Association Between Pre-Existing Anti-Diphtheria Toxoid IgG and Immune Responses to a CRM197-Conjugated 14-Valent Pneumococcal Conjugate Vaccine in Infants: A Post Hoc Analysis of a Multicenter Phase III Trial

Background/Objectives: Maternally transferred antibodies protect infants early in life, but high concentrations can reduce immune responses to primary vaccination. CRM197 is a nontoxic mutant of diphtheria toxin that retains antigenic similarity to the native protein. We therefore investigated whether anti-diphtheria antibodies present before vaccination were related to responses against pneumococcal polysaccharides conjugated to CRM197. Methods: This post hoc analysis used data from a multicenter, randomized, single-blind phase III trial in which Indian infants received BE-PCV14/PNEUBEVAX 14® at 6–8, 10–12, and 14–16 weeks of age (commonly referred to as 6–10–14 weeks). Baseline anti-diphtheria toxoid IgG concentrations measured at 6–8 weeks were assessed in relation to serotype-specific pneumococcal IgG responses 28 days after dose 3. We evaluated these associations using categorical and continuous analyses with false-discovery-rate correction for serotype-specific comparisons. Results: Baseline and post-primary results were available for 603 of 650 infants in the co-administration cohort. Post-primary pneumococcal IgG concentrations did not differ significantly across the baseline anti-diphtheria IgG categories. Individual fold rises differed nominally among baseline anti-diphtheria IgG categories for serotype 5, but the difference did not remain significant after multiplicity correction. In the adjusted continuous models, geometric mean ratios (GMRs) associated with each 2-fold increase in baseline anti-diphtheria IgG ranged from 0.978 to 1.011, with no statistically significant associations after false-discovery-rate correction. Analyses stratified by baseline pneumococcal IgG similarly showed no consistent evidence of reduced responses. Conclusions: In this cohort, pre-existing anti-diphtheria toxoid IgG measured before vaccination, which was likely maternally derived, was not associated with a consistent reduction in post-primary serotype-specific pneumococcal IgG responses to CRM197-conjugated BE-PCV14.