title: Relationship between serum bactericidal activity and serogroup-specific immunoglobulin G concentration for adults, toddlers, and infants immunized with Neisseria meningitidis serogroup C vaccines.
abstract: A new meningococcal group C-CRM(197) conjugate vaccine (MnCC; Meningitec) has been evaluated in multiple clinical trials in the United States and most recently has been approved for routine administration in the United Kingdom. Meningococcal serogroup C (MnC)-specific immunoglobulin G (IgG) antibodies in pre- and postimmunization sera obtained from healthy U.S. adults, toddlers, and infants were quantitated by enzyme-linked immunosorbent assay (ELISA) and by an antibody-dependent, complement-mediated serum bactericidal assay (SBA). Serogroup-specific IgG antibody (micrograms per milliliter) in adults immunized either with the quadrivalent polysaccharide (A, C, Y, and W-135) vaccine or with MnCC showed a strong correlation (r = 0.848 and 0.934, respectively) by linear regression analysis with SBA. Sera from infants immunized with the MnCC (n = 30) and an age-matched unimmunized control group (n = 15) were also analyzed. Linear regression analysis of serum bactericidal and IgG ELISA data from sera obtained at 2 months of age (preimmunization) showed no correlation; however, a high degree of correlation was observed at time points after two (r = 0.877) and three (r = 0.951) immunizations, where significant rises in anti-MnC polysaccharide antibodies occurred relative to the age-matched control group. Infants previously primed with 3 doses of MnCC were given a booster dose of conjugate vaccine at 12 to 15 months of age. The correlation coefficient of ELISA to SBA for combined pre- and postbooster data was r = 0.836 (n = 48 pairs). In conclusion, increases in serum bactericidal activity in immunized adult, toddler, and infant populations were found to correlate very well with increases in serogroup-specific IgG concentrations, whereas the correlation between these two assays in nonimmunized 2-month-old infants was poor. Characterizing the relationship between these methods is important for understanding the significance of antigen-specific antibody concentrations relative to vaccine performance and protection from disease.
authors.affiliation: Wyeth-Lederle Vaccines and Pediatrics, West Henrietta, New York 14586, USA. sikkemad@war.wyeth.com
authors.forename: D J
authors.initials: DJ
authors.lastname: Sikkema
authors.forename: K E
authors.initials: KE
authors.lastname: Friedman
authors.forename: B
authors.initials: B
authors.lastname: Corsaro
authors.forename: A
authors.initials: A
authors.lastname: Kimura
authors.forename: S W
authors.initials: SW
authors.lastname: Hildreth
authors.forename: D V
authors.initials: DV
authors.lastname: Madore
authors.forename: S A
authors.initials: SA
authors.lastname: Quataert
mesh_terms: D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood / Q000276:immunology*; D001426:Bacterial Proteins / Q000276:immunology*; D002675:Child, Preschool; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D006801:Humans; D007074:Immunoglobulin G / Q000097:blood / Q000276:immunology*; D007223:Infant; D007753:Laboratories; D008589:Meningococcal Infections / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control*; D022401:Meningococcal Vaccines / Q000276:immunology*; D009345:Neisseria meningitidis / Q000276:immunology*; D015203:Reproducibility of Results; D014611:Vaccination / Q000379:methods; D018074:Vaccines, Conjugate / Q000276:immunology
chemical_list: D000907:Antibodies, Bacterial; D001426:Bacterial Proteins; D007074:Immunoglobulin G; D022401:Meningococcal Vaccines; D018074:Vaccines, Conjugate; C410218:serogroup C meningococcal conjugate vaccine; C028581:CRM197 (non-toxic variant of diphtheria toxin)