Modified DNA vaccine confers improved humoral immune response and effective virus protection against SARS-CoV-2 delta variant

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has led to a global pandemic. New technologies have been utilized to develop several types of vaccines to prevent the spread of SARS-CoV-2 infection, including mRNA vaccines. Our group previously developed an effective DNA-based vaccine. However, emerging SARS-CoV-2 variants of concern (VOCs), such as the delta variant, have escaped mutations against vaccine-induced neutralizing antibodies. This suggests that modified vaccines accommodating VOCs need to be developed promptly. Here, we first modified the current DNA vaccine to enhance antigenicity. Compared with the parental DNA vaccine, the modified version (GP Delta-DNA vaccine) induced rapid antibody production. Next, we updated the GP Delta-DNA vaccine to spike glycoprotein of the delta variant (GP Delta-delta DNA vaccine) and compared the efficacy of different injection routes, namely intramuscular injection using a needle and syringe and intradermal injection using a pyro-drive jet injector (PJI). We found that the levels of neutralizing antibodies induced by the intradermal PJI injection were higher than intramuscular injection. Furthermore, the PJI-injected GP Delta-delta DNA vaccine effectively protected human angiotensin-converting enzyme 2 (hACE2) knock-in mice from delta-variant infection. These results indicate that the improved DNA vaccine was effective against emerging VOCs and was a potential DNA vaccine platform for future VOCs or global pandemics.

Automated summary

COVID-19, caused by SARS-CoV-2, has become a global pandemic. New technologies, including mRNA vaccines, have been used to develop vaccines to prevent the spread of the virus. Researchers have modified a DNA vaccine to enhance its antigenicity and further updated it to target the Delta variant. The study found that intradermal injection using a pyro-drive jet injector induced higher levels of neutralizing antibodies and effectively protected mice from Delta variant infection.