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 andwithout a history of any of the conditions listed in the exclusion criteria

• Received at least one licensed influenza vaccine from the 2020-2021 influenzaseason through the 2023-2024 influenza season

• Able and willing to complete the informed consent process

• Available for clinic visits for 68 weeks after enrollment, including throughthe 2025-2026 influenza season

• Able to provide proof of identity to the satisfaction of the study cliniciancompleting the enrollment process

• Physical examination and laboratory results without clinically significantfindings and a Body Mass Index (BMI) <= 35 within the 56 days before enrollment

• Agrees to not receive the 2025-2026 licensed influenza vaccination during studyparticipation due to potential confounding of study results

• Willing to have blood and mucosal samples collected, stored indefinitely, andused for research purposes

• Laboratory Criteria within 56 days before enrollment

• White blood cells (WBC) and differential within institutional normal range oraccompanied 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 thePI 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 ofthe 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 orserum) on the day of enrollment

• Agrees to use an effective method of birth control from at least 21 days priorto 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 or received the 2024-2025licensed 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 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 cytotoxicmedications within the 4 weeks prior to enrollment or any within the 14 daysprior to enrollment

• Blood products within 16 weeks prior to enrollment

• Investigational research agents within 4 weeks prior to enrollment or planningto 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 vaccinationsas 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, orimmunodeficiencies

• 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 orbleeding difficulties with IM injections or blood draws

• Malignancy that is active or history of malignancy that is likely to recurduring the period of the study

• Seizure disorder other than 1) febrile seizures, 2) seizures secondary toalcohol withdrawal more than 3 years ago, or 3) seizures that have not requiredtreatment within the last 3 years

• Asplenia, functional asplenia or any condition resulting in the absence orremoval of the spleen

• Guillain-Barre Syndrome

• Any medical, social condition, occupational reason, or other reason that, inthe judgment of the PI or designee, is a contraindication to protocolparticipation or impairs a participant s ability to give informed consent,including but not limited to clinically significant forms of infectiousdiseases, drug or alcohol abuse, autoimmune diseases, psychiatric disorders, orheart disease.