Adaptive immune determinants of viral clearance and protection in mouse models of SARS-CoV-2

Abstract

Description In a mouse model, protective immunity to SARS-CoV-2 following vaccination or recovery is primarily mediated by the antibody response. The importance of SARS-CoV-2 antibodies SARS-CoV-2 vaccines protect against infection, but the relative importance of individual components of the adaptive immune system in promoting viral clearance and conferring protection is not well defined. Israelow et al. used mice expressing the ACE2 receptor in the respiratory tract to determine which cellular and humoral effectors of the adaptive immune response are required for SARS-CoV-2 clearance during primary infection and for protection after vaccination or convalescence. In the context of primary infection, the adaptive immune response was essential for viral clearance, and either the cellular or humoral arms could promote viral clearance and confer protection. Protective immunity to SARS-CoV-2 after vaccination or reinfection of convalescent mice was dominated by the humoral response. These findings highlight the importance of antibodies generated by COVID-19 vaccination. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused more than 160 million infections and more than 3 million deaths worldwide. Although effective vaccines are currently being deployed, the adaptive immune determinants that promote viral clearance and confer protection remain poorly defined. Using mouse models of SARS-CoV-2, we demonstrate that both humoral and cellular adaptive immunity contribute to viral clearance in the setting of primary infection. Furthermore, we find that either convalescent mice or mice that receive mRNA vaccination are protected from both homologous infection and infection with a variant of concern, B.1.351. In addition, we find that this protection is largely mediated by antibody response and not cellular immunity. These results highlight the in vivo protective capacity of antibodies generated to both vaccine and natural infection.