A Randomized Phase I Safety and Immunogenicity Trial of Live Recombinant Canarypox ALVAC-HIV vCP205 Delivered by Alternate Mucosal Routes in HIV-1 Uninfected Adult Volunteers
- Conditions
- HIV Infections
- Interventions
- Biological: MN rgp120/HIV-1 and GNE8 rgp120/HIV-1Biological: ALVAC-HIV MN120TMG (vCP205)Biological: ALVAC-RG Rabies Glycoprotein (vCP65)
- Registration Number
- NCT00000884
- Brief Summary
To compare the safety of ALVAC-HIV vCP205 to that of ALVAC-RG vCP65 rabies glycoprotein, delivered by a variety of mucosal routes. To evaluate the antibody, humoral, and cellular immune responses resulting from ALVAC-HIV vCP205. \[AS PER AMENDMENT 8/3/98: To obtain safety data on AIDSVAX B/B boosting administered by the intramuscular and intranasal routes in the context of previous immunization via alternate mucosal routes or intramuscularly with a canarypox vector expressing HIV-1 antigens (vCP205). To obtain immunogenicity data on AIDSVAX B/B boosting.\] One of the earliest observations in the HIV epidemic was the demonstration of HIV infection at mucosal surfaces of cells in the genital tract. These data suggest that priming of immune defenses of viral infected cells may be an important component in the strategy of developing an effective HIV vaccine. Direct immunization of relevant mucosal surfaces with a vectored vaccine may stimulate mucosal immunity. The ALVAC-HIV vCP205 immunogen is constructed from a live recombinant canarypox vector that has a good safety profile in volunteers and should allow mucosal induction of immunity.
- Detailed Description
One of the earliest observations in the HIV epidemic was the demonstration of HIV infection at mucosal surfaces of cells in the genital tract. These data suggest that priming of immune defenses of viral infected cells may be an important component in the strategy of developing an effective HIV vaccine. Direct immunization of relevant mucosal surfaces with a vectored vaccine may stimulate mucosal immunity. The ALVAC-HIV vCP205 immunogen is constructed from a live recombinant canarypox vector that has a good safety profile in volunteers and should allow mucosal induction of immunity.
This randomized, double-blind trial evaluates the safety of and immune response to vaccination with ALVAC-HIV vCP205 given at 0, 1, 3, and 6 months. Patients are randomly assigned to 1 of 7 drug administration routes as follows:
Group A: Intramuscular Group B: Oral Group C: Intranasal Group D: Intrarectal Group E: Intravaginal Group F: Intranasal/intramuscular Group G: Intrarectal/intramuscular Twelve patients are randomized to each group, 8 of whom receive experimental therapy with ALVAC-HIV vCP205 and 4 of whom receive control therapy with ALVAC-RG vCP2058 (rabies vaccine). Women are preferentially enrolled, with a goal of 60% women (minimum of 4 women per treatment arm); only women are randomized to Group E. Blinding is maintained with respect to drug assignment rather than route of administration, after randomization. NOTE: The protocol will be amended to add 2 boost vaccinations with subunit products at approximately Months 9 and 12 when a suitable boost product is identified. \[AS PER AMENDMENT 8/3/98: The protocol has been modified to include 2 booster vaccinations to be administered at 9 and 12 months. Patients in Group A receive booster vaccination with ALVAC-HIV VCP205 or ALVAC-RG intranasally. Patients in Groups B through G are boosted with AIDSVAX B/B vaccine (a bivalent vaccine consisting of MN rgp120/HIV-1 antigen and GNE8 rgp120/HIV-1 antigen in alum adjuvant) or with Imovax diploid cell rabies vaccine; vaccinations for these patients are given intramuscularly.\] \[AS PER AMENDMENT 11/19/98: The second booster vaccination for group A will be administered at study Month 15.\]
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 84
Not provided
Not provided
Study & Design
- Study Type
- INTERVENTIONAL
- Study Design
- PARALLEL
- Arm && Interventions
Group Intervention Description 3 ALVAC-RG Rabies Glycoprotein (vCP65) Participants will undergo treatment intranasally 4 ALVAC-HIV MN120TMG (vCP205) Participants will undergo treatment intrarectally 6 MN rgp120/HIV-1 and GNE8 rgp120/HIV-1 Participants will undergo treatment intranasally and intramuscularly 1 ALVAC-HIV MN120TMG (vCP205) Participants will undergo treatment intramuscularly 6 ALVAC-RG Rabies Glycoprotein (vCP65) Participants will undergo treatment intranasally and intramuscularly 1 ALVAC-RG Rabies Glycoprotein (vCP65) Participants will undergo treatment intramuscularly 2 ALVAC-HIV MN120TMG (vCP205) Participants will undergo treatment orally 3 ALVAC-HIV MN120TMG (vCP205) Participants will undergo treatment intranasally 5 MN rgp120/HIV-1 and GNE8 rgp120/HIV-1 Participants will undergo treatment intravaginally 6 ALVAC-HIV MN120TMG (vCP205) Participants will undergo treatment intranasally and intramuscularly 2 MN rgp120/HIV-1 and GNE8 rgp120/HIV-1 Participants will undergo treatment orally 2 ALVAC-RG Rabies Glycoprotein (vCP65) Participants will undergo treatment orally 3 MN rgp120/HIV-1 and GNE8 rgp120/HIV-1 Participants will undergo treatment intranasally 4 MN rgp120/HIV-1 and GNE8 rgp120/HIV-1 Participants will undergo treatment intrarectally 4 ALVAC-RG Rabies Glycoprotein (vCP65) Participants will undergo treatment intrarectally 5 ALVAC-HIV MN120TMG (vCP205) Participants will undergo treatment intravaginally 7 MN rgp120/HIV-1 and GNE8 rgp120/HIV-1 Participants will undergo treatment intrarectally and intramuscularly 5 ALVAC-RG Rabies Glycoprotein (vCP65) Participants will undergo treatment intravaginally 7 ALVAC-HIV MN120TMG (vCP205) Participants will undergo treatment intrarectally and intramuscularly 7 ALVAC-RG Rabies Glycoprotein (vCP65) Participants will undergo treatment intrarectally and intramuscularly
- Primary Outcome Measures
Name Time Method To evaluate the antibody, humoral, and cellular immune responses resulting from ALVAC-HIV vCP205 Throughout study To obtain safety data on AIDSVAX B/B boosting administered by the intramuscular and intranasal routes in the context of previous immunization via alternate mucosal routes or intramuscularly with a canarypox vector expressing HIV-1 antigens (vCP205) Throughout study To obtain immunogenicity data on AIDSVAX B/B boosting Throughout study To compare the safety of ALVAC-HIV vCP205 to that of ALVAC-RG vCP65 rabies glycoprotein, delivered by a variety of mucosal routes Throughout study
- Secondary Outcome Measures
Name Time Method
Trial Locations
- Locations (6)
UAB AVEG
🇺🇸Birmingham, Alabama, United States
St. Louis Univ. School of Medicine AVEG
🇺🇸Saint Louis, Missouri, United States
Univ. of Rochester AVEG
🇺🇸Rochester, New York, United States
JHU AVEG
🇺🇸Baltimore, Maryland, United States
UW - Seattle AVEG
🇺🇸Seattle, Washington, United States
Vanderbilt Univ. Hosp. AVEG
🇺🇸Nashville, Tennessee, United States