Selected approaches for increasing HIV DNA vaccine immunogenicity in vivo

Abstract

The safety, stability, and ability for repeat homologous vaccination makes the DNA vaccine platform an excellent candidate for an effective HIV-1 vaccine. However, the immunogenicity of early DNA vaccines did not translate from small animal models into larger non-human primates and was markedly lower than viral vectors. In addition to improvements to the DNA vector itself, delivery with electroporation, the inclusion of molecular adjuvants, and heterologous prime-boost strategies have dramatically improved the immunogenicity of DNA vaccines for HIV and currently makes them a leading platform with many areas warranting further research and clinical development.

Skin Transfection Patterns and Expression Kinetics of Electroporation-Enhanced Plasmid Delivery Using the CELLECTRA-3P, a Portable Next-Generation Dermal Electroporation Device

“…Clearly there are significant differences between skin and muscle as target tissues, but this finding seeks to highlight the benefits of intradermal vaccinations from the perspective of rapid dynamics. In a previous publication, 38 we demonstrated local tissue damage after EP with the CELLECTRA-3P. This damage, however, was extremely localized and was observed only in the direct vicinity of the penetrating electrodes.…”

DNA vaccines: roles against diseases

“…It is a useful technique as it increases the transfection efficiency of DNA vaccines in vivo. 42 Nanoparticles as drug-delivery systems have also been explained by the Editor-inchief of this Journal in a previous editorial. 43 The study of nanoparticles provides a strong platform to combining protein-and DNA-based vaccines/antiretrovirals which can help the production, preclinical evaluation and the clinical testing in the near future.…”

“…The immunogenicity of DNA vaccines for HIV has been increased through improvement of the DNA vector, through the inclusion of molecular adjuvants, heterologous prime-boost strategies, and delivery with electroporation. 42 The principle behind electroporation is that it applies a small electric field across the site of injection that causes temporary membrane instability and produces an electric gradient, which elevates the cellular uptake of DNA. It is a useful technique as it increases the transfection efficiency of DNA vaccines in vivo.…”

Safety and Immunogenicity of DNA Prime and Modified Vaccinia Ankara Virus-HIV Subtype C Vaccine Boost in Healthy Adults

“…Limited potency of DNA alone or as part of a prime-boost strategy has been seen in other trials (15,21,24,45). The DNA backbone, dose, number of administrations, insert, and method of delivery are all variables associated with effectiveness of the DNA (8,46,47). Some studies have shown that DNA alone is immunogenic in humans, albeit with low-magnitude responses as measured by ELISPOT and/or ICS (26,48,49).…”