OUTLINE OF PROTOCOL 014C

Subjects: Healthy, HIV-1 uninfected adult volunteers who have no identifiable high-risk behavior for HIV-1 infection, who have never received smallpox (vaccinia) vaccination.

Schema:

* Enrollment will begin with Group C, with safety assessment at 1 month in half of the volunteers prior to initiating Groups D and E; 5 volunteers in each of Groups D and E will be randomized and enrolled initially. Safety assessment will be performed in these 10 volunteers at 4 weeks after the second immunization, prior to enrolling the remaining individuals in these groups.

** Accrual is 12 volunteers in each group, 10 treatment and 2 controls. Control volunteers will receive DryVax instead of TBC-3B at Months 0 and 2 and alum alone instead of MN rgp120 at Months 8 and 12. Maximal delivered dose of DryVax by intradermal and subcutaneous injection will be the same as its scarification dose.

Notes: TBC: Therion TBC-3B, expressed in pfu per delivered dose, given by one of three routes of administration

MN: VaxGen MN rgp120 (300 µg) in alum, given by the IM route

 

ACCRUAL, IMMUNIZATIONS AND FOLLOW-UP COMPLETED

Product Description:

TBC-3B: Live, recombinant vaccinia virus expressing the env and gag/pol genes of HIV-1 strain IIIB, grown in CV-1 (African green monkey kidney) cells [Therion Biologics]
MN rgp120: CHO cell-derived MN rgp120 combined with alum [VaxGen]

Time Period: 18 months; first volunteer enrolled on 04/03/97 and the last on 01/12/98.

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

Study Chair: Michael Keefer, University of Rochester

INCLUSION CRITERIA

Standard inclusion criteria, with the addition of:

• Negative history of smallpox vaccination
• No envelope bands on HIV-1 Western Blot within 8 weeks of immunization

EXCLUSION CRITERIA

Standard exclusion criteria, with the addition of:

• Eczema within the past year
• Household contacts with, or occupational exposure to, people with any of the following:
  • pregnancy
  • <12 months of age
  • eczema
  • immunodeficiency disease or use of immunosuppressive medications

STUDY GOALS

• To evaluate the safety of administering TBC-3B vaccinations to vaccinia-naive individuals using:
  • A standard vaccinia regimen administered x 2 by scarification
  • Intradermal/subcutaneous first priming vaccination administered at the dose used for scarification
  • Intradermal/subcutaneous second priming vaccination administered at a dose 100-fold higher than the scarification dose
  • Subunit booster immunization x 2 with an HIV-1 MN rgp120/HIV-1 vaccine after each priming regimen.
• To evaluate the immunogenicity of priming with TBC-3B by the scarification, intradermal, and subcutaneous routes, followed by boosting with MN rgp120 MN/HIV-1, primarily by determining whether immunization induces one or more of the following:
  • CD8+ and CD4+ cytotoxic T lymphocyte (CTL) activity directed at env, gag and pol gene products of HIV-1 after priming and boosting vaccinations
  • Neutralizing antibodies to HIV-1 strains MN and IIIB after two doses of MN rgp120/HIV-1 following priming with TBC-3B
  • Cross-neutralizing antibodies to other isolates of HIV-1, including primary isolates, if homologous neutralization is detected
  • Antibody dependent cellular cytotoxicity.
• To compare the immunogenicity of priming with TBC-3B in vaccinia-naive individuals to vaccinia-immune individuals in AVEG Protocol 014A.