HIV Vaccine for Human Immunodeficiency Virus

Not currently recruiting at 10 trial locations

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

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

Must be taking: Antiretrovirals

Must not be taking: Long-acting ART

Disqualifiers: Hepatitis B, Hepatitis C, Diabetes, 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: 2

Duration: 14 weeks

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a potential vaccine for people living with HIV. Researchers aim to evaluate the safety and immune response of a new vaccine combination: 426c.Mod.Core-C4b with 3M-052-AF and aluminum hydroxide (commonly found in vaccines). Participants will be divided into two groups; one group will receive two doses of the vaccine and temporarily pause their current HIV medication. Ideal candidates have maintained a stable HIV treatment (ART) regimen with undetectable virus levels in recent tests. As a Phase 1 trial, the research focuses on understanding how the treatment works in people, offering participants the opportunity to be among the first to receive this new vaccine combination.

Will I have to stop taking my current medications?

The trial requires participants to be on a specific type of HIV medication regimen, which includes at least one integrase inhibitor and one nucleoside reverse transcriptase inhibitor. If you are on a different type of HIV medication, you may need to change to meet the trial's requirements.

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

Research shows that the components of the HIV vaccine under testing have been safe in earlier studies. The 3M-052-AF adjuvant, combined with aluminum hydroxide (Alum), has been used in other vaccine trials. These studies found it was generally well-tolerated, with no serious side effects. For example, in trials for other vaccines, it helped generate a strong immune response without major problems.

The 426c.Mod.Core-C4b component has also been tested with 3M-052-AF and Alum. Previous research suggests this combination is safe, with no serious adverse events. Participants in these studies usually experienced mild and temporary reactions, such as soreness at the injection site or a mild fever, which are common with many vaccines.

As this is a phase 1 trial, it marks the first time this specific combination is tested in humans, making safety a key focus. However, positive results from past studies provide a reassuring starting point for assessing safety in this trial. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they explore a novel approach to HIV prevention through vaccination. Unlike current standard treatments like antiretroviral therapy (ART), which manage the virus's impact on the immune system, these investigational vaccines aim to prevent HIV infection altogether. 3M-052-AF+Alum and 426c.Mod.Core-C4b represent a new strategy by potentially stimulating the immune system to build a protective response against the virus. This could be a game-changer, offering a proactive solution rather than a reactive one.

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

This trial will evaluate two investigational treatments for HIV. One treatment arm will receive a combination of 3M-052-AF with aluminum hydroxide (Alum). Research has shown that this combination can boost the body's immune response, leading to strong antibody responses crucial for fighting HIV. In previous animal studies, these immune responses were both strong and long-lasting, suggesting potential effectiveness in humans.

The other treatment arm will receive the 426c.Mod.Core-C4b component, designed to work with a helper substance to prepare the immune system effectively. This approach activates certain immune cells, which could aid in combating HIV. Together, these elements offer hope for a vaccine that can strengthen the body's defenses against HIV. ^{4 6 7 8 9}

Are You a Good Fit for This Trial?

This trial is for people aged 18-55 living with HIV on stable ART (antiretroviral therapy) for at least 48 weeks, with undetectable viral load and good immune health. They must be in overall good health, not pregnant or planning pregnancy, willing to use contraception, and able to complete the study. Those already in another trial need special approval.

Inclusion Criteria

In good general health according to the clinical judgment of the site investigator

Total serum calcium of ≥ 8.5 mg/dL

I have been on HIV medication for at least 48 weeks.

Exclusion Criteria

I have hepatitis B or C.

Certain medical conditions such as bleeding disorders, seizure disorders, asplenia, active military personnel, and others

I have a weakened immune system from birth or developed over time.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive 2 doses of the vaccine at Week 0 and 12

14 weeks

2 visits (in-person)

ATI with Monitoring

Participants undergo an Analytical Treatment Interruption with monitoring for 24 weeks or until ART re-initiation criteria are met

24 weeks

Follow-up on ART restart

Participants are monitored after ART restart until study week 64

up to 50 weeks

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months following any receipt of study product

What Are the Treatments Tested in This Trial?

Interventions

• 3M-052-AF+Alum
• 426c.Mod.Core-C4b

Trial Overview The trial tests a new vaccine candidate (426c.Mod.Core-C4b) combined with an adjuvant (3M-052-AF+Alum) designed to stimulate immune responses in HIV-positive individuals. It's a phase 1 multicenter controlled interventional study assessing safety and immune response.

How Is the Trial Designed?

Group I: Group 2 (No ATI) Control Experimental Treatment 2 Interventions

Group 2 transitions from Schedule 1 into Schedule 4, "Follow-up on ART," at the Week 14 visit, and remains on Schedule 4 through study week 64.

Group II: Group 1 (ATI) Experimental Treatment 2 Interventions

Group 1 will receive 2 doses of the vaccine at Week 0 and 12. Group 1 will transition to Schedule 2 at the Week 14 visit. The Schedule 2 "ATI with Monitoring" phase can last for 24 weeks OR until any antiretroviral therapy (ART) re-initiation criteria are met, OR the ATI can continue longer with the approval of the Protocol Safety Review Team (PSRT) and the participant's primary HIV healthcare provider. Group 1 will transition to Schedule 3, the "Follow-up on ART restart" phase that lasts until study week 64, regardless of the point where it begins.

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

The study tested HIV clade B/C vaccine candidates in macaques and found that high doses of Aluminum hydroxide (Alum) led to protective serum IgG responses, reducing the risk of acquiring Tier 1 SHIV-C viruses.

In contrast, low doses of Alum increased the risk of acquiring Tier 2 SHIV-C viruses, while the MF59 adjuvant showed a different immune response that effectively decreased the risk of Tier 1 SHIV-C acquisition, highlighting the importance of the adjuvant type in vaccine efficacy.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type. Schifanella, L., Barnett, SW., Bissa, M., et al.[2020]

The novel HIV-1 vaccine candidate, consisting of a recombinant fusion protein (F4) with adjuvant AS01, demonstrated a high immune response rate, particularly in the 10-μg dose group, with 100% response to 3 antigens and 80% to all 4 antigens among 180 healthy volunteers.

The vaccine induced strong and long-lasting CD4(+) T cell responses, especially against reverse transcriptase, suggesting its potential for both preventive and therapeutic applications in HIV-1 infection.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An adjuvanted polyprotein HIV-1 vaccine induces polyfunctional cross-reactive CD4+ T cell responses in seronegative volunteers. Van Braeckel, E., Bourguignon, P., Koutsoukos, M., et al.[2021]

Aluminum hydroxide adjuvant is more effective than aluminum phosphate in promoting a Th1 immune response when used with a mixture of hepatitis B virus antigens and HIV protein CR3.

The order of mixing the antigens did not affect the secretion of CR3-specific interferon-gamma, indicating flexibility in formulation without compromising immune response.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Influence of aluminum-based adjuvant on the immune response to multiantigenic formulation. Iglesias, E., Franch, O., Carrazana, Y., et al.[2013]

A phase 1 trial involving 36 healthy participants demonstrated that shorter, 6-month regimens of a mosaic HIV-1 vaccine elicited strong immune responses comparable to a longer, 12-month regimen, suggesting they could be effective for HIV prevention.

All vaccine regimens were well tolerated, with mild-to-moderate side effects reported, indicating a favorable safety profile, which is crucial for community-level vaccine delivery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparison of shortened mosaic HIV-1 vaccine schedules: a randomised, double-blind, placebo-controlled phase 1 trial (IPCAVD010/HPX1002) and a preclinical study in rhesus monkeys (NHP 17-22). Stephenson, KE., Wegmann, F., Tomaka, F., et al.[2021]

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]

Hybrid Ty virus-like particles carrying the major neutralizing domain of HIV successfully induced high levels of virus-neutralizing antibodies and T-cell responses in animal models when combined with aluminum hydroxide, a safe adjuvant for human use.

The use of aluminum hydroxide in this vaccine formulation suggests a promising pathway for developing an effective and nontoxic HIV vaccine suitable for human trials.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Induction of high-titer neutralizing antibodies, using hybrid human immunodeficiency virus V3-Ty viruslike particles in a clinically relevant adjuvant. Griffiths, JC., Berrie, EL., Holdsworth, LN., et al.[2020]

The RV306 trial, involving 367 healthy HIV-uninfected participants, found that additional vaccine boosts at longer intervals after the initial RV144 regimen significantly improved immune responses, particularly in antibody levels against HIV antigens.

No serious vaccine-related adverse events were reported, indicating that the additional boosts were safe and well-tolerated, which is crucial for the potential efficacy of the vaccine in preventing HIV acquisition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Late boosting of the RV144 regimen with AIDSVAX B/E and ALVAC-HIV in HIV-uninfected Thai volunteers: a double-blind, randomised controlled trial. Pitisuttithum, P., Nitayaphan, S., Chariyalertsak, S., et al.[2021]

Citations

1. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/39235529/

Use of 3M-052-AF with Alum adjuvant in HIV trimer vaccine ... Our findings demonstrate the clinical utility of the 3M-052-AF/Alum adjuvant and support further improvements of trimer-based Env immunogens.

2. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0264410X23003122

Vaccine Recently, an HIV vaccine formulated with 3 M052-Alum adjuvant was shown to elicit high and durable antibody responses in non-human primates, and ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11380150/

Use of 3M-052-AF with Alum adjuvant in HIV trimer vaccine ... The first clinical experience with 3M-052-AF/Alum as a vaccine adjuvant reported here provides a reassuring safety outcome and a promising immune response that ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04177355

Study Details | NCT04177355 | Evaluating the Safety and ... Use of 3M-052-AF with Alum adjuvant in HIV trimer vaccine induces human autologous neutralizing antibodies. J Exp Med. 2024 Oct 7;221(10):e20240604. doi ...

5. withpower.com withpower.com/trial/phase-1-hiv-infections-8-2023-9395b

HIV Vaccine for Human Immunodeficiency Virus Research shows that aluminum hydroxide, a component of the treatment, has been effective in inducing strong immune responses in other HIV vaccine trials, such ...

6. clinicaltrials.gov clinicaltrials.gov/study/NCT04177355

NCT04177355 | Evaluating the Safety and Immunogenicity ... This study will evaluate the safety and immunogenicity of HIV-1 BG505 SOSIP.664 gp140 with TLR agonist and/or alum adjuvants in healthy, HIV-uninfected ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10027959/

Preclinical evaluation of immunogenicity, efficacy and safety of ... 3M-052 has been well studied as an adjuvant component in the development of several vaccine candidates, including vaccines against H1N1 [14], leishmaniasis [15] ...

8. ctv.veeva.com ctv.veeva.com/study/comparing-the-safety-and-immunogenicity-of-426cmodcore-c4b-vaccine-adjuvanted-with-3m-052-af-alu

Safety & Immunogenicity of 426c.Mod.Core-C4b Vaccine With ... The purpose of this study is to evaluate the safety and immunogenicity of 426c.Mod.Core-C4b vaccine adjuvanted with 3M-052-AF + Alum in ...

9. clinicaltrials.gov clinicaltrials.gov/study/NCT06905275

A Clinical Trial to Evaluate the Safety and Immunogenicity ... This is a phase 1, first-in-human (FIH) trial for the combination of UVAX-1107 and UVAX-1197, both adjuvanted with 3M-052-AF + Aluminum Hydroxide Suspension ( ...