Phase 1 Trial of ChAd68 and Ad5 Adenovirus COVID-19 Vaccines Delivered by Aerosol

Inclusion Criteria: 1. Healthy human subjects who are between 18 and 65 years of age. 2. Have completed a COVID vaccine series with at least three doses of a licensed mRNA vaccine at least 3 months prior. 3. HIV antibody negative. 4. Able to understand and comply with protocol requirements and instructions; able to attend scheduled study visits and complete required investigations. 5. For women, negative pregnancy test and for those women of child-bearing potential practising two acceptable forms of contraception for the duration of the study. 6. For men, using barrier contraception for the duration of the study. 7. No history of COVID infection OR history of documented COVID infection at least 6 months prior, dated from either a self-reported positive rapid antigen test or positive PCR test (self-reported or documented). For participants with a history of COVID infection, anti-nucleocapsid antibodies will be measured prior to enrolment to confirm infection. Exclusion Criteria: 1. Subjects who have received any recombinant adenoviral-vectored COVID-19 vaccine, e.g. AstraZeneca COVISHIELD COVID-19 vaccine. 2. Pregnant or lactating women. 3. Subjects who have any acute or chronic illnesses, any relevant findings on physical examination or are receiving any immunosuppressive therapy in the opinion of the investigator likely to affect the immune system including current use of inhaled or nasal steroids. 4. Subjects with a history of any bleeding disorder or receiving any drug treatment that in the opinion of the investigator may increase the risk of bleeding. 5. Subjects with a history of respiratory diseases requiring regular treatment, e.g. asthma, COPD, interstitial lung diseases, bronchiectasis. 6. Current cigarette smokers, current e-cigarette smokers and ex-smokers who have quit less than a year ago, as reported by the subject. 7. Subjects with clinically significant abnormal baseline spirometry tests: FEV1\<80% predicted, FVC\<80% predicted, FEV1/FVC\<70%; DLCO\<70% predicted. 8. Any health-related condition for which study bronchoscopy is contraindicated. 9. Subjects whose baseline laboratory values are outside of the normal range, unless the abnormality is considered not clinically relevant by the investigator. A single repeat test is allowed during the screening period. 10. Subjects whose use of alcohol or drugs would, in the opinion of the investigator, interfere with adherence to the study protocol. 11. Subjects who are using, or have a history of using, inhaled cocaine, metamphetamine or other inhaled or smoked recreational drugs. Subjects who give a history of smoking marijuana more than a year ago may be enrolled as long as they agree not to smoke marijuana for the duration of the study. 12. Failure to provide written consent. 13. Known allergy to vaccine components. 14. Any abnormality on chest x-ray suggestive of clinically significant respiratory disease. 15. Previous receipt of any experimental adenovirus-vector vaccine by the aerosol route. 16. History of severe reaction to a previous COVID vaccination (including hives, difficulty breathing, angioedema, high fever, seizure). 17. History of venous or arterial thrombosis with thrombocytopenia following any vaccination. 18. History of cerebral venous thrombosis with thrombocytopenia. 19. History of heparin induced thrombocytopenia. 20. History of myocarditis or pericarditis. 21. History of Bell's Palsy. 22. History of hospitalization with an admitting diagnosis of primary COVID infection.