Long-term immune response to Omicron-specific mRNA vaccination in mice, hamsters, and nonhuman primates

Yi Wu; Namei Wu; Xiaoying Jia; Yan Wu; Xinghai Zhang; Yang Liu; Yuxia Hou; Yanqiong Shen; Entao Li; Wei Wang; Yucai Wang; Sandra Chiu

doi:10.1002/mco2.460

Long-term immune response to Omicron-specific mRNA vaccination in mice, hamsters, and nonhuman primates

MedComm (2020). 2023 Dec 15;4(6):e460. doi: 10.1002/mco2.460. eCollection 2023 Dec.

Authors

Yi Wu^{1

2}, Namei Wu¹, Xiaoying Jia³, Yan Wu³, Xinghai Zhang³, Yang Liu³, Yuxia Hou^{3

4}, Yanqiong Shen⁵, Entao Li^{1

2

6}, Wei Wang^{3

4}, Yucai Wang^{2

5}, Sandra Chiu^{1

2

6

7}

Affiliations

¹ Department of Laboratory Medicine The First Affiliated Hospital of USTC Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui P. R. China.
² Division of Life Sciences and Medicine University of Science and Technology of China Hefei Anhui P. R. China.
³ State Key Laboratory of Virology Wuhan Institute of Virology Center for Biosafety Mega-Science Chinese Academy of Sciences Wuhan P. R. China.
⁴ University of Chinese Academy of Sciences Beijing P. R. China.
⁵ RNAlfa Biotech Hefei Anhui P. R. China.
⁶ Department Key Laboratory of Anhui Province for Emerging and Reemerging Infectious Diseases Hefei Anhui P. R. China.
⁷ Core Unit of National Clinical Research Center for Laboratory Medicine Hefei Anhui P. R. China.

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron and its subvariants (such as BQ.1, XBB and the latest variants, including XBB.1.16, EG.5, and BA.2.86), as the dominant variants, currently account for almost all new infections in the world due to their high transmissibility and immune escape ability. Omicron-specific mRNA vaccines showed great potential to protect against Omicron infections. However, whether the vaccine could provide long-term protection is unknown. Toward this goal, we evaluated the immunogenicity of a preclinical Omicron (BA.1)-specific mRNA vaccine (S_Omicron-6P) in different animal models. S_Omicron-6P induced the highest levels of antibody titers at 1-2 weeks in different animals after the second dose. Even 9 months after the immunization, we observed modest neutralizing activity against Omicron subvariants in macaques. In addition, immunological memory cells can be rapidly reactivated upon stimulation. S_Omicron-6P at concentrations higher than 10 μg effectively protected hamsters from BA.1 challenge 253 days after the first immunization, which could be attributed to the reactivation of immune systems. In addition, the toxicity tests conducted in rats revealed a highly favorable biosafety profile for S_Omicron-6P, even at high dosages. Our data suggest that the Omicron-specific mRNA vaccine is highly effective and safe in animal models and provides long-term immunologic protection against SARS-CoV-2 Omicron infections.

Keywords: Omicron subvariants; SARS‐CoV‐2; antibody response; immunological memory; long‐term immune response; protective efficacy.