An AAV vaccine targeting the RBD of the SARS-CoV-2 S protein induces effective neutralizing antibody titers in mice and canines

Fei Liu; Canbin Feng; Shiqi Xu; Qiang Wu; Jian Tang; Yan Chen; Ruisheng Xu; Fuliang Chen; Ni Gao; Zhengzheng Xu; Shihui Gu; Yang Lan; Haibo Zhou; Xinde Hu; Xiaojing Wang

doi:10.1016/j.vaccine.2022.01.030

An AAV vaccine targeting the RBD of the SARS-CoV-2 S protein induces effective neutralizing antibody titers in mice and canines

Vaccine. 2022 Feb 23;40(9):1208-1212. doi: 10.1016/j.vaccine.2022.01.030. Epub 2022 Jan 20.

Authors

Fei Liu¹, Canbin Feng², Shiqi Xu³, Qiang Wu⁴, Jian Tang⁵, Yan Chen², Ruisheng Xu², Fuliang Chen⁶, Ni Gao⁴, Zhengzheng Xu², Shihui Gu⁷, Yang Lan⁸, Haibo Zhou², Xinde Hu⁹, Xiaojing Wang¹⁰

Affiliations

¹ Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, Molecular Diagnosis Center, Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital, Bengbu Medical College, No. 287 Changhuai Road, Bengbu, Anhui, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China. Electronic address: liufei_2012mdf@163.com.
² Laboratory of Genome Editing and Brain Diseases, Center for Excellence in Brain Science and Intelligence Technology/Institute of Neuroscience, Chinese Academy of Science, Shanghai 200031, China.
³ CAS Key Laboratory of Molecular Virology & Immunology, Institute Pasteur of Shanghai, Chinese Academy of Sciences, University of Chinese Academy of Sciences, Shanghai, China.
⁴ Laboratory of Genome Editing and Brain Diseases, Center for Excellence in Brain Science and Intelligence Technology/Institute of Neuroscience, Chinese Academy of Science, Shanghai 200031, China; College of Life Sciences, University of Chinese Academy of Sciences, Beijing 100049, China.
⁵ State Key Laboratory of Cellular Stress Biology, Innovation Center for Cell Signaling Network, School of Life Sciences, Xiamen University, Xiamen, China.
⁶ Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, Molecular Diagnosis Center, Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital, Bengbu Medical College, No. 287 Changhuai Road, Bengbu, Anhui, China.
⁷ Department of Hand Surgery, Huashan Hospital, Fudan University, Shanghai, China.
⁸ Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, China.
⁹ Laboratory of Genome Editing and Brain Diseases, Center for Excellence in Brain Science and Intelligence Technology/Institute of Neuroscience, Chinese Academy of Science, Shanghai 200031, China. Electronic address: huxinde@ion.ac.cn.
¹⁰ Anhui Province Key Laboratory of Clinical and Preclinical Research in Respiratory Disease, Molecular Diagnosis Center, Department of Pulmonary and Critical Care Medicine, First Affiliated Hospital, Bengbu Medical College, No. 287 Changhuai Road, Bengbu, Anhui, China. Electronic address: wangxiaojing8888@163.com.

Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has resulted in catastrophic damage worldwide. Accordingly, the development of powerful, safe, easily accessible vaccines with long-term effectiveness is understood as an urgently needed countermeasure against this ongoing pandemic. Guided by this strong promise of using AAVs, we here designed, optimized, and developed an AAV-based vaccines (including AAV-RBD(max), AAV-RBD(wt), AAV-2xRBD, and AAV-3xRBD) that elicit strong immune responses against the RBD domain of the SARS-CoV-2 S protein. These immunogenic responses have proven long-lived, with near peak levels for at least six months in mice. Notably, the sera immunized with AAV-3xRBD vaccine contains powerful neutralizing antibodies against the SARS-CoV-2 pseudovirus. Further evidence proven that potent specific antibodies could also be elicited in canines after vaccination with AAV-3xRBD vaccine.

Keywords: AAV; Neutralizing antibody; SARS-CoV-2; Vaccine.

Publication types

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

MeSH terms

Animals
Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
COVID-19*
Dogs
Humans
Mice
Mice, Inbred BALB C
SARS-CoV-2
Spike Glycoprotein, Coronavirus / genetics
Viral Vaccines* / genetics

Substances

Antibodies, Neutralizing
Antibodies, Viral
COVID-19 Vaccines
Spike Glycoprotein, Coronavirus
Viral Vaccines
spike protein, SARS-CoV-2