HIV-1-infectionPhase 1NCT05471076

Trial to Evaluate the Safety and Immunogenicity of Priming Regimens of 426c.Mod.Core-C4b and Optional Boost Regimen With HIV Trimer BG505 SOSIP.GT1.1 gp140, Both Adjuvanted With 3M-052-AF + Alum in Healthy, Adult Participants Without HIV

A Phase 1 study testing 426c.Mod.Core-C4b 30 mcg, 426c.Mod.Core-C4b 100 mcg and 426c.Mod.Core-C4b 300 mcg in people with HIV-1-infection, run by National Institute of Allergy and Infectious Diseases (NIAID) at 6 sites in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

Search all trials

Trial summary

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: HIV-1-infection
What is being tested?: 426c.Mod.Core-C4b 30 mcg, 426c.Mod.Core-C4b 100 mcg and 426c.Mod.Core-C4b 300 mcg
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 52 participants
Where: 6 sitesUnited States
Study dates: 22 Aug 2022to 13 Apr 2026
Phase: Phase 1
Are there results?: None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages 18 to 55 years
All sexes
Healthy volunteers accepted
Adult

Who may be able to join

Able and willing to complete the informed consent process, including an Assessment of Understanding: volunteer demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of any questionnaire items answered incorrectly.
18-55 years old, inclusive, on day of enrollment.
Available for clinic follow-up through the last clinic visit, willing to under go lymph node fine needle aspiration, and willing to be contacted 12 months after the last vaccine administration.
Agrees not to enroll in another study of an investigational agent during participation in the trial.
In good general health according to the clinical judgement 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 judgement of the site investigator.

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Assessed as low risk for HIV acquisition per low risk guidelines, agrees to discuss HIV infection risks, agrees to risk reduction counseling, and agrees to avoid behavior associated with high risk of HIV exposure through the final study visit. Low risk may include persons stably taking pre-exposure prophylaxis (PrEP) as prescribed for 6 months or longer.
Hemoglobin:
≥ 11.0 g/dL for volunteers who were assigned female sex at birth
≥ 13.0 g/dL for volunteers who were assigned male sex at birth and transgender males who have been on hormone therapy for more than 6 consecutive months
≥ 12.0 g/dL for transgender females who have been on hormone therapy for more than 6 consecutive months
For transgender participants who have been on hormone therapy for less than 6 consecutive months, determine hemoglobin eligibility based on the sex assigned at birth.
White blood cell (WBC) count > 3,500/mm3.
Platelets ≥125,000/mm3.
Alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN) based on the institutional normal range.
Serum creatinine ≤1.1 x ULN based on the institutional normal range.
Blood pressure in the range of 90 to ≤ 150 mmHg systolic and 50 to ≤ 95 mmHg diastolic.
Negative results for HIV infection by an FDA-approved enzyme immunoassay(EIA) or chemiluminescent microparticle immunoassay (CMIA).
Negative for anti-Hepatitis C antibodies (anti-HCV) or negative HCV nucleic acid test (NAT) if anti-HCV antibodies are detected.
Negative for Hepatitis B surface antigen.
For a volunteer capable of becoming pregnant:
Volunteers who were assigned female sex at birth and are of reproductive potential must agree to use effective means of birth control from at least 21 days prior to enrollment through 8 weeks after their last vaccination timepoint.
Has negative β-HCG (human chorionic gonadotropin) pregnancy test (urine or serum) on day of enrollment.

Who cannot join

Volunteer who is breast-feeding or pregnant.
Morbid Obesity. Enrollment of individuals with body mass index (BMI) ≥40, who the site investigator assesses are in good health, may be considered by PSRT on a case-by-case basis.
Diabetes mellitus (DM). Type 2 DM, controlled with diet alone, 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, provided the HgbA1c is ≤8% within the last 6 months (sites may draw these at screening).
International normalized ratio (INR) >1.2.
Previous or current recipient of an investigational HIV vaccine (previous placebo recipients are not excluded).
Receipt of non-HIV experimental vaccine(s) received within the last 1 year. Exceptions may be made by the PSRT for vaccines that have subsequently undergone licensure or Emergency Use Authorization by the FDA or, if outside the United States, by the national regulatory authority or World Health Organization. For volunteers who have received control/placebo in an experimental vaccine trial, the PSRT will determine eligibility on a case-by-case basis.

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Systemic glucocorticoid use equal to or greater than prednisone 10 mg/day within 3 months prior to enrollment, other systemic medication use likely to impair immune response to vaccine in the opinion of the site investigator, or congenital or acquired immunodeficiency.
Blood products or immunoglobulin within 16 weeks prior to enrollment; receipt of immunoglobulin within 16 weeks prior to enrollment requires PSRT approval.
Previous receipt of VRC01 monoclonal antibody.
Receipt of any live replicating vaccine within 4 weeks prior to enrollment. For receipt of ACAM2000 vaccine >28 days prior with a vaccination scab still present.
Receipt of any vaccines that are not covered in exclusion criterion #10 within 14 days prior to enrollment. Please note this includes replication incompetent vaccines such as the Jynneos vaccine for the prevention of monkeypox disease
Initiation of antigen-based immunotherapy for allergies within the previous year (stable immunotherapy is not exclusionary); inclusion of participants who initiated immunotherapy within the previous year requires PSRT approval.
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 greater than 7 days (or unknown half-life) within the past year, PSRT approval is required for enrollment.
History of serious reaction (eg, hypersensitivity, anaphylaxis) to any vaccine or any component of the study vaccine, including imidazoquinolone (eg, imiquimod).
Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.
Idiopathic urticaria within the past year.
Bleeding disorder diagnosed by a doctor (eg, factor deficiency, coagulopathy, or platelet disorder requiring special precautions).
Seizure disorder; febrile seizures as a child or seizures secondary to alcohol withdrawal more than 5 years ago are not exclusionary.
Asplenia or functional asplenia.
Active duty and reserve US military personnel.
Any other chronic or clinically significant condition that in the clinical judgement of the investigator would jeopardize the safety or rights of the study participant, including, but not limited to: clinically significant forms of drug or alcohol abuse, serious psychiatric disorders, or cancer that, in the clinical judgement of the site investigator, has a potential for recurrence (excluding basal cell carcinoma).
Asthma is excluded if the participant has ANY of the following:
Required either oral or parenteral corticosteroids for an exacerbation two or more times within the past year; OR
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 co-existing conditions unrelated to asthma); OR
Uses a short-acting rescue inhaler more than 2 days/week for acute asthma symptoms (ie, not for preventive treatment prior to athletic activity); OR
Uses medium-to-high-dose inhaled corticosteroids (greater than 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 one medication for maintenance therapy daily. Inclusion of anyone on a stable dose of more than one medication for maintenance therapy daily for greater than two years requires PSRT approval.
A participant with a history of an immune-mediated disease, either active or remote. Not exclusionary: 1) remote history of Bell's palsy (>2 years ago) not associated with other neurologic symptoms, 2) mild psoriasis that does not require ongoing systemic treatment.
Investigator concern for difficulty with venous access based upon clinical history and physical examination. For example, history of IV drug abuse or substantial difficulty with previous blood draws.

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

United States6 sites

The Ponce de Leon Center CRS
Atlanta, Georgia, 30308-2012
Alabama CRS
Birmingham, Alabama, 35222
Brigham and Women's Hospital Vaccine CRS (BWH VCRS)
Boston, Massachusetts, 02115-6110
Columbia P&S CRS
New York, New York, 10032
Bridge HIV CRS
San Francisco, California, 94102
Seattle Vaccine and Prevention CRS
Seattle, Washington, 98104

Other trials in United States

About this study

Official title: A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of Priming Regimens of 426c.Mod.Core-C4b and Optional Boost Regimen With HIV Trimer BG505 SOSIP.GT1.1 gp140, Both Adjuvanted With 3M-052-AF + Alum in Healthy, Adult Participants Without HIV

The clinical study is designed to evaluate the ability of two priming vaccine regimens to activate and induce the maturation of cross-reactive CD4 binding site (CD4-bs) antibodies, including VRC01-class antibodies. VRC01- class antibodies are highly desirable to elicit via vaccination because they have broad cover all clades of HIV and passive administration of VRC01 monoclonal antibodies has been demonstrated to prevent acquisition of susceptible HIV strains in clinical trials. The study will assess whether B cells expressing VRC01-like B cell receptors proliferate following immunization with a 'germline-targeting' recombinant Env immunogen. The study will also test whether an immunization strategy based upon fractionated dose delivery of the immunogen may improve the maturation of VRC01-class B cells when compared to traditional bolus dosing. In addition, the study will test whether alterations in the dose of the subsequent boost immunizations affects VRC01-class B cell activation and the rate of antibody affinity maturation.

The primary hypothesis of the optional boost regimen is that BG505 SOSIP.GT1.1 gp140 adjuvated with 3M-052-AF + Alum is safe and well-tolerated and will further mature B-cell lineages elicited by 426c.Mod.Core-C4b priming regimens.

Conditions: HIV-1-infection
Being tested: 426c.Mod.Core-C4b 30 mcg, 426c.Mod.Core-C4b 100 mcg, 426c.Mod.Core-C4b 300 mcg, Placebo, BG505

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

426c.Mod.Core-C4b 30 mcgBiological
Also called Lower dose
Administered via injection as a split dose into the deltoid muscle (both left and right).
426c.Mod.Core-C4b 100 mcgBiological
Also called Medium dose
Administered via injection as a split dose into the deltoid muscle (both left and right).
426c.Mod.Core-C4b 300 mcgBiological
Also called Higher dose
Administered via injection as a split dose into the deltoid muscle (both left and right).
PlaceboOther
Administered via injection as a split dose into the deltoid muscle (both left and right).
BG505Biological
A soluble, cleavage-competent, trimeric HIV-1 envelope glycoprotein gp140 formulated at 2 mg/mL, 0.55 mL per vial, in 20 mM Tris, 100 mM NaCl, pH 7.5 will be admixed with 3M-052-AF (5 mcg) + Alum (500 mcg

Study groups in NCT05471076
Study group	Role	What they receive
Bolus Delivery, Group 1: First injection - Medium dose, Final injection - Lower dose	Experimental	The Bolus Delivery Arm Group 1 will receive injections at 2 visits scheduled 3 months apart. At each injection visit the patient will get one dose divided into 2 injections - one in the deltoid muscle of each arm. Receives: Biological: 426c.Mod.Core-C4b 30 mcg; Biological: 426c.Mod.Core-C4b 100 mcg
Bolus Delivery, Group 2: First injection - Medium dose, Final injection - Higher dose	Experimental	The Bolus Delivery Arm Group 2 will receive injections at 2 visits scheduled 3 months apart. At each injection visit the patient will get one dose divided into 2 injections - one in the deltoid muscle of each arm. Receives: Biological: 426c.Mod.Core-C4b 100 mcg; Biological: 426c.Mod.Core-C4b 300 mcg
Bolus Delivery, Group 3: First injection - Placebo, Final injection - Placebo	Placebo comparator	The Bolus Delivery Arm Group 2 will receive injections at 2 visits scheduled 3 months apart. At each injection visit the patient will get one dose divided into 2 injections - one in the deltoid muscle of each arm. Receives: Other: Placebo
Fractionated Delivery, Group 1: First injection - Medium dose, Final injection - Lower dose	Experimental	The first dose for the Fractionated Delivery Arm Group 1 will be divided into 6 smaller amounts (2 visits per week for 3 weeks). The second dose will be given about 3 months later and will be given all at once. At each injection visit for the first dose, the patient will get one amount divided into 2 injections - one in the deltoid muscle of each arm. Receives: Biological: 426c.Mod.Core-C4b 30 mcg; Biological: 426c.Mod.Core-C4b 100 mcg
Fractionated Delivery, Group 2: First injection - Medium dose, Final injection - Higher dose	Experimental	The first dose for the Fractionated Delivery Arm Group 2 will be divided into 6 smaller amounts (2 visits per week for 3 weeks). The second dose will be given about 3 months later and will be given all at once. At each injection visit for the first dose, the patient will get one amount divided into 2 injections - one in the deltoid muscle of each arm. Receives: Biological: 426c.Mod.Core-C4b 100 mcg; Biological: 426c.Mod.Core-C4b 300 mcg
Fractionated Delivery, Group 3: First injection - Placebo, Final injection - Placebo	Placebo comparator	The first dose for the Fractionated Delivery Arm Group 2 will be divided into 6 smaller amounts (2 visits per week for 3 weeks). The second dose will be given about 3 months later and will be given all at once. At each injection visit for the first dose, the patient will get one amount divided into 2 injections - one in the deltoid muscle of each arm. Receives: Other: Placebo
Optional Boost Regimen with BG505	Experimental	SOSIP.GT1.1 gp140 Receives: Biological: BG505

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of participants showing local vaccination reactogenicity signs and symptoms
Assessed by clinic staff. For a given sign or symptom, each subject's reactogenicity will be counted once under the maximum severity for each injection/ vaccination.
Measured: 14 days following each vaccination
Number of participants showing systemic vaccination reactogenicity signs and symptoms
Assessed by clinic staff. For a given sign or symptom, each subject's reactogenicity will be counted once under the maximum severity for each injection/ vaccination.
Measured: 14 days following each vaccination
Number of serious adverse events (SAEs)
Adverse events (AEs) will be graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 (exceptions apply).
Measured: Through week 64
Number of medically attended adverse events (MAAEs)
Adverse events (AEs) will be graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 (exceptions apply).
Measured: Through week 64
Number of adverse events of special interest (AESIs)
Adverse events (AEs) will be graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 (exceptions apply).
Measured: Through week 64
Number of AEs leading to early participant withdrawal or permanent discontinuation
Adverse events (AEs) will be graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 (exceptions apply).
Measured: Through week 64
Frequency of CD4-bs-specific B cells
Measured by flow cytometry analysis
Measured: Through week 27
Frequency of VRC01-like BCR sequences
Determined by variable heavy chain domain (VH)/variable light chain domain (VL) sequencing of sorted B cells
Measured: Through week 27

Secondary outcomes (22)

Response rate of Env-specific serum IgG binding antibodies.
Measured: Through week 27
Magnitude of Env-specific serum IgG binding antibodies.
Measured: Through week 27
Epitope-specificity of Env-specific serum IgG binding antibodies.
Measured: Through week 27
Avidity of Env-specific serum IgG binding antibodies.
Measured: Through week 27
Frequency of CD4-bs B cells and BCR sequences of isolated CD4-bs and VRC01-class memory B cells induced post-immunization with the traditional bolus dosing versus the fractionated dose delivery approach.
Measured: Through week 27
Frequency of CD4-bs B cells and BCR sequences of isolated CD4-bs and VRC01-class memory B cells induced post-immunization induced following a "low" or "high" dose second dose.
Measured: 14 days following second vaccination
Frequency of VRC01-class memory B cells induced post-immunization with the traditional bolus dosing versus the fractionated dose delivery approach.
Measured: Through week 27
Frequency of VRC01-class memory B cells induced following a "low" or "high" dose second dose.
Measured: 14 days following second vaccination
Response rate of serum antibody neutralization of the vaccine strain
Measured by TZM-bl assay.
Measured: 14 days following each vaccination
Response rate of serum antibody neutralization of a panel of CD4-bs bnAb precursor-sensitive viruses.
Measured by TZM-bl assay.
Measured: 14 days following each vaccination
Magnitude of serum antibody neutralization of the vaccine strain
Measured by TZM-bl assay.
Measured: 14 days following each vaccination
Magnitude of serum antibody neutralization of a panel of CD4-bs bnAb precursor-sensitive viruses.
Measured by TZM-bl assay.
Measured: 14 days following each vaccination
Comparison of CD4-bs-specific B cell frequencies in fractionated dosing versus traditional bolus dosing.
Measured: Through week 27
Comparison of BCR sequences frequencies in fractionated dosing versus traditional bolus dosing.
Measured: Through week 27
Response rate of VH/VL-pair sequence analysis of BCRs isolated from CD-4-bs-specific B cells
Measured: !4 days following each vaccination
Response rate of BG505 SOSIP.GT1.1 gp140 on the neutralizing activities of vaccine-induced antibodies in participants primed with 426c
Measured: Through week 27
Response rate of BG505 SOSIP.GT1.1 gp140 on the quality and quantity of Env-specific binding antibodies elicited after the GT1.1 immunization in participants primed with 426c
Measured: Through week 27
. Magnitude of BG505 SOSIP.GT1.1 gp140 on the quality and quantity of Env-specific binding antibodies elicited after the GT1.1 immunization in participants primed with 426c
Measured: Through week 27
Epitope specificity of BG505 SOSIP.GT1.1 gp140 on the quality and quantity of Env-specific binding antibodies elicited after the GT1.1 immunization in participants primed with 426c
Measured: Through week 27
Comparison of CD4-bs antibodies isolated after the GT.1 immunization, as compared to those elicited by the 426c
Measured: Through week 27
Response rate of BG505 SOSIP.GT1.1 gp140 on the CD4+ T cell response in participants primed with 426c
Measured: Through week 27
Magnitude of BG505 SOSIP.GT1.1 gp140 on the CD4+ T cell response in participants primed with 426c
Measured: Through week 27

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

22 Aug 202213 Apr 2026

First posted22 Jul 2022
Study start22 Aug 2022
Primary completion23 Dec 2025
Study completion13 Apr 2026

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Publications (1)Papers the sponsor has linked to this study.
Other trials for HIV-1-infectionStudies of the same condition, open and under way.
More trials run by National Institute of Allergy and Infectious Diseases (NIAID)The sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 1
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind
Who is masked: Participant, Investigator
Enrolment: 52 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT05471076
Sponsor's protocol ID: HVTN 301
Status last verified: Jul 2026
First submitted: 15 Jul 2022
Last updated: 8 Jul 2026
Results posted: No
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: No

Publications

Libera M, Caputo V, Laterza G, Moudoud L, Soggiu A, Bonizzi L, Diotti RA. The Question of HIV Vaccine: Why Is a Solution Not Yet Available? J Immunol Res. 2024 Apr 8;2024:2147912. doi: 10.1155/2024/2147912. eCollection 2024.
PubMed 38628675

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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Study at a glance

From the registry record, last updated by the sponsor on 8 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1 Clinical Trial to Evaluate the Safety and Immunogenicity of Priming Regimens of 426c.Mod.Core-C4b and Optional Boost Regimen With HIV Trimer BG505 SOSIP.GT1.1 gp140, Both Adjuvanted With 3M-052-AF + Alum in Healthy, Adult Participants Without HIV
ClinicalTrials.gov ID: NCT05471076
Acronym / sponsor ID: HVTN 301
Conditions: HIV-1-infection
Phase: Phase 1
Study type: Interventional
Recruitment status: Completed
Enrolment: 52 participants (actual)
Lead sponsor: National Institute of Allergy and Infectious Diseases (NIAID)US National Institutes of Health
Collaborators: National Institutes of Health (NIH), Department of Health and Human Services
Study start: 22 Aug 2022 (actual)
Primary completion: 23 Dec 2025 (actual)
Study completion: 13 Apr 2026 (actual)
First posted: 22 Jul 2022 (actual)
Results: Not posted in the source record

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Double blind (participant, investigator)
Number of arms: 7

Arm	Type	Receives
Bolus Delivery, Group 1: First injection - Medium dose, Final injection - Lower dose	Experimental	Biological: 426c.Mod.Core-C4b 30 mcg, Biological: 426c.Mod.Core-C4b 100 mcgThe Bolus Delivery Arm Group 1 will receive injections at 2 visits scheduled 3 months apart. At each injection visit the patient will get one dose divided into 2 injections - one in the deltoid muscle of each arm.
Bolus Delivery, Group 2: First injection - Medium dose, Final injection - Higher dose	Experimental	Biological: 426c.Mod.Core-C4b 100 mcg, Biological: 426c.Mod.Core-C4b 300 mcgThe Bolus Delivery Arm Group 2 will receive injections at 2 visits scheduled 3 months apart. At each injection visit the patient will get one dose divided into 2 injections - one in the deltoid muscle of each arm.
Bolus Delivery, Group 3: First injection - Placebo, Final injection - Placebo	Placebo comparator	Other: PlaceboThe Bolus Delivery Arm Group 2 will receive injections at 2 visits scheduled 3 months apart. At each injection visit the patient will get one dose divided into 2 injections - one in the deltoid muscle of each arm.
Fractionated Delivery, Group 1: First injection - Medium dose, Final injection - Lower dose	Experimental	Biological: 426c.Mod.Core-C4b 30 mcg, Biological: 426c.Mod.Core-C4b 100 mcgThe first dose for the Fractionated Delivery Arm Group 1 will be divided into 6 smaller amounts (2 visits per week for 3 weeks). The second dose will be given about 3 months later and will be given all at once. At each injection visit for the first dose, the patient will get one amount divided into 2 injections - one in the deltoid muscle of each arm.
Fractionated Delivery, Group 2: First injection - Medium dose, Final injection - Higher dose	Experimental	Biological: 426c.Mod.Core-C4b 100 mcg, Biological: 426c.Mod.Core-C4b 300 mcgThe first dose for the Fractionated Delivery Arm Group 2 will be divided into 6 smaller amounts (2 visits per week for 3 weeks). The second dose will be given about 3 months later and will be given all at once. At each injection visit for the first dose, the patient will get one amount divided into 2 injections - one in the deltoid muscle of each arm.
Fractionated Delivery, Group 3: First injection - Placebo, Final injection - Placebo	Placebo comparator	Other: PlaceboThe first dose for the Fractionated Delivery Arm Group 2 will be divided into 6 smaller amounts (2 visits per week for 3 weeks). The second dose will be given about 3 months later and will be given all at once. At each injection visit for the first dose, the patient will get one amount divided into 2 injections - one in the deltoid muscle of each arm.
Optional Boost Regimen with BG505	Experimental	Biological: BG505SOSIP.GT1.1 gp140

Who may qualify

Ages: 18 to 55 years
Sex: All
Healthy volunteers: Accepted
Age groups: Adult

Key inclusion criteria (23 listed)

Able and willing to complete the informed consent process, including an Assessment of Understanding: volunteer demonstrates understanding of this study; completes a questionnaire prior to first vaccination with verbal demonstration of understanding of any questionnaire items answered incorrectly.
18-55 years old, inclusive, on day of enrollment.
Available for clinic follow-up through the last clinic visit, willing to under go lymph node fine needle aspiration, and willing to be contacted 12 months after the last vaccine administration.
Agrees not to enroll in another study of an investigational agent during participation in the trial.
In good general health according to the clinical judgement of the site investigator.

Key exclusion criteria (29 listed)

Volunteer who is breast-feeding or pregnant.
Morbid Obesity. Enrollment of individuals with body mass index (BMI) ≥40, who the site investigator assesses are in good health, may be considered by PSRT on a case-by-case basis.
Diabetes mellitus (DM). Type 2 DM, controlled with diet alone, 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, provided the HgbA1c is ≤8% within the last 6 months (sites may draw these at screening).
International normalized ratio (INR) >1.2.
Previous or current recipient of an investigational HIV vaccine (previous placebo recipients are not excluded).

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Intervention	Type	Arms
426c.Mod.Core-C4b 30 mcgAlso: Lower doseAdministered via injection as a split dose into the deltoid muscle (both left and right).	Biological	Bolus Delivery, Group 1: First injection - Medium dose, Final injection - Lower dose, Fractionated Delivery, Group 1: First injection - Medium dose, Final injection - Lower dose
426c.Mod.Core-C4b 100 mcgAlso: Medium doseAdministered via injection as a split dose into the deltoid muscle (both left and right).	Biological	Bolus Delivery, Group 1: First injection - Medium dose, Final injection - Lower dose, Bolus Delivery, Group 2: First injection - Medium dose, Final injection - Higher dose, Fractionated Delivery, Group 1: First injection - Medium dose, Final injection - Lower dose, Fractionated Delivery, Group 2: First injection - Medium dose, Final injection - Higher dose
426c.Mod.Core-C4b 300 mcgAlso: Higher doseAdministered via injection as a split dose into the deltoid muscle (both left and right).	Biological	Bolus Delivery, Group 2: First injection - Medium dose, Final injection - Higher dose, Fractionated Delivery, Group 2: First injection - Medium dose, Final injection - Higher dose
PlaceboAdministered via injection as a split dose into the deltoid muscle (both left and right).	Other	Bolus Delivery, Group 3: First injection - Placebo, Final injection - Placebo, Fractionated Delivery, Group 3: First injection - Placebo, Final injection - Placebo
BG505A soluble, cleavage-competent, trimeric HIV-1 envelope glycoprotein gp140 formulated at 2 mg/mL, 0.55 mL per vial, in 20 mM Tris, 100 mM NaCl, pH 7.5 will be admixed with 3M-052-AF (5 mcg) + Alum (500 mcg	Biological	Optional Boost Regimen with BG505

Primary outcome

Number of participants showing local vaccination reactogenicity signs and symptoms
Time frame: 14 days following each vaccination
Assessed by clinic staff. For a given sign or symptom, each subject's reactogenicity will be counted once under the maximum severity for each injection/ vaccination.
Number of participants showing systemic vaccination reactogenicity signs and symptoms
Time frame: 14 days following each vaccination
Assessed by clinic staff. For a given sign or symptom, each subject's reactogenicity will be counted once under the maximum severity for each injection/ vaccination.
Number of serious adverse events (SAEs)
Time frame: Through week 64
Adverse events (AEs) will be graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 (exceptions apply).
Number of medically attended adverse events (MAAEs)
Time frame: Through week 64
Adverse events (AEs) will be graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 (exceptions apply).
Number of adverse events of special interest (AESIs)
Time frame: Through week 64
Adverse events (AEs) will be graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 (exceptions apply).
Number of AEs leading to early participant withdrawal or permanent discontinuation
Time frame: Through week 64
Adverse events (AEs) will be graded according to the Division of AIDS (DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events, Corrected Version 2.1 (exceptions apply).
Frequency of CD4-bs-specific B cells
Time frame: Through week 27
Measured by flow cytometry analysis
Frequency of VRC01-like BCR sequences
Time frame: Through week 27
Determined by variable heavy chain domain (VH)/variable light chain domain (VL) sequencing of sorted B cells

22 secondary outcomes

Response rate of Env-specific serum IgG binding antibodies.
Time frame: Through week 27
Magnitude of Env-specific serum IgG binding antibodies.
Time frame: Through week 27
Epitope-specificity of Env-specific serum IgG binding antibodies.
Time frame: Through week 27
Avidity of Env-specific serum IgG binding antibodies.
Time frame: Through week 27
Frequency of CD4-bs B cells and BCR sequences of isolated CD4-bs and VRC01-class memory B cells induced post-immunization with the traditional bolus dosing versus the fractionated dose delivery approach.
Time frame: Through week 27
Frequency of CD4-bs B cells and BCR sequences of isolated CD4-bs and VRC01-class memory B cells induced post-immunization induced following a "low" or "high" dose second dose.
Time frame: 14 days following second vaccination
Frequency of VRC01-class memory B cells induced post-immunization with the traditional bolus dosing versus the fractionated dose delivery approach.
Time frame: Through week 27
Frequency of VRC01-class memory B cells induced following a "low" or "high" dose second dose.
Time frame: 14 days following second vaccination
Response rate of serum antibody neutralization of the vaccine strain
Time frame: 14 days following each vaccination
Response rate of serum antibody neutralization of a panel of CD4-bs bnAb precursor-sensitive viruses.
Time frame: 14 days following each vaccination
Magnitude of serum antibody neutralization of the vaccine strain
Time frame: 14 days following each vaccination
Magnitude of serum antibody neutralization of a panel of CD4-bs bnAb precursor-sensitive viruses.
Time frame: 14 days following each vaccination
Comparison of CD4-bs-specific B cell frequencies in fractionated dosing versus traditional bolus dosing.
Time frame: Through week 27
Comparison of BCR sequences frequencies in fractionated dosing versus traditional bolus dosing.
Time frame: Through week 27
Response rate of VH/VL-pair sequence analysis of BCRs isolated from CD-4-bs-specific B cells
Time frame: !4 days following each vaccination
Response rate of BG505 SOSIP.GT1.1 gp140 on the neutralizing activities of vaccine-induced antibodies in participants primed with 426c
Time frame: Through week 27
Response rate of BG505 SOSIP.GT1.1 gp140 on the quality and quantity of Env-specific binding antibodies elicited after the GT1.1 immunization in participants primed with 426c
Time frame: Through week 27
. Magnitude of BG505 SOSIP.GT1.1 gp140 on the quality and quantity of Env-specific binding antibodies elicited after the GT1.1 immunization in participants primed with 426c
Time frame: Through week 27
Epitope specificity of BG505 SOSIP.GT1.1 gp140 on the quality and quantity of Env-specific binding antibodies elicited after the GT1.1 immunization in participants primed with 426c
Time frame: Through week 27
Comparison of CD4-bs antibodies isolated after the GT.1 immunization, as compared to those elicited by the 426c
Time frame: Through week 27
Response rate of BG505 SOSIP.GT1.1 gp140 on the CD4+ T cell response in participants primed with 426c
Time frame: Through week 27
Magnitude of BG505 SOSIP.GT1.1 gp140 on the CD4+ T cell response in participants primed with 426c
Time frame: Through week 27

Results and safety

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 8 Jul 2026.
Derived from this study: PubMed 38628675Libera M, Caputo V, Laterza G, Moudoud L, Soggiu A, Bonizzi L, Diotti RA. The Question of HIV Vaccine: Why Is a Solution Not Yet Available? J Immunol Res. 2024 Apr 8;2024:2147912. doi: 10.1155/2024/2147912. eCollection 2024.
Individual participant dataSharing planned: No

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

Hyman Scott, MD study chair

University of California, San Francisco

Kristen Cohen, MD study chair

Fred Hutch Cancer Center, Seattle, WA

6 sites in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 23 inclusion and 29 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 8 Jul 2026. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 6 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Number of participants showing local vaccination reactogenicity signs and symptoms (time frame: 14 days following each vaccination). The study lists 8 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT05471076, which also lists 1 linked publication.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 8 Jul 2026.