HIV-1 Envelope Trimer Vaccine for HIV Prevention

Recruiting at 11 trial locations

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

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

Must not be taking: Glucocorticoids, Blood products

Disqualifiers: Pregnancy, Diabetes, Immunodeficiency, others

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

Compensation: Varies

Number of Visits: 4

36 Participants Needed

Trial Summary

What is the purpose of this trial?

This trial tests a new two-step HIV treatment in humans for the first time. The first shot introduces a protein to help the immune system recognize HIV. The second shot uses mRNA to boost the immune response by teaching the body to make a part of the virus. The goal is to produce antibodies that can neutralize HIV.

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, like certain steroids, you might need to discuss this with the trial team.

What data supports the effectiveness of the HIV-1 Envelope Trimer Vaccine for HIV Prevention treatment?

Research shows that using a mixture of HIV-1 envelope proteins can lead to stronger immune responses, including neutralizing antibodies, which are important for fighting off the virus. This suggests that the vaccine strategy used in the trial could be effective in enhancing the body's defense against HIV. ^{1 2 3 4 5}

Is the HIV-1 Envelope Trimer Vaccine safe for humans?

The HIV-1 envelope-based vaccines, including those similar to the V3G CH848 mRNA-Tr2 and V3G CH848 Pr-NP1, have been generally well tolerated in clinical trials with no serious long-term side effects. Some participants experienced mild local reactions or temporary systemic reactions, but these were not severe. ^{3 4 6 7 8}

What makes the HIV-1 Envelope Trimer Vaccine for HIV Prevention unique?

This vaccine uses a stabilized HIV-1 envelope glycoprotein trimer, which is designed to induce a strong and broad neutralizing antibody response, potentially offering better protection against diverse HIV strains compared to single-envelope vaccines. ^{3 9 10 11 12}

Eligibility Criteria

Adults aged 18-55 in good health, willing to consent and available for follow-up. They must not be at high risk of HIV, agree to avoid risky behaviors, and use effective birth control if applicable. Excluded are those with BMI ≥ 40, diabetes, immunodeficiencies, certain allergies or conditions that could compromise safety.

Inclusion Criteria

For volunteers of reproductive potential, agreement to use effective means of birth control and negative beta human chorionic gonadotropin (β-HCG) pregnancy test on day of enrollment

Platelets between 125,000 to 550,000/mm3

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

Exclusion Criteria

Previous or current recipient of an investigational HIV vaccine

I have had myocarditis or pericarditis in the past.

Receipt of non-HIV experimental vaccine(s) within the last 1 year with exceptions

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Priming Treatment

Participants receive 3 doses of V3G CH848 Pr-NP1 combined with adjuvants at months 0, 2, and 6

6 months

3 visits (in-person)

Boost Treatment

Participants receive 1 dose of V3G CH848 mRNA-Tr2 at month 10

1 month

1 visit (in-person)

Follow-up

Participants are monitored for safety and immunogenicity, including T-cell and antibody responses

2 weeks after each treatment phase

Treatment Details

Interventions

• V3G CH848 mRNA-Tr2
• V3G CH848 Pr-NP1

Trial Overview The trial tests a prime-boost vaccine strategy against HIV using ferritin nanoparticles (V3G CH848 Pr-NP1) followed by an mRNA lipid nanoparticle (V3G CH848 mRNA-Tr2). It aims to induce antibodies targeting the virus's envelope protein.

Participant Groups

Group I: Group 4: V3G CH848 Pr-NP1 with ACU-026-001-1 Experimental Treatment 3 Interventions

3 doses of V3G CH848 Pr-NP1 (100 mcg) combined with ACU-026-001-1 (2.0 mg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit

Group II: Group 3: V3G CH848 Pr-NP1 with 3M-052-AF + Alum Experimental Treatment 4 Interventions

3 doses of V3G CH848 Pr-NP1 (100 mcg) combined with 3M-052-AF (5 mcg) and Alum (500 mcg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit

Group III: Group 2: Low dose V3G CH848 Pr-NP1 with ACU-026-001-1 Experimental Treatment 3 Interventions

3 doses of V3G CH848 Pr-NP1 (60 mcg) combined with ACU-026-001-1 (2.0 mg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit

Group IV: Group 1: Low dose V3G CH848 Pr-NP1 with 3M-052-AF + Alum Experimental Treatment 4 Interventions

3 doses of V3G CH848 Pr-NP1 (60 mcg) combined with 3M-052-AF (5 mcg) and Alum (500 mcg) at the month 0, 2, and 6 visits, followed by 1 dose of V3G CH848 mRNA-Tr2 (50 mcg) at the month 10 visit

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

Findings from Research

Recent advancements in HIV-1 vaccine development have led to a better understanding of the virus's structure and function, resulting in innovative vaccine strategies that show promise in eliciting immune responses.

Several vaccine candidates are currently in clinical trials, with some demonstrating the ability to reduce disease severity in nonhuman primates, indicating potential effectiveness in humans, even if they do not completely prevent infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Current advances and challenges in HIV-1 vaccines. Rodriguez-Chavez, IR., Allen, M., Hill, EL., et al.[2019]

In a study involving 1398 healthy HIV-negative volunteers across 26 clinical trials, candidate HIV-1 vaccines were generally well tolerated, with only mild to moderate local and systemic reactions linked to certain adjuvants.

No serious adverse effects or significant immunosuppressive events were reported, indicating that the envelope-based recombinant or synthetic HIV-1 vaccines are safe and pave the way for more complex vaccine testing.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety profile of phase I and II preventive HIV type 1 envelope vaccination: experience of the NIAID AIDS Vaccine Evaluation Group. Keefer, MC., Wolff, M., Gorse, GJ., et al.[2007]

Over 1500 healthy individuals have participated in studies of HIV-1 vaccines, which have shown good safety profiles with no serious toxicity reported, indicating that these vaccines are well tolerated.

Candidate vaccines, particularly those using gp120 and vaccinia vectors, successfully induce immune responses, including neutralizing antibodies and cytotoxic T cell activity, although they currently only neutralize laboratory-adapted HIV-1 strains, not primary isolates.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Human studies in the development of human immunodeficiency virus vaccines. Dolin, R.[2019]

The BG505 SOSIP.664 and 1086.C gp140 vaccine candidates showed superior binding to broadly neutralizing antibodies compared to the less effective 1086.C gp120 monomer, indicating their potential as more promising HIV vaccine candidates.

A systematic approach to vaccine selection, focusing on structure, antigenicity, immunogenicity, and efficacy, is recommended to optimize resource use and improve the chances of successful HIV vaccine development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A Systematic Approach to HIV-1 Vaccine Immunogen Selection. Bontempo, A., Garcia, MM., Rivera, N., et al.[2021]

References

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

Current advances in HIV vaccines. [2019]

2. 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]

3. 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]

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

HIV-1 vaccines: challenges and new perspectives. [2021]

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

Current advances and challenges in HIV-1 vaccines. [2019]

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

Safety profile of phase I and II preventive HIV type 1 envelope vaccination: experience of the NIAID AIDS Vaccine Evaluation Group. [2007]

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

Human studies in the development of human immunodeficiency virus vaccines. [2019]

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

Accelerating HIV-1 Vaccine Efficacy Trials. [2018]

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

Stabilized HIV-1 envelope glycoprotein trimers for vaccine use. [2019]

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

Multi-envelope HIV vaccine safety and immunogenicity in small animals and chimpanzees. [2018]

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

A Systematic Approach to HIV-1 Vaccine Immunogen Selection. [2021]

12. 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]