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

Background Pneumococcal 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. Methods 2100 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. Results In 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. Conclusions A 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][1] ID: [NCT03489018][2]. ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Trial ClinicalTrials.gov ID: [NCT03489018][2] ### Funding Statement The Bill & Melinda Gates Foundation (INV007838; PI Anthony Scott), The National Institute of Health Research (NIHR) Global Health Research Unit on Mucosal Pathogens (MPRU) small grant (PI Katherine Gallagher). ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: Ethics approval was obtained from Kenyan Medical Research Institute Scientific & Ethics Review Unit (SERU) and the London School of Hygiene & Tropical Medicine (LSHTM) Ethics Committee. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data produced in the present study are available upon reasonable request to the authors [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT03489018&atom=%2Fmedrxiv%2Fearly%2F2024%2F01%2F24%2F2024.01.24.24301730.atom