DNA Vaccine Development Against SARS-CoV-2 Variants

DNA vaccines represent a versatile platform in which plasmid DNA encoding the SARS-CoV-2 spike antigen is delivered into host cells to elicit both antibody-mediated and T cell-mediated immunity. Rapid synthetic design, ease of large-scale manufacturing and thermal stability underpin their appeal for global deployment. Early constructs focused on the wild-type spike, while later generations have incorporated stabilising mutations (for example HexaPro), lineage-defining substitutions (such as D614G) and variant-specific sequences to counter immune escape. Delivery modalities range from electroporation and electroacupuncture devices to lipid nanoparticles and jet injectors, each optimised for maximal uptake and balanced immune polarisation. Preclinical studies in mice, hamsters and transgenic models demonstrate robust neutralising antibody titres against Alpha, Delta, Gamma and Omicron sublineages, coupled with Th1-biased CD4+ and CD8+ T cell responses. Advances in formulation, adjuvantation and real-time antigen updating establish DNA vaccines as a flexible tool for rapid response to emerging variants and future coronavirus threats.

Research from Nature Portfolio

Recent studies have shown that lipid nanoparticle-encapsulated plasmid DNA encoding a prefusion-stabilised spike (HexaPro) drives potent protection against Gamma and Omicron variants in female animal models. A lead LNP formulation achieved high transfection efficiency in antigen-presenting cells, elicited neutralising titres comparable to authorised mRNA vaccines and reduced viral load and pulmonary pathology. Another investigation described a DNA vaccine encoding the D614G spike mutation that, when administered intramuscularly or intradermally with electroporation, induced strong IgG2a-polarised responses, elevated interferon-γ-secreting CD4+ and CD8+ T cells and conferred near-complete protection in transgenic mice. A further report detailed a modified plasmid incorporating stabilising deletions and mutations of the Delta spike, demonstrating that intradermal jet-injection produced higher neutralising antibody titres than needle injections and protected human ACE2 knock-in mice from Delta infection. These findings underscore the adaptability of DNA platforms to incorporate variant antigens and the importance of delivery optimisation for immunogenicity and protective efficacy.

DNA Vaccine Development Against SARS-CoV-2 Variants publication trend

The graph below shows the total number of articles in dna vaccine development against sars-cov-2 variants across all publications each year (not limited to Nature Index journals).

Technical terms

DNA vaccine: A vaccine delivering plasmid DNA encoding a viral antigen to stimulate immune responses.

Lipid nanoparticle (LNP): A lipid-based carrier that facilitates the cellular delivery of nucleic acids.

Electroporation: Application of brief electric pulses to increase cell membrane permeability for DNA uptake.

Neutralising antibody: An antibody that directly prevents virus entry into host cells.

Th1 response: A T helper cell-driven immune reaction characterised by interferon-γ production and cellular immunity.

Spike protein: The SARS-CoV-2 surface glycoprotein responsible for receptor binding and fusion with host cells.

References

1. Nanoparticle-based DNA vaccine protects against SARS-CoV-2 variants in female preclinical models. Nature Communications (2024).
2. The Coming of Age of Nucleic Acid Vaccines during COVID-19. mSystems (2023).
3. Comparison of DNA vaccines with AS03 as an adjuvant and an mRNA vaccine against SARS-CoV-2. iScience (2023).
4. Immunogenicity and protection efficacy of a COVID-19 DNA vaccine encoding spike protein with D614G mutation and optimization of large-scale DNA vaccine production. Scientific Reports (2024).
5. A DNA vaccine candidate delivered by an electroacupuncture machine provides protective immunity against SARS-CoV-2 infection. npj Vaccines (2022).
6. Modified DNA vaccine confers improved humoral immune response and effective virus protection against SARS-CoV-2 delta variant. Scientific Reports (2022).