Development of an invasive non-typhoidal Salmonella human challenge model

Our vision is to develop an iNTS CHIM programme that dovetails with future iNTS-vaccine efficacy studies, whilst simultaneously addressing fundamental questions on the immunological basis of susceptibility to iNTS disease. Several iNTS candidate vaccines are in development, but the epidemiology of iNTS disease is such that phase-3 trials require a large financial and time commitment before an efficacy readout is obtained. There are several instances where CHIM studies have accelerated vaccine candidates through to licensure, in particular for enteric pathogens such as Vibrio cholerae and Salmonella Typhi. We contend that a safe, reproducible, and well-designed CHIM - with clinically meaningful endpoints - will allow the field to build upon insights from animal models and could have an important role in accelerating vaccine development for iNTS. We will work closely with vaccine developers and regulators to identify a pathway for iNTS vaccine assessment in a CHIM. In particular, we envisage that phase-2 studies could include a CHIM to generate preliminary efficacy-indicating estimates and yield data that would otherwise be difficult to capture in phase 3 efficacy studies (e.g. stool shedding, transmission studies, longitudinal immune response to vaccination and challenge).