This is a Phase 1, single center, randomized, double-blind study designed to evaluate the safety and immunogenicity of live, replication-competent recombinant Adenovirus type 4-HIV vaccine regimens. The oral route will also contain a placebo control. The vaccine candidates Ad4-mgag and Ad4-EnvC150 will be formulated as enteric-coated capsules to be delivered orally, and as an aqueous formulation for intranasal administration. Determining the optimal regimen and route will greatly accelerate investigations of these vectors as HIV vaccine platforms.
Participants volunteering to receive the vaccine orally will be randomized to 1 of 4 treatment arms, and those volunteering to receive the vaccine via the intranasal route will be randomized to 1 of 3 treatment arms. Participants will receive either 1 or both vaccines or placebo, depending on group assignment. The study vaccines will be administered to participants in 3 rounds of vaccination at 0, 2, and 6 months. All participants will receive a booster vaccination with a bivalent HIV gp120 glycoprotein at 8 months. Intranasal vaccine recipients with household contact(s) will receive the first vaccine in the NIH Special Clinical Studies Unit or other appropriate unit and be followed on an inpatient basis to allow for respiratory isolation. Intranasal vaccinees without household contact(s) may also receive the vaccination as inpatients or may opt to receive the vaccine on an outpatient basis if they agree to follow precautions for preventing the spread of adenovirus. Beginning 4 days after vaccination, inpatient participants will be tested daily for respiratory shedding of Ad4 by nasopharyngeal wash. They will be discharged to home with close monitoring on Day 7 or after 2 consecutive negative washes, whichever comes first; they may remain on the unit longer if medically necessary. Prior to receiving the second dose of vaccine on an outpatient basis, seroconversion to Ad4 will be confirmed in the intranasal vaccine recipients. Those who have household contact(s) and have not seroconverted will continue to receive subsequent doses as inpatients until they show seroconversion. Those who do not have household contact(s) and those who have seroconverted may receive the remaining vaccinations as inpatients or may opt to receive the doses on an outpatient basis if they agree to follow precautions for preventing the spread of adenovirus. If they decline these options, they may withdraw from the study and will be replaced. Oral capsule recipients will be vaccinated and discharged to home.
In addition to clinical and laboratory monitoring of safety, the principal assessments will be shedding of this viruses in rectal, cervicovaginal, throat, and nasal swabs, and assessment of the antibody (mucosal and systemic) response to the HIV and to the Ad4 virus.
The candidate vaccines will also be administered to 2 groups of participants who have previously received an unrelated HIV vaccine in another clinical study and/or are Ad4 seropositive. The aim for these groups is to explore the boost potential of the enteric coated capsule and aqueous formulations of the Ad4-mgag and Ad4- EnvC150 vaccines when given to subjects who have previously received another HIV vaccine and/or are Ad4 seropositive.
The adenovirus vaccines will not be retested for stability in 2018, and therefore will be out of specifications on May 9th 2018. In an effort to capture as much information on immunogenicity and adenoviral replication as possible, we will implemement the following change beginning in 2018. The study will continue with enrollment into the remaining treatment groups in a nonrandomized manner such that remaining participants receive both the Ad4-mgag and Ad4-EnvC150 intranasally. These participants will receive 2 rounds of the intranasal vaccine at Months 0 and 2 followed by a single dose of the booster vaccination at Month 4.
All participants will be followed for a total of 6 months following the final dose of study vaccine. Household and intimate contacts will also be enrolled and monitored for Adenovirus and HIV antibodies for up to 8 months.
