Immunogenicity and vaccine-serotype carriage prevalence after full or fractional doses of Pneumococcal Conjugate Vaccines in Kenyan infants: an individually randomised, controlled, non-inferiority trial

BackgroundPneumococcal conjugate vaccines (PCVs) are the most expensive component of the routine immunisation schedule in Gavi-supported countries. As countries transition out of Gavi support, PCV programmes are at risk. We assessed whether immunogenicity was non-inferior after fractional doses of PCV10 (GlaxoSmithKline plc.) or PCV13 (Pfizer Inc.), when compared to full doses, and analysed vaccine serotype (VT) carriage prevalence. Methods2100 healthy infants were enrolled and randomised into seven equal-sized trial arms. Doses were delivered in the 2p+1 schedule (6, 14 weeks and 9-12 months) in six trial arms: A) Full dose PCV13, B) 40%-PCV13, C) 20%-PCV13, D) Full dose PCV10, E) 40%-PCV10, F) 20%-PCV10. Participants in the seventh trial arm received full dose PCV10 at 6, 10 and 14 weeks. Immunogenicity was assessed 4-weeks post-prime and 4-weeks post-boost. Carriage was assessed at 9 and 18 months of age. ResultsIn the per-protocol analysis, 40%-PCV13 met the non-inferiority criteria for 12/13 serotypes post-prime and 13/13 serotypes post-boost. 20%-PCV13 met the criteria for 9/13 serotypes post-prime and 10/13 serotypes post-boost. 40%-PCV10 met the criteria for 8/10 serotypes post-prime and 6/10 serotypes post-boost. 20%-PCV10 met the criteria for 7/10 serotypes post-prime and 1/10 serotype post-boost. ConclusionsA 3-dose schedule of 40%-PCV13 met the non-inferiority criteria at both timepoints and could be implemented by using 4-dose UNICEF vials as 10-dose vials. A 3-dose schedule of 40%-PCV13 would cost UNICEF 3.30 USD and represents the most affordable, effective PCV schedule option currently available for countries transitioning out of Gavi-support. ClinicalTrials.gov ID: NCT03489018.