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.