Phase 2 Shigella Vaccine and Challenge

Summary

This is a trial to evaluate the safety, reactogenicity, immunogenicity and efficacy of a 10\^6 cfu dose of an oral live-attenuated S. sonnei vaccine candidate, WRSs2, in up to 120 healthy males and non-pregnant females aged 18-49, inclusive. This is a two-phase study, an outpatient WRSs2 vaccination phase and an inpatient S. sonnei 53G challenge phase. After the initiation of the study, two participants had Grade 3 diarrhea and/or vomiting in the days following vaccination. The vaccination dose was reduced to 5X10\^5, enrollment was changed to 2 arms and randomized 2:1 (vaccine: placebo). Participants with morbid obesity were excluded and weight loss medications prohibited. The Primary Objective of this study is to estimate combined vaccine efficacy of 2 doses of WRSs2 (10\^6 cfu or 5X10\^5 cfu) in preventing shigellosis, following challenge with S. sonnei strain 53G.

Timeline

Start

2022-10-12

Primary completion

2024-03-11

Completion

2024-07-08

Outcome

Met primary endpoint

paper three (9%) of 34 participants given pooled two-dose vaccine and 21 (81%) of 26 placebo recipients (vaccine efficacy 89% [95% CI 71-96]; p<0·0001). PMID 42379208 ↗

Publications

• Rouphael N, Baqar S, Dickey M, Quigley C, Pham T, Adams J, Kwatra G, Bechnak S, Smith V, Scherer EM, Graciaa DS, El-Khorazaty J, Fraser JA, Heard S, Cato K, Mejia-Galvis J, Barnoy S, Chandrasekharan L, Porter CK, Suvarnapunya AE, Venkatesan MM, Frenck RW Jr; DMID 17-0112 Study Group. Efficacy of WRSs2, a live-attenuated Shigella sonnei vaccine, against shigellosis in a controlled human infection model in the USA: a phase 2, double-blind, randomised, placebo-controlled trial. Lancet Infect Dis. 2026 Jun 30:S1473-3099(26)00224-0. doi: 10.1016/S1473-3099(26)00224-0. Online ahead of print.

Drugs

Indications