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

Abstract

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 (CRM 197 ) 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 CRM 197 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-CRM 197 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.In November 1999, the United Kingdom introduced conjugate vaccines against meningococcal serogroup C disease (MCC vaccines) into its immunization schedule for infants, with promising early reports of efficacy (18). The vaccines were also offered to all children between 1 and 17 years of age as a catch-up program that started in November 1999 and was completed within a year. The evidence of safety and immunogenicity of the MCC vaccines in these age groups was obtained from phase II trials conducted in the United Kingdom and sponsored by the Department of Health. Following promising results of early trials using the 2-, 3-, and 4-month schedule in United Kingdom infants (16), the Department of Health sponsored a comprehensive clinical trials program to evaluate the performance of candidate MCC vaccines in toddlers, children starting school, children leaving school, and young adults (12).One concern was the potential for interaction between the MCC vaccines, which contained either tetanus toxoid (TT) or the CRM 197 derivative of diphtheria toxin as the protein carrier, and the diphtheria and tetanus vaccines given as booster doses at school entry (DT) or school leaving (Td). To address these concerns, trials were conducted in which children received MCC vaccine a month before or after, or at the same time as, their DT or Td booster vaccine. Humoral immune responses against DT and MCC antigens were assessed following each vaccination.Since it was anticipated that licensure of the MCC vaccines would be based on immunogenic...

Validation of Serological Correlate of Protection for Meningococcal C Conjugate Vaccine by Using Efficacy Estimates from Postlicensure Surveillance in England

“…The distributions of rSBA titers post-primary vaccination against MCC in infants, toddlers, and preschool children (Table 1) were taken from a series of studies (16,14,4) in which testing was carried out at the Manchester Public Health Laboratory by standardized rSBA methods (3). All the children received Meningitec, a cross-reactive mutant-based conjugate vaccine produced by Wyeth Lederle Vaccines (Pearl River, N.Y.).…”

Randomized Trial on the Safety, Tolerability, and Immunogenicity of MenACWY-CRM, an Investigational Quadrivalent Meningococcal Glycoconjugate Vaccine, Administered Concomitantly with a Combined Tetanus, Reduced Diphtheria, and Acellular Pertussis Vaccine in Adolescents and Young Adults

“…It is therefore important that studies on concomitant use be performed in adolescents to ascertain the compatibility of new vaccines alongside Tdap. To date, two published studies have investigated the interaction between meningococcal C conjugate (MenC) vaccines and tetanus and reduced-antigen diphtheria (Td) boosters in adolescents 13 to 18 years old; these found no clinically relevant impact on the reactogenicity or immunogenicity of the MenC vaccines (4,21).…”

Maintenance of Immune Response throughout Childhood following Serogroup C Meningococcal Conjugate Vaccination in Early Childhood

“…Our results demonstrate that the current cohorts of children entering adolescence are unlikely to have protective levels of antibody, and thus, herd immunity may also start to wane. Furthermore, children in this study mainly received a MenC-CRM 197 conjugated vaccine, which was found to be the least immunogenic of the three licensed MenC conjugate vaccines (3,5). It was in wide use during the national immunization campaign, so these results could be generalized to a large group of United Kingdom adolescents.…”