Phase II/III Study of AZD2816, for the Prevention of COVID-19 in Adults

AstraZeneca2,843 enrolled

Overview

The aim of the study is to assess the safety, and immunogenicity of AZD2816 for the prevention of coronavirus disease 2019 (COVID-19).

The purpose of this study is to demonstrate the safety and characterize the immunogenicity of AZD2816; AstraZeneca's candidate chimpanzee adenovirus Ox1 (ChAdOx1) vector vaccine against severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) variant strain B.1.351.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Enrollment

2,843

Conditions

COVID-19 SARS-CoV-2

Interventions

AZD1222BIOLOGICAL

10 mM histidine/histidine hydrochloride, 7.5% (w/v) sucrose, 35 mM sodium chloride, 1 mM magnesium chloride, 0.1% (w/v) polysorbate 80, 0.1 mM edetate disodium, 0.5% (w/v) ethanol, at pH 6.6.

AZD2816BIOLOGICAL

10 mM histidine/histidine hydrochloride, 7.5% (w/v) sucrose, 35 mM sodium chloride, 1 mM magnesium chloride, 0.1% (w/v) polysorbate 80, 0.1 mM edetate disodium, 0.5% (w/v) ethanol, at pH 6.6.

Eligibility

Sex: ALLMin age: 18 YearsMax age: 115 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: 1. Adult, ≥ 18 years of age at the time of consent. For inclusion in the SARS-CoV-2 seronegative population: 2. No history of laboratory-confirmed SARS-CoV-2 infection (ie, no positive nucleic acid amplification test and no positive antibody test). 3. Seronegative for SARS-CoV-2 at screening (lateral flow test to detect reactivity to the nucleoprotein). 4. Medically stable such that, according to the judgment of the investigator, hospitalization within the study period is not anticipated and the participant appears likely to be able to remain on study through the end of protocol-specified follow-up. 5. Able to understand and comply with study requirements/procedures (if applicable, with assistance by caregiver, surrogate, or legally authorized representative) based on the assessment of the investigator. 6. Signed informed consent obtained before conducting any study-related procedures. 7. Contraceptive use by women should be consistent with local regulations regarding the methods of contraception for those participating in clinical studies. Previously COVID-19 Vaccinated Participants: 8. Prior completion of a 2-dose primary homologous vaccination regimen against SARSCoV-2 with either AZD1222 (2 standard doses as authorized vaccine or as investigational product in a clinical trial with a 4 to 12-week dosing interval) or with an mRNA vaccine approved for emergency or conditional use. The second dose in all cases should have been administered at least 3 months prior to first administration of study intervention. Exclusion Criteria: 1. History of allergy to any component of AZD1222/AZD2816. 2. History of Guillain-Barré syndrome, any demyelinating disease, or any other neuroimmunologic condition. 3. Significant infection or other acute illness, including fever \> 100 °F (\> 37.8 °C) on the day prior to or day of randomization. 4. Any confirmed or suspected immunosuppressive or immunodeficient state, including asplenia or human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS). 5. Recurrent severe infections and use of immunosuppressant medication within the past 6 months (≥ 20 mg per day of prednisone or its equivalent, given daily or on alternate days for ≥ 15 days within 30 days prior to administration of study intervention). The following exceptions are permitted: Topical/inhaled steroids or short-term oral steroids (course lasting ≤ 14 days). 6. History of primary malignancy (see protocol). 7. History of thrombocytopenia and/or thrombosis, including participants who have experienced major venous and/or arterial thrombosis in combination with thrombocytopenia following vaccination with any COVID-19 vaccine. 8. History of heparin-induced thrombocytopenia, congenital thrombophilia (ie, factor V Leiden, prothrombin G20210A, antithrombin III deficiency, protein C deficiency and protein S deficiency, factor XIII mutation, familial dysfibrinogenemia), auto-immune thrombophilia (antiphospholipid syndrome, anti-cardiolipin antibodies, anti-β2- glycoprotein 1 antibodies), or paroxysmal nocturnal haemoglobinuria. 9. Clinically significant bleeding (eg, factor deficiency, coagulopathy, or platelet disorder), or prior history of significant bleeding or bruising following intramuscular injections or venepuncture. 10. Severe and/or uncontrolled cardiovascular disease, respiratory disease, gastrointestinal disease, liver disease, renal disease, endocrine disorder, or neurological illness, as judged by the Investigator. 11. Any other significant disease, disorder, or finding that 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. 12. Any autoimmune conditions, except mild psoriasis and vitiligo.

Locations (35)

Outcomes

Primary Outcomes

Number of Participants With Local and Systemic Solicited Treatment Emergent Adverse Events (TEAEs) in Primary Vaccination Cohort (PVC):- AZD2816 (4), Booster Cohorts:-AZD1222:AZD2816, and mRNA:AZD2816

An adverse event (AE) is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. Solicited AEs are local or systemic predefined events for assessment of reactogenicity. An e-diary was used to collect information on the timing and severity of the solicited AEs. Local AEs included pain, redness/erythema, tenderness, induration/swelling at the site of the injection. Systemic AEs included fever (\> 100 °F/37.8 °C), chills, muscle pains, fatigue, headache, malaise, nausea, and vomiting.

Time frame: During the 7-day follow-up period after vaccination (vaccines administered on Days 1 and 29 [only for primary vaccination cohort])

Number of Participants With Unsolicited TEAEs, Treatment-emergent Serious AEs (TESAEs), Medically Attended AEs (MAAEs), and Adverse Events of Special Interest (AESIs) in PVC:- AZD2816 (4), Booster Cohorts:- AZD1222:AZD2816, and mRNA:AZD2816

The AEs other than solicited AEs are reported as unsolicited AEs and were collected by "open question" at study visits. AE: any untoward medical occurrence in participant who received study drug without regard to possibility of causal relationship. TEAEs: events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. SAE: an AE resulting in any of following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience; persistent or significant disability/incapacity; congenital anomaly. MAAE: an AE leading to a non-routine/unscheduled medically-attended visit, to or from medical doctor for any reason. AESI: an event of scientific and medical interest specific to further understanding of study drug safety profile and require close monitoring and rapid communication by investigators to Sponsor.

Time frame: During the 28-day follow-up period after vaccination (vaccines administered on Days 1 and 29 [only for primary vaccination cohort])

Data from ClinicalTrials.gov

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Secondary Outcomes

Number of Participants With Local and Systemic Solicited TEAEs

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. Solicited AEs are local or systemic predefined events for assessment of reactogenicity. An e-diary was used to collect information on the timing and severity of the solicited AEs. Local AEs included pain, redness/erythema, tenderness, induration/swelling at the site of the injection. Systemic AEs included fever (\> 100 °F/37.8 °C), chills, muscle pains, fatigue, headache, malaise, nausea, and vomiting.

Time frame: During the 7-day follow-up period after vaccination (vaccines administered on Days 1 and 29 or Day 85 [only for primary vaccination cohorts])

Number of Participants With Unsolicited TEAEs, TESAEs, MAAEs, and AESIs

Time frame: During the 28-day follow-up period after vaccination (vaccines administered on Days 1 and 29 or Day 85 [only for primary vaccination cohorts])

GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Primary Vaccination Cohort:- AZD2816 (4) is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant.

Time frame: 28 days after second dose (Day 57)

GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) with response against B.1.351 variant is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: 28 days after second dose (Day 57)

GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4)

Time frame: 28 days after second dose (Day 57)

GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD2816 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- AZD1222:AZD2816 with response against B.1.351 variant is the comparator group and AZD1222 in Historical Control with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)

GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD2816 and Booster Cohort:- AZD1222:AZD1222

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- AZD1222:AZD2816 is the comparator group and Booster Cohort:- AZD1222:AZD1222 is the reference group, both compared for response against B.1.351 variant.

Time frame: 28 days after booster dose (Day 29)

GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD2816 and AZD1222 in Historical Control

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- AZD1222:AZD2816 is the comparator group and AZD1222 in Historical Control is the reference group, both compared for response against the original Wuhan-Hu-1 strain.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)

GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD2816 and Booster Cohort:- AZD1222:AZD1222

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- AZD1222:AZD2816 is the comparator group and Booster Cohort:- AZD1222:AZD1222 is the reference group, both compared for response against the original Wuhan-Hu-1 strain.

Time frame: 28 days after booster dose (Day 29)

GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD2816 and Primary Vaccination Cohort:- AZD1222 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- AZD1222:AZD2816 is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Primary Vaccination Cohort: 28 days after the second dose (Day 57)

GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD2816 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- mRNA:AZD2816 with response against B.1.351 variant is the comparator group and AZD1222 in Historical Control with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)

GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD2816 and Booster Cohort:- mRNA:AZD1222

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- mRNA:AZD2816 is the comparator group and Booster Cohort:- mRNA:AZD1222 is the reference group, both compared for response against B.1.351 variant.

Time frame: 28 days after booster dose (Day 29)

GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD2816 and AZD1222 in Historical Control

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- mRNA:AZD2816 is the comparator group and AZD1222 in Historical Control is the reference group, both compared for response against the original Wuhan-Hu-1 strain.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)

GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD2816 and Booster Cohort:- mRNA:AZD1222

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- mRNA:AZD2816 is the comparator group and Booster Cohort:- mRNA:AZD1222 is the reference group, both compared for response against the original Wuhan-Hu-1 strain.

Time frame: 28 days after booster dose (Day 29)

GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD2816 and Primary Vaccination Cohort:- AZD1222 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- mRNA:AZD2816 is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Primary Vaccination Cohort: 28 days after the second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD2816 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- AZD1222:AZD2816 with response against B.1.351 variant is the comparator group and AZD1222 in Historical Control with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD2816 and Booster Cohort:- AZD1222:AZD1222

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- AZD1222:AZD2816 is the comparator group and Booster Cohort:- AZD1222:AZD1222 is the reference group, both compared for response against B.1.351 variant.

Time frame: 28 days after booster dose (Day 29)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD2816 and AZD1222 in Historical Control

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- AZD1222:AZD2816 is the comparator group and AZD1222 in Historical Control is the reference group, both compared for response against the original Wuhan-Hu-1 strain.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD2816 and Booster Cohort:- AZD1222:AZD1222

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- AZD1222:AZD2816 is the comparator group and Booster Cohort:- AZD1222:AZD1222 is the reference group, both compared for response against the original Wuhan-Hu-1 strain.

Time frame: 28 days after booster dose (Day 29)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD2816 and Primary Vaccination Cohort:- AZD1222 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- AZD1222:AZD2816 is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Primary Vaccination Cohort: 28 days after the second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD2816 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- mRNA:AZD2816 with response against B.1.351 variant is the comparator group and AZD1222 in Historical Control with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD2816 and Booster Cohort:- mRNA:AZD1222

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- mRNA:AZD2816 is the comparator group and Booster Cohort:- mRNA:AZD1222 is the reference group, both compared for response against B.1.351 variant.

Time frame: 28 days after booster dose (Day 29)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD2816 and AZD1222 in Historical Control

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- mRNA:AZD2816 is the comparator group and AZD1222 in Historical Control is the reference group, both compared for response against the original Wuhan-Hu-1 strain.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD2816 and Booster Cohort:- mRNA:AZD1222

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- mRNA:AZD2816 is the comparator group and Booster Cohort:- mRNA:AZD1222 is the reference group, both compared for response against the original Wuhan-Hu-1 strain.

Time frame: 28 days after booster dose (Day 29)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD2816 and Primary Vaccination Cohort:- AZD1222 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- mRNA:AZD2816 is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Primary Vaccination Cohort: 28 days after the second dose (Day 57)

Number of Participants With TESAEs, MAAEs, and AESIs From Day 1 Through 6 Months Post Last Dose

An AE is any untoward medical occurrence in a participant who received study drug without regard to possibility of causal relationship. An SAE is an AE resulting in any of the following outcomes or deemed significant for any other reason: death; initial or prolonged inpatient hospitalization; life threatening experience (immediate risk of dying); persistent or significant disability/incapacity; congenital anomaly. The TEAEs are defined as events present at baseline that worsened in intensity after administration of study drug or events absent at baseline that emerged after administration of study drug. The MAAEs are defined as AEs leading to medically-attended visits that were not routine visits, or an otherwise unscheduled visit to or from medical doctor for any reason. The AESIs are events of scientific and medical interest specific to the further understanding of study drug safety profile and require close monitoring and rapid communication by the investigators to the Sponsor.

Time frame: During the 6 months follow-up period after vaccination (vaccines administered on Days 1 and 29 or Day 85 [only for primary vaccination cohorts])

GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant.

Time frame: 28 days after second dose (Day 57)

GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against the Original Wuhan-Hu-1 Strain.

Time frame: 28 days after second dose (Day 57)

GMT of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD2816 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Primary Vaccination Cohort:- AZD2816 (4) with response against B.1.351 variant is the comparator group and Primary Vaccination Cohort:- AZD2816 (4) with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: 28 days after second dose (Day 57)

GMT of SARS-CoV-2 nAb Against the B.1.351 Variant and the Original Wuhan-Hu-1 Strain by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) with response against B.1.351 variant is the comparator group and Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: 28 days after second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Primary Vaccination Cohort:- AZD2816 (4) is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant.

Time frame: 28 days after second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Primary Vaccination Cohort:- AZD2816 (4) is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against the original Wuhan-Hu-1 strain.

Time frame: 28 days after second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and the Original Wuhan Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) with response against B.1.351 variant is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: 28 days after second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant.

Time frame: 28 days after second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against the original Wuhan-Hu-1 strain.

Time frame: 28 days after second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD2816 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Primary Vaccination Cohort:- AZD2816 (4) with response against B.1.351 variant is the comparator group and Primary Vaccination Cohort:- AZD2816 (4) with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: 28 days after second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) with response against B.1.351 variant is the comparator group and Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: 28 days after second dose (Day 57)

GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD1222 and Primary Vaccination Cohort:- AZD1222 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- AZD1222:AZD1222 is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Primary Vaccination Cohort: 28 days after the second dose (Day 57)

GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD1222 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- AZD1222:AZD1222 with response against B.1.351 variant is the comparator group and AZD1222 in Historical Control with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)

GMT of SARS-CoV-2 nAb Against the B.1.351 Variant and the Original Wuhan-Hu-1 Strain by Booster Cohort:- AZD1222:AZD2816

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- AZD1222:AZD2816 with response against B.1.351 variant is the comparator group and Booster Cohort:- AZD1222:AZD2816 with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: 28 days after second dose (Day 57)

GMT of SARS-CoV-2 nAb Against the B.1.351 Variant and the Original Wuhan-Hu-1 Strain by Booster Cohort:- AZD1222:AZD1222

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information.Booster Cohort:- AZD1222:AZD1222 with response against B.1.351 variant is the comparator group and Booster Cohort:- AZD1222:AZD1222 with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: 28 days after second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD1222 and AZD1222 in Historical Control

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- AZD1222:AZD1222 is the comparator group and AZD1222 in Historical Control is the reference group, both compared for response against the original Wuhan-Hu-1 strain.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD1222 and Primary Vaccination Cohort:- AZD1222 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- AZD1222:AZD1222 is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 Variant.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Primary Vaccination Cohort: 28 days after the second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- AZD1222:AZD1222 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- AZD1222:AZD1222 with response against B.1.351 variant is the comparator group and AZD1222 in Historical Control with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD2816

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- AZD1222:AZD2816 with response against B.1.351 variant is the comparator group and Booster Cohort:- AZD1222:AZD2816 with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: 28 days after second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- AZD1222:AZD1222

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- AZD1222:AZD1222 with response against B.1.351 variant is the comparator group and Booster Cohort:- AZD1222:AZD1222 with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: 28 days after second dose (Day 57)

GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD1222 and Primary Vaccination Cohort:- AZD1222 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- mRNA:AZD1222 is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 variant.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Primary Vaccination Cohort: 28 days after the second dose (Day 57)

GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD1222 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- mRNA:AZD1222 with response against B.1.351 variant is the comparator group and AZD1222 in Historical Control with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)

GMT of SARS-CoV-2 nAb Against the B.1.351 Variant and the Original Wuhan-Hu-1 Strain by Booster Cohort:- mRNA:AZD2816

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- mRNA:AZD2816 with response against B.1.351 variant is the comparator group and Booster Cohort:- mRNA:AZD2816 with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: 28 days after second dose (Day 57)

GMT of SARS-CoV-2 nAb Against the B.1.351 Variant and the Original Wuhan-Hu-1 Strain by Booster Cohort:- mRNA:AZD1222

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Booster Cohort:- mRNA:AZD1222 with response against B.1.351 variant is the comparator group and Booster Cohort:- mRNA:AZD1222 with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: 28 days after second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD1222 and AZD1222 in Historical Control

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- mRNA:AZD1222 is the comparator group and AZD1222 in Historical Control is the reference group, both compared for response against the original Wuhan-Hu-1 strain.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD1222 and Primary Vaccination Cohort:- AZD1222 (4)

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- mRNA:AZD1222 is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) is the reference group, both compared for response against B.1.351 Variant.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Primary Vaccination Cohort: 28 days after the second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Booster Cohort:- mRNA:AZD1222 and the Original Wuhan-Hu-1 Strain Elicited by AZD1222 in Historical Control

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- mRNA:AZD1222 with response against B.1.351 variant is the comparator group and AZD1222 in Historical Control with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: Booster Cohort: 28 days after booster dose (Day 29) and Historical Control: 28 days after the second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD2816

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- mRNA:AZD2816 with response against B.1.351 variant is the comparator group and Booster Cohort:- mRNA:AZD2816 with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: 28 days after second dose (Day 57)

Percentage of Participants With Seroresponse of SARS-CoV-2 nAb Against B.1.351 Variant and the Original Wuhan-Hu-1 Strain Elicited by Booster Cohort:- mRNA:AZD1222

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline. Booster Cohort:- mRNA:AZD1222 with response against B.1.351 variant is the comparator group and Booster Cohort:- mRNA:AZD1222 with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: 28 days after second dose (Day 57)

GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD2816 (4) and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 (4) on Day 29

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Primary Vaccination Cohort:- AZD2816 (4) with response against B.1.351 variant is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: 28 days after first dose (Day 29)

GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4) on Day 29

Time frame: 28 days after first dose (Day 29)

GMT of SARS-CoV-2 nAb Against B.1.351 Variant Elicited by Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) and the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD1222 (4) on Day 29

Severe acute respiratory syndrome-coronavirus-2 nAb were measured by pseudoneutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information. Primary Vaccination Cohort:- AZD1222 + AZD2816 (4) with response against B.1.351 variant is the comparator group and Primary Vaccination Cohort:- AZD1222 (4) with response against the original Wuhan-Hu-1 strain is the reference group.

Time frame: 28 days after first dose (Day 29)

GMT of SARS-CoV-2 nAb Against the Original Wuhan-Hu-1 Strain Elicited by Primary Vaccination Cohort:- AZD2816 (4) and Primary Vaccination Cohort:- AZD1222 (4) on Day 29

Time frame: 28 days after first dose (Day 29)

GMT of ChAdOx1 nAb in Primary Vaccination Cohorts and Following a Booster Dose of AZD2816

Chimpanzee adenovirus Ox1 (ChAdOx1) vector nAb were measured by neutralisation assay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information.

Time frame: Booster Cohorts: 28 days after booster dose (Day 29) and Primary Vaccination Cohorts: 28 days after the second dose (Day 57 for 4-week dosing interval cohorts and Day 113 for 12-week dosing interval cohort)

Percentage of Participants With Seroresponse of ChAdOx1 nAb in Primary Vaccination Cohorts and Following a Booster Dose of AZD2816

Chimpanzee adenovirus Ox1 vector nAb were measured by neutralisation assay. Seroresponse was defined as \>= 4-fold increase in the GMT of nAb from baseline.

GMT of SARS-CoV-2 Spike Protein Binding Antibodies in Primary Vaccination Cohorts and Booster Cohorts

Severe acute respiratory syndrome-coronavirus-2 spike protein binding antibodies were measured by multiplexed immunoassay. The GMT was calculated as the antilogarithm of Σ(log base 2 transformed titre/n), i.e. as the anti-logarithm transformation of the mean of the log-transformed titre, where 'n' was the number of participants with titre information.

Percentage of Participants With Seroresponse of SARS-CoV-2 Spike Protein Binding Antibodies in Primary Vaccination Cohorts and Booster Cohorts

Severe acute respiratory syndrome-coronavirus-2 spike protein binding antibodies were measured by multiplexed immunoassay. Seroresponse was defined as \>= 4-fold increase in the GMT of spike protein binding antibodies from baseline.

Correlation Between ChAdOx1 nAb and SARS-CoV-2 nAb Titres

Severe acute respiratory syndrome-coronavirus-2 nAb and ChAdOx1 vector nAb were measured by pseudoneutralisation assay. Correlations were based on log2 titre values and assessed by using Spearman rank correlation for all cohorts except Primary Vaccination Cohort:- AZD2816 (12) for which Pearson correlation was used. The correlation coefficient is reported in values from +1 to -1 (+1= perfect association, 0 = no association, and -1= perfect negative association). The closer the correlation coefficient is to zero, weaker the association.