HIV Vaccine for HIV Infection

(NETI Trial)

Recruiting in Palo Alto (17 mi)

+2 other locations

Overseen by Madhu Choudhary, MD

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 1

Waitlist Available

Sponsor: Madhu Chhanda Choudhary

Must be taking: Antiretrovirals

Must not be taking: Immunomodulators, Chemotherapy

Disqualifiers: Pregnancy, Chronic inflammatory conditions, others

Trial Summary

What is the purpose of this trial?

This trial is testing a new vaccine called Trimer 4571 to see if it can help people with HIV by making their immune system produce special proteins that fight the virus. The study will involve about 32 participants over several months. Researchers aim to find out if the vaccine is safe and effective in boosting the body's defense against HIV.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must have been on a stable antiretroviral therapy (ART) for at least 8 weeks before joining. You cannot use certain medications like systemic immunomodulators or investigational therapies within 60 days before the study.

What data supports the effectiveness of the treatment Trimer 4571 Therapeutic Vaccination, Trimer 4571, BG505 DS-SOSIP.664 for HIV infection?

Research shows that the BG505 SOSIP.664 trimer, a component of the treatment, can induce neutralizing antibodies in animal models, which are important for fighting HIV. This suggests that the treatment might help the immune system target the virus effectively. ^{1 2 3 4 5}

Is the Trimer 4571 HIV vaccine safe for humans?

The Trimer 4571 HIV vaccine was tested in a phase 1 clinical trial with healthy adults and was found to be safe and well-tolerated. ^{6 7 8 9 10}

What makes the Trimer 4571 therapeutic vaccination unique compared to other HIV treatments?

Trimer 4571, also known as BG505 DS-SOSIP.664, is unique because it uses a stabilized HIV-1 envelope protein trimer to elicit broadly neutralizing antibodies, which are crucial for effective immune response against diverse HIV strains. This approach focuses on inducing a strong and broad immune response, unlike traditional treatments that primarily manage the virus rather than prevent infection. ^{1 3 5 11 12}

Research Team

Madhu Choudhary, MD

Principal Investigator

University of Pittsburgh

Eligibility Criteria

Adults over 18 living with HIV on stable antiretroviral therapy (ART) for at least 24 months, with undetectable viral loads and no history of severe allergies or chronic inflammatory conditions. Participants must not be pregnant, breastfeeding, or have a BMI over 40kg/m2, and should agree to use contraception during the trial.

Inclusion Criteria

For persons who can become pregnant, negative serum or urine pregnancy test within 48 hours prior to entry

I have been on consistent HIV medication for at least 2 years without a break longer than 30 days.

HIV-1 infection, documented by any FDA-approved assay

Exclusion Criteria

I have been treated for hepatitis C within the last 6 months.

You have a very high body weight for your height.

Currently breastfeeding or pregnant

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive the Trimer 4571 vaccine or placebo at Day 0, Week 8, and Week 20

20 weeks

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment

24 weeks

8 visits (in-person)

Treatment Details

Interventions

• Trimer 4571 Therapeutic Vaccination (Cancer Vaccine)

Trial Overview The Trimer 4571 vaccine is being tested in two different doses combined with alum as an adjuvant against placebo controls. The study aims to see if it's safe for people with HIV and whether it can stimulate the immune system to produce antibodies against HIV.

Participant Groups

Group I: Randomized Blinded Trimer 4571 Vaccine 500mcg Experimental Treatment 1 Intervention

Eighteen (18) participants will receive Trimer 4571 vaccine 500mcg with 500mcg alum adjuvant as a 1.1ml intramuscular injection at Day 0, Week 8 and Week 20.

Group II: Randomized Blinded Trimer 4571 Vaccine 100mcg Experimental Treatment 1 Intervention

Six (6) participants will receive Trimer 4571 vaccine 100mcg with 500mcg alum adjuvant as a 1ml intramuscular injection at Day 0, Week 8 and Week 20.

Group III: Randomized Blinded Placebo for Trimer 4571 Vaccine 100mcg Placebo Group 1 Intervention

Two (2) participants will receive the placebo control for Trimer 4571 vaccine 100mcg as a 1ml intramuscular injection at Day 0, Week 8 and Week 20.

Group IV: Randomized Blinded Placebo for Trimer 4571 Vaccine 500mcg Placebo Group 1 Intervention

Six (6) participants will receive the placebo control for Trimer 4571 vaccine 500mcg as a 1.1ml intramuscular injection at Day 0, Week 8 and Week 20.

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

HIV/AIDS Clinical Research Unit / University of Pittsburgh Pittsburgh, PA

AIDS Clinical Trials Unit/The Ohio State University Columbus, OH

University of Pittsburgh Pittsburgh, PA

Who Is Running the Clinical Trial?

Madhu Chhanda Choudhary

Lead Sponsor

Trials

1

Recruited

30+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3361

Recruited

5,516,000+

Dr. Jeanne Marrazzo

National Institute of Allergy and Infectious Diseases (NIAID)

Chief Executive Officer since 2023

MD, MPH

Dr. H. Clifford Lane

National Institute of Allergy and Infectious Diseases (NIAID)

Chief Medical Officer

MD

Findings from Research

The study successfully developed stable cell lines (293 T and CHO Flp-In™) that produce high-quality HIV-1 envelope glycoprotein SOSIP.664 trimers at yields of 12-15 mg per 1 × 10^9 cells, which is significantly higher than transient transfection methods.

These trimers maintain a native-like structure and appropriate antigenic properties, making them suitable for further immunogenicity testing in animals and potential use in human clinical trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Stable 293 T and CHO cell lines expressing cleaved, stable HIV-1 envelope glycoprotein trimers for structural and vaccine studies. Chung, NP., Matthews, K., Kim, HJ., et al.[2021]

The newly developed HIV-1 vaccine candidate, GT1.1, shows similar physicochemical properties and stability to its parental trimer, BG505 SOSIP.664, indicating it is a viable candidate for further development.

The assessment suggests that the formulation and storage conditions used for the parental trimer can be applied to GT1.1, paving the way for its progression to phase I clinical studies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Developability Assessment of Physicochemical Properties and Stability Profiles of HIV-1 BG505 SOSIP.664 and BG505 SOSIP.v4.1-GT1.1 gp140 Envelope Glycoprotein Trimers as Candidate Vaccine Antigens. Whitaker, N., Hickey, JM., Kaur, K., et al.[2020]

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 LFn-p24C therapeutic HIV vaccine was found to be safe and well-tolerated in a Phase I trial with 30 HIV-positive volunteers, who were already on stable antiretroviral therapy.

After vaccination, participants showed significantly higher CD4 counts and 30% of those who underwent a treatment interruption did not experience viral rebound, indicating potential benefits in boosting immune response against HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Therapeutic immunization in HIV infected Ugandans receiving stable antiretroviral treatment: a Phase I safety study. Kityo, C., Bousheri, S., Akao, J., et al.[2021]

The V-1 Immunitor HIV vaccine was well tolerated in a study of 40 patients, showing no significant adverse effects and resulting in a mean body weight gain of 2.2 kg over 27 weeks.

The vaccine led to significant increases in CD4 and CD8 cell counts, with increases of 51 (18%) and 172 (16%) cells/mm3 respectively, suggesting potential efficacy in enhancing immune response against HIV.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of an oral HIV vaccine (V-1 Immunitor) in AIDS patients at various stages of the disease. Jirathitikal, V., Bourinbaiar, AS.[2004]

Vacc-4x, a peptide-based HIV-1 therapeutic vaccine, was found to be safe and well-tolerated, with immunogenic responses in both CD4 and CD8 T-cell populations, indicating its potential for future HIV cure strategies.

While the vaccine did not significantly reduce the need for cART or improve CD4 counts during treatment interruption, it did lead to a notable reduction in viral load after cART was paused, suggesting it may help control HIV replication.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4x: a phase 2 randomised, double-blind, placebo-controlled trial. Pollard, RB., Rockstroh, JK., Pantaleo, G., et al.[2014]

The study demonstrated that BG505 SOSIP.664-2dCD4S60C and FVCEnv SOSIP.664-2dCD4S60C elicited strong and broadly neutralizing antibody responses in New Zealand white rabbits, achieving 70.5% and 76% potency against a challenging panel of 17 HIV-1 pseudoviruses.

The effectiveness of these immunogens is attributed to novel epitopes that are exposed when the HIV envelope glycoprotein is covalently bound to the 2dCD4S60C, suggesting that this approach could lead to more effective HIV vaccines without complex immunization regimens.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunization with HIV-1 trimeric SOSIP.664 BG505 or founder virus C (FVCEnv) covalently complexed to two-domain CD4S60C elicits cross-clade neutralizing antibodies in New Zealand white rabbits. Tumba, NL., Owen, GR., Killick, MA., et al.[2022]

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. England pubmed.ncbi.nlm.nih.gov

Stable 293 T and CHO cell lines expressing cleaved, stable HIV-1 envelope glycoprotein trimers for structural and vaccine studies. [2021]

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

Developability Assessment of Physicochemical Properties and Stability Profiles of HIV-1 BG505 SOSIP.664 and BG505 SOSIP.v4.1-GT1.1 gp140 Envelope Glycoprotein Trimers as Candidate Vaccine Antigens. [2020]

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

Mapping Neutralizing Antibody Epitope Specificities to an HIV Env Trimer in Immunized and in Infected Rhesus Macaques. [2021]

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

Fusion peptide priming reduces immune responses to HIV-1 envelope trimer base. [2022]

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

Immunogenicity of a Prefusion HIV-1 Envelope Trimer in Complex with a Quaternary-Structure-Specific Antibody. [2018]

6. 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]

7. 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]

8. Netherlands pubmed.ncbi.nlm.nih.gov

Therapeutic immunization in HIV infected Ugandans receiving stable antiretroviral treatment: a Phase I safety study. [2021]

9. England pubmed.ncbi.nlm.nih.gov

Safety and efficacy of an oral HIV vaccine (V-1 Immunitor) in AIDS patients at various stages of the disease. [2004]

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

Safety and efficacy of the peptide-based therapeutic vaccine for HIV-1, Vacc-4x: a phase 2 randomised, double-blind, placebo-controlled trial. [2014]

11. England pubmed.ncbi.nlm.nih.gov

Immunization with HIV-1 trimeric SOSIP.664 BG505 or founder virus C (FVCEnv) covalently complexed to two-domain CD4S60C elicits cross-clade neutralizing antibodies in New Zealand white rabbits. [2022]

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

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