Comparative analysis of SARS-CoV-2 neutralization titers reveals consistency between human and animal model serum and across assays.

The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) requires ongoing monitoring to judge the ability of newly arising variants to escape the immune response. A surveillance system necessitates an understanding of differences in neutralization titers measured in different assays and using human and animal serum samples. We compared 18 datasets generated using human, hamster, and mouse serum and six different neutralization assays. Datasets using animal model serum samples showed higher titer magnitudes than datasets using human serum samples in this comparison. Fold change in neutralization of variants compared to ancestral SARS-CoV-2, immunodominance patterns, and antigenic maps were similar among serum samples and assays. Most assays yielded consistent results, except for differences in fold change in cytopathic effect assays. Hamster serum samples were a consistent surrogate for human first-infection serum samples. These results inform the transition of surveillance of SARS-CoV-2 antigenic variation from dependence on human first-infection serum samples to the utilization of serum samples from animal models. Editor's summary: The gold standard for determining whether a SARS-CoV-2 variant can escape neutralizing antibody responses relies on samples collected from a human during a first exposure with a known viral variant. However, as our SARS-CoV-2 immunological history becomes more complex as a consequence of vaccination and infection, these first-infection samples are going to become increasingly difficult to acquire. This leaves animal models as potentially our best strategy to evaluate immune escape by SARS-CoV-2 variants. But how do serum samples collected from animals, such as mice and hamsters, compare with serum from humans? To answer this question, Mühlemann et al. comprehensively evaluated neutralizing antibody titers against SARS-CoV-2 variants of concern across three species and six neutralization assays, resulting in a comparison of 18 datasets. The authors found that both mice and hamsters elicited neutralizing antibody responses consistent with what was observed in humans, although with limited data for mice, suggesting that neutralizing antibody titers from animal models may be sufficient for ongoing surveillance efforts. —Courtney Malo [ABSTRACT FROM AUTHOR]