OUTLINE OF PROTOCOL 004B

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 12/11/91 and last enrolled on 03/19/92; follow-up of 17 months or 6 months after the final immunization for volunteers receiving the immunization at Months 23-29.

Clinical Sites: Johns Hopkins University, Saint Louis University, 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 purpose of this amendment is to evaluate the safety and immune response to 50 µg of the gp160 candidate vaccine using a different dosage schedule than in the original protocol. The duration of antibody response and its relationship to the dose and frequency of inoculation will also be evaluated.

The aim of the original 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

Gorse GJ, Schwartz DH, Graham BS, Matthews TJ, Stablein DM, Frey SE, Belshe RB, Clements ML, Wright PF, Eibl M, Fast PE, NIAID AIDS Vaccine Clinical Trials Network. HIV-1 recombinant gp160 vaccine given in accelerated dose schedules. Clin Exp Immunol. 1994;98:178-184.