HIV Vaccine + Adjuvant for HIV Prevention

Not currently recruiting at 9 trial locations

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

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

Must not be taking: Immunosuppressants, Monoclonal antibodies

Disqualifiers: Pregnancy, Diabetes, Hypertension, Asthma, 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: Unknown

Duration: 10 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a potential vaccine for preventing HIV, focusing on its safety and ability to trigger an immune response in healthy adults. Researchers test different doses and methods of administering the vaccine to find the safest and most effective approach. The trial divides participants into groups, each trying different methods. Individuals who are HIV-negative, generally healthy, and interested in contributing to HIV prevention might be a good fit for this study. As a Phase 1 trial, participants will be among the first to receive this new treatment, helping researchers understand its effects in people.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like immunosuppressive drugs, recent vaccines, and treatments for specific conditions may affect eligibility. It's best to discuss your current medications with the trial team to determine if they might impact your participation.

Do I need to stop my current medications to join the trial?

The trial protocol does not specify if you need to stop taking your current medications. However, certain medications like immunosuppressive drugs and recent vaccines may affect eligibility, so it's best to discuss your specific situation with the trial team.

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

Research has shown that the N332-GT5 gp140, a component of the HIV vaccine under testing, remains in the early stages of human trials. Detailed safety information is not yet available. However, earlier studies have demonstrated promising safety results for the saponin/MPLA nanoparticles (SMNP), which enhance the immune response to the vaccine. These studies found that SMNP was well-tolerated in pre-human tests.

The current study seeks to determine a safe dose and method for administering the vaccine and adjuvant. As a phase 1 trial, the primary goal is to ensure safety for participants. Although clear data on human side effects is not yet available, the study is carefully designed to minimize risks. Participants will be closely monitored to address any side effects promptly. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about the N332-GT5 gp140 and SMNP treatments because they represent a novel approach to HIV prevention. Unlike standard HIV treatments that focus on managing the virus in infected individuals, these investigational treatments aim to prevent infection altogether by stimulating the immune system to produce protective antibodies before exposure. The combination of N332-GT5 gp140, a designed protein, with the SMNP adjuvant potentially enhances the immune response, distinguishing it from existing vaccines that lack this specific targeting mechanism. This could lead to a more effective preventative strategy against HIV, sparking hope for a significant advancement in global HIV prevention efforts.

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

Research has shown that the N332-GT5 gp140 trimer, an investigational treatment in this trial, helps the immune system recognize and fight HIV by activating certain B cells, which protect the body from infections. Another treatment option in this trial, the adjuvant SMNP, is used with the trimer to further enhance this immune response. Animal studies demonstrated that SMNP improves the body's ability to remember and respond to HIV-like threats. These findings suggest that this combination could be an important step toward preventing HIV infection. ^{1 2 4 5 6}

Who Is on the Research Team?

Lindsey Baden

Principal Investigator

Brigham and Women's Hospital

Are You a Good Fit for This Trial?

Adults aged 18-55, in good health with a low risk of HIV, can join this trial. They must have normal blood counts and organ function tests, live near a participating research site, and commit to the study's duration. Those with certain cancers or lymph disorders cannot participate.

Inclusion Criteria

My overall health is good, as confirmed by recent medical exams and tests.

Assessment of Understanding (AoU): Volunteer demonstrates understanding of this study by completing a questionnaire prior to the first vaccination with verbal demonstration of understanding of all questionnaire items answered incorrectly

I am open to talking about HIV risks and receiving advice on reducing these risks.

Exclusion Criteria

History of angioedema or anaphylaxis with specified conditions

My blood pressure is high.

I have not received any blood products in the last 4 months.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive N332-GT5 gp140 HIV trimer protein adjuvanted with SMNP via subcutaneous or intramuscular route, with 2 bolus immunizations or fractionated escalating dose prime followed by a bolus immunization boost

10 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment, including planned safety holds and Adverse Event of Special Interest (AESI) health contact 1 year after last vaccination

12 months

What Are the Treatments Tested in This Trial?

Interventions

• N332-GT5 gp140
• SMNP

Trial Overview The trial is testing N332-GT5 gp140, an experimental HIV vaccine given with SMNP adjuvant via different methods and schedules. It aims to find safe doses and see if it triggers immune responses without causing HIV.

How Is the Trial Designed?

Group I: Part B SC Immunogenicity - Group 14 Experimental Treatment 2 Interventions

Group II: Part B Immunogenicity - Group 15 Experimental Treatment 4 Interventions

Group 15 N332-GT5 gp140 with SMNP dose and route (SC or IM) is To Be Determined (TBD) based on groups 6 and 12 (Part A).

Group III: Part B IM Immunogenicity - Group 13 Experimental Treatment 2 Interventions

Group IV: Part A Subcutaneous (SC) safety with dose finding - Group 7 Experimental Treatment 2 Interventions

Group V: Part A SC safety with dose finding - Group 9 Experimental Treatment 2 Interventions

Group VI: Part A SC safety with dose finding - Group 8 Experimental Treatment 2 Interventions

Group VII: Part A SC safety with dose finding - Group 12 Experimental Treatment 2 Interventions

Group VIII: Part A SC safety with dose finding - Group 11 Experimental Treatment 2 Interventions

Group IX: Part A SC safety with dose finding - Group 10 Experimental Treatment 2 Interventions

Group X: Part A Intramuscular (IM) safety with dose finding - Group 1 Experimental Treatment 2 Interventions

Group XI: Part A IM safety with dose finding - Group 6 Experimental Treatment 2 Interventions

Group XII: Part A IM safety with dose finding - Group 5 Experimental Treatment 2 Interventions

Group XIII: Part A IM safety with dose finding - Group 4 Experimental Treatment 2 Interventions

Group XIV: Part A IM safety with dose finding - Group 3 Experimental Treatment 2 Interventions

Group XV: Part A IM safety with dose finding - Group 2 Experimental Treatment 2 Interventions

Who Is Running the Clinical Trial?

National Institute of Allergy and Infectious Diseases (NIAID)

Lead Sponsor

Trials

3,361

Recruited

5,516,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

Department of Health and Human Services

Collaborator

Trials

240

Recruited

944,000+

Published Research Related to This Trial

In a study using a simian immunodeficiency virus (SIV) model, a sequential immunization strategy combining DNA, modified vaccinia virus Ankara (MVA), and a protein boost significantly increased antibody responses, with some vaccinated animals showing complete protection against SIV infection after challenges.

The protein boost with virus-like particles (VLPs) enhanced binding antibody titers and neutralizing responses, but highlighted the importance of optimizing CD8 T cell engagement for effective early viral control, indicating a need for further development in HIV vaccine strategies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Virus-Like Particles Displaying Trimeric Simian Immunodeficiency Virus (SIV) Envelope gp160 Enhance the Breadth of DNA/Modified Vaccinia Virus Ankara SIV Vaccine-Induced Antibody Responses in Rhesus Macaques. Iyer, SS., Gangadhara, S., Victor, B., et al.[2021]

In a study involving 50 male mice with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS), treatment with biodegradable nanoparticles coupled to the T2 peptide significantly improved pain thresholds and reduced urinary frequency, indicating potential efficacy in alleviating symptoms of CP/CPPS.

The PLGA-PEMA-T2 treatment not only enhanced the anti-inflammatory cytokine IL-10 but also reduced levels of inflammatory markers like TNF-α and CRP, suggesting a mechanism of action that promotes immune tolerance and reduces inflammation in CP/CPPS.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A nanoparticle-coupled T2 peptide induces immune tolerance and ameliorates chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) in mice model. Cao, Y., Cheng, Y., Ihsan, AU., et al.[2019]

The study identifies poly (I:C) as the most effective adjuvant for enhancing cellular immune responses when combined with the HIV gp140 trimer vaccine, leading to increased production of specific T cells and IFN-γ.

Combining different adjuvants, such as MPL with Alum or MDP, can enhance the quality and magnitude of antibody responses, indicating that the right adjuvant-antigen pairing is crucial for developing an effective HIV vaccine.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

HIV Envelope Trimer Specific Immune Response Is Influenced by Different Adjuvant Formulations and Heterologous Prime-Boost. Apostólico, Jde S., Boscardin, SB., Yamamoto, MM., et al.[2018]

Saponin adjuvants, particularly the newly developed saponin/MPLA nanoparticles (SMNP), enhance immune responses by altering lymph flow and promoting antigen entry into lymph nodes, demonstrating a unique mechanism of action.

In studies with mice and nonhuman primates, SMNP showed greater potency than the AS01B adjuvant, effectively priming strong immune responses, including the production of neutralizing antibodies against HIV, indicating its potential as a promising adjuvant for various vaccines.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A particulate saponin/TLR agonist vaccine adjuvant alters lymph flow and modulates adaptive immunity. Silva, M., Kato, Y., Melo, MB., et al.[2022]

HIV vaccines based on recombinant proteins and plasmid DNA are expected to be less reactogenic but also less immunogenic than traditional vaccines, highlighting the need for improved adjuvants and delivery systems.

The development of new adjuvants, which can enhance immune responses either through targeted delivery to antigen presenting cells or by stimulating the innate immune system, is crucial for creating effective prophylactic and therapeutic HIV vaccines, potentially including mucosal delivery methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Advances in vaccine adjuvants for infectious diseases. Singh, M., Srivastava, I.[2019]

The study evaluated the effectiveness of two adjuvants, activated alpha2-macroglobulin (alpha2M*) and a squalene-based emulsion with monophosphoryl lipid A (MPL-SE) combined with GM-CSF, in enhancing the immunogenicity of HIV-1 subunit vaccines in Balb/c mice.

Using a combination of alpha2M* and MPL-SE/GM-CSF allowed for a significant reduction in the required dose of HIV immunogens, achieving optimal antibody responses with as little as 0.1 microg of the C4-V3(89.6P) peptide, which is up to 100-fold less than traditional adjuvant methods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Increased immunogenicity of HIV envelope subunit complexed with alpha2-macroglobulin when combined with monophosphoryl lipid A and GM-CSF. Liao, HX., Cianciolo, GJ., Staats, HF., et al.[2019]

In a double-blind trial involving 24 patients with chronic non-bacterial prostatitis, pentosanpolysulphate (Elmiron) significantly improved symptoms related to muscles and joints, with a p-value of less than 0.01.

Some patients experienced diarrhea as a side effect, particularly those with a history of gastrointestinal issues, indicating a need for caution in this population.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of sodium pentosanpolysulphate on symptoms related to chronic non-bacterial prostatitis. A double-blind randomized study. Wedrén, H.[2019]

Obacunone (Oba) significantly alleviates chronic pelvic pain syndrome (CPPS) in a mouse model of experimental autoimmune prostatitis (EAP), demonstrating a dose-dependent effect on reducing pain and inflammation.

The mechanism of action involves Oba inhibiting the production of the pro-inflammatory cytokine IL-6 from macrophages, suggesting it may be a promising treatment for CPPS by targeting macrophage activity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Obacunone alleviates chronic pelvic pain and pro-inflammatory depolarization of macrophage induced by experimental autoimmune prostatitis in mice. Wang, Y., Dang, Z., Wang, X., et al.[2023]

The QS-21 saponin adjuvant significantly enhanced antibody production by over 100-fold and broadened the immune response in juvenile rhesus macaques when used with an experimental HIV-1 vaccine, indicating its strong efficacy as an adjuvant.

No toxic effects were observed after administering the QS-21 adjuvant in the vaccine, even after three doses, suggesting it is safe for use in HIV-1 vaccine formulations.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immunogenicity and toxicity testing of an experimental HIV-1 vaccine in nonhuman primates. Newman, MJ., Wu, JY., Coughlin, RT., et al.[2017]

The combination of QS21 and 3D-monophosphoryl lipid A (MPL) as an adjuvant significantly enhances both cellular and humoral immune responses to a recombinant HIV protein, indicating its potential effectiveness in vaccine development.

3D-MPL selectively boosts Th1 cell responses and enhances antigen presentation by macrophages, providing a safer alternative to traditional LPS-based adjuvants without the associated toxicity.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The adjuvant combination monophosphoryl lipid A and QS21 switches T cell responses induced with a soluble recombinant HIV protein from Th2 to Th1. Moore, A., McCarthy, L., Mills, KH.[2019]

In a study of 100 men with chronic prostatitis/chronic pelvic pain syndrome, cernitin pollen extract was found to be more effective than tadalafil in reducing pelvic pain, with significant improvements in pain scores and quality of life after 12 weeks of treatment.

While both treatments helped alleviate chronic pelvic pain, tadalafil was more effective for improving lower urinary tract symptoms, indicating that cernitin may be a better option specifically for pain management in these patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of cernitin pollen extract vs tadalafil therapy for refractory chronic prostatitis/chronic pelvic pain syndrome: A randomized, prospective study. Matsukawa, Y., Naito, Y., Funahashi, Y., et al.[2021]

In a study involving 61 male patients with type IIIa and IIIb chronic prostatitis, rectal administration of Boswellia resin extract and propolis polyphenols for 15 days each month over 3 months resulted in significant improvements in pain and overall symptoms, as measured by the NIH-Chronic Prostatitis Symptom Index (NIH-CPSI).

The treatment was well tolerated with no reported adverse events, indicating its safety, while significant improvements were observed in pain, micturition, and quality of life domains by the end of the study.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Boswellia resin extract and propolis derived polyphenols in patients with type III chronic prostatitis/chronic pelvic pain syndrome: An Italian prospective multicenter study. Presicce, F., Barrese, F., Cantiani, A., et al.[2022]

Matrix-M™ adjuvant, derived from saponins and combined with cholesterol and phospholipids, enhances the immune response by activating innate immune cells and improving antibody responses, making it a powerful component in vaccines.

Clinical trials have shown that Matrix-M-adjuvanted vaccines, including the NVX-CoV2373 candidate for COVID-19, have a favorable safety profile and are well tolerated by participants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Matrix-M™ adjuvant: A critical component of vaccines for the 21st century. Stertman, L., Palm, AE., Zarnegar, B., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT06033209

Study Details | NCT06033209 | A Trial to Evaluate an HIV ... This study will evaluate the safety and immunogenicity of combining 2 FIH products: N332-GT5 gp140 HIV trimer protein adjuvanted with SMNP, co-administered as ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11488660/

mRNA-LNP HIV-1 trimer boosters elicit precursors to broad ... Here, using our established BG18gH mouse model, we found that an mRNA-LNP N332-GT5/B11 or B16 prime-boost regimen was highly effective. The relative ease of ...

3. trialx.com trialx.com/clinical-trials/listings/239645/a-trial-to-evaluate-an-hiv-envelope-trimer-n332-gt5-gp140-adjuvanted-with-smnp-in-adult-participants-without-hiv/

A Trial to Evaluate an HIV Envelope Trimer, N332-GT5 ... The study aims to evaluate the safety and tolerability of N332-GT5 gp140 adjuvanted with SMNP in adult volunteers without HIV and in overall ...

4. centerwatch.com centerwatch.com/clinical-trials/listings/NCT06033209/a-trial-to-evaluate-an-hiv-envelope-trimer-n332-gt5-gp140-adjuvanted-with-smnp-in-adult-participants-without-hiv

A Trial to Evaluate an HIV Envelope Trimer, N332-GT5 ... The study aims to evaluate the safety and tolerability of N332-GT5 gp140 adjuvanted with SMNP in adult volunteers without HIV and in overall good health.

5. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11309785/

Vaccine priming of rare HIV broadly neutralizing antibody ... Here, immunization with N332-GT5, an HIV envelope trimer designed to target precursors of the HCDR3-dominant bnAb BG18, primed bnAb-precursor B cells in 8 of 8 ...

6. withpower.com withpower.com/trial/phase-1-human-immunodeficiency-virus-hiv-infections-9-2023-3c0a6

HIV Vaccine + Adjuvant for HIV Prevention The safety data for the HIV Vaccine + Adjuvant, which includes components like N332-GT5 gp140, HIV envelope trimer, SMNP, and Saponin/MPLA nanoparticles, ...