T-cell responses induced in normal volunteers immunized with a DNA-based vaccine containing HIV-1 env and rev

MacGregor, Rob Roy; Ginsberg, Richard S.; Ugen, Kenneth E.; Baine, Yaela; Kang, Christina U; Tu, Xin; Higgins, Terry J.; Weiner, David B.; Boyer, Jean

doi:10.1097/00002030-200211080-00005

Cited by 96 publications

(48 citation statements)

References 30 publications

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“…In dose escalation studies, env and rev genes as well as regulatory genes appeared safe in HIV-1-infected individuals (71,72). It was possible to show the induction of substantial Ag-specific CD4 ϩ Th cells by DNA vaccination with regulatory genes rev, tat, and nef in patients and decreased viral loads with DNA representing the env and pol genes (73).…”

Section: Therapeutic Dna Vaccinesmentioning

confidence: 99%

DNA Vaccines: Progress and Challenges

Donnelly

Wahrén²,

Liu³

2005

The Journal of Immunology

403

245

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In the years following the publication of the initial in vivo demonstration of the ability of plasmid DNA to generate protective immune responses, DNA vaccines have entered into a variety of human clinical trials for vaccines against various infectious diseases and for therapies against cancer, and are in development for therapies against autoimmune diseases and allergy. They also have become a widely used laboratory tool for a variety of applications ranging from proteomics to understanding Ag presentation and cross-priming. Despite their rapid and widespread development and the commonplace usage of the term “DNA vaccines,” however, the disappointing potency of the DNA vaccines in humans underscores the challenges encountered in the efforts to translate efficacy in preclinical models into clinical realities. This review will provide a brief background of DNA vaccines including the insights gained about the varied immunological mechanisms that play a role in their ability to generate immune responses.

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Section: Therapeutic Dna Vaccinesmentioning

confidence: 99%

DNA Vaccines: Progress and Challenges

Donnelly

Wahrén²,

Liu³

2005

The Journal of Immunology

403

245

View full text Add to dashboard Cite

show abstract

“…DNA vaccination has emerged as an effective and safe strategy for inducing protective T cell immunity in preclinical models of infectious diseases (1). However, experiments in nonhuman primates and human trials suggested that DNA vaccines are not nearly as immunogenic in these species as they are in rodents (2)(3)(4)(5)(6). Several strategies to improve the immunogenicity of DNA vaccines have been described, but the level of improvement has been modest and not applicable to all Ags (7).…”

Section: Modulation Of the Immune Response Induced By Gene Electrotramentioning

confidence: 99%

Modulation of the Immune Response Induced by Gene Electrotransfer of a Hepatitis C Virus DNA Vaccine in Nonhuman Primates

Capone

Zampaglione

Vitelli

et al. 2006

The Journal of Immunology

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Induction of multispecific, functional CD4+ and CD8+ T cells is the immunological hallmark of acute self-limiting hepatitis C virus (HCV) infection in humans. In the present study, we showed that gene electrotransfer (GET) of a novel candidate DNA vaccine encoding an optimized version of the nonstructural region of HCV (from NS3 to NS5B) induced substantially more potent, broad, and long-lasting CD4+ and CD8+ cellular immunity than naked DNA injection in mice and in rhesus macaques as measured by a combination of assays, including IFN-γ ELISPOT, intracellular cytokine staining, and cytotoxic T cell assays. A protocol based on three injections of DNA with GET induced a substantially higher CD4+ T cell response than an adenovirus 6-based viral vector encoding the same Ag. To better evaluate the immunological potency and probability of success of this vaccine, we have immunized two chimpanzees and have compared vaccine-induced cell-mediated immunity to that measured in acute self-limiting infection in humans. GET of the candidate HCV vaccine led to vigorous, multispecific IFN-γ+CD8+ and CD4+ T lymphocyte responses in chimpanzees, which were comparable to those measured in five individuals that cleared spontaneously HCV infection. These data support the hypothesis that T cell responses elicited by the present strategy could be beneficial in prophylactic vaccine approaches against HCV.

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“…Current gene-based immunogens, such as plasmid DNA and rAd5, have been widely studied in animal models [10][11][12][13][14][15], and have entered phase I and II human testing [16][17][18][19]. In addition, numerous groups have utilized vector prime, protein boost regimens to improve the potency or durability of the immune response to HIV or SIV antigens [20][21][22][23][24][25][26][27][28][29][30].…”

Section: Introductionmentioning

confidence: 99%

Efficient protein boosting after plasmid DNA or recombinant adenovirus immunization with HIV-1 vaccine constructs

Shu

Winfrey

Yang

et al. 2007

Vaccine

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DNA plasmids and recombinant adenovirus serotype-5 (rAd5) vectors are being studied in human clinical trials as HIV-1 vaccine candidates. Each elicits robust T-cell responses and modest antibody levels. Since protein immunization alone elicits antibody but not CD8 T-cell responses, we studied protein boosting of DNA and rAd5 HIV-1 vaccine vectors. A single Env protein immunization provided a marked boost in antibody titer in guinea pigs primed with either DNA or rAd5 vaccines, and the resulting antibody binding and neutralization levels were similar to those attained after thee sequential protein immunizations. Since both T-cell immunity and neutralizing antibodies are thought to be required for protection against HIV-1, it may be possible to establish a balanced T-cell and antibody response with appropriate vectored vaccines and improve the neutralizing antibody titer with protein boosting.

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T-cell responses induced in normal volunteers immunized with a DNA-based vaccine containing HIV-1 env and rev

Cited by 96 publications

References 30 publications

DNA Vaccines: Progress and Challenges

DNA Vaccines: Progress and Challenges

Modulation of the Immune Response Induced by Gene Electrotransfer of a Hepatitis C Virus DNA Vaccine in Nonhuman Primates

Efficient protein boosting after plasmid DNA or recombinant adenovirus immunization with HIV-1 vaccine constructs

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