Inclusion:
* Provision of signed and dated informed consent form
* Stated willingness to comply with all study procedures and availability for the duration of the study, as well as have deidentified samples and data stored for future research.
* Able to proficiently speak, read, and write English.
* Participant is allowed to participate in subsequent influenza seasons even if they will be \>40 years old.
* In good general health as evidenced by medical history
Exclusion:
* CBC with differential, lymphocyte phenotyping with T, B, and natural killer cells (TBNK), complete metabolic panel, anti-CMV immunoglobulin (Ig) G and IgM, and/or anti-Epstein-Barr virus (EBV) antibody panel values outside of the Yale Department of Laboratory Medicine normal reference ranges and deemed clinically significant by the PI at the time of screening.
* Positive result for anti-HIV 1/2 antibody screening at the time of screening.
* Prior receipt of a current seasonal influenza vaccine (for the season of participation).
* History of allergy or hypersensitivity to any components of the study vaccine (e.g., egg protein).
* History of severe reactions to vaccines.
* Use of an oral glucocorticoid within the past 30 days.
* Receipt of a live-attenuated vaccine within the past 3 months.
* Receipt of any experimental vaccine.
* Receipt of any other type of vaccine (non-live and non-experimental, e.g., tetanus, diphtheria, and pertussis \[TDaP\]) within the past 3 months.
* Planned vaccination before day 100 after study vaccination.
* Current or recent use (within the past 90 days) of immunoglobulin therapy.
* Surgery within the past 8 weeks, or planned surgery before day 28.
* Current (within the past 30 days) treatment for active malignancy.
* Cancer chemotherapy in the past 2 years.
* Administration of any blood products within 90 days of the screening, or planned administration before day 100.
* History of parasitic, amebic, fungal, or mycobacterial infections within the past 1 year, with the exception of tinea pedis and onychomycosis.
* History of autoimmune or autoinflammatory disease.
a. In particular skin-related (i.e. psoriasis, lichen planus, lupus, neutrophilic dermatoses, atopic dermatitis)
* History of keloids
* History of a bleeding disorder.
* Current use (within the past 30 days) of illicit drugs (per subject report), with the exception of marijuana.
* Current alcohol use disorders (criteria per Diagnostic and Statistical Manual of Mental Disorders, fifth edition), within the past 30 days.
* Serious, ongoing, uncontrolled infection within the past 30 days as per the judgement of the PI.
* History of Guillain-Barre syndrome (GBS).
* Body Mass Index ≥ 30.
* Known or suspected immunodeficiency within 1 year, including documented HIV infection.
* Pregnancy or planning to become pregnant during the study period. (Women of childbearing potential must have a negative urine or serum pregnancy test at screening.)
* Presence of conditions that, in the judgment of the PI, may put the individual at undue risk or compromise the scientific objectives of the study.
Co-enrollment guidelines: Co-enrollment in other trials is restricted, other than enrollment on observational studies. Consideration for co-enrollment in trials evaluating the use of a licensed medication will require the approval of the PI. Study staff should be notified of co-enrollment on any other protocol as it may require the approval of the PI.
