Tensions between research and public health: modelling the risks and benefits of SARS-CoV-2 vaccine field trials versus human infection challenge studies.

Heriot, G. S.; Jamrozik, E.; Selgelid, M. J.

Background: Human infection challenge studies (HICS) with SARS-CoV-2 are under consideration as a way of accelerating vaccine development. We evaluate potential vaccine research strategies under a range of epidemic conditions determined, in part, by the intensity of public health interventions. Methods: We constructed a compartmental epidemiological model incorporating public health interventions, vaccine efficacy trials and a post-trial population vaccination campaign. The model was used to estimate the duration and benefits of large-scale field trials in comparison with HICS accompanied by an expanded safety trial, and to assess the marginal risk faced by HICS participants. Results: Field trials may demonstrate vaccine efficacy more rapidly than a HICS strategy under epidemic conditions consistent with moderate mitigation policies. A HICS strategy is the only feasible option for testing vaccine efficacy under epidemic suppression, and maximises the benefits of post-trial vaccination. Less successful or absent mitigation results in minimal or no benefit from post-trial vaccination, irrespective of trial design. Conclusions: SARS-CoV-2 HICS are the optimal method of vaccine testing for populations maintained under epidemic suppression, where vaccination offers the greatest benefits to the local population.