A Phase I Study to Determine the Safety and Immunogenicity of a Bivalent ChAdOx1 Vectored Vaccine Against Zaire and Sudan Ebola Virus Species in UK Healthy Adult Volunteers
Phase: PHASE1
Conditions: Ebola
Sponsor: University of Oxford

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A phase I study to determine the safety and immunogenicity of a bivalent ChAdOx1 vectored vaccine 
against Zaire and Sudan Ebola virus species in UK healthy adult volunteers 
Study Reference: EBL07 
Protocol Version: 4.0 
Date: 01 Nov 2022 
Chief Investigator: Dr Paola Cicconi 
Principal Investigator: Dr Daniel Jenkin 
Lead Scientific Investigator: Prof Teresa Lambe 
Co-Investigator: Prof Sarah Gilbert 
Sponsor: University of Oxford 
Funder: Innovate UK 
REC Number: 21/FT/0108 
EudraCT Number: 2020-005853-26 
IRAS Reference: 301075 

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EBL07 Protocol V4.0, 01 Nov 2022                                                         
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Full Study Title 
A phase I study to determine the safety and immunogenicity of a 
bivalent ChAdOx1 vectored vaccine against Zaire and Sudan Ebola 
virus species in UK healthy adult volunteers 
Short Study Title 
A study of a new vaccine against two types of Ebola 
Study Code 
EBL07
IRAS Project ID 
301075
ClinicalTrials.gov NCT number 
NCT05079750
REC Details 
REC reference: 21/FT/0108 
Fast Track REC 
Email: fasttrack.rec@hra.nhs.uk
Chief Investigator 
Dr Paola Cicconi 
Centre for Clinical Vaccinology and Tropical Medicine 
Churchill Hospital, Old Road, Headington 
Oxford, OX3 7LE 
Principal Investigator - CCVTM 
Dr Daniel Jenkin 
Centre for Clinical Vaccinology and Tropical Medicine 
Churchill Hospital, Old Road, Headington 
Oxford, OX3 7LE 
Lead Scientific Investigator 
Professor Teresa Lambe 
Jenner Institute, Old Road Campus Research Build, Roosevelt Dr, 
Headington, Oxford, OX3 7DQ 
Co-Investigator 
Professor Sarah Gilbert 
Jenner Institute, Old Road Campus Research Build, Roosevelt Dr, 
Headington, Oxford, OX3 7DQ 
Trial Site 
Centre for Clinical Vaccinology and Tropical Medicine
Churchill Hospital, Old Road, Headington 
Oxford, OX3 7LE 
Sponsoring Institution 
University of Oxford
Research Governance, Ethics and Assurance (Formerly named Clinical 
Trials and Research Governance)  
Boundary Brook House. Churchill Drive. Headington 
Oxford, OX3 7GB 
Tel: 01865 616480 
Email: ctrg@admin.ox.ac.uk
Clinical Trial Monitor  
Research Governance, Ethics and Assurance (Formerly named Clinical 
Trials and Research Governance) 
University of Oxford 
Boundary Brook House. Churchill Drive. Headington 
Oxford, OX3 7GB 
Local Safety Monitor  
Dr Brian Angus
Centre for Clinical Vaccinology and Tropical Medicine 
Churchill Hospital, Old Road, Headington 
Oxford, OX3 7LE 
Tel: 01865 220289 
Email: brian.angus@ndm.ox.ac.uk

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EBL07 Protocol V4.0, 01 Nov 2022                                                         
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Table of Contents  
1
SYNOPSIS ............................................................................................................................. 8
2
SCHEDULE OF PROCEDURES TABLE ........................................................................................ 9
2.1
Schedule of Procedures Table: Screening Visit ................................................................ 9
2.2
Schedule of Procedures Table: Vaccination and Follow up Visits (single dose schedule) . 10
2.3
Schedule of Procedures Table: Vaccination and Follow up Visits (two dose schedule) ... 11
3
BACKGROUND & RATIONALE .............................................................................................. 12
3.1
Ebola Virus Disease (EBOD).......................................................................................... 12
3.2
Zaire Ebolavirus (EBOV) and Sudan ebolavirus (SUDV) .................................................. 12
3.3
Currently Approved Vaccines ....................................................................................... 12
3.3.1
rVSV-ZEBOV (Ebola Zaire vaccine live; trade name: Ervebo) ........................................ 13
3.3.2
Ad26.ZEBOV/MVA-BN-Filo (trade name: Zabdeno/Mvabea) ....................................... 13
3.4
ChAdOx1 biEBOV......................................................................................................... 13
3.4.1
ChAdOx1 biEBOV vaccine .............................................................................................. 13
3.4.2
Preclinical studies .......................................................................................................... 13
3.4.3
Previous clinical experience .......................................................................................... 14
3.5
Rationale for Vaccination ............................................................................................ 14
3.6
Rationale for Selected Doses ....................................................................................... 15
3.6.1
Rationale for ChAdOx1 biEBOV in a homologous 12-week two dose schedule (SA02) 15
3.7
The Influence of Gut Microbiota on Vaccine Responses ................................................ 15
3.8
Potential Risks for Participants .................................................................................... 16
3.8.1
Phlebotomy ................................................................................................................... 16
3.8.2
Common vaccine reactions ........................................................................................... 16
3.8.3
Thrombosis with Thrombocytopenia ............................................................................ 16
3.8.4
Other Potential Rare Vaccine Reactions ....................................................................... 17
3.8.5
Potential Interaction with Other Adenoviral Vectored Vaccines: ................................ 17
3.9
Potential Benefits ........................................................................................................ 18
4
OBJECTIVES AND ENDPOINTS .............................................................................................. 19
4.1
Objectives, Outcome Measures and Evaluation Timepoints .......................................... 19
5
STUDY DESIGN .................................................................................................................... 20
5.1
Study Groups .............................................................................................................. 20
5.2
Trial Duration .............................................................................................................. 20
5.3
Definition of Start and End of Trial ............................................................................... 20
5.4
Sequence of Enrolment ............................................................................................... 20
5.4.1
Sentinel Participants ..................................................................................................... 20
5.4.2
Dose Escalation ............................................................................................................. 21
5.4.3
Second Dose (SA02) Administration Sequence............................................................. 21
5.5
Masking / Blinding ...................................................................................................... 22
6
RECRUITMENT AND WITHDRAWAL OF TRIAL VOLUNTEERS .................................................. 23
6.1
Participant Flow .......................................................................................................... 23
6.2
Recruitment ................................................................................................................ 23
6.3
Online Pre-screening Eligibility Questionnaire .............................................................. 24
6.4
Informed consent ........................................................................................................ 24
6.5
Inclusion and exclusion criteria .................................................................................... 25
6.5.1
Inclusion criteria ............................................................................................................ 25
6.5.2
Exclusion criteria ........................................................................................................... 25
6.5.3
Effective Contraception for Women of Childbearing Potential (WOCBP) .................... 26
6.5.4
Prevention of Over-Volunteering .................................................................................. 27
6.6
Screen Failures ............................................................................................................ 27
6.7
Enrolment and Group Allocation .................................................................................. 27
6.8
Withdrawal of volunteers ............................................................................................ 27

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6.9
Compliance with dosing regime ................................................................................... 28
6.10
Pregnancy ................................................................................................................... 28
7
CLINICAL TRIAL PROCEDURES .............................................................................................. 29
7.1
Study procedures ........................................................................................................ 29
7.2
Demographic Data Collection ...................................................................................... 29
7.3
Medical History ........................................................................................................... 29
7.3.1
Screening Medical History ............................................................................................ 29
7.3.2
Review of Medical Records/ Confirmation of Past Medical History ............................. 29
7.3.3
Targeted Medical History .............................................................................................. 29
7.4
Physical Observations / Vital Signs ............................................................................... 30
7.5
Physical Examinations ................................................................................................. 30
7.5.1
Screening Physical Examination .................................................................................... 30
7.5.2
Targeted Physical Examination ..................................................................................... 30
7.6
Participant Samples ..................................................................................................... 30
7.6.1
Clinical Laboratory Blood Samples ................................................................................ 30
7.6.2
Immunology Samples .................................................................................................... 31
7.6.3
Stool Sample Collection ................................................................................................ 31
7.6.4
Urine Samples ............................................................................................................... 31
7.6.5
Retention of Samples .................................................................................................... 31
7.7
Study visits .................................................................................................................. 32
7.7.1
Screening visit ............................................................................................................... 32
7.7.2
ChAdOx1 biEBOV vaccination visit(s) ............................................................................ 32
7.7.3
Follow up Visits ............................................................................................................. 32
7.7.4
Missed Visits .................................................................................................................. 33
7.8
ChAdOx1 biEBOV vaccinations ..................................................................................... 33
7.9
Electronic Participant Symptom Diary .......................................................................... 33
7.10
COVID-19 Study Considerations ................................................................................... 33
8
INVESTIGATIONAL PRODUCTS ............................................................................................. 35
8.1
Supply (ChAdOx1 biEBOV) ........................................................................................... 35
8.2
Administration of Investigational Medicinal Products .................................................. 35
8.3
Minimising environmental contamination with genetically modified organisms (GMO) 35
9
ASSESSMENT OF SAFETY ..................................................................................................... 36
9.1
Definitions .................................................................................................................. 36
9.2
Solicited Adverse Events Assessment ........................................................................... 37
9.3
Unsolicited Adverse Events Assessment ....................................................................... 37
9.4
Adverse Events of Special Interest (AESI) ..................................................................... 37
9.5
Causality assessment ................................................................................................... 38
9.5.1
Solicited AE Causality Assessment ................................................................................ 38
9.5.2
Unsolicited AE Causality Assessment ............................................................................ 38
9.6
Expectedness assessment ............................................................................................ 39
9.7
Reporting procedures for all Adverse Events ................................................................ 39
9.7.1
Reporting procedures for SAEs ..................................................................................... 40
9.7.2
Reporting Procedures for SUSARS ................................................................................ 40
9.7.3
Development Safety Update Report ............................................................................. 40
9.8
Assessment of severity ................................................................................................ 40
9.9
Procedures to be followed in the event of abnormal findings ....................................... 40
9.10
Local Safety Monitor ................................................................................................... 40
9.11
Interim safety reviews ................................................................................................. 41
9.11.1
First dose vaccination.................................................................................................... 41
9.11.2
Second dose vaccination ............................................................................................... 41
9.12
Safety Holding Rules .................................................................................................... 42

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9.12.1
Group holding rules ...................................................................................................... 42
10
DATA MANAGEMENT ......................................................................................................... 44
10.1
Data Management Plan ............................................................................................... 44
10.2
Data Handling ............................................................................................................. 44
10.3
Record Keeping ........................................................................................................... 44
10.4
Source Data and Case Report Forms (CRFs) .................................................................. 44
10.5
Data Protection ........................................................................................................... 45
10.6
Data Quality ................................................................................................................ 45
10.7
Archiving ..................................................................................................................... 45
11
STATISTICS ......................................................................................................................... 46
11.1
Sample Size Selection .................................................................................................. 46
11.2
Study Analyses ............................................................................................................ 46
11.2.1
Recruitment, Enrolment and Withdrawal Data ............................................................ 46
11.2.2
Demographic and Baseline Data ................................................................................... 46
11.2.3
Safety Data .................................................................................................................... 46
11.2.4
Immunogenicity Data .................................................................................................... 46
12
ETHICS AND REGULATORY CONSIDERATIONS ...................................................................... 47
12.1
Declaration of Helsinki ................................................................................................ 47
12.2
Guidelines for Good Clinical Practice ............................................................................ 47
12.3
Approvals ................................................................................................................... 47
12.4
Reporting .................................................................................................................... 47
12.5
Volunteer Confidentiality ............................................................................................ 47
13
QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES ............................................... 49
13.1
Investigator procedures ............................................................................................... 49
13.2
Monitoring .................................................................................................................. 49
13.3
Protocol deviation ....................................................................................................... 49
13.4
Audit & inspection ...................................................................................................... 49
14
FINANCING AND INSURANCE .............................................................................................. 50
14.1
Financing .................................................................................................................... 50
14.2
Insurance .................................................................................................................... 50
14.3
Participant Financial Compensation ............................................................................. 50
14.4
Contractual Arrangements........................................................................................... 50
15
SERIOUS BREACHES ............................................................................................................ 51
16
PUBLICATION POLICY .......................................................................................................... 51
17
DEVELOPMENT OF A NEW PRODUCT/PROCESS OR THE GENERATION OF INTELLECTUAL 
PROPERTY ................................................................................................................................. 51
18
ABBREVIATIONS ................................................................................................................. 52
19
REFERENCES ....................................................................................................................... 55
20
Appendix A: Investigator Signature and Declarations ........................................................... 58
21
Appendix B: Document History ........................................................................................... 59
22
Appendix C: Severity Grading Criteria .................................................................................. 61

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1
SYNOPSIS 
Trial Title 
A phase I study to determine the safety and immunogenicity of a bivalent 
ChAdOx1 vectored vaccine against Zaire and Sudan Ebola virus species in 
UK healthy adult volunteers 
Trial Site 
Centre for Clinical Vaccinology & Tropical Medicine, University of Oxford, 
Churchill Hospital, Old Road, Headington, Oxford, OX3 7LE 
Trial code 
EBL07 
Study Design 
Open label, non-randomised, dose escalation, first-in-human, single 
centre, phase I clinical trial 
Population 
Healthy adults aged 18  55 years 
Planned Sample Size 
26 volunteers 
Group 
Treatment 
Group 1 (n=6) 
Single IM Dose ChAdOx1 biEBOV 5 × 109 vp 
Group 2 (n=6-9*) 
Single IM Dose ChAdOx1 biEBOV 2.5 × 1010 vp 
Group 3 (n=11-14*) 
Two IM Doses ChAdOx1 biEBOV 5 × 1010 vp, 12 
weeks apart  
*Group 2 may be increased to 9 participants following interim safety 
reviews. In this case group 3 will consist of 11 rather than 14 participants. 
Follow-up duration 
Up to 12 months 
Planned Trial Period 
Q3 2021 to 31 Dec 2022 
Primary Objective 
To assess the safety profile of ChAdOx1 in healthy adult volunteers 
Secondary Objective 
To assess the immunogenicity of ChAdOx1 biEBOV in healthy adult 
volunteers 
Investigational Product 
ChAdOx1 biEBOV 
Dose per Administration ChAdOx1 biEBOV 5 × 109 vp 
ChAdOx1 biEBOV 2.5 × 1010 vp 
ChAdOx1 biEBOV 5 × 1010 vp 
Form 
Liquid 
Route 
Intramuscularly (IM) into the deltoid region of the arm  

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2
SCHEDULE OF PROCEDURES TABLE 
2.1
Schedule of Procedures Table: Screening Visit 
Protocol Section 
Visit Number 
S 
Visit Type 
Screening 
7.5.1 
Timeline 
0 to 90 days 
before D0 
Visit Procedures 
Informed Consent
X 
6.4 
ID Check and Photocopy 
X 
Review inclusion and exclusion 
criteria
X 
6.5 
Record Demographic Data
X 
7.2 
Medical History
X 
7.3 
Vital signs (Heart rate, 
Temperature, Blood Pressure)
X 
7.4 
Screening Physical Examination
X 
7.5 
TOPS Registration
www.tops.org.uk
X 
6.5.4 
Urine Samples 
Urinalysis
X 
7.6.4 
Urinary HCG (WOCBP only)
X 
7.6.4 
Stool Samples (Optional) 
Sample containers and 
instructions provided
X 
3.7 and 7.6.3 
Blood Samples 
HBsAg, HCV Ab, HIV serology (mL)
5 
7.6.1 
Biochemistry, Haematology (mL)
5 
7.6.1 
Blood volume per visit (mL) 
10 
Cumulative blood volume (mL) 
10 

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2.2
Schedule of Procedures Table: Vaccination and Follow up Visits (single dose schedule) 
Trial Period 
Protocol Section 
Visit Number 
1 
2 
3 
4 
5 
6 
7 
8
Visit Type 
Vac 
f/u 
f/u 
f/u 
f/u 
f/u 
f/u 
f/u 
Timeline 
D0 
D2 
D7 
D14 
D28 
D56 
D182
D364
Time window (days) 
±1
±2
±3
±3
±7
±60
±60
Visit Procedures 
Review contraindications, 
inclusion and exclusion criteria
X 
6.5 
Enrolment and Group Allocation
X 
6.7 
ChAdOx1 biEBOV vaccination
X 
7.8 
Vital signs (Heart rate, 
Temperature, Blood Pressure)
X 
X 
X 
7.4 
Targeted Medical History, 
Physical Examination
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
7.5 
Adverse Event Collection 
Solicited AE collection
X 
X 
X 
9.2 
Unsolicited AE collection
X 
X 
X 
X 
X 
9.3 and 9.5.2 
SAEs & AESI collection
X 
X 
X 
X 
X 
X 
X 
X 
9.4 and 9.7.1 
Review Ongoing AEs  
X 
X 
X 
X 
X 
X 
X 
Electronic diary (eDiary) 
Electronic diary started
X 
7.9 
Electronic diary review
X 
X 
X 
X 
7.9 
Electronic diary closed
X 
7.9 
Urine Samples 
Urinary HCG (WOCBP only)
X 
7.6.4 
Stool Samples (Optional) 
Home collection of stool samples
(X) 
 
(X) 
 
(X) 
(X) 
3.7 and 7.6.3 
Blood Samples* 
HLA typing (mL)
4 
7.6.1 
Biochemistry, Haematology (mL)
5 
5 
5 
5 
7.6.1 
Immunology (mL)
50 
50 
50 
50 
50 
50 
50 
7.6.2 
Blood volume per visit (mL) 
59 
5 
55 
50 
55 
50 
50 
50 
Cumulative blood volume (mL) 
69 
74 
129 
179 
234 
284 
334 
384 
() = Optional  
*Minor differences in blood volumes may occur depending on the collection tubes and equipment 
used. 
 (visit added in SA03) 

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2.3
Schedule of Procedures Table: Vaccination and Follow up Visits (two dose schedule) 
Trial Period 
Protocol 
Section 
Visit Number 
1 
2 
3 
4 
5 
6 
7 
8 
9 
10 
11 
12
Visit Type 
Vac 
f/u 
f/u 
f/u 
f/u 
f/u 
Vac2 
f/u 
f/u 
f/u 
f/u 
f/u 
Timeline (days) 
D0 
D2 
D7 
D14 
D28 
D56 
D84 
V2 
+7 
V2 
+14 
V2 
+28 
V2 
+182 
V2 
+280 
Time window (days) 
±1
±2
±3
±3
±7 
D77-
126 
±2
±3
±3
±60 
±60 
Visit Procedures 
Review contraindications, 
inclusion and exclusion 
criteria
X 
X 
6.5 
Enrolment and Group 
Allocation
X 
 
6.7 
ChAdOx1 biEBOV 
vaccination
X 
X 
7.8 
Vital signs (Heart rate, 
Temperature, Blood 
Pressure)
X 
X 
X 
X 
 
X 
7.4 
Targeted Medical History, 
Physical Examination
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
(X) 
7.5 
Adverse Event Collection 
Solicited AE collection
X 
X 
X 
X 
X 
 
9.2 
Unsolicited AE collection
X 
X 
X 
X 
X 
X 
X 
X 
X 
9.3 and 
9.5.2 
SAEs & AESI collection
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
9.4 and 
9.7.1 
Review Ongoing AEs  
 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
X 
Electronic diary (eDiary) 
Electronic diary started
X 
X 
7.9 
Electronic diary review**
X 
X 
X 
X 
X 
X 
X 
X 
7.9 
Electronic diary closed
X 
X 
7.9 
Urine Samples 
Urinary HCG (WOCBP only)
X 
X 
7.6.4 
Stool Samples (Optional) 
Home collection of stool 
samples
(X) 
 
 
(X) 
 
(X) 
 
(X) 
(X) 
(X) 
3.7 and 
7.6.3 
Blood Samples* 
HLA typing (mL)
4 
7.6.1 
Biochemistry, 
Haematology (mL)
5 
5 
5 
5 
5 
5 
5 
5 
7.6.1 
Immunology (mL)
50 
50 
50 
50 
50 
50 
- 
50 
70 
50 
50 
7.6.2 
Blood volume per visit 
(mL) 
59 
5 
55 
50 
55 
50 
55 
5 
55 
75 
50 
50 
Cumulative blood volume 
(mL) 
69 
74 
129 
179 
234 
284 
339 
344 
399 
474 
524 
574 
() = Optional *Minor differences in blood volumes may occur depending on the collection tubes and 
equipment used. ** eDiaries are remotely monitored in (near) real-time for the occurrence of grade 3 Aes. A 
remote review of all eDiary Aes will occur at 48hrs following V2 for the first 3 group 3 volunteers. 
only (visit added in SA03) 

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3
BACKGROUND & RATIONALE 
3.1
Ebola Virus Disease (EBOD) 
Ebola disease (EBOD) is a fatal viral haemorrhagic fever caused by 4 of the 6 known genus Ebolavirus 
species: Zaire ebolavirus (EBOV), Sudan ebolavirus (SUDV), Bundibugyo ebolavirus and Taï Forest 
ebolavirus. Low level endemicity of these viruses occurs in tropical regions of sub-Saharan Africa, 
where periodic outbreaks occur, likely initiated by zoonotic spill over events from local mammalian 
animal reservoirs prior to ongoing human-to-human transmission.  
The WHO records 41 Ebolavirus outbreaks with the first occurring in 19761. The average case fatality 
rate of EBOD is 50%, ranging between 25% and 90% for individual outbreaks1. The 2013-2016 west 
African outbreak, the largest to-date, was estimated to cause 28,000 cases with 11,000 deaths. In 
addition to mortality, survivors can face debilitating long term health sequelae2. Negative secondary 
effects on local healthcare systems can be large and persistent, likely contributing to further indirect 
morbidity and mortality during and after outbreaks3. Healthcare workers face very high risks of 
infection and death with 6 to 8% of the entire healthcare workforce of Liberia and Sierra Leone killed 
during the 2013-2016 outbreak4. 
To date outbreaks have been contained within relatively limited geographical areas. However, the 
possibility of imported cases via returning travellers, especially healthcare workers deployed in crises, 
can require vigilance and health surveillance in distant countries.  
Survivors of EBOD are thought to acquire protective immunity to subsequent infection against the 
same species of ebolavirus5. It remains unknown, however, whether convalescent individuals acquire 
immunity to heterologous ebolavirus species. Cross-reactive binding antibodies6,7 and T-cells7 have 
been observed in some survivors although it is unclear whether these provide any protection against 
disease.  
3.2
Zaire Ebolavirus (EBOV) and Sudan ebolavirus (SUDV) 
Zaire ebolavirus and Sudan ebolavirus species have caused the vast majority of EBOD epidemics, with 
EBOV causing the greatest number of outbreaks (28 total), infections (33,645 total), and deaths 
(14,495 total)1. Five outbreaks have been attributed to SUDV, with the largest in 2000-2001, leading 
to 425 infections and 224 deaths1. Both viruses are within the Ebolavirus genus, part of the filovirus 
RNA virus family, which contains other more distantly related viruses that also cause viral 
haemorrhagic fever in humans, such as Marburg virus. 
Human infection with either virus is usually catastrophic, although viral pathogenesis is incompletely 
understood. A suggested key early step in the infective process is the infection of dendritic cells and 
macrophages,  leading to an initial spread of virus to regional lymphatics and immune dysfunction8. A 
wide range of tissues and cell types can become infected, leading to widespread organ dysfunction in 
addition to a severe systemic inflammatory reaction, shock and disseminated intravascular 
coagulation. 
3.3
Currently Approved Vaccines 
Two ebolavirus vaccine regimens are currently approved for use. rVSV-ZEBOV (Ebola Zaire vaccine live; 
trade name: Ervebo) and Ad26.ZEBOV/MVA-BN-Filo (trade name: Zabdeno/Mvabea). Both vaccine 

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regimens are approved specifically for preventative use against Zaire ebolavirus only, rather than 
other Ebolavirus species. 
3.3.1
rVSV-ZEBOV (Ebola Zaire vaccine live; trade name: Ervebo) 
rVSV-ZEBOV is a live recombinant vesicular stomatitis virus vectored vaccine expressing the native 
Zaire ebolavirus glycoprotein that received conditional marketing authorisation by the EMA in 
November 2019 and WHO pre-qualification shortly afterwards. The approval was granted based on 
several clinical studies conducted in Africa, Europe and North America including an open-label cluster 
RCT efficacy trial in Guinea during the 2014-2016 outbreak, which demonstrated high efficacy against 
EBOV9.  
3.3.2
Ad26.ZEBOV/MVA-BN-Filo (trade name: Zabdeno/Mvabea) 
Ad26.ZEBOV is replication deficient adenovirus serotype 26 vector encoding the EBOV glycoprotein 
(Mayinga variant). MVA-BN-Filo is a multivalent MVA vector expressing four filovirus antigens: Zaire 
ebolavirus, Sudan ebolavirus, and Marburg virus glycoproteins; and nucleoprotein from the Tai Forest 
virus. The combination of Ad26.ZEBOV/MVA-BN-Filo were approved by the EMA as an 8-week 2-dose 
heterologous prime-boost vaccination schedule in May 202010. Although MVA-BN-Filo encodes 
antigens from multiple filovirus species the authorisation is specifically for protection against EBOV 
only. Additionally, t
, without human 
efficacy data, being supported instead by NHP challenge studies, with human efficacy inferred through 
immunological bridging studies11.  
3.4
ChAdOx1 biEBOV 
3.4.1
ChAdOx1 biEBOV vaccine 
ChAdOx1 biEBOV consists of the replication-deficient simian adenovirus vector ChAdOx1 encoding 
two antigens: EBOV glycoprotein and SUDV glycoprotein under the control of a TetR-repressible CMV 
promoter. The ChAdOx1 vector is replication-deficient as the E1 gene region, essential for viral 
replication, has been deleted. This means the virus will not replicate in cells within the human body. 
The E3 locus is additionally deleted in the ChAdOx1 vector. ChAdOx1 propagates only in cells 
expressing E1, such as HEK293 cells and their derivatives, e.g. T-RExTM-293 (InVitrogen) or, other cell 
lines expressing E1 gene region. 
3.4.2
Preclinical studies 
ChAdOx1 biEBOV has been shown to be immunogenic in mice, resulting in antibody and T-cell 
responses against both SUDV and EBOV glycoproteins. Additionally, vaccination has shown complete 
protection against disease in a guinea pig challenge study, using a guinea pig adapted EBOV strain.  
A murine toxicology study (Covance SR79DS) carried out using the toxicology batch of ChAdOx1 
biEBOV showed no evidence of ChAdOx1 biEBOV related toxicity after administration. Treatment with 
the vaccine was safe, well tolerated and not associated with any adverse effects. 
Biodistribution studies have not been conducted with ChAdOx1 biEBOV although these have been 
conducted with two other ChAdOx1 vectored vaccines. In both studies, high levels of detectable vector 
were observed at the administration site at early timepoints, decreasing over time. Lower levels could 
also be detected at distant sites (heart, liver, ovary, testes), also decreasing with time. 
Full details of preclinical studies using ChAdOx1 biEBOV are contained within the ChAdOx1 biEBOV 
Investigator Brochure. 

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3.4.3
Previous clinical experience  
EBL07 is a first-in-human study employing ChAdOx1 biEBOV in healthy volunteers recruited in the UK. 
However, phase I clinical trials of ChAdOx1 vectored vaccines encoding antigens for Influenza (fusion 
protein NP+M1), Tuberculosis (85A), Prostate Cancer (5T4), Malaria (LS2), Chikungunya (structural 
polyprotein), Zika (prM and E), group B Meningococcus (outer membrane protein) and SARS-CoV-2 
have previously been undertaken (refer to ChAdOx1 biEBOV Investigator Brochure) and shown the 
vaccine to be safe and immunogenic.  
Additionally, ChAdOx1 nCoV-19 has now been approved widely and rolled out in a number of 
countries. The vaccine has been shown to be safe in the vast majority of individuals, although a rare 
but serious side effect of thrombosis with thrombocytopenia has been seen in a small number of 
individuals (see section 3.8.3).  
3.5
Rationale for Vaccination 
Multivalent vaccines covering multiple different filovirus species are attractive and the preferred 
approach of the WHO12, offering the advantage of protection against a number of targeted species as 
well as decreasing manufacturing cost and reducing the overall risk compared to developing individual 
monovalent vaccines. NHP and guinea pig challenge studies have demonstrated monovalent 
Ebolavirus glycoprotein vaccines offer only partial cross-protection against heterologous ebolavirus 
species13,14. Although a multivalent MVA-vectored vaccine has been developed, this is currently only 
approved for use with a monovalent adenovirus prime and specifically against Zaire ebolavirus only 
(section 3.3.2). As such, the need for a multivalent vaccine, approved for use against multiple 
Ebolavirus species, remains unmet.  
Adenovirus vaccines are highly scalable, with a well-developed existing manufacturing capability and 
supply chains that support a continuous uninterrupted supply of vaccine and the potential for rapid 
scale up in public health emergencies. Wild type replication competent oral human adenovirus 
vaccines, to protect against acute respiratory illness caused by adenovirus serotype 4 and 7, have been 
administered to millions of military personnel over decades in the USA with no safety issues15.  
ChAdOx1 nCoV-19 (AKA ChAdOx1-S) was shown to be safe, immunogenic and efficacious against 
COVID-19 disease in a number of clinical trials16-19 and has now been approved in multiple territories 
as well as receiving WHO pre-qualification. Additionally, it has been administered to millions of 
individuals, including those with serious medical co-morbidities, across diverse populations. Post-
approval studies following the vaccines rollout have demonstrated high levels of vaccine effectiveness 
against severe COVID-19 following a single dose only20,21. Safety surveillance of ChAdOx1 nCoV-19 has 
demonstrated a very rare association with a syndrome consisting of major thrombosis and 
thrombocytopenia (covered in section 3.8.3). This safety signal remains under intense investigation 
by regulators and researchers. These events remain rare and the vaccine continues to be 
recommended for use as the benefits against COVID-19 outweigh the risks of its use for the majority 
of populations.  
In addition to ChAdOx1 nCoV-19, a further 320 trial volunteers have received other ChAdOx1 vectored 
vaccines encoding antigens against a range of targets in phase 1 trial settings (section 3.4.3). It has 
been shown to be highly immunogenic after single dose administration against the large number of 
inserts used across these trials. Further details of ChAdOx1 studies and associated publications are 
contained within the ChAdOx1 biEBOV IB.  

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ChAdOx1 has a proven record as a platform technology for the development of vaccines against 
emerging pathogens. Experience with ChAdOx1 nCoV-19 has shown the vaccine can be rapidly 
manufactured at high volume for low cost, with storage conditions amenable to use in the developing 
world. This study will provide valuable data on safety and immunological aspects of a novel 
multivalent ChAdOx1 vaccine. 
3.6
Rationale for Selected Doses 
Doses to be administered in this trial have been selected on the basis of clinical experience with the 
ChAdOx1 adenovirus vector expressing a different insert, and similar adenovirus vectored vaccines 
(e.g. ChAdOx1 and ChAd63). ChAdOx1 nCoV-19 has temporary authorisation in the UK under 
Regulation 174 at a dose of 5 × 1010 viral particles. It is well tolerated and immunogenic at this dose. 
Although authorised as a 2-dose schedule 4 to 12 weeks apart, the vaccine is immunogenic and 
efficacious following the first dose19. Phase III trials and post-authorisation effectiveness studies have 
shown a single 5 × 1010 vp dose of vaccine is protective against COVID-19 disease. Over 200 million 5 
× 1010 viral particles doses of ChAdOx1 nCoV-19 have been administered worldwide as of June 2021. 
For safety reasons, the first dose of ChAdOx1 biEBOV proposed in this study (5 × 109 vp) is one tenth 
of the expected tolerated dose (5 × 1010 vp). Doses will be gradually increased aiming to identify an 
optimal dose of ChAdOx1 biEBOV considering the tolerability, reactogenicity and immunogenicity 
profiles. 
3.6.1
Rationale for ChAdOx1 biEBOV in a homologous 12-week two dose schedule (SA02) 
Experience with ChAdOx1 nCoV-19 has shown that a second dose of ChAdOx1 significantly boosts 
binding and neutralising antibody responses to SARS-CoV-2 and vaccine efficacy. A delayed 12-week 
schedule has been shown to be more immunogenic than a 4-week schedule. A second dose of 
ChAdOx1 nCoV-19 is well tolerated and produces lower rates of adverse reactions compared with the 
initial dose 17,22,23. 
The ChAdOx1 biEBOV two-week repeat dose pre-clinical toxicology study (Covance SR79DS 
summarised within ChAdOx1 biEBOV Investigator Brochure) supports the clinical evaluation of 
ChAdOx1 biEBOV in a two dose 12-week schedule in this clinical trial, as advised by WHO guidelines 
on nonclinical evaluation of vaccines24.  
3.7
The Influence of Gut Microbiota on Vaccine Responses
Humans and microbiota, which consist of bacteria, fungi, viruses and eukaryotic species, have co- 
evolved over millions of years and their coexistence is beneficial to both parties. The human immune 
system is constitutively exposed to microbial stimulation and any vaccine design and responsiveness 
needs to be considered in the context of host-microbiota interactions. Manipulation of the microbiota 
functions and composition through diet, engraftment and/or any other means may thus become a 
viable strategy for improving vaccine responsiveness as well as treating malfunctions of the immune 
system25. Reports on the influence of gut microbiota diversity and composition on responses to 
vaccination have been emerging for some time25-29. 
Analysis of faeces microbiota will allow a comprehensive yet non-invasive characterisation of the gut 
microbiome. A thorough characterisation of the gut microbiome composition and function will be 
performed using shotgun sequencing. Extensive metabolomic analyses, showing associations with 
microbial dysbiosis, may also be performed. 

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3.8
Potential Risks for Participants 
The potential risk to participants is considered as low. The potential risks are those associated with 
phlebotomy and vaccination. In general, recombinant adenoviral vectors are safe. Similar vaccines 
encoding different antigens have been given to several thousand volunteers (including children) with 
a good safety profile. Post-marketing experience with ChAdOx1 nCoV-19 has uncovered a very rare 
but serious side effect of thrombosis with thrombocytopenia following use of that vaccine. 
3.8.1
Phlebotomy 
The maximum volume of blood drawn over the study period (Section 2) should not compromise 
these otherwise healthy volunteers. There may be minor bruising, local tenderness or pre-syncopal 
symptoms associated with venepuncture, which will not be documented as AEs if they occur.  
3.8.2
Common vaccine reactions 
Potential foreseeable risks from vaccination include local effects such as pain, redness, warmth, 
swelling, tenderness or itching. Systemic reactions that could potentially occur following 
immunisation with a recombinant adenovirus vaccine include a flu-like illness with feverishness, 
fatigue, malaise, arthralgia, myalgia and headache. Side effect profiles have been consistent across 
different ChAdOx1 vaccines when used in clinical trials. Rates of solicited adverse reactions that occurred 
with ChAdOx1 nCoV-19 in large scale trials are shown in Table 1. 
Table 1Profile of Reactions to ChAdOx1 nCoV-19 in clinical trial participants30
Adverse Reaction 
Frequency (%) 
Injection site tenderness 
64% 
Injection site pain
54% 
Fatigue 
53% 
Headache 
52% 
Malaise 
44% 
Myalgia 
44% 
Feverishness 
34% 
Arthralgia  
26% 
Nausea 
22% 
Fever over 38°C
8% 
3.8.3
Thrombosis with Thrombocytopenia  
In April 2021, MHRA and JCVI conducted a review of extremely rare reports of cerebral venous sinus 
thrombosis (and thrombosis of other major veins) occurring with concurrent thrombocytopenia which 
had been received after large scale use of the ChAdOx1 nCoV-19 vaccine. The potential mechanism of 
these events is yet to be determined. It is currently unknown whether they are related to the ChAdOx1 
vector or to the SARS-CoV-2 spike protein.  
Estimates of incidence of thrombosis with thrombocytopenia following ChAdOx1 nCoV-19 vaccination 
vary and may change further as more cases are gathered and case definitions are finalised. Current 
UK estimates are of cases occurring at a rate of around 1 case per 100,000 prime vaccinations. 

EBL07 Protocol V4.0, 01 Nov 2022                                                         
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On the basis of their ongoing scientific review the UK Medicines Healthcare Regulatory Agency have 
hat the evidence of a link with COVID-19 Vaccine AstraZeneca is stronger 31. The 
European Medicines Agency concluded that unusual blood clots with low blood platelets should be 
listed as very rare side effects of this vaccine. Both the MHRA and EMA have confirmed that the 
evidence to date does not suggest that the COVID-19 Vaccine AstraZeneca causes venous 
thromboembolism without a low platelet count31,32. 
The MHRA data shows a higher reported incidence rate in younger adults. The reported incidence rate 
is also higher in females although this sex difference is small and not consistent across age groups. 
Cases of thrombosis with thrombocytopenia have also been reported after COVID-19 Vaccine Janssen, 
an adenovirus serotype 26 vectored spike-protein based COVID-19 vaccine. The EMA has also 
conducted a review of these cases and concluded there is a likely causal relationship with the Janssen 
vaccine33. 
Thrombosis with thrombocytopenia syndrome has not previously been reported following the use of 
live oral adenovirus serotype 4 and serotype 7 adenovirus vaccines in the United States, where these 
vaccines have been approved for vaccination of military personnel15,34,35. Over 1.3 million doses have 
been administered between 2011 to 2018 with no reports of thrombosis following vaccination to the 
US CDC/FDA Vaccine Adverse Event Reporting System (VAERS) post-marketing passive vaccine safety 
monitoring database15.  
All volunteers will be provided with this information via the study information booklet and will be kept 
updated should further information become available. They will also be specifically counselled on 
symptoms that could be warning signs of serious clotting events, as per public health advice being 
given to people receiving ChAdOx1 nCoV-19. 
3.8.4
Other Potential Rare Vaccine Reactions 
As with any vaccine, Guillain-Barré syndrome or immune-mediated reactions that can lead to organ 
damage may occur, but this should be extremely rare. Serious allergic reactions including anaphylaxis 
could also occur and for this reason volunteers will be vaccinated in a clinical area where Advanced 
Life Support trained physicians, equipment and drugs are immediately available for the management 
of any serious adverse reactions (SAR). 
3.8.5
Potential Interaction with Other Adenoviral Vectored Vaccines: 
The ChAdOx1 vector used in the ChAdOx1 biEBOV experimental vaccine is the same as that used in 
the Oxford AstraZeneca and similar to the one used in the Janssen (Johnson and Johnson) COVID-19 
vaccines (Adenovirus 26). There is a theoretical risk that receiving the experimental ChAdOX1 biEBOV 
vaccine may reduce the benefit of subsequent administrations of certain vaccines such as the Janssen 
(Johnson & Johnson) or the AstraZeneca COVID-19 vaccines. This may be more likely to happen if the 
vaccines are given at short intervals. However, the immune response to the AstraZeneca COVID-19 
vaccine was not affected in a study of individuals who received a previous ChAdOx1-vectored vaccine 
for a non-spike transgene at least one year earlier18,36.  
Other studies suggest that an interval of three months between administrations of two adenoviral 
vectored vaccines reduces the risk of this interference37-41. For this reason, we will enrol participants 
who have been vaccinated with an mRNA Covid vaccine or will have their NHS Covid vaccine offer at 
least three months after the ChAdOx1 biEBOV vaccine. No such theoretical interference will be 
expected with mRNA or protein COVID-19 vaccines (such as Moderna, Pfizer, Novavax) and these can 
be given at least 2 weeks before or after the ChAdOx1 biEBOV. 

EBL07 Protocol V4.0, 01 Nov 2022                                                         
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3.9
Potential Benefits 
The recruitment population in this study are unlikely to benefit directly from participation in this study. 
However, it is hoped that the information gained from this study will contribute to the development 
of a further safe and effective vaccine to protect at-risk populations from ebolavirus disease. The only 
benefits for participants would be information about their general health status. 

EBL07 Protocol V4.0, 01 Nov 2022                                                         
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4
OBJECTIVES AND ENDPOINTS 
4.1
Objectives, Outcome Measures and Evaluation Timepoints 
Outcome 
Objective 
Outcome measure 
Evaluation Timepoints 
Primary 
To assess the safety 
and tolerability of 
ChAdOx1 biEBOV in 
healthy volunteers.  
a) Occurrence of solicited local 
reactogenicity signs and symptoms 
7 days following each vaccination 
(D0 to D7) 
b) Occurrence of solicited systemic 
reactogenicity signs and symptoms 
7 days following each vaccination 
(D0 to D7) 
c) Occurrence of unsolicited 
adverse events (AEs) 
28 days following each vaccination 
(D0 to D28) 
d) Change from baseline for safety 
laboratory measures
1 dose: D0, D2, D7, D28 
2 dose: D0, D2, D7, D28, V2, V2+7 
V2+14, V2+28 
e) SAEs and AESIs 
Whole duration of the study  
1 dose: D0 to D182 (or D364
2 dose: D0 to V2+182, V2+280 
Secondary To assess the 
immunogenicity of 
ChAdOx1 biEBOV in 
healthy adult 
volunteers. 
a) Filovirus GP specific serological 
response as measured by ELISA 
1 dose: D0, D28, D56, D182, D364
2 dose: D0, D28, D56, V2, V2+14, 
V2+28, V2+182, V2+280 
b) Filovirus GP specific T cell 
response measured by IFN-
ELISPOT 
1 dose: D0, D7, D14, D28, D56, 
D182, D364
2 dose: D0, D7, D14, D28, D56, V2, 
V2+14, V2+28, V2+182, V2+280 
Exploratory*Immunological 
Profiling 
a) Filovirus neutralising antibodies 
(using either live or 
pseudoneutralisation assays) 
b) Cellular immune response to 
filovirus GP measured by ICS, 
proliferation and/or whole blood 
assays 
Timepoints will be detailed in the lab 
analysis plan 
To assess anti-vector 
immunity following 
vaccination 
a) Binding and/or neutralising 
antibody responses against 
ChAdOx1 
Timepoints will be detailed in the lab 
analysis plan 
To investigate a 
potential relationship 
between the 
composition of the 
gut microbiota and 
vaccination outcomes
a) Characterisation of the gut 
microbiome composition and 
function using shotgun 
sequencing.  
b) Metabolomic analyses may also 
be performed. 
1 dose: D0, D14, D182, D364
2 dose: D0, D14, V2+14, V2+182, 
V2+280
*Sample analysis for the completion of exploratory endpoints may be performed under the ethically 
approved OVC Biobank protocol (REC 16/SC/014). Further exploratory assays/analyses may be carried 
out (see section 7.6.2). 

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5
STUDY DESIGN 
This is a first-in-human, open-label, dose escalation, phase I clinical trial to assess the safety and 
immunogenicity of the candidate ChAdOx1 biEBOV vaccine in healthy UK volunteers aged 18-55. The 
vaccine will be administered intramuscularly (IM).  
Volunteers will be recruited and vaccinated at the Centre for Clinical Vaccinology and Tropical 
Medicine (CCVTM), Oxford. There will be 3 study groups and it is anticipated that a total of 26 
volunteers will be enrolled. Dose escalation and sentinel participant procedures are detailed in section 
5.4. Volunteers will be first recruited into Group 1 and subsequently into Groups 2 and 3 following 
interim clinical safety reviews (section 5.4). Volunteers will be sequentially allocated to a study group 
by selecting eligible volunteers for enrolment following screening. Sequential allocation will occur 
based on the order in which volunteers are enrolled. 
5.1
Study Groups 
Group 
Treatment 
Follow up Period 
Group 1 (n=6) 
Single IM Dose ChAdOx1 biEBOV 5 × 109 vp 
6 months (section 2.2) 
Group 2 (n=6-9*) 
Single IM Dose ChAdOx1 biEBOV 2.5 × 1010 vp 
6 months (section 2.2) 
Group 3 (n=11-14*)
Two IM Doses ChAdOx1 biEBOV 5 × 1010 vp, 
12-weeks apart (second dose optional) 
12 months** (section 2.3) 
*Group 2 may be increased to 9 participants following interim safety reviews. In this case group 3 will 
consist of 11 rather than 14 participants. 
**Group 3 participants that decline a second dose of ChAdOx1 biEBOV will continue to follow the 
single dose follow up schedule (section 2.2). The follow up period for group 3 participants was 
extended to 12 months as part of SA03. 
5.2
Trial Duration 
The total duration of the study will be 6-12 months from the day of enrolment for each volunteer. 
5.3
Definition of Start and End of Trial 
The start of the trial is defined as the date of the first vaccination of the first volunteer. The end of the 
trial is the date of the last visit of the last volunteer (LVLV). 
5.4
Sequence of Enrolment 
The enrolment sequence is summarised below (Table 2).  
5.4.1
Sentinel Participants 
The first participant in each group (i.e. at each dose level) will be vaccinated alone, ahead of any other 
participants in that group. Their profile of adverse events will be reviewed at least 48 hours post-
vaccination. Provided there are no safety concerns at that point, as assessed by the CI and local safety 
monitor, a further two volunteers will be vaccinated using the same dose at least 1 hour apart from 
each other, bringing the total number of volunteers receiving that dose to 3. The profile of adverse 
events for the second and third participants will then be reviewed by the Local Safety Monitor (LSM) 
and CI after a further 48 hours and if this safety profile is deemed acceptable, the remaining (non-
sentinel) participants in the group may then be vaccinated. 

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5.4.2
Dose Escalation 
An interim safety review with at least 7 days of safety data from all participants of the preceding dose 
group, including the results of day 7 clinical laboratory blood tests, will be performed. The decision to 
proceed to the first participant of the next dose level will be taken on the basis of this review, by the 
LSM and CI. 
Table 2 Sequence of enrolment *The size of group 2 may optionally be extended from n=6 to n=9. If the 
group size is 
Sequence 
Volunteer groups 
Minimum Interval 
before next step 
Local Safety Monitor Interim 
Safety Review prior to 
progression 
Step 1 
Group 1 volunteer 1 
48 hours 
Y 
Step 2 
Group 1 volunteer 2 
1 hour 
N 
Step 3 
Group 1 volunteer 3 
48 hours 
Y 
Step 4 
Group 1 remaining volunteers 
7 days 
Y 
Step 5 
Group 2 volunteer 1 
48 hours 
Y 
Step 6 
Group 2 volunteer 2 
1 hour 
N 
Step 7 
Group 2 volunteer 3 
48 hours 
Y 
Step 8a 
Group 2 volunteers 4 to 6 
7 days 
Y 
(Step 8b)* 
(Group 2 volunteer 7 to 9)* 
(7 days)* 
(Y)* 
Step 9 
Group 3 volunteer 1 
48 hours 
Y 
Step 10 
Group 3 volunteer 2 
1 hour 
N 
Step 11 
Group 3 volunteer 3 
7 days 
Y 
Step 12 
Group 3 remaining volunteers 
n/a 
n/a 
5.4.3
Second Dose (SA02) Administration Sequence 
Group 3 second doses will initially be staggered using the following sequence (Table 3 Sequence of 
second dose administration) and  an interim safety reviews as detailed in section 9.11.2. 

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Table 3 Sequence of second dose administration
Sequence 
Volunteer groups 
Minimum Interval 
before next step 
Local Safety Monitor Interim 
Safety Review prior to 
progression 
Step 1 
Second-dose administered 
to volunteer 1 
48 hours 
Y 
Step 2 
Second dose administered 
to volunteer 2 
1 hour 
N 
Step 3 
Second dose administered 
to volunteer 3  
48 hours 
Y 
Step 4 
Second doses administered 
to remaining group 3 
volunteers 
n/a 
n/a 
Safety holding rules will continue to apply following the second dose and will include real-time 
assessment of ePRO eDiary adverse event data. 
5.5
Masking / Blinding 
This is an open-label trial. Investigators and participants will remain unblinded to study vaccinations 
including dose/group and whether participants are sentinel or non-sentinel participants. 

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6
RECRUITMENT AND WITHDRAWAL OF TRIAL VOLUNTEERS 
6.1
Participant Flow 
6.2
Recruitment 
Volunteers may be recruited by use of an advertisement and/or registration form formally approved 
by the ethics committee(s) and distributed or posted in the following places: 
In public places, including buses and trains, with the agreement of the owner/proprietor. 
In newspapers or other literature for circulation. 
On radio via announcements. 
On a website or social media site operated by our group or with the agreement of the owner 
or operator (including on-line recruitment through our web-site).  
By e-mail distribution to a group or list only with the express agreement of the network 
administrator or with equivalent authorisation. 
By email distribution to individuals who have already expressed an interest in taking part in 
any clinical trial at the Oxford Vaccine Centre. 
On stalls or stands at exhibitions or fairs. 
Via presentations (e.g. presentations at lectures or invited seminars). 
Direct mail-out: This will involve obtaining names and addresses of adults via the most 
recent Electoral Roll. The contact details of individuals who have indicated that they do not 
wish to receive postal mail-shots would be removed prior to the investigators being given 
this information. The company providing this service is registered under the Data Protection 
Act 2018. Investigators would not be given dates of birth or ages of individuals, but the list 
supplied would only contain names of those aged between 18-55 years (as per the inclusion 
criteria). 
Oxford Vaccine Centre databases: We may contact individuals from databases of groups 
within the CCVTM (including the Oxford Vaccine Centre database) of previous trial 
participants who have expressed an interest in receiving information about all future studies 
for which they may be eligible. 
SA02 Note: Recruitment of all volunteers into the trial has now been completed. 
1 
Recruitment through Advertising and other activities 
2 
Completion of Online pre-screening eligibility questionnaire 
3 
Informed Consent (at screening visit, consent form signed) 
4 
Screening Procedures (at screening visit, after informed consent obtained) 
5 
Eligibility Assessment by Investigator (following completion of screening investigations) 
6 
Enrolment & Vaccination of eligible participants 
7 
Completion of trial follow up visits 

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6.3
Online Pre-screening Eligibility Questionnaire  
Prior to invitation for a screening visit, individuals will be directed to an online pre-screening 
questionnaire covering key eligibility criteria such as age. Respondents that are not ineligible at this 
stage will be invited to the trial site for the screening visit.  
6.4
Informed consent 
All volunteers will sign and date the informed consent form before any study specific procedures are 
performed. The information sheet will be made available to the volunteer at least 24 hours prior to 
the screening visit. At the screening visit, the volunteer will be fully informed of all aspects of the trial, 
the potential risks and their obligations. The following general principles will be emphasised: 
Participation in the study is entirely voluntary. 
Refusal to participate involves no penalty or loss of medical benefits. 
The volunteer may withdraw from the study at any time. 
The volunteer is free to ask questions at any time to allow him or her to understand the 
purpose of the study and the procedures involved. 
The study involves research into an investigational vaccine. 
There is no direct benefit to individuals from participating. 
General Practitioner (GP) will be informed of their participation in the study. 
Confirmation of their medical history will be required e.g. through a medical history 
summary from their GP practice or equivalent. 
collaboration with the University of Oxford. These will be de-identified. 
That long term storage of samples after the trial is over is optional and will be covered under 
the Oxford Vaccine Centre Biobank Study protocol which will be consented to separately.  
The aims of the study and all tests to be carried out will be explained. The volunteer will be given the 
opportunity to ask about details of the trial and will then have time to consider whether or not to 
participate. If they decide to participate they will sign and date the consent form once informed 
consent has been obtained. These forms will also be signed and dated by the Investigator. Participants 
will be provided with a copy of the signed consent form. 

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6.5
Inclusion and exclusion criteria 
This study will be conducted in healthy adults, who meet the following inclusion and exclusion criteria: 
6.5.1
Inclusion criteria 
The volunteer must satisfy all the following criteria to be eligible for the study: 
1.
Healthy adults aged 18 to 55 years. 
2.
. 
3.
Willing to allow confirmation of their past medical history either through: provision of a GP 
medical record summary, allowing investigators to obtain a copy of their medical history 
from their GP practice or by providing an alternative acceptable means of confirming their 
past medical history. 
4.
Agreement to refrain from blood donation during the course of the study. 
5.
Provide written informed consent. 
6.
For women of childbearing potential only: Willingness to practice continuous effective 
contraception for the duration of the trial. 
7.
For women of childbearing potential only: A negative pregnancy test within the screening 
window and on the day of vaccinations. 
6.5.2
Exclusion criteria 
The volunteer may not enter the study if any of the following apply:
1.
Participation in another research study involving receipt of an investigational product in the 
30 days preceding enrolment or during the trial follow up period.  
2.
Receipt of a recombinant simian adenoviral vaccine prior to enrolment. 
3.
Planned receipt of another adenoviral vectored vaccine (e.g. Oxford/AstraZeneca or Janssen 
COVID-19 vaccines) within 90 days after vaccination with the ChAdOx1 biEBOV. 
4.
Planned or actual receipt of any vaccines administered within 30 days (before or after) 
 EXCEPT for protein, 
RNA (or other non-adenovirus based) COVID-19 vaccinations which may be given within 14 
days of the trial vaccine. 
5.
Previous receipt of an Ebola virus vaccine. 
6.
Administration of immunoglobulins and/or any blood products within the three months 
preceding the planned administration(s) of the vaccine candidate. 
7.
Any confirmed or suspected immunosuppressive or immunodeficient state, including HIV 
infection; asplenia; recurrent, severe infections and chronic (more than 14 days) systemically 
active immunosuppressant medication within the past 6 months. 
8.
History of allergic disease or reactions likely to be exacerbated by any component of the 
vaccine. Including hypersensitivity to the active substance or to any of the excipients of the 
IMP or Vaxzevria (i.e. the Oxford/AstraZeneca COVID-19 vaccine). 
9.
History of hereditary angioedema, acquired angioedema, or idiopathic angioedema. 
10.
History of anaphylaxis in relation to vaccination. 
11.
History of cancer (except basal cell carcinoma of the skin and cervical carcinoma in situ). 
12.
History of serious psychiatric condition likely to affect participation in the study. 
13.
Ongoing or planned pregnancy or breastfeeding during the trial follow up period. 
14.
Bleeding disorder (eg. Factor deficiency, coagulopathy or platelet disorder), or prior history 
of significant bleeding or bruising following IM injections or venepuncture. 

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15.
History of confirmed major thrombotic event (including cerebral venous sinus thrombosis, 
deep vein thrombosis, pulmonary embolism), history of antiphospholipid syndrome, or 
history of heparin induced thrombocytopenia. 
16.
Individuals who have experienced thrombosis with thrombocytopenia syndrome (TTS) 
following vaccination with Vaxzevria (i.e. the Oxford/AstraZeneca COVID-19 vaccine). 
17.
Individuals who have previously experienced episodes of capillary leak syndrome. 
18.
Any other serious chronic illness requiring hospital specialist supervision. 
19.
Suspected or known current alcohol abuse as defined by an alcohol intake of greater than 42 
units every week. 
20.
Suspected or known injecting drug abuse in the 5 years preceding enrolment. 
21.
Detectable circulating hepatitis B surface antigen (HBsAg). 
22.
Seropositive for hepatitis C virus (antibodies to HCV). 
23.
Any clinically significant abnormal finding on screening biochemistry or haematology blood 
tests or urinalysis. 
24.
Any other significant disease, disorder or finding which may significantly increase the risk to 
the volunteer because of participation in the study, affect the ability of the volunteer to 
participate in the study or impair interpretation of the study data. 
6.5.3
Effective Contraception for Women of Childbearing Potential (WOCBP) 
6.5.3.1
Definition of Women of Childbearing Potential (WOCBP) 
For the purpose of this trial, a woman is considered of childbearing potential (WOCBP) unless they 
meet either of the following criteria: 
Surgical sterilisation including: 
o
Hysterectomy 
o
Bilateral salpingectomy  
o
Bilateral oophorectomy. 
Post-menopausal: 
o
For women aged  45 years, post-
months amenorrhea, without using hormonal contraception or other alternative 
cause. 
6.5.3.2
Acceptable Forms of Contraception for WOCBP:  
Female participants of childbearing potential are required to use an effective form of contraception 
from one month before prime until three months after administration of the IMP.  
Acceptable forms of contraception for volunteers of childbearing potential include:  
Established use of oral, injected or implanted hormonal methods of contraception.  
Placement of an intrauterine device (IUD) or intrauterine system (IUS). 
Barrier methods of contraception (condom or occlusive cap with spermicide).  
Male sterilisation, if the vasectomised partner is the sole partner for the subject.  
True abstinence (defined as refraining from heterosexual intercourse) when this is in line 
with the preferred and usual lifestyle of the subject. Periodic abstinence and withdrawal are 
not acceptable methods of contraception.  

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6.5.4
Prevention of Over-Volunteering 
Volunteers will be excluded from the study if they are concurrently enrolled in another CTIMP trial. In 
order to check this, volunteers will be asked to provide their National Insurance or Passport number 
(if they are not entitled to a NI number) and will be registered on a national database of participants 
in clinical trials (www.tops.org.uk). 
6.6
Screen Failures 
Participants who have signed the informed consent form but are not subsequently enrolled in the trial 
will be regarded as screen failures. For each of these participants, a minimal set of screen failure data 
will be recorded including demographic details and the reason for screening failure. These details will 
be reported as required by Consolidated Standards of Reporting Trials (CONSORT) publishing 
standards. 
6.7
Enrolment and Group Allocation 
Participants will be considered enrolled at the point of receiving their vaccination at the D0 visit. 
Allocation of participants to groups / sentinels will be performed by the investigator and will follow 
the sequence in section 5.4. 
6.8
Withdrawal of volunteers 
In accordance with the principles of the Declaration of Helsinki (2008) and any other applicable 
regulations, a volunteer has the right to withdraw from the study at any time and for any reason, and 
is not obliged to give his or her reasons for doing so. The Investigator may withdraw the volunteer at 
any time in the interests of 
-being. In addition, the volunteer may 
withdraw/be withdrawn for any of the following reasons: 
Administrative decision by the Investigator. 
Ineligibility (either arising during the study or retrospectively, having been overlooked at 
screening). 
Significant protocol deviation. 
Volunteer non-compliance with study requirements. 
An AE, which requires discontinuation of the study involvement or results in inability to 
continue to comply with study procedures. 
The reason for withdrawal will be recorded in the CRF. If withdrawal is due to an AE, appropriate 
follow-up visits or medical care will be arranged, with the agreement of the volunteer, until the AE 
has resolved, stabilised or a non-trial related causality has been assigned. The local safety monitor 
may recommend withdrawal of volunteers on safety grounds. 
Any participant who repeatedly fails to attend for follow-up visits during the study may be considered 
for withdrawal from the study, following an assessment by the trial team and principal investigator. 
Participants should not be withdrawn as lost to follow-up until all efforts contact them have been 
exhausted. 
If a volunteer withdraws from the study, blood and stool samples collected before their withdrawal 
from the trial will be used/ stored unless the volunteer specifically requests otherwise.  

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In all cases of participant withdrawal, excepting those of complete consent withdrawal, long-term 
safety data collection, including some procedures such as safety bloods, will continue as appropriate 
if participants have received at least one dose of the trial IMP.  
6.9
Compliance with dosing regime 
All doses in this vaccine study will be administered by appropriately trained and delegated clinical trial 
staff and administration details will be recorded in an appropriate CRF. The study medication will not 
be in the possession of the volunteer at any time and compliance will therefore not be an issue within 
this trial. 
6.10
Pregnancy 
Should a volunteer become pregnant during the trial, she will be followed up for safety outcomes. 
Additionally, she will be followed until pregnancy outcome. We will not routinely perform 
venepuncture in a pregnant volunteer. 

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7
CLINICAL TRIAL PROCEDURES 
This section describes the procedures for evaluating study participants and follow-up after 
administration of study vaccine.  
7.1
Study procedures 
All participants will receive the ChAdOx1 biEBOV vaccine and subsequently attend the predefined 
follow up visit schedule as indicated in the schedule of procedures table (Section 2). Study procedures 
will depend on the specific visit and include: vaccination with the study IMP, collection and review of 
AEs via symptom e-Diaries, collection of SAE and AESI data, blood sampling for clinical safety 
monitoring and immunogenicity analysis, vital signs and pregnancy testing for WOCBP.  
In certain circumstances, additional visits or procedures may be performed at the discretion of 
investigators. These may include further medical history and targeted physical examinations, 
urinalysis, confirmatory urine testing in the event of positive urinalysis and additional blood tests if 
clinically relevant. 
7.2
Demographic Data Collection 
Demographic data will be collected at the screening visit. This will include: 
Age 
Biological sex 
Ethnicity 
7.3
Medical History 
7.3.1
Screening Medical History 
A past medical history will be recorded at the screening visit which should cover: all significant 
previous and ongoing medical conditions experienced by the participant and concomitant 
medications.  
7.3.2
Review of Medical Records/ Confirmation of Past Medical History 
Investigators will confirm the past medical history of participants through a review of their medical 
records or by another means. This will enable eligibility criteria to be confirmed and ensure accurate 
baseline information is recorded. Acceptable methods of confirming past medical histories include: 
Review of a GP medical summary 
Review of electronic GP records if available 
Investigator discussion with a 
 GP  
Any other method of confirming a participant past medical history that is deemed to be 
acceptable by the investigator.  
7.3.3
Targeted Medical History 
Participants reporting AEs may also be reviewed and targeted histories may take place throughout the 
trial as though appropriate by investigators. 

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7.4
Physical Observations / Vital Signs 
The following vital signs will be measured in clinic at the time-points indicated in the schedule of 
procedures table (Section 2): 
Pulse 
Blood Pressure 
Temperature (Oral) 
Additionally, physical observations may also be measured as part of a physical examination if indicated 
at other timepoints during the study. Pulse oximetry will not be routinely measured unless clinically 
indicated. 
In addition to in-clinic vital signs, participants will self-assess oral temperature daily for 7 days 
following IMP vaccination as part of solicited AE data collection. 
7.5
Physical Examinations 
A physical examination will be performed at the screening visit. Targeted physical examinations may 
also be carried out were indicated at follow up visits. Any abnormal examination findings at 
screening or during will be recorded in the appropriate CRF. 
7.5.1
Screening Physical Examination 
A screening physical examination will generally include assessment of: 
Height & weight 
General appearance 
Skin 
Lymph node examination 
Abdominal examination 
Cardiovascular examination  
Respiratory examination 
7.5.2
Targeted Physical Examination 
A targeted physical examination may include areas suggested by the medical history, clinical signs, 
and symptoms.  
7.6
Participant Samples 
7.6.1
Clinical Laboratory Blood Samples 
Blood will be drawn for the following laboratory tests. These will be carried out at Oxford University 
Hospitals NHS Foundation Trust using NHS standard procedures: 
Haematology: 
o
Full Blood Count (Including: Haemoglobin, platelet count, total white cell count, 
neutrophil count, lymphocyte count, eosinophil count) 
Biochemistry:
o
Urea and Electrolytes (Including: Sodium, Potassium, Urea and Creatinine)  
o
Liver Function Tests (Including: ALT, ALP, Bilirubin, Albumin) 
Diagnostic serology (Screening Only): 
o
Screening tests for Hep B, Hep C and HIV infection (Including: HBsAg, HCV 
antibodies, HIV antibodies) 

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Immunology:
o
Human Leukocyte Antigen (HLA) typing 
Additional safety blood tests may be performed if clinically relevant at the discretion of the medically 
qualified investigators. These generally include, but are not limited to AST, GGT and a coagulation 
screen. 
7.6.2
Immunology Samples 
7.6.2.1
University of Oxford research laboratories: 
Immunogenicity will be assessed by a variety of immunological assays. This may include ex vivo ELISpot 
assays for interferon gamma and flow cytometry assays, functional antibody assays and B cell 
analyses. Other exploratory immunological assays including cytokine analysis and other antibody 
assays, production of monoclonal antibodies, DNA analysis of genetic polymorphisms potentially 
relevant to vaccine immunogenicity and gene expression studies amongst others may be performed. 
7.6.2.2
Other research laboratories:  
Collaboration with other specialist laboratories in the UK, Europe and outside of Europe for further 
exploratory immunological tests may occur. This would involve the transfer of serum, plasma and 
PBMC to these laboratories, but these would remain de-identified. Informed consent for this will be 
gained from volunteers. Immunological assays will be conducted according to local SOPs.  
7.6.3
Stool Sample Collection 
Stool samples will optionally be collected for the study of gut microbiota. Participants will collect 
faecal samples at home, following an established SOP for stool collection and using specific containers 
provided by the trial team. Instructions will be provided, and participants will return samples either 
to the clinic or via post.  
In participants that opt in, samples of faeces will be collected at the following timepoints:  
(Single dose recipients) Before vaccination, at D14 (thought to be the peak of the T-cell 
response), 
(Two dose recipients) Before the first vaccination, at D14, before the second vaccination, 14 
days after the second vaccination (V2+14) 
.  
Stool samples will be taken prior to the above visits, within 24 hours. 
7.6.4
Urine Samples 
Urine will be collected at specified timepoints for the following tests: 
Urinalysis; Urine will be tested for protein, blood and glucose at screening (via bedside 
urinalysis strips) 
Pregnancy Testing; For female volunteers of childbearing potential only, urine will be tested 
for human chorionic gonadotrophin (HCG) at screening and immediately prior to each 
vaccination. -HCG blood sampling may also alternatively be acceptably used to confirm a 
female participant is not pregnant. 
7.6.5
Retention of Samples 
Participants will be informed that they may opt-in to the Oxford Vaccine Centre Biobank study (REC 
16/SC/014) to allow long-term storage of biological samples collected under the EBL07 protocol for 
use in possible future research. The OVC Biobank study is covered by a separate study protocol and 

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consent process. Participants will be informed that declining to take part in the OVC Biobank study 
will not affect their participation in the EBL07 study. If a participant elects to decline to take part in 
the OVC Biobank, all of their leftover samples will be discarded after the required period of storage to 
meet Good Clinical Practice (GCP) and regulatory requirements.  
7.7
Study visits 
The study visits and procedures will be undertaken by one of the clinical trials team. The procedures 
to be included in each visit are documented in the schedule of attendances tables (Section 2). Each 
visit is assigned a time-point and a window period, within which the visit will be conducted. 
7.7.1
Screening visit  
All potential volunteers will have a screening visit, which may take place up to 90 days prior to 
vaccination. Informed consent will be taken before screening, as described in section 6.4. If consent is 
obtained, the screening procedures indicated in section 2.1 will be undertaken. To avoid unnecessary 
additional sampling, if the appropriate results for screening are available for the same volunteer from 
a screening visit for another Jenner Institute Clinical Trials group vaccine study, these results may be 
used for assessing eligibility (provided the results date is within the 3 months preceding enrolment in 
EBL07). 
The participant
participant 
after satisfactory screening as notification that the participant has volunteered for the study. During 
the screening the volunteers will be asked to provide their National Insurance or passport number so 
that this can be entered on to a national database which helps prevent volunteers from participating 
in more than one clinical trial simultaneously or over-volunteering for clinical trials (www.tops.org.uk). 
Abnormal clinical findings from the urinalysis or blood tests at screening will be assessed by the lead 
clinician according to the relevant SOP. Abnormal blood tests following screening will be assessed 
according to laboratory adverse event grading tables. Any abnormal test result deemed clinically 
significant may be repeated to ensure it is not a single occurrence. If an abnormal finding is deemed 
to be clinically significant, the volunteer will be informed and appropriate medical care arranged with 
the permission of the volunteer.  
The eligibility of the volunteer will be reviewed at the end of the screening visit and again when all 
results from the screening visit have been considered. Decisions to exclude the volunteer from 
enrolling in the trial or to withdraw a volunteer from the trial will be at the discretion of the 
Investigator. If eligible, a day 0 visit will be scheduled for the volunteer to receive the vaccine. 
7.7.2
ChAdOx1 biEBOV vaccination visit(s) 
Before vaccination, the eligibility of the volunteer will be reviewed. Pulse, blood pressure and 
temperature will be observed and if necessary, a further medical history and physical examination 
may be undertaken to determine need to postpone vaccination. Vaccinations will be administered as 
described below in section 7.8 and in accordance with relevant SOPs. 
7.7.3
Follow up Visits 
Follow-up visits will take place as per the schedule of procedures table (Section 2). Volunteers will be 
assessed for local and systemic adverse events, interim history, physical examination and a review of 
electronic diaries at the indicated time points. Blood will also be taken for both safety assessments 
(biochemistry and haematology tests listed in section 7.6.1) and immunology purposes at the majority 
of follow up visits.  

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If volunteers experience adverse events (laboratory or clinical), which the investigator (physician), CI 
and/or LSM determine necessary for further close observation, the volunteer may be admitted to an 
NHS hospital for observation and further medical management under the care of the Consultant on 
call. 
7.7.4
Missed Visits 
In exceptional circumstances, where follow up visits would otherwise be missed entirely, visits may 
alternatively be conducted remotely via phone or video calling. This will allow a minimum set of safety 
and adverse event data to be collected. 
7.8
ChAdOx1 biEBOV vaccinations  
Before each vaccination, the on-going eligibility of the volunteer will be reviewed. ChAdOx1 biEBOV 
will be administered intramuscularly according to vaccine administration SOPs as described in section 
8.2. The injection site will be covered with a sterile dressing and the volunteer will stay in the CCVTM 
for observation, in case of immediate adverse events. Observations will be taken 30 minutes after 
vaccination (±5 minutes) and the sterile dressing removed and injection site inspected. Observations 
will also be taken at 60 minutes (±10 minutes), before the volunteer leaves.  
7.9
Electronic Participant Symptom Diary  
An oral thermometer, tape measure and electronic diary access will be given to each volunteer, with 
instructions on use, along with a contact card including the emergency 24 hour telephone number to 
contact the on-call study physician if needed. In the event of technical problems, paper symptom 
diaries may alternatively be issued. 
The eDiary ePRO system collects information on the timing and severity of the solicited AEs listed in 
section 9.2. Volunteers will be instructed on how to self-assess the severity of these AEs. There will 
also be space on the eDiary to self-document unsolicited AEs, and whether medication was taken to 
relieve the symptoms.  
The eDiary database automatically monitors for grade 3 severity adverse events in (near) real-time, 
which are then flagged up to key study site personnel. This allows (near) real-time assessment of 
potential solicited/unsolicited adverse events for holding rules and to ensure individual participant 
safety. Additional scheduled eDiary automatic data checks are carried as detailed in the EBL07 data 
management plan. 
Backup paper versions of the eDiary can be made available in exceptional circumstances e.g. in case 
of technical failures. 
7.10
COVID-19 Study Considerations 
The study will be carried out in line with the latest Public Health England (PHE) advice. Local SOPs for 
the use of appropriate personal protective equipment (PPE) and social distancing will be followed by 
clinical staff. 
Participants must consent to inform the trial team of COVID-19 infection during the study as part of 
the informed consent process, in order to be enrolled in the study. Participants will be reminded to 
follow the up-to-date local public health guidance regarding COVID-19 during the trial. In keeping with 
PHE guidance on vaccine associated fever during the pandemic42, participants experiencing fever 
within the first 48 hours of vaccination, with no other primary symptom of covid-19 (cough, anosmia, 
ageusia) will not be advised to self-isolate unless there is otherwise clinical suspicion of COVID-19. 

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Participants will be able to discuss symptoms with a medically qualified on call study clinician via 
mobile phone at all times during the study. Participants describing potential COVID-19 symptoms may 
be recommend to seek follow up and testing for COVID-19 through healthcare pathways available to 
them. 

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8
INVESTIGATIONAL PRODUCTS 
All participants will receive at least one vaccination with ChAdOx1 biEBOV, with a dose according to 
their allocated group, as outlined in section 5.1. 
8.1
Supply (ChAdOx1 biEBOV) 
ChAdOx1 biEBOV has been manufactured under Good Manufacturing Practice (GMP) conditions at 
the Clinical Biomanufacturing Facility (CBF), University of Oxford. The vaccine will be certified and 
labelled for the trial by a Qualified Person (QP) at the CBF before transfer to the clinical site.  
The ChAdOx1 biEBOV drug substance is a slightly opaque frozen viral solution, essentially free from 
visible particulates. The vaccine is supplied as a liquid in glass vials for intramuscular administration 
and will be stored at nominal -80°C in a secure freezer at the clinical site.  
8.2
Administration of Investigational Medicinal Products 
On vaccination day, ChAdOx1 biEBOV will be allowed to thaw to room temperature and will be 
administered within 1 hour of removal from the freezer. The vaccine will be administered 
intramuscularly into the deltoid of the non-dominant arm (preferably). All volunteers will be observed 
in the unit for 1 hour (±15 minutes) after vaccination.  During administration of the investigational 
products, Advanced Life Support drugs and resuscitation equipment will be immediately available for 
the management of anaphylaxis. Vaccination will be performed and the IMPs handled according to 
the relevant SOPs. 
8.3
Minimising environmental contamination with genetically modified organisms (GMO) 
The study will be performed in accordance with UK Genetically Modified Organisms (Contained Use) 
Regulations (2014). In order to minimise dissemination of the recombinant vectored vaccine virus into 
the environment, ChAdOx1 biEBOV inoculation sites will be covered with a dressing after 
immunisation. This should absorb any virus that may leak out through the needle track. The dressing 
will be removed from the injection site after 30 minutes (+15/- 5 minutes) and will be disposed as 
GMO waste by autoclaving. 

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9
ASSESSMENT OF SAFETY 
Safety will be assessed by the frequency, incidence and nature of adverse events and serious adverse 
events arising during the study. 
9.1
Definitions 
Adverse 
Event (AE) 
Any untoward medical occurrence in a participant to whom a medicinal product has 
been administered, including occurrences which are not necessarily caused by or 
related to that product. 
Adverse 
Reaction 
(AR) 
An untoward and unintended response in a participant to an investigational medicinal 
product which is related to any dose administered to that participant. 
The phrase "response to an investigational medicinal product" means that a causal 
relationship between a trial medication and an AE is at least a reasonable possibility, 
i.e. the relationship cannot be ruled out. 
All cases judged by either the reporting medically qualified professional or the 
Sponsor as having a reasonable suspected causal relationship to the trial medication 
qualify as adverse reactions. 
Serious 
Adverse 
Event (SAE) 
A serious adverse event is any untoward medical occurrence that: 
results in death 
is life-threatening 
requires inpatient hospitalisation or prolongation of existing hospitalisation 
results in persistent or significant disability/incapacity 
consists of a congenital anomaly or birth defect*. 
when, based upon appropriate medical judgement, the event may jeopardise the 
participant and may require medical or surgical intervention to prevent one of the 
outcomes listed above. 
NOTE: The term "life-threatening" in the definition of "serious" refers to an event in 
which the participant was at risk of death at the time of the event; it does not refer 
to an event which hypothetically might have caused death if it were more severe.  
Serious 
Adverse 
Reaction 
(SAR) 
An adverse event that is both serious and, in the opinion of the reporting Investigator, 
believed with reasonable probability to be due to one of the trial treatments, based 
on the information provided. All serious adverse events deemed possible, probably 
or definitely related will be considered SARs in this study. 
Suspected 
Unexpected 
Serious 
Adverse 
Reaction 
(SUSAR) 
A serious adverse reaction, the nature and severity of which is not consistent with the 
Reference Safety Information for the medicinal product in question set out: 
in the case of a product with a marketing authorisation, in the approved 
summary of product characteristics (SmPC) for that product 
in the case of any other investigational medicinal product, in the approved 

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9.2
Solicited Adverse Events Assessment 
Predefined local and systemic solicited AEs for reactogenicity assessment, as listed below (Table 4 
Solicited Adverse Events), will be collected in an electronic diary (details in section 7.9) for 7 days 
following administration of the vaccine. Participants will measure and record their temperature and 
the diameter of any injection site redness with the provided thermometer and tape measure and AE 
severity gradings will be calculated based on these measurements. For all other solicited AEs, solicited 
AE severity will be self-assessed by participants according to severity grading scales provided to them 
as defined in section 9.8.  
Table 4 Solicited Adverse Events 
Local solicited AEs 
Systemic solicited AEs 
Redness at the injection site (measured) 
Fever (measured) 
Warmth at the injection site 
Chills 
Itch at the injection site 
Feverishness 
Pain at the injection site 
Joint pains 
Muscle pains 
Fatigue 
Headache 
Nausea  
Malaise 
9.3
Unsolicited Adverse Events Assessment 
Unsolicited adverse events i.e. those collected through open questioning 
that do not constitute SAEs or AESIs will be collected for 28 days following 
administration of the IMP. These will be recorded in the participant eDiary and relevant eCRF. 
9.4
Adverse Events of Special Interest (AESI) 
AEs of special interest are based on Brighton Collaboration case definitions, clinical experience, and 
scientific interest.  AESIs will be monitored and recorded throughout the study period. These will 
include the list below (Table 5 EBL07 AESIs). Additionally, other adverse events (i.e. not listed below) 
may also be categorised by investigators as AESIs if scientifically warranted. 

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Table 5 EBL07 AESIs 
Neurological 
Transverse Myelitis 
Generalised convulsion 
Guillain-Barre Syndrome (GBS) 
Acute Disseminated Encephalomyelitis (ADEM)  
Other New Neurological Diagnoses 
Haematological / Vascular 
Thrombocytopenia  
Thrombosis with Thrombocytopenia Syndrome 
Major thrombosis (without thrombocytopenia)  
Heparin-Induced Thrombocytopenia 
Immunological 
Anaphylaxis  
Vasculitides 
Other Immune-Mediated Conditions 
9.5
Causality assessment 
9.5.1
Solicited AE Causality Assessment 
Solicited AEs are expected to occur after vaccination and will therefore not be assessed for 
relationship to study intervention. 
9.5.2
Unsolicited AE Causality Assessment 
For unsolicited AEs, an assessment of the relationship of the event to the administration of the vaccine 
will be undertaken by the CI or delegated clinician. An intervention-related AE refers to an AE for 
which there is a possible, probable or definite relationship to administration of a vaccine. An 
interpretation of the causal relationship of the intervention to the AE in question will be made, based 
on the type of event; the relationship of the event to the time of vaccine administration; and the 
known biology of the vaccine therapy (Table 6). Alternative causes of the AE, such as the natural 
history of pre-existing medical conditions, concomitant therapy, other risk factors and the temporal 
relationship of the event to vaccination will be considered and investigated. Causality assessment will 
take place during planned safety reviews, interim analyses (e.g. if a holding rule is activated) and at 
the final safety analysis, except for SAEs, which should be assigned by the reporting investigator. 

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Table 6. Guidelines for assessing the relationship of vaccine administration to an AE. 
0 
No Relationship 
No temporal relationship to study product; and
Alternate aetiology (clinical state, environmental or other interventions); 
and 
Does not follow known pattern of response to study product. 
1 
Unlikely 
Unlikely temporal relationship to study product; and 
Alternate aetiology likely (clinical state, environmental or other 
interventions); and 
Does not follow known typical or plausible pattern of response to study 
product. 
2 
Possible 
Reasonable temporal relationship to study product; or
Event not readily produced by clinical state, environmental or other 
interventions; or
Similar pattern of response to that seen with other vaccines. 
3 
Probable 
Reasonable temporal relationship to study product; and
Event not readily produced by clinical state, environment, or other 
interventions; or
Known pattern of response seen with other vaccines. 
4 
Definite 
Reasonable temporal relationship to study product; and
Event not readily produced by clinical state, environment, or other 
interventions; and
Known pattern of response seen with other vaccines. 
9.6
Expectedness assessment 
All serious adverse reactions related to ChAdOx1 biEBOV administration will be assessed for 
expectedness by the investigator. Expectedness will be determined according to the information set 
out in the reference safety section of the ChAdOx1 biEBOV IB.  
No SARs are currently expected for ChAdOx1 biEBOV. Therefore, any SARs associated with ChAdOx1 
biEBOV will be reported as SUSARs.  
9.7
Reporting procedures for all Adverse Events  
All local and systemic AEs occurring in the 28 days following each IMP vaccination observed by the 
Investigator or reported by the volunteer, whether or not attributed to study medication, will be 
recorded (excluding those expected consequences from venepuncture, described in section 3.8). 
Recording and reporting of all AEs will take place as detailed in relevant trial SOPs.  All AEs that result 
or until a non-study related causality is assigned (if the volunteer consents to this). Serious adverse 
events (SAEs) will be collected throughout the entire trial period. 

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9.7.1
Reporting procedures for SAEs  
In order to comply with current regulations on serious adverse event reporting to regulatory 
authorities, the event will be documented accurately and notification deadlines respected. SAEs will 
be reported on the SAE forms to members of the study team immediately once an Investigator 
becomes aware of their occurrence, as described in SOP OVC005. Copies of all reports will be 
forwarded for review to the CI 
being aware of the suspected SAE. The LSM will be notified of SAEs that are deemed possibly, probably 
or definitely related to study interventions within 24 hours of the Investigator being aware of their 
occurrence. SAEs will not normally be reported immediately to the ethics committee(s) unless there 
is a clinically important increase in occurrence rate, an unexpected outcome, or a new event that is 
likely to affect safety of trial volunteers, at the discretion of the CI and/or LSM. In addition to the 
expedited reporting above, the Investigator shall include all SAEs in the annual Development Safety 
Update Report (DSUR). 
9.7.2
Reporting Procedures for SUSARS 
The CI will report all SUSARs to the Medicines and Healthcare products Regulatory Authority (MHRA) 
and ethical committee(s) within required timelines (15 calendar days for all SUSARs from the date of 
awareness, unless life threatening in which case 7 days, with a final report within a further 8 days 
(total 15)). The CI will also inform all Investigators concerned of relevant information about SUSARs 
that could adversely affect the safety of participants. All SUSARs and deaths occurring during the study 
will be reported to the Sponsor. For all deaths, available autopsy reports and relevant medical reports 
will be made available for reporting to the relevant authorities. 
9.7.3
Development Safety Update Report 
The CI will submit (in addition to the expedited reporting above) Development Safety Update Reports 
(DSURs) once a year throughout the clinical trial, or on request, to the Competent Authority (MHRA 
in the UK), Ethics Committee, HRA (where required), Host NHS Trust and Sponsor. 
9.8
Assessment of severity 
The severity of clinical and laboratory adverse events will be assessed according to scales based on 
FDA toxicity grading scales for healthy and adolescent volunteers enrolled in preventive vaccine 
clinical trials, listed in  

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Appendix C: Severity Grading Criteria and study specific SOPs.  
9.9
Procedures to be followed in the event of abnormal findings 
Laboratory parameters for inclusion/exclusion in the trial will be considered on an individual basis, 
with investigator discretion for interpretation of results and the need for repeated tests. Abnormal 
clinical findings from medical history, examination or blood tests will be assessed as to their clinical 
significance throughout the trial. If a test is deemed clinically significant, it may be repeated, to ensure 
it is not a single occurrence. If a test remains clinically significant, the volunteer will be informed and 
appropriate medical care arranged as appropriate and with the permission of the volunteer. Decisions 
to exclude the volunteer from enrolling in the trial or to withdraw a volunteer from the trial will be at 
the discretion of the Investigator.  
9.10
Local Safety Monitor 
An independent Local Safety monitor (LSM) will be appointed to provide real-time safety oversight. 
The LSM will review SAEs deemed possibly, probably or definitely related to study interventions. The 
has the power to terminate the study if deemed necessary following a study intervention-related SAE. 
At the time of writing, the LSM will be Prof Brian Angus, a Clinical Tutor in Medicine, Honorary 
Consultant Physician and Director, Centre for Tropical Medicine at the University of Oxford. All 
correspondence between investigator and LSM will be conveyed by the investigator to the trial 
Sponsor. 
The LSM may be contacted for advice and independent review by the investigator or trial Sponsor in 
the following situations: 
Following any SAE deemed to be possibly, probably, or definitely related to a study 
intervention. 
Any other situation where the Investigator or trial sponsor feels independent advice or 
review is important. 
9.11
Interim safety reviews 
The safety profile of the IMP will be assessed on an on-going basis by the Investigators with 
communication to the LSM as necessary. The CI and relevant Investigators (as per the trial delegation 
log) will also review safety issues and SAEs as they arise.  
9.11.1 First dose vaccination 
The following interim safety reviews will take place. (Also refer to section 5.4 - Sequence of 
Enrolment): 
48 hours following the vaccination of the first volunteer in each group to decide on whether 
to proceed with vaccination of the next 2 volunteers in the group. 
Following vaccination of the first 3 volunteers in each group to decide whether to proceed 
with vaccinations of the remaining participants in the group. 
Following vaccination of all participants within a group. These reviews will include the 
results of clinical safety blood tests at the D7 visit and will be required to decide on dose 
escalation. 

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Interim safety reports will be produced for interim safety reviews and will contain the relevant adverse 
event / safety data. 
In the event of reactogenicity judged to be significant at the lower doses, 3 more participants may be 
enrolled into the 2.5 x1010 vp dose group (group 2). If utilised, this will enable more reactogenicity 
data to be collected prior to the 5 x1010 vp dose escalation decision. 
9.11.2 Second dose vaccination 
Reduced reactogenicity has previously been observed following second doses of other ChAdOx1 
vaccines (section 3.6.1). However, second dose vaccinations will initially be staggered. Electronic 
patient-reported outcome (ePRO) eDiary adverse event data will be reviewed remotely after (a 
minimum of) 48 hours following administration of second doses for the first three initial second dose 
participants. This data will be presented to the LSM as the following interim safety reports: 
48 hours following the first second-dose vaccination to decide on whether to proceed with 
vaccination of the next 2 volunteers in the group. 
Following vaccination of the first 3 volunteers in each group to decide whether to proceed 
with vaccinations of the remaining participants in the group. 
 Vaccination of the remaining group 3 volunteers with the second dose may only proceed after this 
safety review (see section 5.4.3). 
9.12
Safety Holding Rules 
Safety holding rules are in place as this is a first-in-human dose escalation study. It is expected that a 
small proportion of participants may report transient grade 3 symptoms within 48 hours of 
vaccination, at the 5 x 1010 vp dose. This is based on experience with ChAdOx1 nCoV-19 (which is now 
an approved vaccine) and other ChAdOx1 vectored vaccines used at the 5 x 1010 vp dose.  The following 
safety holding rules below are designed to reflect this. Safety holding rules also apply following the 
second vaccination (SA02). 
9.12.1 Group holding rules 
The group holding rules are as follows; 
Solicited local adverse events: 
If 2 or more vaccinations in a group are followed by the same Grade 3 solicited local adverse event 
beginning within 2 days after vaccination (day of vaccination and one subsequent day) and persisting 
at Grade 3 for >48 hrs. 
Solicited systemic adverse events:  
If 2 or more vaccinations in a group are followed by the same Grade 3 solicited systemic adverse event 
beginning within 2 days after vaccination (day of vaccination and one subsequent day) and persisting 
at Grade 3 for >48 hrs.  
Unsolicited adverse events: 
If 2 or more vaccinations in a group are followed by the same Grade 3 unsolicited adverse event 
(including the same laboratory adverse event) that is considered possibly, probably or definitely 
related to vaccination and persists at Grade 3 for > 48hrs.  
A serious adverse event considered possibly, probably or definitely related to vaccination 
occurs 
Death occurs 

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A life-threatening reaction occurs 
If a holding rule has been met we will inform the regulatory authority; following an internal safety 
review, if it is deemed appropriate to restart dosing, a request to restart dosing with pertinent data 
must be submitted to the regulatory authority as a request for a substantial amendment. The internal 
safety review will consider:  
The relationship of the AE or SAE to the vaccine. 
The relationship of the AE or SAE to the vaccine dose, or other possible causes of the event. 
If appropriate, additional screening or laboratory testing for other volunteers to identify 
those who may develop similar symptoms and alterations to the current Participant 
Information Sheet (PIS). 
New, relevant safety information from ongoing research programs on the various 
components of the vaccine. 
The sponsor, LSM, and vaccine manufacturer (CBF) will also be notified if a holding rule is activated or 
released. All vaccinated volunteers will be followed for safety until the end of their planned 
participation in the study or until resolution or stabilisation (if determined to be chronic sequelae) of 
their AEs, providing they consent to this. 
In addition to these pre-defined criteria, the study can be put on hold upon advice of the LSM, CI, 
Study Sponsor, Regulatory Authority or Ethical Committee(s), for any single event or combination of 
multiple events which they deem jeopardise the safety of the volunteers or the reliability of the data. 

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10 DATA MANAGEMENT 
10.1
Data Management Plan 
A trial specific data management plan will be generated and adopted for this trial. This will describe 
relevant aspects of data management related to the trial in detail. 
10.2
Data Handling 
The Chief Investigator will be responsible for all data that accrues from the study. The data will be 
entered into CRFs in an electronic format (using the study OpenClinica  database). Electronic data 
will be stored on secure servers which are outsourced by OpenClinica . Data will be entered into the 
OpenClinica Database via a secure web browser. OpenClinica  meets FDA part 11B standards. This 
includes safety data, laboratory data (both clinical and immunological) and outcome data.  
Adverse event data will also be entered onto electronic or paper diaries by the volunteer  
10.3
Record Keeping 
The Investigators will maintain appropriate medical and research records for this trial, in compliance 
with GCP and regulatory and institutional requirements for the protection of confidentiality of 
volunteers. The Chief Investigator, co-Investigators and clinical research nurses will have access to 
records. The Investigators will permit authorised representatives of the Sponsor(s), as well as ethical 
and regulatory agencies to examine (and when required by applicable law, to copy) clinical records for 
the purposes of quality assurance reviews, audits and evaluation of the study safety and progress. 
complete, so we may inform them of opportunities to participate in future vaccine related research. 
This will be entirely optional and participation in this study will not be affected by their decision to 
allow or not allow storage of their contact details beyond participation in this trial. Details will be 
stored electronically on a secure server and only authorised individuals at the CCVTM will have access 
to it. We will not, under any circumstances, share their contact details with any third party institutions 
without their permission. Volunteers will be informed that being contacted does not oblige them to 
agree to take part in future research and they can ask us to have their contact details removed from 
our database at any time. 
10.4
Source Data and Case Report Forms (CRFs) 
All protocol-required information will be collected in CRFs designed by the Investigator. All source 
documents will be filed in individual participant files. Source documents are original documents, data, 
are not limited to, volunteer consent form, blood results, GP response letters, laboratory records, 
diaries, and correspondence. In the majority of cases, CRF entries will be considered source data as 
the CRF is the site of the original recording (i.e. there is no other written or electronic record of data). 
In this study this will include, but is not limited to medical history, medication records, vital signs, 
physical examination records, urine assessments, blood results, adverse event data and details of 
vaccinations. All source data and volunteer CRFs will be stored securely.  

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10.5
Data Protection  
The study protocol, documentation, data and all other information generated will be held in strict 
confidence. No information concerning the study or the data will be released to any unauthorised 
third party, without prior written approval of the sponsor. 
10.6
Data Quality 
Data collection tools will undergo appropriate validation to ensure that data is collected accurately 
and completely. Datasets provided for analysis will be subject to quality control processes to ensure 
analysed data is a true reflection of the source data. 
Trial data will be managed in compliance with local data management SOPs (including the overarching 
SOP OVC007 Data and Database Management) and the trial specific data management plan. 
The trial will comply with the UK General Data Protection Regulation (GDPR) and Data Protection Act 
2018, which requires data to be de-identified as soon as it is practical to do so. 
10.7
Archiving 
Study data may be stored electronically on a secure server, and paper notes will be kept in a key-
locked filing cabinet at the CCVTM  Churchill Hospital, University of Oxford. All essential documents 
will be retained for a minimum of 5 years after the study has finished. The need to store study data 
for longer in relation to licensing of the vaccine will be subject to ongoing review. For effective vaccines 
that may be licensed, we may store research data securely at the University of Oxford for at least 15 
years after the end of the study, subject to ad
details will be stored for 7 years in line with University of Oxford financial policy.  
General archiving procedures will be conducted in compliance to Archiving SOP. 

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11 STATISTICS  
11.1
Sample Size Selection 
This is a descriptive dose-escalation study and as such no formal power calculations have been 
performed. The numbers have been therefore chosen on the basis of providing adequate descriptive 
safety information to permit further clinical evaluation in later phase trials.
11.2
Study Analyses 
The analyses for this study will be descriptive and will not include any hypothesis testing or 
presentation of p-values for group comparisons. All confidence intervals for descriptive analyses will 
be set at 95%. Variables will be summarised using appropriate descriptive statistics. 
11.2.1 Recruitment, Enrolment and Withdrawal Data 
The number of individuals screened, screening failures, number enrolled and vaccinated within each 
group and withdrawals will be summarised descriptively. 
11.2.2 Demographic and Baseline Data 
Demographic and baseline medical histories will be summarised and presented for each group. 
11.2.3 Safety Data 
All participants that received a study vaccine will be included in the safety analysis. The self-reported 
solicited AE data collected in the first 7 days after vaccination, will be summarised by severity for each 
day of the first 7 days after the administration of vaccines. Unsolicited AEs, SAEs and AESIs will be 
categorised by MedDRA SOC and PT levels. Abnormal clinical safety laboratory values will be graded 
based on a pre-specified severity scale. The frequency and percentage of unsolicited adverse events 
will be summarised for 28 days following the last vaccine. Serious adverse events (SAEs) will be 
summarised during the entire study and also be described narratively. 
11.2.4 Immunogenicity Data 
Immunogenicity endpoints will be presented by vaccine dose. Details of any immunological analyses 
to be performed will be described in an immunology analysis plan. 

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12 ETHICS AND REGULATORY CONSIDERATIONS 
12.1
Declaration of Helsinki 
The Investigators will ensure that this study is conducted according to the principles of the Declaration 
of Helsinki (2008). 
12.2
Guidelines for Good Clinical Practice 
The Investigators will ensure that this study is conducted in full conformity with the Good Clinical 
Practice (GCP), the requirements of the Medicines for Human Use (Clinical Trials) Regulations 2004, 
and local regulatory requirements. 
12.3
Approvals 
The protocol, informed consent form, participant information sheet and any proposed advertising 
material will be submitted to an appropriate Research Ethics Committee (REC), HRA (where required), 
regulatory authorities (MHRA in the UK), and host institution(s) for written approval. 
The Investigator will submit and, where necessary, obtain approval from the above parties for all 
substantial amendments to the original approved documents. 
No substantial amendments to this protocol will be made without consultation with, and agreement 
of, the Sponsor. Any substantial amendments to the trial that appear necessary during the course of 
the trial must be discussed by the Investigator and Sponsor concurrently. If agreement is reached 
concerning the need for an amendment, it will be produced in writing by the Chief Investigator and 
will be made a formal part of the protocol following ethical and regulatory approval. 
The Investigator is responsible for ensuring that changes to an approved trial, during the period for 
which regulatory and ethical committee(s) approval has already been given, are not initiated without 
val except to eliminate apparent immediate 
hazards to the participant. 
12.4
Reporting 
The CI (on behalf of the sponsor) shall submit once a year throughout the clinical trial, or on request, 
an Annual Progress Report to the REC, HRA (where required), host organisation, funder (where 
required) and Sponsor.  In addition, an End of Trial notification and final report will be submitted to 
the MHRA, the REC, host organisation and Sponsor. 
12.5
Volunteer Confidentiality 
Study participants are required to consent for us to contact their GP. We will write to their GP to 
inform them about your enrolment and study completion status, so they can update your medical 
medical history and give access to any other medical records as required to ensure eligibility criteria 
are met. We would only notify GP practices of results of any medical tests with 
permission. 
All research data will be de-identified: volunteer data will be identified by a unique study number in 
the study database. Data will be entered electronically using the study OpenClinica  database. 
OpenClinica  is stored on a secure European server  data will be entered in a web browser on PCs in 
the CCVTM building and then transferred to the OpenClinica Database by encrypted (Https) transfer.  

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A separate confidential participant file containing identifiable information and source data will be 
stored in a secured location in accordance with the Data Protection Act 2018. All documents will be 
stored securely and only accessible by study staff and authorised personnel. The study staff will 
Photographs taken of vaccination sites (if 
be identified by the date, trial code and participant
will be stored as confidential records, as above. This material may be shown to other professional 
staff, used for educational purposes, or included in a scientific publication. 
We will keep identifiable information about volunteers such as contact details for a minimum of 5 
years after the study has finished. The need to store this information for longer in relation to licensing 
of the vaccine will be subject to ongoing review. For effective vaccines that may be licensed, we may 
store research data securely for at least 15 years after the end of the study, subject to adjustments in 
clinical trials regulations. In addition to the de-identified scientific data, we will also store documents 
containing personal information volunteers provide when registering for the trial (including contact 
details), medical information and signed consent forms during this archiving period. 
The study team will use volunteer name and contact details, to contact them about the research study, 
and make sure that relevant information about the study is recorded for their care, in relation to their 
health during the study and to oversee the quality of the study. At the completion of the study, unless 
volunteers consent otherwise (e.g. if they request to be informed of other trials), volunteer personal 
details will not be used to contact them other than in exceptional circumstances concerning their 
safety. If they consent to take part in another study carried out by the Jenner Institute, personal 
information and medical information including blood test results may be accessed to avoid 
unnecessary repetition. 
A photocopy of volunteer ID (driving licence, passport or national ID card) will be taken at the 
screening visit and retained until the end of the study. 
Volunteer bank details will be stored for 7 years in line with university financial policy.  

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13 QUALITY CONTROL AND QUALITY ASSURANCE PROCEDURES 
13.1
Investigator procedures 
Approved site-specific standard operating procedures (SOPs) will be used at all clinical and laboratory 
sites. 
13.2
Monitoring 
Monitoring will be performed according to GCP by Clinical Trials Research Governance (CTRG). 
Following written SOPs, the monitors will verify that the clinical trial is conducted and data are 
generated, documented and reported in compliance with the protocol, GCP and the applicable 
regulatory requirements. The Investigator site will provide direct access to all trial related source 
data/documents and reports for the purpose of monitoring and auditing by the Sponsor and 
inspection by local and regulatory authorities. 
13.3
Protocol deviation  
Any deviations from the protocol will be documented in a protocol deviation form and filed in the trial 
master file. Each deviation will be assessed as to its impact on volunteer safety and study conduct. 
Significant deviations will be listed in the end of study report.
13.4
Audit & inspection  
The QA manager conducts systems based internal audits to check that trials are being conducted 
according to local procedures and in compliance with GCP and applicable regulations.  
The Sponsor, trial sites, and ethical committee(s) may carry out audits to ensure compliance with the 
protocol, GCP and appropriate regulations.  
GCP inspections may also be undertaken by the MHRA to ensure compliance with protocol and the 
Medicines for Human Use (Clinical Trials) Regulations 2004, as amended. The Sponsor will assist in any 
inspections and will support the response to the MHRA as part of the inspection procedure.

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14 FINANCING AND INSURANCE 
14.1
Financing  
The study is funded by Innovate UK. 
14.2
Insurance 
The University has a specialist insurance policy in place which would operate in the event of any 
participant suffering harm as a result of their involvement in the research (Newline Underwriting 
14.3
Participant Financial Compensation 
Volunteers will be compensated for their time and for the inconvenience caused by procedures. They 
will be compensated £25 for attending the screening visit. For all other trial visits (as outlined in 
section 2.2), compensation will be calculated according to the following: 
Travel expenses: 
o
£15 per visit. Where travel expenses are greater than £10 per visit because the 
volunteer lives outside the city of the trial site, the volunteer will be given further 
reimbursement to meet the cost of travel necessary for study visits following receipt 
of valid proof of costs incurred. 
Inconvenience of blood tests: 
o
£10 per blood donation
Time required for visit:  
o
£20 per hour
The total amount of compensation for an individual participant will depend on the actual number of 
visits attended and whether any repeat or additional visits were necessary. If a participant withdraws 
consent for continued participation in the trial or is withdrawn for any other reason, they will still be 
compensated for any trial visits they attended. 
14.4
Contractual Arrangements 
Appropriate contractual arrangements will be put in place with all third parties. 

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15 SERIOUS BREACHES 
The Medicines for Human Use (Clinical Trials) Regulations contain a requirement for the notification 
of "serious breaches" to the MHRA within 7 days of the Sponsor becoming aware of the breach.  
affect to a 
significant degree  
(a) the safety or physical or mental integrity of the participants of the trial; or 
In the event that a serious breach is suspected the Sponsor will be informed within one working day. 
16 PUBLICATION POLICY 
The Investigators will be involved in reviewing drafts of the manuscripts, abstracts, press releases and 
any other publications arising from the study. Data from the study may also be used as part of a thesis 
for a PhD or MD. 
17 DEVELOPMENT OF A NEW PRODUCT/PROCESS OR THE GENERATION OF 
INTELLECTUAL PROPERTY 
Ownership of IP generated by employees of the University vests in the University.  The protection and 
iversity 
Innovations. 

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18 ABBREVIATIONS 
Abbreviations
AdC 
Chimpanzee adenovirus 
AdC68 
Chimpanzee Adenovirus serotype 68 
ADEM 
Acute Disseminated Encephalomyelitis 
AdHu 
Human adenovirus 
AdHu5 
Human adenovirus serotype 5 
AE 
Adverse event 
AESI 
Adverse Events of Special Interest 
ALP 
Alkaline phosphatase 
ALT 
Alanine aminotransferase 
AR 
Adverse reaction 
AST 
Aspartate aminotransferase 
BAC 
Bacterial artificial chromosome 
CBF  
Clinical Biomanufacturing Facility 
CCVTM 
Centre for Clinical Vaccinology and Tropical Medicine 
CDC
Centers for Disease Control and Prevention
ChAd63
Chimpanzee Adenovirus serotype 63
ChAdOx1 
Chimpanzee Adenovirus Ox1 
ChAdOx2 
Chimpanzee Adenovirus Ox2 
ChAdOx1 
biEBOV 
Recombinant simian adenovirus ChAdOx1 vector expressing the 
glycoproteins from Sudan ebolavirus and Zaire ebolavirus 
CI 
Chief Investigator 
CMV 
Human cytomegalovirus 
CRF 
Case Report Form 
CTIMP 
Clinical Trial of an Investigational Medicinal Product 
CTRG 
Clinical Trials Research Governance (Now renamed as Research 
Governance, Ethics and Assurance) 
DALYs
Disability-adjusted life years
DNA
Deoxyribonucleic acid
DSUR
Development Safety Update Report
EBV
Epstein Barr virus
EBOD
Ebola Virus Disease
EBOV 
Zaire Ebolavirus 
ELISA 
Enzyme linked immunosorbent assay 
ELISpot
Enzyme linked immunospot assay
EMA
European Medicines Agency
ePRO
Electronic patient-reported outcomes
FDA
Food and Drug Administration
Filovirus GP
Filovirus Glycoprotein
GBS
Guillain-Barre Syndrome
GCP
Good Clinical Practice
GGT
Gamma-glutamyl Transferase
GMO
Genetically modified organism
GMP
Good Manufacturing Practice
GP
General Practitioner
HBsAg
Hepatitis B surface antigen
HCG
Human Chorionic Gonadotrophin
HCV
Hepatitis C virus

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Abbreviations 
HCV Ab 
Hepatitis C virus antibody 
HEK 
Human embryonic kidney 
HIV 
Human immunodeficiency virus 
HLA 
Human leukocyte antigen 
HRA 
Health Research Authority 
 
IB
Investigators Brochure
ICH 
International Conference on Harmonisation 
ICS 
Intracellular Cytokine Staining 
IFN 
Interferon 
IM 
Intramuscular/intramuscularly 
IMP 
Investigational medicinal product 
ISF 
Investigator Site File 
IU 
Infectious units 
IUD 
Intrauterine device 
IUS 
Intrauterine system 
JCVI 
Joint Committee on Vaccination and Immunisation 
LSM 
Local Safety Monitor 
LVLV 
Last volunteer last visit 
MHRA 
Medicines and Healthcare products Regulatory Agency 
mRNA 
Messenger ribonucleic acid 
MVA
Modified Vaccinia Virus Ankara
NCT Number
National Clinical Trial number
NHP 
Non-human primate 
OVC 
Oxford vaccine centre 
PBMC 
Peripheral blood mononuclear cell 
PCR 
Polymerase Chain Reaction 
PEP
Post-exposure prophylaxis
PHE
Public Health England
PrEP
Pre-exposure prophylaxis
PIS
Participant information sheet
PT
Preferred terms
QP
Qualified Person
RCT 
Randomised controlled trial 
REC 
Research Ethics Committee 
RGEA
Research Governance, Ethics and Assurance (Formerly named Clinical Trials 
and Research Governance)  
RNA
Ribonucleic acid
RSV
Respiratory syncytial virus
rVSV-ZEBOV
Recombinant vesicular stomatitis virus-Zaire Ebola Virus
SAE
Serious Adverse Event
SAR
Serious Adverse Reaction
SARS-CoV-2
Severe acute respiratory syndrome coronavirus 2
SFC
Spot forming cells
SmPC
Summary of Product Characteristics
SOC
System Organ Classes
SOP
Standard Operating Procedure
SUDV
Sudan Ebolavirus
SUSAR
Suspected Unexpected Serious Adverse Reaction
TMF
Trial Master File

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Abbreviations 
TOPS 
The Over-Volunteering Prevention System 
VAERS 
Vaccine Adverse Event Reporting System 
VNA 
Virus neutralising assay 
vp 
Viral particles 
WHO 
World Health Organisation 
WOCBP 
Women of Childbearing Potential

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19 REFERENCES 
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Ebola 
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Voysey, M. et al. Single-dose administration and the influence of the timing of the booster 
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Bernal, J. L. et al. Early effectiveness of COVID-19 vaccination with BNT162b2 mRNA vaccine 
and ChAdOx1 adenovirus vector vaccine on symptomatic disease, hospitalisations and 
mortality 
in 
older 
adults 
in 
England. 
medRxiv, 
2021.2003.2001.21252652, 
doi:10.1101/2021.03.01.21252652 (2021). 
22 
MHRA. Public Assessment Report National procedure Vaxzevria (previously COVID-19 Vaccine 
AstraZeneca, suspension for injection) COVID-19 Vaccine (ChAdOx1-S [recombinant]) PLGB 
17901/0355 AstraZeneca UK Limited 24 June 2021. 
23 
Barrett, J. R. et al. Phase 1/2 trial of SARS-CoV-2 vaccine ChAdOx1 nCoV-19 with a booster 
dose induces multifunctional antibody responses. Nat Med 27, 279-288, doi:10.1038/s41591-
020-01179-4 (2021). 
24 
WHO Expert Committee on Biological Standardization : fifty-fourth report. Annex 1 WHO 
guidelines on nonclinical evaluation of vaccines. WHO Geneva 2005. 
25 
Collins, N. & Belkaid, Y. Do the microbiota influence vaccines and protective immunity to 
pathogens? Engaging our endogenous adjuvants. Cold Spring Harbor perspectives in biology
10, a028860 (2018). 
26 
Eloe-Fadrosh, E. A. & Rasko, D. A. The human microbiome: from symbiosis to pathogenesis. 
Annual review of medicine 64, 145-163 (2013). 
27 
Oh, J. Z. et al. TLR5-mediated sensing of gut microbiota is necessary for antibody responses to 
seasonal influenza vaccination. Immunity 41, 478-492 (2014). 
28 
Kukkonen, K., Nieminen, T., Poussa, T., Savilahti, E. & Kuitunen, M. Effect of probiotics on 
vaccine antibody responses in infancy
Pediatric allergy and immunology 17, 416-421 (2006). 
29 
Soh, S. E. et al. Effect of probiotic supplementation in the first 6 months of life on specific 
antibody responses to infant Hepatitis B vaccination. Vaccine 28, 2577-2579 (2010). 
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MHRA. COVID-19 Vaccine Astrazeneca Regulation 174 Information for UK Health 
Professionals. 
Date: 
14 
Apr 
2021 
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_
data/file/978194/uk-HCP-covid-19-vaccine-astrazeneca-reg174_proposed_14_Apr_2021.pdf
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MHRA. Medicines and Healthcare products Regulatory Agency: Coronavirus (COVID-19) 
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32 
EMA. European Medicines Agency: COVID-19 vaccine safety update: VAXZEVRIA AstraZeneca 
AB. 29 March 2021. 

EBL07 Protocol V4.0, 01 Nov 2022                                                         
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EMA. European Medicines Agency: Direct healthcare professional communication (DHPC): 
COVID-19 Vaccine Janssen: link between the vaccine and the occurrence of thrombosis in 
combination with thrombocytopenia. 26 April 2021. 
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Teva Pharmaceuticals USA. Adenovirus Type 4 and Type 7 Vaccine, Live, [package insert]. U.S. 
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c546-4c8a-8a37-c8fd2807332c/3048ba4b-c546-4c8a-8a37-c8fd2807332c.xml. Revised April 
2020 Accessed 27 April 2021. 
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Choudhry, A., Mathena, J., Albano, J. D., Yacovone, M. & Collins, L. Safety evaluation of 
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Emary, K. R. et al. Efficacy of ChAdOx1 nCoV-19 (AZD1222) vaccine against SARS-CoV-2 variant 
of concern 202012/01 (B. 1.1. 7): an exploratory analysis of a randomised controlled trial. The 
Lancet (2021). 
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Baden, L. R. et al. Assessment of the Safety and Immunogenicity of 2 Novel Vaccine Platforms 
for HIV-1 Prevention: A Randomized Trial. Annals of internal medicine 164, 313-322 (2016). 
38 
Baden, L. R. et al. First-in-human evaluation of the safety and immunogenicity of a 
recombinant adenovirus serotype 26 HIV-1 Env vaccine (IPCAVD 001). The Journal of infectious 
diseases 207, 240-247 (2013). 
39 
Barouch, D. H. et al. Evaluation of a mosaic HIV-1 vaccine in a multicentre, randomised, 
double-blind, placebo-controlled, phase 1/2a clinical trial (APPROACH) and in rhesus monkeys 
(NHP 13-19). Lancet (London, England) 392, 232-243 (2018). 
40 
Capone, S. et al. Optimising T cell (re)boosting strategies for adenoviral and modified vaccinia 
Ankara vaccine regimens in humans. NPJ vaccines 5, 94 (2020). 
41 
Wilkie, M. et al. A phase I trial evaluating the safety and immunogenicity of a candidate 
tuberculosis vaccination regimen, ChAdOx1 85A prime - MVA85A boost in healthy UK adults. 
Vaccine 38, 779-789 (2020). 
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Public Health England 2020 Publications approval reference: 001559 Clinical guidance for 
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EBL07 Protocol V4.0, 01 Nov 2022                                                        
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20 Appendix A: Investigator Signature and Declarations
Statement of Compliance
The trial will be conducted in compliance with the protocol, the principles of Good Clinical Practice 
Guideline, Medicines for Human Use (Clinical Trials) Regulations 2004 (as amended) and all other 
applicable regulatory requirements.  
Chief Investigator Approval, Agreement and Conflict of Interest statement
I have read the trial protocol and agree to conduct the trial in compliance with the protocol, the 
principles of Good Clinical Practice and all applicable regulatory requirements.
Conflict of interest statement:
I declare that there is no conflict of interest.
Paola Cicconi
02NOV2022
Principal Investigator Approval, Agreement and Conflict of Interest statement
I have read the trial protocol and agree to conduct the trial in compliance with the protocol, the 
principles of Good Clinical Practice and all applicable regulatory requirements.
Conflict of interest statement:
I declare that there is no conflict of interest.
Daniel Jenkin
02NOV2022
Chief Investigator
Name
Signature
Date 
Principal Investigator
Name
Signature
Date 

EBL07 Protocol V4.0, 01 Nov 2022                                                         
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21 Appendix B: Document History 
Version 
Author 
Changes 
1.0 
Daniel Jenkin, 
Teresa Lambe 
Document created 
2.0 
Daniel Jenkin 
SA01: Response to MHRA grounds for non-acceptance: 
Added additional exclusion criteria based on the SmPC-
like document for Vaxzevria [ChAdOx1 nCoV-19]: 
(hypersensitivity to the IMP, history of thrombosis with 
thrombocytopenia following Vaxzervria and history of 
capillary leak syndrome). 
Corrected erroneous reference to urinary beta-HCG and 
replaced with urinary HCG. 
Clarified the blood safety assessments referenced in 
section 7.7.3 are the haematology and biochemistry tests 
listed in section 7.6.1. 
3.0 
Daniel Jenkin 
SA02:  
- Addition of second dose 
Group 3 to receive two doses 12-weeks apart 
Update to schedule of procedures for the new two dose 
group to add in the following visits: V2, V2+14, V2+28 and 
V2+182 
Update to study endpoints timings with new follow up 
schedule timepoints  
Additional stool sampling timepoint following the second 
vaccine dose(V2+14) 
Additional interim safety review after the first 3 
individuals have received a second dose of ChAdOx1 
biEBOV (using remote eDiary data at 48 hours). 
Trial planned (end) date updated to Q4 2022 to account 
for longer follow up period for group 3. 
- Update to eDiary section with details on (near) real-time remote 
monitoring of participant entered AEs 
- Name change of Sponsor and Monitor (from CTRG to RGEA). The 
organisation remains the same but has rebranded. 

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Version 
Author 
Changes 
3.1 
Daniel Jenkin 
NSA01: Correction of minor blood volume typographical errors in 
section 2.3: Schedule of Procedures Table: Vaccination and Follow 
up Visits (two dose schedule) 
V2+28 immunology blood volume corrected to 70ml 
(previously stated as 50ml) and V2+14 immunology blood 
volume corrected to 50ml (previously stated as 70ml). 
These were typographical errors in protocol version 3.0. 
Errors in cumulative blood volume calculations fixed 
resulting in a new total of 524ml (previously listed as 
519ml in error) 
4.0 
Daniel Jenkin 
SA03: 
Extension of follow up visits for group 3 to assess longer 
term durability of vaccine responses. This will include an 
additional follow up visit with the procedures as listed in 
section 2. These include 
o
SAE/AESI collection 
o
Immunology blood sampling 
o
Optional stool sampling 
o
An increase to the cumulative blood volume 
Outcome evaluation timepoints amended to add in the 
new extended group 3 follow up visit 
o
SAE/AESIs now evaluated to D364/V2+280 
o
Secondary immunology outcomes now evaluated 
to D364/V2+280 
Clarification of wording around use of screening results 
and wording of the timing of the inclusion criteria relating 
to pregnancy testing to clarify a sample within the 
screening window is acceptable. 

EBL07 Protocol V4.0, 01 Nov 2022                                                         
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22 Appendix C: Severity Grading Criteria 
Table 7. 
of skin puncture and will therefore not be considered an adverse event
Table 8. Severity grading criteria for local and systemic AEs. NB: A&E assessment in itself does not 
constitute a SAE. Refer to 9.1.3 for SAE definition  
GRADE 0 
None 
GRADE 1 
Mild: Transient or mild discomfort (< 48 hours); No interference with activity; No 
medical intervention/therapy required 
GRADE 2 
Moderate: Mild to moderate limitation in activity 
some assistance may be 
needed; no or minimal medical intervention/therapy required 
GRADE 3 
Severe: Marked limitation in activity, some assistance usually required; medical 
intervention/therapy required. 
GRADE 4 
Potentially Life-threatening: requires assessment in A&E or hospitalisation 
Adverse Event
Grade
Intensity
Pain at injection site 
1 
Pain that is easily tolerated 
2 
Pain that interferes with daily activity 
3 
Pain that prevents daily activity 
4 
A&E visit or hospitalization 
Tenderness 
1 
Mild discomfort to touch 
2 
Discomfort with movement 
3 
Significant discomfort at rest 
4 
A&E visit or hospitalization 
Erythema at injection site* 
1 
2.5 - 5 cm 
2 
5.1 - 10 cm 
3 
>10 cm 
4 
Necrosis or exfoliative dermatitis 
Induration/Swelling at injection site 
1 
2.5  5 cm and does not interfere with activity
2 
5.1 - 10 cm or interferes with activity 
3 
>10 cm or prevents daily activity 
4 
Necrosis 

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Table 9. Severity grading criteria for physical observations (applies to adults only). 
minutes at rest **When resting heart rate is between 60  100 beats per minute. Use clinical judgement 
when characterising bradycardia among some healthy subject populations, for example, conditioned 
athletes. ***Only if symptomatic (e.g. dizzy/ light-headed)
Vital Signs 
Grade 1 
(mild) 
Grade 2 
(moderate) 
Grade 3 
(severe) 
Grade 4 
Potentially 
Life 
threatening 
Fever (oral) 
38.0°C - 38.4°C
38.5°C 38.9°C
39.0°C - 40°C
> 40°C
Tachycardia (bpm)* 
101 - 115 
116  130 
>130 
A&E visit or 
hospitalisation 
for arrhythmia
Bradycardia (bpm)** 
50  54 
45  49 
<45 
A&E visit or 
hospitalisation 
for arrhythmia
Systolic hypertension 
(mmHg) 
141 - 150 
151  155 
A&E visit or 
hospitalisation
for malignant 
hypertension 
Diastolic hypertension 
(mmHg) 
91 - 95 
96  100 
>100 
A&E visit or 
hospitalisation 
for malignant 
hypertension 
Systolic hypotension 
(mmHg)*** 
85 - 89
80 84
<80
A&E visit or 
hospitalisation
for 
hypotensive 
shock 
Respiratory Rate  
(breaths per minute) 
17 - 20 
21-25 
>25 
Intubation