HIV Vaccine for HIV Prevention

Recruiting at 5 trial locations

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)

Must be taking: PrEP

Must not be taking: Glucocorticoids, Immunoglobulin, others

Disqualifiers: Pregnancy, Obesity, Diabetes, Seizure, others

Compensation: Varies

Number of Visits: 4

52 Participants Needed

Trial Summary

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, certain medications like systemic glucocorticoids or recent vaccines might affect eligibility, so it's best to discuss your specific situation with the trial team.

What data supports the effectiveness of the HIV vaccine treatment 426c.Mod.Core-C4b, 426c.Mod.Core-C4b vaccine, 426c.Mod.Core-C4b adjuvanted with 3M-052-AF + Alum?

The RV144 clinical trial showed that a similar HIV vaccine regimen could reduce transmission by 31%, with initial efficacy potentially exceeding 70% before declining over time. Additionally, adjuvants like alum, used in the 426c.Mod.Core-C4b vaccine, are known to enhance immune responses, which is crucial for the effectiveness of vaccines. ^{1 2 3 4 5}

Is the 426c.Mod.Core-C4b vaccine safe for humans?

There is no specific safety data available for the 426c.Mod.Core-C4b vaccine in the provided research articles. ^{1 3 6 7 8}

What makes the 426c.Mod.Core-C4b vaccine unique for HIV prevention?

The 426c.Mod.Core-C4b vaccine is unique because it combines a specific HIV vaccine component with a novel adjuvant, 3M-052-AF, and Alum, which are designed to enhance the immune response. This combination aims to improve the vaccine's effectiveness compared to traditional vaccines that often use only Alum as an adjuvant. ^{1 3 4 5 8}

What is the purpose of this trial?

This trial is testing two vaccine methods to help people at risk of HIV infection produce special antibodies that can fight many types of HIV. The vaccine works by training the immune system to make strong antibodies that block HIV.

Research Team

Hyman Scott, MD

Principal Investigator

University of California, San Francisco

Kristen Cohen, MD

Principal Investigator

Fred Hutch Cancer Center, Seattle, WA

Eligibility Criteria

Healthy adults aged 18-55, at low risk for HIV, not pregnant or breastfeeding, with stable vital signs and normal blood work. Participants must understand the study details and consent to follow-up visits including lymph node sampling. They should not be on other investigational drugs or have conditions that could affect vaccine response.

Inclusion Criteria

I am willing and able to understand and sign the consent form.

Agrees not to enroll in another study of an investigational agent during participation in the trial

Alanine aminotransferase (ALT) < 2.5 x upper limit of normal (ULN)

Exclusion Criteria

Investigator concern for difficulty with venous access based upon clinical history and physical examination

International normalized ratio (INR) >1.2

I do not have a spleen or my spleen does not work properly.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Priming Regimen

Participants receive priming vaccine regimens to activate and induce the maturation of cross-reactive CD4 binding site antibodies

3 months

2 visits (in-person)

Boost Regimen

Optional boost regimen with BG505 SOSIP.GT1.1 gp140 to further mature B-cell lineages

3 months

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

64 weeks

Treatment Details

Interventions

• 426c.Mod.Core-C4b

Trial Overview The trial is testing different doses of a 'germline-targeting' HIV vaccine called 426c.Mod.Core-C4b against a placebo. It aims to see if the vaccine can induce special antibodies known as VRC01-class that are effective across all types of HIV strains.

Participant Groups

Group I: Optional Boost Regimen with BG505 Experimental Treatment 1 Intervention

SOSIP.GT1.1 gp140

Group II: Fractionated Delivery, Group 2: First injection - Medium dose, Final injection - Higher dose Experimental Treatment 2 Interventions

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.

Group III: Fractionated Delivery, Group 1: First injection - Medium dose, Final injection - Lower dose Experimental Treatment 2 Interventions

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.

Group IV: Bolus Delivery, Group 2: First injection - Medium dose, Final injection - Higher dose Experimental Treatment 2 Interventions

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.

Group V: Bolus Delivery, Group 1: First injection - Medium dose, Final injection - Lower dose Experimental Treatment 2 Interventions

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.

Group VI: Bolus Delivery, Group 3: First injection - Placebo, Final injection - Placebo Placebo Group 1 Intervention

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.

Group VII: Fractionated Delivery, Group 3: First injection - Placebo, Final injection - Placebo Placebo Group 1 Intervention

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.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Department of Health and Human Services

Collaborator

Trials

240

Recruited

944,000+

Findings from Research

The Trimer 4571 HIV-1 vaccine was found to be safe and well-tolerated in a phase I trial involving 16 HIV-negative adults, with mild to moderate side effects and no serious adverse events reported.

The vaccine induced specific antibody responses in 44% of participants, particularly at the higher 500 mcg dose, suggesting its potential as a component in future HIV vaccine strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of an HIV-1 prefusion-stabilized envelope trimer (Trimer 4571) vaccine in healthy adults: A first-in-human open-label, randomized, dose-escalation, phase 1 clinical trial. Houser, KV., Gaudinski, MR., Happe, M., et al.[2022]

The RV306 trial, involving 367 healthy HIV-uninfected participants, found that additional vaccine boosts at longer intervals after the initial RV144 regimen significantly improved immune responses, particularly in antibody levels against HIV antigens.

No serious vaccine-related adverse events were reported, indicating that the additional boosts were safe and well-tolerated, which is crucial for the potential efficacy of the vaccine in preventing HIV acquisition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late boosting of the RV144 regimen with AIDSVAX B/E and ALVAC-HIV in HIV-uninfected Thai volunteers: a double-blind, randomised controlled trial. Pitisuttithum, P., Nitayaphan, S., Chariyalertsak, S., et al.[2021]

A phase 1 trial involving 36 healthy participants demonstrated that shorter, 6-month regimens of a mosaic HIV-1 vaccine elicited strong immune responses comparable to a longer, 12-month regimen, suggesting they could be effective for HIV prevention.

All vaccine regimens were well tolerated, with mild-to-moderate side effects reported, indicating a favorable safety profile, which is crucial for community-level vaccine delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of shortened mosaic HIV-1 vaccine schedules: a randomised, double-blind, placebo-controlled phase 1 trial (IPCAVD010/HPX1002) and a preclinical study in rhesus monkeys (NHP 17-22). Stephenson, KE., Wegmann, F., Tomaka, F., et al.[2021]

The study tested HIV clade B/C vaccine candidates in macaques and found that high doses of Aluminum hydroxide (Alum) led to protective serum IgG responses, reducing the risk of acquiring Tier 1 SHIV-C viruses.

In contrast, low doses of Alum increased the risk of acquiring Tier 2 SHIV-C viruses, while the MF59 adjuvant showed a different immune response that effectively decreased the risk of Tier 1 SHIV-C acquisition, highlighting the importance of the adjuvant type in vaccine efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type. Schifanella, L., Barnett, SW., Bissa, M., et al.[2020]

References

1. England pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of an HIV-1 prefusion-stabilized envelope trimer (Trimer 4571) vaccine in healthy adults: A first-in-human open-label, randomized, dose-escalation, phase 1 clinical trial. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

The cost-effectiveness of a modestly effective HIV vaccine in the United States. [2021]

3. Netherlands pubmed.ncbi.nlm.nih.gov

Late boosting of the RV144 regimen with AIDSVAX B/E and ALVAC-HIV in HIV-uninfected Thai volunteers: a double-blind, randomised controlled trial. [2021]

4. Netherlands pubmed.ncbi.nlm.nih.gov

Comparison of shortened mosaic HIV-1 vaccine schedules: a randomised, double-blind, placebo-controlled phase 1 trial (IPCAVD010/HPX1002) and a preclinical study in rhesus monkeys (NHP 17-22). [2021]

5. England pubmed.ncbi.nlm.nih.gov

The role of adjuvants in retroviral vaccines. [2019]

6. Netherlands pubmed.ncbi.nlm.nih.gov

Strong and persistent CD4+ T-cell response in healthy adults immunized with a candidate HIV-1 vaccine containing gp120, Nef and Tat antigens formulated in three Adjuvant Systems. [2010]

7. United States pubmed.ncbi.nlm.nih.gov

The F4/AS01B HIV-1 Vaccine Candidate Is Safe and Immunogenic, But Does Not Show Viral Efficacy in Antiretroviral Therapy-Naive, HIV-1-Infected Adults: A Randomized Controlled Trial. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type. [2020]