Journal of Biomedical Science (Jul 2022)

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,
  • Hui-Feng Chen,
  • Tsung-Yen Chen,
  • Chih-Chao Lin,
  • Chi-Wen Chiu,
  • Chung-Hsuan Hsieh,
  • Cheng-Ying Chuang,
  • Chao-Min Cheng,
  • Hsiu-Ting Lin,
  • Wan-Yu Chen,
  • 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-Yu Chen,
  • Yi-An Ko,
  • Pei-Yu Yu,
  • Tzu-Jing Yang,
  • Po-Cheng Chiang,
  • Shang-Te Hsu,
  • Yi-Ling Lin,
  • Chong-Chou Lee,
  • Han-Chung Wu,
  • Mi-Hua Tao

DOI
https://doi.org/10.1186/s12929-022-00830-1
Journal volume & issue
Vol. 29, no. 1
pp. 1 – 13

Abstract

Read online

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.

Keywords