Background: A newly established human infection model of Streptococcus pyogenes pharyngitis cements the role of experimental human infection as part of S. pyogenes science and vaccine development. Despite over 25 vaccine candidates in development, none has been tested for efficacy in humans for more than 40 years. In the absence of a major vaccine development impetus, and funding to support very large, long, complex and expensive clinical trials, human challenge trials represent attractive approaches to accrue pivotal efficacy data for S. pyogenes vaccines.
Methods: We present the use-case for experimental human infection in S. pyogenes vaccine development and present the protocol for a blinded placebo-controlled randomised human challenge trial to assess novel S. pyogenes vaccines. The primary objective is to evaluate the relative protective effect, safety, and tolerability of an investigational vaccine versus placebo in a healthy adult emm75 S. pyogenes challenge model.
Results: Carefully screened healthy, non-pregnant adult volunteers will receive the vaccine or placebo 4-8 weeks before admission to a clinical trials facility, where the emm75 S. pyogenes human challenge strain will be applied to the pharynx. Considering the lower confidence interval attack rate from the dose-finding trial, a Fisher’s exact test (α = 0.05) with 90% power will detect an 80% protective effect with 22 participants/group. Participants remain inpatients until day 5 post-challenge, with frequent clinical and microbiological monitoring for pharyngitis and all will receive antibiotics before discharge, and 12-months follow-up.
Conclusion: This proof-of-concept trial will provide much needed human data to propel vaccine development efforts.