A Phase I Multicenter, Randomized, Double-Blind Trial to Evaluate the Safety and Immunogenicity of Recombinant Vaccinia Virus Expressing the Envelope Glycoproteins of Human Immunodeficiency Virus

NCT00000683 | Completed Phase 1

• 2 other identifiers: AVEG 00210537
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 1

Brief Summary

Evaluation of the safety and immunogenicity (immunological reactivity) of HIVAC-1e vaccine. An additional goal is to determine which dose level of vaccine might be most effective. Specific questions to be addressed in this part of the study include: Are there adverse reactions to gp160 vaccine when given to vaccinees previously immunized with a vaccinia-recombinant? Does gp160 vaccination of prior HIVAC-1e vaccine result in stimulation of neutralizing antibody and other humoral immune responses? Does vaccination with gp160 enhance the development of cell-mediated immune responses in HIVAC-1e vaccinees? Is the magnitude of immune response to gp160 booster immunization greater following priming with GP160 recombinant vaccinia (HIVAC-1e) vaccination than priming with three doses of purified recombinant gp160? AMENDED: An 80 mcg dose of gp160 has been chosen for the booster because this dose has been shown to be safe and immunogenic in previous trials and allows comparison of the late boost in this protocol with the late boost in the protocol in which patients were primed with three doses of gp160. Original design: HIVAC-1e vaccine is a preparation of the envelope protein of HIV (the virus that causes AIDS). The protein is produced by genetic modification in vaccinia virus. The purpose of a vaccine is to produce an artificially increased immunity to a particular disease, in this case, AIDS. Since there is no known cure for AIDS, the control of this disease necessitates the development of effective prevention such as vaccines.

Conditions

HIV Infections

Keywords

Vaccines, Synthetic; Vaccinia Virus; Viral Envelope Proteins; Acquired Immunodeficiency Syndrome; AIDS Vaccines; HIV Seronegativity; HIV Preventive Vaccine

Interventions

HIVAC-1e BIOLOGICAL

gp160 Vaccine (MicroGeneSys) BIOLOGICAL

Eligibility Criteria

• Age: 18 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Patients must demonstrate the following clinical and laboratory findings:
• Normal history and physical examination.
• Normal chest X-ray (optional).
• Normal urinalysis.
• Negative ELISA.
• Negative Western blot test.
• Negative HIV culture.
• No evidence of smallpox vaccination.
• Note:
• As an operational definition, an individual can be considered "vaccinia naive" only if no scar is observable and the patient claims and/or has evidence of not being vaccinated. If the patient does not know his/her history, it should be presumed that he/she was vaccinated.

You may not qualify if:

• Patients will be excluded from the study for the following reasons:
• Appearance of or serologic or clinical evidence of HIV infection.
• Appearance of or serologic or clinical evidence of clinically active viral infections, including mononucleosis, Epstein-Barr virus, cytomegalovirus which may affect HIV immunocompetence.
• Syphilis, gonorrhea, or any other sexually transmitted diseases including chlamydia or pelvic inflammatory disease in the last 6 months.
• History of immunodeficiency or chronic illness.
• Evidence of depression.
• History of positive PPD (tuberculosis exposure).
• Positive syphilis serology.
• Positive for circulating Hepatitis B antigen.
• Eczema, active or within the past year.
• Household contact with someone who is pregnant.
• Household contact with children less than 12 months old.
• Household contact with anyone with eczema.
• Household contact with anyone with immunodeficiencies.
• Vaccinia immunity.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Univ. of Rochester AVEG

Rochester, New York, 14642, United States

Location

Related Publications (10)

• McElrath MJ, Corey L, Berger D, Hoffman MC, Klucking S, Dragavon J, Peterson E, Greenberg PD. Immune responses elicited by recombinant vaccinia-human immunodeficiency virus (HIV) envelope and HIV envelope protein: analysis of the durability of responses and effect of repeated boosting. J Infect Dis. 1994 Jan;169(1):41-7. doi: 10.1093/infdis/169.1.41.

  PMID: 8277196 BACKGROUND

• Montefiori DC, Graham BS, Zhou JY, Zhou JT, Ahearn JM. Binding of human immunodeficiency virus type 1 to the C3b/C4b receptor CR1 (CD35) and red blood cells in the presence of envelope-specific antibodies and complement. National Institutes of Health AIDS Vaccine Clinical Trials Networks. J Infect Dis. 1994 Aug;170(2):429-32. doi: 10.1093/infdis/170.2.429.

  PMID: 8035031 BACKGROUND

• Montefiori DC, Graham BS, Zhou J, Zhou J, Bucco RA, Schwartz DH, Cavacini LA, Posner MR. V3-specific neutralizing antibodies in sera from HIV-1 gp160-immunized volunteers block virus fusion and act synergistically with human monoclonal antibody to the conformation-dependent CD4 binding site of gp120. NIH-NIAID AIDS Vaccine Clinical Trials Network. J Clin Invest. 1993 Aug;92(2):840-7. doi: 10.1172/JCI116658.

  PMID: 8349820 BACKGROUND

• Graham BS. Clinical trials of AIDS vaccines in seronegative volunteers: vectors and combinations. AIDS Res Hum Retroviruses. 1992 Aug;8(8):1327-8. doi: 10.1089/aid.1992.8.1327. No abstract available.

  PMID: 1466951 BACKGROUND

• Montefiori DC, Graham BS, Kliks S, Wright PF. Serum antibodies to HIV-1 in recombinant vaccinia virus recipients boosted with purified recombinant gp160. NIAID AIDS Vaccine Clinical Trials Network. J Clin Immunol. 1992 Nov;12(6):429-39. doi: 10.1007/BF00918855.

  PMID: 1287035 BACKGROUND

• Cooney EL, Collier AC, Greenberg PD, Coombs RW, Zarling J, Arditti DE, Hoffman MC, Hu SL, Corey L. Safety of and immunological response to a recombinant vaccinia virus vaccine expressing HIV envelope glycoprotein. Lancet. 1991 Mar 9;337(8741):567-72. doi: 10.1016/0140-6736(91)91636-9.

  PMID: 1671940 BACKGROUND

• Graham BS, Matthews TJ, Belshe RB, Clements ML, Dolin R, Wright PF, Gorse GJ, Schwartz DH, Keefer MC, Bolognesi DP, et al. Augmentation of human immunodeficiency virus type 1 neutralizing antibody by priming with gp160 recombinant vaccinia and boosting with rgp160 in vaccinia-naive adults. The NIAID AIDS Vaccine Clinical Trials Network. J Infect Dis. 1993 Mar;167(3):533-7. doi: 10.1093/infdis/167.3.533.

  PMID: 8095059 BACKGROUND

• Graham BS, Rowland JM, Modliszewski A, Montefiori DC. Antifusion activity in sera from persons infected with human immunodeficiency virus type 1. J Clin Microbiol. 1990 Dec;28(12):2608-11. doi: 10.1128/jcm.28.12.2608-2611.1990.

  PMID: 2279989 BACKGROUND

• Hammond SA, Bollinger RC, Stanhope PE, Quinn TC, Schwartz D, Clements ML, Siliciano RF. Comparative clonal analysis of human immunodeficiency virus type 1 (HIV-1)-specific CD4+ and CD8+ cytolytic T lymphocytes isolated from seronegative humans immunized with candidate HIV-1 vaccines. J Exp Med. 1992 Dec 1;176(6):1531-42. doi: 10.1084/jem.176.6.1531.

  PMID: 1460417 BACKGROUND

• Perales MA, Schwartz DH, Fabry JA, Lieberman J. A vaccinia-gp160-based vaccine but not a gp160 protein vaccine elicits anti-gp160 cytotoxic T lymphocytes in some HIV-1 seronegative vaccinees. J Acquir Immune Defic Syndr Hum Retrovirol. 1995 Sep 1;10(1):27-35.

  PMID: 7648281 BACKGROUND

MeSH Terms

Conditions

HIV Infections; Vaccinia; Acquired Immunodeficiency Syndrome

Interventions

HIVAC-1e; VaxSyn HIV-1 (gp160) vaccine

Condition Hierarchy (Ancestors)

Blood-Borne Infections; Communicable Diseases; Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; RNA Virus Infections; Virus Diseases; Genital Diseases; Urogenital Diseases; Immunologic Deficiency Syndromes; Immune System Diseases; Poxviridae Infections; DNA Virus Infections; Slow Virus Diseases

Study Officials

• Koff W

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Masking: DOUBLE
• Purpose: PREVENTION
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 2, 1999
• First Posted: August 31, 2001
• Study Completion: June 1, 1993
• Last Updated: November 2, 2021

Record last verified: 2021-10

Locations

US (1)