Evaluation of de-O-acetylated meningococcal C polysaccharide-tetanus toxoid conjugate vaccine in infancy: Reactogenicity, immunogenicity, immunologicpriming, and bactericidal activity against O-acetylated and de-O-acetylated serogroup C strains

The polysaccharide capsule of serogroup C Neisseria meningitidis (MenC) has been integral to vaccine development. Licensed MenC vaccines contain the O -acetylated (OAc+) form of polysaccharide. Some MenC strains have de-O-acet ylated (OAc-) polysaccharide, which may affect antibody specificity and fun ctional activity when used in a vaccine. We evaluated an OAc-MenC conjugate -tetanus toroid conjugate (MCC-TT) vaccine given concomitantly with whole-c ell diphtheria-tetanus-pertussis, Haemophilus influenzae type b, and oral p olio immunization in 83 infants at 2, 3, and 4 months of age. Serum bacteri cidal activities (SBA) against OAc+ and OAc- MenC strains and OAc+ and OAc- polysaccharide-specific immunoglobulin G (IgG) levels were evaluated. MCC- TT vaccine was well tolerated. All infants produced SEA titers of greater t han or equal to8 after a single dose at 2 months of age. The SEA geometric mean titer for OAc+ strain C11 increased from 2.7 (95% confidence interval [CI] 2.2 to 3.2) to 320 (95% CI, 237 to 432), 773 (95% CI, 609 to 982), and 1,063 (95% CI, 856 to 1319) after one, two, and three doses of MCC-TT, res pectively. OAc- IgG levels were twice as high as OAc+ IgG levels after the primary series of MCC-TT vaccine, and the SEA was significantly higher agai nst the OAc-MenC strain. Antibody responses to booster vaccination with eit her OAc+ MenC polysaccharide vaccine (MACP) or a fourth dose of MCC-TT at 1 4 months of age provided evidence of immunologic memory. The acetylation st atus of the booster vaccine influenced the specificity of the response, wit h significantly higher OAc- IgG levels and SEA after MCC-TT vaccine compare d to MACP vaccine but similar OAc+ antibody levels. MCC-TT vaccine is highl y immunogenic and primes for immunologic memory against OAc+ and OAc-MenC s trains in infancy.