Safety of and Immune Response to Polyvalent HIV-1 Vaccine in HIV Uninfected Adults

Sponsor

National Institute of Allergy and Infectious Diseases (NIAID) (NIH)

Overall Status

Unknown status

CT.gov ID

NCT00061243

Collaborator

(none)

Enrollment

Location

Arms

Duration (Months)

0.5

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

This study will evaluate the safety of and immune response to a new HIV vaccine. The vaccine in this trial uses pieces of HIV DNA and HIV proteins. The vaccine itself cannot cause HIV infection or AIDS.

Condition or Disease	Intervention/Treatment	Phase
HIV Infections	Biological: HIV-1 DNA vaccine with protein vaccine boost	Phase 1

Detailed Description

Unlike other viruses for which effective vaccines have been developed, HIV-1 has evolved mechanisms to evade immune control over virus replication. These mechanisms include the extraordinary genetic diversity of the virus, viral latency, and targeting of the immune system. Evolutional variations of the envelope gene have not only resulted in the development of different groups (M, N, and O) and subgroups (clades) in diverse geographic regions of the world, but also significant genomic variations within clades. These clade variants of HIV will require novel vaccine approaches to elicit population-based protective immunity. Viral latency is the ability of the virus to remain dormant for long periods through integrating its viral DNA into the host genome. Viral latency requires vaccines to produce immune response that are robust enough to kill the virus and that can be maintained over extended periods of time to produce lasting immunity. Finally, HIV-1 targets CD4 cells and thus compromises the immune surveillance mechanisms critical to maintaining both cellular and humoral immunity to HIV-1. Therefore, an effective vaccine against HIV-1 must bolster the development of broadly reactive neutralizing antibodies against genetic variants of HIV-1, as well as induce an effective HIV-specific CTL response to eliminate virus-infected cells. The ideal vaccine approach will produce long-term responses within these arms of host immunity. This study is designed to evaluate the safety, tolerability, and immunogenicity of a novel prophylactic vaccine consisting of DNA priming followed by a protein boost.

The first vaccine component administered in this study is a DNA vaccination; the second component is a recombinant protein vaccination. This combination will be used to determine whether the vaccine strategy can induce a balanced humoral and cell mediated immune responses to HIV-1.

Two HIV antigens, Gag and Env, are included in this study's vaccine formulation. Studies have shown that HIV-1 Gag is a potent inducer of cell mediated immune responses, while Env is the target of neutralizing antibody responses. The vaccine used in this study contains a 5-valent Env design (Env derived from one of 5 clades of HIV) in order to examine if a polyvalent Env formulation may expand the breadth of neutralizing antibody responses induced in human volunteers. For both DNA priming and protein boosting, a set of Env antigens from clades A, B, C, and E of HIV-1 M group will be produced (2 Env antigens from clade B and 1 Env each from the other three clades). All 5 Env antigens are selected from the primary HIV-1 viral isolates with the hope of producing broad antibody responses against the primary viruses circulating in the worldwide human population.

Thirty-six healthy volunteers will be randomized to one of five groups. Groups 1, 2, and 3 will receive different doses of the vaccine to determine the optimal dose. Groups 4 and 5 will receive the vaccine through either intradermal or intramuscular administration. Each group will receive 3 doses of DNA vaccination at weeks 0, 4, and 12, and 2 doses of protein vaccination at weeks 20 and 28. Blood sampling throughout the duration of the study will provide an assessment of the safety and immunogenicity of the vaccine in healthy volunteers. It is expected that volunteers will be enrolled in this study for 1 year.

Study Design

Study Type:

Interventional

Actual Enrollment :

36 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Masking:

None (Open Label)

Primary Purpose:

Prevention

Official Title:

A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of a Multi-Gene, Polyvalent HIV-1 DNA Plasmid Prime/Env Protein Boost Vaccine Formulation, DP6-001 in Healthy Volunteers

Study Start Date :

Apr 1, 2004

Actual Primary Completion Date :

Apr 1, 2005

Anticipated Study Completion Date :

Apr 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Experimental: 1 Participants will receive different doses of the vaccine to determine the optimal dose	Biological: HIV-1 DNA vaccine with protein vaccine boost Three doses of DNA vaccination will be administered at weeks 0, 4, and 12, and 2 doses of protein vaccination at weeks 20 and 28
Experimental: 2 Participants will receive different doses of the vaccine to determine the optimal dose	Biological: HIV-1 DNA vaccine with protein vaccine boost Three doses of DNA vaccination will be administered at weeks 0, 4, and 12, and 2 doses of protein vaccination at weeks 20 and 28
Experimental: 3 Participants will receive different doses of the vaccine to determine the optimal dose	Biological: HIV-1 DNA vaccine with protein vaccine boost Three doses of DNA vaccination will be administered at weeks 0, 4, and 12, and 2 doses of protein vaccination at weeks 20 and 28
Experimental: 4 Participants will receive the vaccine through either intradermal or intramuscular administration	Biological: HIV-1 DNA vaccine with protein vaccine boost Three doses of DNA vaccination will be administered at weeks 0, 4, and 12, and 2 doses of protein vaccination at weeks 20 and 28
Experimental: 5 Participants will receive the vaccine through either intradermal or intramuscular administration	Biological: HIV-1 DNA vaccine with protein vaccine boost Three doses of DNA vaccination will be administered at weeks 0, 4, and 12, and 2 doses of protein vaccination at weeks 20 and 28

Outcome Measures

Primary Outcome Measures

Safety and tolerability [Throughout study]

Secondary Outcome Measures

Cross-clade neutralizing antibody [Throughout study]
Cellular immunity [Throughout study]

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 50 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria

HIV uninfected
Good general health as determined by medical history, physical examination, vital signs, and clinical laboratory measurements
Body Mass Index (BMI) =< 32
Hepatitis B surface antigen negative
Anti-hepatitis C virus antibody (anti-HCV) negative or negative HCV PCR if anti-HCV is positive
Low risk for HIV exposure
No co-existent endocrine conditions
No evidence of hepatic insufficiency, significant renal insufficiency, or proteinuria
Acceptable methods of contraception
Anticipated availability for the planned follow-up period of one year

Exclusion Criteria

Certain medications during the 2 weeks prior to study entry
Donation of a unit of blood within 2 months prior to study entry
Participation in a study of investigational or marketed drugs within 1 month prior to study entry
Blood transfusion within 6 months prior to study entry
Pregnant, breastfeeding, or planning pregnancy during the study period
History of significant adverse reaction to any vaccine
Prior receipt of any experimental HIV vaccine
Morbid obesity (> 195% of ideal body weight)
Hypertension (patients may be taking concomitant antihypertensive medication during the study if approved by study officials)
History of chronic medical illness, malignancy, or autoimmune disorder
History of immunodeficiency or treatment with immunosuppressive medications
History of organ transplant
Medical or psychiatric obstacle to compliance with protocol
Significant urine concentration of any drug that could interfere with the study