Meningococcal C Polysaccharide Vaccine Induces Immunologic Hyporesponsiveness in Adults That Is Overcome by Meningococcal C Conjugate Vaccine

Abstract

Widespread use of meningococcal AC polysaccharide (MACP) vaccines has raised concerns about induction of hyporesponsiveness to C polysaccharide. Whether meningococcal C conjugate (MCC) vaccine overcomes any immunologic refractoriness following MACP vaccination in adults was investigated. University students vaccinated 6 months previously with MACP vaccine were randomized to receive MACP or MCC vaccine, and antibody responses were compared with those of previously unvaccinated students receiving MACP or MCC vaccine. In students primed with MACP vaccine, MCC vaccine induced significantly higher IgG and serum bactericidal antibody levels than did a second dose of MACP vaccine. Responses to a second dose of MACP vaccine were significantly lower than to the first dose. Previous receipt of MACP vaccine reduced serum bactericidal antibody but not IgG responses to MCC vaccine compared with those in previously unvaccinated students. This confirms that MACP vaccine induces immunologic hyporesponsiveness to C polysaccharide in adults, but this can be overcome with MCC vaccine. Repeated vaccination with MACP vaccine may be ineffective, and MCC vaccines should provide better long-term protection.

Immune competence after alemtuzumab treatment of multiple sclerosis

“…Hib and Men C seroconversion and seroprotection rates were compared with control data from other conjugate vaccines. [2][3][4][5][6] Seroconversion was defined as a 4-fold increase in antibody level after vaccination and seroprotection as the minimum antibody level required to protect against disease. 7 Seroprotection and geometric mean titer ratio (GMTR; defined as the geometric mean of individual post-/pre-vaccination titers) control data were available for diphtheria, tetanus, and poliomyelitis vaccine.…”

“…3,10 Seroprotection against the novel antigen Men C was low before vaccination, which induced 91% seroprotection and seroconversion in 19 patients (82.6%) (table 2 and figure), similar to rates after other conjugated Men C vaccines. 2,[4][5][6] All patients given diphtheria, tetanus, and poliomyelitis vaccine had seroprotective levels of antibodies to tetanus and diphtheria before and after vaccination, and nearly all were seroprotected against polio (table 2). High prevaccination antibody titers precluded assessment of seroconversion, but GMTRs indicate that responses to diphtheria, tetanus, and poliomyelitis vaccine antigens after alemtuzumab were equivalent to controls (table 2).…”

Development of a glycoconjugate vaccine to prevent meningitis in Africa caused by meningococcal serogroup X

“…As recognized for other PS, conjugation to an appropriate carrier protein overcomes the limits of PS vaccines, such as poor efficacy in children less than 2 y, lack of immunological memory with poor booster responses, and relatively short duration of protection (19)(20)(21). Meningococcal conjugate vaccines are also able to overcome the immune hyporesponsiveness that is induced by PS vaccines (22,23). Additionally, as documented for group C, meningococcal conjugate vaccines can reduce carriage of N. meningitidis in the nasopharynx, decreasing transmission (24), whereas PS vaccines have not been shown to provide substantial herd immunity (25).…”

Impact of meningococcal C conjugate vaccine in the UK

“…Following promising results in infants vaccinated under the UK 2/3/4 month schedule [11][12][13], the DH initiated further clinical trials to answer key policy-related questions. These trials determined the schedule to be used for catch-up immunisation of older age groups [14], the effect of prior vaccination with plain meningococcal C polysaccharide used for outbreak control on the response to MCC vaccines [15][16][17], and the compatibility of MCC vaccines when given at the same time as other vaccines used in the UK schedule, in particular diphtheria and tetanus vaccines which are similar to the carrier proteins in the MCC vaccines [1]. These DH-funded trials were complemented by manufacturer-sponsored trials designed to provide data required by the licensing authority, such as batch-tobatch variation [18] and the safety and immunogenicity of MCC vaccines compared with the licensed plain polysaccharide vaccine [19].…”

“…The MCC vaccines were shown to be safe and immunogenic in infants following the 2/3/4 month schedule [11][12][13]18] and in adolescents [19]. The hyporesponsiveness reported following meningococcal polysaccharide vaccines in young children and adults is overcome by administration of the MCC vaccine [15,17,20].…”