Study in Adults of AZD1222 and rAd26-S Administered as Heterologous Prime-Boost Regimen for the Prevention of COVID-19

Inclusion Criteria:

1. Adults ≥ 18 years of age at the time of signing the informed consent

2. Overtly healthy as determined by medical evaluation, or

- Medically stable such that, according to the judgment of the investigator,
hospitalisation within the study period is not anticipated and the participant appears
likely to be able to remain in follow-up through the end of protocol-specified
follow-up.

o A stable medical condition is defined as disease not requiring significant change in
therapy or hospitalisation for worsening disease during the 3 months prior to
enrolment

3. Able to understand and comply with study requirements/procedures based on the
assessment of the investigator

4. Reproduction:

Female participants

1. Women of childbearing potential must:

- Have a negative pregnancy test on the day of screening and on Day 1

- Use one highly effective form of birth control for at least 28 days prior to Day
1 and agree to continue using one highly effective form of birth control through
60 days following administration of the second dose of study vaccine. A highly
effective method of contraception is defined as one that can achieve a failure
rate of less than 1% per year when used consistently and correctly.

Periodic abstinence, the rhythm method, and withdrawal are NOT acceptable methods of
contraception.

2. Women are considered of childbearing potential unless they meet either of the
following criteria:

- Surgically sterilised (including bilateral tubal ligation, bilateral
oophorectomy, or hysterectomy), or

- Postmenopausal

6. Capable of giving signed informed consent which includes compliance with the
requirements and restrictions listed in the informed consent form (ICF) and in
this protocol.

Exclusion Criteria:

Medical Conditions

1. Known past laboratory-confirmed SARS-CoV-2 infection.

2. Positive SARS-CoV-2 RT PCR test at screening.

3. Seropositivity to SARS-CoV-2 at screening.

4. Significant infection or other illness, including fever > 37.8°C on the day prior
to or on the day of randomization 5. Thrombocytopenia ≥ Grade 2 (i.e. < 100
000/mm^3) 6. Clinically significant neutropenia (as determined by the
investigator). 7. Clinically significant anaemia (as determined by the
investigator) 8. Any confirmed or suspected immunosuppressive or immunodeficient
state; including human immunodeficiency virus (HIV) infection; asplenia;
recurrent severe infections and use of chronic immunosuppressant medication
(within the past 6 months(≥ 20 mg/day of prednisone or its equivalent, given
daily or on alternate days for ≥ 15 days within 30 days prior to vaccination),
except topical/inhaled steroids or short-term oral steroids ( course lasting ≤ 14
days).

9. History of allergy to any component of the vaccine 10. Any history of anaphylaxis
or angioedema. 11. Current diagnosis of or treatment for cancer (except basal cell
carcinoma of the skin and uterine cervical carcinoma in situ).

12. History of serious psychiatric condition likely to affect participation in the
study.

13. Bleeding disorder (eg, factor deficiency, coagulopathy or platelet disorder), or
prior history of significant bleeding or bruising following IM injections or
venepuncture.

14 Suspected or known current alcohol or drug dependency. 15 History of Guillan-Barré
syndrome or any other demyelinating condition. 16 Any other significant disease,
disorder or finding which may significantly increase the risk to the participant
because of participation in the study, affect the ability of the participant to
participate in the study or impair interpretation of the study data.

17 Severe and/or uncontrolled cardiovascular disease, respiratory disease,
gastrointestinal disease, liver disease, renal disease, endocrine disorder and
neurological illness (mild/moderate well controlled comorbidities are allowed).

18. Prior splenectomy 19. History of cerebral venous sinus thrombosis or experienced
major venous and/or arterial thrombosis.

20. Receipt of any vaccine (licensed or investigational) other than the study
intervention within 30 days before and after each study vaccination.

21. Prior or planned receipt of an investigational or licensed vaccine or product
likely to impact on interpretation of the trial data (eg, adenovirus vectored
vaccines, any coronavirus vaccines).

22. Administration of immunoglobulins and/or any blood products within the 3 months
preceding the planned administration of the vaccine candidate.

23. Continuous use of anticoagulants, such as coumarins and related anticoagulants
(ie, warfarin) or novel oral anticoagulants (ie, apixaban, rivaroxaban, dabigatran and
edoxaban).

24. Participation in COVID-19 prophylactic drug trials for the duration of the study.

25. Involvement in the planning and/or conduct of the study (applies to both
AstraZeneca staff and/or staff at the study site).

26. Judgment by the investigator that the participant should not participate in the
study if the participant is unlikely to comply with study procedures, restrictions,
and requirements.

27. Previous randomisation in the present study 28. For female subjects only -
currently pregnant (confirmed with positive pregnancy test) or breastfeeding.

29. Unwilling to refrain from blood donation during the course of the study