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

NCT07757802 | Not Yet Recruiting Phase 1 FDA Drug

• 1 other identifier: HVTN 324
• Study Type: interventional
• Target: 54
• Locations: 1 country
• Sites: 8

Brief Summary

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.

Conditions

HIV

Keywords

Healthy Individuals; HIV; Healthy participants

Outcome Measures

Primary Outcomes (10)

• Incidence of solicited local reactogenicity

  Incidence and severity of solicited local reactogenicity following study vaccination.

  Through 14 days after each study vaccination

• Incidence of solicited systemic reactogenicity

  Incidence and severity of solicited systemic reactogenicity following study vaccination.

  Through 14 days after each study vaccination

• Incidence of adverse events

  Incidence of adverse events following study vaccination.

  Through 30 days after each study vaccination

• Incidence of serious adverse events

  Incidence of serious adverse events (SAEs).

  Through 52 weeks after the last study vaccination

• Incidence of medically attended adverse events

  Incidence of medically attended adverse events (MAAEs).

  Through 52 weeks after the last study vaccination

• Incidence of adverse events of special interest

  Incidence of adverse events of special interest (AESIs)

  Through 52 weeks after the last study vaccination

• Incidence of adverse events leading to permanent discontinuation of study product or participant withdrawal

  Incidence of adverse events resulting in permanent discontinuation of study product administration or participant withdrawal.

  Through 52 weeks after the last study vaccination

• Frequency of CH505M5.G458Y/GnT1neg-specific IgG+ memory B cells

  Frequency of CH505M5.G458Y/GnT1neg-specific IgG+ memory B cells measured by flow cytometry.

  Baseline and 2 weeks after the second and fourth vaccinations (Groups 1 and 2); baseline and 2 weeks after the second, fourth, and fifth vaccinations (Group 3)

• Response rate of precursor-specific serum neutralizing antibodies

  Response rate of differential serum neutralizing antibody activity against precursor detection viruses and corresponding epitope knockout viruses measured by TZM-bl assay.

  Baseline and 2 weeks after the second and fourth vaccinations (Groups 1 and 2); baseline and 2 weeks after the second, fourth, and fifth vaccinations (Group 3)

• Magnitude of precursor-specific serum neutralizing antibodies

  Magnitude of differential serum neutralizing antibody activity against precursor detection viruses and corresponding epitope knockout viruses measured by TZM-bl assay.

  Baseline and 2 weeks after the second and fourth vaccinations (Groups 1 and 2); baseline and 2 weeks after the second, fourth, and fifth vaccinations (Group 3)

Secondary Outcomes (35)

• Response rate of HIV Env-specific serum IgG binding antibodies

  Baseline and 2 weeks after the second and fourth vaccinations (Groups 1 and 2); baseline and 2 weeks after the second, fourth, and fifth vaccinations (Group 3)

• Magnitude of HIV Env-specific serum IgG binding antibodies as measured by binding Ab multiplex assay (BAMA)

  Baseline and 2 weeks after the second and fourth vaccinations (Groups 1 and 2); baseline and 2 weeks after the second, fourth, and fifth vaccinations (Group 3)

• Epitope specificity of HIV Env-specific serum IgG binding antibodies

  Baseline and 2 weeks after the second and fourth vaccinations (Groups 1 and 2); baseline and 2 weeks after the second, fourth, and fifth vaccinations (Group 3)

• Response rate of ferritin-specific serum IgG binding antibodies

  Baseline and 2 weeks after the second and fourth vaccinations (Groups 1 and 2); baseline and 2 weeks after the second, fourth, and fifth vaccinations (Group 3)

• Magnitude of ferritin-specific serum IgG binding antibodies as measured by binding Ab multiplex assay (BAMA)

  Baseline and 2 weeks after the second and fourth vaccinations (Groups 1 and 2); baseline and 2 weeks after the second, fourth, and fifth vaccinations (Group 3)

Study Arms (5)

Group 1: DV901-NP Low-Dose Prime/DV902-NP Low-Dose Boost

EXPERIMENTAL

Participants receive DV901-NP (100 mcg) adjuvanted with ACU-026-001-1 (2 mg) by bilateral intramuscular (IM) injection at Weeks 0 and 8, followed by DV902-NP (100 mcg) adjuvanted with ACU-026-001-1 (2 mg) at Weeks 16 and 24.

Biological: DV901-NP; Biological: DV902-NP; Biological: ACU-026-001-1

Group 2: DV901-NP High-Dose Prime/DV902-NP High-Dose Boost

EXPERIMENTAL

Participants receive DV901-NP (300 mcg) adjuvanted with ACU-026-001-1 (2 mg) by bilateral IM injection at Weeks 0 and 8, followed by DV902-NP (300 mcg) adjuvanted with ACU-026-001-1 (2 mg) at Weeks 16 and 24.

Biological: DV901-NP; Biological: DV902-NP; Biological: ACU-026-001-1

Group 3: DV901-NP Prime/CH505 mRNA Boosts

EXPERIMENTAL

Participants receive DV901-NP (300 mcg) adjuvanted with ACU-026-001-1 (2 mg) by bilateral IM injection at Weeks 0 and 8, followed by CH505 TF mRNA-gp160 (100 mcg) at Weeks 16 and 24 and CH505 w24 mRNA-gp160 (100 mcg) at Week 32.

Biological: DV901-NP; Biological: CH505 TF mRNA-gp160; Biological: CH505 w24 mRNA-gp160; Biological: ACU-026-001-1

Group 4: Ipsilateral Prime/Contralateral Boost Immunology Cohort

EXPERIMENTAL

Participants receive DV901-NP (150 mcg) adjuvanted with ACU-026-001-1 (1 mg) by IM injection at Weeks 0, 4, and 28. The Week 0 and Week 4 vaccinations are administered in the same deltoid (ipsilateral), and the Week 28 vaccination is administered in the opposite deltoid (contralateral).

Biological: DV901-NP; Biological: ACU-026-001-1

Group 5: Ipsilateral Prime/Ipsilateral Boost Immunology Cohort

EXPERIMENTAL

Participants receive DV901-NP (150 mcg) adjuvanted with ACU-026-001-1 (1 mg) by IM injection at Weeks 0, 4, and 28, with all vaccinations administered in the same deltoid (ipsilateral).

Biological: DV901-NP; Biological: ACU-026-001-1

Interventions

DV901-NP BIOLOGICAL

CH505 HIV-1 envelope protein nanoparticle vaccine administered intramuscularly at doses of 100 mcg, 150 mcg, or 300 mcg, depending on study group. Administered with ACU-026-001-1 adjuvant.

Group 1: DV901-NP Low-Dose Prime/DV902-NP Low-Dose Boost; Group 2: DV901-NP High-Dose Prime/DV902-NP High-Dose Boost; Group 3: DV901-NP Prime/CH505 mRNA Boosts; Group 4: Ipsilateral Prime/Contralateral Boost Immunology Cohort; Group 5: Ipsilateral Prime/Ipsilateral Boost Immunology Cohort

DV902-NP BIOLOGICAL

CH505 HIV-1 envelope protein nanoparticle booster vaccine administered intramuscularly at doses of 100 mcg or 300 mcg with ACU-026-001-1 adjuvant.

Group 1: DV901-NP Low-Dose Prime/DV902-NP Low-Dose Boost; Group 2: DV901-NP High-Dose Prime/DV902-NP High-Dose Boost

CH505 TF mRNA-gp160 BIOLOGICAL

CH505 HIV-1 envelope mRNA vaccine administered intramuscularly as a 100 mcg booster at Weeks 16 and 24.

Group 3: DV901-NP Prime/CH505 mRNA Boosts

CH505 w24 mRNA-gp160 BIOLOGICAL

CH505 HIV-1 envelope mRNA vaccine administered intramuscularly as a 100 mcg booster at Week 32.

Group 3: DV901-NP Prime/CH505 mRNA Boosts

ACU-026-001-1 BIOLOGICAL

Investigational lipid nanoparticle adjuvant administered in combination with DV901-NP or DV902-NP. Dose is 2 mg for Groups 1-3 and 1 mg for Groups 4-5.

Group 1: DV901-NP Low-Dose Prime/DV902-NP Low-Dose Boost; Group 2: DV901-NP High-Dose Prime/DV902-NP High-Dose Boost; Group 3: DV901-NP Prime/CH505 mRNA Boosts; Group 4: Ipsilateral Prime/Contralateral Boost Immunology Cohort; Group 5: Ipsilateral Prime/Ipsilateral Boost Immunology Cohort

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 and willing to be contacted 12 months after the last study product administration of ACU-026-001-1.
• Willing to undergo study procedures as outlined in the schedule of procedures.
• 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.
• 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):
• ≥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.
• 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 (if the participant consented to have leukapheresis as a study procedure).

You may not qualify if:

• Woman who is 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 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 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 more than 28 days prior with a vaccination scab still present
• History of myocarditis and/or pericarditis.
• 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.
• 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).
• Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.
• History of chronic urticaria, urticaria associated with previous vaccination, or any urticarial episode within the past year.

Sponsors & Collaborators

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

Study Sites (8)

Bridge HIV CRS Site# 30305

San Francisco, California, 94102, United States

Location

The Ponce de Leon Center CRS Site# 5802

Atlanta, Georgia, 30308, United States

Location

Brigham and Women's Hospital Vaccine CRS (BWH VCRS) Site# 30007

Boston, Massachusetts, 02115, United States

Location

BIDMC VCRS Site# 32077

Boston, Massachusetts, 02215, United States

Location

University of Rochester Vaccines to Prevent HIV Infection CRS Site# 31467

Rochester, New York, 14642, United States

Location

Penn Prevention CRS Site# 30310

Philadelphia, Pennsylvania, 19104, United States

Location

University of Pittsburgh CRS Site# 1001

Pittsburgh, Pennsylvania, 15213, United States

Location

Vanderbilt Vaccine (VV) CRS Site# 30352

Nashville, Tennessee, 37232, United States

Location

Study Design

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

Study Record Dates

• First Submitted: July 27, 2026
• First Posted: August 11, 2026
• Study Start (Estimated): September 10, 2026
• Primary Completion (Estimated): June 7, 2028
• Study Completion (Estimated): October 7, 2028
• Last Updated: August 11, 2026

Record last verified: 2026-08

Locations

US (8)