title: Early appearance of bactericidal antibodies after polysaccharide challenge of toddlers primed with a group C meningococcal conjugate vaccine: what is its role in the maintenance of protection?
abstract: The contribution of memory responses after meningococcal vaccination to protection may depend on the rapidity of the response. Toddlers were challenged with a licensed polysaccharide (PS) vaccine 1 year after vaccination with a single dose of meningococcal group C-CRM(197) conjugate (MCC) vaccine at the age of 12 to 15 months. Bactericidal antibodies and immunoglobulin G (IgG) antibodies detected by an enzyme-linked immunosorbent assay (ELISA) were measured before challenge and 4, 7, 14, or 21 Days later ("Days" refer to treatment groups, "days" to sampling days). Among 281 subjects in the intent-to-treat population, 173 per-protocol (PP) subjects were challenged with 10 microg PS antigen and 103 others with a 50-microg PS vaccinating dose. Capsular PS-specific ELISA IgG titers were negligible in baseline samples and increased only twofold within 4 days of PS administration. In contrast, the proportion of PP subjects with serum bactericidal antibody (SBA) titers of >or=1:8 or >or=1:128 increased, respectively, from 41% and 16% before challenge to 84% and 74% at Day 4 and to 100% and 97% at Day 7. Recipients of 50 microg PS responded with similar kinetics but showed a trend toward higher antibody levels. Unexpectedly, 69% of subjects bled on days 2 to 3 already had achieved SBA titers of >or=1:8. The majority of toddlers previously immunized with MCC and challenged 1 year later with PS antigen mounted protective levels of bactericidal antibody within 2 to 4 days.
authors.affiliation: Wyeth Research, 500 Arcola Rd., Collegeville, Pennsylvania 19426, USA.
authors.forename: Theodore F
authors.initials: TF
authors.lastname: Tsai
authors.forename: Ray
authors.initials: R
authors.lastname: Borrow
authors.forename: Hanspeter E
authors.initials: HE
authors.lastname: Gnehm
authors.forename: Bernard
authors.initials: B
authors.lastname: Vaudaux
authors.forename: Ulrich
authors.initials: U
authors.lastname: Heininger
authors.forename: Daniel
authors.initials: D
authors.lastname: Desgrandchamps
authors.forename: Christoph
authors.initials: C
authors.lastname: Aebi
authors.forename: Paul
authors.initials: P
authors.lastname: Balmer
authors.forename: Ronald D
authors.initials: RD
authors.lastname: Pedersen
authors.forename: Bernard
authors.initials: B
authors.lastname: Fritzell
authors.forename: Claire-Anne
authors.initials: CA
authors.lastname: Siegrist
mesh_terms: D000907:Antibodies, Bacterial / Q000097:blood*; D005260:Female; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology; D007156:Immunologic Memory; D007223:Infant; D008297:Male; D008585:Meningitis, Meningococcal / Q000276:immunology / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*; D011135:Polysaccharides, Bacterial / Q000276:immunology / Q000494:pharmacology*; D011446:Prospective Studies; D013557:Switzerland; D013997:Time Factors; D016896:Treatment Outcome; D018074:Vaccines, Conjugate / Q000009:adverse effects / Q000276:immunology / Q000627:therapeutic use*
chemical_list: D000907:Antibodies, Bacterial; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines; D011135:Polysaccharides, Bacterial; D018074:Vaccines, Conjugate