Immunologic Signatures of SARS-CoV-2 Vaccination and Disease

ABSTRACT The development of a SARS-CoV-2 vaccine may be critical to ending the COVID-19 pandemic. However, a critical gap in knowledge is the lack of understanding of correlates of SARS-CoV-2 immunity in humans. Our preliminary data suggest that antibodies correlate with protection following vaccination in nonhuman primates and that unique antibody functional profiles appear to predict disease outcome in natural infection in humans. Our data also point to a converging antibody profile, including both the antigen-binding domain driving neutralization and Fc-mediated effector functions driving protective immunity. Another gap in knowledge is the unknown durability of protective immunity following SARS-CoV-2 infection and vaccination in humans. Our preliminary data suggest that antibody titers may wane quickly following SARS-CoV-2 infection in humans, but larger studies and longer follow-up are needed to define the kinetics of antibody responses in convalescent individuals. Moreover, the durability of vaccine-elicited antibody responses remains to be determined. We hypothesize that both convalescent and vaccinated humans will develop the functional antibody signature that correlates with vaccine protection against SARS-CoV-2 challenge in rhesus macaques. We further hypothesize that vaccination will induce antibodies with greater durability than those induced by natural infection and that an immunologic correlate of durability can be defined. Specific Aim 1. Define the antibody profiles following SARS-CoV-2 infection or vaccination that correlate with protection. We will dissect the functional antibody responses elicited in SARS-CoV-2 infected individuals and in SARS-CoV-2 vaccinated individuals to provide insight into correlates of protection. Specific Aim 2. Define the immunologic correlates of durability of SARS-CoV-2 antibody responses following infection or vaccination. We will compare the durability of antibody responses induced in SARS- CoV-2 infected and vaccinated individuals, and we will define an immunologic correlate of durability.