The investigators propose a unique methodology of studying infection and vaccination history and immune responses. As most studies in infection history are conducted on mice, limitations are inherent on their applicability to humans. A longitudinal comparison study following older adults (over the age of 65) hospitalized for influenza are followed through to their hospital discharge and vaccination in the following season. This will allow for the investigation of the course of infection, as well as impact on the response to vaccination.

Significance: This study will provide critical information on the best technique in vaccine candidate testing and improve influenza treatment approaches. The long-term goal of this research is to identify the T-cell responses that are surrogates (biomarkers) of serious complications of influenza in older adults and predict vaccine efficacy (prevention of influenza illness) and vaccine effectiveness (prevention of serious complications). Further, translating new insights into age-related immune dysfunction to the design of new influenza vaccines is critical to addressing this unmet need in the population aged 65 and older.

Innovation: The study will help in the validation of clinical tools and biomarkers as prognostic indicators of influenza illness severity in vaccinated older adults, point-of-care diagnostics that would direct other preventive strategies to reduce the impact of influenza illness in vaccinated older adults, and correlates of protection to evaluate the potential of new influenza vaccines to enhance protection against the serious complications of influenza illness. The investigators have established that GrzB activity and the IFNg: IL-10 ratio in influenza-stimulated PBMC correlate with protection against influenza, and preliminary data to show that low GrzB activity in influenza-stimulated PBMC correlates with more severe disease and higher levels of frailty. The innovations of this project are the established methods for developing correlates of protection, the clinical insights into how frailty affects immune-mediated protection against influenza, and the direct translation of this research to provide a reasonable method for primary care clinicians to estimate vaccine effectiveness in an individual older person. These results will translate to the practical design of clinical trials to evaluate the potential for new influenza vaccines to better protect against the serious complications of influenza and complement those based on antibody titers and/or clinical outcomes alone.

Inclusion Criteria:

1. Written informed consent provided by the participant.

2. Age 65 years of age or older admitted to Health Sciences North with at least one the following:

   • Laboratory confirmed influenza illness
   • Acute exacerbation of chronic obstructive pulmonary disease (AECOPD).
   • Any respiratory or influenza-like symptoms (dyspnea, cough, sore throat, myalgia, arthralgia, fever, delirium/altered level of consciousness) that a test for influenza was negative.

3. Willing to receive influenza vaccination in the subsequent flu season

Exclusion Criteria:

1. Patients whose reason for hospital admission was unrelated to influenza or (for example patients admitted due to trauma, elective surgery, or patients who have an alternative diagnosis that is clearly not respiratory).
2. Chest x-ray positive for pneumonia.
3. Study participants who cannot be vaccinated due to previous severe reaction to influenza vaccine, egg, latex, or thimerosol allergies, or refusal of vaccination.
4. Immunosuppressive disorders or medications (including oral prednisone in doses >10 mg daily).

Older adult patients (over the age of 65) admitted to Health Sciences North with laboratory confirmed influenza illness (LCII) and matched control subjects (non-LCII).