Immunogenicity and Safety of a 14-valent pneumococcal polysaccharide conjugate vaccine (PNEUBEVAX 14TM) administered to 6-8 weeks old healthy Indian Infants: A single blind, randomized, active-controlled, Phase-III study

Abstract

ABSTRACTBackgroundIntroduction of pneumococcal conjugate vaccines (PCV) reduced the cases of pneumococcal disease at global level. However, there is an increase in clinical and economic burden of PD from non-PCV serotypes, particularly in pediatric and elder population. In this study, immunogenicity and safety of the BE’s 14-valent PCV (PNEUBEVAX 14TM; BE-PCV-14) containing two additional epidemiologically important serotypes (22F and 33F) in comparison to PCV-13 was evaluated in infants.MethodsThis is a pivotal phase-3 single blind randomized active-controlled study conducted at 12 sites across India in 6-8 weeks old healthy infants in 6-10-14 weeks dosing schedule to assess immunogenic non-inferiority and safety of a candidate BE-PCV-14. In total, 1290 infants were equally randomized to receive either BE-PCV-14 or PCV-13. Solicited local reactions and systemic events, adverse events (AEs), serious AEs (SAEs) and medically attended AEs (MAAEs) were recorded. Immunogenicity was assessed by measuring anti-PnCPS IgG concentration and functional antibody titers by opsonophagocytic activity (OPA), one month after completing three dose schedule. Cross protection to serotype 6A offered by serotype 6B was also assessed in this study.FindingsThe safety profile of BE-PCV-14 was comparable to PCV-13 vaccine. Majority of reported AEs were mild in nature and no severe or serious AEs were reported. Primary immunogenicity objective was met for all 14 serotypes. For the twelve common serotypes non-inferiority to those 12 serotypes in PCV-13 was met. Additional serotypes in BE-PCV-14 (22F and 33F) also met NI criteria as defined by WHO TRS-977. A significant seroconversion, about 69% for serotype 6A was observed even though this antigen was not present in BE-PCV-14. This indicates that serotype 6B of BE-PCV-14 cross protects serotype 6A. BE-PCV-14 also elicited comparable serotype specific functional OPA immune responses to all the serotypes in PCV-13.InterpretationsBE-PCV-14 was found to be safe and induced robust and functional serotype specific immune responses to all 14 serotypes. All serotype-specific IgG responses were comparable to those in PCV-13. These findings suggest that BE-PCV-14 can be safely administered to infants and achieve protection against pneumococcal disease caused by serotypes covered in the vaccine.The study was prospectively registered with clinical trial registry of India-CTRI/2020/02/023129