A Multicenter, Randomized, Placebo-Controlled, Double-Blind Trial to Evaluate the Safety and Immunogenicity of the Therion Recombinant Vaccinia-HIV-1 IIIB ENV/GAG/POL Vaccine (TCB-3B) and MN RGP 120/HIV-1 In Alum.

To evaluate the safety of administering Therion Recombinant Vaccinia-HIV-1 IIIB env/gag/pol Vaccine (TBC-3B) vaccinations to vaccinia-naive individuals. To evaluate the immunogenicity of priming with TBC-3B by the scarification, intradermal, and subcutaneous routes, followed by booster immunization of MN rgp120 HIV-1. To compare the immunogenicity of priming with TBC-3B in vaccinia-naive individuals to vaccinia-immune individuals.

In prior trials evaluating alternative methods of vaccine administration, scarification has been found to be an imprecise method of administration and allows only 1.0 - 2.5 microliters of immunogen to be given. Since it is not feasible to produce vaccine at concentrations higher than 10 to the 10th pfu/ml, this method limits the maximum deliverable dose. Intradermal and subcutaneous injection routes allow larger volumes of vaccinia to be given, i.e.: up to 200 microliters intradermally and up to 100 ml subcutaneously. In the present study, the initial priming dose will be the same administered by all 3 methods; however, the second priming dose administered at 2 months intradermally and subcutaneously will be 2 logs higher in order to achieve boosting of immune responses, particularly to gag and pol components of TBC-3B.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Biological: TBC-3B Vaccine; Biological: MN rgp120/HIV-1

Detailed Description

In prior trials evaluating alternative methods of vaccine administration, scarification has been found to be an imprecise method of administration and allows only 1.0 - 2.5 microliters of immunogen to be given. Since it is not feasible to produce vaccine at concentrations higher than 10 to the 10th pfu/ml, this method limits the maximum deliverable dose. Intradermal and subcutaneous injection routes allow larger volumes of vaccinia to be given, i.e.: up to 200 microliters intradermally and up to 100 ml subcutaneously. In the present study, the initial priming dose will be the same administered by all 3 methods; however, the second priming dose administered at 2 months intradermally and subcutaneously will be 2 logs higher in order to achieve boosting of immune responses, particularly to gag and pol components of TBC-3B.

After volunteers are recruited, screened and enrolled in the study, they will be randomized to group C, D, or E. Each group will enroll 10 patients and 2 controls. The placebo control for TBC-3B will be standard vaccinia vaccination administered at doses no higher than that administered by scarification; the placebo control for MN rgp120 will be alum. Group C will receive undiluted TBC-3B by scarification, at months 0 and 2. Group D will receive diluted TBC-3B intradermally at month 0 and undiluted TBC-3B at month 2. Group E will receive diluted TBC-3B subcutaneously at month 0 and undiluted TBC-3B at month 2. At months 8 and 12 all groups will receive MN rgp 120/HIV-1 in alum intramuscularly.

• Study Type: Interventional
• Enrollment: 36
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States
      • JHU AVEG
  • Missouri
    • Saint Louis, Missouri, United States
      • St. Louis Univ. School of Medicine AVEG
  • Tennessee
    • Nashville, Tennessee, United States, 37232
      • Vanderbilt Univ. Hosp. AVEG
  • Washington
    • Seattle, Washington, United States, 98144
      • UW - Seattle AVEG

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria

Patients must have:

• Negative FDA-approved ELISA for HIV within 8 weeks of immunization.
• Normal history and physical examination.
• Negativity for Hepatitis B surface antigen.
• Availability for follow-up for planned duration of the study (18 months).

Exclusion Criteria

Co-existing Condition:

Patients with the following symptoms or conditions are excluded:

• Medical or psychiatric condition or occupational responsibilities that preclude subject compliance with the protocol. Specifically excluded are people with a history of suicide attempts, recent suicidal ideation or who have past or present psychosis.
• Active syphilis. NOTE: If the serology is documented to be a false positive or due to a remote (> 6 months) treated infection, the volunteer is eligible.
• Active tuberculosis. NOTE: Patients with a positive PPD and a normal chest X-ray showing no evidence of TB and not requiring INH therapy are eligible.
• Household contacts with, or occupational exposure to, people with any of the following:

Pregnancy. <12 months of age. Eczema or Immunodeficiency disease. Use of immunosuppressive medications.

Patients with the following prior conditions are excluded:

• History of immunodeficiency, chronic illness, malignancy or autoimmune disease.
• History of cancer, unless there has been surgical excision followed by a sufficient observation period to give a reasonable assurance of cure.
• Any history of anaphylaxis or history of other serious adverse reactions to vaccines.
• History of serious allergic reaction to any substance, requiring hospitalization or emergent medical care (e.g., Stevens-Johnson syndrome, bronchospasm, or hypotension).
• Eczema within the past year.
• History of smallpox vaccination.
• Envelope bands on HIV-1 Western blot within 8 weeks of immunization.

Prior Medication: Excluded:

• Use of immunosuppressive.
• Live attenuated vaccines within 60 days of study.
• NOTE: Medically indicated subunit or killed vaccines (e.g. influenza, pneumococcal) do not exclude, but should be given at least 2 weeks prior to HIV immunizations.
• Experimental agents within 30 days prior to study.
• Prior receipt of HIV-1 vaccines or placebo recipient in a previous HIV vaccine trial.

Receipt of blood products or immunoglobulin within past 6 months.

Risk Behavior: Excluded:

• History of injection drug use within the last 12 months prior to enrollment.
• Higher or intermediate risk sexual behavior as defined by the AVEG.
• Lower risk sexual behavior as defined by AIDS Vaccine Evaluation Group (AVEG) procedures.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Masking: Double

Collaborators and Investigators

• Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
• Investigators: Study Chair: Smith C

Publications and helpful links

General Publications

• Keefer MC, McElrath MJ, Weinhold K, Gorse GJ, Mulligan M, Francis D, Panicali D. A phase I trial of vaccina-eng/gag/pol (TBC-3B) given by alternative routes, boosted with rgp120. Int Conf AIDS. 1998;12:278 (abstract no 496/21199)

Study record dates

Study Major Dates

• Study Completion (Actual): July 1, 1999

Study Registration Dates

• First Submitted: November 2, 1999
• First Submitted That Met QC Criteria: August 30, 2001
• First Posted (Estimate): August 31, 2001

Study Record Updates

• Last Update Posted (Actual): October 28, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: October 1, 2021

More Information

Terms related to this study

• Keywords: HIV Seronegativity; HIV-1; Placebos; Vaccines, Synthetic; AIDS Vaccines; HIV Preventive Vaccine; Vaccinia Virus; Genes, env; Genes, pol; Genes, gag
• Additional Relevant MeSH Terms: Virus Diseases; Infections; DNA Virus Infections; Poxviridae Infections; Vaccinia
• Other Study ID Numbers: AVEG 014C; 10562 (Registry Identifier: DAIDS ES Registry Number)