Safety and Immunogenicity Study of Three mRNAs Encoding HIV Immunogens in Adult Participants Without HIV and in Overall Good Health in South Africa.

Exclusion Criteria

• •1. Volunteer is nursing or pregnant.
• •2. Body mass index (BMI) ≥40 kg/m2. Enrollment of individuals with BMI ≥40 kg/m2, whom the site investigator assesses are in good health, may be considered by the IAVI Medical Monitor.
• •3. Diabetes mellitus (DM). Type 2 DM controlled with diet alone (and confirmed by HgbA1c ≤7% within the last 6 months) or a history of isolated gestational diabetes are not exclusionary. Enrollment of individuals with Type 2 DM that is well controlled on hypoglycemic agent(s) may be considered by the IAVI Medical Monitor on a case-by-case basis, provided that the HgbA1c is ≤8% within the last 6 months (CRC staff may draw these at screening).
• •4. Previous or current recipient of an investigational HIV vaccine (previous placebo/control recipients are not excluded).
• •5. Receipt of non-HIV investigational vaccine(s) received within the last 1 year. Exceptions include vaccines that have subsequently undergone licensure or Emergency Use Authorization (EUA) by the FDA or World Health Organization (WHO) Emergency Use Listing (EUL), or if outside the US, by the national Regulatory Authority authorizing this clinical trial.
• •6. Congenital or acquired immunodeficiency, including systemic medication use likely to impair immune response to vaccine in the opinion of the Investigator, such as glucocorticoid use, prednisone ≥10 mg/day within 3 months prior to enrollment.
• •7. Blood products or immunoglobulin within 16 weeks prior to enrollment; receipt of immunoglobulin within 16 weeks prior to enrollment requires approval by the IAVI Medical Monitor.
• •8. Previous receipt of VRC01 or VRC07-523LS monoclonal antibody (mAb).
• •9. Receipt of any vaccine within 4 weeks prior to enrollment or planned receipt within 4 weeks of investigational vaccine administration.
• •10. History of myocarditis and/or pericarditis.
• •11. A past history of immune-mediated disease, including but not limited to thyroid disease, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, celiac disease, seronegative inflammatory arthritis, systemic sclerosis, and Type 1 diabetes (for other examples, see Appendix 8).
• •12. History of or active severe skin conditions, including, but not limited to, cutaneous mastocytosis, psoriasis, atopic dermatitis, lichen planus, hidradenitis suppurativa, bullous pemphigoid, and urticarial vasculitis.
• •13. Systemic or local conditions with urticaria as a manifestation, including urticarial vasculitis, maculo-papular cutaneous mastocytosis (formerly urticaria pigmentosa), mast cell activation syndrome, Gleich's syndrome (episodic angioedema with eosinophilia), Well's syndrome (granulomatous dermatitis with eosinophilia/eosinophilic cellulitis), bullous pemphigoid, or adult-onset Still's disease.
• •14. Receipt of antigen-based immunotherapy.
• •15. 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 of more than 7 days (or unknown half-life) within the past year, approval by the IAVI Medical Monitor is required for enrollment.
• •16. History of serious reaction (eg, hypersensitivity, anaphylaxis) to any vaccine or component of the study-vaccine regimen.
• •17. History of hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.
• •18. History of urticaria and/or dermatographism.
• •19. History of atopy (diagnosed or confirmed by a clinician).
• •20. Bleeding disorder diagnosed by a clinician that would make study procedures a contraindication.
• •21. History of seizure(s) within the past 3 years, or if volunteer has used medications to prevent or treat seizure(s) at any time within the past 3 years.
• •22. Asplenia or functional asplenia.
• •23. Any other chronic or clinically significant condition that, in the clinical judgment of the Investigator, would jeopardize the safety or rights of the study participant, including but not limited to: clinically significant forms of substance use or alcohol use disorder(s), serious psychiatric disorders, any suicide attempt within the past 1 year (if between 1 and 2 years, consult the IAVI Medical Monitor for approval), or cancer that, in the clinical judgment of the Investigator, has potential for recurrence (excluding basal cell carcinoma).
• •24. Asthma (diagnosed or confirmed by a clinician).
• •25. History of allergy to local anesthetic (Novocaine, Lidocaine).
• •26. Investigator concern for difficulty with venous access based on clinical history and physical examination. For example, persons with a history of intravenous drug use or substantial difficulty with previous blood draws.
• •27. Has donated ≥450 mL of blood products within 28 days prior to the Screening Visit or plans to donate blood products within 28 days post study injection.
• •28. Is working or has worked as study personnel or is an immediate family member or house member of study personnel, study site staff, or Sponsor personnel.