title: Correlation between serum bactericidal activity against Neisseria meningitidis serogroups A, C, W-135 and Y measured using human versus rabbit serum as the complement source.
abstract: The surrogate of protection against invasive meningococcal disease is the presence of serum bactericidal activity (SBA) at a titer ≥4 in an assay using human serum as the complement source (hSBA). However, for various practical and logistical reasons, many meningococcal vaccines in use today were licensed based on a modified SBA assay that used baby rabbit serum as the complement source (rSBA). To assess the strength of correlation between the two assay systems for serogroups A, C, W-135 and Y, we analyzed a subset of samples from adolescent subjects enrolled in a Phase II study of Novartis' MenACWY-CRM conjugate vaccine vs. an ACWY polysaccharide vaccine; samples were analyzed in parallel using hSBA and rSBA. We compared geometric mean titers (GMTs), calculated Pearson correlation coefficients between paired hSBA and rSBA results, and calculated sensitivity/specificity and likelihood ratios for an rSBA ≥8 or ≥128 for classifying hSBA ≥4, taking hSBA as the 'gold standard'. Correlations between hSBA and rSBA ranged from 0.46 to 0.78 for serogroup C, but were weaker for serogroups A, W-135 and Y (range -0.15 to 0.57). In post vaccination samples, nearly all subjects had rSBA titers ≥8, though up to 15% remained seronegative by hSBA. In post vaccination settings, rSBA titers at ≥8 or ≥128 was highly sensitive for an hSBA titer ≥4, but non-specific. In conclusion, results generated by rSBA did not accurately classify serostatus according to hSBA for serogroups A, W-135 and Y.
authors.affiliation: Novartis Vaccines and Diagnostics, Cambridge, MA, USA. cgill@bu.edu
authors.forename: C J
authors.initials: CJ
authors.lastname: Gill
authors.forename: S
authors.initials: S
authors.lastname: Ram
authors.forename: J A
authors.initials: JA
authors.lastname: Welsch
authors.forename: L
authors.initials: L
authors.lastname: Detora
authors.forename: A
authors.initials: A
authors.lastname: Anemona
mesh_terms: D000293:Adolescent; D000818:Animals; D001770:Blood Bactericidal Activity; D002648:Child; D017322:Clinical Trials, Phase II as Topic; D003165:Complement System Proteins / Q000276:immunology*; D005260:Female; D006801:Humans; D008297:Male; D022401:Meningococcal Vaccines / Q000008:administration & dosage / Q000276:immunology*; D038381:Neisseria meningitidis, Serogroup A / Q000276:immunology*; D038542:Neisseria meningitidis, Serogroup C / Q000276:immunology*; D038582:Neisseria meningitidis, Serogroup W-135 / Q000276:immunology*; D038581:Neisseria meningitidis, Serogroup Y / Q000276:immunology*; D011817:Rabbits; D016032:Randomized Controlled Trials as Topic
chemical_list: C556088:MenACWY-CRM vaccine; D022401:Meningococcal Vaccines; D003165:Complement System Proteins
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