OUTLINE OF PROTOCOL 002

Subjects: Healthy, HIV-1 uninfected adult, vaccinia-naive volunteers without identifiable high-risk behavior for HIV-1 infection.

Schema:

Product Description: HIVAC-1e: Vaccinia vector containing HIV-1 LAI rgp160 [Bristol Myers-Squibb/Oncogen]
VaxSyn: Baculovirus/insect cell-derived HIV-1 LAI rgp160 in alum [MicroGeneSys]

Time Period: First volunteer entered on 11/29/88 and the last on 02/04/92; follow-up for Dose Levels I and II: >16 months; follow-up for Dose Level III: 14 months.

Clinical Sites: Johns Hopkins University, Saint Louis University (Marshall University), University of Rochester, University of Washington, Vanderbilt University

Study Chair: Barney Graham, Vanderbilt University

INCLUSION CRITERIA

• Age: >18 and <60
• Normal history and physical examination
• Normal complete blood count and differential defined as:
  • Hematocrit >35% for women; >39% for men
  • White count >4000 cells/mm³ with normal differential
  • Total lymphocyte count >800 cells/mm³
  • T4 cells 400 >cells/mm³
  • Platelets (120,000-550,000)
• Normal urinalysis
• Normal ALT (<1.1 x institutional upper normal limit)and creatinine (0.1-1.6 mg/dl)
• Negative ELISA and Western blot test for HIV (i.e., no reactivity at any band on any pre-entry assay)
• Negative HIV p24 antigen test
• Normal cell mediated immune responses using Merieux skin test
• Negative HIV culture
• NO EVIDENCE OF SMALLPOX VACCINATION (As an operational definition an individual can be considered "vaccinia naive" only if no scar is observable and the volunteers claims and/or has evidence of not being vaccinated. If the volunteer does not know his/her history, it should be presumed that he/she was vaccinated.)

EXCLUSION CRITERIA

• Subjects with identifiable high risk behavior for HIV infection as determined by screening questions designed to identify risk factors for HIV infection. Specific exclusions include:
  • Any history of IV (intravenous) drug use
  • Syphilis, gonorrhea, or any other sexually transmitted diseases (including chlamydia or pelvic inflammatory disease) in the last 6 months
  • More than one sexual partner in the last 6 months
• Previous receipt of blood transfusions or cryoprecipitates within the past 6 months
• History of immunodeficiency, chronic illness, or use of immunosuppressive medications
• Evidence of depression or under treatment for psychiatric problems during the past year
• History of positive PPD
• Positive syphilis serology (e.g., VDRL)
• Positive for circulating Hepatitis B antigen
• Eczema, active or recent (within the past year)
• Pregnant spouse or pregnant household contact
• Household contact with children less than 12 months old
• Household contact with anyone with eczema
• Household contact with anyone with immunodeficiencies

STUDY GOALS

• To determine the reactivity and safety of recombinant vaccinia virus expressing envelope glycoproteins of human immunodeficiency virus (HIV) in human volunteers.
• To determine the immunogenicity of recombinant vaccinia virus expressing envelope glycoproteins of HIV in human volunteers.
• To evaluate the safety and immunogenicity of booster doses of rgp160 in live-vector primed volunteers.

REFERENCES

Graham BS, Belshe RB, Clements ML, Dolin R, Corey L, Wright PF, Gorse GJ, Midthun K, Keefer MC, Roberts NJ Jr, Schwartz DH, Agosti JM, Fernie BF, Stablein DM, Montefiori DC, Lambert JS, Hu SL, Esterlitz JR, Lawrence DN, Koff WC, AIDS Vaccine Clinical Trials Network. Vaccination of vaccinia-naive adults with human immunodeficiency virus type 1 gp160 recombinant vaccinia virus in a blinded, controlled, randomized clinical trial. J Infect Dis. 1992;166:244-252.

Graham BS, Gorse GJ, Schwartz DH, Keefer MC, McElrath MJ, Matthews TJ, Wright PF, Belshe RB, Clements ML, Dolin R, Corey L, Bolognesi DP, Stablein DM, Esterlitz JR, Hu SL, Smith GE, National Institute of Allergy and Infectious Diseases AIDS Vaccine Clinical Trials Network. Determinants of antibody response after recombinant gp160 boosting in vaccinia-naive volunteers primed with gp160-recombinant vaccinia virus. J Infect Dis. 1994;170:782-786.