A booster dose of Delta × Omicron hybrid mRNA vaccine produced broadly neutralizing antibody against Omicron and other SARS-CoV-2 variants

  • J Biomed Sci. 2022 Jul 7;29(1):49. doi: 10.1186/s12929-022-00830-1.
I-Jung Lee  1  2 ,  Cheng-Pu Sun   #  1 ,  Ping-Yi Wu   #  1 ,  Yu-Hua Lan  1 ,  I-Hsuan Wang  1 ,  Wen-Chun Liu  3 ,  Joyce Pei-Yi Yuan  3 ,  Yu-Wei Chang  3 ,  Sheng-Che Tseng  1 ,  Szu-I Tsung  1  2 ,  Yu-Chi Chou  3 ,  Monika Kumari  4 ,  Yin-Shiou Lin  3 ,  Hui-Feng Chen  3 ,  Tsung-Yen Chen  3 ,  Chih-Chao Lin  3 ,  Chi-Wen Chiu  1  5 ,  Chung-Hsuan Hsieh  1  5 ,  Cheng-Ying Chuang  1 ,  Chao-Min Cheng  3 ,  Hsiu-Ting Lin  4 ,  Wan-Yu Chen  4 ,  Fu-Fei Hsu  3  4 ,  Ming-Hsiang Hong  3  4 ,  Chun-Che Liao  1 ,  Chih-Shin Chang  3 ,  Jian-Jong Liang  1 ,  Hsiu-Hua Ma  6 ,  Ming-Tsai Chiang  1 ,  Hsin-Ni Liao  1 ,  Hui-Ying Ko  1 ,  Liang-Yu Chen  1 ,  Yi-An Ko  3 ,  Pei-Yu Yu  7 ,  Tzu-Jing Yang  7 ,  Po-Cheng Chiang  3 ,  Shang-Te Hsu  7 ,  Yi-Ling Lin  1  3 ,  Chong-Chou Lee  3 ,  Han-Chung Wu  3  4 ,  Mi-Hua Tao  8  9  10  11
Affiliations
  • 1. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan.
  • 2. Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan.
  • 3. Biomedical Translation Research Center, Academia Sinica, Taipei, Taiwan.
  • 4. Institute of Cellular and Organismic Biology, Academia Sinica, Taipei, Taiwan.
  • 5. Department of Clinical Laboratory Science and Medical Biotechnology, National Taiwan University, Taipei, Taiwan.
  • 6. Genomics Research Center, Academia Sinica, Taipei, Taiwan.
  • 7. Institute of Biological Chemistry, Academia Sinica, Taipei, Taiwan.
  • 8. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan. [email protected].
  • 9. Graduate Institute of Microbiology, College of Medicine, National Taiwan University, Taipei, Taiwan. [email protected].
  • 10. Biomedical Translation Research Center, Academia Sinica, Taipei, Taiwan. [email protected].
  • 11. Department of Clinical Laboratory Science and Medical Biotechnology, National Taiwan University, Taipei, Taiwan. [email protected].
  • # Contributed equally.
PMID: 35799178 DOI: 10.1186/s12929-022-00830-1
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
Booster dose; COVID-19; Cross-protectivity; Hybrid vaccine; Next generation vaccine; Omicron vaccine; SARS-CoV-2; Variants of concern; mRNA vaccine.
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