HIV Vaccine + ALFQ for HIV Prevention

(RV575 Trial)

Overseen By Paul Adjei, MD

Age: 18 - 65

Sex: Any

Trial Phase: Phase 1

Sponsor: U.S. Army Medical Research and Development Command

Must not be taking: Immunosuppressants, Cytotoxics, Immunomodulators, others

Disqualifiers: Cancer, Autoimmune disease, 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: 3

Duration: 3 months

60 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new HIV vaccine combined with a helper substance called ALFQ (Army Liposome Formulation mixed with the saponin QS-21) to assess its safety and tolerability in people without HIV. Researchers will administer the vaccine in three different doses to determine the optimal amount of ALFQ that works effectively with the vaccine. The trial involves three groups, each receiving different doses of ALFQ, injected over several months. The study seeks healthy adults at low risk of contracting HIV who can commit to attending all study visits. As a Phase 1 trial, this research focuses on understanding how the treatment works in people, offering participants the unique opportunity 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, you cannot participate if you are on certain medications like systemic immunosuppressive drugs or if you have received live vaccines recently. It's best to discuss your specific medications with the trial team.

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

Research shows that the HIV vaccine, which includes components A244 and B.63521 along with the ALFQ adjuvant, is generally safe and well-tolerated. Earlier studies have demonstrated promising safety results in healthy adults, with no major side effects reported. The ALFQ adjuvant enhances the immune response and has not caused significant negative reactions. This vaccine remains in the early testing phase, aiming to further confirm its safety and determine the appropriate dose levels. ^{1 2 3 4 5}

Why are researchers excited about this trial's treatments?

Researchers are excited about these treatments because they represent a new approach to HIV prevention using a vaccine combined with an adjuvant called ALFQ. Unlike traditional HIV treatments that focus on managing the virus with antiretroviral therapy (ART), these investigational treatments aim to prevent infection in the first place. The combination of A244 and B.63521 proteins with varying doses of ALFQ adjuvant is designed to enhance the immune response, potentially offering a more effective and long-lasting defense against HIV. This could be a game-changer, as current options primarily involve daily medication, while a vaccine could reduce the need for ongoing treatment.

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

Research has shown that the A244/B.63521 vaccine, combined with the ALFQ booster, could help prevent HIV. In this trial, participants will receive varying doses of the ALFQ adjuvant. In animal studies, a similar vaccine protected 55% of vaccinated monkeys from infection. Earlier trials with ALFQ at doses of 100 and 200 micrograms demonstrated strong immune responses and proved safe. These early results suggest that the vaccine might help the body combat HIV. While more research is necessary, these findings are promising for its potential use in humans. ^{1 5 6 7 8}

Who Is on the Research Team?

Paul Adjei, MD

Principal Investigator

Research Physician at U.S. Military HIV Research Program

Are You a Good Fit for This Trial?

Healthy adults aged 18-55, at low risk for HIV, willing to practice safe sex and effective contraception. Excludes those with immune conditions, serious illnesses, drug abuse history, or plans to become pregnant. Participants must have stable vital signs and agree not to donate blood during the study.

Inclusion Criteria

I cannot have children because I am post-menopausal, or I've had surgery.

I am not pregnant, as confirmed by a negative pregnancy test on enrollment and vaccination days.

Serum creatinine ≤ 1.25 x institutional upper limit of the reference range

Exclusion Criteria

I have been diagnosed with a type of arthritis that is not osteoarthritis.

I haven't had a fever or acute illness around the time of my study injection.

History of autoimmune disease

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive vaccinations via intramuscular injection at months 0, 1, and 2 with varying doses of ALFQ adjuvant

3 months

3 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, including adverse events and immune response assessments

12 months

Regular visits (in-person) for monitoring and blood draws

What Are the Treatments Tested in This Trial?

Interventions

• A244
• ALFQ
• B.65321

Trial Overview The trial tests a new HIV vaccine candidate A244/B.63521 with varying doses of ALFQ adjuvant (50μg, 100μg, or 200μg) in three groups via intramuscular injections over three months. It aims to determine the safest and most effective dose for future use.

How Is the Trial Designed?

Group I: A244/B.63521 + 200 μg of ALFQ adjuvant Active Control 3 Interventions

Arm 1: An injection containing 300 μg A244 plus 300 μg B.63521 with 200 μg of ALFQ adjuvant will be administered as an IM injection into the deltoid muscle at visits 1, 3, and 5 (corresponding to Day 1, Day 29, and Day 57).

Group II: A244/B.63521 + 100 μg of ALFQ adjuvant Active Control 3 Interventions

Arm 2: An injection containing 300 μg A244 plus 300 μg B.63521 with 100 μg of ALFQ adjuvant will be administered as an IM injection into the deltoid muscle at visits 1, 3, and 5 (corresponding to Day 1, Day 29, and Day 57).

Group III: A244/B.63521 + 50 μg of ALFQ adjuvant Active Control 3 Interventions

Arm 3: An injection containing 300 μg of A244 plus 300 μg B.63521 with 50 μg of ALFQ adjuvant will be administered as an IM injection into the deltoid muscle at visits 1, 3, and 5 (corresponding to Day 1, Day 29, and Day 57).

Who Is Running the Clinical Trial?

U.S. Army Medical Research and Development Command

Lead Sponsor

Trials

296

Recruited

249,000+

US Military HIV Research Program

Collaborator

Trials

20

Recruited

3,900+

Henry M. Jackson Foundation for the Advancement of Military Medicine

Collaborator

Trials

103

Recruited

94,300+

National Institute of Allergy and Infectious Diseases (NIAID)

Collaborator

Trials

3,361

Recruited

5,516,000+

Published Research Related to This Trial

Co-adsorbing Army Liposome Formulation (ALF) or ALFQ with aluminum hydroxide (AH) significantly enhances the immune potency of antigens, such as tetanus toxoid and HIV-1 gp140, compared to using aluminum salts alone.

The study found that ALFA primarily induces a Th2-type immune response, while ALFQ and ALFQA promote a more balanced Th1/Th2 response, suggesting that these combinations could improve vaccine effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Immune response to antigen adsorbed to aluminum hydroxide particles: Effects of co-adsorption of ALF or ALFQ adjuvant to the aluminum-antigen complex. Beck, Z., Torres, OB., Matyas, GR., et al.[2021]

Army Liposome Formulations (ALF), specifically ALFlyo and ALFQ, are effective adjuvants used in vaccine development for various diseases, and they are advancing to phase I/IIa clinical trials after successful preclinical studies.

ALFlyo and ALFQ have similar particle size distributions but differ in their lamellar structures, with ALFlyo containing more multilamellar and multivesicular particles, which may influence their adjuvant effectiveness.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Biophysical characterization of polydisperse liposomal adjuvant formulations. Singh, P., Matyas, GR., Anderson, A., et al.[2021]

The Army Liposome Formulation (ALF) is a highly effective and safe vaccine adjuvant that enhances the potency of vaccines, showing promise in clinical trials for various diseases.

Innovations based on ALF, such as ALFA and ALFQ, are being developed for upcoming vaccine trials targeting serious health threats like malaria, HIV-1, and opioid addiction, potentially leading to improved vaccine efficacy and safety.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Army Liposome Formulation (ALF) family of vaccine adjuvants. Alving, CR., Peachman, KK., Matyas, GR., et al.[2021]

The Army Liposome Formulation with QS21 (ALFQ) creates giant unilamellar vesicles (GUVs) greater than 1.0 µm in diameter through a unique fusion process initiated by the addition of QS21 to liposomes, which significantly alters the size distribution of the particles.

Most of the cholesterol and nearly all of the adjuvants (MPLA and QS21) are concentrated in the GUVs, suggesting that the binding of QS21 to cholesterol may facilitate structural changes in the lipid bilayer that promote vesicle fusion, enhancing the potential efficacy of the vaccine adjuvant.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

QS21-Initiated Fusion of Liposomal Small Unilamellar Vesicles to Form ALFQ Results in Concentration of Most of the Monophosphoryl Lipid A, QS21, and Cholesterol in Giant Unilamellar Vesicles. Abucayon, EG., Rao, M., Matyas, GR., et al.[2023]

The novel liposomal monophosphoryl lipid A (MPLA) adjuvant, when used in a prime-boost vaccination strategy in macaques, significantly enhanced antibody-dependent phagocytic responses and provided 90% protection against HIV-1 challenges, compared to no protection with traditional aluminum adjuvant.

In both macaques and humans, the MPLA-liposome-alum adjuvant improved HIV-1-specific immune responses, suggesting that next-generation adjuvants can effectively boost vaccine efficacy by enhancing functional antibody responses.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adjuvanted HIV-1 vaccine promotes antibody-dependent phagocytic responses and protects against heterologous SHIV challenge. Om, K., Paquin-Proulx, D., Montero, M., et al.[2020]

The saponin adjuvant QS-21 significantly enhanced antibody production and immune responses in mice vaccinated with an experimental HIV-1 vaccine, compared to those receiving only the alum-adsorbed vaccine.

QS-21 not only improved antibody responses but also broadened cell-mediated immune responses, indicating its potential to enhance the effectiveness of subunit vaccines by targeting weakly immunogenic epitopes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Saponin adjuvant enhancement of antigen-specific immune responses to an experimental HIV-1 vaccine. Wu, JY., Gardner, BH., Murphy, CI., et al.[2022]

The Army Liposome Formulation (ALF) effectively enhances immune responses to the HIV-1 envelope protein CN54 gp140, with smaller liposomes (SUV) inducing higher antibody levels compared to larger ones (MLV).

When combined with QS21, ALF liposomes significantly boost both Th1 and Th2 immune responses, leading to the production of neutralizing antibodies against HIV-1, indicating their potential as effective vaccine adjuvants.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Differential immune responses to HIV-1 envelope protein induced by liposomal adjuvant formulations containing monophosphoryl lipid A with or without QS21. Beck, Z., Matyas, GR., Jalah, R., et al.[2017]

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 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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT05423418

Safety, Tolerability, and Immunogenicity of ALFQ in a HIV ... This study will evaluate the safety and tolerability (including reactogenicity) of candidate vaccine A244/B.63521 with Army Liposome Formulation (ALF) mixed ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC5472724/

Pentavalent HIV-1 vaccine protects against simian-human ... We find that immunization of rhesus macaques with the pentavalent vaccine results in protection of 55% of pentavalent-vaccine-immunized macaques ...

3. hivresearch.org hivresearch.org/news/news/mhrp-launches-new-hiv-vaccine-trial-optimize-alfq-adjuvant-dosage

MHRP Launches New HIV Vaccine Trial to Optimize ALFQ ... The 100 and 200 micrograms doses have been tested in previous clinical trials and found to be strongly immunogenic with favorable safety ...

4. onlinelibrary.wiley.com onlinelibrary.wiley.com/doi/10.1002/jia2.26351

Abstracts from HIVR4P 2024, the 5th HIV Research for ... Overall, 16 incident HIV infections were reported among 1195 participants, the overall HIV incident rate was 0.96 per 100 person-years (95% CI = ...

5. iasociety.org iasociety.org/sites/default/files/HIVR4P2024/abstract-book/HIVR4P-2024_Abstracts.pdf

HIVR4P 2024 abstract book PrEP_CT captures HIV testing data including. Positive, Negative, and Other results. PrEP_CT does not differentiate between daily and event ...

6. centerwatch.com centerwatch.com/clinical-trials/listings/NCT05423418/safety-tolerability-and-immunogenicity-of-alfq-in-a-hiv-vaccine-containing-a244-and-b65321-in-healthy-adults

Safety, Tolerability, and Immunogenicity of ALFQ in a HIV ... This study will evaluate the safety and tolerability (including reactogenicity) of candidate vaccine A244/B.63521 with Army Liposome Formulation (ALF)

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12180328/

Advances in vaccine adjuvant development and future ... Safety, tolerability, and immunogenicity of ALFQ in a HIV vaccine containing A244 and B.65321 in healthy adults (RV575) U.S. Army Medical ...

8. withpower.com withpower.com/trial/phase-1-acquired-immunodeficiency-syndrome-aids-virus-5-2022-fb020

HIV Vaccine + ALFQ for HIV Prevention (RV575 Trial) This trial is testing a new vaccine with components A244 and B.63521, plus an immune-boosting substance called ALFQ. ALFQ helps enhance immune responses.