Study to evaluate the safety and immunogenicity of an HIV-1 vaccine regimen of adjuvanted UVAX-1107 followed by adjuvanted UVAX-1107 or adjuvanted UVAX-1197 in healthy subjects aged 25-55 years.

INTERVENTION: 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 adjuvate CONDITION: Acquired immune deficiency syndrome (AIDS / HIV); ; Acquired immune deficiency syndrome (AIDS / HIV) Infection ‐ Acquired immune deficiency syndrome (AIDS / HIV) PRIMARY OUTCOME: To assess local and systemic reactogenicity following vaccination (Day 1 to Day 8, inclusive) following each vaccination.[Reactogenicity (local and systemic) will be recorded by the subject using a daily diary after vaccination and for 6 consecutive days thereafter. Days 1 through Day 7 after each vaccination.] To determine if antibody responses are induced at 2 weeks after each vaccination using anti‐HIV‐1 protein IgG.[Serum samples will be collected at specified timepoints for HIV‐1‐specific IgG titers Pre‐vaccination timepoints (Day 1, Day 57, Day 141 and Day 225) and 2 weeks after each vaccination (Day 15, Day 71, Day 155 and Day 239) and Day 337 post enrolment/End of study (EOS).] SECONDARY OUTCOME: To assess changes in chemistry, haematology, and bleeding indices from pre‐vaccination to 7 days following each vaccination.[Lab values for chemistry, haematology and bleeding indices that are obtained during screening will be applied to the priming period calculations and lab values obtained at pre‐vaccination will be applied to the boosting period calculations. Samples of serum or plasma will be collected and results will be applied against the laboratory normal ranges as well as the grading scale for the study. ; Screening visit, Day 8, pre‐dose Day 57, Day 64, pre‐dose Day 141, day 148, pre‐dose Day 225, Day 239 and Day 337 post‐enrolment/End of Study (EOS)] To assess changes in vital signs following each vaccination.[Vital signs assessments will include oral temperature (degrees C) using an oral thermometer, respiratory rate (breaths per minute) using manual assessment of breaths, systolic and diastolic blood pressure (mmHg) and heart rate (bpm) using a digital blood pressure machine. All study visits (Screening, pre‐ and post‐dose Day 1, Day 8, Day 15, Day 29, pre‐ and post‐dose Day 57, Day 64, Day 71, Day 85, pre‐ and post‐dose Day 141, Day 148, Day 156, Day 169, pre‐ and post‐dose Day 225, Day 232, Day 253 and Day 337.] To assess serious adverse events (SAEs) or adverse events of special interest (AESI) attributed to vaccination.[As the proposed trial (UVAX‐HIV‐101) will be the first study of UVAX‐1197 and ‐1107 in humans, there is currently no data regarding AEs associated with either UVAX‐1197 or ‐1107 in humans. UVAX‐1197 and ‐1107 have been administered in animals without significant adverse reactions being observed. Based on preclinical experience and AEs generally observed in other intramuscular administered vaccines using a similar development platform, the vaccinations are expected to result in mild to moderate local reactions and/or systemic reactions. These AEs will be assessed via clinical examination at the reference timepoints and via the use of a subject diary for the 7 days following each vaccination. At all visits, Day 1, Day 8, Day 15, Day 29, Day 57, Day 64, Day 71, Day 85, Day 141, Day 148, Day 156, Day 169, Day 225, Day 232, Day 239, Day 253 and Day 337 post enrolment/End of Study (EOS).] To describe occurrence of Medically Attended Adverse Events (MAAEs).[MAAEs (eg. any AEs that are evaluated by a healthcare professional either at the site or within the community) will be reported from Day 1 through 28 days after the last vaccination was received. They will be assessed using study‐specific questionnaire, clinical examination and data‐linkage to medical records. As the proposed trial (UVAX‐HIV‐101) will be the first study of UVAX‐1197 and ‐1107 in humans, there is currently no data regarding AEs associated with either UVAX‐1197 or ‐1107 in humans. UVAX‐1197 and ‐1107 have been administered in animals without significant adverse reactions being observed. Based on preclinical experience and AEs generally observed in other IM‐administered vaccines using a similar development platform, the vaccinations are expected to result in mild to moderate local reactions and/or systemic reactions. These AEs will be assessed via clinical examination at the reference timepoints and via the use of a subject diary for the 7 days following each vaccination. On pre‐ and post‐dose Day 1, Day 8, Day 15, Day 29, pre‐ and post‐dose Day 57, Day 64, Day 71, Day 85, pre‐ and post‐dose Day 141, Day 148, Day 156, Day 169, pre‐ and post‐dose Day 225, Day 232, and Day 253] To describe occurrence of treatment emergent adverse events (TEAEs) [TEAEs (eg. any AEs that occur after the study product has been administered) will be reported throughout the study period until Day 253 (28 days following the last dose) .They will be assessed, using study‐specific questionnaire, clinical examination and data‐linkage to medical records. As the proposed trial (UVAX‐HIV‐101) will be the first study of UVAX‐1197 and ‐1107 in humans, there is currently no data regarding AEs associated with either UVAX‐1197 or ‐1107 in humans. UVAX‐1197 and ‐1107 have been administered in animals without significant adverse reactions being observed. Based on preclinical experience and AEs generally observed in other IM‐administered vaccines using a similar development platform, the vaccinations are expected to result in mild to moderate local reactions and/or systemic reactions. These AEs will be assessed via clinical examination at the reference timepoints and via the use of a subject diary for the 7 days following each vaccination. ; Endpoint will evaluate TEAEs reported until Day 29 following each vaccination (Day 1, Day 8, Day 15, Day 29, post‐dose Day 57, Day 64, Day 71, Day 85, post‐dose Day 141, Day 148, Day 156, Day 169, post‐dose Day 225, Day 232, and Day 253). ; ] To determine difference in autologous neutralizing antibody response across dose groups[Serum will be collected for assessment of occurrence and level of HIV‐1‐specific neutralization titers against select homologous and heterologous Tier 1 and Tier 2 panels. ; These will be assessed as a composite secondary endpoint. Pre‐vaccinations timepoints (Day 1, Day 57, Day 141 and Day 225), and 2 weeks after each vaccination (Day 15, Day 71, Day 155, and Day 239) and at the EOS (Day 337 post‐enrolment).] To determine difference in autologous neutralizing antibody response across dose groups[Serum will be collected for assessment of occurrence and level of HIV‐1‐specific neutralization titers against vaccine Pre‐vaccinations timepoints (Day 1, Day 57, Day 141 and Day 225), and 2 weeks after each vaccination (Day 15, Day 71, Day 155, and Day 239) and at the EOS (Day 337 post‐enrolment).] 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 highlyle 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: a. Agree not to donate sperm from the time of signing consent until at least 90 days after the last dose of study drug. b. If engaging in sexual intercourse with a female partner who could become pregnant, must agree to use adequate contraception until at least