Quadrivalent influenza HA stem vaccine (SteMos1) with or without ALFQ adjuvant in healthy adults

VRC 329: A Phase I Open-Label, Clinical Trial to Evaluate the Safety, Tolerability, and Immunogenicity of a Quadrivalent Influenza HA Stem Vaccine VRC-FLUMOS0122-00-VP (STEMos1) With and Without ALFQ Adjuvant in Healthy Adults

This will test a new quadrivalent 'stem' flu vaccine called SteMos1 given with or without the ALFQ adjuvant in healthy adults aged 18–50 who have had at least one flu vaccine since 2020.

Quick facts

• Phase: PHASE1
• Study type: Interventional
• Enrollment: 56 (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: NCT07111078 on ClinicalTrials.gov

What this trial studies

This phase 1, open-label, dose-escalation trial enrolls healthy adults 18–50 to receive two intramuscular doses of the SteMos1 HA-stem quadrivalent vaccine given four months apart, with or without the ALFQ adjuvant. Participants are monitored in clinic for at least 30 minutes after each injection, keep a 7-day post-vaccination diary, and return for 12 clinic visits over about 15 months. Primary goals are to measure safety and tolerability, with secondary measures of immune responses including magnitude and breadth against multiple HA stem antigens. The vaccine contains stabilized HA stems from four influenza A strains and the adjuvant is an Army Liposome Formulation containing QS-21 intended to boost immune responses.

Who should consider this trial

Good fit: Healthy adults 18–50 who have received at least one licensed influenza vaccine since 2020, are in generally good health with BMI ≤35, can read English, and can commit to the 68-week follow-up schedule and clinic visits are ideal candidates.

Not a fit: People outside the 18–50 age range, those who are immunocompromised, pregnant, have significant medical conditions, or cannot attend long-term clinic visits are unlikely to benefit from participating.

Why it matters

Potential benefit: If successful, the vaccine plus adjuvant could produce broader and stronger immune protection against multiple influenza A strains and help improve pandemic preparedness.

How similar studies have performed: Early-phase work on HA-stem vaccine concepts and on adjuvanted influenza vaccines has shown promising safety and immune responses, but the specific SteMos1 plus ALFQ combination is novel and still being tested.

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
* The ability to read and comprehend English as all consent and recruitment materials are in English.
* Available for clinic visits for 68 weeks after the first dose, 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 any 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:

* WBC and differential within institutional normal range or accompanied by approval of the site Principal Investigator (PI) or designee
* Total lymphocyte count \>= 800 cells/microliter
* Platelets = 125,000-400,000 cells/mircoliter
* 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 means of birth control from at least 21 days prior to enrollment through the end of the study

EXCLUSION CRITERIA:

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 or lab-confirmed influenza infection within 6 months prior to enrollment.
* Plan to or are required to receive the 2025-2026 or 2026-2027 licensed influenza vaccines
* 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 the HA ferritin influenza vaccine VRC-FLUNPF081-00-VP alone or in prime-boost regimens with VRC-FLUDNA082-00-VP (HA-F A/Sing, DNA A/Sing, VRC 316).
* 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-Barr(SqrRoot)(Copyright) 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: Lesia K Dropulic, M.D. — National Institute of Allergy and Infectious Diseases (NIAID)
• Study coordinator: VRC Clinic

Conditions: Influenza Prevention, Pandemic Influenza Prevention, Dose-Escalation, INFLUENZA VIRUS, Immune Response, Respiratory Illness, Experimental Vaccine, Safety