Inclusion Criteria:
1. An informed consent form (ICF) has been signed and dated by the participant, an investigator, and a witness
2. Adults age between 21 and 30 years inclusive (at the time of consent)
3. Evidence of having had a complete primary COVID-19 vaccination course as recommended by the Ministry of Health\*, with the last vaccination at least 14 days before enrolment
4. Sero-suitable based on the pre-screening serology result 5a) Female participants must be willing and able to use contraception from 2 weeks before the scheduled date of viral challenge until 6 months after receipt of the final dose of study virus. Negative urine pregnancy tests will be required at screening, and on admission to the quarantine unit a negative serum beta human chorionic gonadotropin (β-hCG) is required prior to inoculation.
5b) Male participants who are willing to use one of the contraception methods described in the study protocol, from the time of the date of viral challenge, for 6 months.
6\) In good health with no history of clinically significant medical conditions (as described in Exclusion criteria) that would interfere with subject safety, as defined by medical history, physical examination and routine laboratory tests, ECG, and Chest X-Ray and determined by the Investigator at an admission evaluation.
7\) Willing and able to commit to participation in the study.
Exclusion Criteria:
1. History or evidence of any clinically significant or currently active cardiovascular, (including thromboembolic events), respiratory, dermatological, gastrointestinal, endocrine, haematological, hepatic, immunological, rheumatological, metabolic, urological, renal, neurological, psychiatric illness. Specifically:
1. Participants with any history of physician diagnosed and/or objective test confirmed asthma, chronic obstructive pulmonary disease, pulmonary hypertension, reactive airway disease, or chronic lung condition of any aetiology or who have experienced:
* Significant/severe wheeze in the past
* Respiratory symptoms including wheeze which has ever resulted in hospitalisation
* Known bronchial hyperreactivity to viruses
2. History of thromboembolic, cardiovascular or cerebrovascular disease
3. History or evidence of diabetes mellitus
4. Any concurrent serious illness including history of malignancy that could interfere with the aims of the study or a participant completing the study. Basal cell carcinoma within 5 years of treatment or with evidence of recurrence is also an exclusion
5. Migraine with associated neurological symptoms such as hemiplegia or vision loss. Cluster headache/migraine or prophylactic treatment for migraine
6. History or evidence of autoimmune disease or known immunodeficiency of any cause.
7. Other major disease that, in the opinion of the Investigator, could interfere with a participant completing the study and necessary investigations.
2. Any significant abnormality altering the anatomy or function of the nose or nasopharynx in a substantial way (including loss of or alterations in smell or taste), a clinically significant history of epistaxis (large nosebleeds) within the last 3 months, nasal or sinus surgery within 6 months of inoculation.
3. Clinically active rhinitis (including hay fever) or history of moderate to severe rhinitis, or history of seasonal allergic rhinitis likely to be active at the time of inclusion into the study and/or requiring regular nasal corticosteroids on an at least weekly basis, within 30 days of admission to quarantine.
4. History of anaphylaxis and/or a history of severe allergic reaction or significant intolerance to any food or drug, as assessed by the PI.
5. Significant history or presence of drug or alcohol misuse
6. Current use of any drugs taken through the nasal or inhaled route
7. Psychiatric illness including participants with a history of depression and/or anxiety with associated severe psychiatric comorbidities, for example psychosis.
Consider exclusion in the following cases: (a) Participants with history of anxiety-related symptoms of any severity within the last 2 years if the Generalized Anxiety Disorder-7 score is ≥4; (b)Participants with a history of depression of any severity within the last 2 years if the Patient Health Questionnaire-9 score is ≥4. (c) severe claustrophobia
8. Current active smokers: equivalent to \>5 cigarettes per week, including use of tobacco in any form (e.g., smoking or chewing) or other nicotine-containing products in any form (e.g., gum, patch) or electronic cigarettes.
Ex-smokers: Participants who have smoked \>5 pack years at any time \[5 pack years is equivalent to one pack of 20 cigarettes a day for 5 years\]. Ex-smokers that have smoked \<5 pack years at any time must not have smoked in the last 3 months.
9. Family history of 1st degree relative aged 50 years or less with sudden cardiac or unexplained death
10. Personal or Family History of unexpectedly severe COVID-19 (including a personal history of COVID-19 pneumonia), severe adverse response to any other viral disease e.g., Guillain-Barré, or a family history (described as a 1st degree relative) with clotting disorders
11. A total body weight of ≤ 45kg and a Body Mass Index (BMI) ≤18 kg/m2 and ≥28 kg/m2. The upper limit of BMI may be increased to 30kg/m2 at the PI's discretion, in the case of physically fit muscular individual
12. Venous access deemed inadequate for the phlebotomy demands of the study.
13. Any clinically significant abnormal finding on screening biochemistry, haematology and microbiology blood tests or urinalysis apart from minor deviations which are clinically acceptable and approved by the investigator.
Any of the following:
* Elevated HbA1C
* Positive HIV, active/chronic hepatitis B or C test.
14. A forced expiratory volume in 1 second (FEV1) and a forced vital capacity (FVC) \<80% of predicted value calculated using ATS/ERS guidance
15. Twelve-lead ECG recording with clinically relevant abnormalities as judged by the study investigator.
16. History of, or currently active symptoms suggestive of upper or lower respiratory tract infection (including reduced sense of taste and smell, raised body temperature and/or persistent cough) within 4 weeks prior to viral challenge.
17. Presence of cold-like symptoms and/or fever (defined as participant presenting with a temperature reading of \>37.9ºC) on Day -1 and/or pre-challenge on Day 0.
18. Evidence of any respiratory virus infection (on Respiratory PCR from upper respiratory tract sample) on admission to the quarantine unit, prior to challenge virus inoculation.
19. Receipt of a live vaccine within 60 days prior to the planned date of viral challenge, a non-live vaccine within 30 days prior to the planned date of viral challenge or intention to receive any vaccination(s) before the day 28 follow-up visit.
20. Receipt of blood or blood products, or loss (including blood donations) of 550 mL or more of blood during the 3 months prior to the planned date of viral challenge or planned during the 3 months after the final visit.
21. Medications:
1. Use of any medication or product (prescription or over the counter), for symptoms of allergic rhinitis, nasal congestion or respiratory tract infections or dermatitis/eczema including the use of regular nasal or medium-high potency dermal corticosteroids, and antibiotics within 7 days prior to the planned date of viral challenge apart from those described in Table 7, Permitted Medication or agreed by the investigator
2. Receipt of any investigational drug within 3 months prior to the planned date of viral challenge
3. Receipt of systemic (intravenous and/or oral) glucocorticoids or systemic antiviral drugs within 6 months prior to the planned date of viral challenge.
4. Over the counter medications (e.g., paracetamol or ibuprofen) where the dose taken over the preceding 7 days prior to the planned date of viral challenge had exceeded the maximum permissible 24-hour dose (e.g., \>4g per day of paracetamol over the preceding week).
5. Chronically used medications, including any medication known to be a moderate/potent inducer or inhibitor of cytochrome P450 enzymes, within 21 days prior to the planned date of viral challenge.
6. Participants who have received any systemic chemotherapy agent, immunoglobulins, or other cytotoxic or immunosuppressive drugs at any time.
22. Previous participation in a SARS-CoV-2 vaccine trial of a currently unapproved/unlicensed vaccine in Singapore
23. Participant is mentally or legally incapacitated in the opinion of the Investigator.
24. Females who:
1. Are breastfeeding within 6 months of study commencement, or
2. Had been pregnant within 6 months prior to the study, or
3. Had a positive pregnancy test at any point during screening or prior to inoculation with challenge virus
25. Anyone who is first degree related to anyone who is a delegated member of the research team.
26. Any other reason that the Investigator considered made the participant unsuitable to participate.
27. Participants with no knowledge of their family history.
