Consultation report – considerations for a regulatory pathway for bivalent Salmonella Typhi/Paratyphi A vaccines for use in endemic countries

Journal article

Enteric fever caused by Salmonella enterica serovars Typhi and Paratyphi A and, to a lesser extent, S. Paratyphi B and C, remains a significant cause of mortality and morbidity in resource-constrained settings. Typhoid conjugate vaccines (TCVs) protect against S. Typhi but no vaccine to date protects against paratyphoid fever. There are several bivalent S. Typhi/Paratyphi A products in development; however, the low incidence of paratyphoid fever in many settings limits the feasibility of phase 3 efficacy studies. Two bivalent vaccines adding the S. Paratyphi A-specific O:2 lipopolysaccharide conjugated to a protein carrier to TCV constructs have successfully completed phase 1 studies and will progress rapidly in their development.

The WHO's Product Development for Vaccines Advisory Committee (PDVAC) endorsed a regulatory pathway for a bivalent S. Typhi/Paratyphi A vaccine that contemplates demonstrating protective efficacy against S. Paratyphi A infection in a controlled human infection model (CHIM). Since the use of CHIM data in lieu of phase 3 efficacy studies and to identify markers of immune protection is not yet widely accepted by regulatory bodies, the WHO organized a consultation with vaccine developers, manufacturers, and regulators. The purpose of the meeting was to discuss the feasibility and considerations for the licensure of a bivalent S. Typhi/Paratyphi A vaccine. The aim of the consultation was to gain alignment among key stakeholders and facilitate the pathway to licensure in endemic countries.

Authors: Ibarz-Pavon, AB; Bielsky, M-C; Bose, R; Cavaleri, M; Crump, JA

• Publication status: Published
• Peer review status: Peer reviewed
• Publisher: Elsevier
• Journal: Vaccine
• Volume: 56
• Article number: 127189
• Publication date: 2025-05-01
• Acceptance date: 2025-04-24
• DOI: 10.1016/j.vaccine.2025.127189
• EISSN: 1873-2518
• ISSN: 0264-410X
• Pmid: 40318346
• Language: English
• Keywords: vaccines; enteric fever; regulatory pathway; paratyphoid fever; phase 3 study; Salmonella Paratyphi A