The Safety and Immunogenicity of an Interleukin-12-Enhanced Multiantigen DNA Vaccine Delivered by Electroporation for the Treatment of HIV-1 Infection.

TitleThe Safety and Immunogenicity of an Interleukin-12-Enhanced Multiantigen DNA Vaccine Delivered by Electroporation for the Treatment of HIV-1 Infection.
Publication TypeJournal Article
Year of Publication2016
AuthorsJacobson JM, Zheng L, Wilson CC, Tebas P, Matining RM, Egan MA, Eldridge J, Landay AL, Clifford DB, Luetkemeyer AF, Tiu J, Martinez AL, Janik J, Spitz TA, Hural J, McElrath J, Frahm N
Corporate AuthorsACTG A5281 Protocol Team
JournalJ Acquir Immune Defic Syndr
Volume71
Issue2
Pagination163-71
Date Published2016 Feb 1
ISSN1944-7884
KeywordsAdolescent, Adult, AIDS Vaccines, CD4-Positive T-Lymphocytes, Cytokines, Electroporation, Female, HIV Antigens, HIV Infections, HIV-1, Humans, Interferon-gamma, Interleukin-12, Interleukin-2, Male, Middle Aged, Vaccines, DNA, Young Adult
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 μg HIV MAG pDNA with 0, 50, 250, or 1000 μg of IL-12 pDNA by IM-EP. A fifth cohort received HIV MAG pDNA and 1000 μg of IL-12 pDNA by standard IM injection.

RESULTS: 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.

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.

DOI10.1097/QAI.0000000000000830
Alternate JournalJ. Acquir. Immune Defic. Syndr.
PubMed ID26761518
PubMed Central IDPMC4712745
Grant List2 UM1 AI068636-08 / AI / NIAID NIH HHS / United States
2 UM1 AI069503-08 / AI / NIAID NIH HHS / United States
2UM1AI069412-08 / AI / NIAID NIH HHS / United States
2UM1AI069432 / AI / NIAID NIH HHS / United States
2UM1AI069501 / AI / NIAID NIH HHS / United States
2UM1AI069511-08 / AI / NIAID NIH HHS / United States
5-P30-AI-045008-15 / AI / NIAID NIH HHS / United States
AI069556 / AI / NIAID NIH HHS / United States
HHSN272200800062C / AI / NIAID NIH HHS / United States
P30 AI045008 / AI / NIAID NIH HHS / United States
U01 AI069439 / AI / NIAID NIH HHS / United States
U01 AI69439 / AI / NIAID NIH HHS / United States
UL1 RR024160 / RR / NCRR NIH HHS / United States
UL1 RR024160 / RR / NCRR NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
UL1 TR000124 / TR / NCATS NIH HHS / United States
UL1 TR001082 / TR / NCATS NIH HHS / United States
UL1 TR001082 / TR / NCATS NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068634 / AI / NIAID NIH HHS / United States
UM1 AI068636 / AI / NIAID NIH HHS / United States
UM1 AI069412 / AI / NIAID NIH HHS / United States
UM1 AI069424 / AI / NIAID NIH HHS / United States
UM1 AI069432 / AI / NIAID NIH HHS / United States
UM1 AI069439 / AI / NIAID NIH HHS / United States
UM1 AI069494 / AI / NIAID NIH HHS / United States
UM1 AI069494 / AI / NIAID NIH HHS / United States
UM1 AI069496 / AI / NIAID NIH HHS / United States
UM1 AI069496 / AI / NIAID NIH HHS / United States
UM1 AI069501 / AI / NIAID NIH HHS / United States
UM1 AI069503 / AI / NIAID NIH HHS / United States
UM1 AI069511 / AI / NIAID NIH HHS / United States
UM1 AI069534 / AI / NIAID NIH HHS / United States
UM1 AI069534-08 / AI / NIAID NIH HHS / United States
UM1 AI069556 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States
UM1 AI106701 / AI / NIAID NIH HHS / United States
UM1AI068636 / AI / NIAID NIH HHS / United States