HIV Vaccine for Human Immunodeficiency Virus
Recruiting in Palo Alto (17 mi)
+10 other locations
Age: 18 - 65
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 1
Recruiting
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
No Placebo Group
Trial Summary
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).
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.
12345What 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.
12367Eligibility 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
+15 more
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.
+18 more
Trial 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
Participant Groups
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.
2Treatment groups
Experimental Treatment
Group I: Group 2 (No ATI) ControlExperimental Treatment2 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 Treatment2 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Fred Hutchinson Cancer Research CenterSeattle, WA
The Hope Clinic of the Emory Vaccine Center CRS (Site #31440)Decatur, GA
New York Blood Center CRS (Site #31801)New York, NY
Seattle Vaccine and Prevention CRS (Site # 30331)Seattle, WA
More Trial Locations
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Who Is Running the Clinical Trial?
National Institute of Allergy and Infectious Diseases (NIAID)Lead Sponsor
References
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]Advances in therapeutic drugs have increased life-expectancies for HIV-infected individuals, but the need for an effective vaccine remains. We assessed safety and immunogenicity of HIV-1 vaccine, Trimer 4571 (BG505 DS-SOSIP.664) adjuvanted with aluminum hydroxide (alum), in HIV-negative adults.
Induction of high-titer neutralizing antibodies, using hybrid human immunodeficiency virus V3-Ty viruslike particles in a clinically relevant adjuvant. [2020]The localization of neutralization determinants within the envelope glycoproteins of human immunodeficiency virus (HIV) has been largely achieved by immunizing small animals in conjunction with Freund's adjuvant. However, for eventual use in humans, candidate HIV vaccine components must also be efficacious in a nontoxic formulation. We describe here the production of hybrid Ty viruslike particles carrying the major neutralizing domain of HIV and demonstrate the induction of high-titer virus-neutralizing antibodies and an HIV-specific T-cell proliferative response after immunization in conjunction with aluminum hydroxide. As aluminum hydroxide and aluminum phosphate are the only adjuvants currently licensed for use in humans, these observations have implications for the development of an effective vaccine against HIV.
ALVAC-HIV B/C candidate HIV vaccine efficacy dependent on neutralization profile of challenge virus and adjuvant dose and type. [2020]The ALVAC-HIV clade B/AE and equivalent SIV-based/gp120 + Alum vaccines successfully decreased the risk of virus acquisition in humans and macaques. Here, we tested the efficacy of HIV clade B/C ALVAC/gp120 vaccine candidates + MF59 or different doses of Aluminum hydroxide (Alum) against SHIV-Cs of varying neutralization sensitivity in macaques. Low doses of Alum induced higher mucosal V2-specific IgA that increased the risk of Tier 2 SHIV-C acquisition. High Alum dosage, in contrast, elicited serum IgG to V2 that correlated with a decreased risk of Tier 1 SHIV-C acquisition. MF59 induced negligible mucosal antibodies to V2 and an inflammatory profile with blood C-reactive Protein (CRP) levels correlating with neutralizing antibody titers. MF59 decreased the risk of Tier 1 SHIV-C acquisition. The relationship between vaccine efficacy and the neutralization profile of the challenge virus appear to be linked to the different immunological spaces created by MF59 and Alum via CXCL10 and IL-1β, respectively.
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]The RV144 phase 3 vaccine trial in Thailand demonstrated that ALVAC-HIV (vCP1521) and AIDSVAX B/E administration over 6 months resulted in a 31% efficacy in preventing HIV acquisition. In this trial, we assessed the immunological effect of an additional vaccine boost to the RV144 regimen at varying intervals between the priming vaccine series and the boost.
Influence of aluminum-based adjuvant on the immune response to multiantigenic formulation. [2013]Several adjuvants have been described and tested in humans. However, the aluminum-based adjuvants remain the most widely used component in vaccines today. Emerging data suggest that aluminum phosphate and aluminum hydroxide adjuvants do not promote a strong commitment to the helper T cell type 2 (Th2) pathway when they are coadministered with some Th1 adjuvants. In this regard, subtle differences between both aluminum-based adjuvants have been demonstrated. We have previously shown that subcutaneous immunization, in aluminum phosphate, of a mixture comprising the surface and core antigens of hepatitis B virus (HBV) and the multiepitopic protein CR3 of human immunodeficiency virus type 1 elicits a CR3-specific Th1 immune response. In these experiments, the antigens were adjuvated at the same time. As the final selection of the best adjuvant should be based on experimental evidence, we asked whether aluminum hydroxide allows a better Th1 immune deviation than aluminum phosphate. We also studied several ways to mix the antigens and the impact on CR3-specific interferon (IFN)-gamma secretion. Our findings indicate that aluminum hydroxide allows better Th1 immunodeviation than aluminum phosphate adjuvant for the mixture of HBV antigens and CR3. In addition, CR3-specific IFN-gamma secretion of the various formulations tested was the same irrespective of the order in which the antigens were combined.
An adjuvanted polyprotein HIV-1 vaccine induces polyfunctional cross-reactive CD4+ T cell responses in seronegative volunteers. [2021]This phase I/II partially blinded, randomized, dose-ranging study assessed the safety and immunogenicity of a novel human immunodeficiency virus type 1 (HIV-1) vaccine candidate consisting of a recombinant fusion protein (F4) containing 4 HIV-1 clade B antigens (Gag p24, Pol reverse transcriptase, Nef, and Gag p17) adjuvanted with AS01 in HIV-seronegative volunteers. Methods. Two doses of the recombinant F4 protein (10, 30, or 90 μg/dose), adjuvanted with AS01 or reconstituted with water for injection, were administered 1 month apart to 180 healthy volunteers aged 18-40 years. F4-specific CD4(+) T cell responses were measured using intracellular cytokine staining after in vitro stimulation by overlapping peptide pools covering the 4 individual antigens. Results. Reactogenicity was higher during the 7-day period after each vaccine dose in the adjuvanted than in the nonadjuvanted groups. In the adjuvanted groups, the overall immune response rate was high after the second vaccine dose, with highest responder rates seen in the 10-μg F4/AS01 group (100% to 3 HIV-1 antigens and 80% to all 4 HIV-1 antigens). High and long-lasting CD4(+) T cell frequencies were observed (up to a median value of 1.2% F4-specific CD4(+) T cells at day 44), with strongest responses directed against reverse transcriptase. Antigen-specific CD4(+) T cells exhibited a polyfunctional phenotype, expressing at least CD40 ligand and interleukin 2, often in combination with tumor necrosis factor α and/or interferon γ. Vaccine-induced CD4(+) T cell responses were broadly cross-reactive to all 4 antigens derived from HIV-1 clades A and C. Conclusions. These results support further clinical investigation of this HIV-1 vaccine candidate both in a prophylactic setting (alone, in conjunction with an envelope-based antigen or in combination with other vaccine approaches in a heterologous prime-boost regimen) and as a potentially disease-modifying therapeutic vaccine in HIV-1-infected subjects.
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]Current efficacy studies of a mosaic HIV-1 prophylactic vaccine require four vaccination visits over one year, which is a complex regimen that could prove challenging for vaccine delivery at the community level, both for recipients and clinics. In this study, we evaluated the safety, tolerability, and immunogenicity of shorter, simpler regimens of trivalent Ad26.Mos.HIV expressing mosaic HIV-1 Env/Gag/Pol antigens combined with aluminium phosphate-adjuvanted clade C gp140 protein.