Cellular and Humoral Immunogenicity of a Candidate DNA Vaccine Expressing SARS-CoV-2 Spike Subunit 1

Abstract

The urgent need for effective, safe and equitably accessible vaccines to tackle the ongoing spread of COVID-19 led researchers to generate vaccine candidates targeting varieties of immunogens of SARS-CoV-2. Because of its crucial role in mediating binding and entry to host cell and its proven safety profile, the subunit 1 (S1) of the spike protein represents an attractive immunogen for vaccine development. Here, we developed and assessed the immunogenicity of a DNA vaccine encoding the SARS-CoV-2 S1. Following in vitro confirmation and characterization, the humoral and cellular immune responses of our vaccine candidate (pVAX-S1) was evaluated in BALB/c mice using two different doses, 25 µg and 50 µg. Our data showed high levels of SARS-CoV-2 specific IgG and neutralizing antibodies in mice immunized with three doses of pVAX-S1. Analysis of the induced IgG subclasses showed a Th1-polarized immune response, as demonstrated by the significant elevation of spike-specific IgG2a and IgG2b, compared to IgG1. Furthermore, we found that the immunization of mice with three doses of 50 µg of pVAX-S1 could elicit significant memory CD4+ and CD8+ T cell responses. Taken together, our data indicate that pVAX-S1 is immunogenic and safe in mice and is worthy of further preclinical and clinical evaluation.

Robust and protective immune responses induced by heterologous prime‐boost vaccination with DNA‐protein dimeric RBD vaccines for COVID‐19

“…Most reported COVID-19 DNA vaccines and candidates encode spike, S1, or RBD protein. [31][32][33] In the context of the continuous circulation of SARS-CoV-2, this study provided a new DNA vaccine candidate and a heterologous prime-boost approach with potent immunogenicity to expand the vaccine development pipeline. In this sense, this piece of work showed the privilege of DNA prime for the cellular response, better than the current protein prime.…”

Development of DNA Vaccine Candidate against SARS-CoV-2

“…Thus, the most important requirements for the anti-COVID-19 vaccines that are safeness, protectiveness, accessibility, and inexpensiveness can be achieved via DNA vaccines [ 16 ]. Studies have already demonstrated the positive outcome of the DNA vaccine of SARS-CoV-2 spike protein [ 47 , 48 ]. Interestingly, there are already several DNA vaccines approved for veterinary use including a vaccine against highly pathogenic H5N1 Influenza A virus in chicken [ 49 ], the vaccine against West Nile virus in horses, etc.…”

Improved DNA Vaccine Delivery with Needle-Free Injection Systems

“…The authors commented that NFIS delivery enhanced the immune responses in this study and that combining NFIS with EP delivery should also be investigated to determine if the combination of delivery methods would further enhance the immune response [ 55 ]. The group also tested their pVAX-S1 DNA vaccine in mice given IM with the modified Tropis ( Table 2 ), showing similar results [ 87 ].…”

“…NFIS use has also shown less intra-group variability in immune responses [ 55 , 79 ]. Both humoral and cellular immunity can be effectively induced with NFIS delivery [ 17 , 29 , 30 , 52 , 55 , 81 , 83 , 87 , 94 , 98 ], in addition to producing unique types of immune responses such as a Th1-biased response with COVID-19 vaccines [ 55 , 86 , 87 ]. Additionally, studies discussed here show that pre-clinical results can translate to clinical trial results, with ZyCoV-D as an example, where results observed in NHP were repeated in clinical trials [ 29 , 83 ].…”