HIV Vaccine for HIV Infection

(NETI Trial)

Not currently recruiting at 2 trial locations

Overseen By Stacey Edick, PA-C

Age: 18+

Sex: Any

Trial Phase: Phase 1

Sponsor: Madhu Chhanda Choudhary

Must be taking: Antiretrovirals

Must not be taking: Immunomodulators, Chemotherapy

Disqualifiers: Pregnancy, Chronic inflammatory conditions, others

Compensation: Varies

Number of Visits: 11

Duration: 20 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new vaccine, Trimer 4571, to determine if it can safely help the immune system produce antibodies that fight HIV. Participants will receive either the vaccine or a placebo (a harmless substance used for comparison) to assess its safety and effectiveness. Individuals living with HIV and on stable antiretroviral therapy for at least two years may be suitable for this trial. The study aims to ensure the vaccine is well-tolerated and effectively boosts immune defense against HIV. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new vaccine.

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.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research has shown that Trimer 4571, a new vaccine being tested for HIV, is safe and well-tolerated in early studies. In past trials with healthy volunteers, participants experienced no serious side effects. The vaccine helped the body produce specific antibodies, proteins that assist the immune system in fighting infections. These findings suggest the vaccine is generally safe. However, since Trimer 4571 remains in the early testing stages, experience with its use in people is limited. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Researchers are excited about Trimer 4571 because it represents a novel approach to HIV treatment by focusing on therapeutic vaccination. Unlike current treatments, which primarily rely on antiretroviral therapy to manage HIV, Trimer 4571 aims to boost the body's immune response directly against the virus. This vaccine uses a unique trimeric protein structure to potentially enhance immune system targeting and effectiveness. The inclusion of an alum adjuvant further boosts the immune response, offering a promising alternative that could lead to longer-lasting control of the virus.

What evidence suggests that the Trimer 4571 vaccine could be an effective treatment for HIV?

Research shows that the Trimer 4571 vaccine helps the body produce special antibodies to fight HIV. Early studies with healthy volunteers found Trimer 4571 to be safe and capable of triggering an immune response. This response helps the body recognize and combat parts of the virus. The vaccine uses a protein structure resembling the outside of the HIV virus to train the immune system without causing infection. Although data in people with HIV is limited, early results suggest potential for protection against the virus. Participants in this trial will receive either the Trimer 4571 vaccine at varying dosages or a placebo, enabling researchers to further evaluate its effectiveness and safety. ^{2 3 6 7 8}

Who Is on the Research Team?

Madhu Choudhary, MD

Principal Investigator

University of Pittsburgh

Are You a Good Fit for This Trial?

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

Timeline for a Trial Participant

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)

What Are the Treatments Tested in This Trial?

Interventions

• Trimer 4571 Therapeutic Vaccination

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.

How Is the Trial Designed?

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.

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

3,361

Recruited

5,516,000+

Published Research Related to This Trial

The PGT145 Fab-BG505 SOSIP.664 complex successfully reduced immune recognition of the weakly neutralizing V3 region by approximately 100-fold compared to the ligand-free BG505 SOSIP.664, while still eliciting similar levels of autologous neutralizing antibodies against the BG505 virus in guinea pigs.

This study suggests that modifying trimer immunogens can enhance their specificity and effectiveness as potential HIV-1 vaccine candidates by focusing the immune response on more potent neutralization sites.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity of a Prefusion HIV-1 Envelope Trimer in Complex with a Quaternary-Structure-Specific Antibody. Cheng, C., Pancera, M., Bossert, A., et al.[2018]

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]

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]

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]

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 Trimer 4571 HIV-1 vaccine was found to be safe and well-tolerated in a phase I trial involving 16 HIV-negative adults, with mild to moderate side effects and no serious adverse events reported.

The vaccine induced specific antibody responses in 44% of participants, particularly at the higher 500 mcg dose, suggesting its potential as a component in future HIV vaccine strategies.

NCBI (Pubmed)

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. Houser, KV., Gaudinski, MR., Happe, M., et al.[2022]

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]

In a study involving 49 non-human primates, priming with fusion peptide (FP) conjugates before immunization with SOSIP-stabilized Env trimers significantly reduced the prevalence of trimer-base antibody responses, which are typically high in trimer-only immunizations.

Reducing trimer-base responses through FP-conjugate priming was associated with improved neutralization breadth, suggesting a more effective immune response against HIV when using this priming strategy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Fusion peptide priming reduces immune responses to HIV-1 envelope trimer base. Corrigan, AR., Duan, H., Cheng, C., et al.[2022]

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 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 study isolated 45 neutralizing antibodies from rhesus macaques immunized with the BG505 SOSIP HIV Envelope trimer, indicating its potential to induce a strong immune response against HIV.

The most effective neutralization was linked to specific regions of the virus, suggesting that understanding these antibody interactions is crucial for designing effective HIV vaccines that can elicit broadly neutralizing antibodies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Mapping Neutralizing Antibody Epitope Specificities to an HIV Env Trimer in Immunized and in Infected Rhesus Macaques. Zhao, F., Joyce, C., Burns, A., et al.[2021]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9249552/

Safety and immunogenicity of an HIV-1 prefusion-stabilized ... We assessed safety and immunogenicity of HIV-1 vaccine, Trimer 4571 (BG505 DS-SOSIP.664) adjuvanted with aluminum hydroxide (alum), in HIV- ...

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/35783486/

Safety and immunogenicity of an HIV-1 prefusion ... - PubMed Interpretation: Trimer 4571 was safe, well tolerated, and immunogenic in this first-in-human trial. While this phase 1 trial is limited in size, ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2590136222000821

Immunization with HIV-1 trimeric SOSIP.664 BG505 or ... This study further investigated the impact of SOSIP. 664 (the archetype HIV-1 trimer mimic) on the immunogenicity of the covalently bound complexes locked in ...

4. journals.plos.org journals.plos.org/plospathogens/article?id=10.1371/journal.ppat.1003618

A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 ... A Next-Generation Cleaved, Soluble HIV-1 Env Trimer, BG505 SOSIP.664 gp140, Expresses Multiple Epitopes for Broadly Neutralizing but Not Non-Neutralizing ...

5. medrxiv.org medrxiv.org/content/10.1101/2024.05.08.24306957v1.full.pdf

HIV BG505 SOSIP.664 trimer with 3M-052-AF/alum ... HIV BG505 SOSIP. 664 trimer with novel 3M-052-AF/alum adjuvant in humans appears safe and induces serum neutralizing antibodies to matched ...

6. thelancet.com thelancet.com/journals/eclinm/article/PIIS2589-5370(22)00207-3/fulltext

Safety and immunogenicity of an HIV-1 prefusion-stabilized ... Trimer 4571 was safe, well tolerated, and immunogenic in this first-in-human trial. While this phase 1 trial is limited in size, our results ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10491024/

HIV-1 neutralizing antibodies elicited in humans by a ... To investigate elicitation of HIV-1 neutralizing antibodies in humans, here, we analyze B cells from a phase I clinical trial of the “DS-SOSIP”-stabilized ...

8. cdn.clinicaltrials.gov cdn.clinicaltrials.gov/large-docs/55/NCT04177355/Prot_000.pdf

HVTN 137 4.1.2 Trimer 4571 (BG505 DS-SOSIP.664 gp140): A Stabilized Soluble ... evaluating safety and immunogenicity of recombinant HIV BG505 SOSIP.664.