A Phase I, Multicenter, Randomized Trial to Evaluate the Safety and Immunogenicity of Vaccinia-Derived MN HIV-1 Recombinant Envelope Glycoprotein (rgp160) of Human Immunodeficiency Virus at Two Different Vaccination Schedules

NCT ID: NCT00001043

Last Updated: 2021-11-04

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1
• Total Enrollment: 20 participants
• Study Classification: INTERVENTIONAL
• Study Completion Date: 1997-05-31

Brief Summary

AMENDED 8/94: To expand the safety and immunogenicity profile of MN rgp160 vaccine (Immuno-AG) by administering a higher dose (800 mcg) at 0, 1, 6, and 12 months and 0, 2, 8 and 14 months (these two schedules were compared in VEU 013A using a dose of 200 mcg). To obtain plasma following the fourth immunization. To evaluate skin test reactivity.

ORIGINAL (replaced): To determine in healthy volunteers the safety and immunogenicity of two immunizations of MN rgp160 vaccine (Immuno-AG) in combination with a live recombinant vaccinia virus LAV HIV-1 gp160 vaccine (HIVAC-1e) versus DryVax (the standard smallpox vaccine that was used for many years) control in combination with placebo.

ORIGINAL (replaced): A gp160 vaccine derived from the MN strain, the most prevalent strain of HIV-1 in the United States, has been developed. A previous study showed that a combination vaccine strategy, consisting of priming with HIVAC-1e followed by boosting with a gp160 subunit vaccine, resulted in humoral and cellular immune responses of greater and longer duration than either vaccine alone. Thus, a live vector/subunit boost approach using the MN rgp160 vaccine merits investigation.

Detailed Description

ORIGINAL (replaced): A gp160 vaccine derived from the MN strain, the most prevalent strain of HIV-1 in the United States, has been developed. A previous study showed that a combination vaccine strategy, consisting of priming with HIVAC-1e followed by boosting with a gp160 subunit vaccine, resulted in humoral and cellular immune responses of greater and longer duration than either vaccine alone. Thus, a live vector/subunit boost approach using the MN rgp160 vaccine merits investigation.

AMENDED 8/94: Volunteers are randomized to receive 800 mcg MN rgp160 vaccine (Immuno-AG) or adjuvant control (placebo) on one of two dosing schedules. Sixteen volunteers receive candidate vaccine and four volunteers receive placebo.

ORIGINAL (replaced): Volunteers are randomized to receive either HIVAC-1e on days 0 and 56 followed by immunization with MN rgp160 vaccine on days 224 and 364, or DryVax control on days 0 and 56 followed by placebo on days 224 and 364. Ten volunteers are entered on the MN rgp160 vaccine arm and two volunteers on the placebo arm.

PER AMENDMENT 7/96: Two additional booster immunizations of 600 mcg of MN rgp 120/HIV-1 vaccine given at study months 22 and 24 to consenting St. Louis University volunteers.

Conditions

HIV Infections; HIV Seronegativity

Keywords

Vaccines, Synthetic; Vaccinia Virus; Viral Vaccines; Smallpox Vaccine; HIV-1; HIV Envelope Protein gp160; AIDS Vaccines; HIV Seronegativity; HIV Preventive Vaccine

Study Design

• Primary Study Purpose: PREVENTION

Interventions

gp160 Vaccine (Immuno-AG)

Intervention Type: BIOLOGICAL

Eligibility Criteria

Inclusion Criteria

Subjects must have:

• Normal history and physical exam.
• Negative test for HIV by ELISA within 6 weeks prior to immunization.
• Negative test for HIV by Western blot.
• CD4 count >= 400 cells/mm3.
• No history of smallpox vaccination.
• Normal urine dipstick with esterase and nitrate.
• No history of immunodeficiency, chronic illness, autoimmune disease, or use of immunosuppresssive medications.

Exclusion Criteria

Co-existing Condition:

Subjects with the following conditions are excluded:

• Positive for hepatitis B surface antigen.
• Medical or psychiatric condition or occupational responsibilities that preclude compliance.
• Active syphilis (NOTE: If serology is documented to be a false positive or due to a remote (> 6 months) infection, subject is eligible).
• Active tuberculosis (NOTE: Subjects with a positive PPD and normal x-ray showing no evidence of TB and who do not require INH therapy are eligible).
• Eczema.

Household contact with persons meeting any of the following criteria:

• pregnancy, < 12 months of age, eczema, or immunodeficiency disease or use of immunosuppressive medications.

Subjects with the following prior conditions are excluded:

• History of anaphylaxis or other serious adverse reactions to vaccines.
• Eczema within the past year.
• PER 8/94 AMENDMENT: History of cancer unless surgically excised with reasonable assurance of cure.
• PER 8/94 AMENDMENT: History of serious allergic reaction requiring hospitalization or emergent medical care.

Prior Medication:

Excluded:

• Prior HIV vaccines.
• Live attenuated vaccines within the past 60 days. NOTE: Medically indicated subunit or killed vaccines (e.g., influenza, pneumococcal) do not exclude but should be administered at least 2 weeks prior to HIV immunizations.
• Experimental agents within the past 30 days.

Prior Treatment:

Excluded:

• Blood products or immunoglobulin within the past 6 months.

Higher risk behavior for HIV infection as determined by screening questionnaire, including:

• History of injection drug use within 12 months prior to study entry.
• Higher or intermediate risk sexual behavior.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 60 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

National Institute of Allergy and Infectious Diseases (NIAID)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Gorse G

Role: STUDY_CHAIR

Locations

St. Louis Univ. School of Medicine AVEG

St Louis, Missouri, United States

UW - Seattle AVEG

Seattle, Washington, United States

Countries

United States

References

Gorse GJ, Corey L, Patel GB, Mandava M, Hsieh RH, Matthews TJ, Walker MC, McElrath MJ, Berman PW, Eibl MM, Belshe RB. HIV-1MN recombinant glycoprotein 160 vaccine-induced cellular and humoral immunity boosted by HIV-1MN recombinant glycoprotein 120 vaccine. National Institute of Allergy and Infectious Diseases AIDS Vaccine Evaluation Group. AIDS Res Hum Retroviruses. 1999 Jan 20;15(2):115-32. doi: 10.1089/088922299311547.

Reference Type: BACKGROUND

PMID: 10029244 (View on PubMed)

Gorse GJ, McElrath MJ, Belshe RB, Corey L, Matthews T, Eibl M, Kennedy D, Frey S, Hsieh R, Walker MC. High dose HIV-1 MN recombinant gp160 (rgp160) vaccine induces anti-v3 MN, and IgG1-4 and IgA anti-rgp160 antibodies. Int Conf AIDS. 1996 Jul 7-12;11(1):7 (abstract no MoA153)

Reference Type: BACKGROUND

Other Identifiers

10560

Identifier Type: REGISTRY

Identifier Source: secondary_id

AVEG 013B

Identifier Type: -

Identifier Source: org_study_id