Primary: To determine in healthy volunteers whether priming with a vaccinia HIV-1 gp160 envelope gene recombinant vaccine (HIVAC-1e) followed by boosting with one of two subunit recombinant HIV-1 envelope vaccines (Env 2-3 and gp120) provides enhanced immunogenicity compared to vaccination with the gp120 subunit vaccine alone. (Per 10/01/92 amendment, boosts with VaxSyn (gp160) were eliminated.) To evaluate the immunogenicity of one versus two priming doses of HIVAC-1e prior to a boost with gp120. To compare the relative immunogenicity of the three subunit vaccines when administered as boosters.

Secondary: To examine the safety of administering the individual subunit vaccines in combination with HIVAC-1e and the safety of administering the gp120 subunit vaccine alone.

In a previous study of candidate HIV vaccines, the evidence suggested that administration of a booster vaccination with a different vaccine preparation may produce a better immune response than administration of HIVAC-1e vaccine alone.

In a previous study of candidate HIV vaccines, the evidence suggested that administration of a booster vaccination with a different vaccine preparation may produce a better immune response than administration of HIVAC-1e vaccine alone.

Seventy healthy volunteers are randomized to one of four groups. Groups A and D receive one initial immunization with HIVAC-1e followed by two boosts with subunit gp120 and Env 2-3, respectively, at months 8 and 12. Group B receives two immunizations with HIVAC-1e at months 0 and 8 followed by a single boost with subunit gp120 at month 12. Group C receives three doses of subunit gp120 only at months 0, 8 and 12. (Per 10/01/92 amendment, boosts with VaxSyn (gp160) have been eliminated.) Subjects are followed for 18 months.

Inclusion Criteria

Subjects must have:

• Normal history and physical exam.
• Negative HIV screening by ELISA, Western blot, and p24 antigen (PBMC HIV culture or HIV-specific PCR can be substituted for Western blot and p24 antigen).
• History of smallpox vaccination more than 5 years prior to enrollment.
• Normal urinalysis.
• Absolute CD4 count = or > 500 cells/mm3.

Prior Medication: Required:

• Vaccinia (smallpox) vaccination more than 5 years prior to study enrollment. Identifiable high-risk behavior for HIV infection as determined by screening questionnaire/interview.

Exclusion Criteria

Co-existing Condition:

Subjects with the following symptoms or conditions are excluded:

• Household contacts who are pregnant, < 12 months of age, have eczema, or have immunodeficiency disease or who use immunosuppressive medications.
• Hepatitis B surface antigenemia.
• Medical or psychiatric condition or occupational responsibilities that preclude compliance.

Subjects with the following prior conditions are excluded:

• History of immunodeficiency or chronic illness.
• Eczema within the past year.

Prior Medication:

Excluded:

• Prior experimental HIV vaccine.
• Immunoglobulin administration or use of experimental agent within the past 2 months.
• History of immunosuppressive medications.

Prior Treatment:

Excluded:

• Blood or blood product transfusion within the previous 6 months.