HIV Trimer mRNA Vaccines for HIV Prevention

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

Must not be taking: Immunosuppressants, Blood products

Disqualifiers: Pregnancy, Hypertension, Diabetes, Asthma, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 6 months

108 Participants Needed

Trial Summary

What is the purpose of this trial?

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 gp151 CD4KO HIV trimer mRNA. These trimers are based on the BG505 MD39 native-like trimer reported in Steichen et al. Immunity 2016. The primary hypothesis is that the BG505 MD39.3 soluble and membrane-bound trimer mRNA vaccines will be safe and well-tolerated among HIV-uninfected individuals and will elicit autologous neutralizing antibodies.

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.

What data supports the effectiveness of the HIV Trimer mRNA Vaccines for HIV Prevention treatment?

Research shows that similar HIV vaccines using trimeric envelope proteins can induce strong antibody responses, which are important for neutralizing the virus. For example, studies have demonstrated that these vaccines can trigger the production of antibodies that specifically target and neutralize HIV, suggesting potential effectiveness in preventing the virus. ^{1 2 3 4 5}

Is the HIV Trimer mRNA vaccine safe for humans?

The HIV Trimer mRNA vaccine, evaluated under different names, has been found to be safe and well tolerated in clinical trials, with most adverse events being mild (grade 1 or 2). Serious adverse events were rare and mostly unrelated to the vaccine itself. ^{1 6 7 8 9}

How does the HIV Trimer mRNA vaccine differ from other HIV treatments?

The HIV Trimer mRNA vaccine is unique because it uses mRNA technology to instruct cells to produce HIV-like proteins, potentially triggering an immune response without using live virus. This approach is different from traditional vaccines that often use weakened or inactivated viruses. ^{1 5 6 7 10}

Research Team

Sharon Riddler, MD

Principal Investigator

University of Pittsburgh

Jesse Clark, MD

Principal Investigator

University of California, Los Angeles

Eligibility Criteria

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.

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.

Timeline

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)

Treatment Details

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.

Participant Groups

Group I: Part B, Group 3: BG505 MD39.3 gp151 CD4KO mRNA Experimental Treatment 1 Intervention

18 participants Dose: 250mcg of BG505 MD39.3 gp151 CD4KO mRNA administered at months 0, 2, and 6

Group II: Part B, Group 2: BG505 MD39.3 gp151 mRNA Experimental Treatment 1 Intervention

18 participants Dose: 250mcg of BG505 MD39.3 gp151 mRNA administered at months 0, 2, and 6

Group III: Part B, Group 1: BG505 MD39.3 mRNA Experimental Treatment 1 Intervention

18 participants Dose: 250mcg of BG505 MD39.3 mRNA administered at months 0, 2, and 6

Group IV: Part A, Group 3: Low dose BG505 MD39.3 gp151 CD4KO mRNA Experimental Treatment 1 Intervention

18 participants Dose: 100mcg of BG505 MD39.3 gp151 CD4KO mRNA administered at months 0, 2, and 6

Group V: Part A, Group 2: Low dose BG505 MD39.3 gp151 mRNA Experimental Treatment 1 Intervention

18 participants Dose: 100mcg of BG505 MD39.3 gp151 mRNA administered at months 0, 2, and 6

Group VI: Part A, Group 1: Low dose BG505 MD39.3 mRNA Experimental Treatment 1 Intervention

18 participants Dose: 100mcg of BG505 MD39.3 mRNA formulated administered at months 0, 2, and 6

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+

Findings from Research

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

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]

References

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

Induction of HIV-1-neutralising and syncytium-inhibiting antibodies in uninfected recipients of HIV-1IIIB rgp120 subunit vaccine. [2019]

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

Targeting HIV-1 envelope glycoprotein trimers to B cells by using APRIL improves antibody responses. [2022]

3. England pubmed.ncbi.nlm.nih.gov

Long-term immunotherapy in HIV infection, combined with short-term antiretroviral treatment. [2013]

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

An HIV-1 vaccine based on bacterium-like particles elicits Env-specific mucosal immune responses. [2021]

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

HIV-1-neutralizing antibody induced by simian adenovirus- and poxvirus MVA-vectored BG505 native-like envelope trimers. [2023]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Therapeutic Vaccine in Chronically HIV-1-Infected Patients: A Randomized, Double-Blind, Placebo-Controlled Phase IIa Trial with HTI-TriMix. [2020]

7. England pubmed.ncbi.nlm.nih.gov

Preclinical evaluation of an mRNA HIV vaccine combining rationally selected antigenic sequences and adjuvant signals (HTI-TriMix). [2019]

8. England pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a modified vaccinia Ankara-based HIV-1 vaccine (MVA-B) in HIV-1-infected patients alone or in combination with a drug to reactivate latent HIV-1. [2022]

9. Netherlands pubmed.ncbi.nlm.nih.gov

Long-term safety analysis of preventive HIV-1 vaccines evaluated in AIDS vaccine evaluation group NIAID-sponsored Phase I and II clinical trials. [2019]

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

Production and Study of Immunochemical Properties of Stabilized Env Trimer of Recombinant Form CRF63_02A6 of HIV-1. [2023]