Safety of and Immune Response to an HIV Vaccine (VRC-HIVDNA009-00-VP) Administered With Interleukin-2/Immunoglobulin (IL-2/Ig) DNA Adjuvant in Uninfected Adults

National Institute of Allergy and Infectious Diseases (NIAID)

Status and phase

Completed

Phase 1

Conditions

HIV Infections

Treatments

Biological: VRC-HIVDNA009-00-VP (Gag-Pol-Nef-multiclade-Env) with adjuvant VRC-ADJDNA004-IL2-VP

Study type

Interventional

Funder types

NIH

Identifiers

NCT00069030

HVTN 044

10120 (Registry Identifier)

5K08AI051223-03 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

This study will test the safety of and immune system response to a new HIV vaccine. The vaccine in this study is made from HIV DNA produced in a laboratory. Only part of the virus's DNA is used in the vaccine and the vaccine itself cannot cause HIV infection or AIDS. In addition to HIV DNA, the vaccine contains interleukin-2 (IL-2) DNA fused to a portion of immunoglobulin (Ig) DNA. IL-2 is a chemical that stimulates the immune system and may improve response to the vaccine.

Study hypothesis: The IL-2/Ig plasmid will be very well tolerated in humans.

Full description

Over 90% of the 40 million people infected with HIV live in developing countries and have little or no access to antiretroviral medications. The worldwide HIV/AIDS epidemic will only be controlled through development of a safe and effective vaccine that will prevent HIV infection. DNA vaccines are inexpensive to construct, readily produced in large quantities, and stable for long periods of time. The DNA vaccine in this study, VRC-HIVDNA009-00-VP (Gag-Pol-Nef-multiclade Env), uses multiple gene products to increase the breadth of the immune response across different HIV subtypes. The DNA plasmids in VRC-HIVDNA009-00-VP code for proteins from HIV subtypes A, B, and C, which together represent 90% of new HIV infections in the world.

The study vaccine is administered with an adjuvant. The adjuvant is a DNA plasmid encoding interleukin 2 (IL-2) fused to the Fc portion of IgG for enhanced stability. This IL-2/Ig adjuvant may augment the immune system's response to the vaccine.

Participants in this study will be randomly assigned to receive either the vaccine and adjuvant, the vaccine and placebo, the adjuvant and placebo, or placebo alone. All injections will be administered by needle-free injection in the upper arm. Participants will receive four does of vaccine: one at their first study visit and then at Months 1, 2, and 6. Participants will have a follow-up visit 2 days after each injection. Some participants may receive another injection at this follow-up visit. All study participants will be followed for 18 months and will have 16 to 20 study visits. Study visits will last 1/2 to 2 hours and will include blood and urine tests and a physical exam. Participants will also have six HIV tests over the course of the study.

Enrollment

70 patients

Sex

All

Ages

18 to 40 years old

Volunteers

Accepts Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria

HIV negative
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
Normal thyroid stimulating hormone (TSH) level

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
Clinical depression with pharmacological treatment within the past 2 years
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 judgement of the investigator, would interfere with the study
Pregnant or breast-feeding