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DNA/MVA Vaccines for HIV/AIDS.

Iyer SS, Amara RR - Vaccines (Basel) (2014)

Bottom Line: 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.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.Some of these adjuvants have demonstrated encouraging results in preclinical and clinical studies, and these data will be examined, as well.

View Article: PubMed Central - PubMed

Affiliation: Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA. siyer3@emory.edu.

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.

No MeSH data available.


Related in: MedlinePlus

The timeline of benchmark studies resulting in the development of DNA as a prime for the DNA/MVA HIV vaccine modality. The timeline of key studies resulting in the clinical application of DNA as an immunogen for DNA/MVA HIV vaccines. HGH, human growth hormone; NP, nucleoprotein; CTL, cytotoxic T-cell; Ab, antibody; HA, hemagglutinin; Env, envelope; IM, intramuscular; GM-CSF, granulocyte macrophage colony stimulating factor; SIV, Simian immunodeficiency virus; SHIV, Simian/Human immunodeficiency virus.
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vaccines-02-00160-f002: The timeline of benchmark studies resulting in the development of DNA as a prime for the DNA/MVA HIV vaccine modality. The timeline of key studies resulting in the clinical application of DNA as an immunogen for DNA/MVA HIV vaccines. HGH, human growth hormone; NP, nucleoprotein; CTL, cytotoxic T-cell; Ab, antibody; HA, hemagglutinin; Env, envelope; IM, intramuscular; GM-CSF, granulocyte macrophage colony stimulating factor; SIV, Simian immunodeficiency virus; SHIV, Simian/Human immunodeficiency virus.

Mentions: In this section, we provide a brief timeline of benchmark studies leading to the development of DNA/MVA HIV vaccines beginning with the use of plasmid DNA to induce immunity against influenza more than two decades ago (Figure 2). The first use of naked plasmid DNA as an expression vector was demonstrated in 1990 [5]. In 1992, Tang et al. employed DNA as a simple means to elicit immune responses against non-self antigens [6]. Mice were immunized intradermally with plasmid encoding human growth hormone (HGH) using a gene gun approach. Remarkably, DNA immunization induced serum HGH Ab (antibody) responses, which were augmented by a booster shot. This simple and unique technique of genetic immunization generated considerable excitement for two reasons; first, DNA immunization would overcome the time-consuming need for protein purification necessary for protein immunizations; and second, DNA encoding viral proteins could serve as a vaccine against viral infections.


DNA/MVA Vaccines for HIV/AIDS.

Iyer SS, Amara RR - Vaccines (Basel) (2014)

The timeline of benchmark studies resulting in the development of DNA as a prime for the DNA/MVA HIV vaccine modality. The timeline of key studies resulting in the clinical application of DNA as an immunogen for DNA/MVA HIV vaccines. HGH, human growth hormone; NP, nucleoprotein; CTL, cytotoxic T-cell; Ab, antibody; HA, hemagglutinin; Env, envelope; IM, intramuscular; GM-CSF, granulocyte macrophage colony stimulating factor; SIV, Simian immunodeficiency virus; SHIV, Simian/Human immunodeficiency virus.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494194&req=5

vaccines-02-00160-f002: The timeline of benchmark studies resulting in the development of DNA as a prime for the DNA/MVA HIV vaccine modality. The timeline of key studies resulting in the clinical application of DNA as an immunogen for DNA/MVA HIV vaccines. HGH, human growth hormone; NP, nucleoprotein; CTL, cytotoxic T-cell; Ab, antibody; HA, hemagglutinin; Env, envelope; IM, intramuscular; GM-CSF, granulocyte macrophage colony stimulating factor; SIV, Simian immunodeficiency virus; SHIV, Simian/Human immunodeficiency virus.
Mentions: In this section, we provide a brief timeline of benchmark studies leading to the development of DNA/MVA HIV vaccines beginning with the use of plasmid DNA to induce immunity against influenza more than two decades ago (Figure 2). The first use of naked plasmid DNA as an expression vector was demonstrated in 1990 [5]. In 1992, Tang et al. employed DNA as a simple means to elicit immune responses against non-self antigens [6]. Mice were immunized intradermally with plasmid encoding human growth hormone (HGH) using a gene gun approach. Remarkably, DNA immunization induced serum HGH Ab (antibody) responses, which were augmented by a booster shot. This simple and unique technique of genetic immunization generated considerable excitement for two reasons; first, DNA immunization would overcome the time-consuming need for protein purification necessary for protein immunizations; and second, DNA encoding viral proteins could serve as a vaccine against viral infections.

Bottom Line: 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.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.Some of these adjuvants have demonstrated encouraging results in preclinical and clinical studies, and these data will be examined, as well.

View Article: PubMed Central - PubMed

Affiliation: Emory Vaccine Center, Division of Microbiology and Immunology, Yerkes National Primate Research Center, Emory University, Atlanta, GA 30329, USA. siyer3@emory.edu.

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.

No MeSH data available.


Related in: MedlinePlus