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Infection and Immunity, April 2001, p. 2378-2382, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.2378-2382.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.

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

Peter Richmond,1,2,* Ray Borrow,3 Jamie Findlow,3 Sarah Martin,3 Carol Thornton,4 Keith Cartwright,5 and Elizabeth Miller1

Immunisation Division, Communicable Disease Surveillance Centre, Public Health Laboratory Service, London NW9 5EQ,1 Immunobiology Unit, Institute of Child Health, London WC1N 2AN,2 PHLS Meningococcal Reference Unit, Withington Hospital, Manchester M20 2LR,3 Centre for Applied Microbiology and Research, Porton Down, Salisbury SP4 OJG,4 and Gloucester Vaccine Evaluation Unit, Public Health Laboratory, Gloucestershire Royal Hospital, Gloucester GL1 3NN,5 United Kingdom

Received 18 September 2000/Returned for modification 20 October 2000/Accepted 2 January 2001

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 >= 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.

* Corresponding author. Present address: Department of Paediatrics, University of Western Australia, Princess Margaret Hospital for Children, GPO Box D184, Perth, Australia 6014. Phone: 61 8 9340 7037. Fax: 61 8 9388 2097. E-mail: peterr{at}ichr.uwa.edu.au.

Infection and Immunity, April 2001, p. 2378-2382, Vol. 69, No. 4
0019-9567/01/$04.00+0   DOI: 10.1128/IAI.69.4.2378-2382.2001
Copyright © 2001, American Society for Microbiology. All rights reserved.


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