This is a first in human testing of novel HIV-1 protein nanoparticles vaccine candidates, UVAX-1107 and UVAX-1197 mixed with Aluminum Hydroxide (AH) and CpG 1018 adjuvants. After meeting all eligibility criteria, approximately 34 participants will receive a 4-dose vaccination regimen of either 2 priming vaccinations of UVAX-1107 followed by 2 boosting vaccinations of UVAX-1197, or 4 doses of UVAX-1107, or placebo. Subject participation is expected to last up to 374 days, including up to a 30-day screening period and a 337-day study period during which subjects will be followed for safety and immunogenicity outcomes.

This is a first in human testing of a novel HIV-1 vaccine candidate. Both UVAX-1197 and UVAX-1107 are protein nanoparticle vaccines displaying an uncleaved, prefusion-optimized (UFO) envelope (Env) glycoprotein from HIV-1 BG505 (BG505-UFO). The UVAX-1197 displays fully glycosylated UFO Env trimers with wildtype glycans (WT). UVAX-1107 is derived from UVAX-1197 by enzymatic "glycan trimming" (GT) of N-linked glycans in order to better expose major neutralizing epitopes on the surface of BG505-UFO Env to immune recognition. The optimized vaccine immunogens will be mixed with Aluminum Hydroxide (AH) and CpG 1018 adjuvants to enhance the immune response. Subject participation is expected to last up to 374 days, including up to a 30-day screening period and a 337-day study period.

Part 1 of the study will be a safety lead-in cohort in which 4 participants will receive 2 priming vaccinations of a half dose of adjuvanted UVAX-1107 (administered in 0.5ml intramuscular injection) on Days 1 and 57 followed by boosting vaccinations of a half dose of adjuvanted UVAX-1197 on Days 141 and 225, administered as intra-muscular (IM) injections. Safety will be reviewed after subjects in Part 1 reach Day 8, prior to opening Part 2.

A separate group of participants will be enrolled in Part 2 of the study. Participants in Part 2 will be randomized to the following treatment arms to receive either:

• Priming vaccinations of adjuvanted UVAX-1107 (full dose, administered in 0.5ml intramuscular injection) on Days 1 and 57 followed by boosting vaccinations of adjuvanted UVAX-1197 (full dose, administered in 0.5ml intramuscular injection) on Days 141 and 225.
• Priming vaccinations of adjuvanted UVAX-1107 (full dose) on Days 1 and 57 followed by boosting vaccinations of adjuvated UVAX-1107 (full dose) on Days 141 and 225.

When Part 2 of the study opens, 5 sentinel participants (2 from each of the active treatment groups and 1 from the placebo group) will be randomized. Safety will be reviewed after these first 5 Part 2 participants reach Day 8 prior to opening randomization to the remaining participants in Part 2.

Vaccinations will be administered by trained staff at the study site(s) according to site's SOPs. Details regarding dosing, including the dose administered, arm, and the date and time of dosing, will be recorded in the subjects source notes and electronic case report form (eCRF).

Inclusion Criteria:

1. Male or female, 25-55 years of age, inclusive, at screening.

2. Stable health status, as established by physical examination and medical history.

3. Capable of providing written informed consent.

4. Female participants of reproductive potential must be non-pregnant and non lactating, and if of child-bearing potential must agree to be heterosexually inactive from at least 21 days prior to enrolment (Day 1)and through 90 days following last study vaccination or agrees to consistently use highly effective method of birth control and refrain from donating oocytes from at least 21 days prior to enrolment and through 90 days following last study vaccination.

5. Male participants must:

   1. Agree not to donate sperm from the time of signing consent until at least 90 days after the last dose of study drug.
   2. If engaging in sexual intercourse with a female partner who could become pregnant, must agree to use adequate contraception until at least 90 days after the last dose of study drug.
   3. If engaging in sexual intercourse with a female partner who is not of childbearing potential or a same-sex partner, must agree to use a condom.

Exclusion Criteria:

1. Chronic illness being treated actively and with evidence of recent adjustments in medications for worsening or fluctuating symptoms in the past 3 months, or hospitalizations / procedural interventions in the past 6 months.
2. Body mass index (BMI) of less than 17 and greater than 32 kg/m2 at screening.
3. Vital signs grading greater than 1 at screening
4. Toxicity grading greater than 1 for screening laboratory test results.
5. Any abnormal, clinically significant ECG result at screening.
6. High risk of contracting HIV.
7. History of cancer (malignancy) in the last 10 years.
8. Use of narcotic/illicit drugs or a history of drug/alcohol abuse within the past 2 years.
9. Has donated blood or suffered from blood loss of more than 450 mL (1 unit of blood) within 60 days prior to screening, or donated plasma within 14 days prior to screening.
10. Receipt of immunoglobulin, blood-derived products, high dose systemic corticosteroids, or other immunosuppressant drugs within 90 days prior to Day 1 or who expect to receive immunoglobulin or another blood product during the study.
11. Receipt of a licensed or emergency/provisional approval vaccine within the last 30 days prior to Day 1.
12. Known hypersensitivity to any component of the study vaccines, including history of anaphylaxis or other significant allergy in the opinion of the Investigator.
13. Any autoimmune or immunodeficiency disease/condition (inherited or iatrogenic) or chronic hematologic disorder (anemia, sickle cell, thalassemia).
14. Evidence of HIV, positive hepatitis B surface antigen or core antibody or hepatitis C antibodies by screening test.
15. Any chronic or degenerative neurological disease or history of significant neurological disorder.
16. Evidence of cardiovascular, pulmonary, renal, hepatobiliary disease or any other baseline condition (history and medication review) that has required active treatment or intervention.
17. Evidence of major depression disorder not well controlled in the past 2 years or history of suicidal ideation or attempt in the past 2 years.