Clinical Trial to Evaluate the Safety and Immunogenicity of the V2 Apex-Directed Immunogens DV201P-RNA and DV202B1-RNA in Adult Participants Without HIV

This is a phase 1, multicenter, open-label, dose escalation, first-in-human (FIH) trial to evaluate the safety and immunogenicity of DV201P-RNA and DV202B1-RNA, immunogens designed to induce HIV-1 envelope (Env) V2 apex-specific broadly neutralizing antibodies (V2 apex bnAbs). Both vaccines consist of a modified mRNA encapsulated in lipid nanoparticles (LNP) that when translated in cells produces HIV-1 Env gp150 transmembrane trimers. The trial will enroll adult volunteers without HIV and in overall good health.

Inclusion Criteria: 1. Demonstrates an understanding of the study and is able and willing to complete the informed consent process. 2. At least 18 years old at screening and up to 55 years old on day of enrollment. 3. Available for clinic follow-up through the last clinic visit. 4. Willing to undergo study procedures as outlined in the schedule of procedures (Appendix A). 5. Agrees not to enroll in another study of an investigational agent during participation in the trial. If a potential participant is already enrolled in another clinical trial, approvals from the other trial sponsor and the HVTN 322 PSRT are required prior to enrollment into HVTN 322. 6. In good general health according to the clinical judgment of the site investigator. 7. Physical examination and laboratory results without clinically significant findings that would interfere with assessment of safety or reactogenicity in the clinical judgment of the site investigator. 8. Agrees to discuss their potential for HIV acquisition and agrees to HIV prevention counseling. 9. Hemoglobin (Hgb): * 11.0 g/dL for women * 13.0 g/dL for men 10. White blood cell (WBC) count of 2,500 to 12,000/mm3. WBC over 12,000/mm3 is not exclusionary if further evaluation shows general good health and if PSRT approval is granted. 11. Platelet count of 125,000 to 550,000/mm3. 12. Alanine aminotransferase (ALT) \8.5 mg/dL. 15. Systolic blood pressure of 90 to \250 mcg fluticasone or therapeutic equivalent per day), whether in single-therapy or dual-therapy inhalers (ie, with a long-acting beta agonist \[LABA\]) • Uses more than 1 medication for maintenance therapy daily. Inclusion of anyone on a stable dose of more than 1 medication for maintenance therapy daily for greater than 2 years requires PSRT approval. 24. A participant with a history of a PIMMC, either active or remote. Specific examples are listed in Appendix E (AESI index). Not exclusionary: (1) remote history of Bell's palsy (\>2 years ago) not associated with other neurologic symptoms; (2) mild psoriasis or other mild, uncomplicated, localized, or dermatologic condition that does not require ongoing systemic treatment; (3) remote history (\>10 years ago) of Kawasaki disease without sequelae; (4) celiac disease well controlled for 6 months with diet only. 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.