Possible Cross-Reactivity of Feline and White-Tailed Deer Antibodies against the SARS-CoV-2 Receptor Binding Domain

• Published in: Journal of virology 2022-04, Vol.96 (8), p.e0025022
• Main Authors: Hancock, Trevor J, Hickman, Peyton, Kazerooni, Niloo, Kennedy, Melissa, Kania, Stephen A, Dennis, Michelle, Szafranski, Nicole, Gerhold, Richard, Su, Chunlei, Masi, Tom, Smith, Stephen, Sparer, Tim E
• Format: Article
• Language: English
• Subjects: Animals; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Cats - virology; COVID-19 - diagnosis; COVID-19 - veterinary; Cross Reactions - immunology; Deer - virology; Pathogenesis and Immunity; SARS-CoV-2; Severe acute respiratory syndrome-related coronavirus - immunology; Spike Glycoprotein, Coronavirus - metabolism; Viral Zoonoses - diagnosis; Viral Zoonoses - virology; Virology
• ISSN: 0022-538X; 1098-5514; 1098-5514
• DOI: 10.1128/jvi.00250-22

In late 2019, a novel coronavirus began circulating within humans in central China. It was designated SARS-CoV-2 because of its genetic similarities to the 2003 SARS coronavirus (SARS-CoV). Now that SARS-CoV-2 has spread worldwide, there is a risk of it establishing new animal reservoirs and recombination with native circulating coronaviruses. To screen local animal populations in the United States for exposure to SARS-like coronaviruses, we developed a serological assay using the receptor binding domain (RBD) from SARS-CoV-2. SARS-CoV-2's RBD is antigenically distinct from common human and animal coronaviruses, allowing us to identify animals previously infected with SARS-CoV or SARS-CoV-2. Using an indirect enzyme-linked immunosorbent assay (ELISA) for SARS-CoV-2's RBD, we screened serum from wild and domestic animals for the presence of antibodies against SARS-CoV-2's RBD. Surprisingly prepandemic feline serum samples submitted to the University of Tennessee Veterinary Hospital were ∼50% positive for anti-SARS RBD antibodies. Some of these samples were serologically negative for feline coronavirus (FCoV), raising the question of the etiological agent generating anti-SARS-CoV-2 RBD cross-reactivity. We also identified several white-tailed deer from South Carolina with anti-SARS-CoV-2 antibodies. These results are intriguing, as cross-reactive antibodies toward SARS-CoV-2 RBD have not been reported to date. The etiological agent responsible for seropositivity was not readily apparent, but finding seropositive cats prior to the current SARS-CoV-2 pandemic highlights our lack of information about circulating coronaviruses in other species. We report cross-reactive antibodies from prepandemic cats and postpandemic South Carolina white-tailed deer that are specific for that SARS-CoV RBD. There are several potential explanations for this cross-reactivity, each with important implications to coronavirus disease surveillance. Perhaps the most intriguing possibility is the existence and transmission of an etiological agent (such as another coronavirus) with similarity to SARS-CoV-2's RBD region. However, we lack conclusive evidence of prepandemic transmission of a SARS-like virus. Our findings provide impetus for the adoption of a One Health Initiative focusing on infectious disease surveillance of multiple animal species to predict the next zoonotic transmission to humans and future pandemics.