How Healthy Adults Respond to the Nasal Flu Vaccine

This is a prospective interventional study evaluating mucosal immune and epithelial responses in healthy adults following administration of the FDA-approved live attenuated influenza vaccine (FluMist) given as an intranasal spray. Healthy volunteers aged 18 to 65 years who do not smoke and who meet eligibility criteria will be enrolled.

Participants will complete three study visits over approximately one week. At the first visit, informed consent, screening, baseline nasal swabs and nasal wash will be performed, followed by administration of FluMist. Follow-up nasal samples and safety assessments will be collected at approximately 2 and 4 days after vaccination.

Nasal samples will be analyzed using single-cell RNA sequencing, proteomics, and RT-qPCR to assess local immune, epithelial, and viral responses. Samples will be coded, stored under secure conditions, and retained for up to five years after study completion.

The objective of the study is to characterize early mucosal immune responses to FluMist vaccination and improve understanding of influenza vaccine-induced immunity at the site of infection.

• FluMist (Live Attenuated Influenza Vaccine) (Biological): FluMist is an FDA-approved live attenuated influenza vaccine administered as a nasal spray. Participants will receive a single standard dose of FluMist intranasally, with half the dose administered into each nostril by trained study personnel according to manufacturer instructions. The vaccine is used in this study to evaluate local mucosal and immune responses in the nasal cavity.

Primary outcomes

• Change in Nasal Mucosal Immune Response Following FluMist Vaccination [Baseline through 4 days post-vaccination]: This outcome measure evaluates changes in the nasal mucosal immune and epithelial response following administration of the intranasal live attenuated influenza vaccine (FluMist). Nasal swab and nasal wash samples will be collected at baseline (pre-vaccination) and at approximately 2 and 4 days post-vaccination. Samples will be analyzed using single-cell RNA sequencing, proteomics, and RT-qPCR to assess changes in immune cell populations, gene expression profiles, protein expression, and viral activity over time.

Sex: All, ages: 18 Years to 65 Years, accepts healthy volunteers

Inclusion Criteria:

* Healthy adults aged 18 to 65 years
* Non-smokers (no smoking or vaping within the past 6 months)
* No chronic lung disease or significant chronic medical conditions
* No current or recent (within 1 month) upper or lower respiratory infection
* Able and willing to provide informed consent
* Have not received the current seasonal influenza vaccine
* Able to comply with study procedures and follow-up visits

Exclusion Criteria:

* Age under 18 or over 65 years
* Pregnancy or breastfeeding
* Prisoners
* Non-English speaking individuals
* Immunocompromised individuals (including HIV/AIDS, immunosuppressive therapy, chemotherapy, or primary immunodeficiency)
* Chronic medical conditions including asthma, chronic lung, liver, kidney, neurologic, hematologic, metabolic, or significant cardiovascular disease (except isolated hypertension)
* History of chronic sinusitis or significant nasal allergies requiring frequent or daily treatment
* Acute moderate or severe illness at time of enrollment, with or without fever
* Receipt of influenza vaccine during the current season or within the past 2 weeks
* Receipt of another live vaccine within 4 weeks prior to enrollment or planned during study period
* Use of influenza antiviral medications (e.g., oseltamivir, zanamivir) within 48 hours prior to vaccination or planned use within 14 days after vaccination
* History of severe allergic reaction to influenza vaccine or any component of FluMist (including egg allergy if applicable)
* History of Guillain-Barré syndrome following influenza vaccination
* Any condition that, in the opinion of the investigator, would interfere with study participation or interpretation of results

• Kevin S Harrod, PhD, Principal investigator, UAB All Study (Central)