Enhancement of Cellular Immune Response in HIV-1 Seropositive Individuals: A DNA-Based Trial

Boyer, Jean; Chattergoon, Michael A.; Ugen, Kenneth E.; Shah, Ami; Bennett, Mosi K.; Cohen, Adam D.; Nyland, Susan B.; Lacy, K. E.; Bagarazzi, Mark L.; Higgins, Terry J.; Baine, Yaela; Ciccarelli, Richard B.; Ginsberg, Richard S.; MacGregor, Rob Roy; Weiner, David B.

doi:10.1006/clim.1998.4616

Cited by 73 publications

(32 citation statements)

References 42 publications

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“…Accordingly, vaccines that induce HIV-specific cellular immunity are being pursued (7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22)(23)(24)(25). The exact nature of how the antigen-specific lymphocytes should be armed is still unknown.…”

mentioning

confidence: 99%

“…The exact nature of how the antigen-specific lymphocytes should be armed is still unknown. In the primate simian/HIV (SHIV) and simian immunodeficiency virus (SIV)-challenge models, induction of a high level of CD8 T cell immunity is associated with reduced viremia and protection of CD4 cells (19)(20)(21)(22)(23)(24)(25). A number of studies in primates as well as HIV-infected humans have indicated that suppressed viral replication and long-term nonprogression are associated with higher and more complex cellular immune responses.…”

mentioning

confidence: 99%

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Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid

Boyer

Robinson

Kutzler

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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The cell-mediated immune profile induced by a recombinant DNA vaccine was assessed in the simian/HIV (SHIV) and macaque model. The vaccine strategy included coimmunization of a DNA-based vaccine alone or in combination with an optimized plasmid encoding macaque IL-15 (pmacIL-15). We observed strong induction of vaccine-specific IFN-␥-producing CD8 ؉ and CD4 ؉ effector T cells in the vaccination groups. Animals were subsequently challenged with 89.6p. The vaccine groups were protected from ongoing infection, and the IL-15 covaccinated group showed a more rapidly controlled infection than the group treated with DNA vaccine alone. Lymphocytes isolated from the group covaccinated with pmacIL-15 had higher cellular proliferative responses than lymphocytes isolated from the macaques that received SHIV DNA alone. Vaccine antigen activation of lymphocytes was also studied for a series of immunological molecules. Although mRNA for IFN-␥ was up-regulated after antigen stimulation, the inflammatory molecules IL-8 and MMP-9 were down-regulated. These observed immune profiles are potentially reflective of the ability of the different groups to control SHIV replication. This study demonstrates that an optimized IL-15 immune adjuvant delivered with a DNA vaccine can impact the cellular immune profile in nonhuman primates and lead to enhanced suppression of viral replication.HIV vaccine ͉ immune response ͉ cytokine adjuvant ͉ T cell immunity

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confidence: 99%

mentioning

confidence: 99%

Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid

Boyer

Robinson

Kutzler

et al. 2007

Proc. Natl. Acad. Sci. U.S.A.

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show abstract

“…Although the antibody titers induced in this trial were not as strong as those elicited by the conventional vaccines, the 100% seroconversion is a notable contrast to results of other DNA vaccine studies in which i.m. injection of as much as 5 mg of DNA resulted in low or no antibody responses [20][21][22][23][24][25][26][27][28]. The immunogenicity of the PMED DNA vaccine with up to 1000-fold less DNA per immunization is likely due to the efficiency of the intracellular delivery system and the ability to target the highly active immunologically inductive epidermal tissue.…”

Section: Clinical Results With Pmed Dna Vaccinesmentioning

confidence: 99%

“…Moreover, in humans where DNA doses up to 5 mg administered via i.m. inoculation result in only modest cellular responses and essentially no antibody responses [20][21][22][23][24][25][26][27][28], PMED DNA vaccines have achieved greater success in inducing both humoral and cellular responses using less than 10 Ag DNA [29,30]. The ability of PMED DNA vaccines to elicit immune responses with such small amounts of DNA allows multiple plasmids/genes to be simultaneously delivered for the induction of immunity to multiple antigens [31].…”

Section: Particle-mediated Epidermal Delivery Versus Intramuscular Inmentioning

confidence: 99%

The role of particle-mediated DNA vaccines in biodefense preparedness

Dean¹,

Haynes²,

Schmaljohn

2005

Advanced Drug Delivery Reviews

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“…To this end, a number of Phase I clinical trials have been conducted evaluating pDNA-based vaccine approaches for the treatment of HIV-1 infection [10][11][12][13][14]. Similar to many prophylactic pDNA vaccine trials conducted to date, these therapeutic vaccines appeared safe and well tolerated.…”

mentioning

confidence: 99%

Towards the development of a therapeutic vaccine for the treatment of HIV-1 infection: are we closer than ever?

Egan

2007

Expert Review of Vaccines

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Enhancement of Cellular Immune Response in HIV-1 Seropositive Individuals: A DNA-Based Trial

Cited by 73 publications

References 42 publications

Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid

Protection against simian/human immunodeficiency virus (SHIV) 89.6P in macaques after coimmunization with SHIV antigen and IL-15 plasmid

The role of particle-mediated DNA vaccines in biodefense preparedness

Towards the development of a therapeutic vaccine for the treatment of HIV-1 infection: are we closer than ever?

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