A Trial of a Next Generation COVID-19 Vaccine Delivered by Inhaled Aerosol

Inclusion criteria: 1. Adults who are 18-65 years old on the day of randomization (day 1) 2. Able to read, write and communicate using the English or French language. 3. Received at least 3 doses of an mRNA COVID vaccine. 4. Individuals of childbearing potential must have a negative pregnancy test prior to vaccination and be willing to practice effective contraception for 8 weeks post-vaccination. 5. Able to understand and comply with protocol requirements and instructions; able to report adverse events; able to attend scheduled study visits and complete required investigations. 6. For participants in the BAL sub-study, Complete Blood Count (CBC) and chemistry (creatinine) within normal limits. 7. For participants in the BAL sub-study, forced expiratory volume in 1 second (FEV1) \> the lower limit of normal (LLN), and FEV1/FVC (forced expiratory volume in 1 second/forced vital capacity) ratio above the LLN. 8. Agree not to enroll in any other intervention studies for the duration of the study where the intervention could be reasonably expected to be associated with adverse events overlapping with the inhaled vaccine or the immune responses being measured. Exclusion criteria: 1. Failure to provide informed consent. 2. Women who are pregnant or breastfeeding. 3. Have received any recombinant adenoviral-vectored COVID-19 vaccine (AstraZeneca \[Vaxzeria\] or Johnson \& Johnson (Janssen Jcovden). 4. COVID infection (positive PCR or antigen (Ag) test, self-reported or lab documented) within the last 90 days. 5. Last dose of a COVID vaccine administered less than 90 days prior to study entry. 6. Administration of any vaccine within 2 weeks of study entry. 7. Active pulmonary disease diagnosed by a physician including asthma, chronic bronchitis, interstitial lung disease, pulmonary hypertension, lung cancer, cystic fibrosis, or bronchiectasis. Current use of daily inhaled steroids for any condition. 8. Persons with HIV and a detectable HIV viral load (\>20 copies/mL), self-reported or confirmed. 9. Administration of monoclonal antibodies for treatment of COVID-19 infection within 3 months. 10. Moderately or severely immunocompromised (e.g. transplant recipients/CAR-T cell therapy, currently on chemotherapy for cancer or on potent immunosuppressant therapies e.g. rituximab or high dose steroids \[\>30 mg of prednisone equivalent daily\], or moderate or severe primary immunodeficiency syndrome). 11. History of severe reaction to previous COVID vaccination (e.g. hives, difficulty breathing, high fever, seizures, myocarditis, pericarditis)). 12. Potential contraindication to COVID vaccination (e.g. venous or arterial thrombosis with thrombocytopenia after vaccination, history of cerebral venous thrombosis with thrombocytopenia, history of heparin induced thrombocytopenia, history of myocarditis or pericarditis). 13. Known allergy to vaccine components or previous receipt of any experimental adenovirus-vector vaccine by the aerosol route. 14. Enrolment in any clinical trial of experimental treatment for COVID infection within 90 days. 15. For participants in the BAL sub-study, any health-related condition for which study bronchoscopy is contraindicated. 16. For participants in the BAL sub-study, current use of anticoagulants.