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

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

doi:10.1080/22221751.2021.1887767

Abstract

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.

Highlights

The COVID-19 pandemic has caused over 100 million cases of the novel coronavirus and over 22 million deaths globally
Spike protein (S) of SARS-CoV-2 was selected as the antigen for this COVID-19 vaccine study based on our previous work on a DNA vaccine against the SARS virus more than 15 years ago [40] and recent literature regarding COVID-19 vaccine studies [6, 8,9,10]
The only difference between the expressed sequences and the natural S protein is that wild type S gene nucleic acid sequences (-wt) are replaced with the codon optimized S gene sequences (-opt) using the approach we previously reported for SARS and influenza DNA vaccines [40, 42]

Summary

Introduction

The COVID-19 pandemic has caused over 100 million cases of the novel coronavirus and over 22 million deaths globally. Several leading candidates are using novel vaccine platforms such as viral vector [3,4,5,6,7] or mRNA [812] approaches, which showed exciting levels of protection efficacy in reports from completed Phase III studies [13, 14]. They have received or are expected to receive Emergency Use Authorization (EUA) by respective regulatory agencies. Additional novel approaches are needed to further enrich the COVID-19 vaccine pipeline to both provide a second generation of practical vaccines and learn more about the unique contributions of different technology platforms

Methods

Results

Conclusion