PBS Clinical Trials

Conducted by the HIV Vaccine Trials Network (HVTN), trial 080 (ClinicalTrials.gov identifier NCT00991354; N=48) examined the safety and immunogenicity of three doses of Inovio’s multi-antigen HIV pDNA vaccine (gag, pol, env) delivered on days 0, 28, and 84 via electroporation (EP) with and without Auro Vaccines’ GeneVax IL-12™ in HIV-uninfected healthy adults. The primary endpoints included safety and immunogenicity measured by intra-cellular cytokine staining (ICS) of vaccine responsive CD4 and CD8 T cells in cryopreserved peripheral blood mononuclear cells (PBMC). Secondary endpoints included measuring immunogenicity in the interferon-gamma (IFN-γ) enzyme-linked immuno-spot (ELISpot) assay of vaccine responsive total T cells in cryopreserved PBMC.

Status: Completed

Kalams SA, Parker SD, Elizaga M, et al. Safety and comparative immunogenicity of an HIV-1 DNA vaccine in combination with plasmid interleukin 12 and impact of intramuscular electroporation for delivery. J Infect Dis. 2013;208(5):818-829. doi:10.1093/infdis/jit236

Clinical Results:

GeneVax IL-12™ delivered via EP:

• Safe and well tolerated
• Increased vaccine-specific CD4 ICS response rate from 44% to 81%
• Increased gag-specific CD4 ICS response rate from 33% to 65%
• Increased vaccine-specific CD8 ICS response rate from 33% to 52%
• Increased gag-specific CD8 ICS response rate from 0% to 7%

Program Milestones:

• Clinical validation of GeneVax IL-12™ adjuvant activity
• Highest overall T cell ICS response rate observed for any stand alone or prime boost vaccine tested by the HVTN prior to HVTN trial 087 (below)

Conducted in collaboration with the International AIDS Vaccine Initiative (IAVI) and Ichor Medical Systems, the B004 trial (ClinicalTrials.gov identifier NCT01496989; N=75) examined the safety and immunogenicity of Auro Vaccines’ multi-antigen HIV GeneVax™ vaccine (env, gag, pol, nef, tat, vif) formulated with various dose levels of GeneVax™ IL-12 delivered on days 0, 28, 56 with electroporation, followed by Ad35 GRIN/ENV (gag, rt, int, nef, env) vaccine delivered on day 168 in HIV-uninfected healthy adults. The primary endpoints included safety and immunogenicity measured by the IFN-γ ELISpot assay of vaccine responsive total T cells in cryopreserved PBMC. Secondary endpoints included measuring vaccine-specific responses in the CD4 and CD8 T cell subsets by ICS.

Status: Completed

J. Mpendo, G. Mutua, J. Nyombayire, R. Ingabire, A. Nanvubya, O. Anzala, E. Karita, P. Hayes, J. Kopycinski, L. Dally, D. Hannaman, M.A. Egan, J.H. Eldridge, K. Syvertsen, J. Lehrman, B. Rasmussen, J. Gilmour, J.H. Cox, P.E. Fast, C. Schmidt. A Phase I Double Blind, Placebo-Controlled, Randomized Study of the Safety and Immunogenicity of Electroporated HIV DNA with or without Interleukin 12 in Prime-Boost Combinations with an Ad35 HIV Vaccine in Healthy HIV-Seronegative African Adults. PLoS One.;10(8):e0134287. doi: 10.1371/journal.pone.0134287 (2015).

Interim Clinical Results:

GeneVax™ with electroporation prime/Ad35 GRIN/ENV boost via IM injection:

• Safe and well tolerated at all dose levels
• Vaccine-specific IFN-γ ELISpot total T cell response rate of 94%
• Vaccine-specific binding Ab response rate of 89%
• Assays of CD4 and CD8 subset responses by ICS pending

Program Milestones:

• African trial participants preferred vaccine delivered with the Ichor electroporation device to standard needle and syringe injection
• Multi-antigen HIV GeneVax™ vaccine plus GeneVax™ IL-12 primes for a synergistic INF-γ ELISpot total T cell response to subsequent Ad35 GRIN/ENV boosting

Conducted by the HIV Vaccine Trials Network (HVTN), trial 090 (ClinicalTrials.gov identifier NCT01438606; N=60) examined the safety and immunogenicity of ascending dose levels (10⁴, 10⁵, 10⁶, 10⁷, and 10⁸ plaque-forming units) of a VesiculoVax™ vectored HIV gag vaccine delivered on days 0 and 56 by intramuscular injection to HIV-uninfected healthy adults. The primary endpoints included safety and immunogenicity measured by ICS of vaccine responsive CD4 and CD8 T cells in cryopreserved PBMC. Secondary endpoints included measuring immunogenicity in the IFN-γ ELISpot assay of vaccine responsive total T cells in cryopreserved PBMC.

Status: Completed

J. D. Fuchs, I. Frank, M. L. Elizaga, M. Allen, N. Frahm, N. Kochar, S. Li, S. Edupuganti, S. Kalams, G.D. Tomaras, R. Sheets, M. Pensiero, M.A. Tremblay, T.J. Higgins, T. Latham, M.A. Egan, D.K. Clarke, and J.H. Eldridge for the HVTN 090 Study Group and the National Institutes of Allergy Infectious Diseases HIV Vaccine Trials Network. First-in-Human Evaluation of the Safety and Immunogenicity of a Recombinant Vesicular Stomatitis Virus (rVSV) HIV-1 gag Vaccine (HVTN 090), Open Forum Infect Dis., Vol.2 No. 3 doi:10.1093/ofid/ofv082 (2015).

Clinical Results:

VesiculoVax™ HIV gag vaccine delivered via IM injection:

• Safe and well tolerated at all dose levels
• Vaccine take in 100% of recipients at all dose levels
• Gag-specific CD4 ICS response rate of 38% at 10⁸ PFU dose level
• Gag-specific CD8 ICS response rate of 0% at 10⁸ PFU dose level
• Vaccine-specific IFN-γ ELISpot total T cell response rate of 63%

Program Milestones:

• First-in-Man clinical validation of safety and immunogenicity of the VesiculoVax™ vectored HIV gag vaccine

Conducted by the AIDS Clinical Trials Group (ACTG), trial 5281 (ClinicalTrials.gov identifier NCT01266616; N=60) is examining the safety and immunogenicity of multi-antigen HIV GeneVax™ vaccine (env, gag, pol, nef, tat, vif) formulated with various dose levels of GeneVax™ IL-12 delivered on days 0, 28, 84 with electroporation in HIV infected subjects. The primary endpoints included safety and immunogenicity measured by ICS of vaccine responsive CD4 and CD8 T cells in cryopreserved PBMC.

Status: Completed

J. M Jacobson, L. Zheng, C.C. Wilson, P. Tebas, R.M. Matining, M.A. Egan, Michael A J. Eldridge, A.L. Landay, D.B. Clifford, A.F. Luetkemeyer, J. Tiu, A. L. Martinez, J. Janik, T.A. Spitz, J. Hural, J. McElrath, N. Frahm, ACTG A5281 Protocol Team. The Safety and Immunogenicity of an Interleukin-12-Enhanced Multiantigen DNA Vaccine Delivered by Electroporation for the Treatment of HIV-1 Infection. J Acquir Immune Defic Syndr. 71(2): 163-171 (2016).

Clinical Results:

GeneVax™ HIV Vaccine with GeneVax™ IL-12 molecular adjuvant:

• Safe and well tolerated at all dose levels
• CD4+ T cells expressing IL-2 in response to Gag and Pol and interferon-γ responses to Gag, Pol, and Env increased from baseline to week 14 in the low-dose (50-μg) IL-12 arm vs. placebo (P < 0.05; intracellular cytokine staining). 
• The total increase in the IL-2 expressing CD4+ T-cell responses to any antigen was also higher in the low-dose IL-12 arm vs. placebo (P = 0.04). 

Cytokine responses by CD8 T cells to HIV antigens were not increased in any vaccine arm relative to placebo.

Program Milestones:

• Multi-antigen GeneVax™ HIV Vaccine plus GeneVax™ IL-12 molecular adjuvant delivered by electroporation safe and well tolerated in HIV-infected subjects.

Conducted by the HIV Vaccine Trials Network (HVTN), trial 087 (ClinicalTrials.gov identifier NCT01578889; N=100) examined the safety and immunogenicity of a PBS Vax™ HIV vaccine. Groups of HIV-uninfected healthy adults were primed with three doses of a multi-antigen HIV GeneVax™ vaccine (env, gag, pol, nef, tat, vif) formulated with various dose levels of GeneVax™ IL-12 delivered on days 0, 28, 84 with electroporation, followed by boosting with VesiculoVax™ vectored HIV gag vaccine delivered on day 168. The primary endpoints included safety and immunogenicity measured by ICS of vaccine responsive CD4 and CD8 T cells in cryopreserved PBMC.

Status: Completed

S.S. Li, N. Kochar, M. Elizaga, C. Hay, G. Wilson, K. Cohen, S. De Rosa, R. Xu, A. Ota-Setlik, D. Morris, G. Finak, M. Allen, H-V. Tieu, I. Frank, M. Sobieszczyk, D. Hannaman, R. Gottardo, P. Gilbert, G. Tomaras, L. Corey, D. Clarke, M.A. Egan, J. Eldridge, M. McElrath, and N. Frahm.  DNA priming increases frequency of T-cell responses to a VSV HIV vaccine with specific enhancement of CD8+ T-cell responses by IL-12 pDNA. Clin Vaccine Immunol. 2017 Nov 6;24(11).

M.L. Elizaga, S.S. Li, N. Kochar, G.J. Wilson, M. Allen, H.V. Tieu, I. Frank, M.E. Sobieszczyk, K. Cohen, B. Sanchez, T.E. Latham, D.K. Clarke, M.A. Egan, J.H. Eldridge, D. Hannaman, R. Xu, A. Ota-Setlik, M.J. McElrath, C.M. Hay, on behalf of the HVTN 087 Protocol Team and the NIAID HIV Vaccine Trials Network. Safety and tolerability of HIV-1 multiantigen pDNA vaccine given with IL-12 plasmid DNA via electroporation, boosted with a recombinant vesicular stomatitis virus HIV Gag vaccine in healthy volunteers. PLoS One, 2018 Sep 20;13(9):e0202753.

Clinical Results:

PBS Vax™ HIV vaccine: GeneVax™ with electroporation prime/VesiculoVax™ boost via IM injection:

• Safe and well tolerated at all dose levels
• High-dose pIL-12 increased the magnitude of CD8+ T-cell responses post-boost compared to no pIL-12 (P = 0.02) The VSV boost increased Gag-specific CD4+ and CD8+ T-cell responses in all groups (P < 0.001) The addition of a DNA prime dramatically improved responses to the VSV vaccine tested previously in the HVTN 090 trial, leading to broad epitope targeting and maintained CD8+ T-cell response rates at early memory.

Program Milestones:

• First-in-Man clinical validation of safety and immunogenicity of the PBS Vax™ HIV Vaccine
• Highest T cell response rate observed for any stand alone or prime boost vaccine tested by the HVTN

Conducted by the NIH Division of AIDS, the TheraVax trial (ClinicalTrials.gov identifier NCT01859325; N=30) examined the safety and immunogenicity of a PBS Vax™ HIV vaccine. Groups of HIV-infected adults on stable combined anti-retroviral therapy (cART) were immunized with multi-antigen HIV GeneVax™ vaccine (env, gag, pol, nef, tat, vif) formulated with GeneVax™ IL-12 delivered on days 0, 28, 84, 252 with electroporation, and with VesiculoVax™ vectored HIV gag vaccine delivered on days 168 and 336. The primary endpoints include safety and immunogenicity measured by ICS of vaccine responsive CD4 and CD8 T cells in cryopreserved PBMC.

Status: Completed

M.C. Sneller, J.S. Justement, K.R. Gittens, M.E. Petrone, K.E. Clarridge, M.A. Proschan, R. Kwan, V. Shi, J. Blazkova, E.W. Refsland, D.E. Morris, K.W. Cohen, M.J. McElrath, R. Xu, M.A. Egan, J.H. Eldridge, E. Benko, C. Kovacs, S. Moir, T.-W. Chun, and A.S. Fauci. A randomized controlled trial of the safety and efficacy of therapeutic vaccination in HIVinfected individuals who initiated antiretroviral therapy during acute/early phase of infection. Sci Transl Med. 2017 Dec 6;9(419).

Clinical Results:

PBS Vax™ HIV vaccine: GeneVax™ with electroporation prime/VesiculoVax™ boost via IM injection:

• Vaccinations were well tolerated with no serious adverse events 
• Vaccination resulted in only modest augmentation of existing HIV-specific CD4+ T cell responses, with little augmentation of CD8+ T cell responses. 

Compared with placebo, the vaccination regimen had no significant effect on the kinetics or magnitude of viral rebound after interruption of ART and no impact on the size of the HIV reservoir in the CD4+ T cell compartment. 

Conducted by Auro Vaccines, the rVSV-EBOV-001 clinical study (ClinicalTrials.gov identifier NCT02718469; N=38) examined the safety and immunogenicity of ascending dose levels (10⁴, 10⁵, 10⁶, and 10⁷ plaque-forming units) of a VesiculoVax™ vectored Ebola GP vaccine delivered on days 0 and 28 by intramuscular injection to healthy adults. The primary outcomes were safety and tolerability; immunogenicity, assessed as GP-specific humoral immune response (at 2 weeks after each dose) and cellular immune response (at 1 and 2 weeks after each dose), was a secondary outcome.

Status: Completed

Clarke DK, Xu R, Matassov D, Latham TE, Ota-Setlik A, Gerardi CS, Luckay A, Witko SE, Hermida L, Higgins T, Tremblay M, Sciotto-Brown S, Chen T, Egan MA, Rusnak JM, Ward LA, Eldridge JH. Safety and immunogenicity of a highly attenuated rVSVN4CT1-EBOVGP1 Ebola virus vaccine: a randomised, double-blind, placebo-controlled, phase 1 clinical trial. Lancet Infect Dis. 2020 Apr;20(4):455-466. doi: 10.1016/S1473-3099(19)30614-0. Epub 2020 Jan 14.

Clinical Results:

• The rVSVN4CT1-EBOVGP1 vaccine was well tolerated at all dose levels tested and no severe adverse events were observed.
• A GP-specific IgG response was detected in all vaccine recipients after two doses (and IgG response frequency was 100% after a single high dose).

An Ebola virus neutralizing response was detected in 100% of participants in the high-dose cohort.