Safety of and Immune System Response to an HIV Vaccine (EP HIV-1090) in HIV Uninfected Adults

HIV Infections Clinical Trial

Official title:

A Phase I Dose-Escalation Clinical Trial to Evaluate the Safety and Immunogenicity of the EP HIV-1090 DNA Vaccine in Healthy, HIV-1-Uninfected Adult Participants

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00054860
• Other study ID #: HVTN 048
• Secondary ID: 10197
• Status: Completed
• Phase: Phase 1
• Est. completion date: September 2005

Study information

• Verified date: October 2021
• Source: National Institute of Allergy and Infectious Diseases (NIAID)
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to test the safety of an HIV DNA vaccine (EP HIV-1090) and to test whether or not the vaccine can stimulate immune system responses in HIV uninfected people. This vaccine uses only parts of the virus's DNA and cannot cause HIV infection.

Description:

Epidemiological and animal model data support the hypothesis that HIV specific cytotoxic T lymphocyte (CTL) responses contribute to control and clearance of the virus. Vaccines designed specifically to induce CTL responses are likely to be well suited for protection against HIV infection and disease progression. EP HIV-1090 is a DNA vaccine composed of 21 highly specific CTL epitopes. The vaccine is designed to optimize the immune response in people expressing one of three HLA Class I antigen subtypes: HLA-A2, -A3, and -B7. This design is predicted to induce an immune response in 85% of individuals in the general population. There is also a helper T lymphocyte (HTL) facilitating epitope (PADRE) in the vaccine. The vaccine is formulated with a water soluble polymer (polyvinylpyrrolidone) that protects the DNA and facilitates cellular uptake. This study will assess the safety of and immune response to different doses of EP HIV-1090 in healthy, HIV uninfected adults.

Participants in this study will be randomized to receive either one of three different doses of vaccine or placebo. Participants will receive vaccinations or placebo at study entry and Months 1, 3, and 6. Both vaccinations and placebo are administered by intramuscular injection. Participants will be followed for 18 months and will have 12 study visits. Each study visit will include a physical exam, medical history, and blood and urine tests. Each participant will have four HIV tests during the study. Women will have at least five pregnancy tests during the study.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 42
• Est. completion date: September 2005
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria

• HIV negative

• Positive for one or more of the following HLA supertypes: -A2, -A3, or -B7

• Willing to receive HIV test results

• Good general health

• Acceptable methods of contraception for females of reproductive potential

• Hepatitis B surface antigen negative

• Anti-hepatitis C virus antibody (anti-HCV) negative or negative HCV PCR if anti-HCV is positive

Exclusion Criteria

• HIV vaccines or placebos in prior HIV vaccine trial

• Immunosuppressive medications within 168 days prior to first study vaccine administration

• Blood products within 120 days prior to first study vaccine administration

• Immunoglobulin within 60 days prior to first study vaccine administration

• Live attenuated vaccines within 30 days prior to first study vaccine administration

• Investigational research agents within 30 days prior to first study vaccine administration

• Subunit or killed vaccines within 14 days prior to first study vaccine administration

• Current tuberculosis prophylaxis or therapy

• Active syphilis

• Serious adverse reaction to vaccines. A person who had an adverse reaction to pertussis vaccine as a child is not excluded.

• Autoimmune disease or immunodeficiency

• Unstable asthma

• Type 1 or Type 2 Diabetes Mellitus

• Thyroid disease requiring treatment

• Serious angioedema within the past 3 years

• Uncontrolled hypertension

• Bleeding disorder

• Malignancy unless it has been surgically removed and, in the opinion of the investigator, is not likely to recur during the study period

• Seizure disorder requiring medication within the past 3 years

• Asplenia

• Mental illness that would interfere with compliance with the protocol

• Other conditions that, in the judgment of the investigator, would interfere with the study

• Pregnant or breast-feeding

Related Conditions & MeSH terms

• HIV Infections

Intervention

Biological:
• EP HIV-1090

Locations

Country	Name	City	State
Botswana	Gaborone Prevention/Treatment Trials CRS	Gaborone
United States	Brigham and Women's Hosp. CRS	Boston	Massachusetts
United States	Fenway Community Health Clinical Research Site (FCHCRS)	Boston	Massachusetts
United States	Miriam Hospital's HVTU	Providence	Rhode Island
United States	Saint Louis Univ. School of Medicine, HVTU	Saint Louis	Missouri

Sponsors (1)

Lead Sponsor	Collaborator
National Institute of Allergy and Infectious Diseases (NIAID)

Countries where clinical trial is conducted

United States,  Botswana, 

References & Publications (5)

Altfeld MA, Livingston B, Reshamwala N, Nguyen PT, Addo MM, Shea A, Newman M, Fikes J, Sidney J, Wentworth P, Chesnut R, Eldridge RL, Rosenberg ES, Robbins GK, Brander C, Sax PE, Boswell S, Flynn T, Buchbinder S, Goulder PJ, Walker BD, Sette A, Kalams SA. Identification of novel HLA-A2-restricted human immunodeficiency virus type 1-specific cytotoxic T-lymphocyte epitopes predicted by the HLA-A2 supertype peptide-binding motif. J Virol. 2001 Feb;75(3):1301-11. — View Citation

Hanke T, Samuel RV, Blanchard TJ, Neumann VC, Allen TM, Boyson JE, Sharpe SA, Cook N, Smith GL, Watkins DI, Cranage MP, McMichael AJ. Effective induction of simian immunodeficiency virus-specific cytotoxic T lymphocytes in macaques by using a multiepitope gene and DNA prime-modified vaccinia virus Ankara boost vaccination regimen. J Virol. 1999 Sep;73(9):7524-32. — View Citation

Livingston BD, Newman M, Crimi C, McKinney D, Chesnut R, Sette A. Optimization of epitope processing enhances immunogenicity of multiepitope DNA vaccines. Vaccine. 2001 Sep 14;19(32):4652-60. — View Citation

Sette A, Vitiello A, Reherman B, Fowler P, Nayersina R, Kast WM, Melief CJ, Oseroff C, Yuan L, Ruppert J, Sidney J, del Guercio MF, Southwood S, Kubo RT, Chesnut RW, Grey HM, Chisari FV. The relationship between class I binding affinity and immunogenicity of potential cytotoxic T cell epitopes. J Immunol. 1994 Dec 15;153(12):5586-92. — View Citation

Woodberry T, Gardner J, Mateo L, Eisen D, Medveczky J, Ramshaw IA, Thomson SA, Ffrench RA, Elliott SL, Firat H, Lemonnier FA, Suhrbier A. Immunogenicity of a human immunodeficiency virus (HIV) polytope vaccine containing multiple HLA A2 HIV CD8(+) cytotoxic T-cell epitopes. J Virol. 1999 Jul;73(7):5320-5. — View Citation

External Links

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