The utility of human challenge studies in vaccine development: lessons learned from cholera

Abstract

Experiments in which virulent infectious organisms are administered to healthy adult volunteers with the intent to deliberately induce infection have been practiced for centuries. Many useful applications have developed from these experiments such as the provision of evidence of microbial pathogenicity and the identification of key virulence factors. Challenge studies have also played an important role in the evaluation of preliminary efficacy of potential vaccine candidates. Over the past 40 years, these experimental human challenge studies have found particular utility with regards to the development of both living and nonliving attenuated cholera vaccines. This review highlights some of the important contributions made by these challenge studies to cholera vaccine research.

Tools for Assessing the Protective Efficacy of TB Vaccines in Humans: in vitro Mycobacterial Growth Inhibition Predicts Outcome of in vivo Mycobacterial Infection

“…The studies involving human participants were reviewed and approved by the relevant ethics committees as follows: Study 1 was approved by Oxfordshire Research Ethics Committee A (REC reference 07/Q1604/3). Study 2 (NCT01194180) was approved by the Medicines and Healthcare Products Regulatory Agency (EudraCT 010-018425- 19) and the Berkshire Research Ethics Committee (REC reference 10/H0505/31). The volunteers provided their written informed consent to participate in this study.…”

“…While deliberate infection models are in use for other infectious pathogens (16)(17)(18)(19), it is not ethically viable to infect humans with virulent M.tb. We have previously developed and described an in vivo human challenge model using intradermal Mycobacterium bovis BCG vaccination as a surrogate (20)(21)(22).…”

A framework for Controlled Human Infection Model (CHIM) studies in Malawi: Report of a Wellcome Trust workshop on CHIM in Low Income Countries held in Blantyre, Malawi

“…CHIM have played a pivotal role in the development of vaccines against enteric diseases including the cholera vaccine Dukoral® and typhoid vaccine Ty21a (Vivotif®) 11 , 12 . Additionally, in 2016, a live, oral, cholera vaccine (Vaxchora®) was the first vaccine where CHIM provided the primary evidence of effectiveness required for licensure by the FDA for use in the US.…”

Will Systems Biology Deliver Its Promise and Contribute to the Development of New or Improved Vaccines?

“…Beyond the traditional clinical trial for a new vaccine, coming into the picture is a renewed interest in challenge studies. These studies employ controlled human infection models, where volunteers are deliberately infected with live pathogens, such as Plasmodium falciparum , Salmonella typhi , and Vibrio cholerae , that can be arrested with drugs before too much damage is done, or influenza where healthy nonvulnerable subjects can be studied (Killingley et al 2011; Shirley and McArthur 2011; Seder et al 2013; Darton et al 2014). These types of studies are especially important for pathogens that are difficult to study because of a lack of analogous animal models for either infection or vaccination.…”