HIV Trimer mRNA Vaccines for HIV Prevention

Not currently recruiting at 9 trial locations
Age: 18 - 65
Sex: Any
Trial Phase: Phase 1
Sponsor: National Institute of Allergy and Infectious Diseases (NIAID)
Must be taking: PrEP
No Placebo GroupAll trial participants will receive the active study treatment (no placebo)

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests new mRNA-based vaccines designed to prevent HIV. Researchers aim to determine if these vaccines are safe and can effectively trigger the immune system to combat HIV. Different groups will receive various forms and doses of the vaccine to compare results. Individuals not infected with HIV and considered low-risk for acquiring it, such as those on stable pre-exposure prophylaxis (PrEP), might be suitable candidates for this trial. As a Phase 1 trial, participants will be among the first to receive this new treatment, aiding researchers in understanding its effects in people.

Do I need to stop my current medications to join the trial?

The trial does not specify if you need to stop taking your current medications. However, if you are on immunosuppressive medications, you must not have taken them within 168 days before the first vaccination. It's best to discuss your specific medications with the trial team.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the BG505 MD39.3 mRNA vaccines are generally safe and well-tolerated. In earlier studies, recipients developed immune responses, indicating that the body reacted to the vaccine as intended. However, some side effects have been reported. Specifically, one study found that many participants experienced chronic urticaria, meaning they had itchy skin rashes that persisted after vaccination.

This research remains in the early stages, with the primary focus on studying safety. The information gathered will help researchers understand how people react to the vaccine. For those considering joining a trial, this data helps set expectations about potential outcomes. Always consult a healthcare professional before deciding to participate in a clinical trial.12345

Why are researchers excited about this trial's treatments?

Researchers are excited about these HIV Trimer mRNA vaccines because they represent a novel approach to HIV prevention. Unlike traditional vaccines, which often rely on weakened or inactivated viruses, these vaccines use mRNA technology to instruct cells to produce proteins that mimic parts of the HIV virus, specifically targeting the BG505 MD39.3 protein structure. This method aims to trigger a stronger and more targeted immune response. The use of mRNA technology also allows for faster production and scalability, potentially speeding up the availability of effective vaccines. This approach could pave the way for more efficient and adaptable vaccines against HIV.

What evidence suggests that this trial's HIV trimer mRNA vaccines could be effective for HIV prevention?

Research shows that mRNA technology holds promise for creating an HIV vaccine. Previous studies have demonstrated that mRNA vaccines can stimulate the immune system to produce antibodies, which help fight infections. This trial tests the BG505 MD39.3 series of vaccines, including BG505 MD39.3 gp151 CD4KO mRNA, BG505 MD39.3 gp151 mRNA, and BG505 MD39.3 mRNA, in separate treatment arms. Early trials indicate that these vaccines can trigger an immune response, suggesting they might help prevent HIV. While more research is needed, these initial results are encouraging for the potential of these vaccines in preventing HIV.13567

Who Is on the Research Team?

JC

Jesse Clark, MD

Principal Investigator

University of California, Los Angeles

SR

Sharon Riddler, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

Healthy adults aged 18-55 who are HIV-negative, not pregnant or breastfeeding, and at low risk for HIV infection. They must be willing to use birth control if applicable, have normal blood counts and organ function tests, understand the study requirements, and commit to follow-up visits. Exclusions include poorly controlled hypertension, diabetes (except diet-controlled type 2), previous investigational HIV vaccine recipients (unless placebo), acute illness on vaccination day, recent immunosuppressants or blood products usage.

Inclusion Criteria

- 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
Serum creatinine ≤1.1 x ULN based on the institutional normal range
Negative for Hepatitis B surface antigen.
See 20 more

Exclusion Criteria

I have completed my COVID-19 vaccination series at least 4 weeks ago, or have approval for an exception.
I have a weakened immune system.
History of serious reaction (eg, hypersensitivity, anaphylaxis) to any vaccine or any component of the study vaccine.
See 30 more

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive BG505 MD39.3 mRNA, BG505 MD39.3 gp151 mRNA, or BG505 MD39.3 gp151 CD4KO mRNA at doses of 100 mcg or 250 mcg, administered via intramuscular injections at months 0, 2, and 6

6 months
3 visits (in-person)

Safety Evaluation

Sentinel safety groups are evaluated for safety 2 weeks after the first vaccination, with routine safety evaluations throughout the trial

Throughout the trial

Follow-up

Participants are monitored for safety and effectiveness after treatment, including measurement of serum IgG binding antibodies and CD4+ T-cell responses

52 weeks
Multiple visits (in-person and virtual)

What Are the Treatments Tested in This Trial?

Interventions

  • BG505 MD39.3 gp151 CD4KO mRNA
  • BG505 MD39.3 gp151 mRNA
  • BG505 MD39.3 mRNA
Trial Overview The trial is testing three different mRNA vaccines based on the BG505 MD39 HIV trimer: BG505 MD39.3 alone; with gp151; and with gp151 CD4KO. It's an early-phase study assessing safety and whether these vaccines can stimulate the body's immune system to produce antibodies against HIV in people without the virus.
How Is the Trial Designed?
6Treatment groups
Experimental Treatment
Group I: Part B, Group 3: BG505 MD39.3 gp151 CD4KO mRNAExperimental Treatment1 Intervention
Group II: Part B, Group 2: BG505 MD39.3 gp151 mRNAExperimental Treatment1 Intervention
Group III: Part B, Group 1: BG505 MD39.3 mRNAExperimental Treatment1 Intervention
Group IV: Part A, Group 3: Low dose BG505 MD39.3 gp151 CD4KO mRNAExperimental Treatment1 Intervention
Group V: Part A, Group 2: Low dose BG505 MD39.3 gp151 mRNAExperimental Treatment1 Intervention
Group VI: Part A, Group 1: Low dose BG505 MD39.3 mRNAExperimental Treatment1 Intervention

Find a Clinic Near You

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials
3,361
Recruited
5,516,000+

Department of Health and Human Services

Collaborator

Trials
240
Recruited
944,000+

National Institutes of Health (NIH)

Collaborator

Trials
2,896
Recruited
8,053,000+

Published Research Related to This Trial

The HTI-TriMix vaccine was found to be safe and well tolerated in HIV-1-infected individuals, with only 18% of adverse events related to the vaccine and no significant safety concerns reported.
Despite the safety of the vaccine, the study did not demonstrate significant immunogenic effects or differences in viral load rebound dynamics after antiretroviral therapy interruption, indicating that the vaccine may not effectively enhance immune responses against HIV-1.
Therapeutic Vaccine in Chronically HIV-1-Infected Patients: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Trial with HTI-TriMix.Jong, W., Leal, L., Buyze, J., et al.[2020]
The new mRNA-based therapeutic vaccine, combining activation signals (TriMix) with HIV-specific antigens, effectively activated dendritic cells from HIV-infected individuals, leading to enhanced T-cell responses and cytokine production.
In mouse models, the vaccine not only increased antigen-specific cytotoxic T-lymphocyte responses but also showed that the addition of TriMix further boosted these immune responses, indicating its potential for developing effective therapeutic HIV vaccines.
Preclinical evaluation of an mRNA HIV vaccine combining rationally selected antigenic sequences and adjuvant signals (HTI-TriMix).Guardo, AC., Joe, PT., Miralles, L., et al.[2019]

Citations

Study Details | NCT05217641 | A Clinical Trial to Evaluate ...This is an open-label, multicenter, randomized phase 1 study to evaluate the safety and immunogenicity of BG505 MD39.3, BG505 MD39.3 gp151, and BG505 MD39.3 ...
Vaccination with mRNA-encoded membrane-anchored HIV ...Abstract. mRNA technology might accelerate development of an urgently needed preventive human immunodeficiency virus (HIV) vaccine.
mRNA-based vaccine technology for HIV - PMCThis article provides an overview over HIV infection and introduces mRNA vaccines and their potential in HIV vaccine development.
NIH Launches Clinical Trial of Three mRNA HIV VaccinesThe HVTN 302 study will examine whether the following three experimental HIV mRNA vaccines are safe and can induce an immune response: 1) BG505 ...
Prophylactic HIV-1 vaccine trials: past, present, and futuremRNA. BG505 MD39.3 gp151, BG505 MD39.3 gp151, and BG505. MD39.3 gp151 CD4KO HIV trimer mRNA vaccines. NCT05217641. Germline targeted. mRNA. eOD-GT8 60mer mRNA ...
Vaccination with mRNA-encoded membrane-anchored HIV ...BG505 MD39.3 trimer–specific IgG+ memory B cell responses were detected in all groups after two vaccinations, with response rates of 81.2 to 100 ...
High Frequency of Chronic Urticaria Following an ...Investigational HIV-1 BG505 MD39.3 trimer mRNA vaccines (gp140 soluble trimer, gp151 membrane-bound trimer, and gp151 CD4KO membrane-bound ...
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