HIV InfectionsPhase 1IAVI G004NCT06694753

Safety and Immunogenicity Study of Three mRNAs Encoding HIV Immunogens in Adult Participants Without HIV and in Overall Good Health in South Africa.

A Phase 1 study testing mRNA-1645-eODGT8, mRNA-1645-CoreG28v2 and mRNA-1645-N332GT5 in people with HIV Infections, run by International AIDS Vaccine Initiative at 6 sites in South Africa.

Active, not recruiting

Under way, not looking for participants. Everyone needed has enrolled. The study is still running.

Official record

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Trial summary

The purpose of this study is to evaluate the safety and immunogenicity of mRNAs encoding HIV immunogens (eOD-GT8 60mer, core-g28v2 60mer, N332-GT5 gp151) in adult participants without HIV and in overall good health in South Africa. Read more about this study

Who is it for?: Ages 18 to 55 yearsHealthy volunteers can take part
Conditions the study is for: HIV Infections
What is being tested?: mRNA-1645-eODGT8, mRNA-1645-CoreG28v2 and mRNA-1645-N332GT5
Type of treatment: Injection or infusion
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 96 participants
Where: 6 sitesSouth Africa
Study dates: 15 Dec 2025to 31 Mar 2027
Phase: Phase 1
Are there results?: Not yet: the study is under way

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

Demonstrates an understanding of the study and is able and willing to complete the informed consent process.
18 to ≤ 55 years old, on day of enrollment.
Available for clinic follow-up through the last clinic visit.
Willingness to undergo FNA and leukapheresis.
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 IAVI Medical Monitor are required prior to enrollment into DESIIGN001/IAVI G004.
In good general health according to the clinical judgment of the Investigator.

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Physical examination and laboratory results without clinically significant findings that would interfere with assessment of safety or reactogenicity in the clinical judgment of the Investigator.
Assessed by clinical staff as having a low likelihood of acquiring HIV per guidelines (see Appendix 4), agrees to discuss their potential for HIV acquisition, agrees to prevention counseling, and agrees to avoid behaviors associated with a higher likelihood of acquiring HIV through the final study visit. "Low likelihood" may include persons stably taking pre-exposure prophylaxis (PrEP) as prescribed in Appendix 4.
Hemoglobin (Hgb):
≥12.0 g/dL for AFAB volunteers
≥13.0 g/dL for cisgender AMAB volunteers or for volunteers who have been on masculinizing hormone therapy for more than 6 consecutive months
≥12.0 g/dL for AMAB volunteers who have been on feminizing hormone therapy for more than 6 consecutive months
For volunteers who have been on gender-affirming hormone therapy for less than 6 consecutive months, determine Hgb eligibility based on their sex assigned at birth.
White blood cell (WBC) count = 2,500 to 12,000/mm3.
Platelets = 125,000 to 550,000/mm3.
Alanine aminotransferase (ALT) <2.5 × upper limit of institutional reference range.
Serum creatinine ≤1.1× upper limit of normal (ULN) based on the institutional normal range.
Systolic blood pressure of 90 to <140 mmHg and diastolic blood pressure of 50 to <90 mmHg at the screening visit. The average blood pressure between the screening visit and the enrollment visit must be below 140 mmHg systolic and 90 mmHg diastolic. A single measurement ≥160 mmHg systolic or 100 mmHg diastolic during the current study evaluation is exclusionary.
Negative HIV test results by one of the following options:
A negative European Conformity (CE)-marked enzyme immunoassay (EIA)
A chemiluminescent microparticle immunoassay (CMIA)
A negative result on 2 HIV rapid tests (one of these rapid tests must be CE-marked)
Negative for anti-Hepatitis C virus (HCV) Abs (anti-HCV) or negative HCV nucleic acid test (NAT) if anti-HCV Abs are detected.
Negative for Hepatitis B surface antigen (HBsAg).
For volunteers AFAB or assigned intersex at birth who are capable of becoming pregnant (hereafter referred to as "persons 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 time point (see Appendix 5).
Must have a negative beta human chorionic gonadotropin (β-HCG) pregnancy test (urine or serum) on day of enrollment.
Note: Persons who are NOT of pregnancy potential due to total hysterectomy or bilateral oophorectomy or menopause (no menses for ≥1 year) are not required to undergo pregnancy testing.
Volunteers AFAB or assigned intersex at birth 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 time point.

Who cannot join

Volunteer is nursing or pregnant.
Body mass index (BMI) ≥40 kg/m2. Enrollment of individuals with BMI ≥40 kg/m2, whom the site investigator assesses are in good health, may be considered by the IAVI Medical Monitor.
Diabetes mellitus (DM). Type 2 DM controlled with diet alone (and confirmed by HgbA1c ≤7% 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 by the IAVI Medical Monitor on a case-by-case basis, provided that the HgbA1c is ≤8% within the last 6 months (CRC staff may draw these at screening).
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 authorizing this clinical trial.
Congenital or acquired immunodeficiency, including systemic medication use likely to impair immune response to vaccine in the opinion of the Investigator, such as glucocorticoid use, prednisone ≥10 mg/day within 3 months prior to enrollment.

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Blood products or immunoglobulin within 16 weeks prior to enrollment; receipt of immunoglobulin within 16 weeks prior to enrollment requires approval by the IAVI Medical Monitor.
Previous receipt of VRC01 or VRC07-523LS monoclonal antibody (mAb).
Receipt of any vaccine within 4 weeks prior to enrollment or planned receipt within 4 weeks of investigational vaccine administration.
History of myocarditis and/or pericarditis.
A past history of immune-mediated disease, including but not limited to thyroid disease, rheumatoid arthritis, systemic lupus erythematosus, Sjögren's syndrome, celiac disease, seronegative inflammatory arthritis, systemic sclerosis, and Type 1 diabetes (for other examples, see Appendix 8).
History of or active severe skin conditions, including, but not limited to, cutaneous mastocytosis, psoriasis, atopic dermatitis, lichen planus, hidradenitis suppurativa, bullous pemphigoid, and urticarial vasculitis.
Systemic or local conditions with urticaria as a manifestation, including urticarial vasculitis, maculo-papular cutaneous mastocytosis (formerly urticaria pigmentosa), mast cell activation syndrome, Gleich's syndrome (episodic angioedema with eosinophilia), Well's syndrome (granulomatous dermatitis with eosinophilia/eosinophilic cellulitis), bullous pemphigoid, or adult-onset Still's disease.
Receipt of antigen-based immunotherapy.
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 by the IAVI Medical Monitor is required for enrollment.
History of serious reaction (eg, hypersensitivity, anaphylaxis) to any vaccine or component of the study-vaccine regimen.
History of hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema.
History of urticaria and/or dermatographism.
History of atopy (diagnosed or confirmed by a clinician).
Bleeding disorder diagnosed by a clinician that would make study procedures a contraindication.
History of seizure(s) within the past 3 years, or if volunteer has used medications to prevent or treat seizure(s) at any time within the past 3 years.
Asplenia or functional asplenia.
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 suicide attempt within the past 1 year (if between 1 and 2 years, consult the IAVI Medical Monitor for approval), or cancer that, in the clinical judgment of the Investigator, has potential for recurrence (excluding basal cell carcinoma).
Asthma (diagnosed or confirmed by a clinician).
History of allergy to local anesthetic (Novocaine, Lidocaine).
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.
Has donated ≥450 mL of blood products within 28 days prior to the Screening Visit or plans to donate blood products within 28 days post study injection.
Is working or has worked as study personnel or is an immediate family member or house member of study personnel, study site staff, or Sponsor personnel.

Trial locations and contacts

6 sites in 1 country.

City, postcode or hospital

6 sites in 1 country

South Africa6 sites

Desmond Tutu Health Foundation Emavundleni CRS
Cape Town, Western Cape, 7750
Desmond Tutu Health Foundation- Groote Schuur Hospital/J52
Cape Town, Western Cape, 7925
CAPRISA eThekwini CRS
Durban, KwaZulu-Natal, 4001
Isipingo CRS
Isipingo, KwaZulu-Natal, 4110
Setshaba Research Centre CRS
Soshanguve, Gauteng, 0152
Perinatal HIV Research Unit (PHRU)
Soweto, Gauteng, 1862

Other trials in South Africa

About this study

Official title: A Phase 1, Placebo-controlled, Blinded, Dose-escalation Study to Evaluate the Safety and Immunogenicity of mRNAs Encoding HIV Immunogens (eOD-GT8 60mer, Core-g28v2 60mer, N332-GT5 gp151) in Adult Participants Without HIV and in Overall Good Health in South Africa.

Read the detailed description

This study will evaluate the safety and immunogenicity of 3 experimental HIV vaccines in adult participants without HIV and in overall good health in South Africa. The study vaccines are called mRNA-1645-eODGT8, mRNA-1645-CoreG28v2 and mRNA-1645-N332GT5.

The study will be conducted in two parts (Part A and B). Part A will include two Cohorts, each with 2 groups: Cohort 1A Group 1, Cohort 1A Group 2, Cohort 2A Group 3, and Cohort 2A Group 4. Part B will include two Cohorts, each with 2 groups: Cohort 1B Group 5, Cohort 1B Group 6, Cohort 2B Group 7, and Cohort 2B Group 8.

Participants in Part A Cohort 1A will be randomly assigned to receive mRNA-1645-eODGT8 followed by mRNA-1645-CoreG28v2 or to receive placebo. Participants in Part A Cohort 2A will be randomly assigned to receive two doses of the mRNA-1645-N332GT5 vaccine or to receive placebo. Cohorts 1A and 2A in Part A will be enrolled concurrently, and randomization to study product or placebo will take place in each cohort. Depending on their group, participants will receive 10 mcg of mRNA-1645-eODGT8, mRNA-1645-N332GT5 or Placebo by injection at Week 0 and 10 mcg of mRNA-1645-CoreG28v2, mRNA-1645-N332GT5, or Placebo at Week 8.

Participants in Part B Cohort 1B will be randomly assigned to receive an increased dose of the mRNA-1645-eODGT8 and mRNA-1645-CoreG28v2 vaccine or to receive placebo. Participants in Part B Cohort 2B will be randomly assigned to receive an increased dose of the mRNA-1645-N332GT5 vaccine or to receive placebo. Cohorts 1B and 2B in Part B will be enrolled concurrently, and randomization to study product or placebo will take place in each cohort. Depending on their group, participants will receive 30 mcg of mRNA-1645-eODGT8, mRNA-1645-N332GT5 or Placebo by injection at Week 0 and 30 mcg of mRNA-1645-CoreG28v2, mRNA-1645-N332GT5, or Placebo at Week 8.

Additional study visits will occur at Weeks 2, 7.5, 10, 15.5, and 24. Study visits may include physical examinations, medical history, vaccine injections, blood and urine collection, electrocardiogram, leukapheresis, lymph node cell collection, pregnancy test, HIV testing, risk reduction counseling, and questionnaires.

Conditions: HIV Infections
Being tested: mRNA-1645-eODGT8, mRNA-1645-CoreG28v2, mRNA-1645-N332GT5, Placebo
Keywords: HIV
Medical subject headings: HIV Infections

What participants receive

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

mRNA-1645-eODGT8Biological
Also called eOD-GT8 60mer mRNA
eOD-GT8 60mer is a self-assembling nanoparticle composed of 60 subunits of the engineered HIV-1 gp120 outer domain germline targeting version 8 (eOD-GT8) fused to an engineered form of a bacterial enzyme, Lumazine Synthase, through a 15-amino acid Glycine-Serine linker. eOD-GT8 60mer will be delivered using an mRNA lipid nanoparticle (LNP) platform. To be administered by intramuscular (IM) injection at doses of 10 or 30 mcg.
mRNA-1645-CoreG28v2Biological
Also called core-g28v2 60mer mRNA
core-g28v2 60mer is a nanoparticle composed of 60 protein subunits of an engineered core-gp120 fused to an engineered form of a bacterial enzyme, Lumazine Synthase, through a 21-amino acid Glycine-Serine linker. Core-g28v2 60mer will be delivered using an mRNA-LNP platform. To be administered by IM injection at doses of 10 or 30 mcg.
mRNA-1645-N332GT5Biological
Also called N332-GT5 gp151 mRNA
N332-GT5 gp151 is an HIV envelope glycoprotein gp151 trimer based on BG505 SOSIP MD39 (clade A) trimer with "germline-targeting" mutations added that confer the ability to bind germline precursors of BG18 class B cells. N332-GT5 gp151 will be delivered using an mRNA-LNP platform. To be administered by IM injection at doses of 10 or 30 mcg.
PlaceboBiological
Also called Saline, Diluent
Saline

Study groups in NCT06694753
Study group	Role	What they receive
Cohort 1A Group 1: mRNA-1645-eODGT8 + mRNA-1645-CoreG28v2	Experimental	Participants will receive one injection of 10 mcg mRNA-1645-eODGT8 to be administered as a 0.5 mL IM injection into the deltoid at Week 0 and one injection of 10 mcg mRNA-1645-CoreG28v2 to be administered as a 0.5 mL IM injection into the deltoid at Week 8. Receives: Biological: mRNA-1645-eODGT8; Biological: mRNA-1645-CoreG28v2
Cohort 1A Group 2: Placebo	Placebo comparator	Participants will receive 0.9% sodium chloride to be administered as a 0.5-mL IM injection into the deltoid at Weeks 0 and 8. Receives: Biological: Placebo
Cohort 2A Group 3: mRNA-1645-N332GT5	Experimental	Participants will receive 10 mcg of mRNA-1645-N332GT5 to be administered as a 0.5 mL IM injection into the deltoid at Weeks 0 and 8. Receives: Biological: mRNA-1645-N332GT5
Cohort 2A Group 4: Placebo	Placebo comparator	Participants will receive 0.9% sodium chloride to be administered as a 0.5-mL IM injection into the deltoid at Week 0 and Week 8. Receives: Biological: Placebo
Cohort 1B Group 5: mRNA-1645-eODGT8 + mRNA-1645-CoreG28v2	Experimental	Participants will receive one injection of 30 mcg mRNA-1645-eODGT8 to be administered as a 0.5 mL IM injection into the deltoid at Week 0 and one injection of 30 mcg mRNA-1645-CoreG28v2 to be administered as a 0.5 mL IM injection into the deltoid at Week 8. Receives: Biological: mRNA-1645-eODGT8; Biological: mRNA-1645-CoreG28v2
Cohort 1B Group 6: Placebo	Placebo comparator	Participants will receive 0.9% sodium chloride to be administered as a 0.5-mL IM injection into the deltoid at Week 0 and Week 8. Receives: Biological: Placebo
Cohort 2B Group 7: mRNA-1645-N332GT5	Experimental	Participants will receive 30 mcg of mRNA-1645-N332GT5 to be administered as a 0.5 mL IM injection into the deltoid at Weeks 0 and 8. Receives: Biological: mRNA-1645-N332GT5
Cohort 2B Group 8: Placebo	Placebo comparator	Participants will receive 0.9% sodium chloride to be administered as a 0.5-mL IM injection into the deltoid at Week 0 and Week 8. Receives: Biological: Placebo

What is being measured

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

To assess the incidence of local and systemic reactogenecity and treatment-emergent adverse events [Safety and Tolerability].
- Local and systemic reactogenicity signs and symptoms will be collected for a minimum of 7 days following receipt of any study vaccination.
- AEs leading to early participant withdrawal or permanent discontinuation, SAEs, medically attended adverse events (MAAEs), and AESIs will be collected throughout the study. Additionally, all AEs will be collected for 30 days after any receipt of study vaccination.
Measured: Measured a minimum of 7 days following receipt of any study vaccination
To evaluate the induction of VRC01- or BG18-class IgG B cell responses by the vaccine regimens.
- Proportion of vaccinees with VRC01- or BG18-class IgG B cells, and frequency of VRC01- or BG18-class B cells among IgG+ B cells in PBMCs or in germinal centers, at baseline and after each study product administration, as determined by B-cell phenotyping and BCR sequencing.
Measured: V01 [W0, baseline] V04 [W7.5, 7.5 wks. post 1st vacc.] V06 [W10, 2 wks. post 2nd vacc.] V07 [W15.5, 7.5 wks. post 2nd vacc.]

Secondary outcomes (1)

To evaluate vaccine-specific and epitope-specific binding Ab responses elicited by the vaccine regimens.
Response rate and magnitude of serum IgG binding Abs as assessed by BAMA at baseline and after each study product administration.
Measured: Measured at baseline (at Week 0), 2 weeks post 1st vaccination (at Week 2), 7.5 weeks post 1st vaccination (at Week 7.5), 2 weeks post 2nd vaccination (at Week 10), and 7.5 weeks post 2nd vaccination (at Week 15.5)

Timeline

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

15 Dec 202531 Mar 2027

First posted19 Nov 2024
Study start15 Dec 2025
Primary completion8 Dec 2026 (estimated)
Study completion31 Mar 2027 (estimated)

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Other trials for HIV InfectionsStudies of the same condition, open and under way.
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: Sequential
Model description: Cohorts 1A and 2A in Part A will be enrolled concurrently. Randomization to study product or placebo will take place within each cohort. After Part A is fully enrolled, there will be a planned safety hold to review all safety data from participants for one month following the final participant's first vaccination (week 0) in Part A. Enrollment in Part B will not proceed without the formal approval of the Protocol Safety Review Team (PSRT). Similar to enrollment in Part A, Cohorts 1B and 2B in Part B will be enrolled concurrently. Randomization to study product or placebo will take place within each cohort.
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 96 participants (estimated)

IDs, dates and publications

ClinicalTrials.gov ID: NCT06694753
Sponsor's protocol ID: DESIIGN001/ IAVI G004
Acronym: IAVI G004
Status last verified: Jun 2026
First submitted: 5 Nov 2024
Last updated: 1 Jul 2026
Results posted: No
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: A primary manuscript will be prepared after the data analysis is available and the results of the study will be published in searchable, peer reviewed scientific literature according to the, allowing unrestricted access and reuse of all peer-reviewed published research.Underlying, anonymized datasets will be made publicly available. The final clinical study report will be made available to the principal investigators. The Sponsor will also provide investigators with the full summary of the study results, which the investigators may share with the study participants and stakeholders, as appropriate.

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?

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Study at a glance

From the registry record, last updated by the sponsor on 1 Jul 2026. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase 1, Placebo-controlled, Blinded, Dose-escalation Study to Evaluate the Safety and Immunogenicity of mRNAs Encoding HIV Immunogens (eOD-GT8 60mer, Core-g28v2 60mer, N332-GT5 gp151) in Adult Participants Without HIV and in Overall Good Health in South Africa.
ClinicalTrials.gov ID: NCT06694753
Acronym / sponsor ID: IAVI G004 / DESIIGN001/ IAVI G004
Conditions: HIV Infections
Keywords: HIV
Phase: Phase 1
Study type: Interventional
Recruitment status: Active, not recruiting
Enrolment: 96 participants (estimated)
Lead sponsor: International AIDS Vaccine InitiativeResearch network
Collaborators: ModernaTX, Inc., The Scripps Research Institute, National Institute of Allergy and Infectious Diseases (NIAID), Bill and Melinda Gates Foundation
Study start: 15 Dec 2025 (actual)
Primary completion: 8 Dec 2026 (estimated)
Study completion: 31 Mar 2027 (estimated)
First posted: 19 Nov 2024 (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.

Detailed description

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Sequential
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 8
Model description: Cohorts 1A and 2A in Part A will be enrolled concurrently. Randomization to study product or placebo will take place within each cohort. After Part A is fully enrolled, there will be a planned safety hold to review all safety data from participants for one month following the final participant's first vaccination (week 0) in Part A. Enrollment in Part B will not proceed without the formal approval of the Protocol Safety Review Team (PSRT). Similar to enrollment in Part A, Cohorts 1B and 2B in Part B will be enrolled concurrently. Randomization to study product or placebo will take place within each cohort.

Arm	Type	Receives
Cohort 1A Group 1: mRNA-1645-eODGT8 + mRNA-1645-CoreG28v2	Experimental	Biological: mRNA-1645-eODGT8, Biological: mRNA-1645-CoreG28v2Participants will receive one injection of 10 mcg mRNA-1645-eODGT8 to be administered as a 0.5 mL IM injection into the deltoid at Week 0 and one injection of 10 mcg mRNA-1645-CoreG28v2 to be administered as a 0.5 mL IM injection into the deltoid at Week 8.
Cohort 1A Group 2: Placebo	Placebo comparator	Biological: PlaceboParticipants will receive 0.9% sodium chloride to be administered as a 0.5-mL IM injection into the deltoid at Weeks 0 and 8.
Cohort 2A Group 3: mRNA-1645-N332GT5	Experimental	Biological: mRNA-1645-N332GT5Participants will receive 10 mcg of mRNA-1645-N332GT5 to be administered as a 0.5 mL IM injection into the deltoid at Weeks 0 and 8.
Cohort 2A Group 4: Placebo	Placebo comparator	Biological: PlaceboParticipants will receive 0.9% sodium chloride to be administered as a 0.5-mL IM injection into the deltoid at Week 0 and Week 8.
Cohort 1B Group 5: mRNA-1645-eODGT8 + mRNA-1645-CoreG28v2	Experimental	Biological: mRNA-1645-eODGT8, Biological: mRNA-1645-CoreG28v2Participants will receive one injection of 30 mcg mRNA-1645-eODGT8 to be administered as a 0.5 mL IM injection into the deltoid at Week 0 and one injection of 30 mcg mRNA-1645-CoreG28v2 to be administered as a 0.5 mL IM injection into the deltoid at Week 8.
Cohort 1B Group 6: Placebo	Placebo comparator	Biological: PlaceboParticipants will receive 0.9% sodium chloride to be administered as a 0.5-mL IM injection into the deltoid at Week 0 and Week 8.
Cohort 2B Group 7: mRNA-1645-N332GT5	Experimental	Biological: mRNA-1645-N332GT5Participants will receive 30 mcg of mRNA-1645-N332GT5 to be administered as a 0.5 mL IM injection into the deltoid at Weeks 0 and 8.
Cohort 2B Group 8: Placebo	Placebo comparator	Biological: PlaceboParticipants will receive 0.9% sodium chloride to be administered as a 0.5-mL IM injection into the deltoid at Week 0 and Week 8.

Who may qualify

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

Key inclusion criteria (29 listed)

Demonstrates an understanding of the study and is able and willing to complete the informed consent process.
18 to ≤ 55 years old, on day of enrollment.
Available for clinic follow-up through the last clinic visit.
Willingness to undergo FNA and leukapheresis.
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 IAVI Medical Monitor are required prior to enrollment into DESIIGN001/IAVI G004.

Key exclusion criteria (28 listed)

Volunteer is nursing or pregnant.
Body mass index (BMI) ≥40 kg/m2. Enrollment of individuals with BMI ≥40 kg/m2, whom the site investigator assesses are in good health, may be considered by the IAVI Medical Monitor.
Diabetes mellitus (DM). Type 2 DM controlled with diet alone (and confirmed by HgbA1c ≤7% 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 by the IAVI Medical Monitor on a case-by-case basis, provided that the HgbA1c is ≤8% within the last 6 months (CRC staff may draw these at screening).
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 authorizing this clinical trial.

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
mRNA-1645-eODGT8Also: eOD-GT8 60mer mRNAeOD-GT8 60mer is a self-assembling nanoparticle composed of 60 subunits of the engineered HIV-1 gp120 outer domain germline targeting version 8 (eOD-GT8) fused to an engineered form of a bacterial enzyme, Lumazine Synthase, through a 15-amino acid Glycine-Serine linker. eOD-GT8 60mer will be delivered using an mRNA lipid nanoparticle (LNP) platform. To be administered by intramuscular (IM) injection at doses of 10 or 30 mcg.	Biological	Cohort 1A Group 1: mRNA-1645-eODGT8 + mRNA-1645-CoreG28v2, Cohort 1B Group 5: mRNA-1645-eODGT8 + mRNA-1645-CoreG28v2
mRNA-1645-CoreG28v2Also: core-g28v2 60mer mRNAcore-g28v2 60mer is a nanoparticle composed of 60 protein subunits of an engineered core-gp120 fused to an engineered form of a bacterial enzyme, Lumazine Synthase, through a 21-amino acid Glycine-Serine linker. Core-g28v2 60mer will be delivered using an mRNA-LNP platform. To be administered by IM injection at doses of 10 or 30 mcg.	Biological	Cohort 1A Group 1: mRNA-1645-eODGT8 + mRNA-1645-CoreG28v2, Cohort 1B Group 5: mRNA-1645-eODGT8 + mRNA-1645-CoreG28v2
mRNA-1645-N332GT5Also: N332-GT5 gp151 mRNAN332-GT5 gp151 is an HIV envelope glycoprotein gp151 trimer based on BG505 SOSIP MD39 (clade A) trimer with "germline-targeting" mutations added that confer the ability to bind germline precursors of BG18 class B cells. N332-GT5 gp151 will be delivered using an mRNA-LNP platform. To be administered by IM injection at doses of 10 or 30 mcg.	Biological	Cohort 2A Group 3: mRNA-1645-N332GT5, Cohort 2B Group 7: mRNA-1645-N332GT5
PlaceboAlso: Saline, DiluentSaline	Biological	Cohort 1A Group 2: Placebo, Cohort 1B Group 6: Placebo, Cohort 2A Group 4: Placebo, Cohort 2B Group 8: Placebo

Primary outcome

To assess the incidence of local and systemic reactogenecity and treatment-emergent adverse events [Safety and Tolerability].
Time frame: Measured a minimum of 7 days following receipt of any study vaccination
* Local and systemic reactogenicity signs and symptoms will be collected for a minimum of 7 days following receipt of any study vaccination. * AEs leading to early participant withdrawal or permanent discontinuation, SAEs, medically attended adverse events (MAAEs), and AESIs will be collected throughout the study. Additionally, all AEs will be collected for 30 days after any receipt of study vaccination.
To evaluate the induction of VRC01- or BG18-class IgG B cell responses by the vaccine regimens.
Time frame: V01 [W0, baseline] V04 [W7.5, 7.5 wks. post 1st vacc.] V06 [W10, 2 wks. post 2nd vacc.] V07 [W15.5, 7.5 wks. post 2nd vacc.]
• Proportion of vaccinees with VRC01- or BG18-class IgG B cells, and frequency of VRC01- or BG18-class B cells among IgG+ B cells in PBMCs or in germinal centers, at baseline and after each study product administration, as determined by B-cell phenotyping and BCR sequencing.

1 secondary outcome

To evaluate vaccine-specific and epitope-specific binding Ab responses elicited by the vaccine regimens.
Time frame: Measured at baseline (at Week 0), 2 weeks post 1st vaccination (at Week 2), 7.5 weeks post 1st vaccination (at Week 7.5), 2 weeks post 2nd vaccination (at Week 10), and 7.5 weeks post 2nd vaccination (at Week 15.5)

Results and safety

This study is still under way. Results are not available in the source record yet.

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 1 Jul 2026.
Individual participant dataSharing planned: Yes. A primary manuscript will be prepared after the data analysis is available and the results of the study will be published in searchable, peer reviewed scientific literature according to the, allowing unrestricted access and reuse of all peer-reviewed published research.Underlying, anonymized datasets will be made publicly available. The final clinical study report will be made available to the principal investigators. The Sponsor will also provide investigators with the full summary of the study results, which the investigators may share with the study participants and stakeholders, as appropriate.

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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.

Linda-Gail Bekker principal investigator

Desmond Tutu Health Foundation/Center, University of Cape Town

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

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing mRNA-1645-eODGT8, mRNA-1645-CoreG28v2 and mRNA-1645-N332GT5 in people with HIV Infections, run by International AIDS Vaccine Initiative at 6 sites in South Africa.

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 29 inclusion and 28 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: under way, not looking for participants, as of the sponsor's last update on 1 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 South Africa. 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?

This study is still under way. Results are not available in the source record yet.

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?

To assess the incidence of local and systemic reactogenecity and treatment-emergent adverse events [Safety and Tolerability]. (time frame: Measured a minimum of 7 days following receipt of any study vaccination). The study lists 2 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 NCT06694753.

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 1 Jul 2026.