Feline Coronavirus Infection of Domestic Cats Causes Development of Cross-Reactive Antibodies to SARS-CoV-2 Receptor Binding Domain

Yamamoto, J. K.; Edison, L. K.; Rowe-Haas, D. K.; Takano, T.; Glior, C.; Crews, C. D.; Tuanyok, A.; Arukha, A. P.; Shiomitsu, S.; Walden, H. D. S.; Hohdatsu, T.; Tompkins, S. M.; Morris, J. G.; Sahay, B.; Kariyawasam, S.

doi:10.1101/2022.11.23.517619

bioRxiv · 10.1101/2022.11.23.517619

Feline Coronavirus Infection of Domestic Cats Causes Development of Cross-Reactive Antibodies to SARS-CoV-2 Receptor Binding Domain

Yamamoto, J. K.·Edison, L. K.·Rowe-Haas, D. K.·Takano, T.·Glior, C.·Crews, C. D.·Tuanyok, A.·Arukha, A. P.·Shiomitsu, S.·Walden, H. D. S.·Hohdatsu, T.·Tompkins, S. M.·Morris, J. G.·Sahay, B.·Kariyawasam, S.

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Abstract

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, FCoV2) demonstrated amino acid sequence identity of 11.5% and similarity of 31.8% with FCoV1 RBD, as well as 12.2% identity and 36.5% similarity for FCoV2 RBD. The sera from all three toms and three mated queens cross-reacted with SCoV2 RBD and reacted with FCoV1 RBD and FCoV2 spike-2, nucleocapsid, and membrane proteins of FCoV2 whole-virus, but not with FCoV2 RBD. Additionally, the plasma from all six FCoV2-inoculated laboratory cats reacted with FCoV2 and SCoV2 RBDs, but not with FCoV1 RBD. In another study, eight group-housed laboratory cats from a different lineage 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 of the feline cells, demonstrating their close structural conformations essential as vaccine immunogens. Furthermore, such cross-reactivity to SCoV2 RBD was also detected by the peripheral blood mononuclear cells of both transient and chronically FCoV1-infected cats. Overall, the cross-reactivity with SCoV2 RBD by the sera from both serotypes of FCoV-infected cats also suggests that the cross-reactive epitope(s) on FCoV1 and FCoV2 RBDs may be similar to those of SCoV2 RBD and provides essential insights to developing a pan-CoV vaccine. Author SummaryTo date, there are no reports on the sera from feline coronavirus (FCoV)-infected cats cross-reacting with either SARS-CoV-1 or SARS-CoV2 (SCoV2) receptor binding domains (RBDs). This report describes the presence of cross-reactive antibodies to SCoV2 RBD in the sera of FCoV-infected laboratory cats, even though SCoV2 RBD and each FCoV serotype (FCoV1, FCoV2) RBD had minimal sequence similarity. However, this observation of serum cross-reactivity to SCoV2 RBD was confirmed by more stringent antibody-based assays and viral assays. Furthermore, both serotypes of FCoV-infected cats, including FCoV1-infected pet cats, produced the cross-reactive antibodies, and such cross-reactivity to SCoV2 RBD was also detected, most likely, by the T cells in peripheral blood mononuclear cells of both transient and chronically FCoV1-infected cats. Since SCoV2 RBD is essential component for current vaccines against COVID-19 disease, our findings should provide essential insights to developing a pan-coronavirus vaccine that induces full-scale immunity to completely prevent SCoV2 infection in humans and pet animals.

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Yamamoto, J. K., Edison, L. K., Rowe-Haas, D. K., Takano, T., Glior, C., Crews, C. D., Tuanyok, A., Arukha, A. P., Shiomitsu, S., Walden, H. D. S., Hohdatsu, T., Tompkins, S. M., Morris, J. G., Sahay, B., Kariyawasam, S.. 2022-11-24. Feline Coronavirus Infection of Domestic Cats Causes Development of Cross-Reactive Antibodies to SARS-CoV-2 Receptor Binding Domain. https://doi.org/10.1101/2022.11.23.517619

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