Potentiating the cross-reactive IFN-γ T cell and polyfunctional T cell responses by heterologous GX-19N DNA booster in mice primed with either a COVID-19 mRNA vaccine or inactivated vaccine

Waning vaccine-induced immunity, coupled with the emergence of SARS-CoV-2 variants, has inspired the widespread implementation of COVID-19 booster vaccinations. Here, we evaluated the potentials of the GX-19N DNA vaccine as a heterologous booster to enhance the protective immune response to SARS-CoV-2 in mice primed with either an inactivated virus particle (VP) or mRNA vaccine. We found that in the VP-primed condition, GX-19N enhanced the response of both vaccine-specific antibodies and cross-reactive T-cells to the SARS-CoV-2 variant of concern (VOC) compared to the homologous VP vaccine prime-boost. Under the mRNA-primed condition, GX-19N induced higher vaccine-induced T-cell responses but lower antibody responses than the homologous mRNA vaccine prime-boost. Furthermore, heterologous GX-19N boost induced higher S-specific polyfunctional CD4+ and CD8+ T cell responses than the homologous VP or mRNA prime-boost vaccinations. Our results provide new insights into booster vaccination strategies for the management of novel COVID-19 variants.

Marked enhancement of neutralizing antibody and IFN-γ T-cell responses by GX-19N DNA booster in mice primed with inactivated vaccine

In response to the COVID-19 pandemic, an unprecedented level of vaccine development has occurred. As a result, various COVID-19 vaccines have been approved for use. Among these, inactivated virus particle (VP) vaccines have been widely used worldwide, but additional vaccination strategies are needed because of the short duration of immune responses elicited by these vaccines. Here, we evaluated homologous and heterologous prime-boost regimens using a VP vaccine and GX-19N DNA vaccine for their ability to enhance the protective immune response against SARS-CoV-2. We demonstrated that a heterologous prime-boost regimen with the VP vaccine and GX-19N DNA vaccine resulted in enhanced SRBD- & N-specific antibody responses, compared to the homologous VP vaccine prime-boost vaccination. In addition, the neutralizing antibody response was significantly improved with the heterologous VP prime-DNA boost regimen, and the neutralizing antibody induced with the heterologous prime-boost regimen did not decrease against the SARS-CoV-2 variant of concern (VOC). The heterologous VP prime-DNA boost regimen not only significantly increased S- and N-specific IFN-{gamma} T-cell responses, but also induced an equivalent level of T-cell response against SARS-CoV-2 VOCs. Our results provide new insights into prophylactic vaccination strategies for COVID-19 vaccination.

Soluble Spike DNA vaccine provides long-term protective immunity against SAR-CoV-2 in mice and nonhuman primates

The unprecedented and rapid spread of SARS-CoV-2 has motivated the need for a rapidly producible and scalable vaccine. Here, we developed a synthetic soluble SARS-CoV-2 spike (S) DNA-based vaccine candidate, GX-19. In mice, immunization with GX-19 elicited not only S-specific systemic and pulmonary antibody responses but also Th1-biased T cell responses in a dose-dependent manner. GX-19 vaccinated nonhuman primate seroconverted rapidly and exhibited detectable neutralizing antibody response as well as multifunctional CD4+ and CD8+ T cell responses. Notably, when the immunized nonhuman primates were challenged at 10 weeks after the last vaccination with GX-19, they did not develop fever and reduced viral loads in contrast to non-vaccinated primates as a control. These findings indicate that GX-19 vaccination provides durable protective immune response and also support further development of GX-19 as a vaccine candidate for SARS-CoV-2 in human clinical trials.