Sequential immunizations confer cross-protection against variants of SARS-CoV-2, including Omicron in Rhesus macaques

Wei Deng; Qi Lv; Fengdi Li; Jiangning Liu; Zhiqi Song; Feifei Qi; Qiang Wei; Pin Yu; Mingya Liu; Shasha Zhou; Yaqing Zhang; Hong Gao; Nan Wang; Zijing Jia; Kai Gao; Jiayi Liu; Chong Xiao; Haiquan Shang; Xiangxi Wang; Linlin Bao; Chuan Qin

doi:10.1038/s41392-022-00979-z

Sequential immunizations confer cross-protection against variants of SARS-CoV-2, including Omicron in Rhesus macaques

Signal Transduct Target Ther. 2022 Apr 18;7(1):124. doi: 10.1038/s41392-022-00979-z.

Authors

Wei Deng^#^{1

2}, Qi Lv^#^{1

2}, Fengdi Li^#^{1

2}, Jiangning Liu^#^{1

2}, Zhiqi Song^#^{1

2}, Feifei Qi^{1

2}, Qiang Wei^{1

2}, Pin Yu^{1

2}, Mingya Liu^{1

2}, Shasha Zhou^{1

2}, Yaqing Zhang^{1

2}, Hong Gao^{1

2}, Nan Wang³, Zijing Jia³, Kai Gao^{1

2}, Jiayi Liu⁴, Chong Xiao^{1

2}, Haiquan Shang^{1

2}, Xiangxi Wang⁵, Linlin Bao^{6

7}, Chuan Qin^{8

9}

Affiliations

¹ Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, NHC Key Laboratory of Human Disease Comparative Medicine, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, 100021, China.
² National Center of Technology Innovation for Animal Model, Beijing, China.
³ CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China.
⁴ Department of Radiology, Beijing Anzhen Hospital, Capital Medical University, Beijing, China.
⁵ CAS Key Laboratory of Infection and Immunity, National Laboratory of Macromolecules, Institute of Biophysics, Chinese Academy of Sciences, Beijing, 100101, China. xiangxi@ibp.ac.cn.
⁶ Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, NHC Key Laboratory of Human Disease Comparative Medicine, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, 100021, China. bllmsl@aliyun.com.
⁷ National Center of Technology Innovation for Animal Model, Beijing, China. bllmsl@aliyun.com.
⁸ Beijing Key Laboratory for Animal Models of Emerging and Remerging Infectious Diseases, NHC Key Laboratory of Human Disease Comparative Medicine, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences and Comparative Medicine Center, Peking Union Medical College, Beijing, 100021, China. qinchuan@pumc.edu.cn.
⁹ National Center of Technology Innovation for Animal Model, Beijing, China. qinchuan@pumc.edu.cn.

^# Contributed equally.

Abstract

Variants of concern (VOCs) like Delta and Omicron, harbor a high number of mutations, which aid these viruses in escaping a majority of known SARS-CoV-2 neutralizing antibodies (NAbs). In this study, Rhesus macaques immunized with 2-dose inactivated vaccines (Coronavac) were boosted with an additional dose of homologous vaccine or an RBD-subunit vaccine, or a bivalent inactivated vaccine (Beta and Delta) to determine the effectiveness of sequential immunization. The booster vaccination significantly enhanced the duration and levels of neutralizing antibody titers against wild-type, Beta, Delta, and Omicron. Animals administered with an indicated booster dose and subsequently challenged with Delta or Omicron variants showed markedly reduced viral loads and improved histopathological profiles compared to control animals, indicating that sequential immunization could protect primates against Omicron. These results suggest that sequential immunization of inactivated vaccines or polyvalent vaccines could be a potentially effective countermeasure against newly emerging variants.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Neutralizing
Antibodies, Viral
COVID-19* / prevention & control
Macaca mulatta
SARS-CoV-2* / genetics
Vaccination
Vaccines, Inactivated / genetics

Substances

Antibodies, Neutralizing
Antibodies, Viral
Vaccines, Inactivated

Supplementary concepts

SARS-CoV-2 variants