Peer-reviewed article
Phase II multicentre double-blind randomised controlled trial of a Bivalent VaccInation against Salmonella Typhi and Paratyphi A (BiVISTA) using a controlled human infection model of paratyphoid A infection: study protocol.
Paganotti Vicentine M, McCann N, Hennigan O, Maria N, Juarez Molina CI et al. ·
Summary
Written by AI, not yet AICS's view · claude-haiku-4-5-20251001This is a study protocol for testing a new vaccine that protects against both typhoid and paratyphoid A infections, which are serious diseases affecting children in South Asia. The vaccine will be tested in healthy adults in the UK using a controlled infection model, where volunteers are vaccinated and then intentionally exposed to paratyphoid A bacteria under medical supervision. The study will compare the new bivalent vaccine against an existing typhoid vaccine to see which provides better protection. Results will help determine if this vaccine could be used to prevent these diseases in children living in endemic areas.
Key points
- Enteric fever caused by Salmonella Typhi and Paratyphi A is endemic mainly in South Asia and disproportionately affects school-age children
- While typhoid conjugate vaccines exist, no licensed vaccine currently protects against paratyphoid A
- This Phase II trial will test a bivalent vaccine (SII-TCV(B)) against paratyphoid A using a controlled human infection model in 192 UK adults aged 18-55 years
- Participants will be randomly assigned to receive either the bivalent vaccine or a licensed Vi-polysaccharide typhoid vaccine, then intentionally challenged with paratyphoid A bacteria 28 days after vaccination
- The study will evaluate vaccine efficacy and immune response, with results disseminated through peer-reviewed publications
Limitations
This study uses healthy UK adults rather than children from endemic regions, so results may not directly reflect vaccine performance in the target population of South Asian children. The controlled infection model provides a rapid efficacy assessment but differs from natural infection patterns.
Abstract
Introduction Enteric fever, primarily caused by Salmonella enterica Typhi and Salmonella enterica Paratyphi A (SPA), is endemic mainly in South Asia, disproportionately affecting school-age children. Although typhoid conjugate vaccines (TCVs) are effective and implemented in many countries, no licensed vaccine exists against paratyphoid A. Bivalent vaccines targeting both S. Typhi and SPA may address this gap. Although field efficacy trials are not considered feasible, controlled human infection models (CHIMs) offer an alternative pathway for evaluating vaccine efficacy. This will be the first efficacy study of a bivalent vaccine against typhoid and paratyphoid A using a paratyphoid CHIM. Methods and analysis This is a phase II multicentre, double-blind, randomised controlled trial assessing the efficacy and immunogenicity of a bivalent conjugate vaccine candidate, Serum Institute of India Typhoid Conjugate Vaccine (Bivalent) (SII-TCV(B)), against SPA using a CHIM in healthy UK adults aged 18-55 years. A total of 192 participants will be randomised 1:1 to receive either SII-TCV(B) or a licensed Vi-polysaccharide typhoid vaccine (Vi-PS). All participants will be orally challenged with S. Paratyphi A (strain NVGH308) 28 days postvaccination. Participants will be monitored closely for 14 days and treated at 14 days postchallenge or promptly on diagnosis, according to prespecified criteria. The primary objective is to evaluate vaccine efficacy of SII-TCV(B) against paratyphoid infection using a CHIM. The coprimary immunogenicity objective is to assess non-inferiority of the typhoid IgG response compared with a licensed Vi-PS control. Ethics and dissemination The study has received ethical approval from the Berkshire Research Ethics Committee (24/SC/0309) and regulatory approval from the UK Medicines and Healthcare products Regulatory Agency. Results will be disseminated via peer-reviewed publications and scientific meetings. Trial registration number ISRCTN65855590.