Clinical trial NCT00000956: A Phase I Multicenter Trial to Evaluate the Safety and Immunogenicity of HIV-1 Recombinant Envelope Glycoprotein gp160
Official title: A Phase I Multicenter Trial to Evaluate the Safety and Immunogenicity of HIV-1 Recombinant Envelope Glycoprotein gp160
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: HIV Infections
Keywords: Vaccines, Synthetic
Vaccinia Virus
HIV-1
HIV Envelope Protein gp160
AIDS Vaccines
HIV Seronegativity
HIV Preventive Vaccine
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Sponsor class: NIH
Collaborators: name: Protein Sciences Corporation
First posted: 2001-08-31
Enrollment: 25
Sex: ALL
Minimum age (years): 18
Maximum age (years): 50
Standard ages: ADULT
Accepts healthy volunteers: yes
Primary purpose: PREVENTION

Brief summary: To evaluate the safety and immune response to 640 and 1280 mcg HIV-1 recombinant envelope glycoprotein gp160. To evaluate the duration of antibody response and its relationship to dose and frequency of inoculation.

Evaluation of previous patients who received doses of 40 or 80 mcg gp160 vaccine indicates that, although serum anti-gp160 antibody responses were detected, the level and duration of those responses were limited. A preliminary observation suggests that weak functional antibody responses may develop following the 18 month booster of 40 or 80 mcg; therefore, a dose of gp160 vaccine having potentially greater immunogenicity is of particular interest.

Detailed description: Evaluation of previous patients who received doses of 40 or 80 mcg gp160 vaccine indicates that, although serum anti-gp160 antibody responses were detected, the level and duration of those responses were limited. A preliminary observation suggests that weak functional antibody responses may develop following the 18 month booster of 40 or 80 mcg; therefore, a dose of gp160 vaccine having potentially greater immunogenicity is of particular interest.

In the initial phase of the study, 20 healthy volunteers receive 640 mcg gp160 vaccine and 5 healthy volunteers receive alum placebo. At least 30 days later, 20 additional volunteers receive 1280 mcg gp160 vaccine and 5 volunteers receive placebo. Injections are given on days 0, 30, 180, and 365.

Eligibility criteria: Inclusion Criteria

Patients must have:

* Normal history and physical exam.
* Negative for HIV infection by ELISA and Western blot (i.e., no reactivity at gp160, gp120, gp41, or p24).
* T4 count \>= 800 cells/mm3.
* Normal chest x-ray and urinalysis.
* Negative hepatitis B surface antigen.
* Negative HIV p24 antigen test.
* Normal skin reactivity by Merieux test.

Exclusion Criteria

Co-existing Condition:

Subjects with the following symptoms or conditions are excluded:

* Positive PPD.
* Syphilis, gonorrhea, or any other sexually transmitted diseases (including chlamydia or pelvic inflammatory disease).

Subjects with the following prior conditions are excluded:

* History of immunodeficiency, chronic illness, or use of immunosuppressive medications.
* Syphilis, gonorrhea, or any other sexually transmitted diseases (including chlamydia or pelvic inflammatory disease) in the past 6 months.

Prior Treatment:

Excluded:

* Prior blood transfusions or cryoprecipitates within the past 6 months.

Identifiable high-risk behavior for HIV infection (as determined by prescreening questions designed to identify risk factors for HIV infection), including:

* Any history of IV drug use.
* Syphilis, gonorrhea, or any other sexually transmitted diseases (including chlamydia or pelvic inflammatory disease) in the past 6 months.
* More than two sexual partners, or sexual contact with a high-risk partner, in the past 6 months.

Primary outcomes:
Secondary outcomes:
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: St. Louis Univ. School of Medicine AVEG
state: Missouri
city: Pittsburgh
country: United States
facility: JHU AVEG
state: Pennsylvania
Study officials:
name: Belshe R
role: STUDY_CHAIR
name: Clements ML
role: STUDY_CHAIR
name: Couch R
role: STUDY_CHAIR
name: Dolin R
role: STUDY_CHAIR
name: Levine M
role: STUDY_CHAIR
name: Wright P
role: STUDY_CHAIR
References:
citation: Keefer MC, Wolff M, Gorse GJ, Graham BS, Corey L, Clements-Mann ML, Verani-Ketter N, Erb S, Smith CM, Belshe RB, Wagner LJ, McElrath MJ, Schwartz DH, Fast P. Safety profile of phase I and II preventive HIV type 1 envelope vaccination: experience of the NIAID AIDS Vaccine Evaluation Group. AIDS Res Hum Retroviruses. 1997 Sep 20;13(14):1163-77. doi: 10.1089/aid.1997.13.1163.
citation: VanCott TC, Bethke FR, Burke DS, Redfield RR, Birx DL. Lack of induction of antibodies specific for conserved, discontinuous epitopes of HIV-1 envelope glycoprotein by candidate AIDS vaccines. J Immunol. 1995 Oct 15;155(8):4100-10.
citation: Stanhope PE, Liu AY, Pavlat W, Pitha PM, Clements ML, Siliciano RF. An HIV-1 envelope protein vaccine elicits a functionally complex human CD4+ T cell response that includes cytolytic T lymphocytes. J Immunol. 1993 May 15;150(10):4672-86.
citation: Keefer MC, Graham BS, Belshe RB, Schwartz D, Corey L, Bolognesi DP, Stablein DM, Montefiori DC, McElrath MJ, Clements ML, et al. Studies of high doses of a human immunodeficiency virus type 1 recombinant glycoprotein 160 candidate vaccine in HIV type 1-seronegative humans. The AIDS Vaccine Clinical Trials Network. AIDS Res Hum Retroviruses. 1994 Dec;10(12):1713-23. doi: 10.1089/aid.1994.10.1713.
citation: De Santis C, Robbioni P, Longhi R, Lopalco L, Siccardi AG, Beretta A, Roberts NJ Jr. Cross-reactive response to human immunodeficiency virus type 1 (HIV-1) gp120 and HLA class I heavy chains induced by receipt of HIV-1-derived envelope vaccines. J Infect Dis. 1993 Dec;168(6):1396-403. doi: 10.1093/infdis/168.6.1396.
citation: Schwartz DH, Cosentino LM, Shirai A, Conover J, Daniel S, Klinman DM. Lack of correlation between the number of circulating B cells and the concentration of serum antibodies reactive with the HIV-1 envelope glycoprotein. J Acquir Immune Defic Syndr (1988). 1994 May;7(5):447-53.