Characterisation of a GMP SARS-CoV-2 Delta variant for human challenge

SARS-CoV-2 continues to spread in spite of vaccination due in part to the high transmissibility of the prevalent delta variant. The factors predisposing to breakthrough infection are unknown and correlates of protection remain unclear.

Human challenge studies are uniquely able to control for differences in virus strain, dose and exposure to investigate these factors.

Safety in seronegative participants challenged with a D614G pre-alpha strain was recently shown and a new GMP delta challenge agent is now being manufactured.

We therefore aim - To establish an optimised controlled human infection model using a GMP SARS-CoV-2 Delta (B.1.617.2) challenge agent, characterising virological and immunological readouts therein to enable further assessment and development of COVID-19 vaccines - To identify the determinants of vaccine breakthrough infection and correlates of protection in antigenically-experienced individuals These will be achieved by challenging vaccinated individuals with Delta and optimising the attack rate by sero-screening and dose-escalation.

Using these optimised conditions, 3 groups will then be compared: - vaccinated, uninfected individuals, Delta-challenged; - vaccinated, previously-infected, Delta-challenged; and - vaccinated, uninfected, pre-Alpha-challenged.

Thus, host determinants of differential disease and virological outcome will be identified in the context of pre-existing immunity by vaccination and/or infection to define correlates and mechanisms of homologous and heterologous protection.