INCLUSION CRITERIA:  A subject must meet all of the following criteria:  Healthy adults between the ages of 18-50 years inclusive Based on history and physical examination, in good general health and without history of any of the conditions listed in the exclusion criteria Received at least one licensed influenza vaccine from 2016 through the 2019-2020 influenza season Able and willing to complete the informed consent process Available for clinic visits for 40 weeks after enrollment and through an 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  Laboratory Criteria within 56 days before enrollment  White blood cells (WBC) and differential within institutional normal range or accompanied by the site Principal Investigator (PI) or designee approval Total lymphocyte count >=800 cells/microliter Platelets = 125,000 - 500,000 cells/microliter Hemoglobin within institutional normal range or accompanied by the PI or designee approval 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 the PI or designee approval. Serum creatinine <=1.1 x institutional ULN Negative for HIV infection by an FDA-approved method of detection  Negative for SARS-CoV-2 prior to enrollment  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:  A subject will be excluded if one or more of the following conditions apply:  Breast-feeding or planning to become pregnant during the study  Subject has received any of the following substances:  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 Live attenuated vaccines within 4 weeks prior to enrollment Inactivated vaccines within 2 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 Previous investigational H1, H2, or H10 influenza vaccines Groups 1A, 2A, and 3A only: Receipt of the 2020-2021 season s licensed influenza vaccine at any time prior to enrollment  Groups 1B, 2B, and 3B only: Receipt of the 2020-2021 season s licensed influenza vaccine within 4 months prior to enrollment.  Subject has a history of any of the following clinically significant conditions:  Serious reactions to vaccines that preclude receipt of the study vaccination as determined by the investigator Hereditary angioedema, acquired angioedema, or idiopathic forms of angioedema Asthma that is not well controlled Diabetes mellitus (type I or II), with the exception of gestational diabetes Thyroid disease that is not well controlled Idiopathic urticaria within the past year Autoimmune disease or immunodeficiency 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 Previous or current infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) documented by PCR test Any medical, psychiatric, social condition, occupational reason or other responsibility that, in the judgment of the investigator, is a contraindication to protocol participation or impairs a subject s ability to give informed consent.