Clinical and immunologic risk factors for meningococcal C conjugate vaccine failure in the United Kingdom.
BACKGROUND
The meningococcal serogroup C conjugate (MCC) vaccine was introduced into the United Kingdom with licensure based on immunogenicity data not efficacy data.


METHODS
All subjects with laboratory-confirmed meningococcal serogroup C (MenC) disease from January 2000 to December 2003 in England and Wales were followed up. A vaccine failure was defined as a laboratory-confirmed case of MenC disease occurring > or =10 days after the subject's last scheduled dose of MCC vaccine. Total immunoglobulins, serum bactericidal antibody (SBA) titers, MCC anticapsular antibody levels, and avidity indices (AIs) were measured in acute and convalescent serum samples from subjects with vaccine failure and unvaccinated subjects with MenC disease.


RESULTS
Of 465 subjects with confirmed MenC disease identified among those eligible for vaccination, information on vaccination history was obtained for 462 (99.4%); of these, 53 were subjects with vaccine failure. SBA titers in convalescent serum samples and AIs in acute serum samples were significantly higher in subjects with vaccine failure than in unvaccinated subjects, (6.1-fold higher for SBA titers [P=.03] and 3.2-fold higher for AIs [P=.001]).


CONCLUSIONS
The antibody response in the subjects with vaccine failure was consistent with an anamnestic response, suggesting that MenC disease occurred despite the MCC vaccine priming for immune memory. Persistence of antibodies may be a more appropriate correlate of long-term protection for MCC vaccines than the ability to generate a booster response on exposure.
Auckland
Cressida
C
Immunisation Department, Centre for Infections, Health Protection Agency, Manchester Royal Infirmary, Manchester, United Kingdom.
Gray
Stephen
S
Borrow
Ray
R
Andrews
Nick
N
Goldblatt
David
D
Ramsay
Mary
M
Miller
Elizabeth
E
D000293:Adolescent; D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008589:Meningococcal Infections / Q000276:immunology* / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000008:administration & dosage*; D038542:Neisseria meningitidis, Serogroup C / Q000145:classification / Q000276:immunology* / Q000302:isolation & purification; D012307:Risk Factors; D018571:Sentinel Surveillance; D006113:United Kingdom / Q000453:epidemiology; D014611:Vaccination; D018074:Vaccines, Conjugate / Q000008:administration & dosage
D000907:Antibodies, Bacterial; D015415:Biomarkers; D022401:Meningococcal Vaccines; D018074:Vaccines, Conjugate