a multicenter, randomized, placebo-controlled, double-blind trial to evaluate the safety and immunogenicity of a recombinant vaccinia-hiv-1 iiib env/gag/pol vaccine (tbc-3b)

Conditions: HIV Infections

Summary: to evaluate, in healthy hiv-1 seronegative vaccinia-immune and vaccinia-naive volunteers, the safety and immunogenicity of an hiv-1 candidate vaccine (tbc-3b) consisting of a live recombinant vaccinia virus expressing the env, gag, and pol genes of hiv-1 iiib strain. to evaluate the potential of boosting with one of a variety of hiv-1 recombinant subunit, peptide, or pseudovirion vaccines, if available, to augment the immune responses of the vaccinees. antigenic drift, defined as the genetic variation of the hiv-1 envelope gene that results in antigenic variation during natural infection, may confound attempts to achieve protective immunity using a vaccine based solely on hiv-1 envelope proteins. inclusion of conserved core and polymerase proteins along with envelope protein in a candidate vaccine may address some of the problems with antigenic variability. a prime-boost immunization approach using a novel priming immunogen expressing env, gag, and pol genes of the hiv-1 iiib strain will be attempted in this study.

antigenic drift, defined as the genetic variation of the hiv-1 envelope gene that results in antigenic variation during natural infection, may confound attempts to achieve protective immunity using a vaccine based solely on hiv-1 envelope proteins. inclusion of conserved core and polymerase proteins along with envelope protein in a candidate vaccine may address some of the problems with antigenic variability. a prime-boost immunization approach using a novel priming immunogen expressing env, gag, and pol genes of the hiv-1 iiib strain will be attempted in this study. in part i, vaccinia-immune volunteers are randomized to one of two regimens. group a receives priming with tbc-3b on days 0 and 56, followed by boosting on day 224 (8 months) with one of the following: tbc-3b, an alternative immunogen such as pseudovirion particles or a recombinant hiv-1 subunit or peptide vaccine, or placebo. group b receives priming with control vaccine (dryvax), followed by boosting with an appropriate placebo. at least 50 percent of subjects in part i will be observed for a minimum of 8 weeks before subsequent volunteers are enrolled in part ii. per 11/18/94 amendment, part i boosting is given on day 392. per 5/19/95 amendment, part i boosting is given on day 756 if not available on day 392; if the appropriate product is not available then, the study will end on day 756. in part ii, vaccinia-naive volunteers are randomized to one of three regimens. group c receives tbc-3b on day 0 and saline placebo on day 56. group d receives tbc-3b on days 0 and 56. both group c and d receive boosting with tbc-3b or an alternative immunogen on day 224. group e receives control vaccine (dryvax) on days 0 and 56, followed by appropriate placebo on day 224. per 06/10/94 addendum, volunteers will be contacted once or twice per year for at least 5 years to check on health status. note: part i (part a) of the protocol has closed to accrual.

Eligibility criteria:
inclusion criteria subjects must have: * negative elisa and western blot for hiv-1 within 6 weeks prior to immunization. * normal history and physical exam. * history of smallpox vaccination at least 5 years prior to study entry (part i) or no prior smallpox vaccination (part ii). * absolute cd4 count \>= 400 cells/mm3. * normal urinalysis. note: * no more than 10 percent of volunteers in both parts i and ii may be over 50 years of age. 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. * occupational responsibilities that preclude 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. * eczema. * household contact with persons meeting any of the following criteria: * pregnancy, less than 12 months of age, eczema, immunodeficiency disease, or use of immunosuppressive medications. 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. * eczema within the past year. * history of serious allergic reaction to any substance, requiring hospitalization or emergent medical care (e.g., steven-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: * 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: * receipt of blood products or immunoglobulins within the past 6 months. it is strongly recommended that any activity that might expose subject to hiv (unprotected sex or needle sharing) be avoided.

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