The purpose of this study is to characterize the safety and immunogenicity of AZD9838 and AZD6563 when administered as a single dose vaccination against SARS-CoV-2 in adults.

This is a Phase I, open-label, randomized, active-controlled study to assess the safety and immunogenicity of 2 dosages of AZD9838 and 2 dosages of AZD6563 compared with a licensed SARS-CoV-2 mRNA vaccine in approximately 240 healthy participants. AZD6563 will be assessed in adults 18 years of age and older. AZD9838 will be assessed in adults 18 to 64 years of age only.

The duration of each participant's involvement in the study will be approximately 12 months following administration of study vaccination.

Key Inclusion Criteria:

• Adults ≥ 18 years at the time of signing informed consent.
• Self-reported History of SARS-CoV-2 infection at least 6 months prior to study vaccination AND/OR prior completion of primary series vaccination against COVID-19, with the final dose received at least 6 months prior to study vaccination
• Negative SARS-CoV-2 RT-PCR test at Visit 1
• Body mass index (BMI) of <35 kg/m2 at screening
• Medically stable - according to the judgement of the investigator, hospitalization within the study is not anticipated and participant is likely to remain in the study through the end of the protocol specified follow-up.

Key Exclusion Criteria:

• Acute illness/infection on day prior or day of dosing
• History of hypersensitivity to any component of the study vaccination, severe adverse reaction associated with a vaccine and/or severe allergic reaction
• Positive COVID-19 test result within 6 months of Visit 1
• Receipt of licensed, authorized, or investigational COVID-19 vaccines in the 6 months prior to administration of study intervention or expected receipt through completion of Visit 5.
• Receipt of any COVID-19 monoclonal antibody (licensed or investigational) within 3 months or receipt of immunoglobulin (non-COVID related) or blood products within 6 months prior to administration of study intervention, or expected receipt during the study
• Receipt of any licensed or investigational vaccine (other than licensed influenza vaccines or non-study COVID-19 vaccines) within 30 days prior to Visit 1 or expected receipt prior to completion of Visit 4. Licensed influenza vaccines are permitted beginning > 14 days before and > 14 days after administration of study intervention.
• Previous history of myocarditis or pericarditis
• Woman who are pregnant, lactating, or of child-bearing potential and not using a contraception or abstinence from at least 4 weeks prior to study vaccination and until at least 6 months after study vaccination
• Lab values above ULN (Serum creatinine, AST, ALT), below LLN (hemoglobin, WBC, Platelet count) or any lab value that in the opinion of the investigator is clinically significant or might confound analysis of the study results. Participants with laboratory values outside of the normal range may have the abnormal test repeated within the screening window and if the values are normal, then the participant can be randomized. If the repeated value remains outside of the normal range but it is not felt to be clinically significant by the Investigator, the case can be discussed with the AstraZeneca study physician and if they both agree the value is not clinically significant, the participant can be randomized
• History of malignancy within 5 years (treated non-melanoma skin cancer and locally treated cervical cancers allowed)
• Known or suspected congenital or acquired immunodeficiency
• Known or suspected autoimmune conditions as determined by history and /or physical examination
• Active infection with hepatitis B or C
• Troponin I levels above the normal range at the screening visit
• History of hypersensitivity to kanamycin or any aminoglycoside antibiotics (eg, neomycin, streptomycin, tobramycin, and gentamicin).

Qualified researchers can request access to anonymized individual patient-level data from AstraZeneca group of companies sponsored clinical trials via the request portal Vivli.org. All requests will be evaluated as per the AZ disclosure commitment: https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

"Yes", indicates that AZ are accepting requests for IPD, but this does not mean all requests will be approved.

AstraZeneca will meet or exceed data availability as per the commitments made to the EFPIA/PhRMA Data-Sharing Principles. For details of our timelines, please refer to our disclosure commitment at https://astrazenecagrouptrials.pharmacm.com/ST/Submission/Disclosure.

When a request has been approved AstraZeneca will provide access to the anonymized individual patient-level data via secure research environment Vivli.org. A Signed Data Usage Agreement (non-negotiable contract for data accessors) must be in place before accessing requested information.