Abstract
Since the initial proof-of-concept studies examining the ability of antigen-encoded plasmid DNA to serve as an immunogen, DNA vaccines have evolved as a clinically safe and effective platform for priming HIV-specific cellular and humoral responses in heterologous “prime-boost” vaccination regimens. Direct injection of plasmid DNA into the muscle induces T- and B-cell responses against foreign antigens. However, the insufficient magnitude of this response has led to the development of approaches for enhancing the immunogenicity of DNA vaccines. The last two decades have seen significant progress in the DNA-based vaccine platform with optimized plasmid constructs, improved delivery methods, such as electroporation, the use of molecular adjuvants and novel strategies combining DNA with viral vectors and subunit proteins. These innovations are paving the way for the clinical application of DNA-based HIV vaccines. Here, we review preclinical studies on the DNA-prime/modified vaccinia Ankara (MVA)-boost vaccine modality for HIV. There is a great deal of interest in enhancing the immunogenicity of DNA by engineering DNA vaccines to co-express immune modulatory adjuvants. Some of these adjuvants have demonstrated encouraging results in preclinical and clinical studies, and these data will be examined, as well.
Highlights
The RV144 recombinant canary pox vector, ALVAC/gp120 vaccine efficacy trial was the first to demonstrate a reduction in the risk of HIV acquisition by an HIV vaccine [1]
The main types of vaccines being developed in the clinic for HIV use recombinant protein subunit vaccines, such as the glycoprotein 120-protein fragment of the HIV envelope tested in the RV144 study, recombinant virus-vectored vaccines, such as ALVAC, New York Vaccinia Virus (NYVAC), modified vaccinia Ankara (MVA) and adenovirus serotypes, and DNA vaccines, typically used to prime immune responses in heterologous prime-boost vaccine modalities
In a follow up study using the DMMM vaccination modality, we found that adjuvanting DNA with granulocyte macrophage colony-stimulating factor (GM-CSF) enhanced the avidity of anti-Env binding antibody that was associated with the enhanced control of peak simian/human immunodeficiency virus (SHIV) 89.6P viremia [61]
Summary
The RV144 recombinant canary pox vector, ALVAC/gp120 vaccine efficacy trial was the first to demonstrate a reduction in the risk of HIV acquisition by an HIV vaccine [1]. The first consists of building upon the poxvirus prime, subunit protein boost employed in RV144 with the goal of enhancing immunogenicity and increasing efficacy, and the second involves pursuing diverse vaccine regimens to identify more effective vaccine strategies [3]. The main types of vaccines being developed in the clinic for HIV use recombinant protein subunit vaccines, such as the glycoprotein (gp) 120-protein fragment of the HIV envelope tested in the RV144 study, recombinant virus-vectored vaccines, such as ALVAC, New York Vaccinia Virus (NYVAC), modified vaccinia Ankara (MVA) and adenovirus serotypes, and DNA vaccines, typically used to prime immune responses in heterologous prime-boost vaccine modalities. Subunit proteins: Recombinant HIV proteins e.g., gp120, trimeric gp140, gp41, Gag
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