A Safety, Tolerability and Immunogenicity Study of 2 Different Regimens of Tetravalent Ad26.Mos4.HIV Prime Followed by Boost With Tetravalent Ad26.Mos4.HIV Along With Either Clade C gp140 Plus Adjuvant OR With a Combination of Mosaic and Clade C gp140 Plus Adjuvant in Healthy HIV Uninfected Adults

The primary purpose of this study is to assess safety/tolerability of the different vaccine regimens and of a late boost vaccination; and to assess envelope (Env)-binding antibody (Ab) responses of the 2 different vaccine regimens.

This is a randomized (study medication assigned by chance), double-blind (neither physician nor participant knows the treatment received), placebo-controlled (placebo is an inactive substance that is compared with a drug to test whether the drug has a real effect in a clinical trial), parallel-group (each treatment group will be treated at the same time), multicenter (more than one clinical site) study in healthy human immunodeficiency virus (HIV)-uninfected adults. The main study will be conducted in 3 phases: a 6-week screening period; a 48-week vaccination period; and a follow-up period to the final main study visit at Week 72. A Long-term Extension (LTE) phase (approximately 3 years after Week 72) will be performed for participants randomized to Group 1 or Group 2, who receive all 4 vaccinations and are negative for HIV infection at Week 72. The approximate duration of the study will be approximately 78 weeks for participants not participating in the LTE phase and approximately 222 weeks for participants participating in the LTE phase but not receiving a late boost vaccination and approximately 246 (12-month follow-up) or 294 (24-month follow-up) weeks for participants receiving a late boost vaccination. Participants safety will be monitored throughout the study.

Eligibility Criteria:
Inclusion Criteria:

* Participant must be healthy on the basis of medical history, physical examination, and vital signs measurement performed at screening
* Participants are negative for human immunodeficiency virus (HIV) infection at screening
* Participants are amenable to HIV-risk reduction counseling and committed to maintaining behavior consistent with low risk of HIV exposure through the last required protocol clinic visit
* All female participants of childbearing potential must have a negative serum (beta-human chorionic gonadotropin \[beta-hCG\]) at the screening visit, and a negative urine pregnancy test pre-dose on Day 1
* Participants are willing/able to adhere to the prohibitions and restrictions specified in the protocol and study procedures
* Participant must be enrolled in the LTE phase to receive the late boost vaccination

Exclusion Criteria:

* Has chronic hepatitis B (measured by hepatitis B surface antigen test) or active hepatitis C (measured by hepatitis C virus \[HCV\] Ab test; if positive, HCV ribonucleic acid \[RNA\] polymerase chain reaction (PCR) test will be used to confirm active versus past HCV infection), active syphilis infection, chlamydia, gonorrhea, or trichomonas
* In the 12 months prior to randomization, participant has a history of newly acquired herpes simplex virus type 2 (HSV-2), syphilis, gonorrhea, non-gonococcal urethritis, chlamydia, pelvic inflammatory disease, trichomonas, mucopurulent cervicitis, epididymitis, proctitis, lymphogranulomavenereum, chancroid, or hepatitis B
* Participant has had major surgery (eg, requiring general anesthesia) within the 4 weeks before screening, or will not have fully recovered from surgery, or has surgery planned through the course of the study
* Participant has had a thyroidectomy or active thyroid disease requiring medication during the last 12 months (not excluded: a stable thyroid supplementation)
* Current or past drug/alcohol use that investigator assesses poses any more than a remotely increased risk of the ability of the participant to comply with the protocol requirements
* Has been in receipt of any licensed vaccine within 14 days prior to the first dose of study vaccine or placebo, plans to receive within 14 days after the first study vaccination, or plans to receive within 14 days before or after the second, third or fourth vaccination
* Is a recipient of a prophylactic or therapeutic HIV vaccine candidate at any time, or a recipient of other experimental vaccine(s) within the last 12 months prior to the Day 1 visit (Vaccination 1). For participants who received an experimental vaccine (except HIV vaccine) more than 12 months prior to the Day 1 visit (Vaccination 1), documentation of the identity of the experimental vaccine must be provided to the sponsor, who will determine eligibility on a case-by-case basis