A Phase I, Multicenter, Randomized Trial to Evaluate the Safety and Immunogenicity of Vaccinia-Derived MN HIV-1 Recombinant Envelope Glycoprotein (rgp160) of Human Immunodeficiency Virus at Two Different Vaccination Schedules

A Phase I, Multicenter, Randomized Trial to Evaluate the Safety and Immunogenicity of Vaccinia-Derived MN HIV-1 Recombinant Envelope Glycoprotein (rgp160) of Human Immunodeficiency Virus at Two Different Vaccination Schedules

AMENDED 8/94: To expand the safety and immunogenicity profile of MN rgp160 vaccine (Immuno-AG) by administering a higher dose (800 mcg) at 0, 1, 6, and 12 months and 0, 2, 8 and 14 months (these two schedules were compared in VEU 013A using a dose of 200 mcg). To obtain plasma following the fourth immunization. To evaluate skin test reactivity.

ORIGINAL (replaced): To determine in healthy volunteers the safety and immunogenicity of two immunizations of MN rgp160 vaccine (Immuno-AG) in combination with a live recombinant vaccinia virus LAV HIV-1 gp160 vaccine (HIVAC-1e) versus DryVax (the standard smallpox vaccine that was used for many years) control in combination with placebo.

ORIGINAL (replaced): A gp160 vaccine derived from the MN strain, the most prevalent strain of HIV-1 in the United States, has been developed. A previous study showed that a combination vaccine strategy, consisting of priming with HIVAC-1e followed by boosting with a gp160 subunit vaccine, resulted in humoral and cellular immune responses of greater and longer duration than either vaccine alone. Thus, a live vector/subunit boost approach using the MN rgp160 vaccine merits investigation.

ORIGINAL (replaced): A gp160 vaccine derived from the MN strain, the most prevalent strain of HIV-1 in the United States, has been developed. A previous study showed that a combination vaccine strategy, consisting of priming with HIVAC-1e followed by boosting with a gp160 subunit vaccine, resulted in humoral and cellular immune responses of greater and longer duration than either vaccine alone. Thus, a live vector/subunit boost approach using the MN rgp160 vaccine merits investigation.

AMENDED 8/94: Volunteers are randomized to receive 800 mcg MN rgp160 vaccine (Immuno-AG) or adjuvant control (placebo) on one of two dosing schedules. Sixteen volunteers receive candidate vaccine and four volunteers receive placebo.

ORIGINAL (replaced): Volunteers are randomized to receive either HIVAC-1e on days 0 and 56 followed by immunization with MN rgp160 vaccine on days 224 and 364, or DryVax control on days 0 and 56 followed by placebo on days 224 and 364. Ten volunteers are entered on the MN rgp160 vaccine arm and two volunteers on the placebo arm.

PER AMENDMENT 7/96: Two additional booster immunizations of 600 mcg of MN rgp 120/HIV-1 vaccine given at study months 22 and 24 to consenting St. Louis University volunteers.

Inclusion Criteria

Subjects must have:

• Normal history and physical exam.
• Negative test for HIV by ELISA within 6 weeks prior to immunization.
• Negative test for HIV by Western blot.
• CD4 count >= 400 cells/mm3.
• No history of smallpox vaccination.
• Normal urine dipstick with esterase and nitrate.
• No history of immunodeficiency, chronic illness, autoimmune disease, or use of immunosuppresssive medications.

Exclusion Criteria

Co-existing Condition:

Subjects with the following conditions are excluded:

• Positive for hepatitis B surface antigen.
• Medical or psychiatric condition or occupational responsibilities that preclude compliance.
• Active syphilis (NOTE: If serology is documented to be a false positive or due to a remote (> 6 months) infection, subject is eligible).
• Active tuberculosis (NOTE: Subjects with a positive PPD and normal x-ray showing no evidence of TB and who do not require INH therapy are eligible).
• Eczema.

Household contact with persons meeting any of the following criteria:

• pregnancy, < 12 months of age, eczema, or immunodeficiency disease or use of immunosuppressive medications.

Subjects with the following prior conditions are excluded:

• History of anaphylaxis or other serious adverse reactions to vaccines.
• Eczema within the past year.
• PER 8/94 AMENDMENT: History of cancer unless surgically excised with reasonable assurance of cure.
• PER 8/94 AMENDMENT: History of serious allergic reaction requiring hospitalization or emergent medical care.

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:

• Blood products or immunoglobulin within the past 6 months.

Higher risk behavior for HIV infection as determined by screening questionnaire, including:

• History of injection drug use within 12 months prior to study entry.
• Higher or intermediate risk sexual behavior.