Vaccines for HIV Prevention

Recruiting at 7 trial locations

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

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

Must not be taking: Systemic glucocorticoids, Blood products

Disqualifiers: Pregnancy, Diabetes, Immunodeficiency, Seizure disorder, others

Stay on Your Current Meds You can continue your current medications while participating

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

Compensation: Varies

Number of Visits: 5

Duration: 12 months

45 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, if you are on medications that might impair your immune response, such as certain systemic medications, you may need to discuss this with the trial team.

What data supports the effectiveness of the treatment 16055 NFL Delta Gly4 Env Protein Trimer, Ad4-Env145NFL Viral Particles, Trimer 4571 for HIV prevention?

Research on similar HIV vaccine components, like stabilized Env trimers, shows they can induce strong antibody responses, which are crucial for protection against HIV. Studies have demonstrated that combinations of different Env trimers can enhance the immune response, suggesting that the treatment may be effective in generating protective antibodies. ^{1 2 3 4 5}

Is the HIV vaccine candidate safe for humans?

The HIV vaccine candidates, including those using Env proteins, have been generally well-tolerated in early human trials, with no major safety concerns reported. ^{1 5 6 7 8}

How does the treatment 16055 NFL Delta Gly4 Env Protein Trimer, Ad4-Env145NFL Viral Particles, Trimer 4571 differ from other HIV prevention treatments?

This treatment is unique because it uses a trimeric form of the HIV envelope protein, which better mimics the natural structure of the virus and is designed to induce a stronger immune response by generating broadly neutralizing antibodies. Unlike previous vaccines that used monomeric forms, this approach aims to improve the effectiveness against diverse HIV strains. ^{2 5 7 9 10}

What is the purpose of this trial?

The goal of this clinical trial is to test 16055 NFL delta Gly4 Env protein trimer and Trimer 4571 combined with 3M-052-AF + Alum adjuvant and Ad4-Env145NFL viral particles as heterologous prime-boost regimens in adult participants without HIV. The main question\[s\] it aims to answer are: * Are these vaccine regimens safe and well tolerated? * Are the prime-boost vaccine regimens that include Ad4-Env145NFL and Trimer 4571 as heterologous boosts going contribute to the development of B-cell and antibody responses? Participants will attend scheduled study visits to receive their vaccine and will record symptoms on a daily eDiary.

Eligibility Criteria

This trial is for adults without HIV who are interested in testing new vaccine regimens aimed at preventing HIV/AIDS. Participants must attend scheduled visits and keep a daily eDiary of symptoms.

Inclusion Criteria

Platelet count within specified range

Negative for Hepatitis B surface antigen

Negative HIV test results by specified methods

Exclusion Criteria

I have had cancer within the specified timeframe.

Living with a chronic or clinically significant condition that may jeopardize safety or rights of the study participant

I have asthma.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the study vaccines as heterologous prime-boost regimens at months 0, 2, 4, 8, and 12

12 months

5 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including antibody response measurements

26 weeks

Treatment Details

Interventions

• 16055 NFL Delta Gly4 Env Protein Trimer
• Ad4-Env145NFL Viral Particles
• Trimer 4571

Trial Overview The study tests the safety and immune response to two experimental vaccines (16055 NFL delta Gly4 Env protein trimer and Trimer 4571) with an adjuvant, plus a viral particle booster (Ad4-Env145NFL).

Participant Groups

Group I: Treatment 3 Experimental Treatment 3 Interventions

16055 NFL delta Gly4 trimer, 200 mcg admixed with 3M-052-AF, 5 mcg and Alum, 500 mcg to be administered as 2 separate IM injections (0.27 mL each) at months 0 and 2. Trimer 4571, 100 mcg admixed with 3M-052-AF, 5 mcg and Alum, 500 mcg to be administered as 2 separate IM injections (0.2 mL each) at month 4. Ad4-Env145NFL, 5 x 108 vp to be administered IN (0.07 mL into 1 nostril) at months 8 and 12.

Group II: Treatment 2 Experimental Treatment 3 Interventions

16055 NFL delta Gly4 trimer, 200 mcg admixed with 3M-052-AF, 5 mcg and Alum, 500 mcg to be administered as 2 separate IM injections (0.27 mL each) at months 0 and 2. Ad4-Env145NFL, 5 x 108 viral particles (vp) to be administered intranasally (IN) (0.07 mL into 1 nostril) at month 4. Trimer 4571, 100 mcg admixed with 3M-052-AF, 5 mcg and Alum, 500 mcg to be administered as 2 separate IM injections (0.2 mL each) at months 8 and 12.

Group III: Treatment 1 Experimental Treatment 1 Intervention

16055 NFL delta Gly4 trimer, 200 mcg admixed with 3M-052-AF, 5 mcg and Alum, 500 mcg to be administered as 2 separate intramuscular (IM) injections (0.27 mL each) at months 0, 2, 4, 8, and 12.

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

References

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

Safety and immunogenicity of a genetically engineered human immunodeficiency virus vaccine. [2019]

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

Purification, characterization, and immunogenicity of a soluble trimeric envelope protein containing a partial deletion of the V2 loop derived from SF162, an R5-tropic human immunodeficiency virus type 1 isolate. [2019]

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

Characterization and immunogenicity of a novel mosaic M HIV-1 gp140 trimer. [2021]

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

A multivalent clade C HIV-1 Env trimer cocktail elicits a higher magnitude of neutralizing antibodies than any individual component. [2018]

5. 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]

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

Parainfluenza Virus 5 Priming Followed by SIV/HIV Virus-Like-Particle Boosting Induces Potent and Durable Immune Responses in Nonhuman Primates. [2021]

7. Netherlands pubmed.ncbi.nlm.nih.gov

Safety and immunogenicity of a recombinant oligomeric gp145 subtype C Env protein (gp145 C.6980) HIV vaccine candidate in healthy, HIV-1-uninfected adult participants in the US. [2023]

8. China pubmed.ncbi.nlm.nih.gov

[Progress in HIV-1 Env trimer design]. [2020]

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

Crystal structure, conformational fixation and entry-related interactions of mature ligand-free HIV-1 Env. [2019]

10. Switzerland pubmed.ncbi.nlm.nih.gov

Nanoparticle Vaccines for Inducing HIV-1 Neutralizing Antibodies. [2023]