Production and Evaluation of Anti-Sera Against Severe Acute Respiratory Syndrome Coronavirus 2 Variants Using a Syrian Hamster Model

Abstract

The continuous emergence of novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants continues to influence the global coronavirus 2019 (COVID-19) pandemic. Even vaccinated individuals or those with prior infections may experience reinfection, depending on the immune evasion capacity of the circulating variants. Therefore, analyses of variant characteristics and immune escape are critical for informing public health policy. However, as COVID-19 has been downgraded in terms of infectious disease classification, the availability of patient sera has become increasingly limited, restricting the timely immunological analyses of emerging variants. To address this challenge, we established an antiserum production and neutralization assay system using a hamster model and demonstrated the utility of this animal serum-based approach. In this study, antisera against 10 circulating SARS-CoV-2 variants were generated in golden Syrian hamsters, and they showed high titer of humoral and neutralizing antibody using enzyme-linked immunosorbent assay and plaque reduction neutralization test (PRNT) assay. In addition, we compared serum from an unvaccinated patient (n = 1) infected with the BA.5 variant with serum from a BA.5-infected hamster (n = 1). Although the number of comparable samples was limited, the PRNT₅₀ titer patterns in serum from an unvaccinated individual infected with BA.5 and in hamster antisera were similar. These findings indicate that antisera generated in the hamster model can provide timely immunogenicity assessments of newly emerging SARS-CoV-2 variants, thereby contributing to the rapid characterization of variant immune escape and the generation of essential data for future public health preparedness.