Efficacy Study of T Cell Vaccination in HIV Infection

Phase II Study of Efficacy, Tolerability and Safety of CD4-Specific T-cell Vaccine in HIV Infection

The hallmark of HIV infection and AIDS is the continuous attrition of CD4 T cells. One of the mechanisms that may account for the CD4 attrition , is autoimmunity against the CD4 T cells, caused by autologous immune cells. Vaccination against autoimmune reactive T cells has been successfully tried in animal models of autoimmune diseases and is now being tried in patients with Multiple Sclerosis. The purpose of the present study is to test this hypothesis in HIV infection. We will vaccinate HIV infected patients in whom specific autoimmune reactivity against CD4 is present , with their own CD4 reactive T cells. Following that, we shall study the patients and find out if the T cell vaccination caused a rise in CD4 T cell levels, and whether it influenced HIV viral load, as well as HIV and CD4 specific immunity.

Study Overview

• Status: Completed
• Conditions: HIV Infections
• Intervention / Treatment: Biological: T cell vaccination; Biological: T cell vaccination

Detailed Description

The study will be based on forty HIV infected patients, receiving anti retroviral treatment (HAART), with CD4 levels between 150-350 and HIV plasma viral load < 5000, for at least 12 months and despite continuous anti-retroviral treatment. The patients will be randomly divided into two groups, one that will get the T cell vaccination, and the other that will serve as controls. The T cell vaccine will be prepared from autologous T cells that responded by specific proliferation to recombinant CD4, further expanded in vitro by IL-2, and then fixed by glutaraldehyde. Each vaccine portion will consist of 10,000 such cells suspended in saline and given subcutaneously every three months during the first year of the trial. The outcome measures will be CD4 levels, specific immunity to HIV antigens, immune activation profile and HIV plasma viral loads, determined sequentially during the 24 months of the trial. These outcome measures will be compared between the experimental and the control groups, to determine if this mode of treatment is effective in influencing CD4 levels as an additional mode of treatment during HIV infection.

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Phase 2

Contacts and Locations

Study Locations

• Israel
  • Beer Sheba, Israel
    • Soroka Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. CD4 cell counts -from 150 to 450/mm3 and stable for at least 12 months, and treatment with HAART for at least 6 months.
2. Positive cell proliferation assay to CD4 molecule
3. Low HIV viral load (<400 - 5000 copies/ml) for at least 12 months
4. No change of antiretroviral treatment for at least 6 months
5. Signed informed consent

Exclusion Criteria:

1. Concomitant immunosuppressive or antineoplastic treatment as well as chronic systemic glucocorticoid therapy.
2. Pregnancy and women without any efficacious contraception.
3. Clinically relevant liver disease (AST and/or ALT >2,5x upper limit of normal range, or total bilirubin > 3,5 mg/dl).
4. Serum creatinine >1,8mg/dl or creatinine clearance <30ml/min.
5. Patients who cannot fully understand the treatment protocol or are unable to sign the informed consent.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Vaccination; One arm of open label T cell vaccination in which all participants will receive the T cell vaccine	Biological: T cell vaccination; Approximately 10-20 million glutaraldehyde fixed CD4 responsive autologous T cells in 1-2 ml, per vaccine injection.; Biological: T cell vaccination; Approximately 10-20 million autologous CD4 reactive T cells per each vaccine injection

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
CD4 T cell levels	one year follow up
HIV plasma viral load	one year follow up
Clinical HIV infection	one year follow up

Secondary Outcome Measures

Outcome Measure	Time Frame
HIV specific immune responses	One year follow up
CD4 specific responses	One year follow up
Immune profile	One year follow up

Collaborators and Investigators

• Sponsor: Soroka University Medical Center
• Investigators: Study Director: Klaris Riesenberg, M.D., Soroka U Medical Center

Publications and helpful links

General Publications

• Abulafia-Lapid R, Bentwich Z, Keren-Zur Y, Cohen IR, Atlan H. T-cell vaccination against anti-CD4 autoimmunity in HIV-1 infected patients. J Clin Virol. 2004 Dec;31 Suppl 1:S48-54. doi: 10.1016/j.jcv.2004.09.017.
• Abulafia-Lapid R, Mayan S, Bentwich Z, Keren-Zur Y, Avbramovitz Y, Cohen IR, Atlan H. T-cell vaccination against anti-CD4 autoimmunity in HIV-1 subtypes B and C-infected patients--an extended open trial. Vaccine. 2005 Mar 18;23(17-18):2149-53. doi: 10.1016/j.vaccine.2005.01.054.

Study record dates

Study Major Dates

• Study Start: November 1, 2006
• Primary Completion (Actual): November 1, 2008
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: December 3, 2006
• First Submitted That Met QC Criteria: December 3, 2006
• First Posted (Estimate): December 5, 2006

Study Record Updates

• Last Update Posted (Estimate): December 2, 2009
• Last Update Submitted That Met QC Criteria: December 1, 2009
• Last Verified: November 1, 2006

More Information

Terms related to this study

• Keywords: HIV; HIV Therapeutic Vaccine; Viral load; T cell vaccination; CD4 T cell level; CD4 autoimmunity
• Additional Relevant MeSH Terms: Pathologic Processes; RNA Virus Infections; Virus Diseases; Blood-Borne Infections; Sexually Transmitted Diseases, Viral; Sexually Transmitted Diseases; Lentivirus Infections; Retroviridae Infections; Immunologic Deficiency Syndromes; Immune System Diseases; Disease Attributes; Slow Virus Diseases; HIV Infections; Infections; Communicable Diseases; Acquired Immunodeficiency Syndrome
• Other Study ID Numbers: sor444006ctil