Immunogenicity of Attenuated Vesicular Stomatitis Virus Vectors Expressing HIV Type 1 Env and SIV Gag Proteins: Comparison of Intranasal and Intramuscular Vaccination Routes

Egan, Michael A.; Chong, Siew Yen; Rose, Nina; Megati, Shakuntala; Lopez, Kevin; Schadeck, Eva B.; Johnson, J. Erik; Masood, Amjed; Piacente, Priscilla; Druilhet, Robert E.; Barras, Paul W.; Hasselschwert, Dana L.; Reilly, Patricia; Mishkin, Eric M.; Montefiori, David C.; Lewis, Mark G.; Clarke, David K.; Hendry, R. Michael; Marx, Preston A.; Eldridge, John H.; Udem, Stephen A.; Israel, Zimra R.; Rose, John K.

doi:10.1089/0889222042222746

Cited by 23 publications

(33 citation statements)

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“…For example, VSV primarily infects livestock, including cows, horses, and pigs 43 and it is thought that preexisting immunity to VSV in humans is rare. Furthermore, studies in mice 44 and rhesus macaques 41,45 have demonstrated that effective boosting of the rVSV-elicited immune response can be achieved by immunizing with a second VSV recombinant in which the VSV surface glycoprotein (G) is changed to avoid neutralization by antibodies generated in response to the primary rVSV immunization. In addition, intranasal inoculation of rhesus macaques with a live attenuated rVSV expressing SIVgag and HIVenv is capable of eliciting high level cell-mediated as well as systemic and mucosal antibody responses, 45 suggesting rVSV-based vaccines may be well suited for preventing the sexual transmission of HIV-1.…”

Section: Introductionmentioning

confidence: 99%

Priming with Plasmid DNAs Expressing Interleukin-12 and Simian Immunodeficiency Virus Gag Enhances the Immunogenicity and Efficacy of an Experimental AIDS Vaccine Based on Recombinant Vesicular Stomatitis Virus

Egan

Chong

Megati

et al. 2005

AIDS Research and Human Retroviruses

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Of the various approaches being developed as prophylactic HIV vaccines, those based on a heterologous plasmid DNA prime, live vector boost vaccination regimen appear especially promising in the nonhuman primate/simian-human immunodeficiency virus (SHIV) challenge model. In this study, we sought to determine whether a series of intramuscular priming immunizations with a plasmid DNA vaccine expressing SIVgag p39, in combination with plasmid expressed rhesus IL-12, could effectively enhance the immunogenicity and postchallenge efficacy of two intranasal doses of recombinant vesicular stomatitis virus (rVSV)-based vectors expressing HIV-1 env 89.6P gp160 and SIVmac239 gag p55 in rhesus macaques. In macaques receiving the combination plasmid DNA prime, rVSV boost vaccination regimen we observed significantly increased SIVgag- specific cell-mediated and humoral immune responses and significantly lower viral loads postintravenous SHIV89.6P challenge relative to macaques receiving only the rVSV vectored immunizations. In addition, the plasmid DNA prime, rVSV boost vaccination regimen also tended to increase the preservation of peripheral blood CD4+ cells and reduce the morbidity and mortality associated with SHIV89.6P infection. An analysis of immune correlates of protection after SHIV89.6P challenge revealed that the prechallenge SHIV-specific IFN-gamma ELISpot response elicited by vaccination and the ability of the host to mount a virus-specific neutralizing antibody response postchallenge correlated with postchallenge clinical outcome. The correlation between vaccine-elicited cell-mediated immune responses and an improved clinical outcome after SHIV challenge provides strong justification for the continued development of a cytokine-enhanced plasmid DNA prime, rVSV vector boost immunization regimen for the prevention of HIV infection.

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Section: Introductionmentioning

confidence: 99%

Priming with Plasmid DNAs Expressing Interleukin-12 and Simian Immunodeficiency Virus Gag Enhances the Immunogenicity and Efficacy of an Experimental AIDS Vaccine Based on Recombinant Vesicular Stomatitis Virus

Egan

Chong

Megati

et al. 2005

AIDS Research and Human Retroviruses

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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.…”

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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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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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“…In general, this virus is neuro-toxic for mice (but not humans). However, since neuro-virulence could be attenuated through molecular manipulations (Egan et al 2004;Cooper et al 2008), this prolonged virus persistence should not be of major concern. A more serious concern is a possible feedback loop caused by the VSV itself, which can limit its persistence.…”

Section: Discussion and Biological Implicationsmentioning

confidence: 99%

Multi-Stability and Multi-Instability Phenomena in a Mathematical Model of Tumor-Immune-Virus Interactions

et al. 2011

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Recent advances in virology, gene therapy, and molecular and cell biology have provided insight into the mechanisms through which viruses can boost the anti-tumor immune response, or can infect and directly kill tumor cells. A recent experimental report (Bridle et al. in Molec. Ther. 18(8):1430-1439, 2010) showed that a sequential treatment approach that involves two viruses that carry the same tumor antigen leads to an improved anti-tumor response compared to the effect of each virus alone. In this article, we derive a mathematical model to investigate the anti-tumor effect of two viruses, and their interactions with the immune cells. We discuss the conditions necessary for permanent tumor elimination and, in this context, we stress the importance of investigating the long-term effect of non-linear interactions. In particular, we discuss multi-stability and multi-instability, two complex phenomena that can cause abrupt transitions between different states in biological and physical systems. In the context of cancer immunotherapies, the transitions between a tumor-free and a tumor-present state have so far been associated with the multi-stability phenomenon. Here, we show that multi-instability can also cause the system to switch from one state to the other. In addition, we show that the multi-stability is driven by the immune response, while the multi-instability is driven by the presence of the virus.

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Immunogenicity of Attenuated Vesicular Stomatitis Virus Vectors Expressing HIV Type 1 Env and SIV Gag Proteins: Comparison of Intranasal and Intramuscular Vaccination Routes

Cited by 23 publications

References 0 publications

Priming with Plasmid DNAs Expressing Interleukin-12 and Simian Immunodeficiency Virus Gag Enhances the Immunogenicity and Efficacy of an Experimental AIDS Vaccine Based on Recombinant Vesicular Stomatitis Virus

Priming with Plasmid DNAs Expressing Interleukin-12 and Simian Immunodeficiency Virus Gag Enhances the Immunogenicity and Efficacy of an Experimental AIDS Vaccine Based on Recombinant Vesicular Stomatitis Virus

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

Multi-Stability and Multi-Instability Phenomena in a Mathematical Model of Tumor-Immune-Virus Interactions

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