a phase i safety and immunogenicity trial of live recombinant canarypox alvac-hiv vcp300 and hiv-1 sf-2 rgp120 in hiv-1 uninfected adult volunteers

Conditions: HIV Infections

Summary: to evaluate, in hiv-negative volunteers, the safety and immunogenicity of alvac-hiv mn120tmgnp (vcp300) followed by or combined with boosting using rgp120/hiv-1sf2. to compare alvac-hiv vcp300 with alvac-rg rabies glycoprotein (vcp65) as a control. to evaluate an accelerated immunization schedule at 0, 1, 3, and 6 months versus 0, 1, 6, and 9 months. the combination of a live recombinant primer followed by a subunit boost has the potential to induce not only cytotoxic t lymphocytes but also neutralizing antibody.

the combination of a live recombinant primer followed by a subunit boost has the potential to induce not only cytotoxic t lymphocytes but also neutralizing antibody. volunteers are randomized to one of seven groups to receive immunizations with either alvac-hiv vcp300 or alvac-rg vcp65 (control), plus simultaneous or sequential boosting with rgp120/hiv-1sf2 or placebo. immunizations are given at 0, 1, 6, and 9 months or 0, 1, 3, and 6 months. volunteers are followed for at least 24 months.

Eligibility criteria:
inclusion criteria volunteers must have: * normal history and physical exam. * elisa and western blot negative for hiv. * cd4 count \>= 400 cells/mm3. * normal urine dipstick with esterase and nitrite. * lower risk sexual behavior. exclusion criteria co-existing condition: subjects with the following symptoms or conditions are excluded: * positive hepatitis b surface antigen. * medical or psychiatric condition (such as recent suicidal ideation or present psychosis) that precludes compliance. * active syphilis. note: subjects with serology documented to be a false positive or due to a remote (\> 6 months) treated infection are eligible. * active tuberculosis. note: subjects with a positive ppd and a normal chest x-ray showing no evidence of tb and not requiring isoniazid therapy are eligible. * allergy to egg products or neomycin. subjects with the following prior conditions are excluded: * history of immunodeficiency, chronic illness, autoimmune disease, or use of immunosuppressive medications. * history of anaphylaxis or other serious adverse reactions to vaccines. * prior immunization against rabies. * history of serious allergic reaction to any substance, requiring hospitalization or emergent medical care (e.g., stevens-johnson syndrome, bronchospasm, or hypotension). * prior psychiatric condition (such as history of suicide attempts or past psychosis) that precludes compliance. * history of cancer unless there has been surgical excision that is considered to have achieved cure. prior medication: excluded: * live attenuated vaccines within 60 days prior to study entry. note: medically indicated killed or subunit vaccines (e.g., influenza, pneumococcal) do not exclude if administered at least 2 weeks from hiv immunizations. * experimental agents within 30 days prior to study entry. * prior hiv vaccines. * prior rabies immunization. prior treatment: excluded: * blood products or immunoglobulin within 6 months prior to study entry. identifiable high-risk behavior for hiv infection, such as * injection drug use within past 12 months. * higher or intermediate risk sexual behavior.

Keywords: vaccines, synthetic hiv envelope protein gp120 aids vaccines hiv seronegativity avipoxvirus hiv preventive vaccine