HIV-1 Env vaccine comprised of electroporated DNA and protein co-administered with Talabostat

Cristillo, Anthony D.; Galmin, Lindsey; Restrepo, Sara María Robledo; Hudacik, Lauren; Suschak, John; Lewis, Brad; Draghia-Akli, Ruxandra; Aziz, Nazneen; Weiss, Deborah; Markham, Phillip D.; Pal, Ranajit

doi:10.1016/j.bbrc.2008.02.145

Cited by 8 publications

(5 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Based on the data presented here, we propose that Val-boroPro and other similar compounds with anti-tumor activity would be far more likely to produce clinical tumor responses when used as immunotherapeutic adjuvants rather than in combination with cytotoxic agents. Indeed, in addition to this report demonstrating for the first time that Val-boroPro can produce regression of large tumors when given with DC vaccines, the compound has also shown an adjuvant effect in a viral vaccine model [47]. Furthermore, the inflammatory profile induced by Val-boroPro [20] and the need for an intact host immune system for full antitumor activity suggests that cytotoxic agents might actually impair clinical activity.…”

Section: Discussionmentioning

confidence: 76%

Val-BoroPro Accelerates T Cell Priming via Modulation of Dendritic Cell Trafficking Resulting in Complete Regression of Established Murine Tumors

Walsh

Duncan²,

Larabee³

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

Although tumors naturally prime adaptive immune responses, tolerance may limit the capacity to control progression and can compromise effectiveness of immune-based therapies for cancer. Post-proline cleaving enzymes (PPCE) modulate protein function through N-terminal dipeptide cleavage and inhibition of these enzymes has been shown to have anti-tumor activity. We investigated the mechanism by which Val-boroPro, a boronic dipeptide that inhibits post-proline cleaving enzymes, mediates tumor regression and tested whether this agent could serve as a novel immune adjuvant to dendritic cell vaccines in two different murine syngeneic murine tumors. In mice challenged with MB49, which expresses the HY antigen complex, T cell responses primed by the tumor with and without Val-boroPro were measured using interferon gamma ELISPOT. Antibody depletion and gene-deficient mice were used to establish the immune cell subsets required for tumor regression. We demonstrate that Val-boroPro mediates tumor eradication by accelerating the expansion of tumor-specific T cells. Interestingly, T cells primed by tumor during Val-boroPro treatment demonstrate increased capacity to reject tumors following adoptive transfer without further treatment of the recipient. Val-boroPro -mediated tumor regression requires dendritic cells and is associated with enhanced trafficking of dendritic cells to tumor draining lymph nodes. Finally, dendritic cell vaccination combined with Val-boroPro treatment results in complete regression of established tumors. Our findings demonstrate that Val-boroPro has antitumor activity and a novel mechanism of action that involves more robust DC trafficking with earlier priming of T cells. Finally, we show that Val-boroPro has potent adjuvant properties resulting in an effective therapeutic vaccine.

show abstract

Section: Discussionmentioning

confidence: 76%

Val-BoroPro Accelerates T Cell Priming via Modulation of Dendritic Cell Trafficking Resulting in Complete Regression of Established Murine Tumors

Walsh

Duncan²,

Larabee³

et al. 2013

PLoS ONE

View full text Add to dashboard Cite

show abstract

“…In the HIV vaccine field, few trials have used DNA as the single vaccine modality due to its relatively low immunogenicity in primates, but DNA vaccination was shown to protect macaques from chronic viremia [ 24 , 25 , 26 ]. Yet, DNA vaccination methods that optimize immunogen expression and delivery have made great progress in improving immune responses, and it was further shown that DNA vaccines induce long-lasting immunity against HIV/SIV in non-human primates [ 24 , 27 , 28 , 29 ].…”

Section: Introductionmentioning

confidence: 99%

HIV DNA Vaccine: Stepwise Improvements Make a Difference

et al. 2014

View full text Add to dashboard Cite

Inefficient DNA delivery methods and low expression of plasmid DNA have been major obstacles for the use of plasmid DNA as vaccine for HIV/AIDS. This review describes successful efforts to improve DNA vaccine methodology over the past ~30 years. DNA vaccination, either alone or in combination with other methods, has the potential to be a rapid, safe, and effective vaccine platform against AIDS. Recent clinical trials suggest the feasibility of its translation to the clinic.

show abstract

“…Although in vivo EP has been utilized to improve immune responses to DNA vaccines alone or in prime-boost regimens with both proteins and viral-vectored vaccines against HIV-1 [11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][31][32][33][34][35][36][37], to our knowledge no studies on the effect of in vivo EP on immunogenicity against HIV-1 elicited by DNA-VLP prime-boost immunizations have been reported. Therefore, in the present study we tested the effect of in vivo EP during DNA priming on immunogenicity in the heterologous DNA-VLP prime-boost immunization, in which HIV-1 VLP was produced by a stably transfected Drosophila S2 cell clone as we described before [40].…”

Section: Discussionmentioning

confidence: 99%

In vivo electroporation in DNA-VLP prime-boost preferentially enhances HIV-1 envelope-specific IgG2a, neutralizing antibody and CD8 T cell responses

Huang

Zhu

Huang

et al. 2017

Vaccine

View full text Add to dashboard Cite

Although in vivo electroporation (EP) has been utilized to improve immunogenicity in DNA vaccines alone or in prime-boost regimens with both proteins and viral-vectors, no studies on in vivo EP in DNA-VLP prime-boost regimens against HIV-1 have been reported. Previously we developed stably transfected Drosophila S2 clones to produce HIV-1 virus-like particles (VLP) and demonstrated that priming mice twice with DNA plasmids encoding HIV-1 gp120 and gag and boosting twice with HIV-1 VLP (i.e. DDVV immunization) elicited both envelope-specific antibody and envelope and gag-specific CD8 T cell responses. However, the potency and the breadth of immunogenicity still need to be improved. In this study we tested the effect of in vivo EP during DNA priming on immunogenicity of this DNA-VLP prime-boost regimen. Here we report that although both DDVV and DDVV+EP elicited gp120-specific ELISA-binding antibody responses, average EC values of gp120-specific ELISA-binding total IgG, IgG2a, but not IgG1, antibody responses were significantly higher in DDVV+EP than in DDVV. Moreover, while DDVV elicited neutralizing antibody responses against autologous, but not other five, strains tested, DDVV+EP not only elicited significantly higher anti-autologous neutralizing antibody responses, but also cross-neutralizes four of five other HIV-1 strains tested, including two tier 2 strains. Finally, although CD4 and CD8 T cells from both DDVV and DDVV+EP immunizations secreted IFN-γ, IL-2, TNF-α upon HIV-1 envelope peptide stimulation, average HIV-1 envelope-specific CD8 T cells that secreted IFN-γ, IL-2 and/or TNF-α were significantly higher in DDVV+EP than in DDVV. Thus we conclude that DDVV+EP immunization preferentially increases HIV-1 envelope-specific T1 cytokine-mediated IgG2a responses and significantly enhances the potency and the breadth of neutralizing antibody responses including tier 2 viruses. Further study on this heterologous regimen in large animals is warranted.

show abstract

HIV-1 Env vaccine comprised of electroporated DNA and protein co-administered with Talabostat

Cited by 8 publications

References 34 publications

Val-BoroPro Accelerates T Cell Priming via Modulation of Dendritic Cell Trafficking Resulting in Complete Regression of Established Murine Tumors

Val-BoroPro Accelerates T Cell Priming via Modulation of Dendritic Cell Trafficking Resulting in Complete Regression of Established Murine Tumors

HIV DNA Vaccine: Stepwise Improvements Make a Difference

In vivo electroporation in DNA-VLP prime-boost preferentially enhances HIV-1 envelope-specific IgG2a, neutralizing antibody and CD8 T cell responses

Contact Info

Product

Resources

About