A novel linker-immunodominant site (LIS) vaccine targeting the SARS-CoV-2 spike protein protects against severe COVID-19 in Syrian hamsters

Zhang, Bao-Zhong; Wang, Xiaolei; Yuan, Shuofeng; Li, Wenjun; Dou, Ying; Poon, Vincent Kwok-Man; Chan, Chris Chung-Sing; Cai, Jian-Piao; Chik, Kenn KaHeng; Tang, Kaiming; Chan, Chris Chun-Yiu; Hu, Ye-Fan; Hu, Jing-Chu; Badea, Smaranda Ruxandra; Gong, Hua-Rui; Lin, Xuansheng; Chu, Hin; Li, Xuechen; To, Kelvin Kai-Wang; Liu, Li; Chen, Zhiwei; Hung, Ivan Fan-Ngai; Yuen, Kwok Yung; Chan, Jasper Fuk-Woo; Huang, Jian-Dong

The Coronavirus Disease 2019 (COVID-19) pandemic is unlikely to abate until sufficient herd immunity is built up by either natural infection or vaccination. We previously identified ten linear immunodominant sites on the SARS-CoV-2 spike protein of which four are located within the RBD. Therefore, we designed two linkerimmunodominant site (LIS) vaccine candidates which are composed of four immunodominant sites within the RBD (RBD-ID) or all the 10 immunodominant sites within the whole spike (S-ID). They were administered by subcutaneous injection and were tested for immunogenicity and in vivo protective efficacy in a hamster model for COVID-19. We showed that the S-ID vaccine induced significantly better neutralizing antibody response than RBD-ID and alum control. As expected, hamsters vaccinated by S-ID had significantly less body weight loss, lung viral load, and histopathological changes of pneumonia. The S-ID has the potential to be an effective vaccine for protection against COVID-19.