A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants
I‐Jung Lee, Cheng‐Pu Sun, Ping‐Yi Wu, Yu-Hua Lan, I-Hsuan Wang, Wen‐Chun Liu, Joyce Pei‐Yi Yuan, Yu-Wei Chang, Sheng-Che Tseng, Szu-I Tsung, Yu‐Chi Chou, Monika Kumari, Yin-Shiou Lin, Huifeng Chen, Tsung-Yen Chen, Chih-Chao Lin, Chi-Wen Chiu, Chung-Hsuan Hsieh, Cheng-Ying Chuang, Chao‐Min Cheng, Hsiu-Ting Lin, Chen Wy, Fu‐Fei Hsu, Ming-Hsiang Hong, Chun‐Che Liao, Chih-Shin Chang, Jian‐Jong Liang, Hsiu‐Hua Ma, Ming‐Tsai Chiang, Hsin-Ni Liao, Hui‐Ying Ko, Liang-Yü Chen, Yi-An Ko, Pei‐Yu Yu, Tzu‐Jing Yang, Po-Cheng Chiang, Shang‐Te Danny Hsu, Yi‐Ling Lin, Chong-Chou Lee, Han‐Chung Wu, Mi‐Hua Tao
Abstract
BACKGROUND: With the continuous emergence of new SARS-CoV-2 variants that feature increased transmission and immune escape, there is an urgent demand for a better vaccine design that will provide broader neutralizing efficacy. METHODS: We report an mRNA-based vaccine using an engineered "hybrid" receptor binding domain (RBD) that contains all 16 point-mutations shown in the currently prevailing Omicron and Delta variants. RESULTS: A booster dose of hybrid vaccine in mice previously immunized with wild-type RBD vaccine induced high titers of broadly neutralizing antibodies against all tested SARS-CoV-2 variants of concern (VOCs). In naïve mice, hybrid vaccine generated strong Omicron-specific neutralizing antibodies as well as low but significant titers against other VOCs. Hybrid vaccine also elicited CD8+/IFN-γ+ T cell responses against a conserved T cell epitope present in wild type and all VOCs. CONCLUSIONS: These results demonstrate that inclusion of different antigenic mutations from various SARS-CoV-2 variants is a feasible approach to develop cross-protective vaccines.