DNA Vaccines against Human Immunodeficiency Virus Type 1 in the Past Decade

Giri, Malavika S.; Ugen, Kenneth E.; Weiner, David B.

doi:10.1128/cmr.17.2.370-389.2004

Cited by 80 publications

(48 citation statements)

References 214 publications

(208 reference statements)

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“…Although some DNA vaccines elicit strong immune responses in mice (29), most investigators have found it necessary to add cytokines or chemokines to enhance the response to immunization (2,7,26,49). Alternative or complementary approaches include electroporation (65), gene gun delivery of DNA-coated gold particles (90), and delivery on polymer microparticles (64) or by polymer microencapsulation (52).…”

Section: Discussionmentioning

confidence: 99%

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Multimeric Soluble CD40 Ligand and GITR Ligand as Adjuvants for Human Immunodeficiency Virus DNA Vaccines

Stone¹,

Barzee²,

Snarsky³

et al. 2006

J Virol

115

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For use in humans, human immunodeficiency virus (HIV) DNA vaccines may need to include immunostimulatory adjuvant molecules. CD40 ligand (CD40L), a member of the tumor necrosis factor (TNF) superfamily (TNFSF), is one candidate adjuvant, but it has been difficult to use because it is normally expressed as a trimeric membrane molecule. Soluble trimeric forms of CD40L have been produced, but in vitro data indicate that multimeric, many-trimer forms of soluble CD40L are more active. This multimerization requirement was evaluated in mice using plasmids that encoded either 1-trimer, 2-trimer, or 4-trimer soluble forms of CD40L. Fusion with the body of Acrp30 was used to produce the 2-trimer form, and fusion with the body of surfactant protein D was used to produce the 4-trimer form. Using plasmids for secreted HIV-1 antigens Gag and Env, soluble CD40L was active as an adjuvant in direct proportion to the valence of the trimers (1 < 2 < 4). These CD40L-augmented DNA vaccines elicited strong CD8 ؉ T-cell responses but did not elicit significant CD4 ؉ T-cell or antibody responses. To test the applicability of the multimeric fusion protein approach to other TNFSFs, a 4-trimer construct for the ligand of glucocorticoid-induced TNF family-related receptor (GITR) was also prepared. Multimeric soluble GITR ligand (GITRL) augmented the CD8 ؉ T-cell, CD4 ؉ T-cell, and antibody responses to DNA vaccination. In summary, multimeric CD40L and GITRL are new adjuvants for DNA vaccines. Plasmids for expressing multimeric TNFSF fusion proteins permit the rapid testing of TNFSF molecules in vivo.

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Section: Discussionmentioning

confidence: 99%

“…DNA vaccines directed against human immunodeficiency virus type 1 (HIV-1) and other viruses have been extensively studied in mice, macaques, and humans (17,21,26,29,74). However, there is a need to develop more effective DNA vaccines.…”

mentioning

confidence: 99%

Multimeric Soluble CD40 Ligand and GITR Ligand as Adjuvants for Human Immunodeficiency Virus DNA Vaccines

Stone¹,

Barzee²,

Snarsky³

et al. 2006

J Virol

115

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“…In addition, it has been suggested that the effector profile and other less well-understood properties of discrete TAA-specific T-cell subpopulations may also have an important role in tumor regression. 24 Thus, in light of our data and additional information generated independently, 25,26 we re-evaluated the strengths and limitations of plasmid-based immunization as an option for active immunotherapy in cancer. More specifically, we sought to integrate the concept of immunization by direct intra-lymph node administration with a plasmid prime/peptide boost approach in an attempt to synergize key features of these two immunizing vectors: (i) plasmid priming for induction of a highquality immune response and (ii) peptide boosting for amplification and functional conversion of the immune response.…”

Section: Introductionmentioning

confidence: 96%

Multivalent immunity targeting tumor-associated antigens by intra-lymph node DNA-prime, peptide-boost vaccination

et al. 2010

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Active immunotherapy of cancer has yet to yield effective therapies in the clinic. To evaluate the translatability of DNA-based vaccines we analyzed the profile of T-cell immunity by plasmid vaccination in a murine model, using transcriptome microarray analysis and flow cytometry. DNA vaccination resulted in specific T cells expressing low levels of co-inhibitory molecules (most notably PD-1), strikingly different from the expression profile elicited by peptide immunization. In addition, the T-cell response primed through this dual-antigen-expressing plasmid (MART-1/Melan-A and tyrosinase) translated into a substantial proliferation capacity and functional conversion to antitumor effector cells after tyrosinase and MART-1/Melan-A peptide analog boost. Furthermore, peptide boost rescued the immune response against the subdominant tyrosinase epitope. This immunization approach could be adapted to elicit potent immunity against multiple tumor antigens, resulting in a broader immune response that was more effective in targeting human tumor cells. Finally, this study sheds light on a novel mechanism of immune homeostasis through synchronous regulation of co-inhibitory molecules on T cells, highly relevant to heterologous prime boost approaches involving DNA vaccines as priming agents.

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“…We further tested the transfected cultures for duration of production of the viral protein by measuring p24 concentrations in supernatant fluids. These fluids were collected at 4,8,12,16,20, and 24 h and every 2 days thereafter for 14 days and were analyzed using p24 ELISA. p24 was first detected at (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Further alternative strategies using viral DNA as a vaccine were therefore adopted. Initial clinical trials of certain of the DNA vaccines in humans have demonstrated only a limited degree of immunogenicity thus far (for a review, see reference 20), necessitating further improvement in DNA vaccine construction strategies. Attempts to improve the efficiency of DNA vaccines have been made either by optimization of HIV genes for codon usage in mammalian cells (4,7,18,44,45) or by modifying RNA structures through nucleotide changes facilitating high antigen expression in a Rev-independent manner (32).…”

mentioning

confidence: 99%

Antigen Expression Kinetics and Immune Responses of Mice Immunized with Noninfectious Simian-Human Immunodeficiency Virus DNA

Hegde¹,

Liu²,

Mackay

et al. 2005

J Virol

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Virol 79:3419-3428, 2005). To make this DNA safer, we deleted two more genes, the integrase gene and vif, along with the 3 long terminal repeat. We also replaced the gag, pro, and nef genes (SIVmac239 origin) with those of human immunodeficiency virus (HIV) type 1 strain SF2. The resultant construct, designated ⌬4SHIV KU2 DNA, was used in this study to evaluate gene expression and immunogenicity in BALB/c mice. DNA-transfected human embryonic kidney epithelial cells (HEK 293) produced all of the major viral proteins and released p24 in the supernatant for 12 days. Inoculation of the vaccine DNA into the gastrocnemius muscles resulted in intense mononuclear cell infiltration at the inoculated sites and the production of viral p24 in myocytes, in infiltrating mononuclear cells, and in cells in the spleen and draining lymph nodes between 3 and 10 days postinoculation. Expression of p24 in the muscle cells peaked at day 7 and became undetectable after day 12. The same 12-day period of expression of p24 was observed in mice that were given a second injection 4 weeks after the first. Evaluation of immune responses in BALB/c mice revealed that the DNA induced enzyme-linked immunospot and antigen-specific proliferative cell-mediated immunity responses. The responses were stronger in mice that were coinjected with a second plasmid expressing granulocyte-macrophage colony-stimulating factor. Since new waves of viral antigen production could be induced with each boosting injection of the vaccine DNA, this DNA could be a safe and efficient agent to induce long-term protection against HIV.An effective and safe vaccine against human immunodeficiency virus (HIV)/AIDS still remains elusive even after more than a decade of intense research. Although live vaccines are highly effective in preventing AIDS in macaques, they are not acceptable for use in humans because of concerns about reversion to pathogenicity by mutation or recombination. An alternative strategy using recombinant viral envelope glycoprotein was not effective in clinical trials. Further alternative strategies using viral DNA as a vaccine were therefore adopted. Initial clinical trials of certain of the DNA vaccines in humans have demonstrated only a limited degree of immunogenicity thus far (for a review, see reference 20), necessitating further improvement in DNA vaccine construction strategies. Attempts to improve the efficiency of DNA vaccines have been made either by optimization of HIV genes for codon usage in mammalian cells (4,7,18,44,45) or by modifying RNA structures through nucleotide changes facilitating high antigen expression in a Rev-independent manner (32). Other strategies tried to potentiate DNA vaccines by modulating and enhancing host immune response with the help of cytokine/chemokine adjuvants and T-cell costimulatory molecules (9,10,14,32) or by different enhancers/promoters such as cytomegalovirus (37) or ␤-actin or muscle-specific desmin promoter (13) to obtain high expression of one or two fused genes of HIV (26). The use of these DNA moie...

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DNA Vaccines against Human Immunodeficiency Virus Type 1 in the Past Decade

Cited by 80 publications

References 214 publications

Multimeric Soluble CD40 Ligand and GITR Ligand as Adjuvants for Human Immunodeficiency Virus DNA Vaccines

Multimeric Soluble CD40 Ligand and GITR Ligand as Adjuvants for Human Immunodeficiency Virus DNA Vaccines

Multivalent immunity targeting tumor-associated antigens by intra-lymph node DNA-prime, peptide-boost vaccination

Antigen Expression Kinetics and Immune Responses of Mice Immunized with Noninfectious Simian-Human Immunodeficiency Virus DNA

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