The future of human DNA vaccines

Abstract

DNA vaccines have evolved greatly over the last 20 years since their invention, but have yet to become a competitive alternative to conventional protein or carbohydrate based human vaccines. Whilst safety concerns were an initial barrier, the Achilles heel of DNA vaccines remains their poor immunogenicity when compared to protein vaccines. A wide variety of strategies have been developed to optimize DNA vaccine immunogenicity, including codon optimization, genetic adjuvants, electroporation and sophisticated prime-boost regimens, with each of these methods having its advantages and limitations. Whilst each of these methods has contributed to incremental improvements in DNA vaccine efficacy, more is still needed if human DNA vaccines are to succeed commercially. This review foresees a final breakthrough in human DNA vaccines will come from application of the latest cutting-edge technologies, including “epigenetics” and “omics” approaches, alongside traditional techniques to improve immunogenicity such as adjuvants and electroporation, thereby overcoming the current limitations of DNA vaccines in humans

Immunogenicity of varicella zoster virus glycoprotein E DNA vaccine

“…Following inoculation, the corresponding antigen proteins of the DNA vaccine may express in muscle cells; therefore it was initially hypothesized that muscle cells were the predominant cells exerting antigen-presenting function following immunization with a DNA vaccine. However, further research has demonstrated that muscle cells do not express costimulatory molecules, including CD80, also known as B71, and CD86, also known as B7H; therefore, muscle cells do not have a key role in antigen presentation (31,32). Previously, Zhang et al (33) coated gold particles with plasmid DNA and immunized turbot (Scophthalmus maximus) using a gene gun.…”

How can Improve DNA Vaccine Modalities as a Therapeutic Approach against HIV Infections?

“…Codon optimization of DNA vaccine has been also shown to increase immunogenicity and provide better protection against Schistosoma japonicum, influenza virus, HIV, HPV, RSV, and SIV in mouse models. It should be noted that while codon optimization increases antigen expression, but this may not always enhance vaccine potency [50].…”

“…In an heterologous boost, because the priming and boosting vectors are different, T cells that specifically target the viral vector are not boosted and do not activate cell number control mechanisms, therefore allowing for greater development of the disease antigen-specific T cell populations [11]. Several groups have now established that heterologous prime-boost regimens are the most potent strategies to induce cellular immune responses [12,50]. In a plasmid DNA vaccine priming and viral vector boosting regimen, the order of DNA followed by recombinant virus is important, as the reverse order did not induce higher levels of antigenspecific CD8 + T cells.…”

“…Recent studies have used DNA/protein or DNA/Adenovector regimens for HIV immunization. The essential mechanisms of heterogeneous prime/boost regimens are not well understood but DNA priming results in much lower antigen expression compared to protein vaccines, and this may prime T-helper cell responses with the humoral response subsequently being boosted by the high dose protein or viral vector (e.g., RV 144 tested in clinical trials) [50].…”

Coadministration of a Plasmid Encoding HIV-1 Gag Enhances the Efficacy of Cancer DNA Vaccines

“…11 These genetic adjuvants include cytokines, chemokines, or immune stimulatory molecules, such as toll-like receptor (TLR) agonists or interferon (IFN) regulatory factors. 7,[12][13][14] Most of these adjuvants are used in preclinical studies, and even though they are promising, only a few of them have been evaluated in clinical trials until now. Therefore, there is still a critical need of clinically applicable genetic adjuvants.…”