A novel DNA and protein combination COVID-19 vaccine formulation provides full protection against SARS-CoV-2 in rhesus macaques

Yuzhong Li; Yanwei Bi; Hongjian Xiao; Yueting Yao; Xiaojuan Liu; Zhengrong Hu; Jinmei Duan; Yaoyun Yang; Zhihua Li; Yadong Li; Heng Zhang; Chen Ding; Jianbo Yang; Haiwei Li; Zhanlong He; Longding Liu; Guangnan Hu; Shuying Liu; Yanchun Che; Shixia Wang; Qihan Li; Shan Lu; Wei Cun

doi:10.1080/22221751.2021.1887767

A novel DNA and protein combination COVID-19 vaccine formulation provides full protection against SARS-CoV-2 in rhesus macaques

Emerg Microbes Infect. 2021 Dec;10(1):342-355. doi: 10.1080/22221751.2021.1887767.

Authors

Yuzhong Li¹, Yanwei Bi¹, Hongjian Xiao¹, Yueting Yao¹, Xiaojuan Liu¹, Zhengrong Hu¹, Jinmei Duan¹, Yaoyun Yang¹, Zhihua Li¹, Yadong Li¹, Heng Zhang¹, Chen Ding¹, Jianbo Yang¹, Haiwei Li¹, Zhanlong He¹, Longding Liu¹, Guangnan Hu², Shuying Liu³, Yanchun Che¹, Shixia Wang², Qihan Li¹, Shan Lu², Wei Cun¹

Affiliations

¹ Institute of Medical Biology, Chinese Academy of Medical Sciences & Peking Union Medical College, Kunming, People's Republic of China.
² Department of Medicine, University of Massachusetts Medical School, Worcester, MA, USA.
³ SYL-Consulting, Thousand Oaks, CA, USA.

Abstract

The current study aims to develop a safe and highly immunogenic COVID-19 vaccine. The novel combination of a DNA vaccine encoding the full-length Spike (S) protein of SARS-CoV-2 and a recombinant S1 protein vaccine induced high level neutralizing antibody and T cell immune responses in both small and large animal models. More significantly, the co-delivery of DNA and protein components at the same time elicited full protection against intratracheal challenge of SARS-CoV-2 viruses in immunized rhesus macaques. As both DNA and protein vaccines have been proven safe in previous human studies, and DNA vaccines are capable of eliciting germinal center B cell development, which is critical for high-affinity memory B cell responses, the DNA and protein co-delivery vaccine approach has great potential to serve as a safe and effective approach to develop COVID-19 vaccines that provide long-term protection.

Keywords: DNA vaccine; SARS-CoV-2; non-human primate; protein vaccine; spike glycoprotein.

MeSH terms

Animals
Antibodies, Neutralizing / blood
Antibodies, Neutralizing / immunology
Antibodies, Viral / blood
Antibodies, Viral / immunology
COVID-19 / prevention & control*
COVID-19 Vaccines / immunology*
Cell Line
DNA / immunology
HEK293 Cells
Humans
Lymphocyte Count
Macaca mulatta
Mice
Mice, Inbred C57BL
Plasmids / genetics
Rabbits
Recombinant Proteins / immunology
SARS-CoV-2 / genetics
SARS-CoV-2 / immunology
Spike Glycoprotein, Coronavirus / immunology*
T-Lymphocytes / immunology
Vaccines, DNA / immunology*
Vaccines, Subunit / immunology*

Substances

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

Grants and funding

This work was supported by the Major Science and Technology Projects of Yunnan Province [grant numbers 2019ZF001, 202003AC100003, 202003AF140002]; CAMS Initiative for Innovative Medicine [grant number 2016-I2M-1-019]; Fundamental Research Funds for the Central Universities [grant number 2020HY320001].