HIV-1 Envelope Trimer Vaccine for HIV Prevention

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new vaccine designed to prevent HIV by enhancing the body's immune response with specific antibodies that can combat the virus. Researchers combine two types of vaccine doses, V3G CH848 mRNA-Tr2 and V3G CH848 Pr-NP1, to evaluate their effectiveness in generating these protective antibodies. The trial includes several groups, each receiving slightly different vaccine combinations to identify the most effective approach. It targets individuals in good health, with a low risk of contracting HIV, who are not pregnant or breastfeeding. Participants must also commit to following study procedures and attending regular clinic visits. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the chance 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. 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.

Is there any evidence suggesting that this trial's treatments are likely to be safe?

Research has shown that the V3G CH848 Pr-NP1 has been studied previously. It targets specific immune cells to combat HIV-1. Although direct safety data from these studies is unavailable, its current testing in humans suggests scientists see potential in it.

The V3G CH848 mRNA-Tr2 employs mRNA technology, similar to that used in other vaccines like the COVID-19 vaccines, which have proven safe. However, specific safety data for this mRNA-Tr2 is not yet available.

As this trial is in its early stages, it primarily focuses on assessing safety in humans. Safety information is still being gathered. Like any new treatment, a process ensures it is safe and well-tolerated. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the V3G CH848 Pr-NP1 vaccine for HIV prevention because it represents a novel approach to stimulating the immune system. Unlike current antiretroviral therapies that manage HIV by inhibiting the virus's ability to replicate, this vaccine aims to prevent infection altogether by targeting the HIV-1 envelope trimer, a crucial protein on the virus's surface. This approach could potentially offer long-lasting protection with fewer doses compared to daily medication regimens. Additionally, the inclusion of adjuvants like 3M-052-AF and Alum, or ACU-026-001-1, is designed to enhance the body's immune response, potentially increasing the vaccine's effectiveness.

What evidence suggests that this trial's treatments could be effective for HIV prevention?

Research has shown that the V3G CH848 Pr-NP1 immunogen, which participants in this trial may receive, is designed to help the body produce special antibodies capable of fighting many types of HIV-1. These antibodies are crucial because they might neutralize various strains of the virus. Early studies suggest that targeting specific parts of the HIV-1 virus, such as the Env V3-glycan region, could aid in creating these antibodies. In this trial, the V3G CH848 mRNA-Tr2 serves as a booster to enhance this immune response. Although limited data exist on its effectiveness in humans, these strategies are based on promising early vaccine research. ^{1 3 5 6 7}

Are You a Good Fit for This Trial?

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

Agrees not to enroll in another study of an investigational agent during participation in the trial

Exclusion Criteria

Previous or current recipient of an investigational HIV vaccine

I have had myocarditis or pericarditis in the past.

I have not received any vaccines in the last 4 weeks.

Timeline for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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]

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]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11860913/

Progress and Challenges in HIV-1 Vaccine Research However, the efficacy of these vaccines has been modest, with the best results achieving approximately 30% effectiveness. ... prevention of HIV-1 infection.

2. clinicaltrials.gov clinicaltrials.gov/study/NCT05903339

Study Details | NCT05903339 | Clinical Trial to Evaluate ... The priming immunogen (V3G CH848 Pr-NP1) consists of ferritin NPs expressing 8 copies of an Env trimer. This immunogen will be boosted with an mRNA LNP (V3G ...

3. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/full/10.1002/jia2.25831

Strategies for induction of HIV‐1 envelope‐reactive broadly ... This immunogen, termed V3G-CH848 Pr-NP1, has been investigated as a candidate immunogen to target the naïve BCRs capable of initiating a ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10552807/

Progress with induction of HIV broadly neutralizing ... The purpose of the review is to discuss recent progress made in the design and use of immunogens capable of inducing HIV bnAbs in the Duke Consortia for HIV/ ...

5. treatmentactiongroup.org treatmentactiongroup.org/wp-content/uploads/2024/07/pipeline_HIV_VAX_2024_final.pdf

HIV Vaccines and Passive Immunization Pipeline Report ... Researchers at Oxford University announced results in July 2023 showing successful induction of T cell responses with their chimpanzee adenovirus (ChAd) and ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8606870/

Strategies for induction of HIV‐1 envelope‐reactive broadly ... This immunogen, termed V3G‐CH848 Pr‐NP1, has been investigated as a candidate immunogen to target the naïve BCRs capable of initiating a DH270‐ ...

7. journals.lww.com journals.lww.com/co-hivandaids/fulltext/2023/11000/progress_with_induction_of_hiv_broadly.5.aspx

Progress with induction of HIV broadly neutralizing... Does V3G CH848 Pr-NP1 prime expand DH270-like B cell precursors? •How far down the maturation pathway of DH270 B cell lineage does the V3G CH848 Pr-NP1 prime ...