Protective efficacy of pDNA vaccine candidate against SARS-CoV-2 in Syrian golden hamsters

Seasonal SARS-CoV-2 vaccination is known as an efficient way to control the COVID-19 pandemic. However, the currently approved mRNA and protein vaccines are thermally unstable and require further encapsulation and ultra-cold chain transportation and storage. Therefore, alternative platforms that can overcome this limitation are needed. pDNA has emerged as an attractive next-generation vaccine platform due to its high thermal stability. Here, we developed pDNA-based SARS-CoV-2 vaccine candidate and conducted a preclinical protective efficacy evaluation in Syrian golden hamsters. Administration of S.opt.FL pDNA vaccine was able to induce higher S-specific SARS-CoV-2 binding and neutralising antibody levels. Importantly, S-specific IgG2 which represented Th1-mediated immune responses was predominantly induced after pDNA vaccination. Besides, animal group receiving three doses induced higher neutralising antibody responses compared to animal group receiving two doses. In addition, we determined that the Th1–skewed immune response was important in conferring protection upon virus challenge. These results indicate that intramuscular delivery of S.opt.FL pDNA vaccine is safe and effective in preventing SARS-CoV-2 infection. The study shed new light on the importance of the IgG isotype for the development of SARS-CoV-2 vaccine candidates. Furthermore, our findings can be used to support further testing of several pDNA-based vaccine candidates against other pathogens.