Healthy Volunteer
Conditions
Keywords
Ad4-Env150KN, Ad4-Env145NFL, VRC-HIVRGP096-00-VP (Trimer 4571) with alum, Adenovirus, HIV Vaccine
Brief summary
Background: Researchers want see if three new HIV (human immunodeficiency virus) vaccines are safe. Two vaccines are carried by live adenoviruses, which are natural and typically cause cold symptoms or an eye infection. Researchers want to see if all the vaccines help fight HIV and if the adenoviruses are contagious. Objectives: To test the safety and effects of three new HIV vaccines. Eligibility: Healthy adults 18-49 years old (vaccinees) Their household and intimate contacts 18-65 years old Design: Vaccinees will be screened with: Physical exam Medical history Blood and urine tests Questions about HIV risk Vaccinees will learn how to prevent spreading the viruses and about required contraception during the study. Vaccinees will get consent forms for their household and intimate contacts. All contacts must be age 18-65. All intimate contacts must sign a consent form. Contacts will have 4 visits over 8 months for blood tests and a physical exam. All applicable participants will have a pregnancy test at every visit. Vaccinees will have about 9 visits over 12 months. They will repeat screening tests and get: 1 of the 2 adenovirus vaccines sprayed in the nose at 2 visits The booster vaccine by needle in an arm at 1 visit Nasal swabs taken at some visits Vaccinees will note their temperature and symptoms for at least 1-4 weeks after each vaccine. Vaccinees may choose to have: Leukapheresis. Blood will be removed by needle in a vein in one arm. A machine will remove white blood cells. The rest of the blood will be returned into the other arm. Small pieces of the tonsil removed Sponsoring Institute: National Institute of Allergy and Infectious Diseases ...
Detailed description
This is a Phase 1 study to evaluate the immunogenicity and safety of adenovirus serotype 4 (Ad4)-based HIV vaccines when administered via the intranasal route to healthy human volunteers. It is hypothesized that the vaccines will be safe for human administration and will elicit immune responses to the HIV components. All study activities will be carried out at the NIH. Each study vaccinee will receive 5x10\^8 viral particles of either Ad4-Env150KN or Ad4-Env145NFL, administered as an intranasal spray at months 0 and 2. An intramuscular protein booster vaccination with the heterologous soluble trimeric protein VRC-HIVRGP096-00-VP (Trimer 4571) with alum will be administered to all vaccinees at month 6. Specimens to evaluate immunogenicity will be taken at baseline and at specified time points through month 12. The HIV-specific immune responses will be assessed by cellular immune function assays (intracellular cytokine analysis, flow cytometry-based killing assays), as well as measures of humoral immunity such as neutralization assays. The overall goal will be to compare the safety and immunogenicity of the Ad-HIV vaccine regimens. Participants who have previously received another HIV vaccine and/or are Ad4 seropositive will be enrolled into an exploratory arm to be analyzed separately. Household and intimate contacts willing to participate will also be enrolled and monitored for transmission of the vaccine virus by serology. Intimate contacts (current and/or those expected within the first 3 weeks after vaccination) will be required to enroll if the partner and participant choose not to abstain from mouth-to-mouth kissing, sexual intercourse, or oral sex within the first 21 days following each Ad4-Env vaccination.
Interventions
BIOLOGICALAd4-Env145NFL
10\^8 vp doses of Ad4-Env145NFL formulated as a liquid for intranasal administration.
BIOLOGICALAd4-Env150KN
10\^8 vp doses of Ad4-Env150KN formulated as a liquid for intranasal administration.
BIOLOGICALVRC-HIVRGP096-00-VP (Trimer 4571) with alum
500-mcg dose of protein boost vaccine formulated for intramuscular administration.
Sponsors
National Institute of Allergy and Infectious Diseases (NIAID)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
* INCLUSION CRITERIA: All participants (vaccinees, household contacts, and intimate contacts) must meet all of the following criteria: 1. Age 18 to 49 years for vaccinees. Age 18 to 65 years for household and intimate contacts. 2. Negative FDA-approved HIV test. 3. Available and willing to participate in follow-up visits and tests for the duration of the study. 4. Willing to have samples stored for future research. The following inclusion criteria apply to vaccinees and intimate contacts, but not to household contacts: 1. In good general health without clinically significant medical history. 2. Assessed as low risk for HIV infection by agreeing to discuss HIV infection risks with the study clinicians, agreeing to HIV risk reduction counseling, and agreeing to avoid behavior associated with high risk of HIV exposure through the last required clinic visit in the protocol schedule. 3. Negative beta-HCG pregnancy test for females presumed to be of reproductive potential. 4. Female vaccinees and male intimate contacts must meet one of the following criteria: -The female vaccinee has no reproductive potential because of menopause (1 year without menses) or because of a hysterectomy, bilateral oophorectomy, medically-documented ovarian failure, or tubal ligation. or -The female vaccinee and her male intimate contact(s) agree to be heterosexually inactive or consistently practice contraception at least 21 days prior to each vaccination through 21 days following each vaccination. Acceptable methods of contraception include any of the following: * condoms, male or female, with a spermicide. * diaphragm or cervical cap with spermicide. * contraceptive pills, Norplant, or Depo-Provera (and is not on any medications that would interfere with the effectiveness of these contraceptive agents). * male partner has previously undergone a vasectomy for which there is documentation. * intrauterine device. 5. Male vaccinees and female intimate contacts must agree to consistently practice abstinence or effective birth control (described above) and for 21 days following each vaccination. The following inclusion criteria apply only to vaccinees and not to household or intimate contacts: 1. Willing to receive HIV test results and abide by NIH guidelines for partner notification of positive HIV results. 2. Physical examination and laboratory results without clinically significant findings within the 8 weeks prior to enrollment. 3. Willing to avoid other investigational and/or HIV vaccinations, other than the study agent, from screening through the end-of-study visit. 4. Safety laboratory criteria within 8 weeks prior to enrollment: * Hematologic: * White blood cell count and lymphocyte count within 25% of both the lower limit and upper limit of normal for the NIH CC * Platelet count of least 150,000/mm\^3. * Hemoglobin count within 10% of both the lower limit and upper limit of normal for the NIH CC * Renal: Blood urea nitrogen (BUN) \<23 mg/dL; creatinine within normal limits for the NIH CC * Hepatic: Serum direct bilirubin within normal limits for the NIH CC * Metabolic: Alanine aminotransferase (ALT) \<2 times upper limit of normal range for the NIH CC * Additional laboratory criteria: * Immunologic: No history of hypogammaglobulinemia. * Serologic: Ad4 neutralizing antibody 80% inhibitory dilution \<1:100. (This criterion does not apply to participants in Arm B.) 5. Willing to follow precautions for preventing the spread of adenovirus in the community. 6. Males must agree not to donate sperm for 21 days following each study vaccination.
Exclusion criteria
A participant (vaccinees, household contacts, and intimate contacts) will be excluded if they have the following: 1\. Any condition that, in the investigator's judgement, places the subject at undue risk by participating in the study. The following
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Safety and immunogenicity | ongoing | Laboratory results and Adverse Events |
Countries
United States
Contacts
CONTACTMark Connors, M.D.
PRINCIPAL_INVESTIGATORMark Connors, M.D.
National Institute of Allergy and Infectious Diseases (NIAID)
Outcome results
None listed