Safety, Immunogenicity of Co-Administered Vaccines, and Lot-to-Lot Consistency of a 14-Valent Pneumococcal Conjugate Vaccine (PNEUBEVAX 14®) Administered at 6-10-14 Weeks in Healthy Infants: A Multicenter, Phase IV Trial.

Background

Pneumococcal conjugate vaccines (PCVs) have substantially reduced pneumococcal disease in children; however, serotype distribution varies geographically, and residual disease due to non-PCV13 serotypes persists. Biological E's PNEUBEVAX 14® (BE-PCV14), a WHO-prequalified 14-valent PCV, expands coverage by including serotypes 22F and 33F. As PCVs are co-administered with routine Expanded Programme on Immunization (EPI) vaccines, post-licensure data on safety, co-administration, and lot-to-lot consistency are essential. This multicenter phase IV study evaluated BE-PCV14 in healthy PCV-naïve infants aged 6-8 weeks across 31 sites in India.

Methods

A total of 2600 infants were enrolled and vaccinated at 6, 10, and 14 weeks of age; 2300 received BE-PCV14 and 300 received PCV13. All participants received concomitant DTwP-HepB-IPV-Hib and oral rotavirus vaccines per routine schedule. Safety was assessed through solicited and unsolicited adverse events (AEs) and serious adverse events (SAEs). Immunogenicity subsets evaluated responses to co-administered vaccines and serotype-specific responses across three BE-PCV14 lots.

Results

Among 2600 vaccinated infants, at least one AE occurred in 26.35% (95% CI: 24.59, 28.19) of BE-PCV14 and 24.67% (95% CI: 20.13, 29.84) of PCV13 recipients; most were mild. Injection-site pain and pyrexia were the most common events. Immune responses to co-administered vaccines were comparable between groups and met the non-inferiority criteria: lower bound of the two-sided 95% CI > -10 percentage points for seroprotection/seroconversion rate differences using the Farrington-Manning method. Lot-to-lot consistency was demonstrated, with all GMC ratios within the predefined equivalence margin (0.5-2.0).

Conclusions

BE-PCV14 was well tolerated. Immune responses to co-administered routine EPI vaccines met predefined non-inferiority criteria, supporting the interpretation that BE-PCV14 did not result in clinically meaningful immune interference. Consistent immune responses across manufacturing lots further support its use in infant immunization programs.