Intranasal immunization with recombinant Vaccinia virus encoding trimeric SARS-CoV-2 spike receptor-binding domain induces neutralizing antibody

Xiaoling Cao; Junjie Zai; Qingzhen Zhao; Lilan Xie; Yaoming Li

doi:10.1016/j.vaccine.2022.08.054

Intranasal immunization with recombinant Vaccinia virus encoding trimeric SARS-CoV-2 spike receptor-binding domain induces neutralizing antibody

Vaccine. 2022 Sep 22;40(40):5757-5763. doi: 10.1016/j.vaccine.2022.08.054. Epub 2022 Aug 29.

Authors

Xiaoling Cao¹, Junjie Zai², Qingzhen Zhao³, Lilan Xie⁴, Yaoming Li⁵

Affiliations

¹ College of Life Science and Technology, Wuhan University of Bioengineering, Wuhan, China.
² Immunology Innovation Team, School of Medicine, Ningbo University, Ningbo, China. Electronic address: zaijunjie@nbu.edu.cn.
³ The Affiliated Hospital of Medical School, Ningbo University, Ningbo, China. Electronic address: fyzhaoqingzhen@nbu.edu.cn.
⁴ College of Life Science and Technology, Wuhan University of Bioengineering, Wuhan, China; Hubei Engineering Research Center of Viral Vector, Applied Biotechnology Research Center, Wuhan University of Bioengineering, Wuhan, China. Electronic address: xielilan@webmail.hzau.edu.cn.
⁵ College of Life Science and Technology, Wuhan University of Bioengineering, Wuhan, China; Hubei Engineering Research Center of Viral Vector, Applied Biotechnology Research Center, Wuhan University of Bioengineering, Wuhan, China. Electronic address: limeming@webmail.hzau.edu.cn.

Abstract

Respiratory transmission of SARS-CoV-2 is considered to be the major dissemination route for COVID-19, therefore, mucosal immune responses have great importance in preventing SARS-CoV-2 from infection. In this study, we constructed a recombinant Vaccinia virus (VV) harboring trimeric receptor-binding domain (RBD) of SARS-CoV-2 spike protein (VV_-tRBD), and evaluated the immune responses towards RBD following intranasal immunization against mice and rabbits. In BALB/c mice, intranasal immunization with VV_-tRBD elicited robust humoral and cellular immune responses, with high-level of both neutralizing IgG and IgA in sera against SARS-CoV-2 psudoviruses, and a number of RBD-specific IFN-γ-secreting lymphocytes. Sera from immunized rabbits also exhibited neutralization effects. Notably, RBD-specific secretory IgA (sIgA) in both nasal washes and bronchoalveolar lavage fluids (BALs) were detectable and showed substantial neutralization activities. Collectively, a recombinant VV expressing trimeric RBD confers robust systemic immune response and mucosal neutralizing antibodies, thus warranting further exploration as a mucosal vaccine.

Keywords: Neutralization; SARS-CoV-2; Trimeric RBD; Vaccinia virus.

Publication types

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

MeSH terms

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

Substances

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