a phase i, multicenter, randomized trial to evaluate the safety and immunogenicity of vaccinia-derived mn hiv-1 recombinant envelope glycoprotein (rgp160) of human immunodeficiency virus at two different vaccination schedules

Conditions: HIV Infections; HIV Seronegativity

Summary: amended 8/94: to expand the safety and immunogenicity profile of mn rgp160 vaccine (immuno-ag) by administering a higher dose (800 mcg) at 0, 1, 6, and 12 months and 0, 2, 8 and 14 months (these two schedules were compared in veu 013a using a dose of 200 mcg). to obtain plasma following the fourth immunization. to evaluate skin test reactivity. original (replaced): to determine in healthy volunteers the safety and immunogenicity of two immunizations of mn rgp160 vaccine (immuno-ag) in combination with a live recombinant vaccinia virus lav hiv-1 gp160 vaccine (hivac-1e) versus dryvax (the standard smallpox vaccine that was used for many years) control in combination with placebo. original (replaced): a gp160 vaccine derived from the mn strain, the most prevalent strain of hiv-1 in the united states, has been developed. a previous study showed that a combination vaccine strategy, consisting of priming with hivac-1e followed by boosting with a gp160 subunit vaccine, resulted in humoral and cellular immune responses of greater and longer duration than either vaccine alone. thus, a live vector/subunit boost approach using the mn rgp160 vaccine merits investigation.

original (replaced): a gp160 vaccine derived from the mn strain, the most prevalent strain of hiv-1 in the united states, has been developed. a previous study showed that a combination vaccine strategy, consisting of priming with hivac-1e followed by boosting with a gp160 subunit vaccine, resulted in humoral and cellular immune responses of greater and longer duration than either vaccine alone. thus, a live vector/subunit boost approach using the mn rgp160 vaccine merits investigation. amended 8/94: volunteers are randomized to receive 800 mcg mn rgp160 vaccine (immuno-ag) or adjuvant control (placebo) on one of two dosing schedules. sixteen volunteers receive candidate vaccine and four volunteers receive placebo. original (replaced): volunteers are randomized to receive either hivac-1e on days 0 and 56 followed by immunization with mn rgp160 vaccine on days 224 and 364, or dryvax control on days 0 and 56 followed by placebo on days 224 and 364. ten volunteers are entered on the mn rgp160 vaccine arm and two volunteers on the placebo arm. per amendment 7/96: two additional booster immunizations of 600 mcg of mn rgp 120/hiv-1 vaccine given at study months 22 and 24 to consenting st. louis university volunteers.

Eligibility criteria:
inclusion criteria subjects must have: * normal history and physical exam. * negative test for hiv by elisa within 6 weeks prior to immunization. * negative test for hiv by western blot. * cd4 count \>= 400 cells/mm3. * no history of smallpox vaccination. * normal urine dipstick with esterase and nitrate. * no history of immunodeficiency, chronic illness, autoimmune disease, or use of immunosuppresssive medications. exclusion criteria co-existing condition: subjects with the following conditions are excluded: * positive for hepatitis b surface antigen. * medical or psychiatric condition or occupational responsibilities that preclude compliance. * active syphilis (note: if serology is documented to be a false positive or due to a remote (\> 6 months) infection, subject is eligible). * active tuberculosis (note: subjects with a positive ppd and normal x-ray showing no evidence of tb and who do not require inh therapy are eligible). * eczema. household contact with persons meeting any of the following criteria: * pregnancy, \< 12 months of age, eczema, or immunodeficiency disease or use of immunosuppressive medications. subjects with the following prior conditions are excluded: * history of anaphylaxis or other serious adverse reactions to vaccines. * eczema within the past year. * per 8/94 amendment: history of cancer unless surgically excised with reasonable assurance of cure. * per 8/94 amendment: history of serious allergic reaction requiring hospitalization or emergent medical care. prior medication: excluded: * prior hiv vaccines. * live attenuated vaccines within the past 60 days. note: medically indicated subunit or killed vaccines (e.g., influenza, pneumococcal) do not exclude but should be administered at least 2 weeks prior to hiv immunizations. * experimental agents within the past 30 days. prior treatment: excluded: * blood products or immunoglobulin within the past 6 months. higher risk behavior for hiv infection as determined by screening questionnaire, including: * history of injection drug use within 12 months prior to study entry. * higher or intermediate risk sexual behavior.

Keywords: vaccines, synthetic vaccinia virus viral vaccines smallpox vaccine hiv-1 hiv envelope protein gp160 aids vaccines hiv seronegativity hiv preventive vaccine