HIV Vaccine for Human Immunodeficiency Virus

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

40 Participants Needed

Trial Summary

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.

What data supports the effectiveness of the HIV Vaccine treatment 3M-052-AF+Alum, 3M-052-AF, 3M-052-AF + Alum, 3M-052-AF + Aluminum Hydroxide Suspension, 426c.Mod.Core-C4b, 426c.Mod.Core-C4b vaccine, 426c.Mod.Core-C4b adjuvanted with 3M-052-AF + Alum?

Research shows that aluminum hydroxide, a component of the treatment, has been effective in inducing strong immune responses in other HIV vaccine trials, such as the RV144 trial, which demonstrated a 31% efficacy in preventing HIV acquisition. Additionally, aluminum-based adjuvants are widely used in vaccines and have been shown to enhance immune responses, suggesting potential effectiveness in this treatment. ^{1 2 3 4 5}

What makes the HIV vaccine treatment 3M-052-AF+Alum, 426c.Mod.Core-C4b unique?

The 3M-052-AF+Alum, 426c.Mod.Core-C4b treatment is unique because it combines a novel vaccine component with an adjuvant (a substance that enhances the body's immune response to an antigen) made of 3M-052-AF and aluminum hydroxide, which is designed to boost the immune system's ability to fight HIV by potentially inducing strong and specific immune responses. ^{1 2 3 6 7}

What is the purpose of this trial?

This is a multicenter controlled interventional trial. This phase 1 trial is the first study to assess 426c.Mod.Core-C4b adjuvanted with 3M-052-AF + aluminum hydroxide suspension (Alum) in people living with HIV (PLWH).

Eligibility Criteria

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

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

Total serum calcium of ≥ 8.5 mg/dL

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

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

Treatment Details

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.

Participant Groups

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+

Findings from Research

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 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 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]

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]

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]

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]

References

1. 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]

2. United States 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. [2020]

3. United States 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. [2020]

4. Netherlands 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. [2021]

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

Influence of aluminum-based adjuvant on the immune response to multiantigenic formulation. [2013]

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

An adjuvanted polyprotein HIV-1 vaccine induces polyfunctional cross-reactive CD4+ T cell responses in seronegative volunteers. [2021]

7. Netherlands 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). [2021]