The trial protocol was not approved by the regulatory authorities.

Subjects who have completed the primary mRNA vaccine immunizations and the 1st booster AZD1222 immunization for more than 6 months will be randomized to receive a 2nd booster dose of Ad5-nCoV/O, Ad5-nCoV/O-IH or mRNA-based COVID-19 vaccine in a ratio of 2:2:1.

This is a multicenter, randomized, observer-blind, and parallel-controlled clinical study to evaluate the immune responses and safety profiles in adults (≥ 18 years) receiving investigational products (intramuscular injection or nebulized inhalation) ≥ 180 days after the immunization of 2 doses of BNT162b2 vaccines plus one dose of booster AZD1222 vaccine. This study will enroll about 30% participants aged 60 years and above.

Subjects who have completed the primary mRNA vaccine immunizations and the 1st booster AZD1222 immunization for more than 6 months will be randomized to receive a 2nd booster dose of Ad5-nCoV/O, Ad5-nCoV/O-IH or mRNA-based COVID-19 vaccine in a ratio of 2:2:1.

Inclusion Criteria:

1. Participants aged 18 years and above at the time of screening.
2. Received the 1st booster vaccination at least 180 days earlier.
3. Agree to attend all visits and sign the written informed consent form.

Exclusion Criteria:

1. Have a history of seizures, epilepsy, encephalopathy, psychosis.
2. History of severe anaphylaxis or allergy to any vaccine component.
3. Positive urine pregnancy test result, pregnant, lactating women.
4. Medical history of Guillain-Barré syndrome.
5. Have had asthma attacks within 2 years.
6. Have severe nasal or oral diseases, such as rhinitis (sinusitis), allergic rhinitis, oral ulcer, throat swelling, etc.
7. Bleeding disorder (e.g. protein S or factor deficiency, coagulopathy or platelet disorder).
8. Have chronic systematic infection or chronic obstructive pulmonary disease (COPD), etc.
9. Administration of immunoglobulins and/or any blood products within three months prior to the planned administration of the vaccine candidate.
10. Current diagnosis or receiving treatment for tuberculosis or cancer.
11. History of SARS-CoV-2 infection for less than 3 months.
12. Received or plan to receive any vaccines (licensed or investigational), within 14 days before and after study vaccination.
13. Have an axillary temperature of > 37.0℃.
14. Any other significant diseases, disorders or findings which may significantly increase the risk to the volunteer because of participation in the study, and affect the ability of the volunteer to participate in the study or impair interpretation of the study data.

observer-blind clinical trial