Department of Comparative, Diagnostic, and Population Medicine (CDPM), College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA.
Laboratories of Comparative Immunology & Virology for Companion Animals, CDPM, College of Veterinary Medicine, University of Florida, Gainesville, FL 32610, USA.
Viruses. 2023 Mar 31;15(4):914. doi: 10.3390/v15040914.
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.
当我们的无菌实验室公猫与感染猫冠状病毒（FCoV）的母猫交配时，出人意料地产生了针对人类严重急性呼吸综合征冠状病毒 2 型（SCoV2）受体结合域（RBD）的高交叉反应性抗体，因此启动了本研究。对 SCoV2 武汉 RBD 以及 FCoV 1 型和 2 型（FCoV1 和 FCoV2）的 4 个株系的多序列比对分析表明，FCoV1 RBD 的氨基酸序列同一性为 11.5%，相似性为 31.8%（FCoV2 RBD 的同一性为 12.2%，相似性为 36.5%）。公猫和母猫的血清与 SCoV2 RBD 发生交叉反应，并与 FCoV1 RBD 和 FCoV2 刺突-2、核衣壳和膜蛋白发生反应，但与 FCoV2 RBD 不发生反应。因此，这些母猫和公猫感染了 FCoV1。此外，6 只接种 FCoV2 的猫的血浆与 FCoV2 和 SCoV2 RBD 发生反应，但与 FCoV1 RBD 不发生反应。因此，FCoV1 感染猫和 FCoV2 感染猫的血清均产生了针对 SCoV2 RBD 的交叉反应性抗体。此外，15 个月后，8 只群居的实验室猫的血清对 SCoV2 RBD 具有不同程度的交叉反应性。在 FCoV1 阳性的群居宠物猫中也观察到了这种交叉反应性。高非毒性剂量的 SCoV2 RBD 和低 60-400 倍剂量的 FCoV2 RBD 阻断了体外 FCoV2 的感染，表明它们具有作为疫苗免疫原的紧密结构构象。值得注意的是，FCoV1 感染猫的外周血单核细胞也检测到了这种交叉反应性。人类和猫 RBD 之间的广泛交叉反应性为开发泛冠状病毒疫苗提供了重要的见解。
