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

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. (C) 2011 Elsevier Ltd. All rights reserved.