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

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.

Control of SARS-CoV-2 infection after Spike DNA or Spike DNA+Protein co-immunization in rhesus macaques

“…Here, DNA+Protein immunization induced the most robust anti-Spike antibody responses, evident after a single vaccination, and these levels remained higher throughout the study, also consistent with previously reported in HIV/SIV vaccine studies [28][29][30][31][32][33]. During the completion of our report, Li et al [51] reported a vaccine regimen in which DNA and protein were administered simultaneously (but in separate anatomical sites). They found better protection in this group compared to DNA or protein only vaccines.…”

Boosting with heterologous vaccines effectively improves protective immune responses of the inactivated SARS-CoV-2 vaccine

“…Heterologous prime-boost strategy has been pioneered one decade ago and proved to be effective in previous studies on vaccines against emerging virus such as HIV-1 [ 25 ], influenza [ 24 ] and SARS-CoV-2 [ 26 , 27 ]. Considering the distinct properties between inactivated vaccine and other kinds of vaccines, it’s rational to investigate the impact of homologous or heterologous vaccine boosting strategy based on the current clinical applied regimen of inactivated vaccine.…”

The combined vaccination protocol of DNA/MVA expressing Zika virus structural proteins as efficient inducer of T and B cell immune responses

“…Furthermore, the use of heterologous prime/boost protocols including MVA vector have also demonstrated in human clinical trials to be able to induce good T- and B-cell responses against various pathogens as, for example, human immunodeficiency virus (HIV)-1 [ 17 , 18 ], hepatitis C virus (HCV) [ 19 ], Plasmodium falciparum (the causative agent of malaria) [ 20 ], ebolavirus (EBOV) [ 21 ], and respiratory syncytial virus (RSV) [ 22 ]. Moreover, the recent development of novel vaccine candidates against COVID-19, showed heterologous prime/boost vaccination strategies able to induce more potent T-cell and humoral immune responses and higher efficacy against SARS-CoV-2 [ 23 , 24 ], which will help to find the best-in-class vaccine candidates.…”