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

Ibarz-Pavon AB., Bielsky M-C., Bose R., Cavaleri M., Crump JA., Hombach J., Kaslow DC., Khaman F., MacLennan CA., Mehring-LeDoare K., Pollard AJ., Quadri F., John J., Wilder-Smith A.

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.

DOI

10.1016/j.vaccine.2025.127189

Type

Journal article

Publication Date

2025-05-22T00:00:00+00:00

Volume

56

Keywords

Enteric fever, Paratyphoid fever, Phase 3 study, Regulatory pathway, Salmonella Paratyphi A, Vaccines, Typhoid-Paratyphoid Vaccines, Humans, Salmonella typhi, Typhoid Fever, Salmonella paratyphi A, Paratyphoid Fever, World Health Organization, Endemic Diseases, Vaccine Development, Advisory Committees, Vaccines, Conjugate

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