Prevalence of de-O-acetylated serogroup C meningococci before the introduction of meningococcal serogroup C conjugate vaccines in the United Kingdom.

Meningococcal serogroup C conjugate (MCC) vaccines have been introduced in the UK to combat the rise in serogroup C meningococcal disease. Serogroup C meningococci may occur naturally expressing either O-acetylated (Oac(+)) or de-O-acetylated (Oac(-)) polysaccharide capsules. In a small study in the USA in the 1970s 15% of serogroup C meningococcal case isolates were reported to be Oac(-) though the prevalence of these Oac(-) isolates has not been recorded in the UK. This is of interest as the first MCC vaccines to be introduced are Oac(+) and the potential impact of this on Oac(-) serogroup C isolates is unclear. Serogroup C isolates submitted to the Public Health Laboratory Service Meningococcal Reference Unit in January 1998 (n=113) and January 1999 (n=162) were investigated by dot blotting using monoclonals specific for Oac(+) and Oac(-) serogroup C polysaccharides. This revealed 12% Oac(-) isolates for both January 1998 and January 1999. The proportion of fatal cases was found to similar for both Oac(-) and Oac(+), 14 and 9% for 1998 and 5 and 3% for 1999, indicating that the pathogenic potential of these Oac(-) isolates is similar to Oac(+). The acetylation status of serogroup C isolates needs to be monitored throughout and after the introduction of MCC vaccines.

Meningococcal serogroup C-specific IgG antibody responses and serum bactericidal titres in children following vaccination with a meningococcal A/C polysaccharide vaccine.

In the UK, a co-ordinated series of phase II studies is being undertaken with meningococcal serogroup C conjugate (MCC) vaccines. The use of meningococcal A/C polysaccharide (MACP) vaccines in control arms in young children has been avoided because of the well recognised short comings of these vaccines. Following a cluster of serogroup C disease centred on a day nursery, intervention by MACP vaccination was performed as an outbreak control measure. Using this cohort, serogroup C-specific IgG ELISA and serum bactericidal assays (SBA) were performed using both de-O-acetylated (Oac(-)) and acetylated (Oac(+)) serogroup C antigen, the measurement of primarily high avidity antibody and using baby rabbit or human complement in the SBA. The effect of subject age (either less than or greater than 2 years of age) was assessed for the different assays and significant differences (P<0.05) were found using both antigen sources in the high avidity ELISA and in the rabbit complement SBA but not in the standard ELISA. When assessing results from different studies it is important that methodologies utilised allow such comparisons since the choice of reagents can have a profound influence. The importance of standardised assays is paramount at a time where immunogenicity trials are replacing efficacy trials for the introduction of MCC vaccines.

Reduced antibody response to revaccination with meningococcal serogroup A polysaccharide vaccine in adults.

Widespread use of meningococcal A and C polysaccharide (MACP) vaccines has raised concerns about induction of hyporesponsiveness to these polysaccharides. Immunological hyporesponsiveness to C polysaccharide has been clearly documented in infants, children and adults but only limited data from Gambian children are available for A polysaccharide. We investigated whether a second dose of MACP, given 6 months after an initial dose affected the immunological response as measured by the serum bactericidal assay (SBA) and enzyme-linked immunosorbent assay (ELISA), to serogroup A meningococci in young adults (university students, n=36). Serogroup A SBA responses 1 month following the second dose of MACP (geometric mean titre (GMT) 103.6, 95% CI 45.6-235.1) were approximately one third of the levels observed 1 month post first dose (GMT 281.9, 95% CI 134.9-581.4). The serogroup A-specific IgG levels post second dose (GMC 21.2, 95% CI 15.3-29.4) were also significantly lower at an average of three-quarters the level post first dose (GMC 28.7, 95% CI 20.8-39.7). This confirms that revaccination with MACP vaccine, 6 months following the initial dose, results in a reduced immunological response to A polysaccharide in adults. Repeated vaccination with MACP vaccine may be ineffective and development and use of meningococcal serogroup A conjugate vaccines should be encouraged.