Both Feline Coronavirus Serotypes 1 and 2 Infected Domestic Cats Develop Cross-Reactive Antibodies to SARS-CoV-2 Receptor Binding Domain: Its Implication to Pan-CoV Vaccine Development
Janet K. Yamamoto,
Lekshmi K. Edison,
Dawne K. Rowe-Haas,
Tomomi Takano,
Chen Gilor,
Chiquitha D. Crews,
Apichai Tuanyok,
Ananta P. Arukha,
Sayaka Shiomitsu,
Heather D. S. Walden,
Tsutomu Hohdatsu,
Stephen M. Tompkins,
John G. Morris Jr.,
Bikash Sahay,
Subhashinie Kariyawasam
Affiliations
Janet K. Yamamoto
Department of Comparative, Diagnostic, and Population Medicine (CDPM), College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA
Lekshmi K. Edison
Department of Comparative, Diagnostic, and Population Medicine (CDPM), College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA
Dawne K. Rowe-Haas
Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
Tomomi Takano
Laboratory of Veterinary Infectious Disease, Department of Veterinary Medicine, Kitasato University, Tokyo 108-8641, Japan
Chen Gilor
Department of Small Animal Clinical Science, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA
Chiquitha D. Crews
Department of Small Animal Clinical Science, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA
Apichai Tuanyok
Laboratories of Comparative Immunology & Virology for Companion Animals, CDPM, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA
Ananta P. Arukha
Department of Comparative, Diagnostic, and Population Medicine (CDPM), College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA
Sayaka Shiomitsu
Department of Infectious Diseases and Immunology, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA
Heather D. S. Walden
Department of Comparative, Diagnostic, and Population Medicine (CDPM), College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA
Tsutomu Hohdatsu
Laboratory of Veterinary Infectious Disease, Department of Veterinary Medicine, Kitasato University, Tokyo 108-8641, Japan
Stephen M. Tompkins
Center for Vaccines and Immunology, College of Veterinary Medicine, University of Georgia, Athens, GA 30602, USA
John G. Morris Jr.
Emerging Pathogens Institute, University of Florida, Gainesville, FL 32610, USA
Bikash Sahay
Laboratories of Comparative Immunology & Virology for Companion Animals, CDPM, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA
Subhashinie Kariyawasam
Department of Comparative, Diagnostic, and Population Medicine (CDPM), College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA
The current study was initiated when our specific-pathogen-free laboratory toms developed unexpectedly high levels of cross-reactive antibodies to human SARS-CoV-2 (SCoV2) receptor binding domain (RBD) upon mating with feline coronavirus (FCoV)-positive queens. Multi-sequence alignment analyses of SCoV2 Wuhan RBD and four strains each from FCoV serotypes 1 and 2 (FCoV1 and FCoV2) demonstrated an amino acid sequence identity of 11.5% and a similarity of 31.8% with FCoV1 RBD (12.2% identity and 36.5% similarity for FCoV2 RBD). The sera from toms and queens cross-reacted with SCoV2 RBD and reacted with FCoV1 RBD and FCoV2 spike-2, nucleocapsid, and membrane proteins, but not with FCoV2 RBD. Thus, the queens and toms were infected with FCoV1. Additionally, the plasma from six FCoV2-inoculated cats reacted with FCoV2 and SCoV2 RBDs, but not with FCoV1 RBD. Hence, the sera from both FCoV1-infected cats and FCoV2-infected cats developed cross-reactive antibodies to SCoV2 RBD. Furthermore, eight group-housed laboratory cats had a range of serum cross-reactivity to SCoV2 RBD even 15 months later. Such cross-reactivity was also observed in FCoV1-positive group-housed pet cats. The SCoV2 RBD at a high non-toxic dose and FCoV2 RBD at a 60–400-fold lower dose blocked the in vitro FCoV2 infection, demonstrating their close structural conformations essential as vaccine immunogens. Remarkably, such cross-reactivity was also detected by the peripheral blood mononuclear cells of FCoV1-infected cats. The broad cross-reactivity between human and feline RBDs provides essential insights into developing a pan-CoV vaccine.
