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

Background: Vaccines help the body learn to fight infections. Some vaccines are combined with adjuvants, which are added substances that make vaccines work better. FluMos-v2 is an experimental flu vaccine; ALFQ is an experimental adjuvant. Objective: To test FluMos-v2, with and without the ALFQ adjuvant, in healthy adults. Eligibility: Healthy adults aged 18 to 50 years. They must have received at least one flu vaccine from the 2020-21 season through the 2024-25 flu season. They must also agree not to receive the licensed 2025-26 flu vaccine. Design: Participants will have 12 clinic visits over 15 months. Participants will be screened. They will have a physical exam and blood tests. On 2 visits, about 4 months apart, participants will receive a vaccination. The shots will be given into the muscle of the upper arm. They will get a follow-up call the day after each shot. They will keep a daily diary for 7 days; they will record their temperature and any other symptoms they feel after each shot. All clinic visits will include collection of blood, saliva, and nasal secretions. If participants develop flu symptoms (such as fever, runny nose, sore throat), they will be asked to come to the clinic. About 2 weeks after each vaccination, participants may opt to undergo apheresis: Blood will be taken from the body through a needle inserted into one arm. The blood will pass through a machine that separates out the white blood cells. The remaining blood will be returned to the body through a needle in the other arm.

* 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 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 * Available for clinic visits for 68 weeks after enrollment, 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) \= 800 cells/microL * Platelets = 125,000 - 400,000 cells/microL * Hemoglobin within institutional normal range or accompanied by approval of the PI or designee * Alanine aminotransferase (ALT) \