The efficacy and immune response to an oral live-attenuated Salmonella enterica serovar Paratyphi A vaccine, CVD 1902

Lead Research Organisation: University of Oxford
Department Name: Paediatrics

Abstract

Salmonella Paratyphi A is common cause of morbidity in South and South East Asia, causing an estimated 5 million infections annually, with the majority of this burden occurring in children. Disease control is challenged by socioeconomic barriers to better sanitation, lack of a gold standard diagnostic test and paucity of diagnostic facilities in affected areas coupled with the increase in antimicrobial resistance causing failure of empirical therapy. Vaccination provides an important approach to preventing disease.

Currently there are no licensed S. Paratyphi A vaccines. Recently, the Vi-based vaccination for S. Typhi has shown efficacy in a human challenge model of disease (Jin et al., 2017) and the WHO has recommended typhoid vaccination in high-burden areas. Data from China during the introduction of the Vi-PS typhoid vaccine showed a significant increase in Paratyphi A (Dong et al., 2010); there is real concern that paratyphoid A may assume typhoid's ecological niche hence a vaccine for S. Paratyphi A is more timely than ever.

Testing a vaccine against paratyphoid A in areas of endemicity is fraught with logistic, scientific and financial barriers. The sample size required to test a paratyphoid A vaccine in the field would be in the region of 100,000 volunteers and therefore impractical; in addition
there are no recognized correlates of protection. This makes bringing a vaccine to licensure for such a disease particularly demanding, prompting the field to look at alternative means of evaluating efficacy. Increasingly, human challenge models have been employed to allow costeffective
evaluation of vaccines within realistic timeframes and to investigate correlates of immunity.

The aim of this project is to study the efficacy and immune response to an oral vaccine for paratyphoid A, ultimately in order to protect against infection in endemic areas.

This project will meet this aim by:

i. Testing a live-attenuated oral vaccine for paratyphoid A, CVD 1902, in an experimental human challenge model of paratyphoid A to provide evidence of the protective efficacy of the vaccine

ii. Study the cellular, humoral immune and transcriptomic response to Salmonella serovars in order to identify correlates of protection and thereby further the development of the first paratyphoid vaccine

Publications

10 25 50