OUTLINE OF PROTOCOL 004

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

Schema:

Product Description: Vaccinia/Vero cell-expressed HIV-1 IIIB rgp160 in alum and deoxycholate [IMMUNO-AG]

Time Period: First volunteer entered on 12/13/90 and the last was enrolled on 08/01/91; follow-up of 24 months or 6 months after the final immunization for volunteers on the extended schedule.

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

Study Chair: Robert Belshe, Saint Louis University

INCLUSION CRITERIA

• Age: >18 and <60
• Sex: Male or Female

  NOTE: For females, negative pregnancy test at time of entry and assurance that adequate birth control measures are employed for the duration of the study

• 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 chest x-ray (optional)
• Normal urinalysis
• Normal ALT (<1.1 x institutional upper normal limit) and creatinine (0.1-1.6 mg/dl)
• Negative ELISA for HIV
• Negative Western Blot for HIV; Subject who has a p24 band present at Western Blot may be enrolled if HIV culture or PCR are negative, and after 3 months there are no additional bands or increased intensity of the p24 band [criteria modified 12/91]
• Negative HIV p24 antigen test
• Normal cell mediated immune responses using Merieux skin test
• Availability for one year of follow-up
• Negative HIV culture

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 two sexual partners, or sexual contact with a high risk partner, in the preceding 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 [Current PPD test is required only if Merieux skin reaction to the tuberculin antigen is positive]
• Positive syphilis serology (e.g., VDRL)
• Positive for circulating Hepatitis B antigen

STUDY GOALS

The aim of this Phase I study is to evaluate the safety and immunogenicity of recombinant HIV gp160 in healthy adult volunteers at low risk for acquiring HIV-1 infection. Specific questions to be addressed include:

• Are there any adverse reactions to the recombinant candidate HIV gp160 vaccine (i.e., local or systemic reactions or immunologic impairment)?
• Does the candidate HIV gp160 vaccine stimulate homologous and heterologous anti-HIV neutralizing antibody and other humoral immune responses in healthy volunteers?
• Does the candidate HIV gp160 vaccine stimulate cell-mediated immune responses?

REFERENCES

Belshe RB, Clements ML, Dolin R, Graham BS, McElrath J, Gorse GJ, Schwartz D, Keefer MC, Wright P, Corey L, Bolognesi DP, Matthews TJ, Stablein DM, O'Brien FS, Eibl M, Dorner F, Koff W, National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group Network. Safety and immunogenicity of a fully glycosylated recombinant gp160 human immunodeficiency virus type 1 vaccine in subjects at low risk of infection. J Infect Dis. 1993;168:1387-1395.