Safety of and Immune Response to a Prime-Boost Vaccine Regimen in HIV-Uninfected Vaccine-Naive Adults

Phase 2

Completed

Conditions: HIV Infections

Interventions: Biological: pGA2/JS7 DNA vaccine
Biological: Placebo
Biological: MVA/HIV62 vaccine

Registration Number: NCT00820846

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

Brief Summary: The purpose of this study is to evaluate the safety of and immune response to a two-vaccine regimen in healthy, HIV-uninfected adults who have never received an HIV preventive vaccine before.

Detailed Description: Some of the first HIV vaccines were designed to trigger neutralizing antibody responses as a way to prevent HIV infection. Unfortunately, the first versions of these vaccines were not able to achieve their desired response. An alternative strategy to the antibody approach is the stimulation of HIV-specific CD8 T-lymphocyte (CTL) responses. CTL responses were previously demonstrated to play an important role in the control of simian immunodeficiency virus (SIV), the HIV equivalent seen in rhesus macaque monkeys. Additionally, other studies suggest CTLs play an important role in viral control during chronic infection. Based on this information, several groups have shifted their focus to the development of CTL-based vaccines, some of which have entered advanced clinical trials.

A DNA/rMVA vaccine strategy is structured to bring about both T-cell and antibody responses. The primary vaccination is DNA based and will express only HIV proteins as a way to produce an HIV-focused immune response. An rMVA vaccine strategy expresses both HIV and MVA proteins and may amplify the focused response of a DNA vaccination. Participants in this study will receive either a combined DNA/rMVA vaccine strategy, in which they receive both types of vaccines; an rMVA vaccine strategy, in which they receive only the rMVA vaccine; or a placebo. The DNA and rMVA are physically two different vaccinations given at separate times, but in the DNA/rMVA group, they will be used together to make up one preventive regimen. Both vaccine components express noninfectious virus-like particles.

This study is a multicenter, randomized study that is conducted in two parts and comprised of five groups. In all groups, participants will receive four injections. In Part A, Groups 1 and 2 will be compared. In Group 1, participants will receive two shots of the DNA vaccine and two shots of the rMVA vaccine. In Group 2, participants will receive four placebo injections. In Part B, Groups 3, 4, and 5 will be compared. In Group 3, the combination vaccine strategy will be used again; in Group 4, a single-vaccine strategy of three injections of the rMVA vaccine and one injection of placebo will be given; and in Group 5, participants will again receive four placebo injections. The study will last for a total of 12 months for participants, including enrollment and follow-up.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 299

Inclusion Criteria

Access to a participating HIV Vaccine Trials Network (HVTN) clinical research center and willing to be followed for the planned duration of the study
Ability and willingness to provide informed consent
Assessment of understanding: completion of a questionnaire prior to first vaccination; demonstration of understanding for all questionnaire items answered incorrectly
Willingness to receive HIV test results
Good general health as shown by medical history, physical exam, and screening laboratory tests
Certain specified laboratory values. More information on this criterion can be found in the study protocol.
If pregnancy is possible, must agree to use contraception from at least 21 days prior to enrollment through the last protocol visit for sexual activity that could lead to pregnancy. More information on this criterion can be found in the study protocol.
Willingness to discuss HIV infection risks, amenable to HIV risk reduction counseling, committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit, and willing to continue annual follow-up contact after the last required protocol clinic visit for a total of 5 years following enrollment
Assessed by clinic staff as being at "low risk" of HIV infection on the basis of sexual behaviors within the 12 months prior to enrollment. More information on this criterion can be found in the study protocol.

Exclusion Criteria

HIV vaccine(s) or other experimental vaccines, received in a prior HIV vaccine trial. More information on this criterion can be found in the study protocol.
Receipt of smallpox vaccination
Excessive alcohol use, frequent binge drinking, chronic marijuana abuse, or use of any other illicit drugs, such as cocaine or methamphetamine, within the past 12 months
History of newly acquired or newly diagnosed syphilis; history of newly acquired gonorrhea, nongonococcal urethritis, herpes simplex virus type 2 (HSV2), chlamydia, pelvic inflammatory disease (PID), trichomonas, mucopurulent cervicitis,epididymitis, proctitis, lymphogranuloma venereum, chancroid, or hepatitis B within the past 12 months
Immunosuppressive medication received within 168 days before first vaccination. Certain medications are excluded from this criterion; more information can be found in the study protocol.
Blood products received within 120 days before first vaccination
Immunoglobulin received within 60 days before first vaccination
Live attenuated vaccines other than influenza vaccine received within 30 days before first vaccination or scheduled within 14 days after injection
Influenza vaccine or any vaccines that are not live attenuated and were received within 14 days prior to first vaccination or that are scheduled within 14 days after injection
Allergy treatment with antigen injections within 30 days before first vaccination or scheduled within 14 days after injection
Intent to participate in another study of an investigational research agent during the planned duration of this study
Current anti-tuberculosis (TB) prophylaxis or therapy
Clinically significant medical condition. More information on this criterion can be found in the study protocol.
Any medical, psychiatric, or social condition or occupational or other responsibility that in the opinion of the investigator might interfere with the study protocol
Serious adverse reactions to vaccines. More information on this criterion can be found in the study protocol.
Allergy to eggs and/or egg products
History of or known active cardiac disease. More information on this criterion can be found in the study protocol.
Participants who have two or more of the following cardiac risk factors: (1) participant report of history of elevated blood cholesterol defined as fasting low-density lipoprotein (LDL) greater than 160 mg/dL; (2) first degree relative (e.g., mother, father, sister, or brother) who had coronary artery disease before the age of 50 years; (3) current smoker; or (4) body mass index greater than or equal to 35.
Electrocardiogram (ECG) with clinically significant findings. More information on this criterion can be found in the study protocol.
Autoimmune disease
Immunodeficiency
Asthma other than mild, well-controlled asthma. More information on this criterion can be found in the study protocol.
Diabetes mellitus, type 1 or type 2, including cases controlled with diet alone. Those with a history of isolated gestational diabetes are not excluded.
Thyroidectomy or thyroid disease requiring medication during the last 12 months
Angioedema within the last 3 years if episodes are considered serious or have required medication within the last 2 years
Hypertension. More information on this criterion can be found in the study protocol.
Body mass index greater than or equal to 40
Bleeding disorder diagnosed by a doctor
Malignancy. Participants with surgical excisions and subsequent observation periods, that in the investigator's estimation have a reasonable assurance of sustained cure or are unlikely to recur during the period of study, are not excluded.
Seizure disorder, unless the participant has not required medication or had a seizure within the last 3 years.
Asplenia
Pregnant or breastfeeding

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Part B, Group 3	pGA2/JS7 DNA vaccine	Participants will receive two injections of the pGA2/JS7 DNA vaccine and then two injections of the MVA/HIV62 vaccine
Part A, Group 1	MVA/HIV62 vaccine	Participants will receive two injections of the pGA2/JS7 DNA vaccine and then two injections of the MVA/HIV62 vaccine
Part A, Group 1	pGA2/JS7 DNA vaccine	Participants will receive two injections of the pGA2/JS7 DNA vaccine and then two injections of the MVA/HIV62 vaccine
Part B, Group 4	MVA/HIV62 vaccine	Participants will receive three injections of the MVA/HIV62 vaccine and one injection of the placebo
Part B, Group 5	Placebo	Participants will receive four placebo injections
Part A, Group 2	Placebo	Participants will receive four placebo injections
Part B, Group 3	MVA/HIV62 vaccine	Participants will receive two injections of the pGA2/JS7 DNA vaccine and then two injections of the MVA/HIV62 vaccine
Part B, Group 4	Placebo	Participants will receive three injections of the MVA/HIV62 vaccine and one injection of the placebo

Primary Outcome Measures

Name	Time	Method
Laboratory measures of safety, including boxplots of white blood cells (WBC), neutrophils, lymphocytes, hemoglobin, platelets, alanine aminotransferase (ALT), creatinine, and cardiac troponin results at baseline and following vaccination	At study entry and following vaccinations
Number of participants with early discontinuation of vaccinations, by treatment group and reason for discontinuation	Throughout study
Frequency of severe local and systemic reactogenicity signs and symptoms	Throughout study
Frequency of adverse events and assessed relationship to study products	Throughout study

Secondary Outcome Measures

Name	Time	Method
Responses to individual HIV potential T-cell epitope (PTE) peptide pools representing Env, Gag, and Pol	Throughout study
Percentage of responding CD4+ and CD8+ T cells producing interferon (IFN)-gamma, interleukin (IL)-2, tumor necrosis factor (TNF)-alpha, CD57, perforin, or granzyme B or demonstrating other functions	Measured at study completion
Frequency of vaccine-induced positive results with end of study HIV serological testing by commercial assays	Measured at study completion
Frequency and titer of humoral responses detected by HIV binding antibody assays to p55 Gag and gp140 Env	Measured at study completion
Frequency of CD4+ T-cell responses	Measured 2 weeks following last MVA vaccination
Frequency of CD8+ T-cell responses	Measured 2 weeks following last MVA vaccination

Trial Locations

Locations (12): The Hope Clinic of the Emory Vaccine Center CRS
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Decatur, Georgia, United States
Alabama CRS
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Birmingham, Alabama, United States
Bridge HIV CRS
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San Francisco, California, United States
Fenway Health (FH) CRS
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Boston, Massachusetts, United States
Vanderbilt Vaccine (VV) CRS
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Nashville, Tennessee, United States
Seattle Vaccine and Prevention CRS
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Seattle, Washington, United States
Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
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Boston, Massachusetts, United States
Columbia P&S CRS
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New York, New York, United States
New York Blood Center CRS
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New York, New York, United States
University of Rochester Vaccines to Prevent HIV Infection CRS
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Rochester, New York, United States
ACSA CRS
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Iquitos, Maynas, Peru
Barranco CRS
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Lima, Peru