrews; Gouri Lal; Christine Riley; Rukhsana Rahim; Keith Cartwright; Geraldine Allan; Elizabeth Miller

2003-01-01

12

Physico-chemical properties of Salmonella typhi Vi polysaccharide-diphtheria toxoid conjugate vaccines affect immunogenicity.  

PubMed

In this study it was demonstrated that the immunogenicity of Vi polysaccharide-diphtheria toxoid conjugates was related to the physical and chemical structure of the conjugate. Conjugates were prepared in two steps, firstly binding adipic acid dihydrazide (ADH) spacer molecules to diphtheria toxoid (DT) carrier protein then secondly binding varying amounts of this derivatized DT to a fixed amount of Vi capsular polysaccharide purified from Salmonella enterica Serovar Typhi. As the amount of DT bound to the Vi increased the size of the conjugate increased but also the degree of cross-linking increased. The immunogenicity of the conjugates was tested in mice and measured by ELISA for anti Vi and anti DT IgG responses, and the results revealed a trend that as the amount of DT bound to the Vi increased the anti Vi responses increased. This study establishes a correlation between physico-chemical characteristics of the conjugate and the magnitude of the anti Vi and anti DT responses. PMID:21843575

An, So Jung; Yoon, Yeon Kyung; Kothari, Sudeep; Kothari, Neha; Kim, Jeong Ah; Lee, Eugene; Kim, Deok Ryun; Park, Tai Hyun; Smith, Greg W; Carbis, Rodney

2011-08-16

13

Neonatal mouse protection against infection with multiple group B streptococcal (GBS) serotypes by maternal immunization with a tetravalent GBS polysaccharide-tetanus toxoid conjugate vaccine.  

PubMed Central

Most cases of neonatal sepsis and meningitis caused by group B streptococci (GBS) are attributable to one of four major capsular serotypes: Ia, Ib, II, or III. Because resistance to infection with GBS has been correlated with the presence of serum antibodies to the type-specific capsular polysaccharides in both experimental animals and human neonates, efforts have been made to elicit protective immunity with GBS capsular polysaccharide vaccines. However, the GBS capsular polysaccharides alone are not highly immunogenic in either animals or human volunteers. Therefore, we and other investigators have attempted to enhance immunogenicity by coupling individual capsular polysaccharides to a carrier protein. Here we report the synthesis and immunogenicity in rabbits of a GBS type Ib polysaccharide-tetanus toxoid vaccine prepared by the direct, covalent attachment of tetanus toxoid to a selected number of sialic acid residues on the type-specific polysaccharide. In addition, the Ib polysaccharide-tetanus toxoid conjugate vaccine was combined with similar tetanus toxoid conjugates of GBS type Ia, II, and III polysaccharides to form a tetravalent GBS conjugate vaccine. Protective efficacy of the GBS tetravalent conjugate vaccine was demonstrated in a mouse maternal immunization-neonatal challenge model of GBS infection. The results support testing in human subjects of a multivalent GBS conjugate vaccine of this design, with the eventual goal of protecting newborns against GBS infection.

Paoletti, L C; Wessels, M R; Rodewald, A K; Shroff, A A; Jennings, H J; Kasper, D L

1994-01-01

14

Diphtheria & Tetanus Toxoids & Acellular Pertussis Vaccine ...  

Center for Biologics Evaluation and Research (CBER)

... List of Vaccines Licensed for Immunization and Distribution in the US. -. Diphtheria & Tetanus Toxoids & Acellular Pertussis Vaccine Adsorbed. -. ... More results from www.fda.gov/biologicsbloodvaccines/vaccines/approvedproducts

15

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

PubMed

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

Perry, Caroline M

2013-05-01

16

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

PubMed

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

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

2013-08-17

17

Antibody persistence and immune memory 15 months after priming with an investigational tetravalent meningococcal tetanus toxoid conjugate vaccine (MenACWY-TT) in toddlers and young children.  

PubMed

The present extension study, conducted in children originally vaccinated at 12-14 mo or 3-5 y of age, assessed antibody persistence and immune memory induced by an investigational tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (MenACWY-TT). In the original study, participants were randomized to receive one dose of MenACWY-TT or licensed age-appropriate meningococcal control vaccines. Fifteen months post-vaccination, all participants underwent serum sampling to evaluate antibody persistence and participants previously vaccinated as toddlers received a polysaccharide challenge to assess immune memory development. Exploratory comparisons showed that (1) All children and ? 92.3% of the toddlers maintained serum bactericidal (rSBA) titers ? 1:8 at 15 mo post MenACWY-TT vaccination; statistically significantly higher rSBA geometric mean titers (GMTs) were observed compared with control vaccines. (2) At one month after polysaccharide challenge, all toddlers primed with MenACWY-TT or with the monovalent serogroup C conjugate vaccine had rSBA titers ? 1:8 and ? 1:128 for serogroup C and similar rSBA-GMTs; rSBA-GMTs for serogroups A, W-135 and Y were statistically significantly higher in toddlers primed with MenACWY-TT compared with the control vaccine. Thus, a single dose of MenACWY-TT induced persisting antibodies in toddlers and children and immune memory in toddlers. This study has been registered at www.clinicaltrials.gov NCT00126984. PMID:22485049

Knuf, Markus; Baine, Yaela; Bianco, Veronique; Boutriau, Dominique; Miller, Jacqueline M

2012-04-09

18

Evaluation of De-O-Acetylated Meningococcal C Polysaccharide-Tetanus Toxoid Conjugate Vaccine in Infancy: Reactogenicity, Immunogenicity, Immunologic Priming, and Bactericidal Activity against O-Acetylated and De-O-Acetylated Serogroup C Strains  

Microsoft Academic Search

The polysaccharide capsule of serogroup C Neisseria meningitidis (MenC) has been integral to vaccine development. Licensed MenC vaccines contain the O-acetylated (OAc1) form of polysaccharide. Some MenC strains have de-O-acetylated (OAc2) polysaccharide, which may affect antibody specificity and functional activity when used in a vaccine. We evaluated an OAc-MenC conjugate-tetanus toxoid conjugate (MCC-TT) vaccine given concomitantly with whole-cell diphtheria-tetanus-pertussis, Haemophilus

PETER RICHMOND; RAY BORROW; JAMIE FINDLOW; SARAH MARTIN; CAROL THORNTON; KEITH CARTWRIGHT; ELIZABETH MILLER

2001-01-01

19

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

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.

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

2000-01-01

20

Immunization of pregnant women with group B streptococcal type III capsular polysaccharide-tetanus toxoid conjugate vaccine  

Microsoft Academic Search

Aim: To determine the safety and immunogenicity of group B streptococcal (GBS) type III CPS-TT conjugate vaccine in pregnant women. Methods: Prospective, randomized (2:1, vaccine:placebo), double-blind, placebo-controlled trial in women at 30–32 weeks’ gestation and their infants. Immune responses were measured with IgG-specific ELISA assays; killing of III GBS by 1- and 2-month infant sera was assessed by opsonophagocytosis. Results:

Carol J. Baker; Marcia A. Rench; Pamela McInnes

2003-01-01

21

Effects of Prior Polysaccharide Vaccination on Magnitude, Duration, and Quality of Immune Responses to and Safety Profile of a Meningococcal Serogroup C Tetanus Toxoid Conjugate Vaccination in Adults  

Microsoft Academic Search

Extensive use of meningococcal AC polysaccharide (MACP) vaccines has raised concerns about induction of immunologic hyporesponsiveness to C polysaccharide. We investigated the immunogenicity and safety of a meningococcal C-tetanus conjugate (MCC-TT) vaccine in naïve adults and prior MACP vaccinees. Laboratory staff (n 113) were recruited; 73 were naïve to meningococcal vaccination, and 40 had previously received >1 dose of MACP

Sarah Deane; Lindsey Ashton; Ray Borrow; David Goldblatt; Nick Andrews; Paul Balmer; Rhonwen Morris; J. Simon Kroll; Elizabeth Miller

2004-01-01

22

The use of Haemophilus influenzae type b-tetanus toxoid conjugate vaccine mixed with diphtheria-tetanus-pertussis vaccine in Gambian infants  

Microsoft Academic Search

In preparation for an efficacy trial of PRP-T Haemophilus influenzae type b conjugate vaccine, 251 Gambian infants were randomized to receive three doses of PRP-T and diphtheria-tetanus-pertussis (DTP) vaccines at 2, 3 and 4 months of age, either by separate injections, or combined in the same syringe. One month after the third dose, there was no difference between anti-PRP levels

E. Kim Mulholland; Anne Hoestermann; Joel I. Ward; Nicholas Maine; Chantal Ethevenaux; Brian M. Greenwood

1996-01-01

23

Immunogenicity and safety of measles-mumps-rubella and varicella vaccines coadministered with a fourth dose of Haemophilus influenzae type b and Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine in toddlers: a pooled analysis of randomized trials.  

PubMed

A pooled analysis was conducted of 1257 toddlers who received a fourth dose of Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y-tetanus toxoid conjugate vaccine (HibMenCY-TT) or Hib conjugate vaccine (Hib polysaccharide conjugated to N. meningitidis outer membrane protein) coadministered with measles-mumps-rubella (MMR) and varicella (VAR) vaccines (NCT00134719/NCT00289783). Noninferiority of immunological responses to MMR and VAR was demonstrated between groups and incidences of MMR- and VAR-specific solicited symptoms were similar, indicating that HibMenCY-TT can be coadministered with MMR and VAR. PMID:22617844

Bryant, Kristina; McVernon, Jodie; Marchant, Colin; Nolan, Terry; Marshall, Gary; Richmond, Peter; Marshall, Helen; Nissen, Michael; Lambert, Stephen; Aris, Emmanuel; Mesaros, Narcisa; Miller, Jacqueline

2012-08-01

24

Safety of combined oligosaccharide conjugate Haemophilus influenzae type b (HbOC) and whole cell diphtheria-tetanus toxoids-pertussis vaccine in infancy. The Kaiser Permanente Pediatric Vaccine Study Group.  

PubMed

The safety of the combined oligosaccharide conjugate Haemophilus influenzae (Hib) type b (HbOC) and whole cell diphtheria-tetanus toxoids-pertussis (DTP) vaccine (Tetramune, HbOC-DTP; Lederle) in infancy was evaluated in 6644 recipients of this vaccine and compared with 3914 recipients of separate injections of whole cell DTP and HbOC vaccines when given as a three dose regimen to infants at 2, 4 and 6 months of age in each group. Of the total number of infants in the study, a subset of 1435 were enrolled into the study and then randomly assigned to receive either the Hib-DPT combined vaccine or the separate components. This subset was used to assess local and systemic side effects which were evaluated utilizing telephone interviews 48 to 72 hours after vaccine. The remaining children in the study population were enrolled in a nonrandomized manner. For these children parents were offered the experimental Hib-DPT vaccine and refusers were given HbOC and DTP. Both of these groups of children as well as the randomized subset described above were used to assess rates of episodes of hospitalization, emergency room utilization and sudden infant death syndrome in HbOC-DTP recipients and children who received HbOC and DTP separately. Immunogenicity was evaluated in 123 children by collection of a single serum sample 30 days after the third dose of HbOC-DTP. The observed immunogenicity was comparable to that observed in other recent studies for HbOC and DTP component antigens. The profile of local and systemic side effects observed was virtually identical to that observed after DTP plus HbOC given separately.(ABSTRACT TRUNCATED AT 250 WORDS) PMID:8108224

Black, S B; Shinefield, H R; Ray, P; Lewis, E M; Fireman, B; Hiatt, R; Madore, D V; Johnson, C L; Hackell, J G

1993-12-01

25

Immunogenicity and safety of the quadrivalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (MenACWY-TT) in 2-10-year-old children: results of an open, randomised, controlled study.  

PubMed

In Europe, the introduction of monovalent meningococcal serogroup C (MenC) conjugate vaccines has resulted in a significant decline in MenC invasive disease. However, given the potential for strain evolution and increasing travel to areas of high endemicity, protection against additional serogroups is needed. In this study, the immunogenicity, measured by a serum bactericidal activity assay using rabbit complement (rSBA), and the safety of a quadrivalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (MenACWY-TT) were compared to that of a licensed monovalent MenC conjugate vaccine (MenC-CRM???) in children 2-10 years of age. Children were randomised (3:1) to receive a single dose of either MenACWY-TT or MenC-CRM???. Non-inferiority of the immunogenicity of MenACWY-TT versus MenC-CRM??? in terms of rSBA-MenC vaccine response was demonstrated. Exploratory analyses suggested that rSBA-MenC geometric mean titres adjusted for pre-vaccination titres were lower in children vaccinated with MenACWY-TT compared to MenC-CRM???. Nevertheless, at 1 month post-vaccination, ?99.3 % of the children who received MenACWY-TT had rSBA titres ?1:128 for each of the four vaccine serogroups, which is the more conservative correlate of protection. The reactogenicity and safety profile of MenACWY-TT was clinically acceptable and no serious adverse events considered related to vaccination were reported throughout the study. Conclusion: When administered to European school-age children, MenACWY-TT has a clinically acceptable safety profile and, when compared with MenC-CRM???, the potential to broaden protection against meningococcal disease caused by serogroups A, W-135 and Y while maintaining protection against MenC. This study has been registered at www.clinicaltrials.gov NCT00674583. PMID:23307281

Knuf, Markus; Romain, Olivier; Kindler, Klaus; Walther, Uta; Tran, Phu-My; Pankow-Culot, Heidemarie; Fischbach, Thomas; Kieninger-Baum, Dorothee; Bianco, Véronique; Baine, Yaela; Miller, Jacqueline

2013-01-11

26

A randomized study to assess the immunogenicity, antibody persistence and safety of a tetravalent meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine in children aged 2-10 years  

PubMed Central

Incidence of meningococcal diseases is high in children, and effective vaccines are needed for this age group. In this phase II, open, controlled study, 309 children aged 2–10 y from Finland were randomized (3:1) into two parallel groups to receive one dose of meningococcal ACWY-tetanus toxoid conjugate vaccine (ACWY-TT group; n = 231) or a licensed meningococcal ACWY polysaccharide vaccine (Men-PS group; n = 78). Serum bactericidal activity using rabbit complement (rSBA) was evaluated up to three years post-vaccination. Exploratory comparisons suggested that rSBA vaccine response rates and geometric mean titers (GMTs) for each serogroup at one month post-vaccination and rSBA GMTs for serogroups A, W-135 and Y up to three years post-vaccination were higher in the ACWY-TT compared with Men-PS group, but did not detect any difference between groups in terms of rSBA-MenC GMTs at three years post-vaccination; this is explained by the higher proportion of children from the Men-PS group who were excluded because they were re-vaccinated with a monovalent meningococcal serogroup C vaccine due to loss of protective antibody levels against this serogroup. Although there was a higher incidence of local reactogenicity in the ACWY-TT group, general and unsolicited symptoms reporting rates were comparable in both groups. This study showed that MenACWY-TT was immunogenic with a clinically acceptable safety profile in children aged 2–10 y. MenACWY-TT induced higher functional antibody titers for all serogroups, which persisted longer for serogroups A, W-135 and Y, than the MenACWY polysaccharide vaccine. This study has been registered at www.clinicaltrials.gov NCT00427908.

Vesikari, Timo; Forsten, Aino; Boutriau, Dominique; Bianco, Veronique; Van der Wielen, Marie; Miller, Jacqueline M.

2012-01-01

27

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

PubMed Central

Effective vaccines offering broad protection to toddlers, who are at high risk for invasive meningococcal disease, are needed. Here, the immunogenicity, safety and antibody persistence of the tetravalent meningococcal ACWY tetanus toxoid conjugate vaccine (MenACWY-TT) were evaluated in toddlers. Healthy participants aged 12 to 23 mo (n = 304) were randomized (3:1) to receive one dose of MenACWY-TT or a monovalent meningococcal serogroup C conjugate vaccine (MenC-CRM197). Serum bactericidal activity was evaluated with assays using rabbit (rSBA) and human (hSBA) complement up to three years post-vaccination. MenACWY-TT was demonstrated to be non-inferior to MenC-CRM197 in terms of immunogenicity to serogroup C, and the pre-specified immunogenicity criteria for serogroups A, W-135 and Y were met. Exploratory analyses suggested that rSBA geometric mean titers (GMTs), hSBA GMTs and proportions of toddlers with rSBA titers ? 1:128 and hSBA titers ? 1:4 and ? 1:8 were higher for all serogroups at one month post-vaccination with MenACWY-TT compared with MenC-CRM197. At three years post-vaccination, at least 90.8% and 73.6% of MenACWY-TT recipients retained rSBA titers ? 1:8 for all serogroups and hSBA titers ? 1:4 for serogroups C, W-135 and Y, respectively, but the percentages of toddlers with hSBA titers ? 1:4 for serogroup A decreased to 21.8%. In both groups, grade 3 adverse events were infrequently reported and no serious adverse events were considered causally related to vaccination. These results suggest that one single dose of MenACWY-TT induces a robust and persistent immune response and has an acceptable safety profile in toddlers. This study has been registered at www.clinicaltrials.gov NCT00427908.

Vesikari, Timo; Forsten, Aino; Boutriau, Dominique; Bianco, Veronique; Van der Wielen, Marie; Miller, Jacqueline M.

2012-01-01

28

Protection against pertussis with a monocomponent pertussis toxoid vaccine  

Microsoft Academic Search

This study was undertaken to assess the safety and protective efficacy against pertussis of a monocomponent pertussis toxoid vaccine in a society with hyperendemic pertussis. A total of 3450 healthy infants from child health centers in the Göteborg area of Sweden were enrolled in a double-blind, randomized, placebo-controlled study. A combined diphtheria-tetanus vaccine was given with or without pertussis toxoid

John Taranger; Birger Trollfors; Teresa Lagergård; John B. Robbins

1997-01-01

29

The safety profile of Haemophilus influenzae type b-Neisseria meningitidis serogroups C and Y tetanus toxoid conjugate vaccine (HibMenCY)  

PubMed Central

The safety profile of HibMenCY was compared with licensed Hib conjugate vaccines in a pooled analysis that included more than 8,500 subjects who were administered a four-dose series of HibMenCY or commercially available Hib vaccines at 2, 4, 6 and 12–15 mo of age in two primary vaccination and two fourth dose phase 3 studies. In all studies, HibMenCY or Hib vaccine was co-administered with age-appropriate, routinely recommended vaccines. In one primary and one fourth dose study (n = 4180), local and general symptoms were solicited using diary cards for 4 d after each dose. Serious adverse events (SAEs) and the occurrence of adverse events (AEs) indicating new onset of chronic disease (NOCD), rash, and conditions prompting Emergency Room (ER) visits were reported from dose 1 until 6 mo after dose 4. The incidences of solicited local and general symptoms were similar following HibMenCY and commercially available Hib vaccines. For some solicited symptoms (pain at the injection site and irritability), rates were lower in the HibMenCY group compared with the Hib control group (p value < 0.05). There were no statistically significant differences between groups in the incidences of SAEs, NOCDs, rash, or AEs leading to ER visits, with the exceptions of anemia and viral gastroenteritis, which occurred significantly less frequently in those receiving HibMenCY than those receiving commercially available Hib vaccines. In this pooled safety analysis, the safety profile of HibMenCY was similar to the safety profile of licensed monovalent Hib vaccines, despite the addition of meningococcal antigens.   These studies are registered at www.clinicaltrials.gov NCT00345579 (primary vaccination study), NCT00345683 (fourth dose vaccination study) and NCT00289783 (primary and fourth dose vaccination studies)

Rinderknecht, Stephen; Bryant, Kristina; Nolan, Terry; Pavia-Ruz, Noris; Doniz, Carlos Aranza; Weber, Miguel Angel Rodriguez; Cohen, Christopher; Aris, Emmanuel; Mesaros, Narcisa; Miller, Jacqueline M.

2012-01-01

30

Safety and immunogenicity of a meningococcal (Groups A, C, Y, W-135) polysaccharide diphtheria toxoid conjugate vaccine in healthy children aged 2 to 10 years in Chile.  

PubMed

Immune responses to meningococcal conjugate (Menactra; MCV-4) and plain polysaccharide (Menomune-A/C/Y/W-135; PSV-4) vaccines against serogroups A, C, Y, and W-135 were assessed in 220 of 1037 Chilean children aged 2 to 10 years participating in a comparative safety trial. Both vaccines were generally well tolerated. Geometric mean serum bactericidal antibody (SBA) titers 28 days postvaccination were comparable in both groups for all four serogroups. Seroconversion was evident in > 97% of MCV-4 and > 90% of PSV-4 vaccinees who tested seronegative at baseline. Menactra safely induced broad and robust immune responses against serogroups A, C, Y and W-135 in this population. PMID:17012878

Lagos, Rosanna; Papa, Thomas; Muñoz, Alma; Ryall, Robert; Pina, Miriam; Bassily, Ehab

2005-11-07

31

Immunogenicity of IRIV- versus alum-adjuvanted diphtheria and tetanus toxoid vaccines in influenza primed mice  

Microsoft Academic Search

The immunogenicity and protectivity of two different toxoid vaccines were compared in mice. In one formulation, toxoids (diphtheria or tetanus) were adsorbed to alumoxid, whereas in the other formulation the toxoids were crosslinked to immunopotentiating reconstituted influenza virosomes (IRIVs). A preimmunization with influenza antigens is necessary for a good anti-toxoid antibody response when the IRIV formulation was administered. After two

Rinaldo Zurbriggen; Reinhard Glück

1999-01-01

32

Disparity in Functional Activity between Serum Anticapsular Antibodies Induced in Adults by Immunization with an Investigational Group A and C Neisseria meningitidis-Diphtheria Toxoid Conjugate Vaccine and by a Polysaccharide Vaccine  

Microsoft Academic Search

Polysaccharide-protein conjugate vaccines elicit higher concentrations of serum anticapsular antibody in infants and children than do unconjugated polysaccharide vaccines. The conjugate-induced antibodies also have higher avidity and complement-mediated bactericidal activity. Similar vaccine-related differences in the magnitude or functional activity of antibody are observed infrequently in immunized adults. We compared the antibody responses of adults immunized with an investigational group A

Shannon L. Harris; Adam Finn; Dan M. Granoff

2003-01-01

33

Haemophilus b Conjugate Vaccine Tetanus Toxoid Conjugate ...  

Center for Biologics Evaluation and Research (CBER)

... given at 2, 4, and 6 months of age. The second study, Greenberg et al. (1995), was a randomized trial to evaluate antibody ... More results from www.fda.gov/biologicsbloodvaccines/guidancecomplianceregulatoryinformation/complianceactivities

34

Salivary anti-capsular antibodies in infants and children immunised with Streptococcus pneumoniae capsular polysaccharides conjugated to diphtheria or tetanus toxoid  

Microsoft Academic Search

Saliva samples of infants and children immunised with pneumococcal vaccines were analysed for anti-polysaccharide (PS) antibodies against the Streptococcus pneumoniae (Pnc) vaccine serotypes 6B, 14, 19F, and 23F. The children received Pnc conjugate vaccine (1, 3, or 10 ?g of PSs conjugated to diphtheria or tetanus toxoid) or placebo at 2, 4, and 6 months. At 7 months of age salivary

Maija Korkeila; Hannele Lehtonen; Heidi Åhman; Odile Leroy; Juhani Eskola; Helena Käyhty

2000-01-01

35

Meningococcal Polysaccharide A O-Acetylation Levels Do Not Impact the Immunogenicity of the Quadrivalent Meningococcal Tetanus Toxoid Conjugate Vaccine: Results from a Randomized, Controlled Phase III Study of Healthy Adults Aged 18 to 25 Years.  

PubMed

In this study, we compared the immunogenicities of two lots of meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) that differed in serogroup A polysaccharide (PS) O-acetylation levels and evaluated their immunogenicities and safety in comparison to a licensed ACWY polysaccharide vaccine (Men-PS). In this phase III, partially blinded, controlled study, 1,170 healthy subjects aged 18 to 25 years were randomized (1:1:1) to receive one dose of MenACWY-TT lot A (ACWY-A) (68% O-acetylation), MenACWY-TT lot B (ACWY-B) (92% O-acetylation), or Men-PS (82% O-acetylation). Immunogenicity was evaluated in terms of serum bactericidal activity using rabbit complement (i.e., rabbit serum bactericidal activity [rSBA]). Solicited symptoms, unsolicited adverse events (AEs), and serious AEs (SAEs) were recorded. The immunogenicities, in terms of rSBA geometric mean titers, were comparable for both lots of MenACWY-TT. The vaccine response rates across the serogroups were 79.1 to 97.0% in the two ACWY groups and 73.7 to 94.1% in the Men-PS group. All subjects achieved rSBA titers of ?1:8 for all serogroups. All subjects in the two ACWY groups and 99.5 to 100% in the Men-PS group achieved rSBA titers of ?1:128. Pain was the most common solicited local symptom and was reported more frequently in the ACWY group (53.9 to 54.7%) than in the Men-PS group (36.8%). The most common solicited general symptoms were fatigue and headache, which were reported by 28.6 to 30.3% and 26.9 to 31.0% of subjects, respectively. Two subjects reported SAEs; one SAE was considered to be related to vaccination (blighted ovum; ACWY-B group). The level of serogroup A PS O-acetylation did not affect vaccine immunogenicity. MenACWY-TT (lot A) was not inferior to Men-PS in terms of vaccine response and was well tolerated. PMID:23885033

Lupisan, Socorro; Limkittikul, Kriengsak; Sosa, Nestor; Chanthavanich, Pornthep; Bianco, Véronique; Baine, Yaela; Van der Wielen, Marie; Miller, Jacqueline M

2013-07-24

36

Meningococcal Polysaccharide A O-Acetylation Levels Do Not Impact the Immunogenicity of the Quadrivalent Meningococcal Tetanus Toxoid Conjugate Vaccine: Results from a Randomized, Controlled Phase III Study of Healthy Adults Aged 18 to 25 Years  

PubMed Central

In this study, we compared the immunogenicities of two lots of meningococcal ACWY-tetanus toxoid conjugate vaccine (MenACWY-TT) that differed in serogroup A polysaccharide (PS) O-acetylation levels and evaluated their immunogenicities and safety in comparison to a licensed ACWY polysaccharide vaccine (Men-PS). In this phase III, partially blinded, controlled study, 1,170 healthy subjects aged 18 to 25 years were randomized (1:1:1) to receive one dose of MenACWY-TT lot A (ACWY-A) (68% O-acetylation), MenACWY-TT lot B (ACWY-B) (92% O-acetylation), or Men-PS (82% O-acetylation). Immunogenicity was evaluated in terms of serum bactericidal activity using rabbit complement (i.e., rabbit serum bactericidal activity [rSBA]). Solicited symptoms, unsolicited adverse events (AEs), and serious AEs (SAEs) were recorded. The immunogenicities, in terms of rSBA geometric mean titers, were comparable for both lots of MenACWY-TT. The vaccine response rates across the serogroups were 79.1 to 97.0% in the two ACWY groups and 73.7 to 94.1% in the Men-PS group. All subjects achieved rSBA titers of ?1:8 for all serogroups. All subjects in the two ACWY groups and 99.5 to 100% in the Men-PS group achieved rSBA titers of ?1:128. Pain was the most common solicited local symptom and was reported more frequently in the ACWY group (53.9 to 54.7%) than in the Men-PS group (36.8%). The most common solicited general symptoms were fatigue and headache, which were reported by 28.6 to 30.3% and 26.9 to 31.0% of subjects, respectively. Two subjects reported SAEs; one SAE was considered to be related to vaccination (blighted ovum; ACWY-B group). The level of serogroup A PS O-acetylation did not affect vaccine immunogenicity. MenACWY-TT (lot A) was not inferior to Men-PS in terms of vaccine response and was well tolerated.

Limkittikul, Kriengsak; Sosa, Nestor; Chanthavanich, Pornthep; Bianco, Veronique; Baine, Yaela; Van der Wielen, Marie; Miller, Jacqueline M.

2013-01-01

37

Pneumococcal conjugate vaccine  

MedlinePLUS

... infections, meningitis, and pneumonia in children. See also: Pneumococcal polysaccharide vaccine ... conjugate vaccine is not the same as the pneumococcal polysaccharide vaccine, which is used in children over age 2 ...

38

Safety and immunogenicity of an acellular pertussis diphtheria tetanus vaccine given as a single injection with Haemophilus influenzae b conjugate vaccine  

Microsoft Academic Search

To determine if an acellular pertussis-diphtheria-tetanus vaccine could be combined with a Haemophilus influenzae b conjugate vaccine as a single injection, we randomized 468 children between 17 and 21 months of age previously immunized with three doses of each vaccine to receive a five-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids, and Haemophilus influenzae b-tetanus toxoid conjugate vaccine

Scott A. Halperin; Luis Barreto; Brian J. Eastwood; Lorna Medd; Roland Guasparini; Elaine Mills

1997-01-01

39

[Malaria conjugate vaccine].  

PubMed

Many malarial antigens are poor immunogens in human. Chemical conjugation is one of the ways to enhance the immunogenicity of those poor immunogens. Its value has been demonstrated in malaria vaccine research. This article introduces the chemical linkers and the carrier proteins, which are often used for protein conjugation, and summarizes the research progress in malarial conjugate vaccine development. PMID:23484283

Qian, Feng; Xu, Hu-Ji

2012-10-30

40

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

PubMed

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

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

2013-11-01

41

A randomized comparison between early and late vaccination with tetanus toxoid vaccine after allogeneic BMT  

Microsoft Academic Search

Forty-five adult HLA-matched sibling BMT recipients were randomized to receive tetanus toxoid (TT) vaccine at 6, 8 and 14 months (early group, n = 23) or at 18, 20 and 26 months after BMT (late group, n = 22). At 6 months after BMT, prior to the first vaccination, 90% of the early group patients had a protective tetanus antibody

T Parkkali; R-M Ölander; T Ruutu; K Vuontela; L Volin; J Eskola; P Ruutu

1997-01-01

42

A randomized trial of conjugated group B streptococcal type Ia vaccine in a rabbit model of ascending infection  

Microsoft Academic Search

Objective: Maternal vaccination may become a central strategy in the prevention of early-onset group B Streptococcal sepsis. Unlike earlier group B streptococcal polysaccharide vaccines that were poorly immunogenic, newer vaccines conjugated to tetanus toxoid have been developed and have improved immunogenicity. We sought to evaluate a conjugated vaccine using our rabbit model of ascending infection. Study Design: Rabbit does were

Jill K. Davies; Lawrence C. Paoletti; Robert S. McDuffie; Lawrence C. Madoff; Scott Lee; Joan Eskens; Ronald S. Gibbs

1999-01-01

43

Guillain-Barré syndrome after combined tetanus-diphtheria toxoid vaccination  

Microsoft Academic Search

Guillain-Barré syndrome (GBS), an acute inflammatory polyradiculoneuropathy, is often associated with an antecedent factor, such as an infection, surgery, systemic malignancy, or vaccination. The first case of GBS following a vaccination with combined tetanusdiphtheria toxoid is reported.

Rohit Bakshi; Michael C. Graves

1997-01-01

44

The investigational meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate vaccine (ACWY-TT) and the seasonal influenza virus vaccine are immunogenic and well-tolerated when co-administered in adults.  

PubMed

Co-administration of meningococcal serogroups A, C, W-135 and Y conjugate vaccine (ACWY-TT) with seasonal influenza vaccine was investigated in a subset of adults enrolled in a larger study evaluating lot-to-lot consistency of ACWY-TT and non-inferiority to licensed tetravalent meningococcal polysaccharide vaccine (MenPS). Subjects in this sub-study were randomized (3:1:1) to receive ACWY-TT alone (ACWY-TT group) or with seasonal influenza vaccine (Coad), or licensed MenPS alone. Serum bactericidal antibodies (rSBA) and serum haemagglutination-inhibition (HI) antibody titers were measured pre- and 1 mo post-vaccination. Non-inferiority of the Coad group compared with ACWY-TT group was demonstrated in terms of rSBA geometric mean antibody titers (GMTs) to serogroups A, W-135 and Y. For serogroup C the pre-defined non-inferiority limit was marginally exceeded. Post-vaccination rSBA GMTs were significantly higher (exploratory analysis) in the Coad group compared with the MenPS group for serogroups A, W-135, and Y and were similar to the MenPS group for serogroup C. Overall, > 97% of subjects achieved rSBA titers ? 1:128 for all serogroups. The Coad group met all criteria defined by the Committee on Human Medicinal Products (CHMP) for seroprotection, seroconversion and seroconversion factor for HI antibodies for all three influenza strains. Grade 3 solicited local/general symptoms were reported by ? 1.9% of subjects in any group. These data support the co-administration of ACWY-TT with seasonal influenza vaccine when protection is needed against both diseases. This study is registered at clinicaltrials.gov NCT00453986. PMID:22485048

Aplasca-De Los Reyes, Mari Rose; Dimaano, Efren; Macalalad, Noel; Dbaibo, Ghassan; Bianco, Veronique; Baine, Yaela; Miller, Jacqueline

2012-04-09

45

Preparation and evaluation of immunogenic conjugates of Salmonella enterica serovar Typhi O-specific polysaccharides with diphtheria toxoid.  

PubMed

Typhoid fever, caused by Salmonella enterica serovar Typhi (S. Typhi), is a major health problem particularly in developing countries. The available vaccines have certain limitations regarding their efficacy, and inability to induce an immune response especially in individuals under 2 years of age. Conjugate vaccines which consist of a bacteria-specific polysaccharide chemically bound to a carrier protein overcome these problems by inducing a T-cell dependent immune response characterized by enhanced immunogenicity in all ages. In this study, O-specific polysaccharides (OSP) of S. Typhi were conjugated to diphtheria toxoid (DT) using adipic acid dihydrazide (ADH) as a linker. These conjugates (OSP-AH-DT) were then evaluated for their immunogenicity using mice as a model and showed significantly higher levels of IgG ELISA titers (P = 0.0241 and 0.0245) than lipopolysaccharides alone. Different immunization  schedules were compared and it was found that schedule-B (three injections with 4-weeks interval) induced higher immune responses than schedule-A (three injections with 2-weeks interval). We showed that diphtheria toxoid can be successfully employed as a carrier protein for conjugation with Salmonella OSP and play an important role in facilitating adequate immune response. PMID:22426380

Ali, Aamir; An, So Jung; Cui, Changfa; Haque, Abdul; Carbis, Rodney

2012-02-01

46

Guillain-Barr? syndrome after tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine: a case report  

PubMed Central

Introduction The association of Guillain-Barré syndrome with vaccination has been described in the literature; it is infrequent and controversial. An association with swine influenza, influenza, hepatitis and tetanus vaccination has been documented in few case reports. Case presentation A 40-year-old Caucasian man sustained a small right temporal epidural hematoma and nondisplaced right skull fractures after a fall from a roof. He was managed conservatively; a tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine was administered and a week later he was discharged home. A few days after his discharge, he experienced weakness and numbness in his legs, which progressed to involve his arms. Three weeks after his initial fall, he was readmitted with quadriparesis. A lumbar puncture revealed a cerebrospinal fluid protein of 790 mg/dL and one white blood cell. We diagnosed Guillain-Barré syndrome. Our patient was treated with intravenous immunoglobulin. Three months later his muscle strength had improved, but he continued to have tingling in his hands and feet and used a walker intermittently. Conclusion To the best of our knowledge, this is the first case of Guillain-Barré syndrome to be reported in the English literature after administration of tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine.

2011-01-01

47

The immunogenicity and safety of an investigational meningococcal serogroups A, C, W-135 and Y tetanus toxoid conjugate vaccine (ACWY-TT) compared with a licensed meningococcal tetravalent polysaccharide vaccine  

PubMed Central

Immunogenicity and safety of ACWY-TT compared with licensed ACWY polysaccharide vaccine (MenPS) in healthy adults, and lot-to-lot consistency of three ACWY-TT lots were evaluated in a phase 3, open, controlled study. Adults aged 18–55 y were randomized to receive ACWY-TT (one of three lots) or MenPS. Serum bactericidal antibodies (rSBA) were measured pre- and 1 mo post-vaccination. Adverse events (AEs) were assessed 4 d (solicited symptoms) and 31 d (unsolicited symptoms) post-vaccination. Serious AEs were reported up to 6 mo after vaccination. The number of vaccinated subjects was 1247 (ACWY-TT, n = 935; MenPS, n = 312). ACWY-TT lot-to-lot consistency and non-inferiority of ACWY-TT as compared with MenPS groups were demonstrated according to pre-specified criteria. The percentages of subjects with a vaccine response (VR = rSBA titer ? 1:32 in initially seronegative; ? 4-fold increase in initially seropositive) to ACWY-TT vs. MenPS were 80.1%/69.8% (serogroup A), 91.5%/ 92.0% (C), 90.2%/85.5% (W-135), 87.0%/78.8% (Y). Exploratory analyses showed that for serogroups A, W-135 and Y, VR rates and GMTs were significantly higher for ACWY-TT compared with MenPS. For each serogroup, ? 98.0% of subjects had rSBA titers ? 1:128. Grade 3 solicited AEs were reported in ? 1.6% of subjects in any group. The immunogenicity of ACWY-TT vaccine was non-inferior to MenPS for all four serogroups in adults, with significantly higher VR rates to serogroups A, W-135 and Y and an acceptable safety profile. Consistency of 3 ACWY-TT production lots was demonstrated. These data suggest that, if licensed, ACWY-TT conjugate vaccine may be used for protection against invasive meningococcal disease in healthy adults.   This study is registered at clinicaltrials.gov NCT00453986

Dbaibo, Ghassan; Macalalad, Noel; Reyes, Mari Rose Aplasca-De Los; Dimaano, Efren; Bianco, Veronique; Baine, Yaela; Miller, Jacqueline

2012-01-01

48

The immunogenicity and safety of an investigational meningococcal serogroups A, C, W-135, Y tetanus toxoid conjugate vaccine (ACWY-TT) compared with a licensed meningococcal tetravalent polysaccharide vaccine: a randomized, controlled non-inferiority study.  

PubMed

Immunogenicity and safety of ACWY-TT compared with licensed ACWY polysaccharide vaccine (MenPS) in healthy adults, and lot-to-lot consistency of three ACWY-TT lots were evaluated in a phase 3, open, controlled study. Adults aged 18-55 y were randomized to receive ACWY-TT (one of three lots) or MenPS. Serum bactericidal antibodies (rSBA) were measured pre- and 1 mo post-vaccination. Adverse events (AEs) were assessed 4 d (solicited symptoms) and 31 d (unsolicited symptoms) post-vaccination. Serious AEs were reported up to 6 mo after vaccination. The number of vaccinated subjects was 1247 (ACWY-TT, n = 935; MenPS, n = 312). ACWY-TT lot-to-lot consistency and non-inferiority of ACWY-TT as compared with MenPS groups were demonstrated according to pre-specified criteria. The percentages of subjects with a vaccine response (VR = rSBA titer ? 1:32 in initially seronegative; ? 4-fold increase in initially seropositive) to ACWY-TT vs. MenPS were 80.1%/69.8% (serogroup A), 91.5%/ 92.0% (C), 90.2%/85.5% (W-135), 87.0%/78.8% (Y). Exploratory analyses showed that for serogroups A, W-135 and Y, VR rates and GMTs were significantly higher for ACWY-TT compared with MenPS. For each serogroup, ? 98.0% of subjects had rSBA titers ? 1:128. Grade 3 solicited AEs were reported in ? 1.6% of subjects in any group. The immunogenicity of ACWY-TT vaccine was non-inferior to MenPS for all four serogroups in adults, with significantly higher VR rates to serogroups A, W-135 and Y and an acceptable safety profile. Consistency of 3 ACWY-TT production lots was demonstrated. These data suggest that, if licensed, ACWY-TT conjugate vaccine may be used for protection against invasive meningococcal disease in healthy adults.   This study is registered at clinicaltrials.gov NCT00453986. PMID:22485050

Dbaibo, Ghassan; Macalalad, Noel; Aplasca-De Los Reyes, Mari Rose; Dimaano, Efren; Bianco, Veronique; Baine, Yaela; Miller, Jacqueline

2012-04-09

49

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

Microsoft Academic Search

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 polysac- charide vaccine (PsA\\/C), or tetanus toxoid vaccine. The conjugate vaccine was shown to be

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

2009-01-01

50

New meningococcal C polysaccharide-tetanus toxoid conjugate Physico-chemical and immunological characterization.  

PubMed

The polysaccharides (Ps) are thymus-independent 2 (TI-2) antigens and poor immunogens in infants and young children; as a result of this delayed response to Ps antigens during ontogeny, infants and young children are highly susceptible to infections caused by encapsulated bacteria. Meningococcal group C polysaccharide (PsC)-proteins conjugate vaccines have been reported to induce significant serum IgG antibodies and immunologic memory in infants resulting in very effective vaccines. We describe here the obtainment, by a new method, of a neoglycoconjugate intended to immunize against Neisseria meningitidis serogroup C, its characterization by physico-chemical methods, including (1)H NMR and fluorescence spectroscopy methods, as well as the characterization of the immune response induced in mice by such conjugate. Amine groups generated by basic hydrolysis in the PsC were successfully conjugated to carboxyl groups of tetanus toxoid (TT), using carbodiimide-mediated coupling. The specific anti-Ps IgG and anti-Ps IgG subclasses (IgG1 and IgG2a) were measured by ELISA methods, the bactericidal activity in sera and the cytokines response (IFNgamma or IL5) in spleen cell of mice immunized with conjugated and native Ps were evaluated. The (1)H NMR spectra and the result obtained by the fluorescence spectroscopy method showed that the PsC and TT maintained structural identity after conjugation process. Conjugated PsC elicited an increase of anti-PsC IgG responses, anti-PsC IgG subclass (IgG1, IgG2a), an eight-fold increase in bactericidal activity in sera of mice immunized with conjugate compared with native PsC, was also observed. Higher titres of IFNgamma were observed in mice immunized with conjugated Ps. These results indicated that, the PsC and TT maintained its chemical and antigenic structure after the conjugation process. A change in the immunological pattern of responses of PsC, from TI-2 to a thymus-dependent (TD) pattern, was also demonstrated. PMID:17240485

Cuello, Maribel; Cabrera, Osmir; Martinez, Ileana; Del Campo, Judith M; Camaraza, Maria A; Sotolongo, Franklin; Pérez, Oliver; Sierra, Gustavo

2006-12-05

51

Conjugate vaccines: practice and theory  

Microsoft Academic Search

Conjugate vaccines have already had a major impact on vaccination of infants against H. influenzae type b. The impact of conjugate vaccines will continue to grow as we apply this technology to other important diseases. The design of these vaccines will become more efficient and rational as we continue to understand the various facets and immunological mechanisms important to the

Robert S. Becker; Robert S. Becket

1993-01-01

52

Preventing Tetanus, Diphtheria, and Pertussis Among Adolescents: Use of Tetanus Toxoid, Reduced Diphtheria Toxoid and Acellular Pertussis Vaccines. Recommendations of the Advisory Committee on Immunization Practices (ACIP). Morbidity and Mortality Weekly Report, Vol. 55, No. RR-3, March 24, 2006.  

National Technical Information Service (NTIS)

During spring 2005, two tetanus toxoid, reduced diphtheria toxoid and acellular pertussis vaccine (Tdap) products formulated for use in adolescents (and, for one product, use in adults) were licensed in the United States (BOOSTRIX, GlaxoSmithKline Biologi...

2006-01-01

53

Antibody-secreting peripheral blood lymphocytes induced by immunization with a conjugate consisting of Streptococcus pneumoniae type 12F polysaccharide and diphtheria toxoid.  

PubMed Central

Healthy adult volunteers were injected either with one of two conjugates composed of Streptococcus pneumoniae type 12F polysaccharide (Pn12F) covalently coupled to diphtheria toxoid or with Pn12F alone (as a component of Pnu-Imune, a 23-valent pneumococcus vaccine). The conjugates induced Pn12F-specific antibody-secreting cells in peripheral blood with numbers and isotype distribution similar to those induced by Pnu-Imune, with immunoglobulin A (IgA) as the predominant isotype. The conjugates also elicited high numbers of diphtheria toxoid-specific antibody-secreting cells of the IgG class. There was no distinct booster effect, since a second dose of the conjugates induced antibody-secreting cells at significantly lower numbers than after the first dose. In contrast to the cell numbers, the conjugate vaccines induced higher increases of IgA1 Pn12F antibodies in serum than did Pnu-Imune. However, neither the conjugates nor Pnu-Imune induced a secretory antibody response. Antibody levels in serum and saliva correlated poorly with the frequency of antigen-specific antibody-secreting cells. Circulating antibody-secreting cells present 7 days postimmunization were probably not responsible for the high increase of antibodies in serum but rather represented a population of in vivo-activated B cells with the ability to disseminate the humoral response from the antigen recognition site to distant locations of antibody production.

Lue, C; Prince, S J; Fattom, A; Schneerson, R; Robbins, J B; Mestecky, J

1990-01-01

54

Anti-Sepsis Conjugate Vaccine.  

National Technical Information Service (NTIS)

The present invention provides an immunogenic conjugate comprising biologically deacylated gram-negative bacterial moieties linked to D. discoideum proteinase 1, as well as novel subunits thereof, and methods of making and using the conjugates in vaccines...

D. C. DeBorde G. L. Gustafson

2005-01-01

55

Safety and immunogenicity of a tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis vaccine when co-administered with influenza vaccine in adults.  

PubMed

Annual vaccination with trivalent influenza vaccine (TIV), and a single dose of tetanus toxoid-reduced diphtheria toxoid-acellular pertussis (Tdap) vaccine, are both recommended for adults in the US. This study was conducted to obtain information on the safety and immunogenicity of co-administered TIV and a Tdap vaccine (Boostrix) in US adults. The immunogenicity and safety of Tdap and TIV was evaluated in 1,497 adult subjects 19-64 years of age, who were randomized to receive Tdap and TIV either concomitantly or one month apart (TIV followed by Tdap). Seroprotection rates for diphtheria, tetanus and influenza antigens were high (>or=94.1%) for both vaccine regimens, and immune responses to these antigens in the concomitant group were non-inferior to those observed in the sequential group. Although antibody concentrations for pertussis antigens were lower in the concomitant group than in the sequential group, concomitant administration was shown to be non-inferior to sequential administration with respect to anti-pertussis toxoid concentrations one month after Tdap vaccination. For filamentous haemagglutinin and pertactin, the between-group differences in antibody concentrations marginally exceeded pre-specified limits for defining non-inferiority. In both groups, anti-pertussis antibody concentrations were greater than those observed in infants following primary DTaP vaccination, in whom vaccine efficacy against pertussis was demonstrated. Reporting of adverse events appeared to be similar between groups. The data support the conclusion that Tdap and TIV vaccines may be co-administered without compromising either the effectiveness or tolerability of either vaccine. PMID:19838080

Weston, Wayde M; Chandrashekar, Vijayalakshmi; Friedland, Leonard R; Howe, Barbara

2009-12-31

56

Prior meningococcal A\\/C polysaccharide vaccine does not reduce immune responses to conjugate vaccine in young adults  

Microsoft Academic Search

The immune responses induced in young adults by a meningococcal A\\/C polysaccharide-diphtheria toxoid conjugate vaccine (Mcj) and a meningococcal A\\/C plain polysaccharide vaccine (Mps) were evaluated in unvaccinated subjects and those who had received either vaccine previously. 195 subjects aged 17–30 years received either Mps or Mcj. After 12 months, they were randomised again to receive a second dose of

Raman Lakshman; Roger Burkinshaw; Sharon Choo; Adam Finn

2002-01-01

57

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

Microsoft Academic Search

We evaluated the prevalence and concentration of serum antibodies 18–24 months after primary inoculation with anthrax and botulinum vaccines, and assessed the reactogenicity and immunogenicity of a significantly delayed booster dose of these vaccines. Five hundred and eight male active-duty military personnel received one, two or three inoculations with anthrax vaccine and\\/or botulinum toxoid in 1990\\/1991 in preparation for Operations

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

2002-01-01

58

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

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

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

59

Outbreaks of Group A Streptococcal Abscesses Following Diphtheria-Tetanus Toxoid-Pertussis Vaccination  

Microsoft Academic Search

Two outbreaks of group A streptococcal abscesses following receipt of diphtheria-tetanus toxoid-pertussis (DTP) vaccine from different manufacturers were reported to the Centers for Disease Control (CDC) in 1982. The clustering of the immunization times of cases, the isolation of the same serotype of Streptococcus from all cases in each outbreak, and the absence of reported abscesses associated with receipt of

Harrison C. Stetler; Paul L. Garbe; Diane M. Dwyer; Richard R. Facklam; Walter A. Orenstein; Gary R. West; K. Joyce Dudley; Alan B. Bloch

60

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

PubMed

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

Szu, Shousun Chen

2013-11-01

61

Identification of a novel vaccine adjuvant that stimulates and maintains diphtheria toxoid immunity.  

PubMed

Immunomodulation by plant-derived medicines is well-documented with effects on both innate and adaptive immunity. This study reports potent and long-lasting diphtheria toxoid-specific immunity by the botanical medicinal, Rehmannia Six Formula, using an in vivo mouse model of vaccine immunity. A significant vaccine adjuvant effect was observed with an increase in serum anti-diphtheria toxoid total and IgG antibodies following oral administration of Rehmannia Six Formula to mice. This response was antigen-specific and was still detectable six months following botanical medicinal treatment, suggesting that Rehmannia Six Formula could help maintain protective antibody levels in populations where vaccine coverage is low. Rehmannia Six Formula was well-tolerated with no adverse effects on mouse weight or survival observed in this study and suggests a potential role as a novel vaccine adjuvant preparation. PMID:20197137

Licciardi, Paul V; Underwood, John R

2010-03-01

62

Development of a guinea pig model to assess immunogenicity of Haemophilus influenzae type b capsular polysaccharide conjugate vaccines  

Microsoft Academic Search

There is currently no animal model which reliably predicts the immunogenicity of Haemophilus influenzae type b (Hib) polysaccharide-protein conjugate vaccines in human infants. We evaluated various Hib vaccines in guinea pigs using techniques similar to the United States potency test for adsorbed diphtheria and tetanus toxoids with a view to developing a method for evaluating the potency of a combined

George R. Siber; Roger Anderson; Miriam Habafy; Rajesh K. Gupta

1995-01-01

63

Immunogenicity of group B Streptococcus type III polysaccharide-tetanus toxoid vaccine in baboons.  

PubMed Central

Maternal vaccination has been proposed as a rational approach for the prevention of neonatal group B streptococcal (GBS) disease. In this study, baboons were used as a nonhuman primate model to evaluate the immunogenicity of a GBS type III glycoconjugate vaccine. Type III-specific immunoglobulin G with opsonic activity was induced after vaccination with type III polysaccharide coupled to tetanus toxoid administered with an aluminum adjuvant. This suggests that baboons could be used in evaluating maternal transfer of GBS-specific antibodies by vaccination during pregnancy.

Paoletti, L C; Kennedy, R C; Chanh, T C; Kasper, D L

1996-01-01

64

[Pneumococcal vaccination: conjugated vaccine induces herd immunity and reduces antibiotic resistance].  

PubMed

Pneumococcal infections (pneumonia, otitis media, sinusitis, meningitis) are common and usually involve toddlers and the elderly. Currently, two pneumococcal vaccines are in clinical use. The older vaccine consists of pure capsular polysaccharides from 23 pneumococcal serotypes and induces only a limited B-cell response because polysaccharides are poor antigens that stimulate mainly B-cells. In 2000, a vaccination program with a novel 7-valent pneumococcal conjugate vaccine was launched in the U.S. The conjugation of capsular polysaccharides with a highly immunogenic diphtheria toxoid protein induces both a T cell and B cell response that results in specific humoral and mucosal immunity. Since children are the main reservoir of pneumococci, the 7-valent conjugate vaccine seems to eradicate the respective pneumococcal serotypes within the population, as demonstrated by recent US data. Pronounced herd immunity resulted in a decrease in invasive pneumococcal diseases in vaccinees and non-vaccinees as well as in a reduction of antibiotic resistance rates. However, recent data suggest a replacement of vaccine-serotypes by non-vaccine serotypes, which conquer the ecological niche created by the vaccine. In order to encounter this problem a 13-valent conjugated vaccine is currently under development. PMID:18270917

Pletz, M W; Maus, U; Hohlfeld, J M; Lode, H; Welte, T

2008-02-01

65

A novel glyco-conjugate vaccine against fungal pathogens  

PubMed Central

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.

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

66

A novel glyco-conjugate vaccine against fungal pathogens.  

PubMed

To generate a vaccine to protect against a variety of human pathogenic fungi, we conjugated laminarin (Lam), a well-characterized but poorly immunogenic beta-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-beta-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-beta-glucan IgG fractions, as well as by administration of a beta-glucan-directed IgG2b mAb. Passive protection was prevented by adsorption of antibodies on Candida cells or beta-glucan particles before transfer. Anti-beta-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-beta-glucan antibodies. PMID:16147975

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

2005-09-01

67

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

PubMed

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

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

2013-05-06

68

Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM ...  

Center for Biologics Evaluation and Research (CBER)

... Pneumococcal 13-valent Conjugate Vaccine (Diphtheria CRM 197 Protein). -. Product. Prevnar 13 Wyeth Pharmaceuticals, Inc. -. Contact FDA. ... More results from www.fda.gov/biologicsbloodvaccines/vaccines/approvedproducts

69

Efficacy of Clostridium botulinum types C and D toxoid vaccination in Danish cows.  

PubMed

In the present study the efficacy Botulism vaccine (formalinised aluminum hydroxide gel adsorbed toxoid of Clostridium botulinum types C and D) was evaluated in four Danish dairy cows under field conditions. Other four dairy herds were unvaccinated. Blood serum of all animals was analyzed for specific C. botulinum types A, B, C, D and E antibodies using a developed ELISA. Feces of all animals were analyzed for botulinum neurotoxins (BoNTs) and C. botulinum spores. C. botulinum types C and D antibodies were significantly (p < 0.05) increased in vaccinated animals. Vaccination with botulism vaccine significantly reduced (p < 0.001) BoNTs and C. botulinum spores in cattle feces. Our findings represent that C. botulinum vaccination increases specific blood serum antibodies and reduces free BoNTs and C. botulinum spores in feces. PMID:23831724

Krüger, Monika; Skau, Marie; Shehata, Awad Ali; Schrödl, Wieland

2013-07-04

70

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

PubMed

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

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

2013-03-20

71

Antibody Responses to Natural Rattlesnake Envenomation and a Rattlesnake Toxoid Vaccine in Horses  

PubMed Central

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 from16 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.

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

2013-01-01

72

Vaccination of Rabbits with an Alkylated Toxoid Rapidly Elicits Potent Neutralizing Antibodies against Botulinum Neurotoxin Serotype B?  

PubMed Central

New Zealand White (NZW) rabbits were immunized with several different nontoxic botulinum neurotoxin serotype B (BoNT/B) preparations in an effort to optimize the production of a rapid and highly potent, effective neutralizing antibody response. The immunogens included a recombinant heavy chain (rHc) protein produced in Escherichia coli, a commercially available formaldehyde-inactivated toxoid, and an alkylated toxoid produced by urea-iodoacetamide inactivation of the purified active toxin. All three immunogens elicited an antibody response to BoNT/B, detected by enzyme-linked immunosorbent assay (ELISA) and by toxin neutralization assay, by the use of two distinct mouse toxin challenge models. The induction period and the ultimate potency of the observed immune response varied for each immunogen, and the ELISA titer was not reliably predictive of the potency of toxin neutralization. The kinetics of the BoNT/B-specific binding immune response were nearly identical for the formaldehyde toxoid and alkylated toxoid immunogens, but immunization with the alkylated toxoid generated an approximately 10-fold higher neutralization potency that endured throughout the study, and after just 49 days, each milliliter of serum was capable of neutralizing 107 50% lethal doses of the toxin. Overall, the immunization of rabbits with alkylated BoNT/B toxoid appears to have induced a neutralizing immune response more rapid and more potent than the responses generated by vaccination with formaldehyde toxoid or rHc preparations.

Held, Daniel M.; Shurtleff, Amy C.; Fields, Scott; Green, Christopher; Fong, Julie; Jones, Russell G. A.; Sesardic, Dorothea; Buelow, Roland; Burke, Rae Lyn

2010-01-01

73

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

PubMed

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

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

2002-05-15

74

Development, Characterization, and In Vitro Evaluation of Chitosan and Alginate Microspheres Loaded Tetanus Toxoid Vaccine: A Comparative Study  

Microsoft Academic Search

The feasibility and utility of in vitro methods to assess the release pattern of chitosan and alginate microspheres containing experimental tetanus toxoid (TT) vaccines were evaluated. Herein, TT was stabilized and encapsulated in chitosan (TTCH) and alginate (TTAL) microspheres by a W\\/O\\/W multiple emulsion method using sucrose as a protein stabilizer. Optimization of processing parameters was studied with regard to

Saravanakumar Arthanari; Nachipalayam Muthusamy Ramaswamy; Kavaratti Raju Mani

2011-01-01

75

Oral vaccine models: multiple delivery systems employing tetanus toxoid.  

PubMed

We have not yet directly examined the Th cell responses induced by using Salmonella/BRD 847 as a vector nor have we performed these experiments following immunization with microspheres. However, production of high serum levels of antigen-specific IgG1 may be indicative of a Th2-type response, whereas high serum levels of IgG2a may reflect a Th1-type response. An important issue in using various oral delivery systems is whether the system(s) employed affects the Th cell response to the same antigen. We therefore analyzed the serum antigen-specific IgG subclasses induced in each of the model systems we studied. Table 2 presents these results. Clearly, oral administration of soluble TT with CT as an adjuvant induced an IgG1 subclass, and encapsulation of TT within microspheres had no effect on this Th2-type response. On the other hand, oral immunization with live Salmonella expressing fragment C of tetanus toxin induced a strong IgG2a subclass response indicative of a Th1-type response. It should be noted that protection against a lethal TT challenge was afforded by elevated levels of both anti-TT IgG1 and IgG2a subclasses. We intend to examine the cytokine profiles in spleen CD4+ T cells from mice immunized with microspheres or Salmonella following in vitro antigen stimulation to confirm the T helper type responses suggested by the IgG subclass data. It will also be important to examine the cytokine patterns induced in Peyer's patch CD4+ T cells following immunization of C57BL/6 with Salmonella/BRD 847. Whereas analysis of the serum IgG subclass profile indicated a strong IgG2a response and thus a systemic Th1-type pattern, this vector also induced a good mucosal IgA response. If our current hypothesis concerning S-IgA production is correct, we would expect a predominant Th2-type profile in CD4+ T cells from Peyer's patch in these mice. Such a result would emphasize the bifurcation of T-cell responses in the systemic versus the mucosal immune environments. The data obtained to data suggest that adjuvants and various vehicle delivery systems may influence the induction of distinct T helper cell subsets to a specific antigen. The unique cytokine arrays produced by these T-cell subsets influence the immune responses in terms of systemic Ig subclasses produced, cell-mediated immune responses, and the production of mucosal S-IgA antibodies. Although additional studies are necessary, the manipulation of T-cell subsets employing adjuvants, antigen packaging, or perhaps even the addition of individual cytokines to various formulations holds significant promise for optimizing immune responses to orally administered vaccines. PMID:8080173

Jackson, R J; Staats, H F; Xu-Amano, J; Takahashi, I; Kiyono, H; Hudson, M E; Gilley, R M; Chatfield, S N; McGhee, J R

1994-08-15

76

An adult formulation of a five-component acellular pertussis vaccine combined with diphtheria and tetanus toxoids is safe and immunogenic in adolescents and adults  

Microsoft Academic Search

Pertussis is increasingly being recognized as an important cause of cough illness in adolescents and adults. To evaluate the safety and immunogenicity of an adult formulation of a five-component (pertussis toxoid, filamentous hemagglutinin, pertactin, fimbriae 2 and 3) acellular pertussis vaccine combined with diphtheria and tetanus toxoids, we randomly allocated 749 healthy adolescents and adults from 12–54 years of age

Scott A. Halperin; Bruce Smith; Margaret Russell; Paul Hasselback; Roland Guasparini; Danuta Skowronski; William Meekison; Robert Parker; Pierre Lavigne; Luis Barreto

2000-01-01

77

Humoral Immunity to Aerosolized Staphylococcal Enterotoxin B (SEB), a Superantigen, in Monkeys Vaccinated with SEB Toxoid-Containing Microspheres  

Microsoft Academic Search

Staphylococcal enterotoxin B (SEB) toxoid-containing microspheres were tested for efficacy in rhesus monkeys as a vaccine candidate for respiratory SEB toxicosis and toxic shock. Forty monkeys were randomly separated into 10 groups of four monkeys each: 9 groups were vaccinated with the microspheres via combi- nationsofmucosalandnonmucosalroutes,and1groupservedasnonvaccinatedcontrols.Bothvaccinatedand nonvaccinated monkeys were then challenged with a high lethal dose of SEB aerosol. Monkeys

JEENAN TSENG; JACK L. KOMISAR; RODNEY N. TROUT; ROBERT E. HUNT; JAMES YOK-JEN CHEN; ANTHONY J. JOHNSON; LOUISE PITT; ANDDAVID L. RUBLE

78

Toxoid Vaccines  

Microsoft Academic Search

\\u000a Diphtheria, tetanus, and pertussis represented important causes of morbidity and mortality well into the early part of the\\u000a twentieth century. With advances in bacteriology deriving from the work of Pasteur and Koch during the latter portion of the\\u000a nineteenth century, the organisms responsible for each of these serious infections were cultivated, leading to some of the\\u000a earliest and most dramatic

John D. Grabenstein

79

Maternal Tetanus Toxoid Vaccination and Neonatal Mortality in Rural North India  

PubMed Central

Objectives Preventable neonatal mortality due to tetanus infection remains common. We aimed to examine antenatal vaccination impact in a context of continuing high neonatal mortality in rural northern India. Methods and Findings Using the third round of the Indian National Family Health Survey (NFHS) 2005–06, mortality of most recent singleton births was analysed in discrete-time logistic model with maternal tetanus vaccination, together with antenatal care utilisation and supplementation with iron and folic acid. 59% of mothers reported receiving antenatal care, 48% reported receiving iron and folic acid supplementation and 68% reported receiving two or more doses of tetanus toxoid (TT) vaccination. The odds of all-cause neonatal death were reduced following one or more antenatal dose of TT with odds ratios (OR) of 0.46 (95% CI 0.26 to 0.78) after one dose and 0.45 (95% CI 0.31 to 0.66) after two or more doses. Reported utilisation of antenatal care and iron-folic acid supplementation did not influence neonatal mortality. In the statistical model, 16% (95% CI 5% to 27%) of neonatal deaths could be attributed to a lack of at least two doses of TT vaccination during pregnancy, representing an estimated 78,632 neonatal deaths in absolute terms. Conclusions Substantial gains in newborn survival could be achieved in rural North India through increased coverage of antenatal TT vaccination. The apparent substantial protective effect of a single antenatal dose of TT requires further study. It may reflect greater population vaccination coverage and indicates that health programming should prioritise universal antenatal coverage with at least one dose.

Singh, Abhishek; Pallikadavath, Saseendran; Ogollah, Reuben; Stones, William

2012-01-01

80

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

Microsoft Academic Search

In two double-blind, randomized, comparative studies involving a total of 218 children, an acellular pertussis (DTPa) vaccine containing diphtheria and tetanus toxoids and pertussis components filamentous haemagglutinin (FHA), pertussis toxoid (PT), and 69 kDa outer membrane protein (69 kDa OMP) was administered as a booster to 17-month-old and 5-year-old children with a history of routine whole-cell diphtheria-tetanus-pertussis (DTPw) vaccination. The

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

1993-01-01

81

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

PubMed Central

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 leaving. Children (n = 1,766) received a diphtheria-tetanus booster either 1 month before, 1 month after, or concurrently with one of three MCC vaccines conjugated to CRM197 or TT. All of the MCC vaccines induced high antibody responses to the serogroup C polysaccharide that were indicative of protection. The immune response to the MCC-TT vaccine was reduced as a result of prior immunization with a tetanus-containing vaccine, but antibody levels were still well above the lower threshold for protection. Prior or simultaneous administration of a diphtheria-containing vaccine did not affect the response to MCC-CRM197 vaccines. The immune responses to the carrier proteins were similar to those induced by a comparable dose of diphtheria or tetanus vaccine. The results also demonstrate that, for these conjugate vaccines in these age groups, both standard enzyme-linked immunosorbent assays and those that measure high-avidity antibodies to meningococcal C polysaccharide correlated equally well with assays that measure serum bactericidal antibodies, the established serological correlate of protection for MCC vaccines.

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

2002-01-01

82

Priming with diphtheria-tetanus-pertussis vaccine enhances the response to the Haemophilus influenzae type b tetanus conjugate vaccine in infancy  

Microsoft Academic Search

Haemophilus influenzae type b (Hib) capsular polysaccharide (PS) conjugated to tetanus toxoid (PRP-T) was given at 4 and 6 months of age and anti-Hib PS antibody response to the first and second dose of PRP-T was compared in groups that received diphtheria-tetanus-pertussis (DTP) vaccine either simultaneously with PRP-T (34 infants) or separately at 3, 4 and 5 months of age

Sari Kurikka

1996-01-01

83

Estimated effects of a delay in the recommended vaccination schedule for diphtheria and tetanus toxoids and pertussis vaccine.  

PubMed

The occurrence of adverse events temporally associated with diphtheria and tetanus toxoids and pertussis vaccine (DTP) has led to consideration of a delay in the schedule of initial vaccination. We developed an inferential model estimating the changes in pertussis- and DTP-associated health outcomes that might occur if initial DTP administration were delayed from 2, 4, and 6 months to 8, 10, and 12 months of age. An additional 636 cases of pertussis--115 of which would be associated with complications, including two encephalopathies--were projected to occur under the proposed as compared to the current schedule. Adverse medical events attributable to the vaccine were assumed to remain unchanged following the change in schedule. We projected 353 fewer chance associations with sudden infant death syndrome but 1311 more chance associations between DTP and seizures. These estimates suggest that the current schedule of vaccinating infants at 2, 4, and 6 months of age is casually associated with less morbidity and should be continued. PMID:3493356

Funkhouser, A W; Wassilak, S G; Orenstein, W A; Hinman, A R; Mortimer, E A

1987-03-13

84

Pneumococcal polysaccharide protein D-conjugate vaccine (Synflorix; PHiD-CV).  

PubMed

The pneumococcal polysaccharide protein D-conjugate vaccine (PHiD-CV; Synflorix) contains ten capsular polysaccharide serotypes from the bacterium Streptococcus pneumoniae, eight of which are conjugated to a nonlipidated cell-surface liporotein (protein D) of non-typeable Haemophilus influenzae (NTHi) and two of which are conjugated to either tetanus or diphtheria toxoid. In a three-dose primary vaccination schedule in infants aged <6 months, PHiD-CV elicited high immune responses against all pneumococcal serotypes contained in the vaccine and was noninferior to an approved 7-valent pneumococcal conjugate vaccine (7vCRM) for eight of the ten serotypes (five of the seven common to both vaccines). Moreover, functional antibodies were elicited against all vaccine serotypes in an opsonophagocytic activity (OPA) assay. A fourth booster dose of PHiD-CV during the second year of life elicited an anamnestic response against all ten pneumococcal serotypes, as determined by both antibody concentrations and OPA titers. There were no clinically relevant changes in the immunogenicity of PHiD-CV when coadministered with meningococcal serogroup C conjugate or pentavalent whole cell pertussis combination vaccines, and polio vaccines using two different primary vaccination schedules. 11Pn-PD, an 11-valent prototype of PHiD-CV, demonstrated protection against episodes of acute otitis media (AOM) caused by S. pneumoniae and NTHi in infants aged <27 months. The first occurrence of an episode of AOM caused by pneumococcal vaccine serotypes was reduced by 52.6% in 11Pn-PD vaccinees compared with recipients of a control vaccine (primary endpoint). The tolerability profile of PHiD-CV was generally similar to that of 7vCRM. PMID:19725600

Croxtall, Jamie D; Keating, Gillian M

2009-01-01

85

Haemophilus influenzae type b vaccine formulation and risk of childhood leukaemia  

Microsoft Academic Search

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

F Groves; D Sinha; A Auvinen

2002-01-01

86

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

PubMed Central

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

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

2013-01-01

87

Mass psychogenic illness following tetanus-diphtheria toxoid vaccination in Jordan.  

PubMed Central

In September 1998, more than 800 young people in Jordan believed they had suffered from the side-effects of tetanus-diphtheria toxoid vaccine administered at school; 122 of them were admitted to hospital. For the vast majority, their symptoms did not result from the vaccine but arose from mass psychogenic illness. The role played by the media, the children's parents, and the medical profession in the escalation of this mass reaction appeared, at first sight, to be unusual and even unique to the circumstances in Jordan at the time. A review of the literature showed, however, that this mass reaction was similar in many ways to previous outbreaks, even though the underlying causes varied. There are about 200 published accounts of mass responses to situations involving suspected poisoning or other events. Because such mass reactions are relatively rare and the triggers so diverse, individuals faced with responding to them are unlikely to have prior experience in how to handle them and are unlikely to take bold steps to prevent their escalation. Indeed they may be unaware that such events have been recorded before. The lessons learned from this incident in Jordan may help other immunization programme managers to handle crisis situations elsewhere.

Kharabsheh, S.; Al-Otoum, H.; Clements, J.; Abbas, A.; Khuri-Bulos, N.; Belbesi, A.; Gaafar, T.; Dellepiane, N.

2001-01-01

88

Frequency of medically attended adverse events following tetanus and diphtheria toxoid vaccine in adolescents and young adults: a Vaccine Safety Datalink study  

PubMed Central

Background Local reactions are the most commonly reported adverse events following tetanus and diphtheria toxoid (Td) vaccine and the risk of local reactions may increase with number of prior Td vaccinations. Methods To estimate the risk of medically attended local reactions following Td vaccination in adolescents and young adults we conducted a six-year retrospective cohort study assessing 436,828 Td vaccinations given to persons 9 through 25 years of age in the Vaccine Safety Datalink population from 1999 through 2004. Results Overall, the estimated risk of a medically attended local reaction was 3.6 events per 10,000 Td vaccinations. The lowest risk (2.8 events per 10,000 vaccinations) was found in the 11 to 15 year old age group. In comparison with that group, the event risks were significantly higher in both the 9 to 10 and 21 to 25 year old age groups. The risk of a local reaction was significantly higher in persons who had received another tetanus and diphtheria toxoid containing vaccine (TDCV) in the previous five years (incidence rate ratio, 2.9; 95% confidence interval, 1.2 to 7.2). Twenty-eight percent of persons with a local reaction to Td vaccine were prescribed antibiotics. Conclusion Medically attended local reactions were uncommon following Td vaccination. The risk of those reactions varied by age and by prior receipt of TDCVs. These findings provide a point of reference for future evaluations of the safety profile of newer vaccines containing tetanus or diphtheria toxoid.

2009-01-01

89

Immune suppression induced by Vi capsular polysaccharide is overcome by Vi-DT conjugate vaccine.  

PubMed

The influence pre-exposure of mice to Vi capsular polysaccharide, purified from Salmonella enterica Serovar Typhi, on the subsequent immune response induced by a Vi-diphtheria toxoid (Vi-DT) conjugate was evaluated. Vi induced low anti Vi IgG titers with the dominant subclass being IgG3. The Vi-DT conjugate induced high titers of anti Vi IgG with the dominant subclass being IgG1 but with considerable quantities of IgG2a, IgG2b and IgG3. Priming of mice with Vi suppressed the response to a subsequent dose of conjugate and the suppression was overcome by a second dose of conjugate. Priming with conjugate prevented suppression of the anti Vi response and subsequent dosing with Vi raised titers back to previous levels but did not boost to new higher levels. The anti DT IgG response to one dose of conjugate was relatively strong and protracted and continued to rise for 12 weeks, compared to the response to one dose of DT which was poor and peaked at two weeks. The prolonged anti DT response was most likely due to the slow release of DT from the conjugate lattice as it degrades within the mouse resulting in a continuous stimulation of the immune response. The presence of increasing amounts of un-conjugated Vi, up to 50%, administered with the conjugate resulted in increasingly higher levels of both anti Vi and anti DT. Larger amounts of un-conjugated Vi inhibited the anti Vi response. These findings have implications for vaccine quality and a limit for un-conjugated polysaccharide should not exceed 50% and from a vaccine program perspective if the results presented here translate to humans then a Vi conjugate, once it becomes available, should replace Vi polysaccharide vaccines. PMID:22192846

An, So Jung; Yoon, Yeon Kyung; Kothari, Sudeep; Kim, Deok Ryun; Kim, Jeong Ah; Kothari, Neha; Lee, Eugene; Park, Tai Hyun; Carbis, Rodney

2011-12-20

90

Possible temporal association between diphtheria-tetanus toxoid-pertussis vaccination and sudden infant death syndrome.  

PubMed

Because diphtheria and tetanus toxoids pertussis (DTP) vaccine is routinely given during the period of highest incidence of sudden infant death syndrome (SIDS), this study was undertaken to determine if there is a temporal association between DTP immunization and SIDS. Parents of 145 SIDS victims who died in Los Angeles County between January 1, 1979, and August 23, 1980, were contacted and interviewed regarding their child's recent immunization history. Fifty-three had received a DTP immunization. Of these 53, 27 had received a DTP immunization within 28 days of death. Six SIDS deaths occurred within 24 hours and 17 occurred within 1 week of DTP immunization. These SIDS deaths were significantly more than expected were there no association between DTP immunization and SIDS. An additional 46 infants had a physician/clinic visit without DTP immunization prior to death. Forty of these infants died within 28 days of this visit, seven on the third day and 22 within the first week following the visit. These deaths were also significantly more than expected. These data suggest a temporal association between DTP immunization, physician visits without DTP immunization and SIDS. PMID:6835859

Baraff, L J; Ablon, W J; Weiss, R C

91

A comparison of early and late vaccination with Haemophilus influenzae type b conjugate and pneumococcal polysaccharide vaccines after allogeneic BMT.  

PubMed

Forty-five adult allogeneic BMT recipients were randomized to receive Haemophilus influenzae type b (Hib)-diphtheria toxoid conjugate vaccine (PRP-D) at 6 and pneumococcal polysaccharide vaccine (Pnc PS) at 8 months (early group; n = 23) or at 18 and 20 months (late group; n = 22) after BMT, respectively. Serum antibody concentrations against Hib and Pnc PS types with varying immunogenicity (serotypes 3, 6B, and 19F) were measured by ELISA. The responses at 1 month after vaccination with PRP-D and Pnc PS were poor and similar in the two vaccination groups, except that two-fold responses in the concentration of antibodies to the most immunogenic Pnc serotype 3 occurred more frequently in the late group. In the late group recipients, the antibody responses elicited by Pnc serotypes 3 and 19F correlated with the concentrations of the corresponding antibodies in the donor. This study on allogeneic BMT recipients shows that vaccination at 6-8 months after BMT with one dose of PRP-D and Pnc PS vaccine is as immunogenic as vaccination at 18-20 months after BMT, and suggests that donor immunity to Pnc PS affects recipient responses to Pnc PS vaccination. Consequently, as among allogeneic BMT recipients the greatest risk for infections by encapsulated bacteria occurs during the first 1-2 years after BMT, Hib and Pnc vaccines should not be given later than 6-8 months post-BMT. PMID:8932852

Parkkali, T; Käyhty, H; Ruutu, T; Volin, L; Eskola, J; Ruutu, P

1996-11-01

92

Pneumococcal Conjugate Vaccine (PCV13)  

MedlinePLUS

... treat because some strains are resistant to anti-biotics. This makes prevention through vaccination even more important. ... age range are at greatest risk for serious diseases caused by pneumococcal infection.PCV13 vaccine may also ...

93

Diphtheria and Tetanus Toxoids Adsorbed, STN 103944  

Center for Biologics Evaluation and Research (CBER)

... Diphtheria and Tetanus Toxoids Adsorbed, STN 103944. ... Package Insert - Diphtheria and Tetanus Toxoids Adsorbed, STN 103944 (PDF - 167KB). ... More results from www.fda.gov/biologicsbloodvaccines/vaccines/approvedproducts

94

Collaborative study for the validation of serological methods for potency testing of diphtheria toxoid vaccines-part 1.  

PubMed

A collaborative study on the evaluation of an alternative functional assay, the Vero cell method, to the Ph. Eur. in vivo challenge procedures for potency determination of diphtheria toxoid in 6 different combined vaccines was initiated in January 2001. The study was an extension of a previous study for the validation of serological methods for potency testing of tetanus toxoid vaccines for human use. To allow interim evaluation of test results and to monitor study progress, the project was divided into three consecutive phases. The results of Phase I and II studies are presented in this report. Pre-validation (Phase I) study, performed in two laboratories, indicated that comparable diphtheria potency estimates were obtained in the Ph. Eur. direct intradermal challenge assay in guinea pigs, in Vero cell assay and in indirect ELISA for five vaccines of different potencies (range of estimates: ca. 20-200 IU/ml). The correlation coefficients between the challenge assay and the Vero cell assay corresponded to those between the challenge assay and ELISA, confirming that the antibodies play an important role in protection and that predominantly protective/neutralising antibodies are present in guinea pigs, at the time point investigated. It was observed, for Vero cell assays, that about 16-35 (9-28 in Phase II study) fold lower titre of individual serum samples were obtained when using equine, rather than guinea pig reference serum. The study also provided preliminary information that sera from the same guinea pigs may be used for potency determination of both diphtheria and tetanus toxoid components of vaccines. In Phase II, another five laboratories analysed a subset of the vaccines included in Phase I study plus an additional vaccine. Four laboratories performed the lethal challenge assay and one laboratory carried out the intradermal challenge assay. All laboratories also performed the Vero cell assay and both ELISA for diphtheria antitoxin and ELISA for tetanus antitoxin. One laboratory also performed the tetanus ToBI assay. The correlation coefficient (r) between Vero cell assay and ELISA for diphtheria antitoxin ranged from 0.76 to 0.91 in the different laboratories. The correlation between diphtheria serological assays and challenge assays were confirmed satisfactory as ca. 90 per cent of serum-estimates lead to correct prediction of mortality. All laboratories had identical rankings of the vaccines in all serological assays and in the valid challenge assays. The ranking order was identical to assumed/provided potency for the highest and the lowest vaccine. Two of the vaccines had an inversion in some assays and laboratories. As these two vaccines have almost identical potencies in all assays, these inversions are not significant. As the vaccine doses were optimised for the diphtheria component, serum anti-tetanus toxoid/toxin activities varied widely between the vaccines, making it questionable to apply a parallel line model to calculate exact potencies. However, the dose levels used showed a clear regression and good linearity in general. DTaP vaccines containing the IPV component did not always meet the present Ph. Eur. requirements in the serological assays. It should be further investigated in the Phase III study if this is a general feature of such combined vaccines. Preliminary investigations on samples from two laboratories indicate that the neutralising activity of type 1, 2 and 3 polioviruses can also be detected, in a dose-dependent way. Further studies are in progress with serum samples from other laboratories. In the light of results obtained in the first two phases, it is recommended to proceed with Phase III study to investigate reliability of the in vitro assays. In Phase III it will also be further investigated whether the serological assays for D and T components are suitable for the control of the multi-component vaccines currently marketed in Europe. PMID:14960262

Winsnes, R; Sesardic, D; Daas, A; Behr-Gross, M-E

2004-01-01

95

Developing Novel Conjugate HIV-1 Subunit Therapeutic Vaccines.  

National Technical Information Service (NTIS)

Highly pure preparations of recombinant gp120 were obtained from two different HIV-1 isolates. Conjugates of these HIV-1 gp120 proteins were prepared with tetanus toxoid (TT) and keyhole limpet hemocyanin (KHL) with the hypothesis that very immunogenic ca...

L. D. Giavedoni

1999-01-01

96

Developing Novel Conjugate HIV-1 Subunit Therapeutic Vaccines.  

National Technical Information Service (NTIS)

Highly pure, native preparations of recombinant gp120 have been obtained from the T-tropic HIV-l(LAI) and the macrophage-tropic HIV-l(JR-FL) isolates. Conjugates of these HIV-l gp120 preparations were prepared with tetanus toxoid (TT) and keyhole limpet h...

L. D. Giavedoni

1997-01-01

97

Synthesis and immunological activity of an oligosaccharide-conjugate as a vaccine candidate against Group A Streptococcus.  

PubMed

The synthesis and immunogenicity of a tetanus toxoid (TT)-conjugate of the hexasaccharide portion of the cell-wall polysaccharide (CWPS) of the Group A Streptococcus (GAS) is described. The synthesis relies on the reaction of an allyl glycoside of the hexasaccharide with cysteamine, followed by the reaction of the resultant amine with diethyl squarate to give the monoethyl squarate adduct. Subsequent reaction with the lysine ?-amino groups on TT gives the glycoconjugate containing 30 hexasaccharide haptens per TT molecule. The immunogenicity in mice is similar to that obtained with a native CWPS-TT conjugate, validating the glycoconjugate as a vaccine candidate against GAS infections. PMID:24103300

Auzanneau, France-Isabelle; Borrelli, Silvia; Pinto, B Mario

2013-09-24

98

Changes in TNF and IL-6 production after diphtheria toxoid vaccination: drug modulation of the cytokine levels  

PubMed Central

The effect of vaccination with diphtheria toxoid (AD-M) on TNF and IL-6 production has been studied in humans. In the present study it was demonstrated that immunization with AD-M resulted in changes of in vitro TNF and IL-6 production by peripheral blood mononuclear cells. TNF release was suppressed but IL-6 production was stimulated. On the other hand, serum levels of TNF were markedly increased over a period of 3 weeks. It was also demonstrated that the postvaccinal cytokine production disturbances may be corrected by pretreatment with a new synthetic hexapeptid (Imunofan®). It is possible that the imunofan treatment could prevent some postvaccinal complications.

Bliacher, M. S.; Danilina, A. V.; Kalashnikova, E. A.; Lopatina, T. K.; Fedorova, I. M.

1996-01-01

99

Intranasal stimulation of long-lasting immunity against aerosol ricin challenge with ricin toxoid vaccine encapsulated in polymeric microspheres  

Microsoft Academic Search

Intranasal (i.n.) immunization with ricin toxoid (RT) vaccine encapsulated in poly(lactide-co-glycolide) microspheres (RT-PLG-Ms) and poly(L-lactide) microspheres (RT-PLA-Ms) stimulated systemic and mucosal immune responses and protected mice from aerosolized ricin intoxication. High titers of anti-ricin IgG2a were stimulated in the serum of mice with one or two doses of RT-Ms 6 weeks postimmunization. However, in the lungs, no IgG2a or total

Changhong Yan; Wayne L. Rill; Robert Malli; John Hewetson; Hina Naseem; Ralph Tammariello; Meir Kende

1996-01-01

100

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

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

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

2011-01-01

101

Randomised, controlled trial of concomitant pneumococcal and meningococcal conjugate vaccines  

Microsoft Academic Search

A randomised, open-label study compared the immunogenicity and safety of 7-valent pneumococcal conjugate vaccine (PCV7) and meningococcal C conjugate vaccine (MnCC vaccine) administered concomitantly and individually. Infants received PCV7+MnCC vaccine (n=265), PCV7 alone (n=268) or MnCC vaccine alone (n=178). PCV7 was administered at 2, 3½, 6 and 12 months, and MnCC vaccine at 2, 6 and 12 months. For the

J. Wysocki; S. Tansey; E. Brachet; S. Baker; W. Gruber; P. Giardina; A. Arora

2010-01-01

102

Immunogenicity of a Reduced Schedule of Meningococcal Group C Conjugate Vaccine Given Concomitantly with the Prevenar and Pediacel Vaccines in Healthy Infants in the United Kingdom?  

PubMed Central

This study investigated the use of two doses of three different meningococcal group C conjugate (MCC) vaccines when given for primary immunization with a seven-valent pneumococcal conjugate vaccine (PCV7) and Pediacel, a combination product containing five acellular pertussis components, diphtheria and tetanus toxoids, Haemophilus influenzae type b (Hib) conjugate, and inactivated-poliovirus vaccine. The immune response after a single dose of MCC is also presented. Infants were randomized to receive two doses of one of the MCC vaccines and PCV7 at 2 and 3 months or at 2 and 4 months of age. Meningococcal group C serum bactericidal antibody (SBA) geometric mean titers, Hib-polyribosylribitol phosphate (PRP) immunoglobulin G (IgG) geometric mean concentrations (GMCs), and diphtheria and tetanus antitoxin GMCs, together with the proportions of infants achieving putative protective levels, were determined. A total of 393 infants were recruited. Following the first dose of NeisVac-C (MCC conjugated to tetanus toxoid), 97% of infants achieved protective levels (SBA titer of ?8), compared with 80% and 53%, respectively, for Menjugate and Meningitec (both of which are conjugated to CRM197). SBA responses to MCC vaccines were not significantly different when administered at 2 and 3 or 2 and 4 months of age. Following two doses of each MCC, 98 to 100% of infants achieved protective levels. Both PRP IgG and tetanus responses were significantly enhanced when Pediacel was coadministered with NeisVac-C. This study demonstrates that NeisVac-C and Menjugate generate good immunogenicity after the first dose at 2 months of age when coadministered with PCV7 and Pediacel and merit further investigation in single-dose priming strategies.

Southern, Jo; Borrow, Ray; Andrews, Nick; Morris, Rhonwen; Waight, Pauline; Hudson, Michael; Balmer, Paul; Findlow, Helen; Findlow, Jamie; Miller, Elizabeth

2009-01-01

103

Immunogenicity of a reduced schedule of meningococcal group C conjugate vaccine given concomitantly with the Prevenar and Pediacel vaccines in healthy infants in the United Kingdom.  

PubMed

This study investigated the use of two doses of three different meningococcal group C conjugate (MCC) vaccines when given for primary immunization with a seven-valent pneumococcal conjugate vaccine (PCV7) and Pediacel, a combination product containing five acellular pertussis components, diphtheria and tetanus toxoids, Haemophilus influenzae type b (Hib) conjugate, and inactivated-poliovirus vaccine. The immune response after a single dose of MCC is also presented. Infants were randomized to receive two doses of one of the MCC vaccines and PCV7 at 2 and 3 months or at 2 and 4 months of age. Meningococcal group C serum bactericidal antibody (SBA) geometric mean titers, Hib-polyribosylribitol phosphate (PRP) immunoglobulin G (IgG) geometric mean concentrations (GMCs), and diphtheria and tetanus antitoxin GMCs, together with the proportions of infants achieving putative protective levels, were determined. A total of 393 infants were recruited. Following the first dose of NeisVac-C (MCC conjugated to tetanus toxoid), 97% of infants achieved protective levels (SBA titer of >or=8), compared with 80% and 53%, respectively, for Menjugate and Meningitec (both of which are conjugated to CRM(197)). SBA responses to MCC vaccines were not significantly different when administered at 2 and 3 or 2 and 4 months of age. Following two doses of each MCC, 98 to 100% of infants achieved protective levels. Both PRP IgG and tetanus responses were significantly enhanced when Pediacel was coadministered with NeisVac-C. This study demonstrates that NeisVac-C and Menjugate generate good immunogenicity after the first dose at 2 months of age when coadministered with PCV7 and Pediacel and merit further investigation in single-dose priming strategies. PMID:19091990

Southern, Jo; Borrow, Ray; Andrews, Nick; Morris, Rhonwen; Waight, Pauline; Hudson, Michael; Balmer, Paul; Findlow, Helen; Findlow, Jamie; Miller, Elizabeth

2008-12-17

104

Pneumococcal Conjugate Vaccine (PCV7)  

MedlinePLUS

... the intervals between doses will depend on the child's age. Ask your health care provider for details.Children 2 through 4 Years ... allergy to any vaccine component. Tell your health-care provider if your child has ever had a severe reaction to any ...

105

Pneumococcal Conjugate Vaccine for Adults: A New Paradigm  

PubMed Central

A 13-valent pneumococcal conjugate vaccine has been studied in adults aged ?50 years to compare the immune response to that induced by the 23-valent pneumococcal polysaccharide vaccine, which has been the standard of care over the past 30 years. The results demonstrate that adults, regardless of whether they are naive or previously vaccinated with the polysaccharide vaccine, have an overall superior antibody response when vaccinated with the conjugate vaccine compared with the pneumococcal polysaccharide vaccine. More importantly, the nature of the response is indicative of a T-cell–dependent response that elicits immunological memory and, therefore, primes the immune system for either natural exposure or subsequent booster vaccination with either conjugate or polysaccharide vaccine. The conjugate vaccine, which has been successful in reducing pneumococcal disease in children, now provides a new approach to preventing pneumococcal disease, including community-acquired pneumonia, in adults.

Paradiso, Peter R.

2012-01-01

106

Humoral immunity to aerosolized staphylococcal enterotoxin B (SEB), a superantigen, in monkeys vaccinated with SEB toxoid-containing microspheres.  

PubMed Central

Staphylococcal enterotoxin B (SEB) toxoid-containing microspheres were tested for efficacy in rhesus monkeys as a vaccine candidate for respiratory SEB toxicosis and toxic shock. Forty monkeys were randomly separated into 10 groups of four monkeys each: 9 groups were vaccinated with the microspheres via combinations of mucosal and nonmucosal routes, and 1 group served as nonvaccinated controls. Both vaccinated and nonvaccinated monkeys were then challenged with a high lethal dose of SEB aerosol. Monkeys primed with an intramuscular dose of the microspheres followed by an intratracheal booster all survived the SEB challenge. Overall, monkeys with an intratracheal booster generally had the highest antibody levels, which is consistent with their high survival rate and lower rate of illness. Protective immunity was correlated with antibody levels in both the circulation and the respiratory tract. The protection was not due to the depletion or anergy of SEB-reactive T cells, since SEB-induced proliferation in cultures of circulating lymphocytes was not significantly reduced after the microsphere vaccination. It is evident that the nonsurvivors did not die of systemic anaphylaxis or hypersensitivity because the monkeys did not die immediately after SEB challenge and there were no significant differences in histamine levels between the vaccinated and control monkeys before and after SEB challenge. The antibodies seemed to neutralize the SEB that got into the airway and the circulation.

Tseng, J; Komisar, J L; Trout, R N; Hunt, R E; Chen, J Y; Johnson, A J; Pitt, L; Ruble, D L

1995-01-01

107

Oligosaccharide conjugates of Bordetella pertussis and bronchiseptica induce bactericidal antibodies, an addition to pertussis vaccine  

PubMed Central

Pertussis is a highly contagious respiratory disease that is especially dangerous for infants and children. Despite mass vaccination, reported pertussis cases have increased in the United States and other parts of the world, probably because of increased awareness, improved diagnostic means, and waning vaccine-induced immunity among adolescents and adults. Licensed vaccines do not kill the organism directly; the addition of a component inducing bactericidal antibodies would improve vaccine efficacy. We investigated Bordetella pertussis and Bordetella bronchiseptica LPS-derived core oligosaccharide (OS) protein conjugates for their immunogenicity in mice. B. pertussis and B. bronchiseptica core OS were bound to aminooxylated BSA via their terminal Kdo residues. The two conjugates induced similar anti-B. pertussis LPS IgG levels in mice. B. bronchiseptica was investigated because it is easier to grow than B. pertussis. Using B. bronchiseptica genetically modified strains deficient in the O-specific polysaccharide, we isolated fractions of core OS with one to five repeats of the terminal trisaccharide, having at the nonreducing end a GlcNAc or GalNAc, and bound them to BSA at different densities. The highest antibody levels in mice were elicited by conjugates containing an average of 8–17 OS chains per protein and with one repeat of the terminal trisaccharide. Conjugate-induced antisera were bactericidal against B. pertussis, and the titers correlated with ELISA-measured antibody levels (r = 0.74). Such conjugates are easy to prepare and standardize; added to a recombinant pertussis toxoid, they may induce antibacterial and antitoxin immunity.

Kubler-Kielb, Joanna; Vinogradov, Evgeny; Lagergard, Teresa; Ginzberg, Ariel; King, Jerry D.; Preston, Andrew; Maskell, Duncan J.; Pozsgay, Vince; Keith, Jerry M.; Robbins, John B.; Schneerson, Rachel

2011-01-01

108

Haemophilus influenzae type b conjugate vaccines  

PubMed Central

Haemophilus influenzae type b (Hib) is one of the leading causes of invasive bacterial infection in young children worldwide. During childhood, acquisition of antibody directed against the polysaccharide capsule of the organism, presumably as a result of asymptomatic carriage, confers protection and disease is much less common after the age of 4 years. Like other polysaccharides, the polyribosyl ribitol phosphate (PRP) of the Hib capsule is a T-independent antigen and not immunogenic when administered as a vaccine in infancy. Because the highest rates of disease occur in the first 2 years of life, efficacious Hib vaccines have been designed by covalently linking the PRP capsule to a carrier protein that recruits T-cell help for the polysaccharide immune response and induces anti-PRP antibody production even in the first 6 months of life. Introduction of Hib protein–polysaccharide conjugate vaccines into many industrialized countries over the past 15 years has resulted in the virtual elimination of invasive Hib disease. However, despite the success of the vaccine programme several factors may interfere with the effectiveness of the vaccine in the routine programme, as observed in the UK recently. Such factors may include interference with other concomitant vaccines, waning immunity in the absence of booster doses of vaccine, and reduced natural boosting as a result of decreased transmission of the organism. However, the burden of disease remains highest in resource-poor countries and urgent efforts are needed to provide the benefits of this vaccine for children living in regions where it cannot be used for economic and logistical reasons.

Kelly, Dominic F; Moxon, E Richard; Pollard, Andrew J

2004-01-01

109

A Synthetic Conjugate Polysaccharide Vaccine Against Haemophilus influenzae Type b  

Microsoft Academic Search

Glycoconjugate vaccines provide effective prophylaxis against bacterial infections. To date, however, no commercial vaccine has been available in which the key carbohydrate antigens are produced synthetically. We describe the large-scale synthesis, pharmaceutical development, and clinical evaluation of a conjugate vaccine composed of a synthetic capsular polysaccharide antigen of Haemophilus influenzae type b (Hib). The vaccine was evaluated in clinical trials

V. Verez-Bencomo; V. Fernández-Santana; Eugenio Hardy; Maria E. Toledo; Maria C. Rodríguez; Lazaro Heynngnezz; Arlene Rodriguez; Alberto Baly; Luis Herrera; Mabel Izquierdo; Annette Villar; Yury Valdés; Karelia Cosme; Mercedes L. Deler; Manuel Montane; Ernesto Garcia; Alexis Ramos; Aristides Aguilar; Ernesto Medina; Gilda Toraño; Iván Sosa; Ibis Hernandez; Raydel Martínez; Alexis Muzachio; Ania Carmenates; Lourdes Costa; Félix Cardoso; Concepción Campa; Manuel Diaz; René Roy

2004-01-01

110

Response of calves persistently infected with noncytopathic bovine viral diarrhea virus (BVDV) subtype 1b after vaccination with heterologous BVDV strains in modified live virus vaccines and Mannheimia haemolytica bacterin-toxoid  

Microsoft Academic Search

Seronegative persistently infected (PI) calves with bovine viral diarrhea virus (BVDV) subtype 1b were vaccinated with each of four modified live virus (MLV) BVDV vaccines and a Mannheimia haemolytica bacterin-toxoid. Nasal swabs and peripheral blood leukocytes (PBL) were collected for virus isolation and serums were collected after vaccination and tested for BVDV1a, BVDV1b, BVDV2, bovine herpesvirus-1 (BHV-1), bovine parainfluenza-3 virus

Robert W. Fulton; Douglas L. Step; Julia F. Ridpath; Jeremiah T. Saliki; Anthony W. Confer; Bill J. Johnson; Robert E. Briggs; R. V. Hawley; Lurinda J. Burge; Mark E. Payton

2003-01-01

111

Immunogenicity, Reactogenicity, and Immune Memory after Primary Vaccination with a Novel Haemophilus influenzae-Neisseria meningitidis Serogroup C Conjugate Vaccine?  

PubMed Central

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-CRM197 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 (?1:8) or concentrations of anti-polyribosyl ribitol phosphate (PRP) antibody (?0.15 ?g/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.

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

2007-01-01

112

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

PubMed

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

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

2013-08-17

113

Neither antibody to a group B streptococcal conjugate vaccine nor the vaccine itself is teratogenic in rabbits  

PubMed Central

Group B Streptococcus (GBS) is a leading cause of human neonatal bacterial disease, resulting in pneumonia, sepsis, meningitis and sometimes, death. Supportive preclinical studies of GBS capsular polysaccharide (CPS)-protein conjugate vaccines have led to several phase 1 and phase 2 trials in healthy, non-pregnant adults, which demonstrated that the vaccines, produced at the Channing Laboratory, were safe and immunogenic. However, evaluation of the safety and immunogenicity of a GBS conjugate vaccine administered to pregnant women demanded that it be manufactured under current good manufacturing practices (cGMP) and that it undergo developmental toxicity evaluation. In this report, we describe a GBS type III CPS-tetanus toxoid (III-TT) vaccine lot 3-1-96 manufactured and vialed under cGMP and our evaluation of the effect of this vaccine and of GBS type III CPS-specific antibody on conception and early- and late-stage fetal development in rabbits. III-TT lot 3-1-96 was compositionally similar to prototype III-TT lot 91-1, produced under non-GMP, and was potent in a mouse maternal vaccination-neonatal pup challenge model of GBS disease. Four groups of 30 female rabbits each were randomized to receive III-TT lot 3-1-96 vaccine, saline-alum, or combinations of these treatments before and after insemination. The dose of conjugated CPS on a weight basis was 1 ?g/kg, mimicking the anticipated actual human dose. Based on the weight of the rabbits, this was 20- to 100-fold greater than the expected human dose. Does were pre-assigned to deliver litters naturally or have their kits delivered by Caesarean-section at gestation day 29, to assess late fetal development. Sera from does and kits were collected, and the presence of type III CPS-specific IgG was confirmed by quantitative ELISA. Based on all assessments, GBS type III-TT lot 3-1-96, nor antibody to it did not affect embryo-fetal viability, sex ratio, growth or cause malformations (i.e., it was non-teratogenic). In addition, that III-TT lot 3-1-96 was found to be safe and immunogenic in two clinical studies involving healthy non-pregnant adults supports a clinical evaluation of this vaccine in pregnant women.

Paoletti, Lawrence C.; Guttormsen, Hilde-Kari; Christian, Mildred S.; Hoberman, Alan M.; McInnes, Pamela

2009-01-01

114

Simultaneous administration of HB recombinant vaccine with diphtheria and tetanus toxoid and oral polio vaccine: a pilot study.  

PubMed

An extensive vaccination program to be used in highly endemic areas is the main strategy against the spreading of hepatitis B. The purpose of this study was the evaluation of the immune response to the recombinant HB vaccine administered singly or at the same time as other compulsory vaccines anti-diphtheria, anti-tetanus and oral anti-polio. Evidence was found of the serological efficacy both of HB vaccine and compulsory vaccines with a percentage of seroconversion of 100%. However, the infants who received HB vaccine at birth and at the age of 1 month had titers of antiHBs higher than the infants who received HB vaccine at birth and at 3 months. No difference in antibody levels of compulsory vaccines was observed among the study groups and the controls who received only compulsory vaccines. Our results suggest that HB vaccination must be encouraged and pursued in all newborns. PMID:1838852

Barone, P; Mauro, L; Leonardi, S; Ienna, M; Giammanco Bilancia, G; Falcidia, E; Musumeci, S

1991-08-01

115

Botulinum Toxoids.  

National Technical Information Service (NTIS)

Procedures were developed for preparing purified aluminum-phosphate-absorbed, univalent, bivalent, and pentavalent botulinum toxoids to immunize man. All preparations were well tolerated and elicited satisfactory antitoxin responses in man, whether admini...

M. A. Cardella

1964-01-01

116

Functional Antibodies Elicited by Two Heptavalent Pneumococcal Conjugate Vaccines in the Finnish Otitis Media Vaccine Trial  

Microsoft Academic Search

In the Finnish Otitis Media Vaccine Trial, the now-licensed pneumococcal conjugate vaccine containing polysaccharides conjugated to protein CRM197 (PncCRM) and the experimental pneumococcal polysaccha- ride-meningococcal outer membrane protein complex conjugate vaccine (PncOMPC), showed similar efficacy profiles against acute otitis media despite different antibody concentrations in sera. We now report the opsonophagocytic activities (OPA) in these sera. OPA, antibody concentration, and

Nina Ekstrom; Merja Vakevainen; Jouko Verho; Terhi Kilpi; Helena Kayhty

2007-01-01

117

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

PubMed Central

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

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

1997-01-01

118

The impact of vaccines on pneumonia: Key lessons from Haemophilus influenzae type b conjugate vaccines  

Microsoft Academic Search

This article explores key lessons learned from vaccination with Haemophilus influenzae type b (Hib) conjugate vaccine and how these lessons may provide insight into the impact of emergent pneumococcal vaccines against pneumonia. The worldwide value of Hib vaccination for reducing Hib disease burden and carriage is reviewed. Using comparisons of data for pneumococcus versus Hib, the article concludes that epidemiological

Bradford D. Gessner; Richard A. Adegbola

2008-01-01

119

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

PubMed

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

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

2009-11-11

120

Kinetics of Antibody Persistence following Administration of a Combination Meningococcal Serogroup C and Haemophilus influenzae Type b Conjugate Vaccine in Healthy Infants in the United Kingdom Primed with a Monovalent Meningococcal Serogroup C Vaccine ?  

PubMed Central

The kinetics of antibody persistence following the administration of a combination meningococcal serogroup C and Haemophilus influenzae type b (Hib) conjugate vaccine (Menitorix) in the second year of life in children primed with two doses of one of three monovalent meningococcal serogroup C (MCC) vaccines was investigated. The study subjects were administered either Menitorix at 12 to 15 months of age, followed by the seven-valent pneumococcal conjugate vaccine (PCV7) and the measles, mumps, and rubella vaccine 4 to 6 weeks later, or all three vaccines concomitantly at 12 to 15 months of age. Blood samples were collected before and 1, 2, 12, and 24 months after the boosting. Sera were analyzed for meningococcal serogroup C serum bactericidal antibody (SBA) and IgG as well as Hib-polyribosylribitol phosphate (PRP)-specific IgG. The antibody persistence data from this study were compared to those of a prior study of Southern et al. (Clin. Vaccine Immunol. 14:1328-1333, 2007) in which children were given three primary doses of a vaccine containing both the MCC and the Hib vaccines but were boosted only with a Hib conjugate vaccine. The magnitude of the meningococcal SBA geometric mean titer was higher for those subjects primed with the MCC vaccine conjugated to tetanus toxoid (NeisVac-C) than for those primed with one of two MCC vaccines conjugated to CRM197 (Menjugate or Meningitec) up to 1 year following boosting. Two years after boosting, the percentages of subjects with putatively protective SBA titers of ?8 for children primed with NeisVac-C, Menjugate, and Meningitec were 43%, 22%, and 23%, respectively. Additional booster doses of the MCC vaccine may be required in the future to maintain good antibody levels; however, there is no immediate need for a booster during adolescence, as mathematical modeling has shown that persisting herd immunity is likely to control disease for a number of years.

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

2010-01-01

121

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

PubMed Central

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.

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

122

Maternal immunization with pneumococcal polysaccharide vaccine in the Philippines  

Microsoft Academic Search

A randomized, controlled study was conducted to evaluate the immunogenicity and reactogenicity of the 23-valent pneumococcal (Pnc) polysaccharide (PS) vaccine among pregnant women and to ascertain the transfer of anti-Pnc antibody (Ab) from mother to infant. One hundred and sixty women received either one dose of Pnc PS vaccine, Haemophilus influenzae type b conjugate vaccine and tetanus toxoid (TT) (Pnc

B. P. Quiambao; H. Nohynek; H. Käyhty; J. Ollgren; L. Gozum; C. P. Gepanayao; V. Soriano; P. H. Mäkela

2003-01-01

123

Serotype-Specific and Age-Dependent Generation of Pneumococcal Polysaccharide-Specific Memory B-Cell and Antibody Responses to Immunization with a Pneumococcal Conjugate Vaccine?  

PubMed Central

Glycoconjugate vaccines have dramatically reduced the incidence of encapsulated bacterial diseases in toddlers under 2 years of age, but vaccine-induced antibody levels in this age group wane rapidly. We immunized adults and 12-month-old toddlers with heptavalent pneumococcal conjugate vaccine to determine differences in B-cell and antibody responses. The adults and 12-month-old toddlers received a pneumococcal conjugate vaccine. The toddlers received a second dose at 14 months of age. The frequencies of diphtheria toxoid and serotype 4, 14, and 23F polysaccharide-specific plasma cells and memory B cells were determined by enzyme-linked immunospot assay. The toddlers had no preexisting polysaccharide-specific memory B cells or serum immunoglobulin G (IgG) antibody but had good diphtheria toxoid-specific memory responses. The frequencies of plasma cells and memory B cells increased by day 7 (P < 0.0001) in the adults and the toddlers following a single dose of conjugate, but the polysaccharide responses were significantly lower in the toddlers than in the adults (P = 0.009 to <0.001). IgM dominated the toddler antibody responses, and class switching to the IgG was serotype dependent. A second dose of vaccine enhanced the antibody and memory B-cell responses in the toddlers but not the ex vivo plasma cell responses. Two doses of pneumococcal conjugate vaccine are required in toddlers to generate memory B-cell frequencies and antibody class switching for each pneumococcal polysaccharide equivalent to that seen in adults.

Clutterbuck, Elizabeth A.; Oh, Sarah; Hamaluba, Mainga; Westcar, Sharon; Beverley, Peter C. L.; Pollard, Andrew J.

2008-01-01

124

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

PubMed

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

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

2013-10-01

125

Protein Conjugate Polysaccharide Vaccines: Challenges in Development and Global Implementation  

PubMed Central

Pneumonia and meningitis caused by Haemophilus influenzae type b, Streptococcus pneumoniae, and Neisseria meningitidis are among the leading causes of under five mortality and morbidity. Polysaccharide vaccines to prevent these infections are available since 1980s, but these are not effective in infants and children who are the common targets; therefore, protein conjugated were developed. The aim of this article is to understand the need for peumococcal protein conjugate vaccines, the challenges related to their development and global implementation, and the impact of these vaccines on global child health. Challenges in development of new vaccines are as follows: While pneumonia is a major threat in developing countries, available vaccine 7-valent pneumococcal conjugate vaccine (PCV7) protects against only 30% of invasive disease.Serogroup B of Neisseria meningitidis causes 32% of the cases in the USA and 45–80% or more in Europe. Due to similarity of its capsular polysaccharide with the cell surface glycoprotein on fetal brain tissue, developing a vaccine against this bacterium remains a challenge. Challenges in implementation are as follows: Replacement by nonvaccine serotypes;capsule switching;time duration of the antibody protective effect following vaccination;costs of the vaccines, programme costs, lack of knowledge of the disease burden, and targeting population groups for vaccination.

Nair, Manisha

2012-01-01

126

Phase I clinical evaluation of a synthetic oligosaccharide-protein conjugate vaccine against Haemophilus influenzae type b in human adult volunteers.  

PubMed

Since 1989, we have been involved in the development of a vaccine against Haemophilus influenzae type b. The new vaccine is based on the conjugation of synthetic oligosaccharides to tetanus toxoid. Our main goals have been (i) to verify the feasibility of using the synthetic antigen and (ii) to search for new production alternatives for this important infant vaccine. Overall, eight trials have already been conducted with adults, children (4 to 5 years old), and infants. We have described herein the details from the first two phase I clinical trials conducted with human adult volunteers under double blind, randomized conditions. The participants each received a single intramuscular injection to evaluate safety and initial immunogenicity. We have found an excellent safety profile and an antibody response similar to the one observed for the control vaccine. PMID:16960118

Toraño, Gilda; Toledo, Maria E; Baly, Alberto; Fernandez-Santana, Violeta; Rodriguez, Francisco; Alvarez, Yunia; Serrano, Teresita; Musachio, Alexis; Hernandez, Ibis; Hardy, Eugenio; Rodríguez, Arlene; Hernandez, Hector; Aguilar, Aristides; Sánchez, Raydel; Diaz, Manuel; Muzio, Verena; Dfana, Jorgelina; Rodríguez, Maria C; Heynngnezz, Lazaro; Verez-Bencomo, Vicente

2006-09-01

127

Safety and immunogenicity of two octavalent pneumococcal conjugate vaccines in American Indian infants.  

PubMed

We evaluated the safety and immunogenicity of two octavalent pneumococcal polysaccharide vaccines (serotypes 3, 4, 6B, 9V, 14, 18C, 19F, and 23F) conjugated to either diphtheria toxoid (PncD) or tetanus protein (PncT) among White Mountain Apache and Gila River Indian Community infants. This was a prospective, non-randomized, open label, comparative pilot study of PncD and PncT. Since this was a pilot study, a small sample size of 60 infants was enrolled. Enrolled healthy infants received either PncD or PncT at 2, 4, and 6 months of age. Antibody concentrations were measured by enzyme-immunoassay (EIA) prior to each dose and 1 month after the last dose. Local reaction rates were similar between PncD and PncT groups. The geometric mean concentrations (GMCs) were significantly higher for PncD than PncT for serotype 3 whereas GMCs were significantly higher for PncT for serotype 4. For this pilot study, both vaccines appeared to be safe and immunogenic in this group of American Indian infants. PMID:15003655

Eick, Angelia; Croll, Janné; Weatherholtz, Robert; Croll, Larry; Santosham, Mathuram

2004-03-12

128

Response of calves persistently infected with noncytopathic bovine viral diarrhea virus (BVDV) subtype 1b after vaccination with heterologous BVDV strains in modified live virus vaccines and Mannheimia haemolytica bacterin-toxoid.  

PubMed

Seronegative persistently infected (PI) calves with bovine viral diarrhea virus (BVDV) subtype 1b were vaccinated with each of four modified live virus (MLV) BVDV vaccines and a Mannheimia haemolytica bacterin-toxoid. Nasal swabs and peripheral blood leukocytes (PBL) were collected for virus isolation and serums were collected after vaccination and tested for BVDV1a, BVDV1b, BVDV2, bovine herpesvirus-1 (BHV-1), bovine parainfluenza-3 virus (PI-3V), and bovine respiratory syncytial virus (BRSV) antibodies. M. haemolytica and Pasteurella multocida antibodies were detected using ELISA procedures. None of the PI calves developed mucosal disease (MD) after MLV vaccination. None of the BVDV PI calves seroconverted to BVDV1b after MLV vaccination. Calves receiving MLV vaccines seroconverted to the respective type/subtype in the vaccine. Calves receiving a MLV vaccine with noncytopathic (NCP) BVDV1 (subtype not designated) did not seroconvert to BVDV1a, BVDV1b, or BVDV2. The PI calves were positive for BVDV subtype 1b, in the PBL and nasal swabs throughout the study. Calves receiving each of three vaccines with known BVDV1a strains had BVDV1a positive samples after vaccination, in some but not all calves, up to Day 28. The PI BVDV1b calves did not respond with increased M. haemolytica antibodies after vaccination compared to BVDV negative calves receiving the same M. haemolytica vaccine. PMID:12798641

Fulton, Robert W; Step, Douglas L; Ridpath, Julia F; Saliki, Jeremiah T; Confer, Anthony W; Johnson, Bill J; Briggs, Robert E; Hawley, R V; Burge, Lurinda J; Payton, Mark E

2003-06-20

129

Isotypes and Opsonophagocytosis of Pneumococcus Type 6B Antibodies Elicited in Infants and Adults by an Experimental Pneumococcus Type 6B-Tetanus Toxoid Vaccine  

Microsoft Academic Search

Streptococcus pneumoniae is a major respiratory pathogen of infants, children, and the elderly. Polysaccha- ride vaccines have been useful in adult populations but do not elicit protective immunity in infants and young children. To enhance their immunogenicity, vaccines of pneumococcal polysaccharides conjugated to proteins are being developed. In this study antibody levels and opsonic activities were compared in sera of

GESTUR VIDARSSON; SIGURVEIG T. SIGURDARDOTTIR; THOROLFUR GUDNASON; SVEINN KJARTANSSON; KARL G. KRISTINSSON; GUNNHILDUR INGOLFSDOTTIR; STEINN JONSSON; HELGI VALDIMARSSON; GERALD SCHIFFMAN; RACHEL SCHNEERSON; INGILEIF JONSDOTTIR

1998-01-01

130

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

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-\\\

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

2003-01-01

131

Economic evaluation of pneumococcal conjugate vaccination in The Gambia  

Microsoft Academic Search

BACKGROUND: Gambia is the second GAVI support-eligible country to introduce the 7-valent pneumococcal conjugate vaccine (PCV7), but a country-specific cost-effectiveness analysis of the vaccine is not available. Our objective was to assess the potential impact of PCVs of different valences in The Gambia. METHODS: We synthesized the best available epidemiological and cost data using a state-transition model to simulate the

Sun-Young Kim; Gene Lee; Sue J Goldie

2010-01-01

132

Diphtheria, Tetanus, and Pertussis (DTaP) Vaccine  

MedlinePLUS

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

133

Protection against nontypeable Haemophilus influenzae challenges by mucosal vaccination with a detoxified lipooligosaccharide conjugate in two chinchilla models  

PubMed Central

Otitis media (OM) can occur following outset of upper respiratory tract infections. Inhibition of bacterial colonization in nasopharynx (NP) by mucosal vaccination may prevent OM by reducing bacterial invasion of the middle ears (MEs). In this study, 80 chinchillas were intranasally (i.n.) immunized with a detoxified lipooligosaccharide (dLOS)-tetanus toxoid conjugate vaccine of nontypeable Haemophilus influenzae (NTHi) mixed with cholera toxin (CT) or CT alone. All vaccinated animals responded with elevated levels of mucosal and serum anti-LOS antibodies. Two weeks after the last immunization, 40 chinchillas were challenged i.n. with NTHi to evaluate NP colonization and ME infection while the rest of the animals were challenged transbullarly (T.B.) to examine the development of OM. Compared to the control group, the vaccination inhibited not only bacterial colonization in NP and transmission to MEs in the i.n. challenge group but also bacterial colonization in NP and transmission to unchallenged ears in the T.B. challenge group. Though no difference was found in the challenged ears of either group right after the T.B. challenge, an early clearance of NTHi from NP and unchallenged ears as well as less severity of OM in the unchallenged ears were observed in vaccinated animals. Current results along with our previous data indicate that mucosal vaccination is capable of inhibiting NTHi NP colonization and preventing OM occurrence in chinchillas; the i.n. challenge model is preferable for testing the mucosal vaccines while the T.B. challenge model is superior for testing the systemic vaccines.

Hong, Wenzhou; Peng, Daxin; Rivera, Maritza; Gu, Xin-Xing

2009-01-01

134

Phase I trial of two recombinant vaccines containing the 19kd carboxy terminal fragment of Plasmodium falciparum merozoite surface protein 1 (msp-1 19) and T helper epitopes of tetanus toxoid  

Microsoft Academic Search

The safety and immunogenicity of 2 yeast-derived, blood-stage malaria vaccines were evaluated in a phase l trial. Healthy adults were given 2 or 3 doses of alum-adsorbed vaccine containing the 19 kDa carboxy-terminal fragment of the merozoite surface protein-1 (MSP-119) derived from the 3D7 or the FVO strain of Plasmodium falciparum fused to tetanus toxoid T-helper epitopes P30 and P2.

W. A Keitel; K. E Kester; R. L Atmar; A. C White; N. H Bond; C. A Holland; U Krzych; D. R Palmer; A Egan; C Diggs; W. R Ballou; B. F Hall; D Kaslow

1999-01-01

135

Vaccination against meningococcal disease in Europe: review and recommendations for the use of conjugate vaccines  

Microsoft Academic Search

At the end of 2005, six European countries had implemented public immunization campaigns with serogroup C conjugate vaccines, and all had experienced sub- stantial declines in the incidence of serogroup C disease. A quadrivalent ACWY meningococcal vaccine is in use in the USA, but serogroup A is extremely rare in Europe and serogroups Y and W135 are infrequent causes of

Caroline L. Trotter; Mary E. Ramsay

2007-01-01

136

Impact of meningococcal C conjugate vaccine in the UK  

Microsoft Academic Search

This review details the impact of the introduction of meningococcal serogroup C conjugate (MCC) vaccines in the UK. An overall reduction of 86.7% in the incidence of serogroup C infection in the targeted age groups has been observed from 1999 to 2001, with a concomitant decrease in deaths, from 67 in 1999 to 5 in 2001. The enhanced surveillance programme

P. BALMER; R. BORROW; E. MILLER

137

A synthetic conjugate polysaccharide vaccine against Haemophilus influenzae type b.  

PubMed

Glycoconjugate vaccines provide effective prophylaxis against bacterial infections. To date, however, no commercial vaccine has been available in which the key carbohydrate antigens are produced synthetically. We describe the large-scale synthesis, pharmaceutical development, and clinical evaluation of a conjugate vaccine composed of a synthetic capsular polysaccharide antigen of Haemophilus influenzae type b (Hib). The vaccine was evaluated in clinical trials in Cuba and showed long-term protective antibody titers that compared favorably to licensed products prepared with the Hib polysaccharide extracted from bacteria. This demonstrates that access to synthetic complex carbohydrate-based vaccines is feasible and provides a basis for further development of similar approaches for other human pathogens. PMID:15273395

Verez-Bencomo, V; Fernández-Santana, V; Hardy, Eugenio; Toledo, Maria E; Rodríguez, Maria C; Heynngnezz, Lazaro; Rodriguez, Arlene; Baly, Alberto; Herrera, Luis; Izquierdo, Mabel; Villar, Annette; Valdés, Yury; Cosme, Karelia; Deler, Mercedes L; Montane, Manuel; Garcia, Ernesto; Ramos, Alexis; Aguilar, Aristides; Medina, Ernesto; Toraño, Gilda; Sosa, Iván; Hernandez, Ibis; Martínez, Raydel; Muzachio, Alexis; Carmenates, Ania; Costa, Lourdes; Cardoso, Félix; Campa, Concepción; Diaz, Manuel; Roy, René

2004-07-23

138

Pneumococcal 7-valent Conjugate Vaccine (Diphtheria ...  

Center for Biologics Evaluation and Research (CBER)

Text Version... molded vials 175 (150) Full-scale manufacturing lot uN" Lederle AIP04 adjuvant; sinQle dose tubinQ vials 175 (150) Control ... More results from www.fda.gov/downloads/biologicsbloodvaccines/vaccines

139

Pneumococcal 7-valent Conjugate Vaccine (Diphtheria ...  

Center for Biologics Evaluation and Research (CBER)

Text Version... CSF, joint fluid) obtained from a child presenting with an ... b) declaration of efficacy at early or primary ... FDA did not recommend the earliest look at 8 ... More results from www.fda.gov/downloads/biologicsbloodvaccines/vaccines

140

Pneumococcal 7-valent Conjugate Vaccine (Diphtheria ...  

Center for Biologics Evaluation and Research (CBER)

Text Version... vomiting, diarrhea. hives, change in skin tone. fever) and other systemic events (wheezing, convulsions, lethargic/limp. loss of consciousness. ... More results from www.fda.gov/downloads/biologicsbloodvaccines/vaccines

141

Pneumococcal 7-valent Conjugate Vaccine (Diphtheria ...  

Center for Biologics Evaluation and Research (CBER)

Text Version... devoted to the use ofthis carrier protein in the ... related to a pre-planned set of interim ... missing dose situations for the invasive disease analysis sets . ... More results from www.fda.gov/downloads/biologicsbloodvaccines/vaccines

142

Nasopharyngeal microbial interactions in the era of pneumococcal conjugate vaccination.  

PubMed

The nasopharynx of children is often colonised by microorganisms such as Streptococcus pneumoniae (the pneumococcus) that can cause infections including pneumonia and otitis media. In this complex environment, bacteria and viruses may impact each other through antagonistic as well as synergistic interactions. Vaccination may alter colonisation dynamics, evidenced by the rise in non-vaccine serotypes following pneumococcal conjugate vaccination. Discovery of an inverse relationship between S. pneumoniae and Staphylococcus aureus carriage generated concern that pneumococcal vaccination could increase S. aureus carriage and disease. Here we review data on co-colonisation of pathogens in the nasopharynx, focusing on S. pneumoniae and the impact of pneumococcal vaccination. Thus far, pneumococcal vaccination has not had a sustained impact on S. aureus carriage but it is associated with an increase in non-typeable Haemophilus influenzae in acute otitis media aetiology. Advances in bacterial and viral detection methodologies have facilitated research in nasopharyngeal microbiology and will aid investigation of potential vaccine-induced changes, particularly when baseline studies can be conducted prior to pneumococcal vaccine introduction. PMID:23523773

Dunne, Eileen M; Smith-Vaughan, Heidi C; Robins-Browne, Roy M; Mulholland, E Kim; Satzke, Catherine

2013-03-19

143

Pneumococcal 7-valent Conjugate Vaccine (Diphtheria ...  

Center for Biologics Evaluation and Research (CBER)

Text Version... Amendments 2 and 4 to 118-12 provided for immunization of control subjects at 7 and 9 ... Protocol amendment 1 provided for a 4th dose to be ... More results from www.fda.gov/downloads/biologicsbloodvaccines/vaccines

144

Immunologic memory in Haemophilus influenzae type b conjugate vaccine failure  

PubMed Central

Aims: To compare the convalescent antibody response to invasive Haemophilus influenzae type b (Hib) disease between conjugate vaccine immunised and unimmunised children, to look for evidence of priming for immunologic memory. Methods: Unmatched case-control study in the UK and Eire 1992–2001 and Victoria, Australia 1988–1990. A total of 93 children were identified as having invasive Hib disease following three doses of conjugate vaccine in infancy through post licensure surveillance throughout the UK and Eire; 92 unvaccinated children admitted to an Australian paediatric hospital with invasive Hib disease were used as historical controls. Convalescent serum was taken for measurement of Hib antibody concentration, and clinical information relating to potential disease risk factors was collected. The geometric mean concentrations of convalescent Hib antibodies were compared between immunised and unimmunised children, using raw and adjusted data. Results: Hib conjugate vaccine immunised children had higher serum Hib antibody responses to disease (geometric mean concentration (GMC) 10.81 µg/ml (95% CI 6.62 to 17.66) than unimmunised children (1.06 µg/ml (0.61 to 1.84)) (p < 0.0001). However, following adjustment for the significant confounding influences of age at presentation and timing of serum collection, a difference persisted only in children presenting with meningitis (vaccinated GMC 3.78 µg/ml (2.78 to 5.15); unvaccinated GMC 1.48 µg/ml (0.90 to 2.21); p = 0.003). Conclusions: Higher antibody responses to invasive Hib disease in vaccinated children with meningitis reflect priming for immunologic memory by the vaccine. Although a majority of children in the UK are protected from Hib disease by immunisation, the relative roles of immunologic memory and other immune mechanisms in conferring protection remain unclear.

McVernon, J; Johnson, P; Pollard, A; Slack, M; Moxon, E

2003-01-01

145

Immunogenicity and Tolerance of a 7Valent Pneumococcal Conjugate Vaccine in Nonresponders to the 23Valent Pneumococcal Vaccine  

Microsoft Academic Search

There is still a lack of effective vaccination strategies for patients with a deficient antibody response to bacterial polysaccharide antigens. In an open trial, we evaluated the immunogenicity and tolerance of a new 7-valent pneumococcal conjugate vaccine in 22 infection-prone nonresponders to pneumococcal polysaccharide vaccine and 21 controls. In the patient group, nonresponsiveness was confirmed by repeated vaccination with a

S. Zielen; I. Buhring; N. Strnad; J. Reichenbach; D. Hofmann

2000-01-01

146

Current knowledge regarding the investigational 13-valent pneumococcal conjugate vaccine.  

PubMed

The introduction of a 7-valent pneumococcal conjugate vaccine (PCV-7) into the routine childhood vaccination schedule has been shown to be effective in preventing invasive pneumococcal disease (IPD), pneumonia, otitis media and meningitis in infants and young children as determined by epidemiological surveillance studies. There has been a rise in IPD due to nonvaccine serotypes; however, this rise is small compared with the overall reduction in IPD. Non-PCV-7 serotypes and vaccine-related serotypes, such as serotypes 1, 5, 7F, 6A and 19A, have also been reported to cause IPD in some parts of the world where morbidity and mortality from pneumococcal disease are higher. An investigational 13-valent pneumococcal conjugate vaccine (PCV-13) uses CRM(197) as a carrier, similar to the current PCV-7, and covers serotypes 1, 3, 5, 6A, 7F and 19A, in addition to the serotypes of PCV-7 (serotype 4, 6B, 9V, 14, 18C, 19F and 23F). PCV-13 is safe and well tolerated with other pediatric vaccines in infants according to clinical trials. IgG anticapsular polysaccharide-binding concentrations and opsonophagocytic assay responses are similar and noninferior between PCV-13 and PCV-7 and, according to immunogenicity studies, PCV-13 has more potential to protect against pneumococcal diseases with the additional six serotypes. With the addition of these new serotypes, it could be possible to cover potential pneumococcal serotypes causing IPD throughout the world. The cost of the vaccine, its length of duration, optimal scheduling, combination and boosting with PCV-7 are still unresolved issues. Assessment of the vaccine's effectiveness and efficacy following potential licensure will require carefully designed cohort and case-control studies that can assess the indirect effects of PCV-13. PMID:19627181

Dinleyici, Ener Cagri; Yargic, Zeynel Abidin

2009-08-01

147

Immunologic memory in Haemophilus influenzae type b conjugate vaccine failure  

Microsoft Academic Search

Aims: To compare the convalescent antibody response to invasive Haemophilus influenzae type b (Hib) disease between conjugate vaccine immunised and unimmunised children, to look for evidence of priming for immunologic memory.Methods: Unmatched case-control study in the UK and Eire 1992–2001 and Victoria, Australia 1988–1990. A total of 93 children were identified as having invasive Hib disease following three doses of

J McVernon; P D R Johnson; A J Pollard; M P E Slack; E R Moxon

2003-01-01

148

Effects of Alum Adjuvant or a Booster Dose on Immunogenicity during Clinical Trials of Group B Streptococcal Type III Conjugate Vaccines  

PubMed Central

Phase 1 and 2 clinical trials of group B streptococcal (GBS) capsular polysaccharide (CPS)-protein conjugate vaccines in healthy adults have demonstrated their safety and improved immunogenicity compared with uncoupled CPSs. Two recent trials sought to determine (i) whether adsorption of conjugate vaccine to aluminum hydroxide would improve immunogenicity and (ii) whether the CPS-specific immunoglobulin G (IgG) response could be boosted by administration of a second dose. Adsorption of GBS type III CPS-tetanus toxoid (III-TT) conjugate vaccine to alum did not improve the immune response to a 12.5-?g dose in healthy adult recipients. Four weeks after vaccination, the geometric mean antibody concentrations (GMCs) for the 15 recipients of III-TT with or without alum were 3.3 and 3.6 ?g/ml, respectively. In the second trial, 36 healthy adults vaccinated previously with GBS III-TT conjugate were given a second 12.5-?g dose 21 months later. At 4 weeks after the second dose, the GMCs of type III CPS-specific IgG were similar to those measured 4 weeks after the primary vaccination, suggesting a lack of a booster response. However, 8 (22%) of the 36 participants who had undetectable III CPS-specific IgG (<0.05 ?g/ml) before the first dose of III-TT conjugate exhibited a booster response to the second dose, with a fourfold-greater GMC of type III CPS-specific IgG than after the initial immunization. These results suggest that prior natural exposure to type III GBS or a related antigen may be responsible for the brisk IgG response to CPS noted in most adults after vaccination. However, a second dose of GBS III-TT conjugate vaccine may be required for adults whose initial CPS-specific IgG concentrations are very low and would also restore the initial peak-specific III CPS-IgG in responders to previous vaccination.

Paoletti, L. C.; Rench, M. A.; Kasper, D. L.; Molrine, D.; Ambrosino, D.; Baker, C. J.

2001-01-01

149

Serological characterisation of anti-endotoxin sera directed against the conjugates of oligosaccharide core of Escherichia coli type R1, R2, R3, J5 and Salmonella Ra with tetanus toxoid.  

PubMed

The covalent conjugates of oligosaccharide core: Escherichia coli type R1, R2, R3, J5 and Salmonella Ra with tetanus toxoid have been prepared using reaction of reductive amination. The neoglycoconjugates were good immunogens in rabbits yielding a high level of anti-lipopolysaccharide antibodies of IgG class. The antibodies were used to examine the possibility of their reactions with smooth lipopolysaccharides. We have found that all antisera were able to react with the lipopolysaccharide molecules of identical or related core type, possessing core oligosaccharides substituted with O-specific chains. These reactions were shown in both the ELISA assay and the immunoblotting test. PMID:8954349

Lugowski, C; Jachymek, W; Niedziela, T; Rowinski, S

1996-11-01

150

Safety and Immunogenicity of a Meningococcal Quadrivalent Conjugate Vaccine in Five- to Eight-Year-Old Saudi Arabian Children Previously Vaccinated with Two Doses of a Meningococcal Quadrivalent Polysaccharide Vaccine  

PubMed Central

Saudi Arabian children respond poorly to 2 doses of meningococcal quadrivalent polysaccharide vaccine (MPSV4) when given before 2 years of age. This study examined whether such children were able to respond to 1 dose of quadrivalent meningococcal diphtheria toxoid conjugate vaccine (MCV4) when they were older. Saudi Arabian children 5 to 8 years of age who had previously been vaccinated with 2 doses of MPSV4 when they were under 2 years of age (termed the prior-MPSV4 group) were enrolled in a controlled, open-label, multicenter study. In the prior-MPSV4 group, children (n = 153) received 1 dose of MCV4, as did a group of age-matched meningococcal vaccine-naïve children (n = 85). Blood samples collected prevaccination and 28 days postvaccination were measured for serogroup-specific serum bactericidal antibody (SBA) levels in the presence of baby rabbit complement (rSBA) and for IgG antibody levels. Vaccine tolerability and safety were also evaluated. For all of the measured serogroups (A, C, Y, and W-135), the meningococcal vaccine-naïve participants achieved higher postvaccination rSBA geometric mean titers (GMTs) than did those in the prior-MPSV4 group. This was statistically significant for serogroup C (512 versus 167). Percentages of participants with postvaccination titers of ?8 and with ?4-fold increases in prevaccination to postvaccination titers appeared to be quite similar in the 2 groups. No worrisome safety signals were detected. MCV4 induced robust immune responses and was well tolerated in Saudi Arabian children who previously received 2 doses of MPSV4 as well as in those who were previously meningococcal vaccine naïve.

Khalil, Mohamed; Al-Mazrou, Yagob; Chadha, Helen; Bosch Castells, Valerie; Johnson, David R.; Borrow, Ray

2012-01-01

151

Safety and immunogenicity of a meningococcal quadrivalent conjugate vaccine in five- to eight-year-old Saudi Arabian children previously vaccinated with two doses of a meningococcal quadrivalent polysaccharide vaccine.  

PubMed

Saudi Arabian children respond poorly to 2 doses of meningococcal quadrivalent polysaccharide vaccine (MPSV4) when given before 2 years of age. This study examined whether such children were able to respond to 1 dose of quadrivalent meningococcal diphtheria toxoid conjugate vaccine (MCV4) when they were older. Saudi Arabian children 5 to 8 years of age who had previously been vaccinated with 2 doses of MPSV4 when they were under 2 years of age (termed the prior-MPSV4 group) were enrolled in a controlled, open-label, multicenter study. In the prior-MPSV4 group, children (n = 153) received 1 dose of MCV4, as did a group of age-matched meningococcal vaccine-naïve children (n = 85). Blood samples collected prevaccination and 28 days postvaccination were measured for serogroup-specific serum bactericidal antibody (SBA) levels in the presence of baby rabbit complement (rSBA) and for IgG antibody levels. Vaccine tolerability and safety were also evaluated. For all of the measured serogroups (A, C, Y, and W-135), the meningococcal vaccine-naïve participants achieved higher postvaccination rSBA geometric mean titers (GMTs) than did those in the prior-MPSV4 group. This was statistically significant for serogroup C (512 versus 167). Percentages of participants with postvaccination titers of ?8 and with ?4-fold increases in prevaccination to postvaccination titers appeared to be quite similar in the 2 groups. No worrisome safety signals were detected. MCV4 induced robust immune responses and was well tolerated in Saudi Arabian children who previously received 2 doses of MPSV4 as well as in those who were previously meningococcal vaccine naïve. PMID:22855388

Khalil, Mohamed; Al-Mazrou, Yagob; Findlow, Helen; Chadha, Helen; Bosch Castells, Valerie; Johnson, David R; Borrow, Ray

2012-08-01

152

10-valent pneumococcal nontypeable Haemophilus influenzae PD conjugate vaccine: Synflorix.  

PubMed

The global burden of disease due to Streptococcus pneumoniae remains high. The licensed 7-valent pneumococcal conjugate vaccine (7vCRM, Prevenar/Prevnar) has successfully reduced invasive disease in the USA, but serotype coverage is incomplete and some evidence suggests that serotype replacement has occurred. Recently, a new 10-valent pneumococcal nontypeable Haemophilus influenzae (NTHi) protein D (PD) conjugate vaccine (PHiD-CV, Synflorix) has been licensed in more than 40 countries, including Europe, for the prevention of invasive disease and acute otitis media (AOM) due to pneumococcus in infants and children. PHiD-CV is immunogenic in infants when administered as a three-dose primary vaccination in a range of schedules and has a safety profile comparable to that of 7vCRM. Additional serotypes in PHiD-CV (1, 5 and 7F) increase overall serotype coverage and improve coverage in specific age groups and against specific disease syndromes. The use of the PD carrier, which provided protection against AOM caused by NTHi in a large efficacy trial testing a prototype of the final vaccine formulation, suggests that PHiD-CV will also provide some protection against AOM due to NTHi. PMID:19863240

Prymula, Roman; Schuerman, Lode

2009-11-01

153

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

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.

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

2011-01-01

154

Results from a randomized clinical trial of coadministration of RotaTeq, a pentavalent rotavirus vaccine, and NeisVac-C, a meningococcal serogroup C conjugate vaccine.  

PubMed

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

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

2011-03-09

155

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

PubMed Central

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.

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

2011-01-01

156

Economic Evaluation of a Universal Childhood Pneumococcal Conjugate Vaccination Strategy in Ireland  

Microsoft Academic Search

ObjectiveTo evaluate the cost-effectiveness of implementing a universal infant 7-valent pneumococcal conjugate vaccine (PCV7) vaccination program in the Irish health-care setting from the health-care payers' perspective.

Lesley Tilson; Cara Usher; Karina Butler; John Fitzsimons; Fiona O'Hare; Suzanne Cotter; Darina O'Flanagan; Howard Johnson; Michael Barry

2008-01-01

157

Pneumococcal conjugate vaccination : clinical impact, reduced-dose schedules and immunologic responses  

Microsoft Academic Search

In the first 2 years after nationwide implementation (2006-2008), the pneumococcal conjugate vaccination proved to be highly effective in reducing invasive pneumococcal disease caused by vaccine serotypes in the vaccinated children. However, the rapid increase in non-vaccine serotype IPD reduced the net vaccine benefit. These emerging non-vaccine serotypes are also invasive and result in serious burden of disease. Pneumococcal disease

G. D. Rodenburg

2011-01-01

158

[Pneumococcal vaccine: protection of adults and reduction of antibiotic resistence by vaccination of children with a conjugated vaccine].  

PubMed

Pneumococcal infections (pneumonia, otitis media, sinusitis, meningitis) are common and usually involve toddlers, immunocompromised and the elderly. Main reservoir of pneumococci is the nasopharyngeal zone of healthy carriers, especially of toddlers. Currently, two types of pneumococcal vaccines are in clinical use, which induce production of antibodies against capsular polysaccharides. The older vaccine consists of pure capsular polysaccharides. It induces a limited immunity, because polysaccharides are poor antigens that stimulate mainly B-cells. In children under two years of age this vaccine is not used, because it does not induce a sufficient immunologic response, presumably because of the immaturity of their immune system. In 2000, a vaccination program with a novel pneumococcal vaccine was launched in the USA. This vaccine contains capsular polysaccharides, that are conjugated with a highly immunogenic protein. It induces both a T cell and B cell response that results in specific humoral and mucosal immunity. U.S. data demonstrate, that serotypes covered by the conjugated vaccine can be reduced in the whole population by vaccination of children being the main reservoir of pneumococci. This so called ,,herd protection" results in a decrease in invasive pneumococcal diseases in vaccinees and non-vaccinees as well as in a reduction of antibiotic resistance rates by reducing resistant pneumococcal cones. PMID:21812250

Pletz, Mathias W

2011-06-01

159

Economic evaluation of pneumococcal conjugate vaccination in The Gambia  

PubMed Central

Background Gambia is the second GAVI support-eligible country to introduce the 7-valent pneumococcal conjugate vaccine (PCV7), but a country-specific cost-effectiveness analysis of the vaccine is not available. Our objective was to assess the potential impact of PCVs of different valences in The Gambia. Methods We synthesized the best available epidemiological and cost data using a state-transition model to simulate the natural histories of various pneumococcal diseases. For the base-case, we estimated incremental cost (in 2005 US dollars) per disability-adjusted life year (DALY) averted under routine vaccination using PCV9 compared to no vaccination. We extended the base-case results for PCV9 to estimate the cost-effectiveness of PCV7, PCV10, and PCV13, each compared to no vaccination. To explore parameter uncertainty, we performed both deterministic and probabilistic sensitivity analyses. We also explored the impact of vaccine efficacy waning, herd immunity, and serotype replacement, as a part of the uncertainty analyses, by assuming alternative scenarios and extrapolating empirical results from different settings. Results Assuming 90% coverage, a program using a 9-valent PCV (PCV9) would prevent approximately 630 hospitalizations, 40 deaths, and 1000 DALYs, over the first 5 years of life of a birth cohort. Under base-case assumptions ($3.5 per vaccine), compared to no intervention, a PCV9 vaccination program would cost $670 per DALY averted in The Gambia. The corresponding values for PCV7, PCV10, and PCV13 were $910, $670, and $570 per DALY averted, respectively. Sensitivity analyses that explored the implications of the uncertain key parameters showed that model outcomes were most sensitive to vaccine price per dose, discount rate, case-fatality rate of primary endpoint pneumonia, and vaccine efficacy against primary endpoint pneumonia. Conclusions Based on the information available now, infant PCV vaccination would be expected to reduce pneumococcal diseases caused by S. pneumoniae in The Gambia. Assuming a cost-effectiveness threshold of three times GDP per capita, all PCVs examined would be cost-effective at the tentative Advance Market Commitment (AMC) price of $3.5 per dose. Because the cost-effectiveness of a PCV program could be affected by potential serotype replacement or herd immunity effects that may not be known until after a large scale introduction, type-specific surveillance and iterative evaluation will be critical.

2010-01-01

160

Maintaining protection against invasive bacteria with protein–polysaccharide conjugate vaccines  

Microsoft Academic Search

Polysaccharide-encapsulated organisms are the leading cause of bacterial meningitis and pneumonia in children. The use of protein–polysaccharide conjugate vaccines in developed countries over the past two decades has markedly decreased the burden of disease and mortality from these organisms through direct protection of the immunized and through herd immunity. In the next decade, the widespread use of conjugate vaccines in

Kirsten P. Perrett; Peter C. Beverley; Andrew J. Pollard

2009-01-01

161

Pneumococcal Conjugate Vaccines Overcome Splenic Dependency of Antibody Response to Pneumococcal Polysaccharides  

PubMed Central

Protection against infections with Streptococcus pneumoniae depends on the presence of antibodies against capsular polysaccharides that facilitate phagocytosis. Asplenic patients are at increased risk for pneumococcal infections, since both phagocytosis and the initiation of the antibody response to polysaccharides take place in the spleen. Therefore, vaccination with pneumococcal polysaccharide vaccines is recommended prior to splenectomy, which, as in the case of trauma, is not always feasible. We show that in rats, vaccination with a pneumococcal conjugate vaccine can induce good antibody responses even after splenectomy, particularly after a second dose. The spleen remains necessary for a fast, primary response to (blood-borne) polysaccharides, even when they are presented in a conjugated form. Coadministration of a conjugate vaccine with additional nonconjugated polysaccharides of other serotypes did not improve the response to the nonconjugated polysaccharides. We conclude that pneumococcal conjugate vaccines can be of value in protecting asplenic or hyposplenic patients against pneumococcal infections.

Breukels, Mijke A.; Zandvoort, Andre; van den Dobbelsteen, Germie P. J. M.; van den Muijsenberg, Adrie; Lodewijk, Monique E.; Beurret, Michel; Klok, Pieter A.; Timens, Wim; Rijkers, Ger T.

2001-01-01

162

Pneumococcal conjugate vaccines overcome splenic dependency of antibody response to pneumococcal polysaccharides.  

PubMed

Protection against infections with Streptococcus pneumoniae depends on the presence of antibodies against capsular polysaccharides that facilitate phagocytosis. Asplenic patients are at increased risk for pneumococcal infections, since both phagocytosis and the initiation of the antibody response to polysaccharides take place in the spleen. Therefore, vaccination with pneumococcal polysaccharide vaccines is recommended prior to splenectomy, which, as in the case of trauma, is not always feasible. We show that in rats, vaccination with a pneumococcal conjugate vaccine can induce good antibody responses even after splenectomy, particularly after a second dose. The spleen remains necessary for a fast, primary response to (blood-borne) polysaccharides, even when they are presented in a conjugated form. Coadministration of a conjugate vaccine with additional nonconjugated polysaccharides of other serotypes did not improve the response to the nonconjugated polysaccharides. We conclude that pneumococcal conjugate vaccines can be of value in protecting asplenic or hyposplenic patients against pneumococcal infections. PMID:11705936

Breukels, M A; Zandvoort, A; van Den Dobbelsteen, G P; van Den Muijsenberg, A; Lodewijk, M E; Beurret, M; Klok, P A; Timens, W; Rijkers, G T

2001-12-01

163

Implementation and impact of a meningococcal C conjugate vaccination program in 13- to 25-year-old individuals in Galicia, Spain.  

PubMed

BACKGROUND: In response to increased case numbers of meningococcal group C disease, catch-up vaccination strategies have been shown to be successful. This paper describes the results of a repeat vaccination program in Galicia, Spain, and the strategy used for it. METHODS AND RESULTS: Three vaccination waves were performed: first, in 1996/1997 with a meningococcal group A and C polysaccharide vaccine in individuals aged 18 months to 19 years; second, in 2000 with a conjugate serogroup C polysaccharide vaccine in children born since 1993 and all children and adolescents up to 19 years not previously vaccinated; third, a campaign in 2006 that became necessary because of the development of a new Neisseria strain and an increase in both the incidence and lethality of meningococcal C disease. The conjugate vaccine de-O-acetylated group C meningococcal polysaccharide coupled to tetanus toxoid was used (GCMP-TT; brand name, NeisVac-C). Results: Applying a strategy based on model calculations derived from the UK setting and focusing on a population aged 13-25 years, including students, employees of companies, and underage individuals, a total of 286,000 subjects were vaccinated, resulting in global vaccination coverage of 82.2% (all age groups over 74%). Only 17 adverse events in 17 individuals were reported, which all were mild. Incidence of meningococcal disease serogroup C by season was reduced from 0.84 cases per 100,000 in 2004/05 to 0.76 cases per 100,000 in 2005/2006 to 0.18/100,000 in 2007/08. In parallel, mortality was also decreased from 8 cases during 2005/06 (0.29 per 100,000) to 1 case in 2007/2008 (0.03 per 100,000). No cases of breakthrough disease occurred in the vaccinated population. CONCLUSION: In Galicia, a series of vaccination campaigns, particularly focusing on high-risk groups, has shown high effectiveness, with a marked reduction in the disease incidence in the vaccination cohort accompanied by a relevant reduction in the overall population. PMID:21957332

Rego Romero, Elena; Nartallo Penas, Victoria; Taboada Rodríguez, José Antonio; Malvar Pintos, Alberto; Hervada Vidal, Xurxo; López Pimentel, María José

2011-03-16

164

Do pneumococcal conjugate vaccines provide any cross-protection against serotype 19A?  

Microsoft Academic Search

BACKGROUND: Introduction of the 7-valent pneumococcal conjugate vaccine (7vCRM) in several countries has led to a rapid, significant drop in vaccine-type invasive pneumococcal disease (IPD) in immunized children. In the United States and some other countries with high antibiotic use, a subsequent rise in serotype 19A IPD has been taken to indicate that the 19F conjugate in the vaccine provides

William P Hausdorff; Bernard Hoet; Lode Schuerman

2010-01-01

165

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

Microsoft Academic Search

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

Metka Paragi; Jana Kolman; Alenka Kraigher; Milan ?ižman; Marija Gubina; Helena Ribi?

2003-01-01

166

Response to conjugate pneumococcal and Haemophilus influenzae type b vaccines in asplenic patients.  

PubMed

We determined the immunogenicity of conjugated Haemophilus influenzae type b and pneumococcal vaccines by quantitative analysis of the antibody response in asplenic patients. To that end, we vaccinated 92 patients with a conjugated Hib vaccine and 54 received two doses of conjugated pneumococcal vaccine (PCV7), followed at six months by a plain polysaccharide pneumococcal vaccine (PPV23). Antibody concentrations were measured before and three weeks after vaccination. After one dose of pneumococcal conjugate vaccine, 46% of the patients reached the antibody threshold of ? 1.0 ?g/mL for all 7 tested vaccine serotypes. This percentage rose to 54% after the second dose of PCV7 and did not increase further after PPV23. Over 90% of patients had antibody concentrations ? 1.0 ?g/mL for at least 5 out of the 7 conjugated pneumococcal serotypes after 2 doses of PCV7. For serotypes, included in the PPV23 vaccine only, 25% (PPS3)-100% (PPS19A) of the patients reached antibody concentrations ? 1.0 ?g/mL after one dose of PPV23. For Hib, 97% of the patients reached the threshold concentration of ? 1.0 ?g/mL after one dose of vaccine. It can be concluded that the majority of asplenic patients had a sufficient response to conjugated vaccines against Streptococcus pneumoniae and Hib, reflected by a ? 1.0 ?g/mL antibody response. Inclusion of conjugated pneumococcal polysaccharide vaccines might be of additional value in the vaccination schedule for asplenic patients because of their high immunogenicity. PMID:21115060

Meerveld-Eggink, A; de Weerdt, O; van Velzen-Blad, H; Biesma, D H; Rijkers, G T

2010-11-27

167

The Vi Conjugate Typhoid Vaccine Is Safe, Elicits Protective Levels of IgG Anti-Vi, and Is Compatible with Routine Infant Vaccines ? †  

PubMed Central

Typhoid fever remains a serious problem in developing countries. Current vaccines are licensed for individuals who are 5 years old or older. A conjugate of the capsular polysaccharide (CP) of Salmonella enterica serovar Typhi (Vi) bound to recombinant exoprotein A of Pseudomonas aeruginosa (Vi-rEPA) enhanced Vi immunogenicity and protected 2- to 5-year-olds in Vietnam. In this study, Vi-rEPA was evaluated for use in infants. A total of 301 full-term Vietnamese infants received Expanded Program on Immunization (EPI) vaccines alone or with Vi-rEPA or Haemophilus influenzae type b-tetanus toxoid conjugate (Hib-TT) at 2, 4, and 6 months and Vi-rEPA or Hib-TT alone at 12 months. Infants were visited 6, 24, and 48 h after each injection to monitor adverse reactions. Maternal, cord, and infant sera were assayed for IgG anti-Vi and for IgG antibodies to Hib CP and the diphtheria, tetanus, and pertussis toxins at 7, 12, and 13 months. No vaccine-related serious adverse reactions occurred. In the Vi-rEPA group, the IgG anti-Vi geometric mean (GM) increased from the cord level of 0.66 to 17.4 enzyme-linked immunosorbent assay units (EU) at 7 months, declined to 4.76 EU at 12 months, and increased to 50.1 EU 1 month after the 4th dose (95% of infants had levels of ?3.5 EU, the estimated protective level). Controls had no increase of the IgG anti-Vi GM. Infants with cord anti-Vi levels of <3.5 EU responded with significantly higher IgG anti-Vi levels than those with levels of ?3.5 EU. Anti-diphtheria, -tetanus, and -pertussis toxin levels were similar in all groups. Vi-rEPA was safe, induced protective anti-Vi levels, and was compatible with EPI vaccines, and it can be used in infants. High cord IgG anti-Vi levels partially suppressed infant responses to Vi-rEPA.

Thiem, Vu Dinh; Lin, Feng-Ying C.; Canh, Do Gia; Son, Nguyen Hong; Anh, Dang Duc; Mao, Nguyen Duc; Chu, Chiayung; Hunt, Steven W.; Robbins, John B.; Schneerson, Rachel; Szu, Shousun C.

2011-01-01

168

Cost Effectiveness of Pneumococcal Conjugate Vaccination against Acute Otitis Media in Children: A Review  

Microsoft Academic Search

While pneumococcal conjugate vaccines have shown to be highly effective against invasive pneumococcal disease, their potential effectiveness against acute otitis media (AOM) might become a major economic driver for implementing these vaccines in national immunization programmes. However, the relationship between the costs and benefits of available vaccines remains a controversial topic. Our objective is to systematically review the literature on

Chantal W. B. Boonacker; Pieter H. Broos; Elisabeth A. M. Sanders; Anne G. M. Schilder; Maroeska M. Rovers

2011-01-01

169

Short and Long-Term Effects of Pneumococcal Conjugate Vaccination of Children on Penicillin Resistance  

Microsoft Academic Search

Recent observations have shown that wide-scale vaccination with pneumococcal conjugate vaccines was associated with a reduction in invasive disease, supporting the expectation that vaccination could help reduce carriage of Streptococcus pneumoniae and control the spread of resistant strains. However, it is too early to assess whether these effects can be sustained in the long term. Here, we used mathematical modeling

L. Temime; D. Guillemot; P. Y. Boelle

2004-01-01

170

Haemophilus influenzae type b conjugate vaccine trial in Oxford: implications for the United Kingdom  

Microsoft Academic Search

The safety and immunogenicity of a Haemophilus influenzae type b conjugate vaccine was investigated in 103 infants immunised at 3, 5, and 9 months of age; the infants also received diphtheria, pertussis, and tetanus and polio vaccines. Side effects were compared with 99 matched infants receiving diphtheria, pertussis, and tetanus and polio vaccines only. No serious side effects were observed

G Tudor-Williams; J Frankland; D Isaacs; R T Mayon-White; J A MacFarlane; D G Rees; E R Moxon

1989-01-01

171

Immune Response to Meningococcal Serogroup C Conjugate Vaccine in Asplenic Individuals  

Microsoft Academic Search

Asplenic individuals are known to be at increased risk of infection with encapsulated bacteria. Recent United Kingdom recommendations stated that this at-risk group should receive one dose of the meningococcal serogroup C conjugate (MCC) vaccine. However, the immune response of asplenic individuals to MCC vaccine is unknown. The immune response of asplenics (n 130) to immunization with the MCC vaccine

Paul Balmer; Michelle Falconer; Paula McDonald; Nick Andrews; Emily Fuller; Christine Riley; Edward Kaczmarski; Raymond Borrow

2004-01-01

172

Decrease in Pneumococcal Co-Colonization following Vaccination with the Seven-Valent Pneumococcal Conjugate Vaccine  

PubMed Central

Understanding the epidemiology of pneumococcal co-colonization is important for monitoring vaccine effectiveness and the occurrence of horizontal gene transfer between pneumococcal strains. In this study we aimed to evaluate the impact of the seven-valent pneumococcal conjugate vaccine (PCV7) on pneumococcal co-colonization among Portuguese children. Nasopharyngeal samples from children up to 6 years old yielding a pneumococcal culture were clustered into three groups: pre-vaccine era (n?=?173), unvaccinated children of the vaccine era (n?=?169), and fully vaccinated children (4 doses; n?=?150). Co-colonization, serotype identification, and relative serotype abundance were detected by analysis of DNA of the total bacterial growth of the primary culture plate using the plyNCR-RFLP method and a molecular serotyping microarray-based strategy. The plyNCR-RFLP method detected an overall co-colonization rate of 20.1%. Microarray analysis confirmed the plyNCR-RFLP results. Vaccination status was the only factor found to be significantly associated with co-colonization: co-colonization rates were significantly lower (p?=?0.004; Fisher's exact test) among fully vaccinated children (8.0%) than among children from the pre-PCV7 era (17.3%) or unvaccinated children of the PCV7 era (18.3%). In the PCV7 era there were significantly less non-vaccine type (NVT) co-colonization events than would be expected based on the NVT distribution observed in the pre-PCV7 era (p?=?0.024). In conclusion, vaccination with PCV7 resulted in a lower co-colonization rate due to an asymmetric distribution between NVTs found in single and co-colonized samples. We propose that some NVTs prevalent in the PCV7 era are more competitive than others, hampering their co-existence in the same niche. This result may have important implications since a decrease in co-colonization events is expected to translate in decreased opportunities for horizontal gene transfer, hindering pneumococcal evolution events such as acquisition of antibiotic resistance determinants or capsular switch. This might represent a novel potential benefit of conjugate vaccines.

Valente, Carina; Hinds, Jason; Pinto, Francisco; Brugger, Silvio D.; Gould, Katherine; Muhlemann, Kathrin; de Lencastre, Herminia; Sa-Leao, Raquel

2012-01-01

173

Impact of pediatric vaccination with pneumococcal conjugate vaccine on the risk of bacteremic pneumococcal pneumonia in adults  

Microsoft Academic Search

Invasive pneumococcal disease in adults may be declining, reflecting a form of herd protection from a new pediatric pneumococcal conjugate vaccine. Our aim was to determine whether vaccination of children protects adults in the same home from bacteremic pneumococcal pneumonia. We conducted a case–control study with 43 participating hospitals across a five-county region in Pennsylvania. Eligible cases were adults with

Joshua P. Metlay; Neil O. Fishman; Marshall Joffe; Paul H. Edelstein

2006-01-01

174

Cost effectiveness of adding 7-valent pneumococcal conjugate (PCV7) vaccine to the Norwegian childhood vaccination program  

Microsoft Academic Search

BackgroundStreptococcus pneumoniae is a frequent bacterial cause of serious infections that may cause permanent sequelae and death. A 7-valent conjugate vaccine may reduce the incidence of pneumococcal disease, but some previous studies have questioned the cost-effectiveness of the vaccine. The aim of this study was to estimate costs and health consequences of adding this pneumococcal vaccine to the Norwegian childhood

Torbjørn Wisløff; Tore G. Abrahamsen; Marianne A. Riise Bergsaker; Øistein Løvoll; Per Møller; Maren Kristine Pedersen; Ivar Sønbø Kristiansen

2006-01-01

175

Clinical experience of a tricomponent acellular pertussis vaccine combined with diphtheria and tetanus toxoids for primary vaccination in 22,505 infants  

Microsoft Academic Search

OBJECTIVES: To assess the safety and tolerability of 12 lots of SmithKline Beecham Biologicals' diphtheria-tetanus-tricomponent acellular pertussis vaccine (DTaP) in a large cohort of 22,000 vaccinees, with detailed analyses of reactivity, immunogenicity, and immune response to pertussis toxin in subsets. METHODS: In a prospective, double-blind, multicenter trial in Germany, 22,505 healthy infants received three vaccinations of DTaP at age 3,

Heinz J. Schmitt; Anne Schuind; Markus Knuf; Karin Beutel; Hermann Schulte-Wissermann; Manfred Gahr; Rainer Schult; Jens Folkens; Wolfgang Rauh; Hugues Bogaerts; Hans L. Bork; Ralf Clemens

1996-01-01

176

Immunity against Neisseria meningitidis Serogroup C in the Dutch Population before and after Introduction of the Meningococcal C Conjugate Vaccine  

PubMed Central

Background In 2002 a Meningococcal serogroup C (MenC) conjugate vaccine, with tetanus toxoid as carrier protein, was introduced in the Netherlands as a single-dose at 14 months of age. A catch-up campaign was performed targeting all individuals aged 14 months to 18 years. We determined the MenC-specific immunity before and after introduction of the MenC conjugate (MenCC) vaccine. Methods and Findings Two cross-sectional population-based serum banks, collected in 1995/1996 (n?=?8539) and in 2006/2007 (n?=?6386), were used for this study. The main outcome measurements were the levels of MenC polysaccharide(PS)-specific IgG and serum bactericidal antibodies (SBA) after routine immunization, 4–5 years after catch-up immunization or by natural immunity. There was an increasing persistence of PS-specific IgG and SBA with age in the catch-up immunized cohorts 4–5 years after their MenCC immunization (MenC PS-specific IgG, 0.25 µg/ml (95%CI: 0.19–0.31 µg/ml) at age 6 years, gradually increasing to 2.34 µg/ml,(95%CI: 1.70–3.32 µg/ml) at age 21–22 years). A comparable pattern was found for antibodies against the carrier protein in children immunized above 9 years of age. In case of vaccination before the age of 5 years, PS-specific IgG was rapidly lost. For all age-cohorts together, SBA seroprevalence (?8) increased from 19.7% to 43.0% in the pre- and post-MenC introduction eras, respectively. In non-immunized adults the SBA seroprevalence was not significantly different between the pre- and post-MenC introduction periods, whereas PS-specific IgG was significantly lower in the post-MenC vaccination (GMT, age ?25 years, 0.10 µg/ml) era compared to the pre-vaccination (GMT, age ?25 years, 0.43 µg/ml) era. Conclusion MenCC vaccination administered above 5 years of age induced high IgG levels compared to natural exposure, increasing with age. In children below 14 months of age and non-immunized cohorts lower IgG levels were observed compared to the pre-vaccination era, whereas functional levels remained similar in adults. Whether the lower IgG poses individuals at increased risk for MenC disease should be carefully monitored. Large-scale introduction of a MenCC vaccine has led to improved protection in adolescents, but in infants a single-dose schedule may not provide sufficient protection on the long-term and therefore a booster-dose early in adolescence should be considered.

de Voer, Richarda M.; Mollema, Liesbeth; Schepp, Rutger M.; de Greeff, Sabine C.; van Gageldonk, Pieter G. M.; de Melker, Hester E.; Sanders, Elisabeth A. M.; Berbers, Guy A. M.; van der Klis, Fiona R. M.

2010-01-01

177

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

PubMed Central

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.

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

178

Pneumococcal conjugate vaccines: The potential to alter antibiotic use and nasopharyngeal carriage  

Microsoft Academic Search

In recent decades, the incidence of drug-resistant pneumococcal strains has increased dramatically due to the overuse or inappropriate use of antibiotics. In addition, attendance at day care centers and previous treatment with certain classes of antibiotics are predisposing factors for infections with these drug-resistant strains. Implementation of widespread vaccination of infants and young children with the pneumococcal saccharide conjugated vaccine,

Ron Dagan

2002-01-01

179

Size fractionation of bacterial capsular polysaccharides for their use in conjugate vaccines  

Microsoft Academic Search

We have developed a chromatographic method suitable for the fractionation of polysaccharides having a negatively charged group. The method permits the removal of all those polysaccharide fragments having a short sequence and which are likely unsuitable for conjugate vaccine construction. The selected polysaccharide fragments can be used to produce glycoconjugate vaccines containing a restricted saccharide polydispersion. We have applied this

Paolo Costantino; Francesco Norelli; Aldo Giannozzi; Sandro D'Ascenzi; Antonella Bartoloni; Surinder Kaur; Dazhi Tang; Robert Seid; Stefano Viti; Roberto Paffetti; Massimo Bigio; Carlo Pennatini; Giovanni Averani; Valentina Guarnieri; Eugenia Gallo; Neil Ravenscroft; Carla Lazzeroni; Rino Rappuoli; Costante Ceccarini

1999-01-01

180

Effect of combined pneumococcal conjugate and polysaccharide vaccination on recurrent otitis media with effusion  

Microsoft Academic Search

BACKGROUND: Otitis media with effusion (OME) is very common during childhood. Because Streptococcus pneumoniae is one of the most common bacterial pathogens involved in OME, pneumococcal vaccines may have a role in the prevention of recurrent OME. OBJECTIVE: We sought to assess the effect of combined pneumococcal conjugate and polysaccharide vaccinations on the recurrence of OME. METHODS: A randomized, controlled

Niels van Heerbeek; Masja Straetemans; Selma P. Wiertsema; Koen J. A. O. Ingels; Ger T. Rijkers; A. G. M. Schilder; E. A. M. Sanders; G. A. Zielhuis

2006-01-01

181

Maleimide conjugation markedly enhances the immunogenicity of both human and murine idiotype-KLH vaccines.  

PubMed

The collection of epitopes present within the variable regions of the tumor-specific clonal immunoglobulin expressed by B cell lymphomas (idiotype, Id) can serve as a target for active immunotherapy. Traditionally, tumor-derived Id protein is chemically conjugated to the immunogenic foreign carrier protein keyhole limpet hemocyanin (KLH) using glutaraldehyde to serve as a therapeutic vaccine. While this approach offered promising results for some patients treated in early clinical trials, glutaraldehyde Id-KLH vaccines have failed to induce immune and clinical responses in many vaccinated subjects. We recently described an alternative conjugation method employing maleimide-sulfhydryl chemistry that significantly increased the therapeutic efficacy of Id-KLH vaccines in three different murine B cell lymphoma models, with protection mediated by either CD8(+) T cells or antibodies. We now define in detail the methods and parameters critical for enhancing the in vivo immunogenicity of human as well as murine Id-KLH conjugate vaccines. Optimal conditions for Id sulfhydryl pre-reduction were determined, and maleimide Id-KLH conjugates maintained stability and potency even after prolonged storage. Field flow fractionation analysis of Id-KLH particle size revealed that maleimide conjugates were far more uniform in size than glutaraldehyde conjugates. Under increasingly stringent conditions, maleimide Id-KLH vaccines maintained superior efficacy over glutaraldehyde Id-KLH in treating established, disseminated murine lymphoma. More importantly, human maleimide Id-KLH conjugates were consistently superior to glutaraldehyde Id-KLH conjugates in inducing Id-specific antibody and T cell responses. The described methods should be easily adaptable to the production of clinical grade vaccines for human trials in B cell malignancies. PMID:19046770

Kafi, Kamran; Betting, David J; Yamada, Reiko E; Bacica, Michael; Steward, Kristopher K; Timmerman, John M

2008-11-28

182

MER5101, a novel A?1-15:DT conjugate vaccine, generates a robust anti-A? antibody response and attenuates A? pathology and cognitive deficits in APPswe/PS1?E9 transgenic mice  

PubMed Central

Active amyloid-? (A?) immunotherapy is under investigation to prevent or treat early Alzheimer's disease (AD). In 2002, a Phase II clinical trial (AN1792) was halted due to meningoencephalitis in ?6% of the AD patients, possibly caused by a T-cell-mediated immunological response. Thus, generating a vaccine that safely generates high anti-A? antibody levels in the elderly is required. In this study, MER5101, a novel conjugate of A?1-15 peptide (a B-cell epitope fragment) conjugated to an immunogenic carrier protein, diphtheria toxoid (DT), and formulated in a nanoparticular emulsion-based adjuvant, was administered to 10 mo-old APPswe/PS1?E9 transgenic (Tg) and wild-type (Wt) mice. High anti-A? antibody levels were observed in both vaccinated APPswe/PS1?E9 Tg and Wt mice. Antibody isotypes were mainly IgG1 and IgG2b, suggesting a Th2-biased response. Re-stimulation of splenocytes with the A?1-15:DT conjugate resulted in a strong proliferative response, whereas proliferation was absent after re-stimulation with A?1-15 or A?1-40/42 peptides, indicating a cellular immune response against DT while avoiding an A?-specific T cell response. Moreover, significant reductions in cerebral A? plaque burden, accompanied by attenuated microglial activation and increased synaptic density, were observed in MER5101 vaccinated APPswe/PS1?E9 Tg mice compared to Tg adjuvant controls. Lastly, MER5101 immunized APPswe/PS1?E9 Tg mice showed improvement of cognitive deficits in both Contextual Fear Conditioning (CFC) and the Morris Water Maze (MWM). Our novel, highly immunogenic A? conjugate vaccine, MER5101, shows promise for improving A? vaccine safety and efficacy and therefore, may be useful for preventing and/or treating early AD.

Liu, Bin; Frost, Jeffrey L.; Sun, Jing; Fu, Hongjun; Grimes, Stephen; Blackburn, Peter; Lemere, Cynthia A.

2013-01-01

183

MER5101, a novel A?1-15:DT conjugate vaccine, generates a robust anti-A? antibody response and attenuates A? pathology and cognitive deficits in APPswe/PS1?E9 transgenic mice.  

PubMed

Active amyloid-? (A?) immunotherapy is under investigation to prevent or treat early Alzheimer's disease (AD). In 2002, a Phase II clinical trial (AN1792) was halted due to meningoencephalitis in ?6% of the AD patients, possibly caused by a T-cell-mediated immunological response. Thus, generating a vaccine that safely generates high anti-A? antibody levels in the elderly is required. In this study, MER5101, a novel conjugate of A?1-15 peptide (a B-cell epitope fragment) conjugated to an immunogenic carrier protein, diphtheria toxoid (DT), and formulated in a nanoparticular emulsion-based adjuvant, was administered to 10-month-old APPswe/PS1?E9 transgenic (Tg) and wild-type (Wt) mice. High anti-A? antibody levels were observed in both vaccinated APPswe/PS1?E9 Tg and Wt mice. Antibody isotypes were mainly IgG1 and IgG2b, suggesting a Th2-biased response. Restimulation of splenocytes with the A?1-15:DT conjugate resulted in a strong proliferative response, whereas proliferation was absent after restimulation with A?1-15 or A?1-40/42 peptides, indicating a cellular immune response against DT while avoiding an A?-specific T-cell response. Moreover, significant reductions in cerebral A? plaque burden, accompanied by attenuated microglial activation and increased synaptic density, were observed in MER5101-vaccinated APPswe/PS1?E9 Tg mice compared with Tg adjuvant controls. Last, MER5101-immunized APPswe/PS1?E9 Tg mice showed improvement of cognitive deficits in both contextual fear conditioning and the Morris water maze. Our novel, highly immunogenic A? conjugate vaccine, MER5101, shows promise for improving A? vaccine safety and efficacy and therefore, may be useful for preventing and/or treating early AD. PMID:23595760

Liu, Bin; Frost, Jeffrey L; Sun, Jing; Fu, Hongjun; Grimes, Stephen; Blackburn, Peter; Lemere, Cynthia A

2013-04-17

184

Modelling the effect of conjugate vaccines in pneumococcal disease: Cohort or population models?  

Microsoft Academic Search

Cohort and population models estimate vaccine impact on disease events, and yield different estimates in countries with different demographic compositions. We compared administration of the new 10-valent pneumococcal Haemophilus influenzae–protein D conjugate vaccine (PHiD-CV) with no vaccination in two countries, the United Kingdom (UK) and Mexico, using two modelling strategies: a cohort model and a population model. The cohort model

Baudouin Standaert; Nadia Demarteau; Sandra Talbird; Josephine Mauskopf

2010-01-01

185

Efficacy of pneumococcal conjugate vaccine against PCR-positive acute otitis media  

Microsoft Academic Search

We aimed to assess the efficacy of a pneumococcal conjugate vaccine against acute otitis media (AOM) positive by pneumolysin-PCR (Ply-PCR). 1662 infants vaccinated with PncCRM or control vaccine using random allocation were followed for AOM up to 24 months of age. When AOM was diagnosed a middle ear fluid sample was obtained for etiological assays. During the per protocol follow-up

Arto A. Palmu; Annika Saukkoriipi; Jukka Jokinen; Maija Leinonen; Terhi M. Kilpi

2009-01-01

186

Effect of nationwide vaccination of 3-month-old infants in The Netherlands with conjugate Haemophilus influenzae type b vaccine: High efficacy and lack of herd immunity  

Microsoft Academic Search

Objective: The effect of nationwide vaccination in The Netherlands with conjugate Haemophilus influenzae type b vaccine on the incidence of H. influenzae meningitis was assessed in the first 3 years after the introduction of vaccination to the birth cohort at 3 months of age. Study design: Children in The Netherlands born after April 1, 1993, were vaccinated at the age

Loek van Alphen; Lodewijk Spanjaard; Arie van der Ende; Ilse Schuurman; Jacob Dankert

1997-01-01

187

A new meningococcal conjugate vaccine: What should physicians know and do?  

PubMed Central

A quadrivalent meningococcal conjugate vaccine for serogroups A, C, Y and W135 (MCV4 [Menactra, sanofi pasteur, Canada]) was introduced in Canada in 2007 for persons two years of age or older. MCV4 adds three serogroups to the meningococcal serogroup C conjugate vaccine, which has been used for several years. The rates of invasive meningococcal serogroup C infection have decreased over the past decade, attributable to the meningococcal C conjugate vaccine. However, the incidence of infection caused by serogroups A, B, Y and W135 have not changed substantially. MCV4 induces the production of protective antibodies to serogroups A, C, Y and W135 in adults and children older than two years of age. Serious adverse events from MCV4 are low. In view of the effectiveness of the meningococcal C conjugate vaccine for young infants and the historic high number of meningococcal serogroup C infections in Canada, physicians should encourage and promote publicly funded immunization programs for infants starting at two months of age. MCV4 should also be given to children aged two years who are at increased risk for meningococcal infection. MCV4 may also be considered for HIV-positive children two years of age or older. All adolescents should be offered a booster dose with MCV4 or a meningococcal C conjugate vaccine at approximately 12 years of age. Both vaccines are generally safe and well tolerated.

Bortolussi, R; Salvadori, M

2009-01-01

188

Development of a group A meningococcal conjugate vaccine, MenAfriVac(TM).  

PubMed

Group A meningococcal disease has been an important public health problem in sub-Saharan Africa for over a century. Outbreaks occur there annually, and large epidemics occur at intervals ranging between 8 and 12 y. The Meningitis Vaccine Project was established in 2001 with funding from the Gates Foundation with the goal of developing, testing, licensing, and introducing an affordable group A meningococcal conjugate vaccine into Africa. From 2003 to 2009 a monovalent group A conjugate vaccine, MenAfriVac(TM) , was developed at the Serum Institute of India, Ltd through an innovative public/private partnership. Preclinical studies of the new conjugate vaccine were completed in 2004 and a Phase 1 study began in India in 2005. Phase 2/3 studies in African 1-29 y olds were completed in 2009 showing the new meningococcal A conjugate vaccine to be as safe as currently licensed meningococcal polysaccharide vaccines, but much more immunogenic. After Indian market authorization (December 2009) and WHO prequalification (June 2010), MenAfriVac(TM) was introduced at public health scale using a single 10 µg dose in individuals 1-29 y of age in Burkina Faso, Mali, and Niger in December 2010. We summarize the laboratory and clinical studies leading to prequalification of MenAfriVac(TM). The 2011 epidemic season ended with no reported case of group A meningitis in vaccinated individuals. PMID:22495119

Frasch, Carl E; Preziosi, Marie-Pierre; LaForce, F Marc

2012-04-12

189

Compared effectiveness of the 7-valent pneumococcal conjugate vaccine in children with the 13-valent vaccine in adults.  

PubMed

13-valent-pneumococcal conjugated vaccine was recently approved in the USA and Europe for adults 50 years of age or more. But this approval was followed by recommendations limiting its use to immunocompromised and asplenic patients. The extension of indications to adults was based on the well-demonstrated clinical effectiveness in infants less than 2 years of age, and on a better immune response either quantitatively or qualitatively with conjugated vaccines compared to the immunogenicity of plain polysaccharide vaccines. Nevertheless, the issue was to know whether results observed with the 7-valent pneumococcal conjugate vaccine in children are reproducible in adults with the 13-valent. The answer was given by comparing the epidemiological and physiopathological data, and the immunological response of the two populations. Very few clinical effectiveness studies in adults are available. We had for aim to assess these various issues in infants and adults. A lot of questions remain, such as the unknown impact of serotype replacement with the 13-valent pneumococcal conjugated vaccine on the clinical epidemiology and emergent Streptococcus pneumoniae pathogenicity, while waiting for the CAPITA study results expected in 2014. PMID:23769155

Gaillat, J

2013-06-13

190

Adverse events associated with childhood vaccines other than pertussis and rubella. Summary of a report from the Institute of Medicine.  

PubMed

In September 1993, the Institute of Medicine released a report entitled Adverse Events Associated With Childhood Vaccines: Evidence Bearing on Causality. The report examined putative serious adverse consequences associated with administration of diphtheria and tetanus toxoids; measles, mumps, and measles-mumps-rubella vaccines; oral polio vaccine and inactivated polio vaccine; hepatitis B vaccines; and Haemophilus influenzae type b (Hib) vaccines. The committee spent 18 months reviewing all available scientific and medical data, from individual case reports (published and unpublished) to controlled clinical trials. The committee found that the evidence favored the rejection of a causal relation between diphtheria and tetanus toxoids and encephalopathy, infantile spasms, and sudden infant death syndrome, and between conjugate Hib vaccines and susceptibility to Hib disease. The committee found that the evidence favored acceptance of a causal relation between diphtheria and tetanus toxoids and Guillain-Barré syndrome and brachial neuritis, between measles vaccine and anaphylaxis, between oral polio vaccine and Guillain-Barré syndrome, and between unconjugated Hib vaccine and susceptibility to Hib disease. The committee found that the evidence established causality between diphtheria and tetanus toxoids and anaphylaxis, between measles vaccine and death from measles vaccine-strain viral infection, between measles-mumps-rubella vaccine and thrombocytopenia and anaphylaxis, between oral polio vaccine and poliomyelitis and death from polio vaccine-strain viral infection, and between hepatitis B vaccine and anaphylaxis. For five vaccine-related adverse events, there was no evidence identified. For the remaining 33 vaccine-related adverse events, the evidence was inadequate to accept or reject a causal relation. PMID:8182813

Stratton, K R; Howe, C J; Johnston, R B

1994-05-25

191

Safety and immunogenicity of 13-valent pneumococcal conjugate vaccine in infants: A meta-analysis.  

PubMed

Pneumococcal infections are a major cause of morbidity and mortality worldwide. Pneumococcal conjugate vaccines represent major progress in the prevention of invasive pneumococcal disease in the paediatric population. We performed a meta-analysis, in accordance with the PRISMA statement, in order to assess the immunogenicity and safety of 13-valent pneumococcal conjugate vaccines in infants. A literary search was conducted using electronic databases and specialized journals were searched manually. Inclusion criteria were: clinical trials with infants vaccinated with 13-valent pneumococcal conjugate, compared to 7-valent vaccine. We recorded the results in terms of the immunogenicity and safety of the vaccines. The quality of the studies included was assessed using the CASP and Jadad checklists. We included nine randomized clinical trials of 258 potentially relevant references in the meta-analysis. The studies included had high-moderate quality. Both vaccines were well tolerated in all groups of infants, and most local reactions and systemic events were of mild or medium intensity and typical of any injected vaccine. All studies included in the meta-analysis showed high immunogenicity for both pneumococcal vaccines in all tested serotypes. An anti-polysaccharide antibody concentration of ?0.35?g/mL was achieved in at least 89% of the infants. Our results suggest that the 13-valent pneumococcal conjugate vaccine has a similar safety profile, and is as effective as, the 7-valent vaccine in the prevention of invasive pneumococcal disease caused by the seven common serotypes, and could provide expanded protection against the six additional serotypes. PMID:24055349

Ruiz-Aragón, J; Peláez, S Márquez; Molina-Linde, J M; Grande-Tejada, A M

2013-09-19

192

Booster Effect of Low Doses of Tetanus Toxoid in Elderly Vaccinees  

Microsoft Academic Search

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

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

2000-01-01

193

Cost effectiveness analysis of heptavalent pneumococcal conjugate vaccine in Germany considering herd immunity effects  

Microsoft Academic Search

Background  In Germany the heptavalent pneumococcal conjugate vaccine (PCV7) has been recommended as a general infant vaccination since\\u000a 2006. Data from similar programmes in the USA have reported a reduction of pneumococcal diseases in both vaccinated and unvaccinated\\u000a populations, suggesting herd immunity effects. This study analyses the cost-effectiveness of a general vaccination with PCV7\\u000a in Germany based on these findings.\\u000a \\u000a \\u000a \\u000a Methods  A

Christa Claes; Ralf René Reinert; Johann-Matthias Graf von der Schulenburg

2009-01-01

194

Vaccination with parenteral toxoid B protects hamsters against lethal challenge with toxin A-negative, toxin B-positive clostridium difficile but does not prevent colonization.  

PubMed

Toxin A has historically been regarded as the primary virulence determinant in Clostridium difficile infection, but naturally occurring toxin A-negative, toxin B-positive (A-/B+) C. difficile strains are known to be virulent. To determine the role of toxin B in these strains, we immunized hamsters with a toxoid prepared from purified toxin B to determine whether they would be protected from lethal challenge with an A-/B+ strain of C. difficile. PMID:22124129

Siddiqui, Farida; O'Connor, Jennifer R; Nagaro, Kristin; Cheknis, Adam; Sambol, Susan P; Vedantam, Gayatri; Gerding, Dale N; Johnson, Stuart

2011-11-28

195

Immunogenicity and Efficacy against Lethal Aerosol Staphylococcal Enterotoxin B Challenge in Monkeys by Intramuscular and Respiratory Delivery of Proteosome-Toxoid Vaccines  

Microsoft Academic Search

StaphylococcalenterotoxinB(SEB),aprimarycauseoffoodpoisoning,isalsoasuperantigenthatcancause toxic shock after traumatic or surgical staphylococcal would infections or viral influenza-associated staphy- lococcal superinfections or when aerosolized for use as a potential biologic warfare threat agent. Intranasal or intramuscular (i.m.) immunization with formalinized SEB toxoid formulated with meningococcal outer mem- brane protein proteosomes has previously been shown to be immunogenic and protective against lethal respiratory or parenteral SEB

GEORGE H. LOWELL; CURTIS COLLETON; DENZIL FROST; ROBERT W. KAMINSKI; MICHAEL HUGHES; JENNIFER HATCH; CHARLES HOOPER; JAMES ESTEP; LOUISE PITT; MICHAEL TOPPER; ROBERT E. HUNT; WILLIAM BAKER; ANDWALLACE B. BAZE

1996-01-01

196

Reactogenicity and immunogenicity of combined Haemophilus influenzae type b-meningococcal serogroup C conjugate vaccine booster dose coadministered with measles, mumps, and rubella vaccine.  

PubMed

A booster dose of Haemophilus influenzae type b-Neisseria meningitidis serogroup C conjugate (Hib-MenC-TT) vaccine simultaneously administered with measles, mumps, and rubella (MMR) vaccine in 13- to 14-month-old Spanish toddlers, primed with 3 doses of a combined Diphteria-Tetanus-Acellular Pertusis DTPa-Hib-containing vaccine and a MenC-CRM197 conjugate vaccine, had a good reactogenicity profile and induced similar Hib and MenC booster responses and MMR seropositivity rates as the vaccines given alone. PMID:19952860

Carmona, Alfonso; Miranda, Mariano; Barrio, Francisco; De Vicente, Ana; Mares, Josep; Muñoz, Eulalia; Diez-Delgado, Javier; Alonso, Angeles; Giménez-Sánchez, Francisco; Merino, José; García-Corbeira, Pilar; Maechler, Gudrun; Boutriau, Dominique

2010-03-01

197

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

PubMed

Patients undergoing hematopoietic cell transplantation (HCT) are at increased risk for infections with Streptococcus pneumoniae and have long-lasting, impaired antibody responses to pneumococcal polysaccharide vaccines. We examined whether donor immunization with a heptavalent pneumococcal conjugate vaccine (PCV7) would elicit protective antibody responses to additional doses of vaccine administered early after transplantation. Ninety-six patients scheduled to receive an allogeneic hematopoietic cell transplant were randomized with their donors to receive either a dose of PCV7 vaccine or no vaccine before transplantation. All patients received PCV7 at 3 months, 6 months, and 12 months following transplantation, and serotype-specific antibody concentrations were determined after each dose. Following HCT, geometric mean antibody concentrations of patients in the immunized donor group were significantly higher for 5 of the 7 vaccine serotypes after one dose (P <.05) and for 4 of the 7 serotypes after 2 doses of vaccine (P <.03). Sixty-seven percent of patients in the immunized donor group had presumed protective IgG concentrations more than or equal to 0.50 microg/mL to all 7 serotypes following the first dose of vaccine compared to 36% in the unimmunized donor group (P =.05). After the third dose of vaccine, both groups had more than 60% of patients with concentrations at least 0.50 microg/mL to all vaccine serotypes. Donor immunization enhances early antibody responses of patients undergoing HCT to pneumococcal conjugate vaccine. A 3-dose schedule of PCV7 vaccine at 3, 6, and 12 months is immunogenic in these patients regardless of donor immunization. PMID:12393732

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

2002-09-19

198

Guillain-Barré syndrome following immunisation with Haemophilus influenzae type b conjugate vaccine  

Microsoft Academic Search

The Guillain-Barré syndrome (GBS) is an immune-mediated disease often associated with viral or bacterial infections and with immunisation. IgM antibodies have been implicated as the main trigger event in GBS. So far, only four cases of GBS have been observed following immunisation with a conjugate vaccine againstHaemophilus influenzae type b. We report another patient with GBS after this vaccination. We

A. Gervaix; M. Caflisch; S. Suter; Ch.-A. Haenggeli

1993-01-01

199

Comparative Cost Effectiveness of Varicella, Hepatitis A, and Pneumococcal Conjugate Vaccines  

Microsoft Academic Search

Background. Several state and local U.S. governments are considering making varicella, hepatitis A, and\\/or pneumococcal conjugate vaccination conditions of day care or school entry. These requirements will likely be issued sequentially, because simultaneous mandates exacerbate budget constraints and complicate communication with parents and providers. Cost-effectiveness assessments should aid the establishment of vaccination priorities, but comparing results of published studies is

R. Jake Jacobs; Allen S. Meyerhoff

2001-01-01

200

Immunogenicity following one, two, or three doses of the 7-valent pneumococcal conjugate vaccine  

Microsoft Academic Search

The aim was to identify an appropriate infant pneumococcal vaccination strategy for resource poor countries. Fijian infants received zero, one, two, or three doses of 7-valent pneumococcal conjugate vaccine (PCV) in early infancy. Following three PCV doses, geometric mean concentration (GMC) to all seven serotypes were ?1.0?g\\/mL, and >85% of children achieved antibody levels ?0.35?g\\/mL at 18 weeks. Following two

F. M. Russell; A. Balloch; M. L. K. Tang; J. R. Carapetis; P. Licciardi; J. Nelson; A. W. J. Jenney; L. Tikoduadua; L. Waqatakirewa; J. Pryor; G. B. Byrnes; Y. B. Cheung; E. K. Mulholland

2009-01-01

201

Safety and immunogenicity of coadministering a combined meningococcal serogroup C and Haemophilus influenzae type b conjugate vaccine with 7-valent pneumococcal conjugate vaccine and measles, mumps, and rubella vaccine at 12 months of age.  

PubMed

The coadministration of the combined meningococcal serogroup C conjugate (MCC)/Haemophilus influenzae type b (Hib) vaccine with pneumococcal conjugate vaccine (PCV7) and measles, mumps, and rubella (MMR) vaccine at 12 months of age was investigated to assess the safety and immunogenicity of this regimen compared with separate administration of the conjugate vaccines. Children were randomized to receive MCC/Hib vaccine alone followed 1 month later by PCV7 with MMR vaccine or to receive all three vaccines concomitantly. Immunogenicity endpoints were MCC serum bactericidal antibody (SBA) titers of ?8, Hib-polyribosylribitol phosphate (PRP) IgG antibody concentrations of ?0.15 ?g/ml, PCV serotype-specific IgG concentrations of ?0.35 ?g/ml, measles and mumps IgG concentrations of >120 arbitrary units (AU)/ml, and rubella IgG concentrations of ?11 AU/ml. For safety assessment, the proportions of children with erythema, swelling, or tenderness at site of injection or fever or other systemic symptoms for 7 days after immunization were compared between regimens. No adverse consequences for either safety or immunogenicity were demonstrated when MCC/Hib vaccine was given concomitantly with PCV and MMR vaccine at 12 months of age or separately at 12 and 13 months of age. Any small differences in immunogenicity were largely in the direction of a higher response when all three vaccines were given concomitantly. For systemic symptoms, there was no evidence of an additive effect; rather, any differences between schedules showed benefit from the concomitant administration of all three vaccines, such as lower overall proportions with postvaccination fevers. The United Kingdom infant immunization schedule now recommends that these three vaccines may be offered at one visit at between 12 and 13 months of age. PMID:21191076

Miller, Elizabeth; Andrews, Nick; Waight, Pauline; Findlow, Helen; Ashton, Lindsey; England, Anna; Stanford, Elaine; Matheson, Mary; Southern, Joanna; Sheasby, Elizabeth; Goldblatt, David; Borrow, Ray

2010-12-29

202

Safety and Immunogenicity of Coadministering a Combined Meningococcal Serogroup C and Haemophilus influenzae Type b Conjugate Vaccine with 7-Valent Pneumococcal Conjugate Vaccine and Measles, Mumps, and Rubella Vaccine at 12 Months of Age ?  

PubMed Central

The coadministration of the combined meningococcal serogroup C conjugate (MCC)/Haemophilus influenzae type b (Hib) vaccine with pneumococcal conjugate vaccine (PCV7) and measles, mumps, and rubella (MMR) vaccine at 12 months of age was investigated to assess the safety and immunogenicity of this regimen compared with separate administration of the conjugate vaccines. Children were randomized to receive MCC/Hib vaccine alone followed 1 month later by PCV7 with MMR vaccine or to receive all three vaccines concomitantly. Immunogenicity endpoints were MCC serum bactericidal antibody (SBA) titers of ?8, Hib-polyribosylribitol phosphate (PRP) IgG antibody concentrations of ?0.15 ?g/ml, PCV serotype-specific IgG concentrations of ?0.35 ?g/ml, measles and mumps IgG concentrations of >120 arbitrary units (AU)/ml, and rubella IgG concentrations of ?11 AU/ml. For safety assessment, the proportions of children with erythema, swelling, or tenderness at site of injection or fever or other systemic symptoms for 7 days after immunization were compared between regimens. No adverse consequences for either safety or immunogenicity were demonstrated when MCC/Hib vaccine was given concomitantly with PCV and MMR vaccine at 12 months of age or separately at 12 and 13 months of age. Any small differences in immunogenicity were largely in the direction of a higher response when all three vaccines were given concomitantly. For systemic symptoms, there was no evidence of an additive effect; rather, any differences between schedules showed benefit from the concomitant administration of all three vaccines, such as lower overall proportions with postvaccination fevers. The United Kingdom infant immunization schedule now recommends that these three vaccines may be offered at one visit at between 12 and 13 months of age.

Miller, Elizabeth; Andrews, Nick; Waight, Pauline; Findlow, Helen; Ashton, Lindsey; England, Anna; Stanford, Elaine; Matheson, Mary; Southern, Joanna; Sheasby, Elizabeth; Goldblatt, David; Borrow, Ray

2011-01-01

203

Immune Response in Infants to the Heptavalent Pneumococcal Conjugate Vaccine against Vaccine-Related Serotypes 6A and 19A ?  

PubMed Central

The currently available 7-valent pneumococcal conjugate vaccine (PCV7) elicits good immune response to and is effective against vaccine serotypes. However, its effectiveness against vaccine-related serotypes is variable. Serum samples were obtained 1 month after the last vaccination from 31 infants immunized with PCV7 at 2, 4, and 6 months of age. The sera were used to determine immunoglobulin G antibody levels to eight serotypes (seven vaccine serotypes and serotype 19A) with enzyme-linked immunosorbent assay (ELISA) and opsonic capacity against 11 serotypes (seven vaccine serotypes, serotypes 19A and 6A, and nonvaccine serotypes 5 and 7F) using a multiplexed opsonization assay. ELISA results showed antibody concentrations varied between 1.84 and 10.49 ?g/ml, and all subjects had antibody concentrations of ?0.35 ?g/ml for all serotypes, including serotype 19A. In contrast, the opsonic index was detectable (i.e., opsonic index ? 8) in all children for the seven vaccine serotypes, 81% for serotype 6A, and merely 19% for serotype 19A. PCV7 shows good immunogenicity for vaccine serotypes in infants after a primary series. PCV7 does not elicit opsonic antibodies to serotype 19A. ELISA may thus be an inadequate surrogate assay for evaluating the response for cross-reactive serotypes in infants.

Lee, Hyunju; Nahm, Moon H.; Burton, Robert; Kim, Kyung-Hyo

2009-01-01

204

Simple, direct conjugation of bacterial O-SP-core antigens to proteins: development of cholera conjugate vaccines.  

PubMed

Bacterial O-SP-core antigens can be conjugated to proteins in the same, simple way as synthetic, linker-equipped carbohydrates by applying squaric acid chemistry. Introduction of spacers (linkers) to either O-SP-core antigens or protein carriers, which is involved in commonly applied protocols, is not required. The newly developed method described here consists of preparation of a squaric acid monoester derivative of O-SP-core antigen, utilizing the amino group inherent in the core, and reaction of the monoester with the carrier protein. The intermediate monoester can be easily purified; its conjugation can be monitored by SELDI-TOF mass spectrometry and, thus, readily controlled, since the conjugation can be terminated when the desired carbohydrate-protein ratio is reached. Here, we describe production of conjugates containing the O-SP-core antigen of Vibrio cholerae O1, the major cause of cholera, a severe dehydrating diarrheal disease of humans. The resultant products are recognized by convalescent phase sera from patients recovering from cholera in Bangladesh, and anti-O-SP-core-protein responses correlate with plasma antilipopolysaccharide and vibriocidal responses, which are the primary markers of protection from cholera. The results suggest that such conjugates have potential as vaccines for cholera and other bacterial diseases. PMID:21899371

Xu, Peng; Alam, Mohammad Murshid; Kalsy, Anuj; Charles, Richelle C; Calderwood, Stephen B; Qadri, Firdausi; Ryan, Edward T; Ková?, Pavol

2011-09-30

205

Pneumococcal Antibody Concentrations of Subjects in Communities Fully or Partially Vaccinated with a Seven-Valent Pneumococcal Conjugate Vaccine  

PubMed Central

Background A recent trial with PCV-7 in a rural Gambian community showed reduced vaccine-type pneumococcal carriage in fully vaccinated compared with control communities. We measured pneumococcal polysaccharide antibody concentrations in this trial to understand further the mechanisms underlying the observed changes. Methods A single-blind, cluster-randomized (by village) trial was conducted in 21 Gambian villages. In 11 villages, all residents received PCV-7 (Vaccine group); in 10 control villages only children <30 months old or those born during the study received PCV-7. Subjects over the age of 30 months resident in vaccine villages received a single dose of PCV-7 whilst those in control villages received a single dose of a serogroup C meningococcal conjugate vaccine. Serum antibody concentrations against specific pneumococcal polysaccharides were measured in approximately 200 age-stratified subjects before, 4–6, 12 and 24 months following vaccination. Results Baseline pneumococcal antibody concentrations were generally high and increased with age up to 10 years. One dose of PCV-7 increased geometric mean antibody concentrations (GMC) in vaccinated versus control villages for vaccine serotypes 6B and 18C, and 4 and 18C, in the young (under 5 years) and older age groups (5+ years) respectively. There were significantly higher proportions of subjects in the vaccinated than in the control communities with an antibody concentration believed to protect against carriage (>5.0 µg/mL) for all but serotype 9V of the PCV-7 serotypes in the older group, but not in the younger age group. Conclusion Higher antibodies in vaccinated communities provide an explanation for the lower pneumococcal carriage rates in fully vaccinated compared to control communities. Trial Registration Controlled-Trials.com ISRCTN51695599 51695599.

Ota, Martin O. C.; Roca, Anna; Bottomley, Christian; Hill, Philip C.; Egere, Uzochukwu; Greenwood, Brian; Adegbola, Richard A.

2012-01-01

206

Haemophilus influenzae type b conjugate vaccines - a South African perspective.  

PubMed

Introduction of Hib vaccine is known to positively impact on reduction of both morbidity and mortality in children less than 5 years of age. Incorporation of this vaccine into a National EPI, however, does come at a significant cost, which is especially important in non-GAVI funded countries. Compounded reduction in response in certain patient populations and possible indication of booster doses further impacts on cost-benefit analyses. Despite these issues, South Africa has supplied Hib vaccine as part of the National EPI in the form of a combination vaccine, Pentaxim, which combines Hib with Diphtheria, Tetanus, acellular Pertussis (DTP) and Poliomyelitis since 2009. Prior to this, another combination vaccine was utilized containing Hib and DTP. This has subsequently lead to a significant reduction in invasive Hib disease post-introduction, therefore largely justifying utilization. PMID:22939022

Visser, Adele; Hoosen, Anwar

2012-09-01

207

Effects of Pneumococcal Conjugate Vaccine 2 Years after Its Introduction, the Netherlands  

PubMed Central

In the Netherlands, the 7-valent pneumococcal conjugate vaccine (PCV-7) was implemented in a 3+1-dose schedule in the national immunization program for infants born after April 1, 2006. To assess the vaccine’s effectiveness, we compared disease incidence before and after vaccine implementation (June 2004–June 2006 and June 2006–June 2008, respectively). We serotyped 2,552 invasive pneumococcal isolates from throughout the Netherlands, covering 25% of the country’s population. Clinical characteristics were extracted from hospital records. After June 2006, vaccine-serotype invasive pneumococcal disease (IPD) decreased 90% (95% confidence interval [CI] 68%–97%) in children age eligible for PCV-7; simultaneously, however, non–vaccine-serotype IPD increased by 71% (not significant), resulting in a 44% total net IPD reduction (95% CI 7%–66%). IPD rates did not change for other age groups. In the Netherlands, PCV-7 offered high protection against vaccine-serotype IPD in vaccinated children, but increases of non–vaccine-serotype IPD reduced net vaccine benefits.

de Greeff, Sabine C.; Jansen, Angelique G.C.S.; de Melker, Hester E.; Schouls, Leo M.; Hak, Eelko; Spanjaard, Lodewijk; Sanders, Elisabeth A.M.; van der Ende, Arie

2010-01-01

208

Haemophilus influenzae Infections in the H. influenzae Type b Conjugate Vaccine Era ?  

PubMed Central

The widespread use of Haemophilus influenzae type b (Hib) conjugate vaccines has nearly eradicated invasive Hib disease where the vaccines are used. This success was accompanied by a shift in capsular serotypes of invasive H. influenzae disease, with nontypeable strains replacing type b strains as the most common bloodstream isolate, but there is no convincing evidence of a true increase in the incidence of non-serotype b invasive infections. H. influenzae causes predominantly mucosal infections. The introduction of vaccines for otitis media and global shifts in antimicrobial susceptibility emphasize the importance of continued surveillance of H. influenzae colonization and disease patterns.

Agrawal, Aarti; Murphy, Timothy F.

2011-01-01

209

9 CFR 113.114 - Tetanus Toxoid.  

Code of Federal Regulations, 2010 CFR

...Products 1 2010-01-01 2010-01-01 false Tetanus Toxoid. 113.114 Section 113.114 Animals... Inactivated Bacterial Products § 113.114 Tetanus Toxoid. Tetanus Toxoid shall be produced from a culture of...

2010-01-01

210

9 CFR 113.114 - Tetanus Toxoid.  

Code of Federal Regulations, 2010 CFR

...Products 1 2009-01-01 2009-01-01 false Tetanus Toxoid. 113.114 Section 113.114 Animals... Inactivated Bacterial Products § 113.114 Tetanus Toxoid. Tetanus Toxoid shall be produced from a culture of...

2009-01-01

211

Decline in Invasive Pneumococcal Disease after the Introduction of Protein-Polysaccharide Conjugate Vaccine  

Microsoft Academic Search

background In early 2000, a protein-polysaccharide conjugate vaccine targeting seven pneumococ- cal serotypes was licensed in the United States for use in young children. methods We examined population-based data from the Active Bacterial Core Surveillance of the Centers for Disease Control and Prevention to evaluate changes in the burden of invasive disease, defined by isolation of Streptococcus pneumoniae from a

Cynthia G. Whitney; Monica M. Farley; James Hadler; Lee H. Harrison; Nancy M. Bennett; Ruth Lynfield; Arthur Reingold; Paul R. Cieslak; Tamara Pilishvili; Delois Jackson; Richard R. Facklam; James H. Jorgensen; Anne Schuchat

2010-01-01

212

Haemophilus influenzae type b conjugate vaccine impact against purulent meningitis in Rwanda  

Microsoft Academic Search

Rwanda introduced Haemophilus influenzae type b (Hib) conjugate vaccine in January 2002 and simultaneously implemented pediatric bacterial meningitis surveillance at a major referral hospital in the capital Kigali. We reviewed clinical and laboratory information collected during January 2002 to June 2006. Due to a variety of laboratory limitations, only eight confirmed Hib cases were identified, all before 2004. However, the

Narcisse Muganga; Jeannine Uwimana; Ngabo Fidele; Laetitia Gahimbare; Bradford D. Gessner; Judith E. Mueller; Bekithemba R. Mhlanga; Reggis Katsande; Karl-Heinz Herbinger; Celse Rugambwa

2007-01-01

213

Effect of Pneumococcal Conjugate Vaccine on Nasopharyngeal Bacterial Colonization During Acute Otitis Media  

Microsoft Academic Search

The authors have indicated they have no financial relationships relevant to this article to disclose. ABSTRACT The heptavalent pneumococcal conjugate vaccine (PCV7) has been shown to reduce the incidence of acute otitis media (AOM) caused by Streptococcus pneumoniae by 34% and reduces the overall incidence of AOM by 6% to 8%. More recent studies have shown increases in the proportion

Krystal Revai; David P. McCormick; Janak Patel; James J. Grady; Kokab Saeed

2010-01-01

214

Reduction in the incidence of invasive pneumococcal disease after general vaccination with 7-valent pneumococcal conjugate vaccine in Germany.  

PubMed

General vaccination with the 7-valent pneumococcal conjugate vaccine was recommended in Germany in July 2006 for all children <2 years. The proportion of reported invasive pneumococcal disease (IPD) caused by vaccine serotypes before vaccine introduction was considerably lower than in the US. We report data from nationwide surveillance of IPD in children with two reporting sources, pediatric hospitals and microbiological laboratories in Germany. Incidence rates with regard to age groups and pneumococcal serotypes are based on capture recapture estimates combining the two reporting sources. Between July 1, 1997 and June 30, 2003, 2680 cases (an average 447 yearly cases) of IPD were observed in children <16 years in Germany compared to 223 cases between July 1, 2007 and June 30, 2008. A significant reduction in overall incidence (4/100,000-3.2/100,000) was attributed to significant reductions in children younger than 2 years (20.0/100,000-11.0/100,000). While the incidence of all serotypes included in the vaccine was reduced in the age group <2 years, the incidence of non-vaccine serotypes remained stable. These data show a first success of the pneumococcal vaccination program in Germany. Further changes in incidence and serotype distribution of IPD are subject to future surveillance. PMID:19406190

Rückinger, Simon; van der Linden, Mark; Reinert, Ralf René; von Kries, Rüdiger; Burckhardt, Florian; Siedler, Anette

2009-05-09

215

Combined schedule of 7-valent pneumococcal conjugate vaccine followed by 23-valent pneumococcal vaccine in children and young adults with sickle cell disease  

Microsoft Academic Search

We compared the immunogenicity of 7-valent pneumococcal-conjugate vaccine plus 23-valent pneumococcal vaccine to immunization with 23-valent vaccine only in individuals ?2 years of age with sickle cell disease. IgG pneumococcal antibody concentrations were higher in the combined schedule group with no increase in side effects observed after immunization with 23-valent vaccine. (J Pediatr 1998;133:275-8)

Louis Vernacchio; Ellis J. Neufeld; Kristin MacDonald; Susan Kurth; Saya Murakami; Courtney Hohne; Michelle King; Deborah Molrine

1998-01-01

216

Huge impact of assumptions on indirect effects on the cost-effectiveness of routine infant vaccination with 7-valent conjugate vaccine (Prevnar ®)  

Microsoft Academic Search

Several recently published European cost-effectiveness studies on the 7-valent pneumococcal conjugate vaccine (PCV-7: Prevnar®) have included net-indirect vaccine benefits for non-vaccine protected groups into their studies, which might be too optimistic an approach given recent data. Net-indirect effects result from herd protection minus serotype replacement effects. In this study we analyze the impact of net-indirect effects in non-vaccine protected groups

Mark H. Rozenbaum; Albert Jan van Hoek; Eelko Hak; Maarten J. Postma

2010-01-01

217

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

Microsoft Academic Search

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

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

2001-01-01

218

Immunogenicity of a combination vaccine containing pneumococcal conjugates and meningococcal PorA OMVs  

Microsoft Academic Search

The pre-clinical immunogenicity of a combination vaccine containing 13-valent pneumococcal conjugate (13vPnC) vaccine (serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F and 23F conjugated to CRM197) and nine-valent meningococcal B PorA vaccine (NonaMen; serosubtypes P1.7,16; P1.5-1,2-2; P1.19,15-1; P1.5-2,10; P1.12-1,13; P1.7-2,4; P1.22,14; P1.7-1,1 and P1.18-1,3,6), and any potential immunological interference between pneumococcal and MenB components of

Germie P. J. M. van den Dobbelsteen; Harry H. van Dijken; Subramonia Pillai; Loek van Alphen

2007-01-01

219

Preparation, characterization, and immunogenicity of conjugate vaccines directed against Actinobacillus pleuropneumoniae virulence determinants.  

PubMed Central

Conjugate vaccines were prepared in an attempt to protect pigs against swine pleuropneumonia induced by Actinobacillus pleuropneumoniae (SPAP). Two subunit conjugates were prepared by coupling the A. pleuropneumoniae 4074 serotype 1 capsular polysaccharide (CP) to the hemolysin protein (HP) and the lipopolysaccharide (LPS) to the HP. Adipic acid dihydrazide was used as a spacer to facilitate the conjugation in a carbodiimide-mediated reaction. The CP and the LPS were found to be covalently coupled to the HP in the conjugates as determined by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and detergent gel chromatography analyses. Following a booster vaccination, pigs exhibited significantly high (P less than 0.05) immunoglobulin G antibodies against CP, LPS, and HP. The anti-CP and anti-LPS immunoglobulin G antibodies were found to function as opsonins in the phagocytosis of A. pleuropneumoniae by polymorphonuclear leukocytes, whereas antibodies to the HP neutralized the cytotoxic effect of the HP on polymorphonuclear leukocytes. No killing of A. pleuropneumoniae was observed when the effects of the antibodies were tested in the presence of complement. Thus, polysaccharide-protein A. pleuropneumoniae conjugates elicit significant antibody responses against each component of each conjugate, which could be instrumental in protecting swine against SPAP. Images

Byrd, W; Kadis, S

1992-01-01

220

Designing a new antifungal glycoconjugate vaccine.  

PubMed

Bacterial capsular polysaccharides have been used as effective vaccines for adults but infants and seniors respond poorly to these immunogens because pure polysaccharides are unable to activate T-cells resulting in antibodies of low affinity and poor immunological memory. These deficiencies are addressed by conjugate vaccines composed of bacterial polysaccharide covalently attached to protein carriers such as tetanus or diphtheria toxoids. These vaccines activate T-cells and have been hugely effective in reducing the incidence of dangerous infectious diseases such as bacterial meningitis in infants and adults. The methods of conjugation often produce conjugate vaccines that contain polysaccharides with several cross links to one or more protein carrier molecules. Synthesis of large oligosaccharides derivatized to achieve single site attachment to protein has established the minimal size of an oligosaccharide that is required to produce protective antibody. Several examples are described where such oligosaccharides range in size from 8 to 16 monosaccharides. A more limited set of examples show that protective antibodies may be elicited by conjugate vaccines composed of tri and tetrasaccharide epitopes. One example is the ?-mannan present in the phosphomannan glycoprotein of Candida albicans. Reverse engineering a protective antibody that recognizes this oligosaccharide revealed that a disaccharide was the minimal epitope. Further epitope mapping by functional group modification established that the internal mannose residue of a disaccharide was involved in the most important antibody-disaccharide interactions. NMR binding studies in combination with homology modeling of the bound ?-mannan antigen suggested an optimum oligosaccharide for inclusion in a conjugate vaccine. Several conjugate vaccines were developed to test these conclusions. Immunization of mice or rabbits with conjugates containing disaccharide or trisaccharide conjugated to immunogenic proteins followed by live challenge experiments showed that the vaccines reduced fungal burden. The results of these and other studies suggest new approaches to novel synthetic conjugate vaccines. PMID:23232662

Johnson, Margaret A; Bundle, David R

2012-12-11

221

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

PubMed

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 and elderly populations and potential barriers to the introduction of a conjugate vaccine in adults are discussed. PMID:15037021

Parijs, Betsy Abraham-Van; Malinoski, Frank J

2004-02-01

222

Pneumococcal Conjugate Vaccines and Otitis Media: An Appraisal of the Clinical Trials  

PubMed Central

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.

Fletcher, Mark A.; Fritzell, Bernard

2012-01-01

223

Evidence that pneumococcal serotype replacement in Massachusetts following conjugate vaccination is now complete  

PubMed Central

Invasive pneumococcal disease (IPD) has been reduced in the US following conjugate vaccination (PCV7) targeting seven pneumococcal serotypes in 2000. However, increases in IPD due to other serotypes have been observed, in particular 19A. How much this “serotype replacement” will erode the benefits of vaccination and over what timescale is unknown. We used a population genetic approach to test first whether the selective impact of vaccination could be detected in a longitudinal carriage sample, and secondly how long it persisted for following introduction of vaccine in 2000. To detect the selective impact of the vaccine we compared the serotype diversity of samples from pneumococcal carriage in Massachusetts children collected in 2001, 2004 and 2007 with others collected in the pre-vaccine era in Massachusetts, the UK and Finland. The 2004 sample was significantly (p >0.0001) more diverse than pre-vaccine samples, indicating the selective pressure of vaccination. The 2007 sample showed no significant difference in diversity from the pre-vaccine period, and exhibited similar population structure, but with different serotypes. In 2007 the carriage frequency of 19A was similar to that of the most common serotype in pre-vaccine samples. We suggest that serotype replacement involving 19A may be complete in Massachusetts due to similarities in population structure to pre-vaccine samples. These results suggest that the replacement phenomenon occurs rapidly with high vaccine coverage, and may allay concerns about future increases in disease due to 19A. For other serotypes, the future course of replacement disease remains to be determined.

Hanage, William P.; Finkelstein, Jonathan A.; Huang, Susan S.; Pelton, Stephen I.; Stevenson, Abbie E.; Kleinman, Ken; Hinrichsen, Virginia L.; Fraser, Christophe

2010-01-01

224

Re: Global serotype distribution among Streptococcus pneumoniae isolates causing otitis media in children: potential implications for pneumococcal conjugate vaccines.  

PubMed

Acute otitis media (AOM) is one of the most commonly diagnosed childhood infections. Analysis of global serotype distribution among Streptococcus pneumonia isolates causing otitis media in children may improve coverage of future pneumococcal conjugate vaccines. Serotypes like 3 or 19A should not only be included in future vaccine formulations but they should preferably protect against these serotypes. To construct future AOM vaccine with higher vaccine efficacy also other pathogens causing AOM need to be taken into consideration. PMID:19540951

Prymula, Roman

2009-06-21

225

Pneumococcal Conjugate Vaccine Serotypes of Streptococcus pneumoniae Isolates and the Antimicrobial Susceptibility of Such Isolates in Children with Otitis Media  

Microsoft Academic Search

The ability of the recently licensed 7-valent pneumococcal conjugate vaccine to cover isolates that cause otitis media, especially drug-resistant ones, was assessed using 500 recently obtained US isolates. Of these isolates, 418 (84%) belonged to vaccine-related serogroups, whereas 82 (16%) belonged to non-vaccine-related sero- groups. Serotype 3 accounted for 48 (59%) of the non-vaccine-related serogroups. In addition, 93% of the

Anne Windau; Saralee Bajaksouzian

2001-01-01

226

Increased Protection against Pneumococcal Disease by Mucosal Administration of Conjugate Vaccine plus Interleukin-12  

PubMed Central

Streptococcus pneumoniae is a common cause of respiratory tract infections, its main entry route being the nasal mucosa. The recent development of pneumococcal polysaccharide conjugate vaccines has led to a dramatic improvement in protection against invasive disease in infants and children, but these vaccines have been found to be only 50 to 60% protective against bacterial carriage. In this study, we investigated the efficacy of intranasal (i.n.) conjugate vaccine delivery using interleukin-12 (IL-12) as a mucosal adjuvant. Immunized mice treated with IL-12 demonstrated increased expression of lung and splenic gamma interferon and IL-10 mRNAs; high levels of antibody, particularly serum immunoglobulin G2a (IgG2a) and respiratory IgA; and significantly increased opsonic activity. After intraperitoneal challenge with type 3 pneumococci, there was 75% survival of i.n. vaccinated mice compared to 0% survival of unvaccinated mice. In addition, after i.n. challenge with type 14 pneumococci, vaccinated mice possessed fewer bacterial colonies in the upper respiratory tract than unvaccinated mice. However, no significant difference in type 14 carriage was observed between vaccinated and unvaccinated groups following intramuscular vaccination, the typical route of vaccination in humans. Using mice with a genetic disruption in IgA expression, it was found that pneumococcus-specific IgA played a significant role in the clearance of bacteria from the upper respiratory tract. We conclude that i.n vaccination in the presence of IL-12 is able to enhance systemic and mucosal immune responses to pneumococci and efficiently protect against both invasive infection and bacterial carriage.

Lynch, Joyce M.; Briles, David E.; Metzger, Dennis W.

2003-01-01

227

Do pneumococcal conjugate vaccines provide any cross-protection against serotype 19A?  

PubMed Central

Background Introduction of the 7-valent pneumococcal conjugate vaccine (7vCRM) in several countries has led to a rapid, significant drop in vaccine-type invasive pneumococcal disease (IPD) in immunized children. In the United States and some other countries with high antibiotic use, a subsequent rise in serotype 19A IPD has been taken to indicate that the 19F conjugate in the vaccine provides no cross-protection against the immunologically related 19A. Discussion We systematically assessed the clinical efficacy and effectiveness of 19F-containing vaccines against 19A disease or nasopharyngeal carriage by searching English-language articles in the electronic databases PubMed, Current contents, Scopus, and Embase from 1985 to 2008. The vaccine efficacy and effectiveness point estimates were consistently positive for modest protection against 19A IPD and acute otitis media (AOM). However, statistical significance was not reached in any individual study. No consistent impact of 7vCRM on 19A nasopharyngeal colonization could be detected. These findings are discussed in context of immunogenicity analyses indicating that 7vCRM induces functionally active anti-19A antibodies after the booster dose, and that other 19F-containing vaccine formulations may elicit higher levels of such antibodies after both primary and booster doses. Summary Taken together, these results suggest that 19F-conjugates can provide some protection against 19A disease. The magnitude of this protection in a given setting will likely depend on several factors. These include the anti-19A immunogenicity of the specific vaccine formulation, the number of doses of that formulation needed to elicit the response, and the burden of 19A disease that occurs after those doses. It is possible that a modest protective effect may be obscured by the presence of countervailing selection pressures (such as high antibiotic use) that favor an increase in colonization with antibiotic-non-susceptible strains of 19A.

2010-01-01

228

A pilot study to quantify parental anxiety associated with enrollment of an infant or toddler in a phase III vaccine trial  

Microsoft Academic Search

We sought to measure the anxiety felt by parents at the time of entry into a randomized controlled vaccine trial, and to determine if anxiety level was associated with parental demographic variables or past experience. The children were 2-month-old infants entering a randomized controlled clinical trial (RCT) of a diphtheria–tetanus toxoid–acellular pertussis vaccine adsorbed with Haemophilus influenzae B conjugate, or

Joanne M Langley; Scott A Halperin; Bruce Smith

2003-01-01

229

Estimating the direct impact of new conjugate vaccines against invasive pneumococcal disease.  

PubMed

New pneumococcal conjugate vaccines (PCVs) are now becoming available. These formulations differ from the heptavalent diphtheria toxin variant conjugate vaccine (7vCRM, Prevenar/Prevnar) both in the number of serotypes and in serotype-specific immunogenicity. This review proposes an algorithm that attempts to predict the overall impact of these differences in vaccine formulation and immunogenicity on invasive pneumococcal disease (IPD) effectiveness. It builds on the principles underlying WHO licensure criteria for new PCVs, that serotype-specific anti-polysaccharide immunogenicity is potentially predictive of effectiveness. The algorithm used three sources of information: serotype-specific effectiveness data for 7vCRM, serotype-specific head-to-head immunogenicity data with 7vCRM and a recently licensed 10-valent pneumococcal non-typeable H. influenzae protein D-conjugate vaccine (PHiD-CV, Synflorix), and epidemiological information regarding the serotypes causing IPD in young children. Based on this algorithm, PHiD-CV and 7vCRM are predicted to prevent approximately 60-80% and 45-80%, respectively of IPD in young children worldwide, with significant variability by country and region. PMID:19833248

Hausdorff, W P; Dagan, R; Beckers, F; Schuerman, L

2009-10-13

230

Protective antibody responses to pneumococcal conjugate vaccine after autologous hematopoietic stem cell transplantation.  

PubMed

Patients undergoing autologous hematopoietic stem cell transplantation (autoHCT) are at increased risk for infection with Streptococcus pneumoniae and have impaired antibody responses to pneumococcal polysaccharide vaccines. We performed this study to examine the ability of autoHCT patients to respond to a heptavalent pneumococcal conjugate vaccine (PCV7) given after transplantation and to determine whether there was a potential benefit of immunizing these patients before stem cell collection. Sixty-one patients scheduled for autoHCT were randomized to receive either PCV7 or no vaccine before stem cell collection. After stem cell reinfusion, all study patients were immunized with PCV7 at 3, 6, and 12 months. Pneumococcal immunoglobulin G antibody concentrations were measured at the time of each immunization and 1 month after the 12-month dose. Serotype-specific pneumococcal antibody concentrations were significantly higher in patients immunized with PCV7 before stem cell collection compared with patients not immunized before their stem cells were collected for 6 of 7 serotypes at 3 months, 6 of 7 serotypes at 6 months, 4 of 7 serotypes at 12 months, and 3 of 7 serotypes at 13 months. After the 3-dose series of PCV7 after autoHCT, >60% of study patients had protective concentrations of antibody to all 7 vaccine serotypes regardless of immunization before stem cell collection. Pneumococcal conjugate vaccine is immunogenic in autoHCT patients and may be an effective strategy to prevent invasive disease after transplantation. PMID:15744240

Antin, Joseph H; Guinan, Eva C; Avigan, David; Soiffer, Robert J; Joyce, Robin M; Martin, Victoria J; Molrine, Deborah C

2005-03-01

231

Post-licensure safety of the meningococcal group C conjugate vaccine.  

PubMed

Passive surveillance reports of adverse events following meningococcal group C conjugate vaccine (MCCV) in the United Kingdom suggested a possible increased risk of convulsions and purpura. To investigate this further, hospital admissions for convulsions and purpura were obtained for the period November 1999 to September 2003 in children from the South East of England and these were linked to vaccine records for MCCV, Diphtheria/Tetanus/Pertussis vaccine (DTP) and Measles/Mumps/Rubella vaccine (MMR). A total of 1,715 children with convulsions and 363 with purpura were successfully linked to vaccination records. The self-controlled case-series method was then used to investigate whether there was any epidemiological evidence of an increased risk of convulsions or purpura following vaccination. The results showed that there was no evidence of an increased relative incidence (RI) of convulsions in the two weeks following MCCV with RI estimates (95% confidence intervals) of 0.57 (0.36-0.86), 1.03 (0.62-1.69) and 0.81 (0.51-1.30) for children aged <1, 1, 2-17 years respectively. There was also no increased relative incidence of purpura in the 4 weeks following MCCV, with an overall RI of 1.15 (0.80-1.67). There was evidence of an increased risk of convulsions and idiopathic thrombocytopenic purpura following MMR vaccination as previously documented. PMID:17312400

Andrews, Nick; Stowe, Julia; Miller, Elizabeth; Taylor, Brent

2007-03-17

232

Serogroup quantitation of multivalent polysaccharide and polysaccharide-conjugate meningococcal vaccines from China.  

PubMed

The active components of most meningococcal vaccines are four antigenic serogroup capsular polysaccharides (A, C, Y, W135). The vaccines, monovalent or multivalent mixtures of either free polysaccharides or polysaccharides conjugated to antigenic carrier proteins, may be in liquid or lyophilised formulations, with or without excipients. Acid hydrolysis and chromatographic methods for serogroup quantitation, which were previously optimised and qualified using polysaccharide-based standards and a narrow range of real vaccines, are here challenged with multiple lots of a broad assortment of additional multivalent polysaccharide-based meningococcal vaccine products. Centrifugal filtration successfully removed all interfering lactose excipient without loss of polysaccharides to allow for the determination of Y and W135 serogroups. Replicate operations by three different analysts indicated high method reproducibility. Results indicated some lot-to-lot and product-to-product variations. However, all vaccines were within general specifications for each serogroup polysaccharide, with the exception of all lots of one polysaccharide vaccine - which by these methods were found to be deficient in the serogroup A component only. These robust techniques are very useful for the evaluation of antigen content and consistency of manufacture. The deformulation, hydrolysis and chromatographic methods may be adaptable for the evaluation of other types of polysaccharide-based vaccines. PMID:23665303

Cook, Matthew C; Gibeault, Sabrina; Filippenko, Vasilisa; Ye, Qiang; Wang, Junzhi; Kunkel, Jeremy P

2013-05-09

233

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

Microsoft Academic Search

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

Betsy Abraham-Van Parijs; Frank J Malinoski

2004-01-01

234

[Pneumococcal vaccine: overview about the protective efficacy in different high risk groups and new progress in the development of a conjugate pneumococcal vaccine].  

PubMed

The author presents a review about the protective efficacy of polyvalent pneumococcal polysaccharide vaccines in different groups at high risk for severe pneumococcal infection and the difficulties in the development of a conjugate pneumococcal vaccine capable of offering protection to younger children. PMID:14688878

Bricks, L F

235

Combined Administration of Meningococcal Serogroup B Outer Membrane Vesicle Vaccine and Conjugated Serogroup C Vaccine Indicated for Prevention of Meningococcal Disease Is Safe and Immunogenic  

Microsoft Academic Search

MenBvac and Menjugate are safe and efficacious vaccines. The purpose of this study was to evaluate safety and immunogenicity of the combination (MenB\\/C) of the lyophilized active components of the conjugated group C vaccine Menjugate when reconstituted with the full liquid group B outer membrane vesicle vaccine MenBvac compared to MenBvac and Menjugate given separately. At 6-week intervals, healthy adults

Ingeborg S. Aaberge; Philipp Oster; Oddveig S. Helland; Anne-Cathrine Kristoffersen; Ellen Ypma; E. Arne Høiby; Berit Feiring; H. Nokleby

2005-01-01

236

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

PubMed Central

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.

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

1988-01-01

237

Population-Based Impact of Pneumococcal Conjugate Vaccine in Young Children  

Microsoft Academic Search

ABSTRACT. Objective. To determine the population impact of pneumococcal conjugate vaccine (PCV) on pneumococcal-related diseases, including pneumonia and otitis media. Methods. Using administrative data from Tennessee Medicaid and 3 commercial insurance plans in upstate New York, we measured annual rates of medical visits for pneumococcal-related diseases (pneumococcal and nonspecific pneumonia and invasive disease; otitis me- dia) and pneumococcal-unrelated diseases (other

Katherine A. Poehling; Mph Bonnie J. Lafleur; Mph Peter G. Szilagyi; Kathryn M. Edwards; Ed Mitchel; Richard Barth; Benjamin Schwartz; Marie R. Griffin

238

Intranasal immunisation with conjugate vaccine protects mice from systemic and respiratory tract infection with Pseudomonas aeruginosa  

Microsoft Academic Search

We tested intranasal application of anti-Pseudomonas conjugate vaccine in mice. Comparison of immunisation via the intra-muscular versus intranasal routes showed the induction of equivalent levels of specific serum IgG and IgG subclasses antibodies if cholera toxin was used as an adjuvant. In contrast, secretion of specific mucosal IgA antibodies in the upper respiratory tract was only observed after intranasal immunisation

Adrian W. Zuercher; Michael P. Horn; Hong Wu; Zhijun Song; Cathrine J. Bundgaard; Helle Krogh Johansen; Niels Høiby; Paul Marcus; Alois B. Lang

2006-01-01

239

Neisseria meningitidis serogroup C polysaccharide and serogroup B outer membrane vesicle conjugate as a bivalent meningococcus vaccine candidate  

Microsoft Academic Search

Neisseria meningitidis serogroup C polysaccharide (PS C) was conjugated to serogroup B outer membrane vesicles (OMV) in order to test the possibility of obtaining a bivalent group B and C meningococcus vaccine. The conjugate and controls were injected intraperitoneally into groups of ten mice with boosters on days 14 and 28 after the primary immunization. The following groups were used

Lucila O. Fukasawa; Maria Cec??lia O. Gorla; Rocilda P. F. Schenkman; Ligiane R. Garcia; Sylvia M. Carneiro; Isaias Raw; Martha M. Tanizaki

1999-01-01

240

Immunogens consisting of oligosaccharides from the capsule of Haemophilus influenzae type b coupled to diphtheria toxoid or the toxin protein CRM197.  

PubMed Central

Haemophilus influenzae type b (Hib) capsular polysaccharide (PRP) was selectively hydrolyzed to reducing oligosaccharides, and the fraction containing 3-10 ribosylribitolphosphate repeating units (VS) was conjugated by reductive amination to diphtheria toxin (DTx), its nontoxic derivative CRM197 (Dcr), or diphtheria toxoid (DTd). Conjugate DTx-VS retained approximately 1% of native toxicity, which was eliminated by treatment with formalin. Immunization of rabbits with the conjugates elicited antibody (Ab) to PRP and to DTx but not to a model for the linkage determinant. Human adults given single subcutaneous injections had rises in serum Ab to PRP and in bactericidal activity in vitro; the Ab protected infant rats challenged with Hib. Adults had rises also in Ab to DTd, and these Ab protected rabbits against DTx. A series of two injections of the conjugates Dcr-VS and DTd-VS was tested in infants beginning at 19-23 mo of age. Rises in anti-PRP Ab after the primary resembled the rises after PRP vaccine. In contrast to PRP, the conjugates elicited large rises after the secondary vaccinations and a substantial IgG component. Development of bactericidal activity paralleled the rises in anti-PRP Ab. Secondary rises after Dcr-VS were higher than after DTd-VS. In infants 12-16 mo of age, Dcr-VS (but not DTd-VS) elicited strong primary and secondary Ab responses that included IgG and bactericidal activity. Both conjugates produced consistent rises in Ab to DTd. Images

Anderson, P; Pichichero, M E; Insel, R A

1985-01-01

241

Sortase-conjugation generates a capsule vaccine that protects guinea pigs against Bacillus anthracis  

PubMed Central

Capsules protect bacteria against phagocytic clearance. Capsular polysaccharides or polyglutamates have evolved also to resist antigen presentation by immune cells, thereby interfering with the production of opsonophagocytic antibodies. Linking capsular material to a carrier protein stimulates its presentation to the immune system. For many conjugate vaccines this is achieved by a process of random chemical cross-linking. Here we describe a new technology, designated sortase-conjugation, which generates a single amide bond between the C-terminal end of a carrier protein and the capsular material. Sortase-conjugation was used to link the poly-D-?-glutamic acid (PDGA) capsule of Bacillus anthracis to the receptor binding domain (D4) of protective antigen (PagA). When used as a vaccine, PDGA-D4 conjugate elicited robust antibody responses against both capsule and D4. Immunization with PDGA-D4 afforded guinea pigs complete protection against anthrax challenge with wild-type or pagA mutant B. anthracis Ames.

Garufi, Gabriella; Wang, Ya-Ting; Oh, So-Young; Maier, Hannah; Missiakas, Dominique M.; Schneewind, Olaf

2012-01-01

242

Sortase-conjugation generates a capsule vaccine that protects guinea pigs against Bacillus anthracis.  

PubMed

Capsules protect bacteria against phagocytic clearance. Capsular polysaccharides or polyglutamates have evolved also to resist antigen presentation by immune cells, thereby interfering with the production of opsonophagocytic antibodies. Linking capsular material to a carrier protein stimulates its presentation to the immune system. For many conjugate vaccines this is achieved by a process of random chemical cross-linking. Here we describe a new technology, designated sortase-conjugation, which generates a single amide bond between the C-terminal end of a carrier protein and the capsular material. Sortase-conjugation was used to link the poly-D-?-glutamic acid (PDGA) capsule of Bacillus anthracis to the receptor binding domain (D4) of protective antigen (PagA). When used as a vaccine, PDGA-D4 conjugate elicited robust antibody responses against both capsule and D4. Immunization with PDGA-D4 afforded guinea pigs complete protection against anthrax challenge with wild-type or pagA mutant B. anthracis Ames. PMID:22449424

Garufi, Gabriella; Wang, Ya-Ting; Oh, So-Young; Maier, Hannah; Missiakas, Dominique M; Schneewind, Olaf

2012-03-23

243

Immune Response to Meningococcal Serogroup C Conjugate Vaccine in Asplenic Individuals  

PubMed Central

Asplenic individuals are known to be at increased risk of infection with encapsulated bacteria. Recent United Kingdom recommendations stated that this at-risk group should receive one dose of the meningococcal serogroup C conjugate (MCC) vaccine. However, the immune response of asplenic individuals to MCC vaccine is unknown. The immune response of asplenics (n = 130) to immunization with the MCC vaccine was investigated. Asplenic individuals had a significantly lower geometric mean titer (GMT) (157.8; 95% confidence interval [CI], 94.5 to 263.3) of bactericidal antibody in serum (SBA) than an age-matched control group (n = 48) (1448.2; 95% CI, 751.1 to 2792.0). However, 80% of asplenic individuals achieved the proposed protective SBA titer of ?8. No differences were observed between the two groups in the serogroup C-specific immunoglobulin G geometric mean concentration. A significant reduction in SBA GMT or the number of responders achieving an SBA titer of ?8 was observed if the reason for splenectomy was a medical cause or if MCC vaccination occurred <10 years after splenectomy. Individuals (n = 29) who did not achieve an SBA titer of ?16 were offered a second dose of MCC vaccine. Analysis of the SBA response revealed that 61% (14 of 23) of the individuals who received a second dose achieved a protective titer. In total, 93% of asplenic individuals achieved a titer of ?8 following MCC vaccination (one or two doses combined). We recommend that, following vaccination of asplenics, either the level of functional antibody should be determined, with a second dose of MCC vaccine offered to nonresponders, or two doses of MCC vaccine should be routinely offered.

Balmer, Paul; Falconer, Michelle; McDonald, Paula; Andrews, Nick; Fuller, Emily; Riley, Christine; Kaczmarski, Edward; Borrow, Raymond

2004-01-01

244

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

PubMed Central

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.

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

2013-01-01

245

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

PubMed Central

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.

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

2012-01-01

246

Correlation of Group C Meningococcal Conjugate Vaccine Response with B- and T-Lymphocyte Activity  

PubMed Central

Despite the success of conjugate vaccination against meningococcal group C (MenC) disease, post-vaccination, some individuals still exhibit rapid waning of initially protective bactericidal antibody levels. The mechanism of this relative loss of humoral protection remains undetermined. In this report we have investigated the relationship between T- and B-cell activation and co-stimulation and the loss of protective antibody titers. We have found that healthy volunteers who lose protective MenC antibody levels one year after receipt of glycoconjugate vaccine exhibit no detectable cellular defect in polyclonal B- or T-cell activation, proliferation or the B-memory pool. This suggests that the processes underlying the more rapid loss of antibody levels are independent of defects in either initial T- or B-cell activation.

Wing, James B.; Smart, Lynne; Borrow, Ray; Findlow, Jamie; Findlow, Helen; Lees, Andrew; Read, Robert C.; Heath, Andrew W.

2012-01-01

247

Evaluation of a novel Vi conjugate vaccine in a murine model of salmonellosis.  

PubMed

Immunisation of BALB/c mice with a vaccine containing Vi polysaccharide conjugated to the Klebsiella pneumoniae outer membrane 40 kDa protein (rP40), in combination with Escherichia coli heat-labile toxin adjuvant (LT), elicited anti-Vi IgG antibodies after administration using different routes. Testing of the immune serum in opsonisation assays demonstrated the specific enhancement of Vi-positive bacterial uptake by cultured murine bone marrow derived macrophages. Intra-peritoneal challenge of mice immunised with the Vi-based vaccine elicited a degree of protection against virulent Vi+ Salmonella enterica serovar typhimurium (S. typhimurium). In contrast, Vi vaccination did not confer protection against oral challenge with virulent Vi-positive S. typhimurium or S. dublin. PMID:16600446

Hale, Christine; Bowe, Frances; Pickard, Derek; Clare, Simon; Haeuw, Jean-Francois; Powers, Ultan; Menager, Nathalie; Mastroeni, Pietro; Dougan, Gordon

2006-03-20

248

Clonal replacement among 19A Streptococcus pneumoniae in Massachusetts, prior to 13 valent conjugate vaccination  

PubMed Central

As part of an ongoing study of the response of the Streptococcus pneumoniae population to conjugate vaccination, we applied multi-locus sequence typing (MLST) to 291 isolates sampled from nasopharyngeal carriage in Massachusetts children. We found 94 distinct sequence types (STs), including 19 that had not been previously recorded, and a xpt allele containing a large insertion. Comparison with a similar sample collected in 2007 revealed no significant overall difference in the ST composition (p=0.51) suggesting that the population has reached a new equilibrium following the introduction of 7 valent vaccination in 2000. Within serotypes, a large and statistically significant increase (p=0.014 Fisher’s Exact test) was noted in the prevalence of the major multiresistant clone ST 320, which is apparently outcompeting ST 199 among serotype 19A strains. This sample will be used as a baseline to study the future evolution of the pneumococcal population in Massachusetts following introduction of vaccines with higher valency.

Bishop, C. J.; Lee, G. M.; Lipsitch, M.; Stevenson, A; Rifas-Shiman, S. L.; Pelton, S. I.; Huang, S. S.; Finkelstein, J. A.

2011-01-01

249

Safety and immunogenicity in man of a synthetic peptide malaria vaccine against Plasmodium falciparum sporozoites  

Microsoft Academic Search

A 12 ammo-acid synthetic peptide (NANP)3 comprising the immunodominant epitope of Plasmodium falciparum circum-sporozoite protein was conjugated to tetanus toxoid (TT), adjuvan-ted with aluminium hydroxide, and administered intramuscularly in three doses at monthly intervals to 35 healthy males as a malaria vaccine. No significant adverse reactions were noted, with mild soreness at the injection site the only common symptom. Serocon-versions

Deirdre A. Herrington; David F. Clyde; Genevieve Losonsky; Manuel Cortesia; James R. Murphy; Jonathan Davis; Shahida Baqar; Arthur M. Felix; Edgar P. Heimer; Dieter Gillessen; Elizabeth Nardin; Ruth S. Nussenzweig; Victor Nussenzweig; Michael R. Hollingdale; Myron M. Levine

1987-01-01

250

Live attenuated influenza vaccine, but not pneumococcal conjugate vaccine, protects against increased density and duration of pneumococcal carriage after influenza infection in pneumococcal colonized mice.  

PubMed

Secondary bacterial infections due to Streptococcus pneumoniae and Staphylococcus aureus, responsible for excess morbidity and mortality during influenza epidemics, are often preceded by excess bacterial density within the upper respiratory tract. Influenza and pneumococcal vaccines reduce secondary infections within the lungs; however, their effects on upper respiratory tract carriage remain unknown. We demonstrate that a live attenuated influenza vaccine significantly reduces pneumococcal growth and duration of carriage during subsequent influenza to levels seen in influenza-naive controls. No benefit was seen after pneumococcal conjugate vaccine. Our results suggest that live attenuated influenza vaccines may significantly reduce bacterial disease during influenza epidemics. PMID:23852122

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

2013-07-11

251

Development of immunologic memory against tetanus toxoid and pertactin antigens from the diphtheria-tetanus-pertussis vaccine in atopic versus nonatopic children  

Microsoft Academic Search

Background: Recent findings suggest that a hallmark of the atopic phenotype is reduced capacity to respond to vaccine antigens, as well as to environmental allergens, during infancy. This deficiency, which is most marked for the cytokine IFN-?, appears transient but can result in a long-lasting imbalance within T helper cell (TH) memory responses to allergens. Indirect evidence suggests that parallel

Patrick G. Holt; Anna Rudin; Claudia Macaubas; Barbara J. Holt; Julie Rowe; Richard Loh; Peter D. Sly

2000-01-01

252

Transcutaneous Immunization with Cross-Reacting Material CRM197 of Diphtheria Toxin Boosts Functional Antibody Levels in Mice Primed Parenterally with Adsorbed Diphtheria Toxoid Vaccine  

Microsoft Academic Search

Transcutaneous immunization (TCI) capitalizes on the accessibility and immunocompetence of the skin, elicits protective immunity, simplifies vaccine delivery, and may be particularly advantageous when frequent boosting is required. In this study we examined the potential of TCI to boost preexisting immune responses to diphtheria in mice. The cross-reacting material (CRM197) of diphtheria toxin was used as the boosting antigen and

Paul Stickings; Marisa Peyre; Laura Coombes; Sylviane Muller; Rino Rappuoli; Giuseppe Del Giudice; Charalambos D. Partidos; Dorothea Sesardic

2008-01-01

253

Measuring the impact of conjugate vaccines on invasive Haemophilus influenzae type b infection in Western Australia.  

PubMed

Haemophilus influenzae type b (Hib) causes serious infections in 26-59 per 100,000 non-Aboriginal Australian children under five years of age. Aboriginal children suffer much higher rates of infection (> or = 150 per 100,000), and at an earlier age, and have a greater risk of death and disability due to Hib infection. In 1992 and 1993, four conjugate Hib vaccines were introduced in Australia, and a nationally funded program of infant vaccination was begun in July 1993. This study aimed at evaluating the effectiveness of Hib vaccination in Aboriginal and non-Aboriginal children in Western Australia using a population-based active surveillance system for non-Aboriginal children and a case control study for Aboriginal children. The incidence of invasive Hib disease in non-Aboriginal children fell from 30.9 per 100,000 before vaccination was available to 6.3 per 100,000 in the second year after its introduction. The vaccine efficacy was estimated to be 80 per cent for Aboriginal children (odds ratio 0.20, 95 per cent CI 0.01-2.76) and, after adjustment for confounders, 75 per cent (odds ratio 0.25, CI 0.02-3.66). Based on the adjusted value (75 per cent), and using a Bayesian approach, we estimate that the posterior probability was 0.55 that the true vaccine efficacy is greater than 70 per cent, and 0.69 that the efficacy is greater than 50 per cent. We conclude that Hib vaccination is effective in preventing invasive Hib disease in Aboriginal and non-Aboriginal children in Australia. PMID:9599855

Bower, C; Condon, R; Payne, J; Burton, P; Watson, C; Wild, B

1998-02-01

254

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

PubMed Central

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.

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

255

Evaluation of pneumococcal polysaccharide immunoassays using a 22F adsorption step with serum samples from infants vaccinated with conjugate vaccines.  

PubMed

The history of the pneumococcal polysaccharide enzyme-linked immunosorbent assay (ELISA) is characterized by a continuous search for increased specificity. A third-generation ELISA that uses 22F polysaccharide inhibition has increased the specificity of the assay, particularly at low antibody concentrations. The present work compared various 22F ELISAs and non-22F ELISAs. The comparisons involved three different laboratories, including a WHO reference laboratory, and included sera from subjects from different geographic areas immunized with different pneumococcal conjugate vaccines, including the licensed 7-valent Prevenar vaccine and the 10-valent Synflorix vaccine. All comparisons led to the same conclusion that the threshold defined as 0.35 microg/ml for the WHO non-22F ELISA is lower when any 22F ELISA is used. The use of highly purified polysaccharides for coating further improved the specificity of the assay. In conclusion, we confirm that the 22F ELISA can be recommended as a reference method for the determination of antibodies against pneumococcal polysaccharides. PMID:19889940

Poolman, Jan T; Frasch, Carl E; Käyhty, Helena; Lestrate, Pascal; Madhi, Shabir A; Henckaerts, Isabelle

2009-11-04

256

Evaluation of Pneumococcal Polysaccharide Immunoassays Using a 22F Adsorption Step with Serum Samples from Infants Vaccinated with Conjugate Vaccines? †  

PubMed Central

The history of the pneumococcal polysaccharide enzyme-linked immunosorbent assay (ELISA) is characterized by a continuous search for increased specificity. A third-generation ELISA that uses 22F polysaccharide inhibition has increased the specificity of the assay, particularly at low antibody concentrations. The present work compared various 22F ELISAs and non-22F ELISAs. The comparisons involved three different laboratories, including a WHO reference laboratory, and included sera from subjects from different geographic areas immunized with different pneumococcal conjugate vaccines, including the licensed 7-valent Prevenar vaccine and the 10-valent Synflorix vaccine. All comparisons led to the same conclusion that the threshold defined as 0.35 ?g/ml for the WHO non-22F ELISA is lower when any 22F ELISA is used. The use of highly purified polysaccharides for coating further improved the specificity of the assay. In conclusion, we confirm that the 22F ELISA can be recommended as a reference method for the determination of antibodies against pneumococcal polysaccharides.

Poolman, Jan T.; Frasch, Carl E.; Kayhty, Helena; Lestrate, Pascal; Madhi, Shabir A.; Henckaerts, Isabelle

2010-01-01

257

Antibody responses in the serum and respiratory tract of mice following oral vaccination with liposomes coated with filamentous hemagglutinin and pertussis toxoid.  

PubMed Central

Mice were orally vaccinated with liposomes coated with filamentous hemagglutinin (FHA) and detoxified pertussis toxin (PT) of Bordetella pertussis. FHA- and PT-specific immunoglobulin G (IgG) was detected in serum, and both IgG and IgA were detected in lung washes following the immunization. Antibody responses in mice immunized with liposomes coated with FHA and PT were significantly higher than those in mice immunized with free FHA and PT, which demonstrated the adjuvanticity of the liposome carrier. The results indicate the potential usefulness of this approach for eliciting immune responses against FHA and PT (and perhaps other pertussis antigens) in humans and its possible utility in large-scale vaccination to protect against both B. pertussis infection and disease. Images

Guzman, C A; Molinari, G; Fountain, M W; Rohde, M; Timmis, K N; Walker, M J

1993-01-01

258

Signal sequence deletion and fusion to tetanus toxoid epitope augment antitumor immune responses to a human carcinoembryonic antigen (CEA) plasmid DNA vaccine in a murine test system  

Microsoft Academic Search

Carcinoembryonic antigen (CEA, CEACAM5) is expressed on several human carcinomas including colon cancer. CEA contains signal peptides that target the protein through the endoplasmic reticulum and to the cell membrane. We constructed a plasmid DNA vaccine encoding a truncated CEA (?CEA), devoid of its signal peptides, and demonstrated that it was retained inside the cell, while full-length CEA (wtCEA) was

Lars H Lund; Karolina Andersson; Bartek Zuber; Anneli Karlsson; Gunnel Engström; Jorma Hinkula; Britta Wahren; Gösta Winberg

2003-01-01

259

Comparison of pneumococcal polysaccharide and CRM197-conjugated pneumococcal oligosaccharide vaccines in young and elderly adults.  

PubMed Central

Conjugation of carbohydrate antigens to protein carriers significantly improves the immune response to many carbohydrates. In order to evaluate the potential for this approach to improve the performance of pneumococcal vaccine in the elderly, we evaluated pneumococcal polysaccharide-derived oligosaccharides conjugated to cross-reacting material 197 (CRM197) (CRM-OS) in 49 older adults over 60 years of age (median age, 66 years) and compared the results to those from 50 younger adults under age 45 (median age, 27 years). Subjects were randomly assigned to receive licensed 23-valent polysaccharide vaccine (PS) which contain 25 micrograms of polysaccharide per serotype, or 5-valent CRM-OS, which contains 10 micrograms of oligosaccharide per serotype, in double-blind fashion. Both vaccines were associated with moderate local pain on administration. Antibody responses to type 14 were seen in the majority of both younger and older subjects following administration of both CRM-OS and PS, and there was no significant improvement of responses with CRM-OS in either age group. Antibody responses in young adults to the less immunogenic type 6B were seen in only 36% of subjects receiving PS and in 56% of subjects receiving CRM-OS (P = 0.15), and the geometric mean 6B titer 1 month after vaccination was higher in CRM-OS recipients (10.9 versus 3.7 micrograms/ml; P = 0.04). However, 6B responses were poor following the administration of either vaccine to elderly adults and there was no difference between results with CRM-OS and those with PS in this age group. Relatively few subjects developed measurable mucosal immunoglobulin A responses in nasal secretions following administration of either vaccine. Revaccination of CRM-OS recipients with PS at 2 months did not result in significant additional responses to 6B or 14. Though CRM-OS is possibly more immunogenic in young adults, the formulation of the pneumococcal glycoconjugate vaccine used in this study does not appear to offer an advantage to the elderly for types 6B or 14.

Shelly, M A; Jacoby, H; Riley, G J; Graves, B T; Pichichero, M; Treanor, J J

1997-01-01

260

Immunogenicity following one, two, or three doses of the 7-valent pneumococcal conjugate vaccine.  

PubMed

The aim was to identify an appropriate infant pneumococcal vaccination strategy for resource poor countries. Fijian infants received zero, one, two, or three doses of 7-valent pneumococcal conjugate vaccine (PCV) in early infancy. Following three PCV doses, geometric mean concentration (GMC) to all seven serotypes were > or = 1.0 microg/mL, and >85% of children achieved antibody levels > or = 0.35 microg/mL at 18 weeks. Following two doses, GMC were lower for 6B, 14, and 23F, but higher for 19F compared with three doses. Following a single dose, significant responses were seen for all serotypes post-primary series compared with the unvaccinated. By 12 months, differences between two and three doses persisted for serotype 14 only. Although GMC following three doses are higher than after two doses, the differences were small. A single dose may offer some protection for most serotypes. PMID:19616498

Russell, F M; Balloch, A; Tang, M L K; Carapetis, J R; Licciardi, P; Nelson, J; Jenney, A W J; Tikoduadua, L; Waqatakirewa, L; Pryor, J; Byrnes, G B; Cheung, Y B; Mulholland, E K

2009-07-17

261

Immunogenicity Following One, Two, or Three Doses of the 7-valent Pneumococcal Conjugate Vaccine  

PubMed Central

The aim was to identify an appropriate infant pneumococcal vaccination strategy for resource poor countries. Fijian infants received 0, 1, 2, or 3 doses of 7-valent pneumococcal conjugate vaccine (PCV) in early infancy. Following 3 PCV doses, geometric mean concentration (GMC) to all 7 serotypes were ? 1.0?g/mL, and >85% of children achieved antibody levels ?0.35?g/mL at 18 weeks. Following 2 doses, GMC were lower for 6B, 14, and 23F, but higher for 19F compared with 3 doses. Following a single dose, significant responses were seen for all serotypes post primary series compared with the unvaccinated. By 12 months, differences between 2 and 3 doses persisted for serotype 14 only. Although GMC following 3 doses are higher than after 2 doses, the differences were small. A single dose may offer some protection for most serotypes.

Russell, FM; Balloch, A; Tang, MLK; Carapetis, JR; Licciardi, P; Nelson, J; Jenney, AWJ; Tikoduadua, L; Waqatakirewa, L; Pryor, J; Byrnes, GB; Cheung, YB; Mulholland, EK

2009-01-01

262

Randomized, controlled trial of a 13-valent pneumococcal conjugate vaccine administered concomitantly with an influenza vaccine in healthy adults.  

PubMed

A randomized, double-blind, phase 3 trial evaluated the immunogenicity, safety, and tolerability of a 13-valent pneumococcal conjugate vaccine (PCV13) coadministered with trivalent inactivated influenza vaccine (TIV) in pneumococcal vaccine-naive adults. Participants ages 50 to 59 years (n = 1,116) received TIV with PCV13 (group 1) or placebo (group 2) (1:1 randomization); 1 month later, group 1 received placebo and group 2 received PCV13. A hemagglutination inhibition (HAI) assay for TIV and a standardized enzyme-linked immunosorbent assay for pneumococcal serotype-specific immunoglobulin G (IgG) were performed and opsonophagocytic activity (OPA) titers (assessed post hoc) were measured at baseline and 1 and 2 months postvaccination. The rises in HAI assay geometric mean titer (GMT) and percentage of participants in groups 1 and 2 with ? 4-fold increases in HAI responses (A/H1N1, 84.0% and 81.2%, respectively; A/H3N2, 71.1% and 69.5%, respectively; and B, 60.6% and 60.3%, respectively) were similar. In group 1, all serotypes met the predefined IgG geometric mean concentration (GMC) ratio noninferiority criterion relative to group 2, but GMCs were lower in group 1 than group 2. When comparing group 1 with group 2, 5 serotypes did not meet the OPA GMT ratio noninferiority criterion, and OPA GMTs were significantly lower for 10 serotypes. PCV13 injection site reactions were similar and mostly mild in both groups. Systemic events were more frequent in group 1 (86.2%) than group 2 (76.7%; P < 0.001); no vaccine-related serious adverse events occurred. Coadministration of PCV13 and TIV was well tolerated but associated with lower PCV13 antibody responses and is of unknown clinical significance. Given the positive immunologic attributes of PCV13, concomitant administration with TIV should be dictated by clinical circumstances. PMID:22739693

Frenck, Robert W; Gurtman, Alejandra; Rubino, John; Smith, William; van Cleeff, Martin; Jayawardene, Deepthi; Giardina, Peter C; Emini, Emilio A; Gruber, William C; Scott, Daniel A; Schmöle-Thoma, Beate

2012-06-27

263

Randomized, Controlled Trial of a 13-Valent Pneumococcal Conjugate Vaccine Administered Concomitantly with an Influenza Vaccine in Healthy Adults  

PubMed Central

A randomized, double-blind, phase 3 trial evaluated the immunogenicity, safety, and tolerability of a 13-valent pneumococcal conjugate vaccine (PCV13) coadministered with trivalent inactivated influenza vaccine (TIV) in pneumococcal vaccine-naive adults. Participants ages 50 to 59 years (n = 1,116) received TIV with PCV13 (group 1) or placebo (group 2) (1:1 randomization); 1 month later, group 1 received placebo and group 2 received PCV13. A hemagglutination inhibition (HAI) assay for TIV and a standardized enzyme-linked immunosorbent assay for pneumococcal serotype-specific immunoglobulin G (IgG) were performed and opsonophagocytic activity (OPA) titers (assessed post hoc) were measured at baseline and 1 and 2 months postvaccination. The rises in HAI assay geometric mean titer (GMT) and percentage of participants in groups 1 and 2 with ?4-fold increases in HAI responses (A/H1N1, 84.0% and 81.2%, respectively; A/H3N2, 71.1% and 69.5%, respectively; and B, 60.6% and 60.3%, respectively) were similar. In group 1, all serotypes met the predefined IgG geometric mean concentration (GMC) ratio noninferiority criterion relative to group 2, but GMCs were lower in group 1 than group 2. When comparing group 1 with group 2, 5 serotypes did not meet the OPA GMT ratio noninferiority criterion, and OPA GMTs were significantly lower for 10 serotypes. PCV13 injection site reactions were similar and mostly mild in both groups. Systemic events were more frequent in group 1 (86.2%) than group 2 (76.7%; P < 0.001); no vaccine-related serious adverse events occurred. Coadministration of PCV13 and TIV was well tolerated but associated with lower PCV13 antibody responses and is of unknown clinical significance. Given the positive immunologic attributes of PCV13, concomitant administration with TIV should be dictated by clinical circumstances.

Gurtman, Alejandra; Rubino, John; Smith, William; van Cleeff, Martin; Jayawardene, Deepthi; Giardina, Peter C.; Emini, Emilio A.; Gruber, William C.; Scott, Daniel A.; Schmole-Thoma, Beate

2012-01-01

264

Safety, immunogenicity and efficacy of pneumococcal conjugate vaccine in HIV-infected individuals  

PubMed Central

Streptococcus pneumoniae is the leading bacterial opportunistic infection in HIV-infected individuals. Anti-retroviral treatment (ART) of HIV-infected individuals reduces their risk of invasive pneumococcal disease (IPD), however, it remains 20- to 40-fold greater compared with age-matched general population. This review summarizes the available published data on the immunogenicity, safety and efficacy of pneumococcal polysaccharide-protein conjugate vaccines (PCV) in HIV-infected children and adults.   Several studies have demonstrated that PCV are safe in the HIV-infected persons. Although PCV are immunogenic in HIV-infected infants, the antibodies produced are functionally impaired, there is possibly a lack or loss of anamnestic responses and immunity declines in later life However, quantitative and qualitative antibody responses to PCV in HIV-infected infants are enhanced when vaccination occurs whilst on ART, as well as if vaccination occurs when the CD4+ cell percentage is ? 25% and if the nadir CD4+ is >15%. Although the efficacy of PCV was lower, the vaccine preventable burden of hospitalization for IPD and clinical pneumonia were 18-fold and 9-fold greater, respectively, in HIV-infected children compared with –uninfected children. In HIV-infected adults, PCV vaccination induces more durable and functional antibody responses in individuals on ART at the time of vaccination than in ART-naive adults, independently of baseline CD4+ cell count, although there does not appear to be much benefit from a second-dose of PCV. PCV has also been shown to reduce the risk of recurrent IPD by 74% in HIV-infected adults not on ART, albeit, also with subsequent decline in immunity and protection.

Nunes, Marta C.; Madhi, Shabir A.

2012-01-01

265

Carbohydrate vaccines in cancer: immunogenicity of a fully synthetic globo H hexasaccharide conjugate in man.  

PubMed

The complex carbohydrate molecule globo H hexasaccharide has been synthesized, conjugated to keyhole limpet hemocyanin, and administered with the immunologic adjuvant QS-21 as a vaccine for patients with prostate cancer who have relapsed after primary therapies such as radiation or surgery. Globo H is one of several candidate antigens present on prostate cancer cells that can serve as targets for immune recognition and treatment strategies. The vaccine, given as five subcutaneous vaccinations over 26 weeks, has been shown to be safe and capable of inducing specific high-titer IgM antibodies against globo H. Its immunogenicity was confirmed in prostate cancer patients with a broad range of stages and tumor burdens. Observations of several patients who had evidence of disease relapse restricted to a rising biochemical marker, prostate-specific antigen (PSA), indicated that a treatment effect could occur within 3 months after completion of the vaccine therapy. This effect was manifested as a decline of the slope of the log of PSA concentration vs. time plot after treatment compared with values before treatment. Five patients continue to have stable PSA slope profiles in the absence of any radiographic evidence of disease for more than 2 years. The concept of using PSA slope profiles in assessing early treatment effects in biological therapies such as vaccines awaits further validation in phase II and III trials. The use of a variety of lesser known candidate glycoprotein and carbohydrate antigens in prostate cancer serves as a focus for the development of a multivalent vaccine of the treatment of relapsed prostate cancer in patients with minimal tumor burden. PMID:10318949

Slovin, S F; Ragupathi, G; Adluri, S; Ungers, G; Terry, K; Kim, S; Spassova, M; Bornmann, W G; Fazzari, M; Dantis, L; Olkiewicz, K; Lloyd, K O; Livingston, P O; Danishefsky, S J; Scher, H I

1999-05-11

266

Carbohydrate vaccines in cancer: Immunogenicity of a fully synthetic globo H hexasaccharide conjugate in man  

PubMed Central

The complex carbohydrate molecule globo H hexasaccharide has been synthesized, conjugated to keyhole limpet hemocyanin, and administered with the immunologic adjuvant QS-21 as a vaccine for patients with prostate cancer who have relapsed after primary therapies such as radiation or surgery. Globo H is one of several candidate antigens present on prostate cancer cells that can serve as targets for immune recognition and treatment strategies. The vaccine, given as five subcutaneous vaccinations over 26 weeks, has been shown to be safe and capable of inducing specific high-titer IgM antibodies against globo H. Its immunogenicity was confirmed in prostate cancer patients with a broad range of stages and tumor burdens. Observations of several patients who had evidence of disease relapse restricted to a rising biochemical marker, prostate-specific antigen (PSA), indicated that a treatment effect could occur within 3 months after completion of the vaccine therapy. This effect was manifested as a decline of the slope of the log of PSA concentration vs. time plot after treatment compared with values before treatment. Five patients continue to have stable PSA slope profiles in the absence of any radiographic evidence of disease for more than 2 years. The concept of using PSA slope profiles in assessing early treatment effects in biological therapies such as vaccines awaits further validation in phase II and III trials. The use of a variety of lesser known candidate glycoprotein and carbohydrate antigens in prostate cancer serves as a focus for the development of a multivalent vaccine of the treatment of relapsed prostate cancer in patients with minimal tumor burden.

Slovin, S. F.; Ragupathi, G.; Adluri, S.; Ungers, G.; Terry, K.; Kim, S.; Spassova, M.; Bornmann, W. G.; Fazzari, M.; Dantis, L.; Olkiewicz, K.; Lloyd, K. O.; Livingston, P. O.; Danishefsky, S. J.; Scher, H. I.

1999-01-01

267

Clonal analysis of invasive pneumococcal isolates in Scotland and coverage of serotypes by the licensed conjugate polysaccharide pneumococcal vaccine: possible implications for UK vaccine policy  

Microsoft Academic Search

A 7-valent pneumococcal conjugate vaccine (PCV7) has gained licensure and has proven successful in the USA for preventing pneumococcal disease and reducing the incidence of antibiotic-resistant pneumococcal strains. The ability, therefore, to accurately monitor the likely effect of the introduction of PCV7 vaccine on invasive pneumococcal disease in the UK is essential. Serotyping and multilocus sequence typing was performed on

S. M. McChlery; K. J. Scott; S. C. Clarke

2005-01-01

268

A comparison of multiple regimens of pneumococcal polysaccharide–meningococcal outer membrane protein complex conjugate vaccine and pneumococcal polysaccharide vaccine in toddlers  

Microsoft Academic Search

Children who had been randomized to receive one dose of either heptavalent pneumococcal polysaccharide–meningococcal outer membrane protein complex conjugate vaccine (PCV) or 23-valent pneumococcal polysaccharide vaccine (PN23) at 12, 15, or 18 months of age were subsequently randomized to receive a booster injection of either PCV or PN23 12 months later. For those children who received a priming dose of

Michael D. Blum; Ron Dagan; Paul M. Mendelman; Vered Pinsk; Michael Giordani; Shu Li; Norman Bohidar; Tessie B. McNeely

2000-01-01

269

Potential Impact of Conjugate Vaccine on the Incidence of Invasive Pneumococcal Disease among Children in Scotland  

PubMed Central

We sought to determine the potential impact of seven-valent pneumococcal conjugate vaccine on the incidence of invasive pneumococcal disease (IPD) among children in Scotland. Invasive pneumococci from blood and cerebrospinal fluid, isolated between 2000 and 2004 from all children aged less than 5 years in Scotland, were characterized by serotyping. Using reported efficacy data of the seven-valent pneumococcal conjugate vaccine (PCV7) along with likely coverage rates, we made an estimation of the potential impact on the incidence of IPD among children in Scotland. A total of 217 pneumococci were characterized into 22 different serogroups/types, the most common, in rank order, being 14, 19F, 6B, 18C, 23F, 9V, 4, 1, 19A, and 6A. Estimated serotype coverage for PCV7 was 76.5% in those aged less than 5 years of age but increased to 88.9% for those aged 1 year. By using serotype coverage and estimates of vaccine efficacy and uptake, the potential impact of the vaccine for those greater than 2 months of age, but less than 5 years, was estimated as 67.3%, leading to an average of 29 preventable cases per year. The introduction of PCV7 into the childhood immunization schedule would reduce the burden of pneumococcal disease in children, and the incidence would be particularly reduced in those children aged 1 year. Additional benefits may be gained in adults through herd protection. Continued surveillance of IPD is required before, during, and after the introduction of PCV7.

Clarke, Stuart C.; Jefferies, Johanna M.; Smith, Andrew J.; McMenamin, Jim; Mitchell, Timothy J.; Edwards, Giles F. S.

2006-01-01

270

Impact of the introduction of pneumococcal conjugate vaccine on immunization coverage among infants  

PubMed Central

Background The introduction of pneumococcal conjugate vaccine (PCV) to the U.S. recommended childhood immunization schedule in the year 2000 added three injections to the number of vaccinations a child is expected to receive during the first year of life. Surveys have suggested that the addition of PCV has led some immunization providers to move other routine childhood vaccinations to later ages, which could increase the possibility of missing these vaccines. The purpose of this study was to evaluate whether introduction of PCV affected immunization coverage for recommended childhood vaccinations among 13-month olds in four large provider groups. Methods In this retrospective cohort study, we analyzed computerized data on vaccinations for 33,319 children in four large provider groups before and after the introduction of PCV. The primary outcome was whether the child was up to date for all non-PCV recommended vaccinations at 13 months of age. Logistic regression was used to evaluate the association between PCV introduction and the primary outcome. The secondary outcome was the number of days spent underimmunized by 13 months. The association between PCV introduction and the secondary outcome was evaluated using a two-part modelling approach using logistic and negative binomial regression. Results Overall, 93% of children were up-to-date at 13 months, and 70% received all non-PCV vaccinations without any delay. Among the entire study population, immunization coverage was maintained or slightly increased from the pre-PCV to post-PCV periods. After multivariate adjustment, children born after PCV entered routine use were less likely to be up-to-date at 13 months in one provider group (Group C: OR = 0.5; 95% CI: 0.3 – 0.8) and were less likely to have received all vaccine doses without any delay in two Groups (Group B: OR = 0.4, 95% CI: 0.3 – 0.6; Group C: OR = 0.5, 95% CI: 0.4 – 0.7). This represented 3% fewer children in Group C who were up-to-date and 14% (Group C) to 16% (Group B) fewer children who spent no time underimmunized at 13 months after PCV entered routine use compared to the pre-PCV baseline. Some disruptions in immunization delivery were also observed concurrent with temporary recommendations to suspend the birth dose of hepatitis B vaccine, preceding the introduction of PCV. Conclusion These findings suggest that the introduction of PCV did not harm overall immunization coverage rates in populations with good access to primary care. However, we did observe some disruptions in the timely delivery of other vaccines coincident with the introduction of PCV and the suspension of the birth dose of hepatitis B vaccine. This study highlights the need for continued vigilance in coming years as the U.S. introduces new childhood vaccines and policies that may change the timing of existing vaccines.

Lin, Nancy D; Kleinman, Ken; Chan, K Arnold; Yu, Xian-Jie; France, Eric K; Xu, Stanley; Wei, Feifei; Mullooly, John; Santoli, Jeanne; Lieu, Tracy A

2005-01-01

271

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

PubMed Central

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.

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

272

Conjugating recombinant proteins to Pseudomonas aeruginosa ExoProtein A: a strategy for enhancing immunogenicity of malaria vaccine candidates  

PubMed Central

Conjugation of polysaccharides to carrier proteins has been a successful approach for producing safe and effective vaccines. In an attempt to increase the immunogenicity of two malarial vaccine candidate proteins of Plasmodium falciparum, apical membrane antigen 1 (AMA1) for blood stage vaccines and surface protein 25 (Pfs25) for mosquito stage vaccines, each was chemically conjugated to the mutant, nontoxic Pseudomonas aeruginosa ExoProtein A (rEPA). AMA1 is a large (66 kD) relatively good immunogen in mice; Pfs25 is a poorly immunogenic protein when presented on alum to mice. Mice were immunized on days 0 and 28 with AMA1 or Pfs25 rEPA conjugates or unconjugated AMA1 or Pfs25, all formulated on Alhydrogel. Remarkably, sera from mice 14 days after the second immunization with Pfs25-rEPA conjugates displayed over a 1000 fold higher antibody titers as compared to unconjugated Pfs25. In contrast, AMA1 conjugated under the same conditions induced only a 3 fold increase in antibody titers. When tested for functional activity, antibodies elicited by the AMA1-rEPA inhibited invasion of erythrocytes by blood-stage parasites and antibodies elicited by the Pfs25-rEPA conjugates blocked the development of the sexual stage parasites in the mosquito midgut. These results demonstrate that conjugation to rEPA induces a marked improvement in the antibody titer in mice for the poor immunogen (Pfs25) and for the larger protein (AMA1). These conjugates now need to be tested in humans to determine if mice are predictive of the response in humans.

Qian, Feng; Wu, Yimin; Muratova, Olga; Zhou, Hong; Dobrescu, Gelu; Duggan, Peter; Lynn, Lambert; Song, Guanhong; Zhang, Yanling; Reiter, Karine; MacDonald, Nicholas; Narum, David L.; Long, Carole A.; Miller, Louis H.; Saul, Allan; Mullen., Gregory E. D.

2007-01-01

273

Effectiveness of the 7Valent Pneumococcal Conjugate Vaccine in Children With Sickle Cell Disease in the First Decade of Life  

Microsoft Academic Search

BACKGROUND.The incidence of and mortality from invasive pneumococcal disease are significantly higher in children with sickle cell disease than in the general pediatric population. The objective of this population-based study was to assess the effect of pneumococcal conjugate vaccine on rates of invasive pneumococcal disease among children with sickle cell disease. PATIENTS AND METHODS.Records, including the history of pneumococcal conjugate

Thomas V. Adamkiewicz; Benjamin J. Silk; James Howgate; Wendy Baughman; Gregory Strayhorn; Kevin Sullivan; Monica M. Farley

2010-01-01

274

Molecular epidemiology of pneumococcal colonization in response to pneumococcal conjugate vaccination in children with recurrent acute otitis media  

Microsoft Academic Search

A randomized double-blind trial with a 7-valent pneumococcal conjugate vaccine was conducted in The Netherlands among 383 children, aged 1 to 7 years, with a history of recurrent acute otitis media. No effect of vaccination on the pneumococcal colonization rate was found. However, a shift in serotype distribution was clearly observed (R. Veenhoven et al., Lancet 361:2189-2195, 2003). We investigated

D. Bogaert; R. H. Veenhoven; M. Sluijter; W. J. B. Wannet; G. T. Rijkers; T. J. Mitchell; S. C. Clarke; W. H. F. Goessens; A. G. M. Schilder; E. A. M. Sanders; R. de Groot; P. W. M. Hermans

2005-01-01

275

Pneumococcal conjugate vaccination in adults: circulating antibody secreting cell response and humoral antibody responses in saliva and in serum  

Microsoft Academic Search

The results from our previous study showed IgA dominated ASC responses to pneumococcal polysaccharide vaccine and to pneumococcal polysaccharide meningococcal outer membrane protein conjugate vaccine (PncOMPC) in adult volunteers. The results indicated that a high IgA ASC response is a useful indicator of a secretory IgA response in saliva. We believe that the mucosal immune responses is potentially an important

T. Nieminen; J. Eskola; H. Käyhty

1998-01-01

276

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

PubMed Central

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

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

2010-01-01

277

Cost-effectiveness of heptavalent conjugate pneumococcal vaccine (Prevenar) in Germany: considering a high-risk population and herd immunity effects  

Microsoft Academic Search

In Germany, the seven-valent conjugate vaccine Prevenar is recommended for use in children at high risk of pneumococcal disease.\\u000a Recent data suggest that giving conjugate vaccine to all children may lead to a decline in pneumococcal disease in unvaccinated\\u000a adults, a phenomenon known as herd immunity. This analysis evaluated the cost and economic consequences in Germany of vaccinating\\u000a (1) children

Adam Lloyd; Nishma Patel; David A. Scott; Claus Runge; Christa Claes; Markus Rose

2008-01-01

278

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

PubMed Central

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

2012-01-01

279

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

PubMed

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

Plosker, Greg L

2013-10-01

280

Randomized, Controlled, Multicenter Study of the Immunogenicity and Safety of a Fully Liquid Combination Diphtheria-Tetanus Toxoid-Five-Component Acellular Pertussis (DTaP5), Inactivated Poliovirus (IPV), and Haemophilus influenzae Type b (Hib) Vaccine Compared with a DTaP3-IPV/Hib Vaccine Administered at 3, 5, and 12 Months of Age.  

PubMed

This study compared the levels of immunogenicity and safety of diphtheria-tetanus toxoid-five-component acellular pertussis (DTaP5), inactivated poliovirus (IPV), and Haemophilus influenzae type b (Hib) (DTaP5-IPV-Hib) and DTaP3-IPV/Hib vaccines for study participants 3, 5, and 12 months of age. Post-dose 3 noninferiority criteria comparing DTaP5-IPV-Hib to DTaP3-IPV/Hib using rates of seroprotection were demonstrated against diphtheria, tetanus, and polio types 1 to 3, but not for polyribosylribitol phosphate (PRP). While PRP did not meet noninferiority criteria, the seroprotection rate and geometric mean concentration (GMC) were high, indicating a clinically robust immune response. GMCs or titers for other antigens (including pertussis) and the safety profiles were generally similar between groups. Fully liquid DTaP5-IPV-Hib can be administered using the 3-, 5-, and 12-month vaccination schedule. (This study has been registered at ClinicalTrials.gov under registration no. NCT00287092.). PMID:23966556

Vesikari, Timo; Silfverdal, Sven Arne; Boisnard, Florence; Thomas, Stéphane; Mwawasi, Grace; Reynolds, Donna

2013-08-21

281

Serogroup C meningococci in Italy in the era of conjugate menC vaccination  

PubMed Central

Background To assess changes in the pattern of Invasive Meningococcal Disease (IMD) in Italy after the introduction of conjugate menC vaccine in the National Vaccine Plan 2005–2007 and to provide information for developing timely and appropriate public health interventions, analyses of microbiological features of isolates and clinical characteristics of patients have been carried out. In Italy, the number of serogroup C meningococci fell progressively following the introduction of the MenC conjugate vaccine, recommended by the Italian Ministry of Health but implemented according to different regional strategies. Methods IMD cases from January 2005 through July 2008 reported to the National Meningococcal Surveillance System were considered for this study. Serogrouping and sero/subtyping were performed on 179 serogroup C strains received at the National Reference Laboratory of the Istituto Superiore di Sanità. Antibiotic susceptibility testing was possible for 157 isolates. MLST (Multilocus sequence typing), porA VRs (Variable Region) typing, PFGE (Pulsed Field Gel Electrophoresis), VNTR (Variable Number Tandem Repeats) analyses were performed on all C:2a and C:2b meningococci (n = 147), following standard procedures. Results In 2005 and 2008, IMD showed an incidence of 0.5 and 0.3 per 100,000 inhabitants, respectively. While the incidence due to serogroup B remained stable, IMD incidence due to serogroup C has decreased since 2006. In particular, the decrease was significant among infants. C:2a and C:2b were the main serotypes, all C:2a strains belonged to ST-11 clonal complex and all C:2b to ST-8/A4. Clinical manifestations and outcome of infections underlined more severe disease caused by C:2a isolates. Two clusters due to C:2a/ST-11 meningococci were reported in the North of Italy in December 2007 and July 2008, respectively, with a high rate of septicaemia and fatal outcome. Conclusion Public health surveillance of serogroup C invasive meningococcal disease and microbiological/molecular characterization of the isolates requires particular attention, since the hyper-invasive ST-11 predominantly affected adolescents and young adults for whom meningococcal vaccination was not recommended in the 2005–2007 National Vaccine Plan.

2009-01-01

282

Invasive Pneumococcal Disease after Routine Pneumococcal Conjugate Vaccination in Children, England and Wales  

PubMed Central

We assessed known risk factors, clinical presentation, and outcome of invasive pneumococcal disease (IPD) in children 3–59 months of age after introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in England and Wales. During September 2006–March 2010, a total of 1,342 IPD episodes occurred in 1,332 children; 14.9% (198/1,332) had comorbidities. Compared with IPD caused by PCV7 serotypes (44/248; 17.7%), comorbidities were less common for the extra 3 serotypes in the 10-valent vaccine (15/299; 5.0%) but similar to the 3 additional PCV13 serotypes (45/336; 13.4%) and increased for the 11 extra serotypes in 23-valent polysaccharide vaccine (PPV23) (39/186; 21.0%) and non-PPV23 serotypes (38/138; 27.5%). Fifty-two (3.9%) cases resulted from PCV7 failure; 9 (0.7%) case-patients had recurrent IPD. Case-fatality rate was 4.4% (58/1,332) but higher for meningitis (11.0%) and children with comorbidities (9.1%). Thus, comorbidities were more prevalent in children with IPD caused by non-PCV13 serotypes and were associated with increased case fatality.

Slack, Mary P.E.; Andrews, Nick J.; Waight, Pauline A.; Borrow, Ray; Miller, Elizabeth

2013-01-01

283

Dynamic models of pneumococcal carriage and the impact of the Heptavalent Pneumococcal Conjugate Vaccine on invasive pneumococcal disease  

Microsoft Academic Search

BACKGROUND: The 7-valent pneumococcal conjugate vaccine has been introduced in national immunisation programmes of most industrialised countries and recently in two African GAVI eligible countries (Rwanda and The Gambia). However the long term effects of PCV are still unclear, as beneficial direct and herd immunity effects might be countered by serotype replacement. METHOD: A dynamic, age-structured, compartmental model of Streptococcus

Alessia Melegaro; Yoon Hong Choi; Robert George; W John Edmunds; Elizabeth Miller; Nigel J Gay

2010-01-01

284

Serological Basis for Use of Meningococcal Serogroup C Conjugate Vaccines in the United Kingdom: Reevaluation of Correlates of Protection  

Microsoft Academic Search

The antibody data supporting the use of meningococcal serogroup C conjugate (MCC) vaccines in the United Kingdom were generated by serum bactericidal assay (SBA) using rabbit complement (rSBA). This may give higher titers than those obtained with human complement (hSBA), for which the \\

RAY BORROW; NICK ANDREWS; DAVID GOLDBLATT; ELIZABETH MILLER

2001-01-01

285

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

PubMed Central

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

2011-01-01

286

Combined effects of antenatal receipt of influenza vaccine by mothers and pneumococcal conjugate vaccine receipt by infants: results from a randomized, blinded, controlled trial.  

PubMed

A 2 × 2 factorial trial was performed to determine the efficacy of antennal influenza vaccination of mothers plus pneumococcal conjugate vaccination of their infants against respiratory illness during early infancy. The efficacy of trivalent inactivated influenza vaccine (TIV; delivered to mothers) plus 7-valent pneumococcal vaccine (PCV7; delivered to infants) was higher than the efficacy of TIV alone or PCV7 alone. During the period of the study in which influenza was circulating, the efficacy of TIV plus PCV7 was 72.4% (95% confidence interval, 30.2%-89.1%) against febrile respiratory illness and 66.4% (95% CI, 14.3%-86.9%) against medically attended acute respiratory illness. PMID:23300160

Omer, Saad B; Zaman, Khalequ; Roy, Eliza; Arifeen, Shams E; Raqib, Rubhana; Noory, Laila; Seib, Katherine; Breiman, Robert F; Steinhoff, Mark C

2013-01-08

287

9 CFR 113.115 - Staphylococcus Aureus Bacterin-Toxoid.  

Code of Federal Regulations, 2010 CFR

...2009-01-01 2009-01-01 false Staphylococcus Aureus Bacterin-Toxoid. 113.115 Section...Bacterial Products § 113.115 Staphylococcus Aureus Bacterin-Toxoid. Staphylococcus Aureus Bacterin-Toxoid shall be...

2009-01-01

288

9 CFR 113.115 - Staphylococcus Aureus Bacterin-Toxoid.  

Code of Federal Regulations, 2010 CFR

...2010-01-01 2010-01-01 false Staphylococcus Aureus Bacterin-Toxoid. 113.115 Section...Bacterial Products § 113.115 Staphylococcus Aureus Bacterin-Toxoid. Staphylococcus Aureus Bacterin-Toxoid shall be...

2010-01-01

289

Impact of the 7-valent pneumococcal conjugate vaccine on the incidence of childhood pneumonia.  

PubMed

In September 2006, the 7-valent pneumococcal conjugate vaccine (PCV7) was added to the UK immunization programme. We aimed to evaluate the impact of PCV7 on the incidence of all-cause community-acquired pneumonia (CAP) in children. A prospective survey was undertaken in 2008-2009 at 11 hospitals in North East England of children aged 0-16 years with radiologically confirmed pneumonia. Data were compared to those from a similar survey undertaken in the same hospitals in 2001-2002. A total of 542 children were enrolled, of which 74% were aged <5 years. PCV7 uptake was 90?7%. The incidence of pneumonia was 11?8/10,000 [95% confidence interval (CI) 10?9-12?9], and the hospitalization rate was 9?9/10,000 (95% CI 9?0-10?9). Compared to 2001, there was a 19% (95% CI 8-29) reduction in the rate of CAP in those aged <5 years, and in those <2 years a 33?1% (95% CI 20-45) reduction in the incidence of CAP and 38?1% (95% CI 24-50) reduction in hospitalization rates. However, for those unvaccinated aged ?5 years, there was no difference in the incidence of CAP and hospitalization rate between both surveys. Since 2001, the overall reduction in incidence was 17?7% (95% CI 8-26) and for hospitalization 18?5% (95% CI 8-28). For the <5 years age group there was a lower incidence of CAP in PCV7-vaccinated children (25?2/10,000, 95% CI 22?6-28?2) than in those that were not vaccinated (37?4/10,000, 95% CI 29?2-47?1). In conclusion, PCV7 has reduced both incidence and rate of hospitalization of pneumonia in children, particularly in the <2 years age group. PMID:23084696

Elemraid, M A; Rushton, S P; Shirley, M D F; Thomas, M F; Spencer, D A; Eastham, K M; Hampton, F; Gorton, R; Pollard, K; Gennery, A R; Clark, J E

2012-10-19

290

Immunogenicity and Safety of a Meningococcal Quadrivalent Conjugate Vaccine in Saudi Arabian Adolescents Previously Vaccinated with One Dose of Bivalent and Quadrivalent Meningococcal Polysaccharide Vaccines: a Phase III, Controlled, Randomized, and Modified Blind-Observer Study  

PubMed Central

Reduced immune responses to repeated polysaccharide vaccination have been previously reported, but there are limited immunogenicity data on the use of meningococcal polysaccharide vaccine (PSV) followed by meningococcal conjugate vaccine. Saudi Arabian adolescents (aged 16 to 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, randomized, and modified observer-blind study (collectively termed the PSV-exposed group). The PSV-exposed group was randomized to receive either quadrivalent meningococcal conjugate vaccine (MCV4) (n = 145 PSV-exposed/MCV4 group) or MPSV4 (n = 142 PSV-exposed/MPSV4 group), and a PSV-naïve group received MCV4 (n = 163). Serum samples collected prevaccination and 28 days postvaccination were measured by baby rabbit serum bactericidal antibody (rSBA) assay, and vaccine tolerability and safety were also evaluated. For each serogroup, the postvaccination geometric mean titers (GMTs) were significantly higher in the PSV-naïve group than in either group comprised of the PSV-exposed participants. The postvaccination serogroup C rSBA GMT was significantly higher in the PSV-MCV4 group than in the PSV-MPSV4 group after adjusting for prevaccination GMTs. Although not statistically significant, similar differences were observed for serogroups A, Y, and W-135. No worrisome safety signals were detected. This study demonstrated MCV4 to be safe and immunogenic in those who had previously received polysaccharide vaccination, and it suggests that conjugate vaccine can partially compensate for the hyporesponsiveness seen with repeated doses of polysaccharide vaccine.

Al-Mazrou, Yagob; Khalil, Mohamed; Chadha, Helen; Bosch Castells, Valerie; Johnson, David R.; Borrow, Ray

2012-01-01

291

Immunogenicity and safety of a meningococcal quadrivalent conjugate vaccine in Saudi Arabian adolescents previously vaccinated with one dose of bivalent and quadrivalent meningococcal polysaccharide vaccines: a phase III, controlled, randomized, and modified blind-observer study.  

PubMed

Reduced immune responses to repeated polysaccharide vaccination have been previously reported, but there are limited immunogenicity data on the use of meningococcal polysaccharide vaccine (PSV) followed by meningococcal conjugate vaccine. Saudi Arabian adolescents (aged 16 to 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, randomized, and modified observer-blind study (collectively termed the PSV-exposed group). The PSV-exposed group was randomized to receive either quadrivalent meningococcal conjugate vaccine (MCV4) (n = 145 PSV-exposed/MCV4 group) or MPSV4 (n = 142 PSV-exposed/MPSV4 group), and a PSV-naïve group received MCV4 (n = 163). Serum samples collected prevaccination and 28 days postvaccination were measured by baby rabbit serum bactericidal antibody (rSBA) assay, and vaccine tolerability and safety were also evaluated. For each serogroup, the postvaccination geometric mean titers (GMTs) were significantly higher in the PSV-naïve group than in either group comprised of the PSV-exposed participants. The postvaccination serogroup C rSBA GMT was significantly higher in the PSV-MCV4 group than in the PSV-MPSV4 group after adjusting for prevaccination GMTs. Although not statistically significant, similar differences were observed for serogroups A, Y, and W-135. No worrisome safety signals were detected. This study demonstrated MCV4 to be safe and immunogenic in those who had previously received polysaccharide vaccination, and it suggests that conjugate vaccine can partially compensate for the hyporesponsiveness seen with repeated doses of polysaccharide vaccine. PMID:22552602

Al-Mazrou, Yagob; Khalil, Mohamed; Findlow, Helen; Chadha, Helen; Bosch Castells, Valerie; Johnson, David R; Borrow, Ray

2012-05-02

292

Staphylococcus aureus vaccine conjugate--Nabi: Nabi-StaphVAX, StaphVAX.  

PubMed

Staphylococcus aureus is a major cause of hospital-acquired infections and infections in kidney dialysis patients. Over 90% of these infections are due to types 5 and 8. Nabi, under a CRADA agreement with the US National Institutes of Health, is developing a bivalent vaccine against S. aureus types 5 and 8 [Nabi-StaphVAX, StaphVAX]. The vaccine contains type 5 and type 8 S. aureus capsular polysaccharides conjugated to a protein carrier (recombinant exoprotein A, a genetically detoxified form of Pseudomonas aeruginosa exotoxin A). Nabi changed its name to Nabi Biopharmaceuticals on 5 March 2002. StaphVAX is available for licensing (http://www.nabi.com). Nabi's preference is for a licensee that can provide non-US marketing and regulatory capabilities in addition to financial resources to accelerate the vaccine's development. Nabi intends to develop a second-generation version of StaphVAX that will include antigen from Staphylococcus type 336. This would increase the vaccine's coverage of staphylococcal infection. Nabi also intends to develop two combination vaccines. The first, StaphVAX+ will contain both StaphVAX and EpiVAX trade mark in a single vial and the second, CombiVAX, will contain components of StaphVAX, EpiVAX trade mark and EnteroVAX trade mark. The vaccine has completed phase II clinical trials in chronic, ambulatory, peritoneal dialysis patients. Nabi-StaphVAX completed a multicentre, phase III trial in the US involving 1800 end-stage renal disease patients on haemodialysis. In September 2000, Nabi announced preliminary results from the phase III trial; these indicated that although Nabi-StaphVAX elicited a significant decrease in S. aureus bacteraemias in the first 10 months after vaccination, statistical significance was not reached in the primary endpoint of the study, a decrease after 1-year follow up. As a result, the US FDA indicated that US registration would require a second phase III trial in which the primary endpoint is reached. Following discussions with the US FDA, Nabi stated that the initiation of a second phase III trial in collaboration with a corporate partner was likely. Nabi intends to request either an accelerated- or fast-track review by the FDA, on the basis that the vaccine prevents a fatal disease for which no other prophylactics are available. In the meantime, Nabi initiated a boosting study of Nabi-StaphVAX in July 2001. This trial is administering a second dose of Nabi-StaphVAX to 100 patients enrolled in the phase III trial. Nabi plans to begin the confirmatory phase III study of the vaccine, as requested by the US FDA, in 3000 end-stage kidney patients in Q4 2003. The primary endpoint will be a statistically significant reduction of S. aureus bacteraemia caused by type 5 and 8 S. aureus through 8 months post-vaccination, the peak efficacy point in the first phase III trial. This trial will include a booster vaccination at 8 months and vaccinees will be followed up for up to 6 months after the booster to evaluate the vaccine's ability to generate antibodies, efficacy and safety. Results from this study will be used to support eventual product registration, now planned for 2005. In July 2003, Nabi reported that proceeds totalling 32.9 million US dollars from the private placement of its common stock to selected investors will enable the planned confirmatory phase III trial to proceed. In June 2003, Nabi Biopharmaceuticals announced the start of a clinical trial (a bridging study) to evaluate the safety and immunogenicity of a newly manufactured lot of StaphVAX produced by the contract manufacturer, Dow Biopharmaceutical Contract Manufacturing, intended for use in a planned confirmatory phase III trial later in 2003. The study demonstrated that the new batch of vaccine generated antibody levels that were equivalent to the levels generated by the vaccine produced at Nabi's R&D pilot plant and used in previous phase III studies. PMID:14584973

2003-01-01

293

Cost-effectiveness of 2 + 1 dosing of 13-valent and 10-valent pneumococcal conjugate vaccines in Canada  

PubMed Central

Background Thirteen-valent pneumococcal conjugate vaccine (PCV13) and 10-valent pneumococcal conjugate vaccine (PCV10) are two recently approved vaccines for the active immunization against Streptococcus pneumoniae causing invasive pneumococcal disease in infants and children. PCV13 offers broader protection against Streptococcus pneumoniae; however, PCV10 offers potential protection against non-typeable Haemophilus influenza (NTHi). We examined public health and economic impacts of a PCV10 and PCV13 pediatric national immunization programs (NIPs) in Canada. Methods A decision-analytic model was developed to examine the costs and outcomes associated with PCV10 and PCV13 pediatric NIPs. The model followed individuals over the remainder of their lifetime. Recent disease incidence, serotype coverage, population data, percent vaccinated, costs, and utilities were obtained from the published literature. Direct and indirect effects were derived from 7-valent pneumococcal vaccine. Additional direct effect of 4% was attributed to PCV10 for moderate to severe acute otitis media to account for potential NTHi benefit. Annual number of disease cases and costs (2010 Canadian dollars) were presented. Results In Canada, PCV13 was estimated to prevent more cases of disease (49,340 when considering both direct and indirect effects and 7,466 when considering direct effects only) than PCV10. This translated to population gains of 258 to 13,828 more quality-adjusted life-years when vaccinating with PCV13 versus PCV10. Annual direct medical costs (including the cost of vaccination) were estimated to be reduced by $5.7 million to $132.8 million when vaccinating with PCV13. Thus, PCV13 dominated PCV10, and sensitivity analyses showed PCV13 to always be dominant or cost-effective versus PCV10. Conclusions Considering the epidemiology of pneumococcal disease in Canada, PCV13 is shown to be a cost-saving immunization program because it provides substantial public health and economic benefits relative to PCV10.

2012-01-01

294

Polysaccharide-protein conjugates  

US Patent & Trademark Office Database

Vi capsular polysaccharides conjugated to toxin-dependent proteins can be used to enhance antibody response and to convert T-dependent properties to the Vi capsular polysaccharide. A heterobifunctional crosslinking agent can be used to bind thiol derivatives of the Vi capsular polysaccharides to the proteins, such as diphtheria, tetanus toxoids, cholera toxin and Haemophilus influenzae.

1993-04-20

295

Safety and immunogenicity of an investigational quadrivalent meningococcal conjugate vaccine after one or two doses given to infants and toddlers  

Microsoft Academic Search

With the emergence of multiple meningococcal serogroups in different geographic areas, broad vaccine protection from infancy\\u000a is desirable. One hundred and seventy-five infants received either two doses of a meningococcal quadrivalent (A, C, W-135,\\u000a Y) conjugate vaccine (MenACWY-CRM) at 6 and 12 months, one dose of MenACWY-CRM at 12 months, or MenC at 12 months and MenACWY-CRM\\u000a at 18 months.

S. A. Halperin; F. Diaz-Mitoma; P. Dull; A. Anemona; F. Ceddia

2010-01-01

296

Safety and Immunogenicity of Vi Conjugate Vaccines for Typhoid Fever in Adults, Teenagers, and 2- to 4YearOld Children in Vietnam  

Microsoft Academic Search

The capsular polysaccharide of Salmonella typhi, Vi, is an essential virulence factor and a protective vaccine for people older than 5 years. The safety and immunogenicity of two investigational Vi conjugate vaccines were evaluated in adults, 5- to 14-year-old children, and 2- to 4-year-old children in Vietnam. The conjugates were prepared with Pseudomonas aeruginosa recombinant exoprotein A (rEPA) as the

ZUZANA KOSSACZKA; FENG-YING C. LIN; VOANH HO; NGUYEN THI THANH THUY; PHAN VAN BAY; TRAN CONG THANH; DANG DUC TRACH; ARTHUR KARPAS; STEVEN HUNT; DOLORES A. BRYLA; RACHEL SCHNEERSON; JOHN B. ROBBINS; SHOUSUN C. SZU

1999-01-01

297

Mice vaccinated with the O-antigen of Francisella tularensis LVS lipopolysaccharide conjugated to bovine serum albumin develop varying degrees of protective immunity against systemic or aerosol challenge with virulent type A and type B strains of the pathogen  

Microsoft Academic Search

The purpose of this study was to evaluate the efficacy of a vaccine consisting of the O-polysaccharide of the lipopolysaccharide (LPS) of Francisella tularensis chemically conjugated to bovine serum albumin. The results show that conjugation preserved both the antigenicity and immunogenicity of the polysaccharide moiety. Mice vaccinated with the glyco-conjugate, but not with BSA alone, were completely protected against an

J. Wayne Conlan; Hua Shen; Ann Webb; Malcolm B Perry

2002-01-01

298

Pneumococcal conjugate vaccination at birth in a high-risk setting: No evidence for neonatal T-cell tolerance  

PubMed Central

Concerns about the risk of inducing immune deviation-associated “neonatal tolerance” as described in mice have restricted the widespread adoption of neonatal vaccination. The aim of this study was to demonstrate the immunological feasibility of neonatal pneumococcal conjugate vaccination (PCV) which could potentially protect high-risk infants in resource poor countries against severe pneumococcal disease and mortality in the early critical period of life. Papua New Guinean infants were randomized to be vaccinated with the 7-valent PCV (7vPCV) at birth, 1 and 2 months (neonatal group, n = 104) or at 1, 2 and 3 months of age (infant group, n = 105), or to not receive 7vPCV at all (control group, n = 109). Analysis of vaccine responses at 3 and 9 months of age demonstrated persistently higher type-1 (IFN-?) and type-2 (IL-5 and IL-13) T-cell responses to the protein carrier CRM197 and IgG antibody titres to 7vPCV serotypes in children vaccinated with 7vPCV according to either schedule as compared to unvaccinated children. In a comprehensive immuno-phenotypic analysis at 9 months of age, no differences in the quantity or quality of vaccine-specific T cell memory responses were found between neonatal vaccinations versus children given their first PCV dose at one month. Hospitalization rates in the first month of life did not differ between children vaccinated with PCV at birth or not. These findings demonstrate that neonatal 7vPCV vaccination is safe and not associated with immunological tolerance. Neonatal immunisation schedules should therefore be considered in high-risk areas where this may result in improved vaccine coverage and the earliest possible protection against pneumococcal disease and death.

van den Biggelaar, Anita H.J.; Pomat, William; Bosco, Anthony; Phuanukoonnon, Suparat; Devitt, Catherine J.; Nadal-Sims, Marie A.; Siba, Peter M.; Richmond, Peter C.; Lehmann, Deborah; Holt, Patrick G.

2011-01-01

299

Dose-specific efficacy of Haemophilus influenzae type b conjugate vaccines: a systematic review and meta-analysis of controlled clinical trials  

PubMed Central

SUMMARY Global coverage of infant Haemophilus influenzae type b (Hib) vaccination has increased considerably during the past decade, partly due to GAVI Alliance donations of the vaccine to low-income countries. In settings where large numbers of children receive only one or two vaccine doses rather than the recommended three doses, dose-specific efficacy estimates are needed to predict impact. The objective of this meta-analysis is to determine Hib vaccine efficacy against different clinical outcomes after receiving one, two or three doses of vaccine. Studies were eligible for inclusion if a prospective, controlled design had been used to evaluate commercially available Hib conjugate vaccines. Eight studies were included. Pooled vaccine efficacies against invasive Hib disease after one, two or three doses of vaccine were 59%, 92% and 93%, respectively. The meta-analysis provides robust estimates for use in decision-analytical models designed to predict the impact of Hib vaccine.

GRIFFITHS, U. K.; CLARK, A.; GESSNER, B.; MINERS, A.; SANDERSON, C.; SEDYANINGSIH, E. R.; MULHOLLAND, K. E.

2012-01-01

300

Competition between tetanus toxoid and toxin  

Microsoft Academic Search

Experiments on albino mice showed that preliminary injection of tetanus toxoid increases the resistance of animals to tetanus toxin, as manifested by an increase in LD50. The effect is enhanced by increasing the dose of toxoid or by giving it in fractional doses. The use of protagon and unpurified mitochondrial fraction, isolated from the brain, as receptor of tetanus toxin

G. N. Kryzhanovskii; A. Ya. Rozanov; O. A. Kirilenko; N. G. Bondarchuk

1975-01-01

301

Immunogenicity of a meningococcal serogroup C conjugate vaccine in HIV-infected children, adolescents, and young adults.  

PubMed

Children and adolescents infected with HIV typically have a lower response to immunization than do those in the general population. In most developed countries, meningococcal serogroup C conjugate vaccine is one of the recommended vaccines for such individuals. However, there have been no studies evaluating the antibody response to this vaccine in HIV-infected children, adolescents or young adults. In this study, we evaluated that response using serum bactericidal antibody (SBA) and enzyme-linked immunosorbent assay, comparing HIV-infected with non-HIV-infected patients, as well as analysing the occurrence of side effects. In non-responders, we assessed the antibody response to revaccination. This clinical trial involved 92 patients between 10 and 20 years of age: 43 HIV-infected patients (HIV+ group) and 49 non-HIV-infected patients (HIV- group). After one dose of the vaccine, 72.1% of the HIV+ group patients and 100% of the HIV- group patients were considered protected. Of the HIV+ group patients who received a second dose of the vaccine, only 40% acquired protection. Overall, 81.4% of the HIV+ group patients acquired protection (after one or two doses of the vaccine). Side effects occurred in 16.3% and 44% of the HIV+ group and HIV- group patients, respectively. Therefore, the meningococcal serogroup C conjugate vaccine proved to be safe and effective for use in HIV-infected children, adolescents, and young adults, although their antibody response was weaker than that shown by non-HIV-infected patients. This indicates the need to discuss changes to the immunization schedule for children, adolescents, and young adults infected with HIV, in order to ensure more effective protection against meningococcal disease. PMID:22771509

Bertolini, Daniela Vinhas; Costa, Luciana Scarlazzari; van der Heijden, Inneke Marie; Sato, Helena Keiko; Marques, Heloísa Helena de Sousa

2012-07-06

302

Evolving microbiology of complicated acute otitis media before and after introduction of the pneumococcal conjugate vaccine in France.  

PubMed

We compare the microbiology of otopathogens causing recurrent acute otitis media (AOM) or AOM treatment failure in 600 children during 2000 to 2008 before and after the introduction of 7-valent pneumococcal conjugate vaccine (PCV-7). Streptococcus pneumoniae predominated before PCV-7 introduction and during 2007 to 2008, whereas Haemophilus influenzae predominated during 2005 to 2006. S. pneumoniae 19A became the most frequent serotype after PCV-7 introduction. PMID:20727478

Dupont, Damien; Mahjoub-Messai, Farah; François, Martine; Doit, Catherine; Mariani-Kurkdjian, Patricia; Bidet, Philippe; Bonacorsi, Stéphane; Carol, Agnès; Bingen, Edouard

2010-09-01

303

Population-based seroprevalence of Neisseria meningitidis serogroup C capsular antibody before the introduction of conjugate vaccine, in Australia  

Microsoft Academic Search

Neisseria meningitidis serogroup C (NMC) conjugate vaccine was introduced, in Australia, in 2003. Our aims were to determine pre-immunisation IgG NMC seroprevalence and evaluate an enzyme-linked immunosorbent assay (ELISA), previously validated against the serum bactericidal assay (SBA). 2409 sera, collected in 2002, from subjects aged 2–34 years, were tested. The geometric mean concentration (GMC) of NMC anticapsular IgG was 0.38U\\/mL

J. L. Backhouse; H. F. Gidding; C. R. MacIntyre; P. B. McIntyre; G. L. Gilbert

2007-01-01

304

Serotype-Specific Immune Unresponsiveness to Pneumococcal Conjugate Vaccine following Invasive Pneumococcal Disease?  

PubMed Central

Following the introduction of the pneumococcal 7-valent conjugate vaccine (PCV7) into the routine infant immunization schedule in England, Wales, and Northern Ireland, pneumococcal serotype-specific immunoglobulin G (IgG) antibody testing was offered as a clinical service to all children within the program with invasive pneumococcal disease (IPD) to confirm an adequate antibody response to PCV7. As of March 2008, serum samples taken within 14 to 90 days of vaccination had been submitted from 107 children who had received one or more doses in the second year of life. Sera were assayed by a multiplexed microsphere assay incorporating both cell wall polysaccharide and serotype 22F adsorption. A protective serotype-specific antibody level was defined as a concentration of ?0.35 ?g/ml. Eight children failed to develop a response to their infecting serotype (6B [n = 4], 18C [n = 2], 4 [n = 1], and 14 [n = 1]), despite receiving at least three doses of PCV7 in the second year of life or two doses in the second and two or three in the first year of life. A further two children were nonresponsive to a serotype (6B) different than that causing disease. None of the 10 children had a clinical risk factor for IPD. Two had marginally low levels of total serum IgG but mounted adequate responses to the other six PCV serotypes. This serotype-specific unresponsiveness may reflect immune paralysis due to large pneumococcal polysaccharide antigen loads and/or a potential genetic basis for nonresponse to individual pneumococcal serotypes.

Borrow, Ray; Stanford, Elaine; Waight, Pauline; Helbert, Matthew; Balmer, Paul; Warrington, Rosalind; Slack, Mary; George, Robert; Miller, Elizabeth

2008-01-01

305

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

PubMed

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

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

2011-05-13

306

Pneumococcal vaccines: mechanism of action, impact on epidemiology and adaption of the species.  

PubMed

Pneumococcal infections elicited by Streptococcus pneumoniae (pneumococcus) (pneumonia, otitis media, sinusitis, meningitis) are frequently occurring diseases that are associated with considerable morbidity and mortality even in developed countries. Pneumococci colonise the nasopharynx of up to 50% of children, and up to 5% of adults are pneumococcal carriers. Two pneumococcal vaccines are currently in clinical use. One of them contains 23 capsular polysaccharides of the as yet known 91 different pneumococcal serotypes. Because polysaccharide vaccines primarily induce a B-cell-dependent immune response, this type of vaccine prevents bacteraemia but does not efficiently protect the host against pneumococcal infection. In 2000, a vaccination programme was launched in the USA making use of a novel pneumococcal conjugate vaccine containing capsular polysaccharides derived from the seven most frequent pneumococcal serotypes causing pneumococcal disease in children <2 years of age. Conjugation of capsular polysaccharides with a highly immunogenic protein, i.e. a non-toxic diphtheria toxoid, induces a B- and T-cell response resulting in mucosal immunity and thus effectively protects against vaccine serotypes that induce invasive pneumococcal disease, thereby at the same time reducing vaccine serotype carrier rates. Pronounced herd immunity resulted in a decrease in invasive pneumococcal diseases in vaccinees and non-vaccinees as well as reduced antibiotic resistance rates. However, recent studies report that serotypes eradicated by the vaccine are being replaced by non-vaccine pneumococcal serotypes. This so-called 'replacement' might soon threaten the success of vaccine use. PMID:18378430

Pletz, Mathias W; Maus, Ulrich; Krug, Norbert; Welte, Tobias; Lode, Hartmut

2008-04-18

307

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

PubMed Central

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.

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

2012-01-01

308

Peptide-conjugated PAMAM dendrimer as a universal DNA vaccine platform to target antigen-presenting cells.  

PubMed

DNA-based vaccines hold promise to outperform conventional antigen-based vaccines by virtue of many unique features. However, DNA vaccines have thus far fallen short of expectations, due in part to poor targeting of professional antigen-presenting cells (APC) and low immunogenicity. In this study, we describe a new platform for effective and selective delivery of DNA to APCs in vivo that offers intrinsic immune-enhancing characteristics. This platform is based on conjugation of fifth generation polyamidoamine (G5-PAMAM) dendrimers, a DNA-loading surface, with MHC class II-targeting peptides that can selectively deliver these dendrimers to APCs under conditions that enhance their immune stimulatory potency. DNA conjugated with this platform efficiently transfected murine and human APCs in vitro. Subcutaneous administration of DNA-peptide-dendrimer complexes in vivo preferentially transfected dendritic cells (DC) in the draining lymph nodes, promoted generation of high affinity T cells, and elicited rejection of established tumors. Taken together, our findings show how PAMAM dendrimer complexes can be used for high transfection efficiency and effective targeting of APCs in vivo, conferring properties essential to generate effective DNA vaccines. PMID:21987727

Daftarian, Pirouz; Kaifer, Angel E; Li, Wei; Blomberg, Bonnie B; Frasca, Daniela; Roth, Felix; Chowdhury, Raquibul; Berg, Eric A; Fishman, Jordan B; Al Sayegh, Husain A; Blackwelder, Pat; Inverardi, Luca; Perez, Victor L; Lemmon, Vance; Serafini, Paolo

2011-10-10

309

Pneumococcal conjugate vaccination in Canadian infants and children younger than five years of age: Recommendations and expected benefits  

PubMed Central

Introduction Streptococcus pneumoniae infection may result in invasive pneumococcal disease (IPD), such as bacteremia, meningitis and bacteremic pneumonia, or in non-IPD, such as pneumonia, sinusitis and otitis media. In June 2001, a heptavalent pneumococcal conjugate vaccine (PCV7) (Prevnar, Wyeth Pharmaceuticals, Canada) was approved for use in children in Canada. The objective of the present paper is to review S pneumoniae-induced disease incidence and vaccine recommendations in Canadian infants and children younger than five years of age. Particular attention is given to the expected benefits of vaccination in Canada based on postmarketing data and economic modelling. Methods Searches were performed on PubMed and Web of Science databases and specific Canadian journals using the key words 'pneumococc*', 'vaccine', 'conjugate', 'infant' and 'Canadian'. Results and Discussion PCV7 appears to be safe and effective against IPD and non-IPD in children younger than five years of age and, more importantly, in children younger than two years of age (who are at highest risk for IPD). An examination of postmarketing data showed a reduction in incidence of pneumococcal disease in age groups that were vaccinated and in older age groups, indicating the likelihood of herd protection. Concurrently, there was a reduction in the occurrence of antimicrobial-resistant isolates. Conclusions The results from the present review suggest that PCV7 is currently benefiting Canadian children and society by lowering S pneumoniae-associated disease. Additional gains from herd protection and further reductions in antimicrobial resistance will be achieved as more Canadian children younger than five years of age are routinely vaccinated with PCV7.

McClure, Carol A; Ford, Michael W; Wilson, Jeff B; Aramini, Jeff J

2006-01-01

310

Uptake of meningococcal conjugate vaccine among adolescents in large managed care organizations, United States, 2005: Demand, supply and seasonality  

PubMed Central

Background In February 2005, the US Advisory Committee on Immunization Practices recommended the new meningococcal conjugate vaccine (MCV4) for routine use among 11- to 12-year-olds (at the preadolescent health-care visit), 14- to 15-year-olds (before high-school entry), and groups at increased risk. Vaccine distribution started in March; however, in July, the manufacturer reported inability to meet demand and widespread MCV4 shortages were reported. Our objectives were to determine early uptake patterns among target (11-12 and 14-15 year olds) and non-target (13- plus 16-year-olds) age groups. A post hoc analysis was conducted to compare seasonal uptake patterns of MCV4 with polysaccharide meningococcal (MPSV4) and tetanus diphtheria (Td) vaccines. Methods We analyzed data for adolescents 11-16 years from five managed care organizations participating in the Vaccine Safety Datalink (VSD). For MCV4, we estimated monthly and cumulative coverage during 2005 and calculated risk ratios. For MPSV4 and Td, we combined 2003 and 2004 data and compared their seasonal uptake patterns with MCV4. Results Coverage for MCV4 during 2005 among the 623,889 11-16 years olds was 10%. Coverage for 11-12 and 14-15 year olds was 12% and 11%, respectively, compared with 8% for 13- plus 16-year-olds (p < 0.001). Of the 64,272 MCV4 doses administered from March-December 2005, 73% were administered June-August. Fifty-nine percent of all MPSV4 doses and 38% of all Td doses were administered during June-August. Conclusion A surge in vaccine uptake between June and August was observed among adolescents for MCV4, MPSV4 and Td vaccines. The increase in summer-time vaccinations and vaccination of non-targeted adolescents coupled with supply limitations likely contributed to the reported shortages of MCV4 in 2005.

2009-01-01

311

Response to Pneumococcal Polysaccharide and Protein-Conjugate Vaccines Singly or Sequentially in Adults who have Recovered from Pneumococcal Pneumonia  

PubMed Central

Background Controversy persists over the benefits of pneumococcal polysaccharide vaccine (PPV) in at-risk adults. We studied PPV, protein-conjugate pneumococcal vaccine (PCV), or immunologic ‘priming’ with PCV followed by ‘boosting’ with PPV in adults who recovered from pneumococcal pneumonia. Methods Subjects received PPV followed in 6 months by PCV, or vice-versa. IgG to capsular polysaccharide and opsonophagocytic killing activity (OPK) were studied at baseline, 4–8 weeks and 6 months after each vaccination. Results PPV and PCV stimulated similar IgG levels and OPK at 4–8 weeks. Six months post-PPV, antibody declined to baseline but remained modestly elevated post-PCV. PCV given 6 months post-PPV stimulated modest IgG increases that failed to reach post-PPV peaks. In contrast, PPV 6 months after PCV caused dramatic increases in IgG and OPK to all polysaccharides, consistent with a booster effect. Six months after the second vaccination, however, IgG and OPK in all patients fell precipitously, returning toward original baseline levels. Conclusions In high-risk subjects, the effect of PPV is short-lived; PCV stimulates a more prolonged response. PPV as a booster following PCV causes early antibody rises, but IgG declines rapidly thereafter, consistent with induction of suppressor cells or tolerance. Protein vaccines may be needed for high-risk adults.

Musher, Daniel M.; Rueda, Adriana M.; Nahm, Moon H.; Graviss, Edward A.; Rodriguez-Barradas, Maria C.

2008-01-01

312

The development of synthetic antitumour vaccines from mucin glycopeptide antigens.  

PubMed

Based on important cell-biological and biochemical results concerning the structural difference between membrane glycoproteins of normal epithelial cells and epithelial tumour cells, tumour-associated glycopeptide antigens have been chemically synthesised and structurally confirmed. Glycopeptide structures of the tandem repeat sequence of mucin MUC1 of epithelial tumour cells constitute the most promising tumour-associated antigens. In order to generate a sufficient immunogenicity of these endogenous structures, usually tolerated by the immune system, these synthetic glycopeptide antigens were conjugated to immune stimulating components: in fully synthetic two-component vaccines either with T-cell peptide epitopes or with Toll-like receptor2 lipopeptide ligands or in three-component vaccines with both these stimulants. Alternatively, the synthetic glycopeptide antigens were coupled to immune stimulating carrier proteins. In particular, MUC1 glycopeptide conjugates with Tetanus toxoid proved to be efficient vaccines inducing very strong immune responses in mice. The antibodies elicited with the fully synthetic vaccines showed selective recognition of the tumour-associated glycopeptides as was shown by neutralisation and micro-array binding experiments. After booster immunisations, most of the immune responses showed the installation of an immunological memory. Immunisation with fully synthetic three-component vaccines induced immune reactions with therapeutic effects in terms of reduction of the tumour burden in mice or in killing of tumour cells in culture, while MUC1 glycopeptide-Tetanus toxoid vaccines elicited antibodies in mice which recognised tumour cells in human tumour tissues. The results achieved so far are considered to be promising for the development of an active immunisation against tumours. PMID:23440054

Gaidzik, Nikola; Westerlind, Ulrika; Kunz, Horst

2013-02-25

313

Opsonophagocytic Activity Following a Reduced Dose 7-valent Pneumococcal Conjugate Vaccine Infant Primary Series and 23-valent Pneumococcal Polysaccharide Vaccine at 12 Months of Age  

PubMed Central

Opsonophagocytic activity (OPA) was measured following reduced infant doses of 7-valent pneumococcal conjugate vaccine (PCV-7) with or without 23-valent pneumococcal polysaccharide vaccine (PPV-23) at 12 months, and subsequent re-exposure to a small dose of pneumococcal polysaccharide antigens (mPPS) at 17 months. Fijian infants were randomized to receive 0, 1, 2, or 3 PCV-7 doses. Half received PPV-23 at 12 months and all received mPPS at 17 months. OPA was performed on up to 14 serotypes. Three and 2 PCV-7 doses resulted in similar OPA for most PCV-7 serotypes up to 9 months and for half of the serotypes at 12 months. A single dose improved OPA compared with the unvaccinated group. PPV-23 significantly improved OPA for all serotypes tested but in general, was associated with diminished responses following re-challenge.

Russell, FM; Carapetis, JR; Burton, RL; Lin, J; Licciardi, PV; Balloch, A; Tikoduadua, L; Waqatakirewa, L; Cheung, YB; Tang, MLK; Nahm, MH; Mulholland, EK

2010-01-01

314

Opsonophagocytic activity following a reduced dose 7-valent pneumococcal conjugate vaccine infant primary series and 23-valent pneumococcal polysaccharide vaccine at 12 months of age.  

PubMed

Opsonophagocytic activity (OPA) was measured following reduced infant doses of 7-valent pneumococcal conjugate vaccine (PCV-7) with or without 23-valent pneumococcal polysaccharide vaccine (PPV-23) at 12 months, and subsequent re-exposure to a small dose of pneumococcal polysaccharide antigens (mPPS) at 17 months. Fijian infants were randomized to receive 0, 1, 2, or 3 PCV-7 doses. Half received PPV-23 at 12 months and all received mPPS at 17 months. OPA was performed on up to 14 serotypes. Three and 2 PCV-7 doses resulted in similar OPA for most PCV-7 serotypes up to 9 months and for half of the serotypes at 12 months. A single dose improved OPA compared with the unvaccinated group. PPV-23 significantly improved OPA for all serotypes tested but in general, was associated with diminished responses following re-challenge. PMID:21044669

Russell, F M; Carapetis, J R; Burton, R L; Lin, J; Licciardi, P V; Balloch, A; Tikoduadua, L; Waqatakirewa, L; Cheung, Y B; Tang, M L K; Nahm, M H; Mulholland, E K

2010-10-31

315

Sentinel versus population-based surveillance of pneumococcal conjugate vaccine effectiveness  

PubMed Central

Abstract Objective To compare sentinel and population-based surveillance of the effect of seven-valent pneumococcal conjugate vaccine (PCV7), introduced in 2000, on the hospitalization of children aged under 5 years with invasive pneumococcal disease (IPD) in the United States of America. Methods Population surveillance data were used to identify children hospitalized between 1998 and 2006 with IPD caused by Streptococcus pneumoniae serotypes. The change from 1998 and 1999 (baseline) to 2006 in the number of hospitalized IPD cases recorded by sentinel surveillance systems involving single hospitals or groups of hospitals was compared with the change in the incidence of hospitalized IPD cases measured by population-based surveillance. Findings The change in incidence in the eight surveillance areas varied from ?37 to ?82% for IPD caused by any serotype and from ?96 to ?100% for IPD caused by serotypes contained in PCV7. All individual sentinel hospitals with more than three cases annually at baseline reported a decrease in cases by 2006. In addition, over 95% of sentinel systems with an average of more than 30 cases annually at baseline recorded a change by 2006 in the number of cases caused by any serotype that fell within the 95% confidence interval for the change in the incidence of hospitalized cases in the corresponding population surveillance area. The change in cases caused by PCV7 serotypes was accurately measured by 93% and 100% of sentinel systems with ??20 and >?20 cases annually at baseline, respectively. Conclusion Sentinel surveillance can accurately measure the effect of PCV7 on the number of children hospitalized with IPD, provided sufficient cases are detected at baseline. Serotyping increases accuracy.

Zell, Elizabeth R; Schrag, Stephanie; Cohen, Adam L

2012-01-01

316

Increased paediatric hospitalizations for empyema in Australia after introduction of the 7-valent pneumococcal conjugate vaccine  

PubMed Central

Abstract Objective To examine rates of paediatric hospitalization for empyema and pneumonia in Australia before and after the introduction of the seven-valent pneumococcal conjugate vaccine (PCV7). Methods Rates of paediatric hospitalization for empyema and pneumonia (bacterial, viral and all types) were calculated following the codes of the International Classification of Diseases, tenth revision (ICD-10) as a principal diagnosis. The expected number of hospitalizations after the PCV7 was introduced was estimated on the basis of the observed number of hospitalizations before the introduction of the PCV7. Incidence rate differences (IRDs) and incidence rate ratios (IRRs) were calculated. Hospitalization incidence in each study period was expressed as the number of hospitalizations per million (106) person–years. The population of children aged 0–19 years in Australia from 1998 to 2004 and from 2005 to 2010, as reported by the Australian Bureau of Statistics, was used to calculate the number of person–years in each period. Findings In the 5 years following the introduction of the PCV7, hospitalizations for pneumonia were fewer than expected (15?304 fewer; 95% confidence interval, CI: 14?646–15?960; IRD: ?552 per 106 person–years; 95% CI: ?576 to ?529 per 106 person–years; IRR: 0.78; 95% CI: 0.77–0.78). Hospitalizations for empyema, on the other hand, were more than expected (83 more; 95% CI: 37–128; IRD: 3 per 106 person–years; 95% CI: 1–5 per 106 person–years; IRR: 1.35; 95% CI: 1.14–1.59). Reductions in hospitalizations were observed for all ICD-10 pneumonia codes across all age groups. The increase in empyema hospitalizations was only significant among children aged 1 to 4 years. Conclusion The introduction of the PCV7 in Australia was associated with a substantial decrease in hospitalizations for childhood pneumonia and a small increase in hospitalizations for empyema.

Snelling, Thomas L; Jaffe, Adam

2013-01-01

317

Progress in introduction of pneumococcal conjugate vaccine - worldwide, 2000-2012.  

PubMed

Pneumococcal conjugate vaccines (PCVs) are safe and effective for reducing illness and deaths caused by Streptococcus pneumoniae. Recommendations for PCV use from the World Health Organization (WHO) and funding from the GAVI Alliance have resulted in an increase in PCV introductions into national immunization programs, especially in lower-income countries. Additionally, new formulations that cover more serotypes commonly causing disease in lower- and middle-income countries have become available. This report uses WHO data from 2000-2012, stratified by country disease burden characteristics and World Bank country income groups, to describe global progress in PCV introduction. As of December 2012, a total of 86 (44%) WHO member states have added PCV to the routine infant immunization schedule of their national immunization programs; among those, 23 have introduced PCV with GAVI Alliance support. PCV introduction among WHO member states was most common in the Americas Region (60% of member states), followed by the Eastern Mediterranean Region (50%), European Region (49%), African Region (41%), and Western Pacific Region (33%); none of 11 WHO member states in the South-East Asia Region have introduced PCV. Proportions of low- and middle-income countries with PCV introductions were similar. The proportion of the world's birth cohort living in countries with PCV in national immunization programs increased from 1% in 2000 to 31% in 2012. These findings suggest that efforts to increase PCV introduction and use globally are succeeding; however, gaps in PCV use remain in Asia and countries with large birth cohorts, where concerted efforts should be focused. PMID:23615674

2013-04-26

318

Induction of systemic and mucosal antibody responses in mice immunized intranasally with aluminium-non-adsorbed diphtheria toxoid together with recombinant cholera toxin B subunit as an adjuvant  

Microsoft Academic Search

Nasal mucosal immunization is very attractive for vaccination to prevent various bacterial and viral infectious diseases because of induction of systemic and mucosal immune responses. The aim of the present study was to investigate the possibility of changing the immunization procedure of diphtheria toxoid (Dt) from intramuscular or subcutaneous injection to intranasal administration. Intranasal immunization with aluminium-non-adsorbed diphtheria toxoid (nDt)

Masanori Isaka; Yoko Yasuda; Satoshi Kozuka; Tooru Taniguchi; Keiko Matano; Jun-ichi Maeyama; Takako Komiya; Kunio Ohkuma; Norihisa Goto; Kunio Tochikubo

1999-01-01

319

Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine for adults with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP).  

PubMed

On June 20, 2012, the Advisory Committee on Immunization Practices (ACIP) recommended routine use of 13-valent pneumococcal conjugate vaccine (PCV13; Prevnar 13, Wyeth Pharmaceuticals, Inc., a subsidiary of Pfizer, Inc.) for adults aged ?19 years with immunocompromising conditions, functional or anatomic asplenia, cerebrospinal fluid (CSF) leaks, or cochlear implants. PCV13 should be administered to eligible adults in addition to the 23-valent pneumococcal polysaccharide vaccine (PPSV23; Pneumovax 23, Merck & Co. Inc.), the vaccine currently recommended for these groups of adults. The evidence for the benefits and risk of PCV13 vaccination of adults with immunocompromising conditions was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework and designated as a Category A recommendation. This report outlines the new ACIP recommendations for PCV13 use; explains the recommendations for the use of PCV13 and PPSV23 among adults with immunocompromising conditions, functional or anatomic asplenia, CSF leaks, or cochlear implants; and summarizes the evidence considered by ACIP to make its recommendations. PMID:23051612

2012-10-12

320

A novel and efficient method for synthetic carbohydrate conjugate vaccine preparation: synthesis of sialyl Tn-KLH conjugate using a 4-(4-N-maleimidomethyl) cyclohexane-1-carboxyl hydrazide (MMCCH) linker arm  

Microsoft Academic Search

STn (NeuAca2?6GalNAca-O-Ser\\/Thr) is a carbohydrate epitope overexpressed in various human carcinomas. Clinical trials are underway using synthetic STn or STn trimeric glycopeptides [STn, cluster; STn(c) conjugated with keyhole limpet hemocyanin (KLH) as active specific immunotherapy for these cancers. These vaccines have been prepared by conjugating a crotyl ethyl amide derivative of STn or STn(c) to KLH by direct reductive amination

Govindaswami Ragupathi; R. Rao Koganty; Dongxu Qiu; Kenneth O. Lloyd; Philip O. Livingston

1998-01-01

321

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

PubMed Central

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.

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

322

Effectiveness of the 7-valent pneumococcal conjugate vaccine against vaccine-type invasive disease among children in Uruguay: an evaluation using existing data.  

PubMed

The 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the routine immunization program in Uruguay in March 2008 with a 2-dose primary series (given at 2 and 4 months) plus a booster (at 12 months) and a catch-up campaign (two doses given at 15 and 17 months). We used a case-control methodology and existing laboratory surveillance and immunization registry data from Uruguay to evaluate PCV7 effectiveness against vaccine-type invasive pneumococcal disease (VT-IPD). Cases of VT-IPD (with pneumococcus obtained from a normally sterile site) were identified through the National Reference Laboratory. Age- and neighborhood-matched controls were obtained through a national immunization registry in which all children are enrolled at birth regardless of vaccine receipt; all eligible controls were included. Immunization status of cases and controls was assessed through the immunization registry, and conditional logistic regression was used to calculate PCV7 effectiveness. Between April 2008 and February 2010, 44 cases of VT-IPD among children<5 years were identified; 43 (98%) of those children were located in the registry. Among located case patients, 7 (16.3%) were age-eligible to have received at least one dose of PCV7. A total of 637 matched controls were included. Vaccine effectiveness was 91.3% (95% CI: 46.4, 98.6) for ? 1 PCV7 doses and 94.8% (95% CI: 43.1, 99.5) for ? 2 PCV7 doses. Using existing data we demonstrated high effectiveness of PCV7 against VT-IPD in Uruguay-a middle-income country using a 2-dose primary series plus a booster dose and a limited catch-up campaign. These data also highlight the utility of surveillance and high-quality immunization registries for evaluating the effectiveness of vaccines. PMID:23777683

Picón, Teresa; Alonso, Lucía; García Gabarrot, Gabriela; Speranza, Noelia; Casas, Mariana; Arrieta, Fernando; Camou, Teresa; Rosa, Raquel; De Oliveira, Lucia Helena; Verani, Jennifer Rabke

2013-07-01

323

Development of Sandwich Enzyme?Linked Immunosorbent Assay for Determination of Tetanus Toxoid Concentration  

Microsoft Academic Search

According to the recommendation of the World Health Organization (WHO), the use of an in vivo test for measuring of the potency of tetanus toxoid vaccine (TTdV) is still unavoidable, but the establishment of a convenient in vitro test would significantly improve the work in this field. A sandwich enzyme?linked immunosorbent assay (sELISA) was developed for a rapid and sensitive

Saša Šeatovi?; Marijana Stojanovi?; Irena Živkovi?; Ratko M. Jankov; Ljiljana Dimitrijevi?

2005-01-01

324

Pneumococcal Carriage in Young Children One Year after Introduction of the 13-Valent Conjugate Vaccine in Italy  

PubMed Central

Background In mid 2010, the 7-valent pneumococcal conjugate vaccine (PCV7) was replaced by the 13-valent conjugate vaccine (PCV13) for childhood immunization in Italy. Our objective in this study was to obtain a snapshot of pneumococcal carriage frequency, colonizing serotypes, and antibiotic resistance in healthy children in two Italian cities one year after PCV13 was introduced. Methods Nasopharyngeal swabs were obtained from 571 children aged 0-5 years from November 2011-April 2012. Pneumococcal isolates were serotyped and tested for antimicrobial susceptibility. Penicillin and/or erythromycin non-susceptible isolates were analyzed by Multi Locus Sequence Typing (MLST). Results Among the children examined, 81.2% had received at least one dose of PCV7 or PCV13 and 74.9% had completed the recommended vaccination schedule for their age. Among the latter, 57.3% of children had received PCV7, 27.1% PCV13, and 15.6% a combination of the two vaccines. The overall carriage rate was 32.9%, with children aged 6-35 months the most prone to pneumococcal colonization (6-23 months OR: 3.75; 95% CI: 2.19-6.43 and 24-35 months OR: 3.15, 95%CI: 2.36-4.22). A total of 184 pneumococcal isolates were serotyped and divided into PCV7 (5.4%), PCV13 (18.0%), and non-PCV13 (82.0%) serotypes. Serotypes 6C, 24F, and 19A were the most prevalent (10.3%, 8.6%, and 8.1%, respectively). The proportion of penicillin non-susceptible (MIC >0.6 mg/L) isolates was 30.9%, while 42.3% were erythromycin resistant. Non-PCV13 serotypes accounted for 75.4% and 70.8% of the penicillin and erythromycin non-susceptible isolates, respectively. Conclusions Our results revealed low rates of PCV7 and PCV13 serotypes in Italian children, potentially due to the effects of vaccination. As the use of PCV13 continues, its potential impact on vaccine serotypes such as 19A and cross-reactive serotypes such as 6C will be assessed, with this study providing a baseline for further analysis of surveillance isolates.

Camilli, Romina; Daprai, Laura; Cavrini, Francesca; Lombardo, Donatella; D'Ambrosio, Fabio; Del Grosso, Maria; Vescio, Maria Fenicia; Landini, Maria Paola; Pascucci, Maria Grazia; Torresani, Erminio; Garlaschi, Maria Laura; Sambri, Vittorio; Pantosti, Annalisa

2013-01-01

325

Comparison of the reactogenicity and immunogenicity of a combined diphtheria, tetanus, acellular pertussis, hepatitis B, inactivated polio (DTPa–HBV–IPV) vaccine, mixed with the Haemophilus influenzae type b (Hib) conjugate vaccine and administered as a single injection, with the DTPa–IPV\\/Hib and hepatitis B vaccines administered in two simultaneous injections to infants at 2, 4 and 6 months of age  

Microsoft Academic Search

An open, randomised, multicentre trial was performed to compare the reactogenicity and safety profile of the administration of a hexavalent diphtheria-tetanus-acellular pertussis–hepatitis B–inactivated polio (DTPa–HBV–IPV) vaccine administered in one injection mixed with Haemophilus influenzae type b (Hib) conjugate vaccine (Group 1) with that of a pentavalent DTPa–IPV vaccine mixed with a Hib vaccine (DTPa–IPV\\/Hib), simultaneously administered with HBV (Group 2)

J Ar??stegui; R Dal-Ré; J D??ez-Delgado; J Marés; J. M Casanovas; P Garc??a-Corbeira; E De Frutos; D Van Esso; J Verdaguer; J De la Flor; F Moraga; R Boceta; J. A Garc??a-Mart??nez

2003-01-01

326

Persistence of antibody response 1.5 years after vaccination using 7-valent pneumococcal conjugate vaccine in patients with arthritis treated with different antirheumatic drugs  

PubMed Central

Introduction The aim of this study was to explore the persistence of an antibody response 1.5 years after vaccination with 7-valent pneumococcal conjugate vaccine in patients with rheumatoid arthritis (RA) or spondyloarthropathy (SpA) treated with different antirheumatic drugs. Methods Of 505 patients initially recruited, data on current antirheumatic treatment and blood samples were obtained from 398 (79%) subjects after mean (SD, range) 1.4 (0.5; 1 to 2) years. Antibody levels against pneumococcal serotypes 23F and 6B were analyzed by using enzyme-linked immunosorbent assay (ELISA). Original treatment groups were as follows: (a) RA receiving methotrexate (MTX); (b) RA taking anti-TNF monotherapy; (c) RA taking anti-TNF+MTX; (d) SpA with anti-TNF monotherapy; (e) SpA taking anti-TNF+MTX; and (f) SpA taking NSAID/analgesics. Geometric mean levels (GMLs; 95% CI) and proportion (percentage) of patients with putative protective antibody levels ?1 mg/L for both serotypes, calculated in different treatment groups, were compared with results 4 to 6 weeks after vaccination. Patients remaining on initial treatment were included in the analysis. Possible predictors of persistence of protective antibody response were analysed by using logistic regression analysis. Results Of 398 patients participating in the 1.5-year follow up, 302 patients (RA, 163, and SpA, 139) had unchanged medication. Compared with postvaccination levels at 1.5 years, GMLs for each serotype were significantly lower in all groups (P between 0.035 and <0.001; paired-sample t test), as were the proportions of patients with protective antibody levels for both serotypes (P < 0.001; ?2 test). Higher prevaccination antibody levels for both serotypes 23F and 6B were associated with better persistence of protective antibodies (P < 0.001). Compared with patients with protective antibody levels at 1.5 years, those not having protective antibody levels were older, more often women, had longer disease duration and higher HAQ and DAS, and had a lower proportion of initial responders to both serotypes. Concomitant anti-TNF treatment and MTX were identified as negative predictors of the persistence of protective antibodies among RA patients (P = 0.024 and P = 0.065, respectively). Only age 65 years or older (P = 0.017) and not antirheumatic treatment was found to be a negative predictor of protective antibodies in patients with SpA. Conclusions After initial increase, 1.5 years after pneumococcal vaccination with 7-valent conjugate vaccine, postvaccination antibody levels decreased significantly, reaching levels before vaccination in this cohort of patients with established arthritis treated with different antirheumatic drugs. MTX and anti-TNF treatment predicted low persistence of protective immunity among patients with RA. To boost antibody response, early revaccination with conjugate vaccine might be needed in patients receiving potent immunosuppressive remedies. Trial registration number EudraCT EU 2007-006539-29 and NCT00828997.

2013-01-01

327

Safety and reactogenicity of primary vaccination with the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine in Vietnamese infants: a randomised, controlled trial  

PubMed Central

Background Pneumococcal infections are major causes of child mortality and morbidity worldwide and antibiotic resistance of Streptococcus pneumoniae is a major concern, especially in Asian countries. The present study was designed to evaluate the reactogenicity and safety of the 10-valent pneumococcal non-typeable Haemophilus influenzae protein D conjugate vaccine (PHiD-CV) when co-administered with the licensed diphtheria, tetanus, acellular pertussis, hepatitis B virus, inactivated poliovirus and H. influenzae type b vaccine (DTPa-HBV-IPV/Hib) in a 3-dose primary vaccination course in Vietnamese infants. Methods This phase III, open, randomised study was conducted in one centre in Ho Chi Minh City between February and July 2011. Healthy infants (N=300) were randomised (2:1) to receive either PHiD-CV co-administered with DTPa-HBV-IPV/Hib (PHiD-CV group) or DTPa-HBV-IPV/Hib alone (Control group) at 2, 3, and 4 months of age. Results Within 31 days post-vaccination, 8.2% of overall doses in the PHiD-CV group and 3.0% of overall doses in the Control group were followed by at least one solicited and/or unsolicited, local and/or general adverse event of grade 3 intensity. Pain at injection site was the most common grade 3 solicited symptom, which was reported following 6.5% and 1.0% of overall doses in the PHiD-CV and Control groups, respectively. Within 4 days post-vaccination, the most common solicited local and general symptoms reported with any intensity were pain (48.9% and 31.0% of doses in the PHiD-CV and Control groups) and irritability (58.0% and 40.4% of doses in the PHiD-CV and Control groups). Within 31 days post-vaccination, the incidence of unsolicited symptoms was comparable in both groups (following 12.3% and 14.8% of doses in the PHiD-CV and Control groups, respectively). Throughout the study, 13 serious adverse events (SAEs) were reported in 9 infants in the PHiD-CV group and 11 SAEs in 6 infants in the Control group. None of them were fatal or considered causally related to vaccination. Conclusions PHiD-CV had a clinically acceptable safety profile when co-administered with DTPa-HBV-IPV/Hib in Vietnamese infants. The reactogenicity of PHiD-CV was comparable to that observed in other South-East Asian populations. Trial registration ClinicalTrials.gov: http://NCT01153841

2013-01-01

328

A Pneumococcal Carriage Study in Danish Pre-school Children before the Introduction of Pneumococcal Conjugate Vaccination  

PubMed Central

We present data on pneumococcal carriage before the introduction of the heptavalent-pneumococcal conjugated vaccine (PCV7) in Denmark. In the pre-PCV7 period, the incidence of invasive pneumococcal disease (IPD) among children younger than 5 years was approximately 25 per 100.000 population, with the highest incidence rates observed in children younger than 2 years of age. The study included 437 children aged 12-72 months attending day care centres (DCC) and was conducted during 48 months. In total, 56% (n=247) of children were pneumococcal carriers with the highest prevalence in children aged 12–23 months (69%), the proportion significantly declining with increasing age. PCV7 serotypes accounted for 33%, PCV10 for 34%, and PCV13 for 57% of all carried isolates. The proportion of serotypes included in the three conjugate vaccines was higher among IPD isolates compared to carrier isolates (range 35– 90%). We found that the frequency of carriage was high among Danish pre-school children attending DCC and serotypes were not frequently covered by PCV7 in the pre-PCV7 period.

Harboe, Zitta B; Slotved, Hans-Christian; Konradsen, Helle B; Kaltoft, Margit S

2012-01-01

329

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

Microsoft Academic Search

BackgroundCombining 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 FindingsIn this phase II, double blind, randomized, controlled study, 280 infants were

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

2008-01-01

330

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

Microsoft Academic Search

SUMMARY 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

J. M C VERNON; A. R. M C LEAN

2008-01-01

331

Pneumococcal Conjugate Vaccine Given Shortly After Birth Stimulates Effective Antibody Concentrations and Primes Immunological Memory for Sustained Infant Protection  

PubMed Central

Background.?In developing countries, newborn immunization with pneumococcal conjugate vaccines (PCVs) could protect young infants who are at high risk of invasive pneumococcal disease (IPD) but might lead to immune tolerance. Methods.?In a randomized trial, young infants received 7-valent PCV at 6, 10, and 14 weeks (Expanded Programme on Immunization [EPI] group) or 0, 10, and 14 weeks (newborn group). Safety was monitored actively at 2–7 days and then passively. Serum samples obtained at birth and 6, 10, 14, 18, 36, and 37 weeks were assayed by enzyme-linked immunosorbent assay for anticapsular immunoglobulin G concentration and avidity. Infants were boosted with either 7-valent PCV or one-fifth dose of pneumococcal polysaccharide vaccine at 36 weeks. Nasopharyngeal swab samples were obtained at 18 and 36 weeks. Results.?Three-hundred neonates and young infants were enrolled. Newborn vaccination was well tolerated. Adverse events occurred equally in each group; none was related to immunization. One infant, immunized at birth, died of unrelated neonatal sepsis. At 18 weeks, protective concentrations (?0.35 ?g/mL) were achieved against each serotype by ?87% of infants with no significant differences between groups. Geometric mean concentrations were higher in the EPI group for serotypes 4, 9V, 18C, and 19F at 18 weeks and for serotype 4 at 36 weeks. Avidity was greater in the newborn group for serotypes 4, 6B, and 19F at 18 weeks and for serotype 19F at 36 weeks. Booster responses and vaccine-type/nonvaccine-type carriage prevalence did not differ between groups. Conclusions.?PCV was safe, immunogenic, and primed for memory when given at birth. There was no evidence of immune tolerance. Vaccination beginning at birth offers an alternative to control IPD in vulnerable young infants.

Ojal, John; Ashton, Lindsey; Muhoro, Anne; Burbidge, Polly; Goldblatt, David

2011-01-01

332

Aluminum salts in vaccines--US perspective.  

PubMed

Aluminum in the form of aluminum hydroxide, aluminum phosphate or alum has been commonly used as an adjuvant in many vaccines licensed by the US Food and Drug Administration. Chapter 21 of the US Code of Federal Regulations [610.15(a)] limits the amount of aluminum in biological products, including vaccines, to 0.85 mg/dose. The amount of aluminum in vaccines currently licensed in the US ranges from 0.85-0.125 mg/dose. Clinical studies have demonstrated that aluminum enhances the antigenicity of some vaccines such as diphtheria and tetanus toxoids. Moreover, aluminum-adsorbed diphtheria and tetanus toxoids are distinctly more effective than plain fluid toxoids for primary immunization of children. There is little difference between plain and adsorbed toxoids for booster immunization. Aluminum adjuvants have a demonstrated safety profile of over six decades; however, these adjuvants have been associated with severe local reactions such as erythema, subcutaneous nodules and contact hypersensitivity. PMID:12184360

Baylor, Norman W; Egan, William; Richman, Paul

2002-05-31

333

Enhancement of Serum and Mucosal Immune Responses to a Haemophilus influenzae Type B Vaccine by Intranasal Delivery.  

PubMed

Intranasal (i.n.) vaccination is potentially the most direct method for conveying upper respiratory and mucosal immunity to respiratory pathogens. However, for unclear reasons, vaccines introduced into the nasal sinuses often have lower efficacy than vaccines administered by the more frequently used parenteral routes. We examined i.n. vaccination in a mouse immune-response model with a commonly used Haemophilus influenzae type B vaccine (Hibv) composed of the polyribosylribitol phosphate (PRP) capsule antigen conjugated to tetanus toxoid. Intranasal vaccination with Hibv using a Toll-like receptor 4 (TLR4) agonist as an adjuvant significantly increased the levels of IgA specific for the PRP capsule antigen in blood serum, saliva, and mucosal secretion specimens. In contrast, control mice vaccinated transdermally (t.d.) with Hibv did not produce significant levels of PRP-specific IgA in the blood serum and saliva, and anti-PRP IgG was increased only in serum. The i.n. and t.d. vaccinations resulted in equivalent bactericidal antibody responses in blood serum, suggesting that vaccine-derived IgG is protective against infection. Elevated levels of IgG specific for the tetanus toxoid carrier protein were measured in nasal sinuses and vaginal secretions in mice vaccinated by either the t.d. or i.n. route. Tissue culture studies confirmed that the nasopharynx-associated lymphoid tissue (NALT) was at least one of the sources of PRP-specific IgA and carrier-specific IgG within the nasal sinuses. We conclude that i.n. vaccination aided by a TLR4 agonist results in robust immune responses to both the carrier protein and bacterial polysaccharide components of the Hibv. PMID:23986319

Fernandez, Stefan; Cisney, Emily D; Ulrich, Robert G

2013-08-28

334

TETANUS AND DIPHTHERIA TOXOIDS ADSORBED  

Center for Biologics Evaluation and Research (CBER)

Text Version... The bovine material used in these extracts is sourced from countries which the United States Department of Agriculture has determined neither ... More results from www.fda.gov/downloads/biologicsbloodvaccines/vaccines

335

Evaluation of a diphtheria–tetanus–acellular pertussis–inactivated poliovirus–Haemophilus influenzae type b vaccine given concurrently with meningococcal group C conjugate vaccine at 2, 3 and 4 months of age  

Microsoft Academic Search

Background and objective: In view of the possible introduction of diphtheria–tetanus–acellular pertussis–inactivated poliovirus–Haemophilus influenzae type b (DTaP-IPV-Hib, eg Pediacel) vaccine in the UK, a study of the immunogenicity of Pediacel when given with one of two different meningococcal group C conjugate (MCC) vaccines at 2, 3 and 4 months of age was conducted.Methods: Randomised controlled study in 241 infants.Results: Post

N R E Kitchin; R Morris; F Hemme; S Thomas; M W Watson; K Cartwright; E Miller

2007-01-01

336

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

PubMed Central

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.

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

337

Determination of saccharide content in pneumococcal polysaccharides and conjugate vaccines by GC-MSD  

Microsoft Academic Search

A simple and sensitive gas chromatographic method was designed for quantitative analysis of Streptococcus pneumoniae capsular polysaccharides, activated polysaccharides, and polysaccharide conjugates. Pneumococcal serotypes 1, 3, 4, 5, 6A, 6B, 7F, 9V, 14, 18C, 19A, 19F, and 23F polysaccharide or conjugate were subjected to methanolysis in 3N hydrochloric acid in methanol followed by re-N-acetylation and trimethylsilylation. Derivatized samples were chromatographed

John S. Kim; Erin R. Laskowich; Rasappa G. Arumugham; Raymond E. Kaiser; Gregory J. MacMichael

2005-01-01

338

Immunologic Memory Induced by a Glycoconjugate Vaccine in a Murine Adoptive Lymphocyte Transfer Model  

PubMed Central

We have developed an adoptive cell transfer model in mice to study the ability of a glycoprotein conjugate vaccine to induce immunologic memory for the polysaccharide moiety. We used type III capsular polysaccharide from the clinically relevant pathogen group B streptococci conjugated to tetanus toxoid (GBSIII-TT) as our model vaccine. GBS are a major cause of neonatal infections in humans, and type-specific antibodies to the capsular polysaccharide protect against invasive disease. Adoptive transfer of splenocytes from mice immunized with the GBSIII-TT conjugate vaccine conferred anti-polysaccharide immunologic memory to naive recipient mice. The transfer of memory occurred in a dose-dependent manner. The observed anamnestic immune response was characterized by (i) more rapid kinetics, (ii) isotype switching from immunoglobulin M (IgM) to IgG, and (iii) 10-fold-higher levels of type III-specific IgG antibody than for the primary response in animals with cells transferred from placebo-immunized mice. The adoptive cell transfer model described in this paper can be used for at least two purposes: (i) to evaluate conjugate vaccines with different physicochemical properties for their ability to induce immunologic memory and (ii) to study the cellular interactions required for an immune response to these molecules.

Guttormsen, Hilde-Kari; Wetzler, Lee M.; Finberg, Robert W.; Kasper, Dennis L.

1998-01-01

339

Impact of 7-valent pneumococcal conjugate vaccine (PVC7) on the incidence and treatment of pneumonia diagnosed in primary care in children and adolescents in UK  

Microsoft Academic Search

BackgroundStreptococcus pneumonia is the main cause of bacterial pneumonia in children in the UK. In September 2006, a 7-valent pneumococcal conjugate vaccine (PCV7) was introduced into the UK childhood immunisation schedule following a successful campaign in the USA, where all cause pneumonia admissions in children under 2 years of age fell by 39% within 2 years. Hospital admission data in

A El Turki; Y Hsia; S Saxena; P Long; I Wong; M Sharland

2011-01-01

340

Biodegradable and biocompatible poly(DL-lactide-co-glycolide) microspheres as an adjuvant for staphylococcal enterotoxin B toxoid which enhances the level of toxin-neutralizing antibodies.  

PubMed Central

Microspheres composed of biocompatible, biodegradable poly(DL-lactide-co-glycolide) (DL-PLG) and staphylococcal enterotoxin B (SEB) toxoid were evaluated as a vaccine delivery system when subcutaneously injected into mice. As measured by circulating immunoglobulin G (IgG) antitoxin titers, the delivery of SEB toxoid via DL-PLG microspheres, 1 to 10 microns in diameter, induced an immune response which was approximately 500 times that seen with nonencapsulated toxoid. The kinetics, magnitude, and duration of the antitoxin response induced with microencapsulated toxoid were similar to those obtained when an equal toxoid dose was administered as an emulsion with complete Freund adjuvant. However, the microspheres did not induce the inflammation and granulomata formation seen with complete Freund adjuvant. The adjuvant activity of the microspheres was not dependent on the superantigenicity of SEB toxin and was equally effective at potentiating circulating IgG antitrinitrophenyl levels in response to microencapsulated trinitrophenyl-keyhole limpet hemocyanin. Empty DL-PLG microspheres were not mitogenic, and SEB toxoid injected as a mixture with empty DL-PLG microspheres was no more effective as an immunogen than toxoid alone. Antigen-containing microspheres 1 to 10 microns in diameter exhibited stronger adjuvant activity than those greater than 10 microns, which correlated with the delivery of the 1- to 10-microns, but not the greater than 10-microns, microspheres into the draining lymph nodes within macrophages. The antibody response induced through immunization with microencapsulated SEB toxoid was protective against the weight loss and splenic V beta 8+ T-cell expansion induced by intravenous toxin administration. These results show that DL-PLG microsphere vaccine delivery systems, which are composed of pharmaceutically acceptable components, possess a strong adjuvant activity for their encapsulated antigens.

Eldridge, J H; Staas, J K; Meulbroek, J A; Tice, T R; Gilley, R M

1991-01-01

341

Pneumococcal Nasopharyngeal Carriage following Reduced Doses of a 7-Valent Pneumococcal Conjugate Vaccine and a 23-Valent Pneumococcal Polysaccharide Vaccine Booster? †  

PubMed Central

This study was conducted to evaluate the effect of a reduced-dose 7-valent pneumococcal conjugate vaccine (PCV) primary series followed by a 23-valent pneumococcal polysaccharide vaccine (23vPPS) booster on nasopharyngeal (NP) pneumococcal carriage. For this purpose, Fijian infants aged 6 weeks were randomized to receive 0, 1, 2, or 3 PCV doses. Within each group, half received 23vPPS at 12 months. NP swabs were taken at 6, 9, 12, and 17 months and were cultured for Streptococcus pneumoniae. Isolates were serotyped by multiplex PCR and a reverse line blot assay. There were no significant differences in PCV vaccine type (VT) carriage between the 3- and 2-dose groups at 12 months. NP VT carriage was significantly higher (P, <0.01) in the unvaccinated group than in the 3-dose group at the age of 9 months. There appeared to be a PCV dose effect in the cumulative proportion of infants carrying the VT, with less VT carriage occurring with more doses of PCV. Non-PCV serotype (NVT) carriage rates were similar for all PCV groups. When groups were pooled by receipt or nonreceipt of 23vPPS at 12 months, there were no differences in pneumococcal, VT, or NVT carriage rates between the 2 groups at the age of 17 months. In conclusion, there appeared to be a PCV dose effect on VT carriage, with less VT carriage occurring with more doses of PCV. By the age of 17 months, NVT carriage rates were similar for all groups. 23vPPS had no impact on carriage, despite the substantial boosts in antibody levels.

Russell, F. M.; Carapetis, J. R.; Satzke, C.; Tikoduadua, L.; Waqatakirewa, L.; Chandra, R.; Seduadua, A.; Oftadeh, S.; Cheung, Y. B.; Gilbert, G. L.; Mulholland, E. K.

2010-01-01

342

Polysaccharide responsiveness is not biased by prior pneumococcal-conjugate vaccination.  

PubMed

Polysaccharide responsiveness is tested by measuring antibody responses to polysaccharide vaccines to diagnose for humoral immunodeficiency. A common assumption is that this responsiveness is biased by any previous exposure to the polysaccharides in the form of protein-coupled polysaccharide vaccines, such as those used in many childhood vaccination programmes. To examine this assumption, we investigated the effect of protein-coupled polysaccharide vaccination on subsequent polysaccharide responsiveness. HIV-infected adults (n?=?47) were vaccinated twice with protein-coupled polysaccharides and six months later with pure polysaccharides. We measured immunoglobulin G responses against three polysaccharides present in only the polysaccharide vaccine (non-memory polysaccharides) and seven recurring polysaccharides (memory polysaccharides). Responsiveness was evaluated according to the consensus guidelines published by the American immunology societies. Impaired responsiveness to non-memory polysaccharides was more frequent than to memory polysaccharides (51% versus 28%, P?=?0.015), but the individual polysaccharides did not differ in triggering sufficient responses (74% versus 77%, P?=?0.53). Closer analysis revealed important shortcomings of the current evaluation guidelines. The interpreted response? number and their specificities influenced the likelihood of impaired responsiveness in a complex manor. This influence was propelled by the dichotomous approaches inherent to the American guidelines. We therefore define a novel more robust polysaccharide responsiveness measure, the Z-score, which condenses multiple, uniformly weighted responses into one continuous variable. Using the Z-score, responsiveness to non-memory polysaccharides and memory-polysaccharides were found to correlate (R(2)?=?0.59, P<0.0001). We found that polysaccharide responsiveness was not biased by prior protein-coupled polysaccharide vaccination in HIV-infected adults. Studies in additional populations are warranted. PMID:24146796

Bernth-Jensen, Jens Magnus; Søgaard, Ole Schmeltz

2013-10-11

343

Polysaccharide Responsiveness Is Not Biased by Prior Pneumococcal-Conjugate Vaccination  

PubMed Central

Polysaccharide responsiveness is tested by measuring antibody responses to polysaccharide vaccines to diagnose for humoral immunodeficiency. A common assumption is that this responsiveness is biased by any previous exposure to the polysaccharides in the form of protein-coupled polysaccharide vaccines, such as those used in many childhood vaccination programmes. To examine this assumption, we investigated the effect of protein-coupled polysaccharide vaccination on subsequent polysaccharide responsiveness. HIV-infected adults (n?=?47) were vaccinated twice with protein-coupled polysaccharides and six months later with pure polysaccharides. We measured immunoglobulin G responses against three polysaccharides present in only the polysaccharide vaccine (non-memory polysaccharides) and seven recurring polysaccharides (memory polysaccharides). Responsiveness was evaluated according to the consensus guidelines published by the American immunology societies. Impaired responsiveness to non-memory polysaccharides was more frequent than to memory polysaccharides (51% versus 28%, P?=?0.015), but the individual polysaccharides did not differ in triggering sufficient responses (74% versus 77%, P?=?0.53). Closer analysis revealed important shortcomings of the current evaluation guidelines. The interpreted response? number and their specificities influenced the likelihood of impaired responsiveness in a complex manor. This influence was propelled by the dichotomous approaches inherent to the American guidelines. We therefore define a novel more robust polysaccharide responsiveness measure, the Z-score, which condenses multiple, uniformly weighted responses into one continuous variable. Using the Z-score, responsiveness to non-memory polysaccharides and memory-polysaccharides were found to correlate (R2?=?0.59, P<0.0001). We found that polysaccharide responsiveness was not biased by prior protein-coupled polysaccharide vaccination in HIV-infected adults. Studies in additional populations are warranted.

Bernth-Jensen, Jens Magnus; S?gaard, Ole Schmeltz

2013-01-01

344

Questions and Answers for Parents about Pre-teen Vaccines  

MedlinePLUS

... conjugate vaccine •Human papillomavirus (HPV) vaccines •In?uenza vaccine (?u vaccine) Tdap and meningococcal vaccines are recommended for all ... to get this vaccine to prevent genital warts. Flu vaccines are recommended for everyone older than 6 months, ...

345

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

PubMed Central

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.

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

346

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

PubMed

A baseline serotype distribution was established by age and region for 2058 invasive Streptococcus pneumoniae isolates collected during the implementation period of the 13-valent pneumococcal conjugate vaccine (PCV13) program in many parts of Canada in 2010. Serotypes 19A, 7F, and 3 were the most prevalent in all age groups, accounting for 57% in <2 year olds, 62% in 2-4 year olds, 45% in 5-14 year olds, 44% in 15-49 year olds, 41% in 50-64 year olds, and 36% in ?65 year olds. Serotype 19A was most predominant in Western and Central Canada representing 15% and 22%, respectively, of the isolates from those regions, whereas 7F was most common in Eastern Canada with 20% of the isolates. Other prevalent serotypes include 15A, 23B, 12F, 22F, and 6C. PCV13 serotypes represented 65% of the pneumococci isolated from <2 year olds, 71% of 2-4 year olds, 61% of 5-14 year olds, 60% of 15-49 year olds, 53% of 50-64 year olds, and 49% of the ?65 year olds. Continued monitoring of invasive pneumococcal serotypes in Canada is important to identify epidemiological trends and assess the impact of the newly introduced PCV13 vaccine on public health. PMID:22827750

Demczuk, Walter H B; Martin, Irene; Griffith, Averil; Lefebvre, Brigitte; McGeer, Allison; Shane, Amanda; Zhanel, George G; Tyrrell, Gregory J; Gilmour, Matthew W

2012-07-24

347

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

PubMed Central

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

2012-01-01

348

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

PubMed

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

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

2013-04-13

349

Determination of glycation sites by tandem mass spectrometry in a synthetic lactose-bovine serum albumin conjugate, a vaccine model prepared by dialkyl squarate chemistry  

PubMed Central

RATIONALE Neoglycoconjugate vaccines synthesized by the squaric acid spacer method allow single point attachment of the carbohydrate antigen to the protein carrier. However, the localization of the carbohydrate antigen sites of conjugation on the protein carrier has been an elusive task difficult to achieve. METHOD Covalent attachment of the lactose antigen to the bovine serum albumin (BSA) was prepared by the squaric acid method using a hapten:BSA ratio of 20:1. Different reaction times were used during the conjugation reaction and two different lactose-BSA glycoconjugate vaccines were obtained. The carbohydrate antigen hapten:BSA ratios of these lactose-BSA glycoconjugate vaccines were determined by MALDI-TOF/RTOF-MS and the glycation sites in the neoglycoconjugates were determined using nano-LC/ESI-QqTOF-MS/MS analysis of the trypsin and GluC V8 digests of the conjugates. RESULTS We have identified a total of 15 glycation sites located on the BSA lysine residues for the neoglycoconjugate vaccine formed with a hapten:BSA ratio of 5.1:1, However, the tryptic and GluC V8 digests of the hapten-BSA glycoconjugate with a hapten:BSA ratio of 19.0:1 allowed identification of 30 glycation sites located on the BSA. These last results seem to indicate that this conjugation results in formation of various glycoforms. CONCLUSIONS It was observed that the number of identified glycation sites increased when the hapten:BSA ratio of glycoconjugate formation increased, and that the location of the glycation sites appears to be mainly on the outer surface of the BSA carrier molecule which is in line with the assumption that the sterically more accessible lysine residues, namely those located on the outer surface of the BSA, would be conjugated preferentially.

Jahouh, Farid; Hou, Shu-jie; Kovac, Pavol; Banoub, Joseph H.

2012-01-01

350

Neonatal pneumococcal conjugate vaccine immunization primes T cells for preferential Th2 cytokine expression: A randomized controlled trial in Papua New Guinea  

PubMed Central

The effects of neonatal immunization with 7-valent pneumococcal conjugate vaccine (7vPCV) on development of T-cell memory and general immune maturation were studied in a cohort of Papua New Guinean newborns. Neonatal 7vPCV priming (followed by a dose at 1 and 2 months of age) was associated with enhanced Th2, but not Th1, cytokine responses to CRM197 compared to 7vPCV at 1 and 2 months of age only. T cell responses to non-7vPCV vaccine antigens were similar in all groups, but TLR-mediated IL-6 and IL-10 responses were enhanced in 7vPCV vaccinated compared to controls. Neonatal 7vPCV vaccination primes T cell responses with a polarization towards Th2 with no bystander effects on other T cell responses.

van den Biggelaar, Anita. H.J.; Richmond, Peter C.; Pomat, William S.; Phuanukoonnon, Suparat; Nadal-Sims, Marie A.; Devitt, Catherine J.; Siba, Peter M.; Lehmann, Deborah; Holt, Patrick G.

2009-01-01

351

Effect of combination with an acellular pertussis, diphtheria, tetanus vaccine on antibody response to Hib vaccine (PRP-T)  

Microsoft Academic Search

Acellular pertussis vaccines provide protection against whooping cough with few adverse effects. Their introduction to routine immunisation programmes would be facilitated by their incorporation with other routinely administered vaccines. 262 infants were immunised with an acellular pertussis vaccine containing pertussis toxin and filamentous haemagglutinin, combined with diphtheria and tetanus toxoids. This vaccine was mixed with Haemophilus influenzae type b tetanus

Frank Bell; Paul Heath; Fiona Shackley; Jenny MacLennan; Nicola Shearstone; Linda Diggle; Helen Griffiths; E. Richard Moxon; Adam Finn

1998-01-01

352

Children with otitis media mount a pneumococcal serotype specific serum IgG and IgA response comparable to healthy controls after pneumococcal conjugate vaccination.  

PubMed

It has been suggested that otitis-prone children have an impaired antibody response. To investigate this in the context of pneumococcal vaccination, we used a multiplex bead-based assay to measure serum IgG and IgA levels against pneumococcal serotypes included in the 7-valent pneumococcal conjugate vaccine (PCV7; serotypes 4, 6B, 9V, 14, 18C, 19F and 23F) and 4 non-PCV7 serotypes (1, 5, 7F and 19A) in healthy (n=43) and otitis-prone children (n=75) before, 6 weeks after and 1 year after vaccination with one dose of PCV7. Pre-vaccination, otitis-prone children had significantly higher serum IgG levels against serotypes 4, 9V and 23F and against all non-PCV7 serotypes. One year following vaccination, there was no difference in IgG or IgA levels between healthy and otitis-prone children. The effect of the administration of one or two doses of PCV7 was investigated in otitis-prone children. After a second dose of PCV7, pneumococcal serotype specific IgG levels, but not IgA titres, were higher compared to the levels measured after the initial dose of PCV7. One year post PCV7 vaccination there was no difference in either IgG or IgA antibody levels to any of the PCV7 serotypes between children who received either one or two doses of PCV7. The finding that otitis-prone children do not have an impaired pneumococcal serotype-specific serum IgG or IgA response suggests that new pneumococcal conjugate vaccines may be immunogenic in otitis-prone children, however, further investigations are necessary to determine the clinical impact of such vaccines against the development of recurrent acute otitis media. PMID:22326775

Menon, Vinay J; Corscadden, Karli J; Fuery, Angela; Thornton, Ruth B; Kirkham, Lea-Ann S; Richmond, Peter C; Wiertsema, Selma P

2012-02-08

353

Assessment of functional antibacterial opsonophagocytic antibodies elicited by 13-valent pneumococcal conjugate vaccine administered concomitantly with trivalent influenza vaccine in a randomized clinical trial in adults aged ?65 years.  

PubMed

A randomized, double-blind clinical trial compared immune responses elicited by concomitant administration of 13-valent pneumococcal conjugate vaccine (PCV13) and trivalent inactivated influenza vaccine (PCV13+TIV), with PCV13 given 1 month after TIV, in healthy, pneumococcal vaccine-naïve adults aged ?65 years. Serotype-specific pneumococcal anti-polysaccharide IgG antibody concentrations 1-month post-vaccination were uniformly lower after PCV13+TIV, than after PCV13 alone (Vaccine 2011;29:5195-202). Therefore, post hoc analyses to evaluate the functional antibody titers at 1-month post-vaccination, as measured by opsonophagocytic activity (OPA) assays, were performed. The anti-pneumococcal functional responses, while also generally lower after vaccine co-administration, nonetheless showed a greater degree of similarity between the two vaccine groups than was apparent from the anti-polysaccharide antibody responses. In particular, the proportion of OPA responders after PCV13 and TIV co-administration was similar to that observed after PCV13 alone for all serotypes evaluated. Concomitant use of PCV13 and TIV should therefore be guided by clinical circumstances. PMID:23123107

Schwarz, Tino F; Schmoele-Thoma, Beate

2012-11-02

354

Pneumonia Hospitalizations Among Young Children Before and After Introduction of Pneumococcal Conjugate Vaccine - United State, 1997-2006. Morbidity and Morality Weekly Report, Vol. 58, No. 1, january 16, 2009.  

National Technical Information Service (NTIS)

Streptococcus pneumoniae is the leading bacterial cause of community-acquired pneumonia hospitalizations and an important cause of bacteremia and meningitis, especially among young children and older adults. A 7-valent pneumococcal conjugate vaccine (PCV7...

2009-01-01

355

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

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.

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

2010-01-01

356

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

PubMed Central

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

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

357

Heat-Labile- and Heat-Stable-Toxoid Fusions (LTR192G-STaP13F) of Human Enterotoxigenic Escherichia coli Elicit Neutralizing Antitoxin Antibodies ?  

PubMed Central

Enterotoxigenic Escherichia coli (ETEC) strains are a major cause of diarrheal disease in humans and animals. Adhesins and enterotoxins, including heat-labile (LT) and heat-stable (STa) toxins, are the key virulence factors. Antigenic adhesin and LT antigens have been used in developing vaccines against ETEC diarrhea. However, STa has not been included because of its poor immunogenicity and potent toxicity. Our recent study showed that porcine-type STa toxoids became immunogenic and elicited neutralizing anti-STa antibodies after being genetically fused to a full-length porcine-type LT toxoid, LTR192G (W. Zhang et al., Infect. Immun. 78:316-325, 2010). In this study, we mutated human-type LT and STa genes, which are highly homologous to porcine-type toxin genes, for a full-length LT toxoid (LTR192G) and a full-length STa toxoid (STaP13F) and genetically fused them to produce LT192-STa13 toxoid fusions. Mice immunized with LT192-STa13 fusion antigens developed anti-LT and anti-STa IgG (in serum and feces) and IgA antibodies (in feces). Moreover, secretory IgA antibodies from immunized mice were shown to neutralize STa and cholera toxins in T-84 cells. In addition, we fused the STa13 toxoid at the N terminus and C terminus, between the A1 and A2 peptides, and between the A and B subunits of LT192 to obtain different fusions in order to explore strategies for enhancing STa immunogenicity. This study demonstrated that human-type LT192-STa13 fusions induce neutralizing antitoxin antibodies and provided important information for developing toxoid vaccines against human ETEC diarrhea.

Liu, Mei; Ruan, Xiaosai; Zhang, Chengxian; Lawson, Steve R.; Knudsen, David E.; Nataro, James P.; Robertson, Donald C.; Zhang, Weiping

2011-01-01

358

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

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

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

359

Reduction in pediatric invasive pneumococcal disease in the Basque Country and Navarre, Spain, after introduction of the heptavalent pneumococcal conjugate vaccine  

Microsoft Academic Search

This study evaluated the incidence of invasive pneumococcal disease, identified the causal serotypes, and tracked the evolution\\u000a of the antibiotic susceptibility of Streptococcus pneumoniae isolates in the regions of the Basque Country and Navarre, Spain, before and after the introduction of the heptavalent pneumococcal\\u000a conjugate vaccine. The study included all children aged between birth and 5 years diagnosed with bacteremia, meningitis,

J. Aristegui; E. Bernaola; I. Pocheville; C. García; L. Arranz; G. Durán; L. Pérez; M. Bastida; C. Canduela; M. Herranz Aguirre; E. Garrote; M. A. Fletcher; C. Pérez

2007-01-01

360

Specific Polysaccharide Conjugate Vaccine-Induced IgG Antibodies Prevent Invasion of Shigella into Caco-2 Cells and May Be Curative [Corrected title: \\  

Microsoft Academic Search

The O-specific polysaccharide (O-SP) domain of Shigella LPS is both an essential virulence factor and a protective antigen for this genus. A critical level of serum IgG anti-O-SP was shown to confer immunity to shigellosis, likely by complement-mediated bacteriolysis of the inoculum. Conjugate Shigella O-SP vaccines were shown to be safe and immunogenic in children, and, in a preliminary study,

Yehuda Chowers; Joachim Kirschner; Nathan Keller; Iris Barshack; Simon Bar-Meir; Shai Ashkenazi; Rachel Schneerson; John Robbins; Justen H. Passwell

2007-01-01

361

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

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

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

362

Association of Serotype-Specific Antibody Concentrations and Functional Antibody Titers with Subsequent Pneumococcal Carriage in Toddlers Immunized with a 9-Valent Pneumococcal Conjugate Vaccine  

PubMed Central

Association of pneumococcal nasopharyngeal carriage with the concentration and opsonophagocytic activity (OPA) of serum serotype-specific antibodies was determined for toddlers 1 month after immunization with a 9-valent pneumococcal conjugate vaccine. Higher anti-serotype 14 and anti-serotype 19F IgG and anti-serotype 14 IgM correlated with a lowered probability of pneumococcal acquisition. Postvaccination OPA did not correlate with pneumococcal carriage.

Nurkka, Anu; Lahdenkari, Mika; Givon-Lavi, Noga; Kayhty, Helena; Dagan, Ron; Jokinen, Jukka

2012-01-01

363

Changes in molecular epidemiology of streptococcus pneumoniae causing meningitis following introduction of pneumococcal conjugate vaccination in England and Wales.  

PubMed

The introduction of the 7-valent pneumococcal conjugate vaccine (PCV7) in September 2006 has markedly reduced the burden of invasive pneumococcal disease (IPD) including meningitis in England and Wales. This study examined changes in the molecular epidemiology of pneumococcal isolates causing meningitis from July 2004 to June 2009. The Health Protection Agency conducts enhanced pneumococcal surveillance in England and Wales. In addition to serotyping, pneumococcal isolates causing meningitis were genotyped by multilocus sequence typing (MLST). A total of 1,030 isolates were both serotyped and genotyped over the 5-year period. Fifty-two serotypes, 238 sequence types (STs), and 87 clonal complexes were identified, with no significant difference in the yearly Simpson's diversity index values (range, 0.974 to 0.984). STs commonly associated with PCV7 serotypes declined following PCV implementation, with a proportionally greater decline in ST124 (commonly associated with serotype 14). No other ST showed significant changes in distribution, even within individual serotypes. Replacement disease following PCV7 introduction was mainly due to serotypes 1, 3, 7F, 19A, 22F, and 33F through clonal expansion. A single instance of possible capsule switching was identified where one ST4327 clone expressed a serotype 14 capsule in 2005 and a serotype 28A capsule in 2009. In 2008 to 2009, ST191 (7F) became the most prevalent clone causing meningitis (10.3%). Case fatality (145 fatalities/1,030 cases; 14.1%) was high across all age groups and serotype groups. Thus, the introduction of PCV7 resulted in an increase in non-PCV7 serotypes, including some not covered by the 13-valent vaccine, such as serotypes 22F and 33F, emphasizing the importance of long-term epidemiological and molecular surveillance. PMID:23269742

Pichon, Bruno; Ladhani, Shamez N; Slack, Mary P E; Segonds-Pichon, Anne; Andrews, Nick J; Waight, Pauline A; Miller, Elizabeth; George, Robert

2012-12-26

364

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

Microsoft Academic Search

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

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

2007-01-01

365

Immunogenicity of a Fourth Dose of Haemophilus influenzae Type b (Hib) Conjugate Vaccine and Antibody Persistence in Young Children from the United Kingdom Who Were Primed with Acellular or Whole-Cell Pertussis Component-Containing Hib Combinations in Infancy  

Microsoft Academic Search

In response to the rising incidence of Haemophilus influenzae type b (Hib) disease in the United Kingdom, a national campaign to give a booster dose of single-antigen Hib conjugate vaccine to children aged 6 months to 4 years was undertaken in 2003. Children (n 386) eligible for Hib vaccine in the campaign were recruited. Hib antibody concentrations were measured before

Jodie McVernon; David Gelb; Nick Andrews; Rhonwen Morris; Annette Crowley-Luke; David Goldblatt; Elizabeth Miller

2007-01-01

366

The acylated form of protein D of Haemophilus influenzae is more immunogenic than the nonacylated form and elicits an adjuvant effect when it is used as a carrier conjugated to polyribosyl ribitol phosphate.  

PubMed

The nonacylated form of protein D (PDm) of Haemophilus influenzae has been shown to induce the production of antibodies that are bactericidal to homologous and heterologous nontypeable H. influenzae (NTHi) strains. In this study, immunization of rats with lipoprotein D (LPD) induced higher levels of anti-protein D immunoglobulin G and A serum antibodies than immunization with PDm, and the bactericidal activities of sera from LPD-immunized rats were greater than those of sera from PDm-immunized rats. Immunization with LPD or PDm did not prevent the development of acute otitis media (AOM) when rats were challenged with 10(4) CFU of an NTHi strain. However, on the eighth day of bacterial challenge, 50% (5 of 10) of LPD-immunized rats had recovered from otitis media and 30% (3 of 10) had negative middle ear cultures, whereas only 30% (3 of 10) of PDm-immunized rats had recovered, though none was culture positive. Immunization with an inactivated homologous bacterial strain elicited 70% protection (i.e., 7 of 10 rats) in the rat otitis media model. LPD and PDm were also conjugated to the H. influenzae type b (Hib) capsular polysaccharide, polyribosyl ribitol phosphate (PRP), to test protein D-conjugated PRP vaccine's potential for protection against Hib infection. When two LPD-conjugated and two PDm-conjugated PRP vaccines, each containing a different protein concentration, and a tetanus toxoid-conjugated vaccine (ACT-HIB) were tested in the experimental model of rat otitis induced with a Hib strain (Minn A), both of the LPD-conjugated and one of the PDm-conjugated vaccines induced significant protection from AOM, the level of protection being highest in animals given the vaccine with the highest LPD content. Sera from these rats also manifested the highest anti-PRP and anti-LPD antibody levels and the highest bactericidal activities against a Hib strain and an NTHi strain. PMID:9393790

Akkoyunlu, M; Melhus, A; Capiau, C; van Opstal, O; Forsgren, A

1997-12-01

367

The acylated form of protein D of Haemophilus influenzae is more immunogenic than the nonacylated form and elicits an adjuvant effect when it is used as a carrier conjugated to polyribosyl ribitol phosphate.  

PubMed Central

The nonacylated form of protein D (PDm) of Haemophilus influenzae has been shown to induce the production of antibodies that are bactericidal to homologous and heterologous nontypeable H. influenzae (NTHi) strains. In this study, immunization of rats with lipoprotein D (LPD) induced higher levels of anti-protein D immunoglobulin G and A serum antibodies than immunization with PDm, and the bactericidal activities of sera from LPD-immunized rats were greater than those of sera from PDm-immunized rats. Immunization with LPD or PDm did not prevent the development of acute otitis media (AOM) when rats were challenged with 10(4) CFU of an NTHi strain. However, on the eighth day of bacterial challenge, 50% (5 of 10) of LPD-immunized rats had recovered from otitis media and 30% (3 of 10) had negative middle ear cultures, whereas only 30% (3 of 10) of PDm-immunized rats had recovered, though none was culture positive. Immunization with an inactivated homologous bacterial strain elicited 70% protection (i.e., 7 of 10 rats) in the rat otitis media model. LPD and PDm were also conjugated to the H. influenzae type b (Hib) capsular polysaccharide, polyribosyl ribitol phosphate (PRP), to test protein D-conjugated PRP vaccine's potential for protection against Hib infection. When two LPD-conjugated and two PDm-conjugated PRP vaccines, each containing a different protein concentration, and a tetanus toxoid-conjugated vaccine (ACT-HIB) were tested in the experimental model of rat otitis induced with a Hib strain (Minn A), both of the LPD-conjugated and one of the PDm-conjugated vaccines induced significant protection from AOM, the level of protection being highest in animals given the vaccine with the highest LPD content. Sera from these rats also manifested the highest anti-PRP and anti-LPD antibody levels and the highest bactericidal activities against a Hib strain and an NTHi strain.

Akkoyunlu, M; Melhus, A; Capiau, C; van Opstal, O; Forsgren, A

1997-01-01

368

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

PubMed Central

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

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

2008-01-01

369

Prediction of Pneumococcal Conjugate Vaccine Effectiveness against Invasive Pneumococcal Disease Using Opsonophagocytic Activity and Antibody Concentrations Determined by Enzyme-Linked Immunosorbent Assay with 22F Adsorption ?  

PubMed Central

We compared the abilities of two serological readouts, antipolysaccharide IgG antibody concentrations and opsonophagocytic activity (OPA) titers, to predict the clinical effectiveness of the 7-valent pneumococcal conjugate vaccine (7vCRM) against invasive pneumococcal disease (IPD). We also assessed the accuracy of the previously established thresholds for GlaxoSmithKline's enzyme-linked immunosorbent assay with 22F adsorption (22F-ELISA) (?0.2 ?g/ml) and OPA assay (titer, ?8) in predicting effectiveness. We showed that following a 3-dose 7vCRM primary vaccination, the serological response rates as determined using thresholds of ?0.2 ?g/ml IgG and an OPA titer of ?8 corresponded well with overall effectiveness against IPD. In addition, the OPA assay seemed to better predict serotype-specific effectiveness than enzyme-linked immunoassay. Finally, when applied to post-dose-2 immune responses, both thresholds also corresponded well with the overall IPD effectiveness following a 2-dose 7vCRM primary vaccination. These results support the importance of the OPA assay in evaluating immune responses to pneumococcal conjugate vaccines.

Schuerman, L.; Wysocki, J.; Tejedor, J. C.; Knuf, M.; Kim, K.-H.; Poolman, J.

2011-01-01

370

Microneedle-Based Transcutaneous Immunisation in Mice with N-Trimethyl Chitosan Adjuvanted Diphtheria Toxoid Formulations  

Microsoft Academic Search

Purpose  The purpose of this study was to gain insight into the delivery and immunogenicity of N-trimethyl chitosan (TMC) adjuvanted\\u000a diphtheria toxoid (DT) formulations applied transcutaneously with microneedles.\\u000a \\u000a \\u000a \\u000a \\u000a Methods  Mice were vaccinated with DT-loaded TMC nanoparticles, a solution of TMC and DT (TMC\\/DT) or DT alone. The formulations were\\u000a applied onto the skin before or after microneedle treatment with two different 300-µm-long

Suzanne M. Bal; Zhi Ding; Gideon F. A. Kersten; Wim Jiskoot; Joke A. Bouwstra

2010-01-01

371

Diphtheria and Tetanus Toxoids and Acellular Pertussis ...  

Center for Biologics Evaluation and Research (CBER)

Text Version... added as a preservative. Concentrate vaccine is transported to Connaught under connolled refrigeration. The diphtheria and ... More results from www.fda.gov/downloads/biologicsbloodvaccines/vaccines

372

Single Nucleotide Polymorphisms in the Toll-Like Receptor 3 and CD44 Genes Are Associated with Persistence of Vaccine-Induced Immunity to the Serogroup C Meningococcal Conjugate Vaccine  

PubMed Central

The rate of decay of antibody concentration following serogroup C meningococcal (MenC) polysaccharide-protein conjugate vaccination varies between individuals. This depends partly on vaccination age but may be influenced by human genetics. We studied 721 single nucleotide polymorphisms (SNPs) across 131 candidate genes in a first cohort of 905 Caucasians (11 to 21 years old; mean time after vaccination, 4.9 years) and 30 SNPs across 17 genes in a replication study using 155 children, aged 6 to 12 years (mean time after vaccination, 6.7 years), and 196 infants (1 year old; mean time after vaccination, 8 months). Individuals were classified as responders or nonresponders for total MenC IgG concentration and MenC serum bactericidal antibody (SBA) measurements. Associated genes were examined further for quantitative outcome measures. Fifty-nine SNPs in 37 genes were associated with IgG persistence (adjusted for age at measurement), and 56 SNPs in 36 genes were associated with SBA persistence (adjusted for age at measurement and vaccine used). Three SNPs each within the Toll-like receptor 3 (TLR3) (rs3775291, rs3775292, and rs5743312) and CD44 (rs11033013, rs353644, and rs996076) genes were associated with IgG (adjusted for age at measurement) or SBA (adjusted for age at measurement and vaccine used) persistence in the initial genetic study (P, 0.02 to 0.04). Single SNPs within the TLR3 (rs7657186) (P = 0.004 [unadjusted]) and CD44 (rs12419062) (P = 0.01 [unadjusted]) genes were associated with IgG persistence in the replication study. These results suggest that genetic polymorphisms in the TLR3 and CD44 genes are associated with the persistence of the immune response to MenC vaccines 1 to 6 years after vaccination.

Hennig, Branwen J.; Perrett, Kirsten P.; Hoe, J. Claire; Lee, Sue J.; Fletcher, Helen; Brocklebank, Denise; O'Connor, Daniel; Snape, Matthew D.; Hall, Andrew J.; Segal, Shelley; Hill, Adrian V. S.; Pollard, Andrew J.

2012-01-01

373

Toxicity and Immunogenicity of Enterotoxigenic Escherichia coli Heat-Labile and Heat-Stable Toxoid Fusion 3xSTaA14Q-LTS63K/R192G/L211A in a Murine Model  

PubMed Central

Diarrhea is the second leading cause of death to young children. Enterotoxigenic Escherichia coli (ETEC) are the most common bacteria causing diarrhea. Adhesins and enterotoxins are the virulence determinants in ETEC diarrhea. Adhesins mediate bacterial attachment and colonization, and enterotoxins including heat-labile (LT) and heat-stable type Ib toxin (STa) disrupt fluid homeostasis in host cells that leads to fluid hyper-secretion and diarrhea. Thus, adhesins and enterotoxins have been primarily targeted in ETEC vaccine development. A recent study reported toxoid fusions with STa toxoid (STaP13F) fused at the N- or C-terminus, or inside the A subunit of LTR192G elicited neutralizing antitoxin antibodies, and suggested application of toxoid fusions in ETEC vaccine development (Liu et al., Infect. Immun. 79:4002-4009, 2011). In this study, we generated a different STa toxoid (STaA14Q) and a triple-mutant LT toxoid (LTS63K/R192G/L211A, tmLT), constructed a toxoid fusion (3xSTaA14Q-tmLT) that carried 3 copies of STaA14Q for further facilitation of anti-STa immunogenicity, and assessed antigen safety and immunogenicity in a murine model to explore its potential for ETEC vaccine development. Mice immunized with this fusion antigen showed no adverse effects, and developed antitoxin antibodies particularly through the IP route. Anti-LT antibodies were detected and were shown neutralizing against CT in vitro. Anti-STa antibodies were also detected in the immunized mice, and serum from the IP immunized mice neutralized STa toxin in vitro. Data from this study indicated that toxoid fusion 3xSTaA14Q-tmLT is safe and can induce neutralizing antitoxin antibodies, and provided helpful information for vaccine development against ETEC diarrhea.

Zhang, Chengxian; Knudsen, David E.; Liu, Mei; Robertson, Donald C.; Zhang, Weiping

2013-01-01

374

Toxicity and Immunogenicity of Enterotoxigenic Escherichia coli Heat-Labile and Heat-Stable Toxoid Fusion 3xSTaA14Q-LTS63K/R192G/L211A in a Murine Model.  

PubMed

Diarrhea is the second leading cause of death to young children. Enterotoxigenic Escherichia coli (ETEC) are the most common bacteria causing diarrhea. Adhesins and enterotoxins are the virulence determinants in ETEC diarrhea. Adhesins mediate bacterial attachment and colonization, and enterotoxins including heat-labile (LT) and heat-stable type Ib toxin (STa) disrupt fluid homeostasis in host cells that leads to fluid hyper-secretion and diarrhea. Thus, adhesins and enterotoxins have been primarily targeted in ETEC vaccine development. A recent study reported toxoid fusions with STa toxoid (STaP13F) fused at the N- or C-terminus, or inside the A subunit of LTR192G elicited neutralizing antitoxin antibodies, and suggested application of toxoid fusions in ETEC vaccine development (Liu et al., Infect. Immun. 79:4002-4009, 2011). In this study, we generated a different STa toxoid (STaA14Q) and a triple-mutant LT toxoid (LTS63K/R192G/L211A, tmLT), constructed a toxoid fusion (3xSTaA14Q-tmLT) that carried 3 copies of STaA14Q for further facilitation of anti-STa immunogenicity, and assessed antigen safety and immunogenicity in a murine model to explore its potential for ETEC vaccine development. Mice immunized with this fusion antigen showed no adverse effects, and developed antitoxin antibodies particularly through the IP route. Anti-LT antibodies were detected and were shown neutralizing against CT in vitro. Anti-STa antibodies were also detected in the immunized mice, and serum from the IP immunized mice neutralized STa toxin in vitro. Data from this study indicated that toxoid fusion 3xSTaA14Q-tmLT is safe and can induce neutralizing antitoxin antibodies, and provided helpful information for vaccine development against ETEC diarrhea. PMID:24146989

Zhang, Chengxian; Knudsen, David E; Liu, Mei; Robertson, Donald C; Zhang, Weiping

2013-10-11

375

Use of 13-valent pneumococcal conjugate vaccine and 23-valent pneumococcal polysaccharide vaccine among children aged 6-18 years with immunocompromising conditions: recommendations of the Advisory Committee on Immunization Practices (ACIP).  

PubMed

On February 20, 2013, the Advisory Committee on Immunization Practices (ACIP) recommended routine use of 13-valent pneumococcal conjugate vaccine (PCV13; Prevnar 13, Wyeth Pharmaceuticals, Inc., a subsidiary of Pfizer, Inc.) for children aged 6-18 years with immunocompromising conditions, functional or anatomic asplenia, cerebrospinal fluid (CSF) leaks, or cochlear implants who have not previously received PCV13. PCV13 should be administered to these children regardless of whether they received the 7-valent pneumococcal conjugate vaccine (PCV7) or the 23-valent pneumococcal polysaccharide vaccine (PPSV23). Recommendations for PPSV23 use for children in this age group remain unchanged. The evidence for the benefits and risks associated with PCV13 vaccination of children with immunocompromising conditions was evaluated using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. This recommendation reflects a policy change from permissive and off-label recommendation of PCV13 in the pediatric immunocompromised population to a category A recommendation. This report summarizes the evidence considered by ACIP to make this recommendation and reviews the recommendations for use of PCV13 and PPSV23 for children aged 6-18 years. PMID:23803961

2013-06-28

376

Optimization and Application of a Multiplex Bead-Based Assay To Quantify Serotype-Specific IgG against Streptococcus pneumoniae Polysaccharides: Response to the Booster Vaccine after Immunization with the Pneumococcal 7-Valent Conjugate Vaccine ?  

PubMed Central

We describe the optimization and application of a multiplex bead-based assay (Luminex) to quantify antibodies against polysaccharides of 13 pneumococcal serotypes. In the optimized multiplex immunoassay (MIA), intravenous immune globulin was introduced as an in-house reference serum, and nonspecific reacting antibodies were adsorbed with the commercial product pneumococcal C polysaccharides Multi. The antibody concentrations were assessed in 188 serum samples obtained pre- and post-booster vaccination at 11 months after administration of a primary series of the pneumococcal seven-valent conjugate vaccine (PCV-7) at 2, 3, and 4 months of age. The results of the MIA were compared with those of the ELISA for the serotypes included in the seven-valent conjugated polysaccharide vaccine and for a non-vaccine serotype, serotype 6A. The geometric mean concentrations of the antibodies determined by MIA were slightly higher than those determined by ELISA. The correlations between the assays were good, with R2 values ranging from 0.84 to 0.91 for all serotypes except serotype 19F, for which R2 was 0.70. The concentrations of antibody against serotype 6A increased after the administration of PCV-7 due to cross-reactivity with serotype 6B. The differences between the results obtained by ELISA and MIA suggest that the internationally established protective threshold of 0.35 ?g/ml should be reevaluated for use in the MIA and may need to be amended separately for each serotype.

Elberse, Karin E. M.; Tcherniaeva, Irina; Berbers, Guy A. M.; Schouls, Leo M.

2010-01-01

377

Engineering, conjugation, and immunogenicity assessment of Escherichia coli O121 O antigen for its potential use as a typhoid vaccine component.  

PubMed

State-of-the-art production technologies for conjugate vaccines are complex, multi-step processes. An alternative approach to produce glycoconjugates is based on the bacterial N-linked protein glycosylation system first described in Campylobacter jejuni. The C. jejuni N-glycosylation system has been successfully transferred into Escherichia coli, enabling in vivo production of customized recombinant glycoproteins. However, some antigenic bacterial cell surface polysaccharides, like the Vi antigen of Salmonella enterica serovar Typhi, have not been reported to be accessible to the bacterial oligosaccharyltransferase PglB, hence hamper development of novel conjugate vaccines against typhoid fever. In this report, Vi-like polysaccharide structures that can be transferred by PglB were evaluated as typhoid vaccine components. A polysaccharide fulfilling these requirements was found in Escherichia coli serovar O121. Inactivation of the E. coli O121 O antigen cluster encoded gene wbqG resulted in expression of O polysaccharides reactive with antibodies raised against the Vi antigen. The structure of the recombinantly expressed mutant O polysaccharide was elucidated using a novel HPLC and mass spectrometry based method for purified undecaprenyl pyrophosphate (Und-PP) linked glycans, and the presence of epitopes also found in the Vi antigen was confirmed. The mutant O antigen structure was transferred to acceptor proteins using the bacterial N-glycosylation system, and immunogenicity of the resulting conjugates was evaluated in mice. The conjugate-induced antibodies reacted in an enzyme-linked immunosorbent assay with E. coli O121 LPS. One animal developed a significant rise in serum immunoglobulin anti-Vi titer upon immunization. PMID:23053636

Wetter, Michael; Kowarik, Michael; Steffen, Michael; Carranza, Paula; Corradin, Giampietro; Wacker, Michael

2012-10-06

378

Predictors of adverse events after the administration of acellular and whole-cell diphtheria-tetanus-pertussis vaccines  

Microsoft Academic Search

Recurrence of adverse events, the effect of site of injection, and concurrent administration of oral polio vaccine (OPV) and hepatitis B vaccine (HBV) on reactogenicity were assessed in recipients of two acellular pertussis vaccines given in combination with diphtheria and tetanus toxoids (DTaP), one whole-cell DTP vaccine (DTPwc) and one DT vaccine during a double blind, randomized, controlled clinical trial.

Alberto Eugenio Tozzi; Marta Luisa Ciofi degli Atti; Steven Gary Fite Wassilak; Stefania Salmaso; Pietro Panei; Alessandra Anemona; Stefania Luzi; Donato Greco

1998-01-01

379

Synthesis, characterization, and immunologic properties of detoxified lipooligosaccharide from nontypeable Haemophilus influenzae conjugated to proteins.  

PubMed Central

Nontypeable Haemophilus influenzae (NTHi) is an important cause of otitis media in children and of pneumonitis in adults with depressed resistance. Lipooligosaccharide (LOS) is a major surface antigen of NTHi and elicits bactericidal and opsonic antibodies. We prepared detoxified LOS (dLOS) protein conjugates from NTHi for use as experimental vaccines. LOS from NTHi 9274 was treated with anhydrous hydrazine and had its toxicity reduced to clinically acceptable levels. dLOS was bound to tetanus toxoid (TT) or high- molecular-weight proteins (HMPs) from NTHi through a linker of adipic acid dihydrazide to form dLOS-TT or dLOS-HMP. The molar ratio of the dLOS to protein carriers ranged from 26:1 to 50:1. The antigenicity of the conjugates was similar to that of the LOS alone as determined by double immunodiffusion. Subcutaneous or intramuscular injection of the conjugates elicited a 28- to 486-fold rise in the level of immunoglobulin G antibodies in mice to the homologous LOS after two or three injections and a 169- to 243-fold rise in the level of immunoglobulin G antibodies in rabbits after two injections. The immunogenicity of the conjugates in mice and rabbits was enhanced by formulation with monophosphoryl lipid A plus trehalose dimycolate. In rabbits, conjugate-induced LOS antibodies induced complement-mediated bactericidal activity against the homologous strain 9274 and prototype strain 3189. These results indicate that a detoxified LOS-protein conjugate is a candidate vaccine for otitis media and pneumonitis caused by NTHi.

Gu, X X; Tsai, C M; Ueyama, T; Barenkamp, S J; Robbins, J B; Lim, D J

1996-01-01

380

Haemophilus b Conjugate (Meningococcal Protein Conjugate ...  

Center for Biologics Evaluation and Research (CBER)

Text Version... to contain 7.5 mcg of PRP conjugated to approximately 125 meg of OMPC, 5 meg of HBsAg, approximately 225 mcg aluminum as aluminum ... More results from www.fda.gov/downloads/biologicsbloodvaccines/vaccines