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.
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