Immunity to Neisseria meningitidis in university students

Abstract

In October 1997 a cluster of meningitidis serogroup C infection occurred amongst first year students at an English university. Six cases were reported, with three fatalities. The measurement of complement-mediated serum bactericidal activity (SBA) is the generally accepted serological correlate of immunity to meningococci. In this thesis, the relationship between SBA and antibody reactivity to individual meningococcal antigens was explored. Individuals who became infected showed low levels of SBA against the outbreak strain; survivors developed SBA that correlated with production of antibodies to group C capsular polysaccharide but not to lipopolysaccharide (LPS) or major outer membrane proteins. Sera obtained one month before the outbreak from asymptomatic classmates of one of the cases, also showed a strong correlation between SBA and the presence of anti-capsular antibodies. No effective vaccine exists for N. meningitidis serogroup B, therefore levels of immunity to group B were investigated in the same student population. In contrast to group C, no association was demonstrated between BA directed against group B and the presence of antibodies to the group B capsular polysaccharide but there was a correlation between antibodies reacting with PorA and PorB proteins, and SBA. A follow-up carrier study was conducted on first year university students in which the dynamics of group B meningococcal carriage and the contribution of carriage to protective immunity against group B was investigated. Acquisition of carriage was always associated with specific SBA, indicating that carriage can induce natural immunity to meningococci. This immunity protected students against both homologous and heterologous strains, and was not associated with antibodies to LPS or group B capsular polysaccharide. A relationship between antibodies reacting with PorA and PorB proteins and bactericidal antibodies was noted. The results presented in this thesis indicate that antibodies to group B capsular polysaccharide and LPS are not involved in immune protection against group B meningococci. This work validates strategies for prevention of group B infection based on vaccines containing PorA and suggests that PorB may also be an important component of such vaccines.

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