Trial to Evaluate the Safety, Tolerability, and Immunogenicity of a Mosaic Hexavalent Influenza Vaccine VRC-FLUMOS0116-00-VP (FluMos-v2) in Healthy Adults

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 2018 through the 2022-2023 influenza season Able and willing to complete the informed consent process Available for clinic visits for 40 weeks after enrollment, including through the 2023-2024 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 2023-2024 licensed influenza vaccination during study participation due to potential confounding of study results Willing to have blood 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 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 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 for sample collection. 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 (Note: SARS-CoV-2 vaccines licensed and/or approved by emergency use authorization are not exclusionary, but are subject to the criteria for timing of inactivated vaccines or mRNA vaccines) mRNA vaccines within 4 weeks prior to enrollment Current allergy treatment with allergen immunotherapy with antigen injections, unless on maintenance schedule Current anti-TB prophylaxis or therapy Receipt of investigational ferritin-based nanoparticle influenza vaccines, with the exception of participants previously enrolled in the VRC 316 study as follows: Group 2 (HA-F A/Sing prime, HA-F A/Sing boost), 3A (DNA A/Sing prime, HA-F A/Sing boost) or 4A (HA-F A/Sing prime, HA-F A/Sing boost). Receipt of the mosaic quadrivalent influenza vaccine VRC-FLUMOS0111-00-VP (FluMos-v1) Receipt of any licensed influenza vaccine within 6 months prior to enrollment. Receipt of the 2023-2024 licensed influenza vaccine Subject 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 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 Any medical, psychiatric, or 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, including but not limited to clinically significant forms of infectious diseases, drug or alcohol abuse, autoimmune diseases, psychiatric disorders, or heart disease.