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

NCT07390474 | Recruiting Phase 1 FDA Drug

• 1 other identifier: HVTN 322
• Study Type: interventional
• Target: 40
• Locations: 1 country
• Sites: 7

Brief Summary

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.

Conditions

HIV

Keywords

Healthy Participants; HIV Vaccine

Outcome Measures

Primary Outcomes (11)

• Local reactogenicity for a minimum of 14 days following receipt of any study vaccine

  Day 0 (vaccination) through 14 days post-vaccination; at days 15, 99, 183, and 295

• Systemic reactogenicity for a minimum of 14 days following receipt of any study vaccine

  Day 0 (vaccination) through 14 days post-vaccination; at days 15, 99, 183, and 295

• Serious adverse events (SAEs), medically attended AEs (MAAEs), AEs of special interest (AESIs), and AEs leading to withdrawal/discontinuation collected throughout study; additionally, all AEs collected for 30 days after receipt of any study vaccination

  From informed consent through end of study for SAEs, MAAEs, AESIs, and AEs leading to withdrawal/discontinuation; all AEs for 30 days after receipt of any study vaccination

• Response rate of V2 apex-specific IgG+ B cells as assessed by flow cytometry 2 weeks after second vaccination

  2 weeks after the second vaccination (Day 99)

• Frequency of V2 apex-specific IgG+ B cells as assessed by flow cytometry 2 weeks after second vaccination

  2 weeks after the second vaccination (Day 99)

• Response rate of differential serum Ab neutralization of precursor detection viruses and corresponding epitope knock-out mutant forms of the viruses, as measured by the TZM-bl assay at 2 weeks after second vaccination

  2 weeks after the second vaccination (Day 99)

• Magnitude of differential serum Ab neutralization of precursor detection viruses and corresponding epitope knock-out mutant forms of the viruses, as measured by the TZM-bl assay at 2 weeks after second vaccination

  2 weeks after the second vaccination (Day 99)

• Response rate of serum IgG binding antibodies to autologous HIV Env stabilized trimers, as assessed by binding antibody multiplex assay (BAMA) at 2 weeks after second vaccination

  2 weeks after the second vaccination (Day 99)

• Magnitude of serum IgG binding antibodies to autologous HIV Env stabilized trimers, as assessed by BAMA at 2 weeks after second vaccination

  2 weeks after the second vaccination (Day 99)

• Response rate of differential serum Ab neutralization of precursor detection viruses and corresponding epitope knock-out mutant forms of the viruses as measured by TZM-bl pseudovirus assay 2 weeks after the third and fourth vaccinations (Groups 1-3)

  2 weeks after the third vaccination and 2 weeks after the fourth vaccination (Days 183 and 295)

• Magnitude of differential serum Ab neutralization of precursor detection viruses and corresponding epitope knock-out mutant forms of the viruses as measured by TZM-bl pseudovirus assay 2 weeks after third and fourth vaccinations (Groups 1-3)

  2 weeks after the third vaccination and 2 weeks after the fourth vaccination (Days 183 and 295)

Secondary Outcomes (10)

• Response rate of serum IgG binding to HIV Env-stabilized trimers as assessed by BAMA at 2 weeks after third and fourth vaccinations (Groups 1-3)

  2 weeks after the third vaccination and 2 weeks after the fourth vaccination (Days 183 and 295)

• Magnitude of serum IgG binding to HIV Env-stabilized trimers as assessed by BAMA at 2 weeks after third and fourth vaccinations (Groups 1-3)

  2 weeks after the third vaccination and 2 weeks after the fourth vaccination (Days 183 and 295)

• V2 specificity of serum IgG binding to HIV Env-stabilized trimers as assessed by BAMA at 2 weeks after third and fourth vaccinations (Groups 1-3)

  2 weeks after the third vaccination and 2 weeks after the fourth vaccination (Days 183 and 295)

• Breadth of serum IgG binding to HIV Env-stabilized trimers as assessed by BAMA at 2 weeks after third and fourth vaccinations (Groups 1-3)

  2 weeks after the third vaccination and 2 weeks after the fourth vaccination (Days 183 and 295)

• Response rate of V2 apex-specific IgG+ B cells as assessed by flow cytometry at 2 weeks after third and fourth vaccinations (Groups 1-3)

  2 weeks after the third vaccination and 2 weeks after the fourth vaccination

Study Arms (4)

Group 1: 50 mcg

EXPERIMENTAL

DV201P-RNA (50 mcg) at weeks 0 and 12. Followed by: DV202B1-RNA (50 mcg) at weeks 24 and 40.

Biological: DV201P-RNA; Biological: DV202B1-RNA

Group 2: 100 mcg

EXPERIMENTAL

DV201P-RNA (100 mcg) at weeks 0 and 12. Followed by: DV202B1-RNA (100 mcg) at weeks 24 and 40.

Biological: DV201P-RNA; Biological: DV202B1-RNA

Group 3: 150 mcg

EXPERIMENTAL

DV201P-RNA (150 mcg) at weeks 0 and 12. Followed by: DV202B1-RNA (150 mcg) at weeks 24 and 40.

Biological: DV201P-RNA; Biological: DV202B1-RNA

Group 4: TBD*

EXPERIMENTAL

DV202B1-RNA (50 mcg or 100 mcg or 150 mcg; highest dose that is determined to be safe and well tolerated from Groups 1-3) at weeks 0 and 12.

Biological: DV202B1-RNA

Interventions

DV201P-RNA BIOLOGICAL

To be administered intramuscularly as a split dose.

Group 1: 50 mcg; Group 2: 100 mcg; Group 3: 150 mcg

DV202B1-RNA BIOLOGICAL

To be administered intramuscularly as a split dose.

Group 1: 50 mcg; Group 2: 100 mcg; Group 3: 150 mcg; Group 4: TBD*

Eligibility Criteria

• Age: 18 Years - 55 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Demonstrates an understanding of the study and is able and willing to complete the informed consent process.
• At least 18 years old at screening and up to 55 years old on day of enrollment.
• Available for clinic follow-up through the last clinic visit.
• Willing to undergo study procedures as outlined in the schedule of procedures (Appendix A).
• 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.
• In good general health according to the clinical judgment of the site investigator.
• 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.
• Agrees to discuss their potential for HIV acquisition and agrees to HIV prevention counseling.
• Hemoglobin (Hgb):
• g/dL for women
• g/dL for men
• Platelet count of 125,000 to 550,000/mm3.
• Alanine aminotransferase (ALT) \<2.5× the upper limit of institutional reference range.
• Serum creatinine ≤1.1× the upper limit of normal (ULN) based on the institutional normal range.
• Total measured serum calcium level \>8.5 mg/dL.

You may not qualify if:

• Women who are breastfeeding or pregnant.
• 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 PSRT approval.
• Previous or current recipient of an investigational HIV vaccine (previous placebo/control recipients are not excluded).
• 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.
• 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.
• Blood products or immunoglobulin within 16 weeks prior to enrollment; receipt of immunoglobulin within 16 weeks prior to enrollment requires PSRT approval.
• 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 \>28 days prior with a vaccination scab still present
• History of myocarditis and/or pericarditis.
• History of serious reaction (eg, hypersensitivity, anaphylaxis) 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).
• Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.
• Urticarial episode (idiopathic or known etiology) within the past year.
• History of chronic urticaria.

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (7)

The Ponce de Leon Center CRS

Atlanta, Georgia, 30308, United States

NOT YET RECRUITING

The Hope Clinic of the Emory Vaccine Research Center; Emory University

Decatur, Georgia, 30030, United States

RECRUITING

Beth Israel Deaconess Medical Center VCRS (BIDMC VCRS Site # 32077)

Boston, Massachusetts, 02215, United States

NOT YET RECRUITING

Columbia P&S CRS

New York, New York, 10032, United States

NOT YET RECRUITING

University of Rochester Vaccines to Prevent HIV Infection CRS

Rochester, New York, 14642, United States

NOT YET RECRUITING

Penn Prevention CRS

Philadelphia, Pennsylvania, 19104, United States

NOT YET RECRUITING

University of Pittsburgh CRS

Pittsburgh, Pennsylvania, 15213, United States

NOT YET RECRUITING

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SEQUENTIAL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 29, 2026
• First Posted: February 5, 2026
• Study Start: March 25, 2026
• Primary Completion (Estimated): December 14, 2027
• Study Completion (Estimated): December 14, 2027
• Last Updated: April 8, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (7)