Safety and Immunogenicity of Biological E's 14-valent Pneumococcal Conjugate Vaccine (PNEUBEVAX 14(R)) Administered in a 3p+1 Schedule to Healthy Indian Infants and Toddlers: A Prospective, Multicenter, Active Controlled Phase IV Trial

BackgroundBiological Es PNEUBEVAX 14(R) (BE-PCV14) is a WHO-prequalified 14-valent pneumococcal conjugate vaccine that adds emerging serotypes 22F and 33F to PCV13 coverage. We compared the safety and immunogenicity of a 3p+1 infant schedule of BE-PCV14 versus Prevenar 13(R) (PCV13) in Indian infants. MethodsIn this prospective, open-label, multicentre phase IV trial, PCV-naive infants aged 6-8 weeks received three primary doses of BE-PCV14 or PCV13 followed by a booster at 12-15 months. 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 IgG [≥] 0.35 {micro}g/mL), IgG geometric mean concentrations (GMCs), and frequency of solicited / unsolicited adverse events (AEs) / serious AEs (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. ResultsPost-booster immunogenicity was assessed in 559 BE-PCV14 and 147 PCV13 recipients. AEs occurred at similarly low frequencies in both groups ([~]6%), 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 >90% 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 approximately 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. ConclusionsWhen used as a booster in a 3p+1 schedule, PNEUBEVAX 14(R) is well tolerated and elicits robust booster responses comparable to PCV13 while extending serotype coverage to 15 serotypes, including emerging 22F and 33F and cross-protective 6A.