Phase 1 Study of CH505 HIV Vaccine Nanoparticles and mRNA Boosters in Healthy Adults

This Phase 1 study will evaluate the safety, tolerability, and immune responses of investigational CH505 HIV vaccine regimens in adults in overall good health without HIV. Participants will receive CH505 protein nanoparticle vaccines (DV901-NP) formulated with the investigational adjuvant ACU-026-001-1, followed by either CH505 protein nanoparticle (DV902-NP) or CH505 mRNA vaccine boosters. The study will assess the ability of these regimens to induce HIV-specific immune responses, including B-cell responses associated with the development of broadly neutralizing antibodies. An immunology cohort will also evaluate how the location of booster vaccination affects immune responses.

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 and willing to be contacted 12 months after the last study product administration of ACU-026-001-1. 4. Willing to undergo study procedures as outlined in the schedule of procedures. 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 are required prior to enrollment into HVTN 324. 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 Note: If receiving exogenous hormones for more than 6 consecutive months with dosing equivalent to parenteral testosterone ≥1000 mg every 12 weeks or estradiol valerate ≥2 mg/week, determine hemoglobin eligibility based on the exogenous hormone reported. 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 approval is granted. 11. Platelet count of 125,000 to 550,000/mm3. 12. Alanine aminotransferase (ALT) \8.5 mg/dL (if the participant consented to have leukapheresis as a study procedure). 15. Systolic blood pressure of 90 to \