a multicenter, randomized, placebo-controlled, double-blind trial to evaluate the safety and immunogenicity of the therion recombinant vaccinia-hiv-1 iiib env/gag/pol vaccine (tcb-3b) and mn rgp 120/hiv-1 in alum.

Conditions: HIV Infections

Summary: to evaluate the safety of administering therion recombinant vaccinia-hiv-1 iiib env/gag/pol vaccine (tbc-3b) vaccinations to vaccinia-naive individuals. to evaluate the immunogenicity of priming with tbc-3b by the scarification, intradermal, and subcutaneous routes, followed by booster immunization of mn rgp120 hiv-1. to compare the immunogenicity of priming with tbc-3b in vaccinia-naive individuals to vaccinia-immune individuals. in prior trials evaluating alternative methods of vaccine administration, scarification has been found to be an imprecise method of administration and allows only 1.0 - 2.5 microliters of immunogen to be given. since it is not feasible to produce vaccine at concentrations higher than 10 to the 10th pfu/ml, this method limits the maximum deliverable dose. intradermal and subcutaneous injection routes allow larger volumes of vaccinia to be given, i.e.: up to 200 microliters intradermally and up to 100 ml subcutaneously. in the present study, the initial priming dose will be the same administered by all 3 methods; however, the second priming dose administered at 2 months intradermally and subcutaneously will be 2 logs higher in order to achieve boosting of immune responses, particularly to gag and pol components of tbc-3b.

in prior trials evaluating alternative methods of vaccine administration, scarification has been found to be an imprecise method of administration and allows only 1.0 - 2.5 microliters of immunogen to be given. since it is not feasible to produce vaccine at concentrations higher than 10 to the 10th pfu/ml, this method limits the maximum deliverable dose. intradermal and subcutaneous injection routes allow larger volumes of vaccinia to be given, i.e.: up to 200 microliters intradermally and up to 100 ml subcutaneously. in the present study, the initial priming dose will be the same administered by all 3 methods; however, the second priming dose administered at 2 months intradermally and subcutaneously will be 2 logs higher in order to achieve boosting of immune responses, particularly to gag and pol components of tbc-3b. after volunteers are recruited, screened and enrolled in the study, they will be randomized to group c, d, or e. each group will enroll 10 patients and 2 controls. the placebo control for tbc-3b will be standard vaccinia vaccination administered at doses no higher than that administered by scarification; the placebo control for mn rgp120 will be alum. group c will receive undiluted tbc-3b by scarification, at months 0 and 2. group d will receive diluted tbc-3b intradermally at month 0 and undiluted tbc-3b at month 2. group e will receive diluted tbc-3b subcutaneously at month 0 and undiluted tbc-3b at month 2. at months 8 and 12 all groups will receive mn rgp 120/hiv-1 in alum intramuscularly.

Eligibility criteria:
inclusion criteria patients must have: * negative fda-approved elisa for hiv within 8 weeks of immunization. * normal history and physical examination. * negativity for hepatitis b surface antigen. * availability for follow-up for planned duration of the study (18 months). exclusion criteria co-existing condition: patients with the following symptoms or conditions are excluded: * medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol. specifically excluded are people with a history of suicide attempts, recent suicidal ideation or who have past or present psychosis. * active syphilis. note: if the serology is documented to be a false positive or due to a remote (\> 6 months) treated infection, the volunteer is eligible. * active tuberculosis. note: patients with a positive ppd and a normal chest x-ray showing no evidence of tb and not requiring inh therapy are eligible. * household contacts with, or occupational exposure to, people with any of the following: pregnancy. \<12 months of age. eczema or immunodeficiency disease. use of immunosuppressive medications. patients with the following prior conditions are excluded: * history of immunodeficiency, chronic illness, malignancy or autoimmune disease. * history of cancer, unless there has been surgical excision followed by a sufficient observation period to give a reasonable assurance of cure. * any history of anaphylaxis or history of other serious adverse reactions to vaccines. * history of serious allergic reaction to any substance, requiring hospitalization or emergent medical care (e.g., stevens-johnson syndrome, bronchospasm, or hypotension). * eczema within the past year. * history of smallpox vaccination. * envelope bands on hiv-1 western blot within 8 weeks of immunization. prior medication: excluded: * use of immunosuppressive. * live attenuated vaccines within 60 days of study. * note: medically indicated subunit or killed vaccines (e.g. influenza, pneumococcal) do not exclude, but should be given at least 2 weeks prior to hiv immunizations. * experimental agents within 30 days prior to study. * prior receipt of hiv-1 vaccines or placebo recipient in a previous hiv vaccine trial. receipt of blood products or immunoglobulin within past 6 months. risk behavior: excluded: * history of injection drug use within the last 12 months prior to enrollment. * higher or intermediate risk sexual behavior as defined by the aveg. * lower risk sexual behavior as defined by aids vaccine evaluation group (aveg) procedures.

Keywords: vaccines, synthetic vaccinia virus placebos hiv-1 aids vaccines hiv seronegativity genes, env genes, pol genes, gag hiv preventive vaccine