Amsterdam UMC Clinical Trial With a Native-like HIV-1 Envelope Vaccine

Inclusion Criteria: 1. Men and women, aged between 18 and 50 years on the day of screening. 2. Willing to comply with the requirements of the protocol and available for follow-up for he planned duration of the study. 3. Willing and able to give written informed consent. 4. Willing to undergo HIV testing, risk reduction counselling and receive HIV test results, including the possibility of vaccine-induced seropositivity (VISP). 5. All female individuals engaging in sexual activity that could lead to pregnancy must commit to use an effective method of contraception for four months following Investigational Medicinal Product administration. 6. All female volunteers who are not heterosexually active at screening, must agree to utilise an effective method of contraception if they become heterosexually active. 7. All female volunteers must be willing to undergo urine pregnancy tests at designated time points. 8. All sexually active male volunteers, regardless of reproductive potential, must be willing to use an effective method of contraception (such as consistent condom use) from the day of first vaccination until at least four months after the last vaccination to avoid exposure of partners to Investigational Medicinal Product in ejaculate and to prevent conception with female partners. 9. Willing to abstain from donating blood, eggs or sperm from the day of first vaccination until at least 3 months after the end of their participation in the trial and, for those who test HIV-positive due to vaccine-induced antibodies, until the anti-HIV antibody titres become undetectable. 10. All volunteers must be registered with a general practitioner. Exclusion Criteria: 1. Confirmed HIV-1 or HIV-2 infection (HIV Ag/Ab plus HIV RNA testing). 2. Self-reported risk for HIV exposure or STIs prior to screening. 3. If female, pregnant or planning a pregnancy during the period of enrolment until four months after the last study vaccination; or lactating. 4. Any clinically relevant medical condition that is considered in the opinion of the investigator to make the volunteer unsuitable for participation in the study (under which underlying haematological disorders, auto-immune disease, immunodeficiency, gastrointestinal, hepatic and cardiopulmonary disorders). This also includes a history of malignancy in the past five years (prior to screening) or ongoing malignancy. (Note: A history of a completely excised malignancy that is considered cured is not an exclusion). 5. Infectious disease in the six months before screening: acute and chronic hepatitis B infection (HbsAg-positive), hepatitis C infection (anti-HCV and HCV RNA positive), treatment for chronic hepatitis C infection in the past year, or active syphilis (positive chemiluminescence immunoassay (LIAISON XL), confirmed by positive RPR). 6. History of hyposplenia (anatomical or functional). 7. Bleeding disorder that was diagnosed by a physician (e.g., factor deficiency, coagulopathy or platelet disorder that requires special precautions.) (Note: A volunteer who states that he or she has easy bruising or bleeding, but does not have a formal diagnosis and has intramuscular injections and blood draws without any adverse experience, is eligible). 8. Receipt of any vaccine within 60 days of vaccination with the Investigational Medicinal Product. 9. Receipt of blood products or blood-derived products within four months of screening. 10. Participation in another clinical trial of an Investigational Medicinal Product currently, within the previous three months or expected participation during this study. Concurrent participation in an observational study, not involving medicinal products and not requiring any blood or tissue sample collection is not an exclusion criterion. 11. Prior receipt of another investigational HIV vaccine or HIV monoclonal antibody (product). (Note: receipt of placebo in a previous HIV vaccine trial will not exclude a volunteer from participation if documentation is available.) 12. Known hypersensitivity to any component of the vaccine formulation used in this trial, or severe or multiple allergies to drugs or pharmaceutical agents. 13. Positive reaction in antinuclear antibody (ANA) screen and/or subsequent anti-dsDNA and/or anti-ENA assessment; or clinically significant immunoglobulin (IgA, IgG or IgM) values. 14. Use of any medications, including over-the-counter products, which, in the opinion of the investigators, would either interfere with the study or potentially cause harm to the volunteer. Use of corticosteroids, immunosuppressants, chemotherapeutics, anti-tuberculosis or other medications considered significant by the investigator within the previous six months. The following exceptions are permitted and will not exclude study participation: use of corticosteroid nasal spray for rhinitis, topical corticosteroids for an acute uncomplicated dermatitis (except for steroids applied to the non-dominant upper arm); or a short course (duration of ten days or less, or a single injection) of corticosteroid for a non-chronic condition (based on investigator clinical judgment) at least two weeks prior to enrolment in this study. 15. Unable to read and speak Dutch or English to a fluency level adequate for the full comprehension of procedures required in participation and consent. 16. Active, serious infections requiring (par)enteral antibiotic, antiviral or antifungal therapy within 30 days prior to enrolment. 17. Seizure disorder: A participant who has had a seizure in the last three years prior to screening is excluded. (Not excluded: a participant with a history of seizures who has neither required medications nor had a seizure for three years). 18. Grade ≥ 1 clinically significant routine safety laboratory parameters. 19. If, in the opinion of the Principal Investigator, it is not in the best interest of the volunteer to participate in the trial.