A Randomized, Double-blinded, Placebo-controlled, Dose-escalation Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of Recombinant HIV Envelope Protein BG505 SOSIP.664 gp140 Vaccine, Adjuvanted, in Healthy, HIV-1 Uninfected Adults

1. Confirmed HIV-1 or HIV-2 infection

2. Any clinically relevant abnormality on history or examination including history of immunodeficiency or autoimmune disease; use of corticosteroids (the use of topical, nasal, or inhaled steroids is permitted), immunosuppressive, anticancer, anti-tuberculosis or other medications considered significant by the investigator within the previous 6 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; or a short course (duration of 10 days or less, or a single injection) of corticosteroid for a non-chronic condition (based on investigator clinical judgment) at least 2 weeks prior to enrolment in this study

3. Any clinically significant acute or chronic medical condition that is considered progressive or in the opinion of the investigator makes the volunteer unsuitable for participation in the study

4. Reported risky behavior for HIV infection within 12 months prior to vaccination

5. If female, pregnant or planning a pregnancy during the period of enrolment until 4 months after the last study vaccination; or lactating

6. 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 IM injections and blood draws without any adverse experience, is eligible)

7. Infectious disease: chronic hepatitis B infection (HbsAg-positive), current hepatitis C infection (for US sites: HCV Ab positive and HCV RNA positive, for African site: HCV Ab positive only) treatment for chronic hepatitis C infection in the past year, or active syphilis (positive RPR confirmed by TPHA); active tuberculosis (for African site only)

8. History of splenectomy

9. Any of the following abnormal laboratory parameters listed below:

Hematology

* Absolute Neutrophil Count (ANC) - all volunteers: ≤1,000/mm3

* Absolute Lymphocyte Count (ALC) - all volunteers: ≤650/mm3

* Hemoglobin - African volunteers: \<9.5 g/dl in females; \<11.0 g/dl in males

* Hemoglobin - US volunteers: \<10.5 g/dl in females; \<11.0 g/dl in males

* Platelets - African volunteers: \<100,000 cells/mm3

* Platelets - US volunteers: \<125,000 cells/mm3

Chemistry

* Creatinine \>1.1 x upper limit of normal (ULN)

* ALT \>1.25 x ULN

* AST \>1.25 x ULN

Urinalysis

Clinically significant abnormal dipstick confirmed by microscopy:

* Protein = 1+ or more

* Blood = 2+ or more (not due to menses)

10. Receipt of live attenuated vaccine within the previous 30 days or planned receipt within 30 days after vaccination with Investigational Product; or receipt of other vaccine within the previous 14 days or planned receipt within 14 days after vaccination with Investigational Product. (Exception is live attenuated influenza vaccine within 14 days)

11. Receipt of blood transfusion or blood-derived products within the previous 3 months

12. Participation in another clinical trial of an Investigational Product currently, within the previous 3 months or expected participation during this study; Concurrent participation in an observational study not requiring any blood or tissue sample collection is not an exclusion

13. Prior receipt of another investigational HIV vaccine candidate or HIV monoclonal antibody (Note: receipt of placebo in a previous HIV vaccine trial will not exclude a volunteer from participation if documentation is available and the Medical Monitor gives approval)

14. History of severe local or systemic reactogenicity to vaccines (e.g., anaphylaxis, respiratory difficulties, angioedema, injection site necrosis or ulceration)

15. Psychiatric condition that compromises safety of the volunteer and precludes compliance with the protocol. Specifically excluded are persons with psychoses within the past 3 years prior to screening, ongoing risk for suicide, or history of suicide attempt or gesture within the past 3 years

16. Seizure disorder: A participant who has had a seizure in the last 3 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 3 years)

17. A history of malignancy in the past 5 years (prior to screening) or ongoing malignancy (A history of a completely excised malignancy that is considered cured is not an exclusion)

18. Active, serious infections requiring parenteral antibiotic, antiviral or antifungal therapy within 30 days prior to enrolment

19. Body mass index (BMI) ≥35

20. Body weight \<110 pounds (55 kg); for US sites only

21. If, in the opinion of the Principal Investigator, it is not in the best interest of the volunteer to participate in the trial

What this study is about