OUTLINE OF PROTOCOL 010

Subjects: Healthy, HIV-1 uninfected adult volunteers without identifiable high-risk behavior for HIV-1 infection, who never received smallpox (vaccinia) vaccination.

Schema:

Product Description:

HIVAC-1e: vaccinia vector containing HIV-1 LAI rgp160 [Bristol Myers-Squibb/Oncogen]
CHO cell-derived HIV-1 SF-2 rgp120 in combination with MF59 adjuvant emulsion. [Chiron/Biocine]
CHO cell-derived HIV-1 IIIB rgp120 in alum [Genentech]
CHO cell-derived HIV-1 MN rgp120 in alum [Genentech]
Vaccinia/Vero cell-expressed HIV-1 MN rgp160 in alum and doxycholate (DOC) [IMMUNO-AG].

Time Period: First volunteer entered original protocol on 07/16/92; the last enrolled on 06/16/93; follow-up of 18 months.

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

Study Chair: Julie McElrath, University of Washington

INCLUSION CRITERIA

Negative history of smallpox vaccination

• Age: 18-60
• Sex: Male or nonpregnant females
• Normal history and physical examination
• Normal complete blood count and differential defined as:
  • HCT >34% for women, >38% for men
  • WBC >4000 cells/mm³ with normal differential
  • Absolute CD4 count >500 cells/mm³
• Normal urinalysis
• ALT <3X institutional upper normal limit
• Creatinine <1.6 mg/dl
• Negative HIV ELISA, Western Blot, and p24 antigen (PBMC HIV culture or HIV-specific PCR can be substituted for Western Blot and p24 antigen)
• Availability for 18 months of follow-up

EXCLUSION CRITERIA

• Persons currently in a high risk group for HIV transmission (persons previously in a high risk group can be enrolled if they have a negative HIV screening and high risk behavior has not been practiced in the last 6 months)
• Blood or blood product transfusion within the previous 6 months
• History of immunodeficiency, chronic illness, or use of immunosuppressive medications
• Lactating women
• Eczema within the past year
• Household contacts with any of the following: Pregnancy; <12 months of age; Eczema; immunodeficiency disease or use of immunosuppressive medications
• Prior receipt of an experimental HIV vaccine
• Immunoglobulin administration or use of an experimental agent within 2 months of enrollment
• Hepatitis B surface antigenemia
• Medical or psychiatric condition or occupational responsibilities which preclude subject compliance with the protocol

STUDY GOALS

The primary objective of this study is to extend the ongoing studies on the use of vaccine combinations to the HIV envelope with an attempt to improve immunogenicity as defined by functional neutralizing antibodies to homologous and heterologous isolates of HIV-1. We will target the study to vaccinia-naive individuals where the previous studies have given the best results and will aim to:

• Determine if combination vaccination, i.e., priming with a vaccinia recombinant containing HIV envelope followed by boosting with a recombinant subunit envelope protein, provides enhanced immunogenicity to subunit vaccination with the individual recombinant envelope proteins.
• Compare the relative immunogenicity of a panel of HIV envelope subunit vaccines when administered as boosters following recombinant HIV-vaccinia priming.
• Evaluate the relative immunogenicity of one vs two doses of recombinant HIV-vaccinia prior to the subunit protein boost.

The secondary objective of this study is to examine the safety of the administration of the individual subunit vaccines in combination with the HIV envelope vaccinia recombinant; and to extend the population to whom these proteins have been administered. It is anticipated that the protocol will be amended to include several other subunit vaccines as products become available.

REFERENCE

Corey L, McElrath MJ, Weinhold K, Matthews T, Stablein D, Graham B, Keefer M, Schwartz D, Gorse G, AIDS Vaccine Evaluation Group. Cytotoxic T cell and neutralizing antibody responses to human immunodeficiency virus type 1 envelope with a combination vaccine regimen. J Infect Dis. 1998;177:301-309.