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Journal article
The Safety and Immunogenicity of an Interleukin-12-Enhanced Multiantigen DNA Vaccine Delivered by Electroporation for the Treatment of HIV-1 Infection
JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, v 71(2), pp 163-171
01 Feb 2016
PMID: 26761518
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background:Therapeutic vaccination is being studied in eradication and functional cure strategies for HIV-1. The Profectus Biosciences multiantigen (MAG) HIV-1 DNA vaccine encodes HIV-1 Gag/Pol, Nef/Tat/Vif, and Envelope, and interleukin-12 (IL-12) and is delivered by electroporation combined with intramuscular injection (IM-EP).Methods:Sixty-two HIV-1-infected patients on antiretroviral therapy (plasma HIV-1 RNA levels 200 copies/mL; CD4(+) T-cell counts 500 cells/mm(3)) were randomly allocated 5:1 to receive vaccine or placebo. At weeks 0, 4, and 12, 4 consecutive cohorts received 3000 g HIV MAG pDNA with 0, 50, 250, or 1000 g of IL-12 pDNA by IM-EP. A fifth cohort received HIV MAG pDNA and 1000 g of IL-12 pDNA by standard IM injection.Results:CD4(+) T cells expressing IL-2 in response to Gag and Pol and interferon- responses to Gag, Pol, and Env increased from baseline to week 14 in the low-dose (50-g) 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.Conclusions:HIV-1 MAG/low-dose IL-12 DNA vaccine delivered by IM-EP augmented CD4(+) but not CD8(+) T-cell responses to multiple HIV-1 antigens.
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Details
- Title
- The Safety and Immunogenicity of an Interleukin-12-Enhanced Multiantigen DNA Vaccine Delivered by Electroporation for the Treatment of HIV-1 Infection
- Creators
- Jeffrey M. Jacobson - Drexel UniversityLu Zheng - Harvard UniversityCara C. Wilson - University of Colorado SystemPablo Tebas - University of PennsylvaniaRoy M. Matining - Harvard UniversityMichael A. Egan - Profectus Biosciences (United States)John Eldridge - Profectus Biosciences (United States)Alan L. Landay - Rush UniversityDavid B. Clifford - Washington University in St. LouisAnne F. Luetkemeyer - University of California SystemJennifer Tiu - Social and Scientific Systems (United States)Ana L. Martinez - National Institutes of HealthJennifer Janik - Frontier Science & Technology Research FoundationTeresa A. Spitz - Washington University in St. LouisJohn Hural - University of WashingtonJuliana McElrath - Fred Hutchinson Canc Res Ctr, 1124 Columbia St, Seattle, WA 98104 USANicole Frahm - University of WashingtonACTG A5281 Protocol Team
- Publication Details
- JAIDS-JOURNAL OF ACQUIRED IMMUNE DEFICIENCY SYNDROMES, v 71(2), pp 163-171
- Publisher
- Lippincott Williams & Wilkins
- Number of pages
- 9
- Grant note
- UL1 RR024160 / CRC Grant 2UM1AI069501 / University of Cincinnati CRS ACTG CTU Grant A1069424 / UCLA CARE Center CRS ACTG CTU Grant Merck; Merck & Company UM1 AI068634; UM1 AI068636; UM1 AI106701 / National Institute of Allergy and Infectious Diseases of the National Institutes of Health; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) UL1TR000124 / NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Advancing Translational Sciences (NCATS) 2UM1AI069412-08 / Massachusetts General Hospital (MGH) CRS ACTG CTU Grant 2UM1AI069432; UL1 TR001082 / University of Colorado Hospital CRS ACTG CTU Grant N01 AI80062C / NIAID; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) UM1 AI069496 / UCSF AIDS CRS ACTG CTU UL1RR024160 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) U01 AI69439 / Washington University in St. Louis CRS ACTG CTU Grant UM1 AI069534-08 / Penn Therapeutics CRS ACTG CTU Grant 5-P30-AI-045008-15 / CFAR Grant UM1AI069534 / NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Allergy & Infectious Diseases (NIAID) 2UM1AI069412-08 / Brigham and Women's Hospital CRS ACTG CTU Grant 2 UM1 AI069503-08; 2 UM1 AI068636-08 / HART CRS ACTG CTU Grant 2UM1AI069511-08 / University of Rochester/Trillium Health ACTG CTU Grant UL1 TR000124 / CTRC Grant AI069556 / Stanford University ACTG CTU Grant UM1 AI069494 / University of Pittsburgh CRS ACTG CTU Grant
- Resource Type
- Journal article
- Language
- English
- Web of Science ID
- WOS:000368803900006
- Scopus ID
- 2-s2.0-84955608409
- Other Identifier
- 991019335238504721
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- Collaboration types
- Industry collaboration
- Domestic collaboration
- Web of Science research areas
- Immunology
- Infectious Diseases