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

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.

Serological Survey of Retrovirus and Coronavirus Infections, including SARS-CoV-2, in Rural Stray Cats in The Netherlands, 2020–2022

“…Based on the temporal spread of the SARS-CoV-2-ELISA-positive sera, exposure of stray cats to Omicron BA.1 and consequently low cross-reactivity with the ancestral SARS-CoV-2 strain as used in the pseudo-VNT can insufficiently explain the lack of neutralizing antibodies. Cross-reactivity between antibodies induced by other coronaviruses that might infect stray cats was considered another explanation for the SARS-CoV-2-ELISA-positive results in the absence of SARS-CoV-2-neutralizing antibodies [ 50 , 84 , 85 ]. In this study, there was no association between the ELISA OD values of SARS-CoV-2 S1/RBD and FCoV S1 ( Figure S3A,B ).…”

“…In other studies, cross-reactivity between FCoV-specific antibodies and SARS-CoV-2 antigen had also been excluded in cats sampled since the SARS-CoV-2 pandemic [ 23 , 49 , 50 , 74 , 86 ]. In contrast to these studies, experimental FCoV-infected SPF cats showed cross-reactivity in a SARS-CoV-2 RBD-specific ELISA [ 85 ]. In addition, pre-pandemic sera from cats sampled in the USA tested positive in a SARS-CoV-2 RBD-specific ELISA [ 84 ].…”