Clinical Study of TUTI-16 in HIV-1 Infected and Uninfected Subjects (THYMON-10001)

This protocol represents the second in human study of TUTI-16, and is being conducted to continue to gather safety and human immunogenicity (anti-HIV-1 Tat titers) data of subcutaneously administered TUTI-16.

HIV-1 Tat protein, a virally encoded toxin, is secreted by HIV-1 infected cells and acts on uninfected cells, rendering them permissive for HIV-1 replication. HIV-1 Tat enhances chronic viral replication and induces immune suppression. Antibodies to Tat inhibit this Tat-mediated transcellular activation in vitro and minimize chronic plasma viremia. HIV-1 Tat activities can be blocked in vitro and in vivo by anti-Tat antibodies. The Thymon Universal Tat Immunogen (TUTI-16) is a fully synthetic, self-adjuvanting lipopeptide vaccine that is water soluble and administered by subcutaneous injection. In preclinical studies, a priming dose and a three week boost in rats induced a high titer antibody response to the eight known distinct epitope variants of HIV-1 Tat protein. These antibodies block the function of the HIV-1 Tat protein (toxin), which is essential to the maintenance of chronic HIV-1 viremia. Therefore, TUTI-16 has potential as a therapeutic vaccine for HIV-1 in humans.

Inclusion Criteria: Males and Females Age ≥18 and ≤50 years at Screening HIV negative healthy subjects or HIV-1 seropositive subjects on effective ART for >2 months (undetectable HIV plasma viremia), viral set point before ART >3,000 CD4+ T-cell count ≥ 500/mm3. Exclusion Criteria: Pregnant/nursing females Positive for HBV or HCV Acute Herpetic event Any clinically significant out-of range laboratory value Routine or PRN consumption of immune suppressive medications that the subject is unable or unwilling to discontinue during the study Participation in another investigational drug/vaccine study within 30 days preceding the first injection of investigational agent in this study.

Goldstein G, Chicca JJ. Exploratory clinical studies of a synthetic HIV-1 Tat epitope vaccine in asymptomatic treatment-naive and antiretroviral-controlled HIV-1 infected subjects plus healthy uninfected subjects. Hum Vaccin Immunother. 2012 Apr;8(4):479-85. doi: 10.4161/hv.19184. Epub 2012 Feb 16.