Testing a new flu vaccine with and without an adjuvant in healthy adults

VRC 328: A Phase I Open-Label Clinical Trial to Evaluate the Dose, Safety, Tolerability, and Immunogenicity of Mosaic Hexavalent Influenza Vaccine VRC-FLUMOS0116-00-VP (FluMos-v2) With and Without ALFQ Adjuvant in Healthy Adults

This study is testing a new flu vaccine with and without an added booster to see if it helps healthy adults aged 18 to 50 build a stronger immune response.

Quick facts

• Phase: Phase 1
• Study type: Interventional
• Enrollment: 45 (estimated)
• Ages: 18 Years to 50 Years
• Sex: All
• Sponsor: National Institutes of Health Clinical Center (CC) (NIH)
• Drugs / interventions: immunotherapy
• Locations: 1 site (Bethesda, Maryland)
• Trial ID: NCT06863142 on ClinicalTrials.gov

What this trial studies

This Phase I clinical trial evaluates the safety, tolerability, and immune response of an experimental flu vaccine called FluMos-v2, both with and without an adjuvant known as ALFQ. Healthy adults aged 18 to 50 who have received at least one flu vaccine in recent seasons will participate in the study, which involves 12 clinic visits over 15 months. Participants will receive two vaccinations approximately four months apart and will monitor their health through daily diaries and follow-up calls. The study aims to determine if the addition of the ALFQ adjuvant enhances the immune response to the vaccine.

Who should consider this trial

Good fit: Ideal candidates are healthy adults aged 18 to 50 who have received at least one flu vaccine from the 2020-21 season through the 2023-24 season.

Not a fit: Patients who are not healthy or who have not received a recent flu vaccine may not benefit from this study.

Why it matters

Potential benefit: If successful, this vaccine could provide improved protection against seasonal influenza.

How similar studies have performed: Other studies have shown promise with similar vaccine approaches, but this specific combination is novel.

Eligibility criteria

* INCLUSION CRITERIA:
* A participant must meet all of the following criteria:

  * Healthy adults between the ages of 18-50 years, inclusive
  * Based on history and physical examination, be in good general health and without a history of any of the conditions listed in the exclusion criteria
  * Received at least one licensed influenza vaccine from the 2020-2021 influenza season through the 2024-2025 influenza season
  * Able and willing to complete the informed consent process
  * Available for clinic visits for 68 weeks after enrollment, including through the 2025-2026 influenza season
  * Able to provide proof of identity to the satisfaction of the study clinician completing the enrollment process
  * Physical examination and laboratory results without clinically significant findings and a Body Mass Index (BMI) \<= 35 within the 56 days before enrollment
  * Agrees to not receive the 2025-2026 licensed influenza vaccination during study participation due to potential confounding of study results
  * Willing to have blood and mucosal samples collected, stored indefinitely, and used for research purposes
* Laboratory Criteria within 56 days before enrollment

  * White blood cells (WBC) and differential within institutional normal range or accompanied by approval of the site Principal Investigator (PI) or designee
  * Total lymphocyte count \>= 800 cells/microL
  * Platelets = 125,000 - 400,000 cells/microL
  * Hemoglobin within institutional normal range or accompanied by approval of the PI or designee
  * Alanine aminotransferase (ALT) \<= 1.25 x institutional upper limit of normal (ULN)
  * Aspartate aminotransferase (AST) \<= 1.25 x institutional ULN
  * Alkaline phosphatase (ALP) \< 1.1 x institutional ULN
  * Total bilirubin within institutional normal range or accompanied by approval of the PI or designee
  * Serum creatinine \<= 1.1 x institutional ULN
  * Negative for HIV infection by an FDA-approved method of detection
* Criteria applicable to women of childbearing potential:

  * Negative beta-human chorionic gonadotropin (Beta-HCG) pregnancy test (urine or serum) on the day of enrollment
  * Agrees to use an effective method of birth control from at least 21 days prior to enrollment through the end of the study.

EXCLUSION CRITERIA:

* A participant will be excluded if one or more of the following conditions apply:

  \-- Women who are breast-feeding or planning to become pregnant during the study
* A Participant has received any of the following substances:

  * Receipt of any licensed influenza vaccine within 6 months prior to enrollment.
  * Plan to or are required to receive the 2025-2026 licensed influenza vaccine
  * Live attenuated vaccines within 4 weeks prior to enrollment
  * Inactivated vaccines within 2 weeks prior to enrollment
  * mRNA vaccines within 4 weeks prior to enrollment
  * Receipt of 20 mcg of the influenza vaccine VRC-FLUNPF081-00-VP (HA-F A/Sing, VRC 316, Group 1)
  * Receipt of the mosaic quadrivalent influenza vaccine VRC-FLUMOS0111-00-VP (FluMos-v1, VRC 325)
  * Receipt of the mosaic hexavalent influenza vaccine VRC-FLUMOS0116-00-VP (FluMos-v2, VRC 326)
  * More than 10 days of systemic immunosuppressive medications or cytotoxic medications within the 4 weeks prior to enrollment or any within the 14 days prior to enrollment
  * Blood products within 16 weeks prior to enrollment
  * Investigational research agents within 4 weeks prior to enrollment or planning to receive investigational products while on the study
  * Current allergy treatment with allergen immunotherapy with antigen injections, unless on maintenance schedule
  * Current anti-TB prophylaxis or therapy
* Participant has a history of any of the following clinically significant conditions:

  * Serious reactions to vaccines that preclude receipt of the study vaccinations as determined by the PI or designee
  * Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema
  * Asthma that is not well controlled
  * Diabetes mellitus (type I or II), except for gestational diabetes
  * Thyroid disease that is not well controlled
  * Idiopathic urticaria within the past year
  * Immune-mediated diseases, such as autoimmune or autoinflammatory diseases, or immunodeficiencies
  * Hypertension that is not well controlled
  * Bleeding disorder diagnosed by a doctor (e.g., factor deficiency, coagulopathy, or platelet disorder requiring special precautions) or significant bruising or bleeding difficulties with IM injections or blood draws
  * Malignancy that is active or history of malignancy that is likely to recur during the period of the study
  * Seizure disorder other than 1) febrile seizures, 2) seizures secondary to alcohol withdrawal more than 3 years ago, or 3) seizures that have not required treatment within the last 3 years
  * Asplenia, functional asplenia or any condition resulting in the absence or removal of the spleen
  * Guillain-Barre Syndrome
  * Any medical, social condition, occupational reason, or other reason that, in the judgment of the PI or designee, is a contraindication to protocol participation or impairs a participant s ability to give informed consent, including but not limited to clinically significant forms of infectious diseases, drug or alcohol abuse, autoimmune diseases, psychiatric disorders, or heart disease.

Where this trial is running

Bethesda, Maryland

• National Institutes of Health Clinical Center — Bethesda, Maryland, United States (Recruiting)

Study contacts

• Principal investigator: Lasonji A Holman, C.R.N.P. — National Institute of Allergy and Infectious Diseases (NIAID)
• Study coordinator: VRC Clinic

Conditions Influenza Prevention; Seasonal Influenza; Dose - Escalation; Immune Response; Viral Infection; Respiratory Illness; Experimental Vaccine; Experimental Adjuvant