This study aims to test the hypothesis that gene transcriptional changes occur within 24 hours of virus exposure in the blood and nasal mucosa, and to identify early biomarker signatures that are predictive of higher viral shedding at the peak of disease

This study will systematically investigate the early pre-symptomatic period following exposure to influenza in humans. The data obtained will be essential for further understanding of the natural history of human antiviral responses, and will allow us to identify a panel of biomarkers that can predict which individuals will go on to more severe symptoms and higher viral shedding, so that treatments and other interventions can be made at an early stage.

Inclusion Criteria:

• Healthy persons aged 18 to 55 years, able to give informed consent

Exclusion Criteria:

• Chronic respiratory disease (asthma, chronic obstructive pulmonary disease, rhinitis, sinusitis) in adulthood
• Inhaled bronchodilator or steroid use within the last 12 months
• Use of any medication or other product (prescription or over-the-counter) for symptoms of rhinitis or nasal congestion within the last 6 months
• Acute upper respiratory infection or sinusitis in the past 6 weeks
• Smoking in the past 6 months OR >5 pack-year lifetime history
• Subjects with allergic symptoms present at baseline
• Clinically relevant abnormality on chest X-ray
• Those in close domestic contact (i.e. sharing a household with, caring for, or daily face to face contact) with children under 3 years, the elderly (>65 years), immunosuppressed persons, or those with chronic respiratory disease
• Subjects with known or suspected immune deficiency
• Receipt of systemic glucocorticoids (in a dose ≥ 5 mg prednisone daily or equivalent) within one month, or any other cytotoxic or immunosuppressive drug within 6 months prior to challenge
• Known immunoglobulin A deficiency, immotile cilia syndrome, or Kartagener's syndrome
• History of frequent nose bleeds
• Any significant medical condition or prescribed drug deemed by the study doctor to make the participant unsuitable for the study
• Pregnant or breastfeeding women
• Positive urine drug screen
• Detectable baseline haemagglutination inhibition titres against influenza challenge strains
• History of hypersensitivity to eggs, egg proteins, gentamicin, gelatin or arginine, or with life-threatening reactions to previous influenza vaccinations

All women of childbearing age will have a pregnancy test performed prior to virus inoculation to exclude pregnancy and be required to use contraception throughout the study.

Data will be shared with Duke university, such as ethnicity and age. It will be identifiable only by their unique study code, with no personal details.