Evaluation of De-O-acetylated meningococcal C polysaccharide-tetanus toxoid conjugate vaccine in infancy: reactogenicity, immunogenicity, immunologic priming, 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-acetylated (OAc-) polysaccharide, which may affect antibody specificity and functional activity when used in a vaccine. We evaluated an OAc-MenC conjugate-tetanus toxoid conjugate (MCC-TT) vaccine given concomitantly with whole-cell diphtheria-tetanus-pertussis, Haemophilus influenzae type b, and oral polio immunization in 83 infants at 2, 3, and 4 months of age. Serum bactericidal 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 SBA titers of > or = 8 after a single dose at 2 months of age. The SBA 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, respectively. OAc- IgG levels were twice as high as OAc+ IgG levels after the primary series of MCC-TT vaccine, and the SBA was significantly higher against the OAc- MenC strain. Antibody responses to booster vaccination with either OAc+ MenC polysaccharide vaccine (MACP) or a fourth dose of MCC-TT at 14 months of age provided evidence of immunologic memory. The acetylation status of the booster vaccine influenced the specificity of the response, with significantly higher OAc- IgG levels and SBA after MCC-TT vaccine compared to MACP vaccine but similar OAc+ antibody levels. MCC-TT vaccine is highly immunogenic and primes for immunologic memory against OAc+ and OAc- MenC strains in infancy.
Immunisation Division, Communicable Disease Surveillance Centre, Public Health Laboratory Service, London NW9 5EQ, United Kingdom. peterr@ichr.uwa.edu.au
P
P
Richmond
R
R
Borrow
J
J
Findlow
S
S
Martin
C
C
Thornton
K
K
Cartwright
E
E
Miller
D000907:Antibodies, Bacterial / Q000097:blood; D001770:Blood Bactericidal Activity; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood; D007156:Immunologic Memory; D007223:Infant; D008297:Male; D022401:Meningococcal Vaccines / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology*; D013745:Tetanus Toxoid / Q000276:immunology*; D018074:Vaccines, Conjugate / Q000276:immunology*
D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines; D013745:Tetanus Toxoid; D018074:Vaccines, Conjugate; C410218:serogroup C meningococcal conjugate vaccine