Safety and immunogenicity of a 14-valent pneumococcal conjugate vaccine (BE-PCV14) administered in a 3p + 1 schedule to healthy Indian infants and toddlers: a prospective, multicenter, active-controlled phase IV trial

Biological E’s PNEUBEVAX 14 ® (BE-PCV14) is a WHO-prequalified 14-valent pneumococcal conjugate vaccine that includes emerging serotypes 22F and 33F, which are not included in PCV13 coverage. We compared the safety and immunogenicity of a 3p + 1 (3 primary doses followed by a booster dose) infant-toddler schedule of BE-PCV14 versus Prevenar 13 ® (PCV13) in Indian children. In this prospective, open-label, multicenter phase IV trial, PCV-naïve infants aged 6–8 weeks received three primary doses of BE-PCV14 or PCV13 followed by a booster at 12–15 months of age. In the immunogenicity subset, serotype-specific IgG to the 14 vaccine serotypes and cross-protective 6A was measured 28 days post-booster. Endpoints were seroresponse rates (SRR, defined as percentage of participants with serotype specific IgG ≥ 0.35 µg/mL), IgG geometric mean concentrations (GMCs), and the frequency of solicited and unsolicited adverse events (AEs) and serious adverse events (SAEs) through 28 days post-booster. Post hoc non-inferiority of BE-PCV14 to PCV13 for all 14 serotypes was assessed by calculating the SRR differences and GMC ratios. For the SRR difference, non-inferiority was to be concluded if the lower limit of the 95% confidence interval was >-10%, and for the GMC ratio if the lower limit of the 95% confidence interval was > 0.5. Post-booster immunogenicity was assessed in 559 BE-PCV14 and 147 PCV13 recipients. AEs occurred at similarly low frequencies in both groups, were mainly mild local reactions or pyrexia, and the two SAEs after BE-PCV14 were considered unrelated to vaccination. Post-booster SRRs with BE-PCV14 were ≥ 92.8% for all 14 serotypes and 96.2% for 6A, comparable to PCV13 for shared serotypes. BE-PCV14 induced strong responses to the additional serotypes 22F and 33F, and post-booster/pre-booster GMC ratios were 2.4–5.3 across serotypes. Post hoc analyses showed BE-PCV14 was non-inferior to PCV13 for all 14 serotypes by both SRR and GMC criteria. When used as a booster in a 3p + 1 schedule, PNEUBEVAX 14 ® is well tolerated and elicits robust booster responses comparable to PCV13 with respect to shared serotypes while extending serotype coverage to 15 serotypes, including emerging 22F and 33F and cross-protective 6A. The protocol was approved by the Central Drugs Standard Control Organisation and registered prospectively on ctri.nic.in (CTRI/2023/09/057894) on 20 September 2023.