Safety, Reactogenicity, and Immunogenicity of a Tetravalent Meningococcal Polysaccharide–Diphtheria Toxoid Conjugate Vaccine Given to Healthy Adults

Campbell, James D.; Edelman, Robert; King, James C.; Papa, Thomas; Ryall, Robert; Rennels, Margaret B.

doi:10.1086/345763

Cited by 78 publications

(37 citation statements)

References 15 publications

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“…Our SBA results were comparable to those in previous studies of the quadrivalent meningococcal conjugate vaccine used (4,11,16); nevertheless, the relationship between functional antibody activity and IgG subclass is unknown.…”

Section: Discussionsupporting

confidence: 82%

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

Findlow

Southern

Mabey

et al. 2006

Clin Vaccine Immunol

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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 meningococcalpolysaccharide diphtheria toxoid conjugate vaccine against serogroups A, C, Y, and W135. Serologic responses were determined by serum bactericidal antibody assay and serogroup-specific IgG, IgG1, and IgG2 enzyme-linked immunosorbent assay. Prevaccination serogroup A-specific IgG1/IgG2 ratios were <1 for all subjects and differed by subject for C, Y, and W-135. Postvaccination, significant increases in IgG, IgG1, and IgG2, were observed for all serogroups. Serogroup-specific IgG1/IgG2 ratios increased for group A (14/17 subjects, 88%), decreased in more than half of subjects for groups C (9/17, 53%) and W135 (12/17, 71%) and decreased for serogroup Y (16/17, 94%). IgG1/IgG2 ratios differed between individual vaccinees and were similar to the responses of adults who received pneumococcal conjugate vaccines or a monovalent C conjugate vaccine. Further studies on IgG subclasses following meningococcal polysaccharide and conjugate vaccination are needed.A quadrivalent serogroup A, C, W135, and Y polysaccharide conjugate vaccine (Menactra) has recently been licensed in those of ages 11 to 55 years in the United States on the basis of safety and immunogenicity data collected from American children and adults (2). Conjugation of four meningococcal polysaccharides to a protein carrier produces T-cell-dependent responses, unlike the T-cell-independent responses induced by plain polysaccharide vaccines. Avidity indices have been used to measure immune responses to vaccines in infants and young children to demonstrate antibody maturation (3); however, such indices are not as useful in adults, most of whom have had previous exposure to pathogens, with the result that vaccination provides a booster, rather than a primary, immune response in this age group (6). It has been suggested that a vaccine's ability to increase the immunoglobulin G1 (IgG1)/ IgG2 ratio may indicate the activation of cellular control mechanisms typical for T-cell-dependent responses, as has been observed for pneumococcal conjugate vaccines in children (12,19,20). However, available data for meningococcal vaccines are scant; a single study of IgG subclasses after monovalent meningococcal group C conjugate vaccine has been published (8). In general, IgG subclass data for adults have been equivocal (8,12,19,20), making the acquisition of further data of interest. We report the IgG1 and IgG2 subclass response to Menactra vaccine in 17 healthy adults evaluated in the United Kingdom. MATERIALS AND METHODSEthical approval for the study was obtained from the Central and South Bristol research ethics committee (E5554). Seventeen healthy adults were recruited from the Bristol HPA laboratory, University of Bristol, and United Bristol Healthca...

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Section: Discussionsupporting

confidence: 82%

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

Findlow

Southern

Mabey

et al. 2006

Clin Vaccine Immunol

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“…Although 13 serogroups of meningococci have been identified based upon the structural identity of their polysaccharide capsules, the vast majority of disease is caused by only five groups (A, B, C, Y, and W-135) [3]. Recently, efficacious vaccines targeting four of these serogroups (A, C, Y and W-135) have been developed by direct conjugation of polysaccharide antigens to protein carriers [3][4][5][6][7]. These vaccines provide benefit over traditional, unconjugated polysaccharide (Ps) vaccines by inducing T-cell memory, and afford long-term immunity in both children and adults [2].…”

Section: Introductionmentioning

confidence: 99%

Development of a Multi-Plex Electrochemiluminescent Assay for the Detection of Serum Antibody Responses to Meningococcal Conjugate Vaccines

Indrawati

Heinrichs²,

Wen³

et al. 2012

WJV

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Neisseria meningitidis is a gram negative diplococcal bacterium. Worldwide, N. meningitidis is the leading cause of bacterial meningitis and sepsis, with five serogroups (A, B, C, Y, and W-135) responsible for the majority of the disease. Multivalent (A, C, Y, and W-135) polysaccharide and conjugate vaccines have been licensed in the United States and elsewhere and are widely available. We have developed a multi-plexed electrochemiluminescent assay to quantitate serum antibody responses to meningococcal polysaccharides A, C, Y, and W-135 to allow for rapid evaluation of licensed and investigational vaccines. A 96-well plate containing a carbon electrode arrayed with polysaccharides A, C, Y, and W-135 on separate spots within each well has been developed for simultaneous detection of polysaccharidespecific antibodies in serum samples from vaccinated individuals. The assay conditions were optimized using the antimeningococcal serogroup A/C reference serum pool, CDC 1992 (NIBSC 99/706), through evaluation of plate types, coating polysaccharide concentrations, and blocking and serum diluent buffers. Comparison of single and multi-plex assays demonstrated the sensitivity, specificity, and speed of the multi-plex format for the quantification of serum antibody responses to N. meningitidis polysaccharides A, C, Y and W-135.

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“…New multivalent meningococcal polysaccharide-protein conjugate vaccines are currently in development (5,30) and will likely be licensed in Europe and North America in the next few years (28). The low incidence of meningococcal disease in these populations precludes performing prospective randomized clinical trials to determine the efficacy of these new vaccines.…”

mentioning

confidence: 99%

Naturally Acquired Passive Protective Activity against Neisseria meningitidis Group C in the Absence of Serum Bactericidal Activity

Welsch¹,

Granoff²

2004

Infect Immun

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The hallmark of immunity to meningococcal disease is a bactericidal titer in serum of >1:4 measured with human complement, but this threshold titer may underestimate the extent of protection. We used the infant rat model of meningococcal bacteremia to measure group C passive protective activity in serum samples from 91 unimmunized adults living in California. A total of 35 sera (38.5%) had passive protective activity. Sera with complement-mediated bactericidal titers of >1:4 were 3.4-fold more likely to confer protection (89%) than nonbactericidal sera (26%; P < 0.0001). Thus, bactericidal titers of >1:4 are a marker of protection, but this threshold lacks sensitivity for predicting protective activity. We investigated the 73 sera with bactericidal titers of <1:4 to determine the basis of protective activity. The 19 sera with protective activity had a higher geometric mean group C anticapsular antibody concentration (0.72 g/ml) than the 54 sera that lacked protective activity (0.16 g/ml; P < 0.001). Thus, protective activity in the absence of bactericidal activity was associated with higher concentrations of anticapsular antibodies, but not all sera with anticapsular antibodies conferred protection. Of 18 nonbactericidal sera with anticapsular antibody concentrations between 0.31 and 0.99 g/ml, the 11 sera that conferred protection had a higher mean antibody avidity constant (21.9 nM ؊1 ) than the 7 nonprotective sera (14.6 nM ؊1 ; P < 0.03). Thus, in sera with titers of <1:4, protective activity is associated with higher-avidity group C anticapsular antibodies, which are present in concentrations insufficient to elicit complement-mediated bacteriolysis in vitro but sufficient to confer protection in an in vivo bacteremia model.

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Safety, Reactogenicity, and Immunogenicity of a Tetravalent Meningococcal Polysaccharide–Diphtheria Toxoid Conjugate Vaccine Given to Healthy Adults

Cited by 78 publications

References 15 publications

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

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

Development of a Multi-Plex Electrochemiluminescent Assay for the Detection of Serum Antibody Responses to Meningococcal Conjugate Vaccines

Naturally Acquired Passive Protective Activity against Neisseria meningitidis Group C in the Absence of Serum Bactericidal Activity

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