Exploratory clinical studies of a synthetic HIV-1 Tat epitope vaccine in asymptomatic treatment-naïve and antiretroviral-controlled HIV-1 infected subjects plus healthy uninfected subjects

Human Vaccines & Immunotherapeutics
Gideon Goldstein, John Chicca

Abstract

TUTI-16 is a synthetic universal HIV-1 Tat epitope vaccine, designed to induce anti-Tat antibodies that block the function of circulating Tat, an HIV encoded protein secreted by HIV-1 infected cells. Circulating Tat activates CD4 T cells, permitting HIV replication and sustained viremia. Safety, immunogenicity and antiretroviral potential of TUTI-16 were explored in a randomized double-blind dose-escalating study in asymptomatic treatment-naïve HIV-1 infected subjects. TUTI-16 was safe, with mild local and systemic injection-related adverse reactions, but the antibody response was barely detectable. Surprisingly, a highly statistically significant reduction of HIV-1 viral load was found in the lowest 30 μg vaccine dose group (p < 0.01) but not at the higher doses. We posited that an anti-Tat antibody response below the limit of detection inhibited HIV viral load at this dose, an effect nullified at higher vaccine doses by activating cytokines induced by adjuvant components in TUTI-16. To clarify this immunogenicity/activation conundrum open label immunogenicity studies were performed in healthy HIV uninfected and aviremic ART-controlled HIV-infected subjects. These established that (1) healthy HIV negative subjects had robust a...Continue Reading

References

Dec 1, 1995·The Journal of Experimental Medicine·S I StapransM B Feinberg
Sep 1, 1996·Nature Medicine·G Goldstein
Apr 10, 1997·The New England Journal of Medicine·R A RoyceM S Cohen
Jul 22, 1997·Proceedings of the National Academy of Sciences of the United States of America·C J LiA B Pardee
Sep 15, 1999·Proceedings of the National Academy of Sciences of the United States of America·S S CohenD I Cohen
Oct 23, 2002·The Journal of Immunology : Official Journal of the American Association of Immunologists·Weiguang ZengDavid C Jackson
Sep 13, 2005·American Journal of Physiology. Regulatory, Integrative and Comparative Physiology·Thomas HübschleJoachim Roth
Mar 28, 2008·Proceedings of the National Academy of Sciences of the United States of America·Bita SahafLeonore A Herzenberg
Apr 17, 2008·Proceedings of the National Academy of Sciences of the United States of America·Hannah H AlphsRichard B S Roden
Feb 12, 2009·Vaccine·Olimpia LongoBarbara Ensoli
Jun 3, 2009·The Journal of Experimental Medicine·Zabrina L Brumme, Bruce D Walker
Sep 23, 2009·AIDS·UNKNOWN HIV-CAUSAL CollaborationMiguel A Hernán
Nov 3, 2009·Vaccine·Barbara EnsoliEnrico Garaci
Dec 17, 2009·Nature Reviews. Immunology·Andrew J McMichaelBarton F Haynes
Jul 20, 2011·The New England Journal of Medicine·Myron S CohenUNKNOWN HPTN 052 Study Team

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Citations

Mar 10, 2015·AIDS Research and Human Retroviruses·Chandra Nath RoyHitoshi Oshitani
Jan 1, 2012·Biology·Guillaume Mousseau, Susana Valente

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