An RBD-Fc mucosal vaccine provides variant-proof protection against SARS-CoV-2 in mice and hamsters

作者：Yanjun Zhang, Yan Wu, Meng‐Qian Zhang, Haiyue Rao, Zhaoyong Zhang, Xiaobo He, Yiwen Liang, Raoqing Guo, Yaochang Yuan, Jing Sun, Helen M. E. Duyvesteyn, Elizabeth E. Fry, David I. Stuart, Jingxian Zhao, Jingxian Zhao, XiaoYan Pan, Shulin Liu, Jiandong Huo, Jincun Zhao, Jiandong Huo · 发表于：npj Vaccines · 年份：2025 · DOI：10.1038/s41541-025-01155-4 · 被引用次数：11 · 研究领域：SARS-CoV-2 and COVID-19 Research、Animal Virus Infections Studies、Viral gastroenteritis research and epidemiology

Current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) vaccines are effective against severe disease and death, but do not prevent viral infections, probably due to the limited mucosal immunity induced by intramuscular administration of the vaccine. Fusion of SARS-CoV-2 subunit immunogens with a human IgG Fc backbone can be used as a mucosal vaccine but its effectiveness in delivery in animal models, and its immunogenicity and the vaccine-induced protection against viral infections requires further studies. Here we investigate a bivalent RBD-Fc vaccine that includes the spike receptor-binding domains (RBDs) of the ancestral and BQ.1.1 variant of SARS-CoV-2. Ex vivo fluorescent imaging demonstrates that this vaccine can be effectively delivered to the lungs of mice through intranasal administration, with enhancement of retention in the nasal cavity and lung parenchyma. In mice, the vaccine elicited potent and broad-spectrum antibody responses against different variants including KP.3 which could persist for at least 3 months after booster. Importantly, it was able to induce RBD-specific mucosal IgA responses. Further, heterologous intranasal immunisation with adeno-vectored Chadv1 and RBD-Fc elicited both potent neutralising antibody and T cell responses. Immunised BALB/c and K18-hACE2-transgenic mice were also protected against viral challenge of XBB.1 and viral transmission was effectively limited in hamsters through intranasal immunisation. This work thus demo...