Safety and Immunogenicity of Co-Administration of Meningococcal Type A and Measles Rubella Vaccines with Typhoid Conjugate Vaccine in Children Aged 15-23 Months in Burkina Faso

Abstract

Background. The World Health Organization (WHO) pre-qualified a single-dose typhoid conjugate vaccine (TCV) in December 2017. WHO requested data on co-administration of TCV with Expanded Programme on Immunisation vaccines in typhoid-endemic countries. We tested co-administration of Typbar TCV® [Bharat Biotech International] with routine group A meningococcal conjugate vaccine (MCV-A) and measles-rubella (MR) vaccine. Methods: We conducted a double-blind, randomised, controlled trial at Schiphra Protestant Hospital outpatient paediatric clinic, Ouagadougou, Burkina Faso. Children recruited at routine 15-month vaccination visits were randomly assigned (1:1:1) to intramuscularly receive: Group 1) TCV plus control vaccine (inactivated polio vaccine) and MCV-A 28 days later; Group 2) TCV and MCV-A; or, Group 3) MCV-A and control vaccine. Routine MR vaccine was administered subcutaneously at day 0 to all participants. The primary outcome was safety, assessed by local and systemic reactions at 0, 3, and 7 days after immunisation; and unsolicited adverse events and serious adverse events 28 days and 6 months after immunisation, respectively. Primary analysis included all participants receiving at least one intramuscular vaccine. Immunogenicity was assessed as a secondary endpoint. ClinicalTrials.gov identifier NCT03614533. Findings: Between December 3, 2018 and February 18, 2019, we recruited and vaccinated 150 children: Group 1 (n=49), Group 2 (n=50), and Group 3 (n=51). Solicited local and systemic symptoms were infrequent and similar for TCV and control recipients, as were adverse events (Group 1: 61·2%, 95% CI 46·2-74·8; Group 2: 64·0%, 95% CI 49·2-77·1; Group 3: 68·6%, 95% CI 54·1-80·9) and serious adverse events (Group 1: 2·0%, 95% CI 0·1-10·9; Group 2: 8·0%, 95% CI 2·2-19·2; Group 3: 5·9%, 95% CI 1·2-16·2). No serious adverse events were related to vaccination. TCV generated robust immunity without interference with MCV-A or MR vaccine. Interpretation: TCV can be safely co-administered with routine MCV-A and MR vaccine. Trial Registration: y. The trial is registered at ClinicalTrials.gov, Identifier NCT03614533. Funding: Bill & Melinda Gates Foundation. Declaration of Interests: The authors have no competing interests to declare. Ethics Approval Statement: The study was approved by ethics committees in Burkina Faso (Comite d’Ethique pour la Recherche en Sante [CERS], Ouagadougou, Burkina Faso) and Maryland, USA (Institutional Review Board, University of Maryland, Baltimore), and by the Regulatory Authority in Burkina Faso (L’Agence Nationale de Regulation Pharmaceutique, Ouagadougou, Burkina Faso).