Rising to the Strep A human challenge: Investigating protection against experimental human infection to predict vaccine efficacy.

There is a compelling case for vaccine development targeting the immense global burden of disease caused by the human-restricted pathogen Streptococcus pyogenes (‘group A strep’ or ‘StrepA’). Despite widespread enthusiasm for the mission, developers are acutely aware that the StrepA vaccine ecosystem remains fragile. As highlighted in the 2018 WHO StrepA vaccine roadmap, the lack of standardised immunoassays and a correlate of protection are key impediments to development. Our team of StrepA research leaders have established several cohort studies and the world’s only StrepA human infection study, which have changed the vaccine development landscape and advanced understanding of human immune responses to StrepA. Here, we will run human infection studies in Australia and The Gambia, tuned to demonstrate protection, with samples tested in a curated set of standardised immunoassays to define humoral and cellular correlates of protection. The overall design and analysis will be guided by leading infectious diseases data scientists and informed by an ‘Industry and Innovation’ advisory group. This program will deliver standardised immunoassays, directly assess protection in human infection studies, and use powerful data analytics and exploratory immunology techniques to realise the potential of correlates of protection to accelerate StrepA vaccines towards trials, licensure, and use.