Evaluating the Dose, Safety, Tolerability, and Immunogenicity of Mosaic Hexavalent Influenza Vaccine VRCFLUMOS0116-00-VP (FluMos-v2) With and Without ALFQ Adjuvant in Healthy Adults

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.