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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

Phase I/II clinical trials (ongoing/scheduled) of HIV vaccines. (Left) the table shows Phase I/II HIV vaccine trials by vaccine modality obtained from the International AIDS Vaccine Initiative (IAVI) database of vaccine candidates in clinical trials [4].
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vaccines-02-00160-f001: Phase I/II clinical trials (ongoing/scheduled) of HIV vaccines. (Left) the table shows Phase I/II HIV vaccine trials by vaccine modality obtained from the International AIDS Vaccine Initiative (IAVI) database of vaccine candidates in clinical trials [4].

Mentions: Post RV144, at least two strategies of vaccine development can be identified. 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]. Currently, 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. Vaccine modalities based on DNA prime comprise a significant fraction of the current scheduled or ongoing Phase I and II HIV vaccine trials across the world (Figure 1). While plasmid DNA has demonstrated limited efficacy as a stand-alone vaccine, DNA in combination with viral vectors/protein shows a striking synergy in immune responses compared to either component alone. Innovations in the DNA platform with improved DNA delivery methods, such as electroporation and adjuvanting DNA with immunomodulatory molecules, have enhanced DNA immunogenicity. Here, we will briefly review the immunogenicity and efficacy studies using DNA as a prime in non-human primates and focus on pre-clinical and clinical studies of DNA/MVA HIV vaccines.


DNA/MVA Vaccines for HIV/AIDS.

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

Phase I/II clinical trials (ongoing/scheduled) of HIV vaccines. (Left) the table shows Phase I/II HIV vaccine trials by vaccine modality obtained from the International AIDS Vaccine Initiative (IAVI) database of vaccine candidates in clinical trials [4].
© Copyright Policy
Related In: Results  -  Collection

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

vaccines-02-00160-f001: Phase I/II clinical trials (ongoing/scheduled) of HIV vaccines. (Left) the table shows Phase I/II HIV vaccine trials by vaccine modality obtained from the International AIDS Vaccine Initiative (IAVI) database of vaccine candidates in clinical trials [4].
Mentions: Post RV144, at least two strategies of vaccine development can be identified. 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]. Currently, 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. Vaccine modalities based on DNA prime comprise a significant fraction of the current scheduled or ongoing Phase I and II HIV vaccine trials across the world (Figure 1). While plasmid DNA has demonstrated limited efficacy as a stand-alone vaccine, DNA in combination with viral vectors/protein shows a striking synergy in immune responses compared to either component alone. Innovations in the DNA platform with improved DNA delivery methods, such as electroporation and adjuvanting DNA with immunomodulatory molecules, have enhanced DNA immunogenicity. Here, we will briefly review the immunogenicity and efficacy studies using DNA as a prime in non-human primates and focus on pre-clinical and clinical studies of DNA/MVA HIV vaccines.

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