Macaque-human differences in SARS-CoV-2 Spike antibody response elicited by vaccination or infection.

Non-human primates, including macaques, are considered the best animal model for studying infectious diseases that infect humans. Vaccine candidates for SARS-CoV-2 are first tested in macaques to assess immune responses prior to advancing to human trials, and macaques are also used to model the human immune response to SARS-CoV-2 infection. However, there may be differences in how macaque and human antibodies recognize the SARS-CoV-2 entry protein, Spike. Here we characterized the locations on Spike that are recognized by antibodies from vaccinated or infected macaques and humans. We also made mutations to the viral sequence and assessed how these affected antibody binding, enabling a comparison of antibody binding requirements between macaques and humans at a very precise level. We found that macaques and humans share some responses, but also recognize distinct regions of Spike. We also found that in general, antibodies from different individuals had unique responses to viral mutations, regardless of species. These results will yield a better understanding of how macaque data can be used to inform human immunity to SARS-CoV-2.