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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

Adjuvant activity of GM-CSF in modulating T- and B-cell responses. GM-CSF influences critical steps in antigen presentation, which could enhance vaccine-induced T-and B-cell responses. GM-CSF increases the recruitment of myeloid progenitor cells, induces their differentiation and maturation, resulting in enhanced Class II expression and antigen presentation. Enhanced migration of activated APCs to lymphoid tissue could enhance vaccine-induced T- and B-cell responses.
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vaccines-02-00160-f003: Adjuvant activity of GM-CSF in modulating T- and B-cell responses. GM-CSF influences critical steps in antigen presentation, which could enhance vaccine-induced T-and B-cell responses. GM-CSF increases the recruitment of myeloid progenitor cells, induces their differentiation and maturation, resulting in enhanced Class II expression and antigen presentation. Enhanced migration of activated APCs to lymphoid tissue could enhance vaccine-induced T- and B-cell responses.

Mentions: In all three studies, protection conferred by DNA adjuvanted with GM-CSF appeared to be mediated by the effects of GM-CSF in the B-cell compartment, as the magnitude of T-cell responses were not significantly enhanced by GM-CSF. It is possible, however, that the quality of the B-cell helper CD4 responses may have been enhanced by GM-CSF, although this was not directly determined. Another possibility was that GM-CSF mediated the enhancement in DC maturation and function, especially that of myeloid DCs, which express receptors for GM-CSF, which could play a role in augmenting the quantity and quality of anti-Env B-cell response. The schematic in Figure 3 outlines the points of action of GM-CSF in adjuvanting immune responses. The GEO-D03 DNA vaccine that co-expresses HIV-1 clade B proteins, Gag, protease, RT, gp160 Env, Tat, Vpu and Rev, as non-infectious VLPs and human GM-CSF [63], has completed a human Phase I study in the U.S.


DNA/MVA Vaccines for HIV/AIDS.

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

Adjuvant activity of GM-CSF in modulating T- and B-cell responses. GM-CSF influences critical steps in antigen presentation, which could enhance vaccine-induced T-and B-cell responses. GM-CSF increases the recruitment of myeloid progenitor cells, induces their differentiation and maturation, resulting in enhanced Class II expression and antigen presentation. Enhanced migration of activated APCs to lymphoid tissue could enhance vaccine-induced T- and B-cell responses.
© Copyright Policy
Related In: Results  -  Collection

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

vaccines-02-00160-f003: Adjuvant activity of GM-CSF in modulating T- and B-cell responses. GM-CSF influences critical steps in antigen presentation, which could enhance vaccine-induced T-and B-cell responses. GM-CSF increases the recruitment of myeloid progenitor cells, induces their differentiation and maturation, resulting in enhanced Class II expression and antigen presentation. Enhanced migration of activated APCs to lymphoid tissue could enhance vaccine-induced T- and B-cell responses.
Mentions: In all three studies, protection conferred by DNA adjuvanted with GM-CSF appeared to be mediated by the effects of GM-CSF in the B-cell compartment, as the magnitude of T-cell responses were not significantly enhanced by GM-CSF. It is possible, however, that the quality of the B-cell helper CD4 responses may have been enhanced by GM-CSF, although this was not directly determined. Another possibility was that GM-CSF mediated the enhancement in DC maturation and function, especially that of myeloid DCs, which express receptors for GM-CSF, which could play a role in augmenting the quantity and quality of anti-Env B-cell response. The schematic in Figure 3 outlines the points of action of GM-CSF in adjuvanting immune responses. The GEO-D03 DNA vaccine that co-expresses HIV-1 clade B proteins, Gag, protease, RT, gp160 Env, Tat, Vpu and Rev, as non-infectious VLPs and human GM-CSF [63], has completed a human Phase I study in the U.S.

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