A Clinical Trial to Evaluate the Safety and Immunogenicity of BG505 MD39.3, BG505 MD39.3 gp151, and BG505 MD39.3 gp151 CD4KO HIV Trimer mRNA Vaccines in Healthy, HIV-uninfected Adult Participants

1. Volunteer who is breast-feeding or pregnant.

2. Hypertension that is not well controlled. If a person has been found to have elevated blood pressure or hypertension during screening or previously, exclude for blood pressure that is not well controlled. Well-controlled blood pressure is defined in this protocol as consistently \< 140 mm Hg systolic and \< 90 mm Hg diastolic, with or without medication, with only isolated, brief instances of higher readings, which must be ≤ 150 mm Hg systolic and ≤ 100 mm Hg diastolic. For these volunteers, blood pressure must be \< 140 mm Hg systolic and \< 90 mm Hg diastolic at enrollment. If a person has NOT been found to have elevated blood pressure or hypertension during screening or previously, exclude for systolic blood pressure ≥ 150 mm Hg at enrollment or diastolic blood pressure ≥ 100 mm Hg at enrollment.

3. Diabetes mellitus type 1 or type 2. (Not exclusionary: type 2 cases controlled with diet alone or a history of isolated gestational diabetes).

4. Previous or current recipient of an investigational HIV vaccine (previous placebo recipients are not excluded).

5. Acutely ill or febrile (temperature ≥ 38.0°C/100.4°F) on the day of the first vaccination. Participants meeting this criterion may be rescheduled within the enrollment window period. Afebrile participants with minor illnesses can be enrolled at the discretion of the Investigator.

6. Immunosuppressive medications received within 168 days before first vaccination (Not exclusionary: \[1\] corticosteroid nasal spray; \[2\] inhaled corticosteroids; \[3\] topical corticosteroids for mild, uncomplicated dermatologic condition; or \[4\] a single course of oral/parenteral prednisone or equivalent at doses \< 60 mg/day and length of therapy \< 11 days with completion at least 30 days prior to enrollment).

7. Blood products or immunoglobulin within 16 weeks prior to enrollment; receipt of immunoglobulin within 16 weeks prior to enrollment requires PSRT approval.

8. Receipt of any of the following:

* Within 4 weeks prior to enrollment:

* Any licensed live, attenuated vaccine

* Any emergency use authorized (EUA) or licensed mRNA-based SARS-CoV-2 vaccine

* Within 2 weeks prior to enrollment:

* Any licensed killed/subunit/inactivated vaccine

* Any EUA or licensed adenoviral-vectored or protein SARS-CoV-2 vaccines Receipt of any SARS-CoV-2 vaccination series should be completed 4 weeks prior to enrollment when possible; however, exceptions may be made by approval of the HVTN 302 PSRT.

9. Initiation of antigen-based immunotherapy for allergies within the previous year (stable immunotherapy is not exclusionary); inclusion of participants who initiated immunotherapy within the previous year requires PSRT approval.

10. Receipt of investigational research agents with a half-life of 7 or fewer days within 4 weeks prior to enrollment. If a potential participant has received investigational agents with a half-life greater than 7 days (or unknown half-life) within the past year, PSRT approval is required for enrollment.

11. History of serious reaction (eg, hypersensitivity, anaphylaxis) to any vaccine or any component of the study vaccine.

12. History of myocarditis and/or pericarditis.

13. Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.

14. Idiopathic urticaria within the past year.

15. Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions).

16. Seizure disorder; febrile seizures as a child or seizures secondary to alcohol withdrawal more than 5 years ago are not exclusionary.

17. Asplenia or functional asplenia.

18. Active duty and reserve US military personnel.

19. Any other chronic or clinically significant condition that in the clinical judgement of the investigator would jeopardize the safety or rights of the study participant, including, but not limited to: clinically significant forms of drug or alcohol abuse, serious psychiatric disorders, or cancer that, in the clinical judgement of the site investigator, has a potential for recurrence (excluding basal cell carcinoma).

20. Asthma is excluded if the participant has ANY of the following:

* Required either oral or parenteral corticosteroids for an exacerbation two or more times within the past year; OR

* Needed emergency care, urgent care, hospitalization, or intubation for an acute asthma exacerbation within the past year (eg, would NOT exclude individuals with asthma who meet all other criteria but sought urgent/emergent care solely for asthma medication refills or co-existing conditions unrelated to asthma); OR

* Uses a short-acting rescue inhaler more than 2 days/week for acute asthma symptoms (ie, not for preventive treatment prior to athletic activity); OR

* Uses medium-to-high-dose inhaled corticosteroids (greater than 250 mcg fluticasone or therapeutic equivalent per day), whether in single-therapy or dual-therapy inhalers (ie, with a long-acting beta agonist \[LABA\]); OR

* Uses more than one medication for maintenance therapy daily. Inclusion of anyone on a stable dose of more than one medication for maintenance therapy daily for greater than two years requires PSRT approval.

21. A participant with a history of an immune-mediated disease, either active or remote. Not exclusionary: 1) remote history of Bell's palsy (\>2 years ago) not associated with other neurologic symptoms, 2) mild psoriasis that does not require ongoing systemic treatment.

22. Immunodeficiency

What this study is about