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

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) \<2.5× the upper limit of institutional reference range. 13. Serum creatinine ≤1.1× the upper limit of normal (ULN) based on the institutional normal range. 14. Total measured serum calcium level \>8.5 mg/dL (if the participant consented to have leukapheresis as a study procedure). 15. Systolic blood pressure of 90 to \<140 mm Hg and diastolic blood pressure of 50 to \<90 mm Hg at screening visit. The average blood pressure between the screening visit and the enrollment visit must be below 140 mm Hg systolic and 90 mmHg diastolic. A single measurement of ≥160 mm Hg systolic or ≥100 mm Hg diastolic during the current study evaluation is exclusionary. 16. Negative HIV test results by one of the following options: For US volunteers: * Negative US Food and Drug Administration (FDA)-approved enzyme immunoassay (EIA) or chemiluminescent microparticle immunoassay (CMIA) or * Negative results on 2 different brands of HIV rapid tests (one of which must be FDA-approved) 17. Negative for anti-hepatitis C virus (HCV) antibodies (Abs) or negative HCV nucleic acid test (NAT) if anti-HCV Abs are detected. 18. Negative for hepatitis B surface antigen (Ag). 19. For women of pregnancy potential: * Must agree to use effective means of contraception from at least 21 days prior to enrollment through 8 weeks after their last scheduled vaccination timepoint. * Must have a negative beta human chorionic gonadotropin (β-HCG) pregnancy test (urine or serum) on day of enrollment. Note: Women who have had a total hysterectomy, bilateral oophorectomy, or bilateral salpingectomy (verified by medical records), tubal ligation, or menopause (no menses for ≥1 year) are not required to undergo pregnancy testing. 20. Women of pregnancy potential must agree to not seek pregnancy through alternative methods, such as oocyte retrieval, artificial insemination, or in vitro fertilization from at least 21 days prior to enrollment through 8 weeks after their last scheduled vaccination timepoint. Exclusion Criteria: 1. Woman who is breastfeeding or pregnant. 2. Body mass index (BMI) ≥40. Enrollment of individuals with BMI ≥40 who are in good health, as assessed by the site investigator, may be considered by approval. 3. Diabetes mellitus (DM). Type 2 DM controlled with diet alone (and confirmed by HgbA1c ≤8% 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 on a case-by-case basis, provided that the HgbA1c is ≤8% within the last 6 months (sites 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 (RA) 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 site investigator, such as glucocorticoid use or prednisone dose of ≥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. 8. Receipt of any of the following within 4 weeks prior to enrollment: * Live replicating vaccine * Any mRNA-based vaccine with FDA licensure, FDA EUA, or WHO EUL * ACAM2000 vaccine more than 28 days prior with a vaccination scab still present 9. Receipt of any vaccine that is not covered in exclusion criterion #8 within 14 days prior to enrollment. Please note this includes replication-incompetent vaccines such as the Jynneos vaccine for the prevention of mpox (formerly known as monkeypox) disease. 10. History of myocarditis and/or pericarditis. 11. Initiation of Ag-based immunotherapy for allergies within the past year (stable immunotherapy is not exclusionary); inclusion of participants who initiated immunotherapy within the previous year requires approval. 12. 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 is required for enrollment. 13. History of serious reaction (eg, hypersensitivity, anaphylaxis) to any related vaccine, to any mRNA vaccine, including Comirnaty (Pfizer) and Spikevax (Moderna), or to any drug administered systemically as a polyethylene glycol containing LNP, including doxorubicin (Doxil, Caelyx, ThermoDox), cisplatin (Lipoplatin) and irinotecan (Onivyde). 14. Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema. 15. History of chronic urticaria, urticaria associated with previous vaccination, or any urticarial episode within the past year. 16. Bleeding disorder (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions) diagnosed by a clinician, or current therapeutic systemic anticoagulation for any clinical indication. Systemic anticoagulation includes oral anticoagulants (eg, warfarin, dabigatran, rivaroxaban, apixaban, edoxaban), injectable anticoagulants (eg, low-molecular-weight heparin, unfractionated heparin), or other similar prescription anticoagulants. 17. History of seizure(s) within the past 3 years. Also exclude if volunteer has used medications in order to prevent or treat seizure(s) at any time within the past 3 years. 18. Asplenia or functional asplenia. 19. Active duty and reserve US military personnel. 20. 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 recent suicide attempt, or cancer that, in the clinical judgment of the site investigator, has potential for recurrence (excluding basal cell carcinoma). 21. Asthma is excluded if the volunteer meets any of the following criteria: * Required either oral or parenteral corticosteroids for an exacerbation 2 or more times within the past year * 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 coexisting conditions unrelated to asthma) * Uses a short-acting rescue inhaler more than 2 days per week for acute asthma symptoms (ie, not for preventive treatment prior to athletic activity) * Uses medium- to high-dose inhaled corticosteroids (\>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 approval. 22. A volunteer with a history of a potential immune-mediated medical condition (PIMMC), either active or remote. Specific examples are listed in Appendix I (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. 23. History of allergy to local anesthetic (Novocaine, Lidocaine). 24. 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.