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 withouthistory 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, includingthrough the 2023-2024 influenza season

• For Part B: Available for clinic visits for 40 weeks after enrollment, includingthrough 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 cliniciancompleting the enrollment process

• Physical examination and laboratory results without clinically significant findingsand a Body Mass Index (BMI) <= 35 within the 56 days before enrollment

• For both Parts A and B: Agrees to not receive any licensed influenza vaccine duringstudy participation due to potential confounding of study results

• Willing to have blood samples collected, stored indefinitely, and used for researchpurposes

• For Part B: Willing to have lymph node samples collected, stored indefinitely, andused for research purposes

Laboratory Criteria within 56 days before enrollment

• White blood cells (WBC) and differential within institutional normal range oraccompanied 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 designeeapproval

• 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 ordesignee 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 orserum) on the day of enrollment

• Agrees to use an effective means of birth control from at least 21 days prior toenrollment through the end of the study for sample collection.

EXCLUSION CRITERIA:

A participant will be excluded if one or more of the following conditions apply:

-Women breast-feeding or planning to become pregnant during the study

Participant has received any of the following substances:

• More than 10 days of systemic immunosuppressive medications or cytotoxic medicationswithin 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 toreceive investigational products while on the study (Note: SARS-CoV-2 vaccineslicensed and/or approved by emergency use authorization are not exclusionary, butare 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 theexception 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.

• For Part A: Receipt of the 2023-2024 licensed influenza vaccine

• For Part B: Plan to or are required to receive the 2024-2025 licensed influenzavaccine

• For Part B: Receipt of any licensed seasonal influenza vaccine since the 2022-2023influenza season; including the 2023-2024 influenza season through the 2024-2025influenza season.

Subject has a history of any of the following clinically significant conditions:

• Serious reactions to vaccines that preclude receipt of the study vaccinations asdetermined 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, orplatelet disorder requiring special precautions) or significant bruising or bleedingdifficulties with IM injections or blood draws

• Malignancy that is active or history of malignancy that is likely to recur duringthe period of the study

• Seizure disorder other than 1) febrile seizures, 2) seizures secondary to alcoholwithdrawal more than 3 years ago, or 3) seizures that have not required treatmentwithin the last 3 years

• Asplenia, functional asplenia or any condition resulting in the absence or removalof the spleen

• Guillain-Barre Syndrome

• Any medical, psychiatric, or social condition, occupational reason, or otherresponsibility that, in the judgment of the investigator, is a contraindication toprotocol 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.