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

Background: Influenza (flu) virus causes 3 to 5 million cases of severe illness and up to 650,000 deaths per year worldwide. Current vaccines work well against single strains of flu virus. But no single vaccine works well against all flu viruses that can cause illness. Objective: To test an experimental flu vaccine (FluMos-v2) in healthy adults. Eligibility: Healthy adults aged 18 to 50 years. Design: Participants will have 11 clinic visits in 10 months. They must agree not to get a licensed flu vaccine while taking part in this study. FluMos-v2 will be given with a needle injected into a muscle in the upper arm. Participants will receive a follow-up phone call the following day. Participants will be given a diary card, a ruler, and a thermometer. They will take their temperature every day for 7 days after receiving the shot. They will measure any skin changes at the injection site. They will record their findings and how they feel. Participants will receive a second FluMos-v2 shot after 4 months. They will repeat the other follow-up steps. Participants will have 9 other clinic follow-up visits. Blood will be drawn at each visit. Participants should also come to the clinic if they develop flu-like symptoms during the study. Participants may opt for an apheresis 2 weeks after each shot: Blood will be removed through a needle in the vein of 1 arm. The blood will run through a machine that separates out the white blood cells. The remaining blood is returned through a needle in the other arm.

* 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 * For Part A: Received at least one licensed influenza vaccine from 2018 through the 2022-2023 influenza season * Able and willing to complete the informed consent process * For Part A: Available for clinic visits for 40 weeks after enrollment, including through the 2023-2024 influenza season * For Part B: Available for clinic visits for 40 weeks after enrollment, including through the 2024-2025 influenza season * For Part B: Agrees to undergo four lymph node FNAs. * 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) \= 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) \