Exposure history shapes SARS-CoV-2 viral dynamics in non-human primates and provides insights into correlates of protection against infection and transmission.

In the SARS-CoV-2 Omicron-variant era, the efficacy of vaccination in preventing viral replication is poorly understood and is further complicated by heterogeneous and hybrid immunity in the population. Here, we analysed by mathematical models the kinetics of both viral load and antibodies in non-human primates with different exposure histories, conferred by infection or vaccination with mono- or bi-valent vaccines. The model describes the control of viral replication by antibodies that accelerate the clearance and reduce the infectivity of viral particles, and suggests that a previous infection leads to a faster elimination of infected cells, which is not mediated by antibodies. Finally, we used the model to simulate natural infections and show that binding, neutralization and exposure history all need to be taken into account to predict risks of infection and transmission. Protection from infection could be reached at binding levels of 3 × 104 AU ml-1 for individuals who received both monovalent and bivalent vaccinations, whereas hybrid immunity (infection followed by bivalent vaccination) could provide complete protection irrespective of antibody levels. These findings highlight the importance of exposure history in shaping immune responses and suggest correlates of protection for future vaccine and monoclonal antibodies strategies. This article is part of the Theo Murphy meeting issue 'Evaluating anti-infective drugs'.