A Phase 1/2a, Observer-blind, Randomized, Controlled, Two-stage, Multi-country Study to Evaluate the Safety, Reactogenicity, and Immune Response of the Trivalent Vaccine Against Invasive Nontyphoidal Salmonella (iNTS) and Typhoid Fever in Healthy European and African Adults
Phase: PHASE1
Conditions: Salmonella Infections
Sponsor: GlaxoSmithKline

Protocol Amendment 2
Study ID:  216152
Official Title of Study: A Phase 1/2a, observer-blind, randomized, controlled, two-
stage, multi-country study to evaluate the safety, reactogenicity, and immune response of 
the trivalent vaccine against invasive nontyphoidal Salmonella (iNTS) and Typhoid 
Fever in healthy European and African adults 
NCT number: NCT05480800
Date of Document: 09-Jun-2023

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TITLE PAGE 
Protocol Title: A Phase 1/2a, observer-blind, randomized, controlled, two-stage, 
multi-country study to evaluate the safety, reactogenicity, and immune response of the 
trivalent vaccine against invasive nontyphoidal Salmonella (iNTS) and Typhoid Fever in 
healthy European and African adults 
Protocol Number: 216152 (INTS-GMMA GVGH-002) (H08_01TP) 
Amendment Number: 2 
Product: GVGH iNTS-TCV Investigational Vaccine 
Short Title: A study to evaluate safety, reactogenicity, and immune response of GVGH 
iNTS-TCV vaccine against invasive nontyphoidal Salmonella and Typhoid Fever 
Study Phase: 1/2a (2 stages) 
Sponsor Name: GlaxoSmithKline Biologicals SA 
Legal Registered Address: Rue de l’Institut 89, Rixensart, 1330 Belgium 
Site Details: Centre for Evaluation of Vaccination (CEV), University of Antwerp, 
Belgium 
Principal Investigator: Kanchanamala Withanage 
Malawi-Liverpool-Wellcome Trust Clinical Research Programme, Malawi 
Principal Investigator: Melita Gordon 
Regulatory Agency Identifier Number: 2021-005178-25 
Date of Protocol: Final, 27 April 2022 
Date of Protocol Amendment: Amendment 1 Final, 15 August 2022 
Amendment 2 Final, 08 June 2023 

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Sponsor Signatory: 
 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
 
Ashwani Kumar Arora 
Head of Clinical Development and Regulatory 
Affairs 
 
Date 
 
Refer to the Study Reference Manual for Medical Monitor’s name and contact 
information. 

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PROTOCOL AMENDMENT SUMMARY OF CHANGES 
TABLE 
DOCUMENT HISTORY 
Document 
Date 
Substantial 
Region 
Amendment 2 
08 June 2023 
Yes 
Global 
Amendment 1 
15 August 2022 
Yes 
Global 
Original Protocol 
27 April 2022 
- 
- 
Amendment 2 
This amendment is considered to be substantial based on the criteria set forth in 
Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union. 
Overall Rationale for the Amendment: 
The Protocol Amendment 1 has been amended to include requirements from Malawi site, 
and to update Stage 2 grading scale for hematology and biochemistry safety laboratory 
assessment, according to local ranges provided by the site. 
Section # and Name 
Description of Change 
Brief Rationale 
Throughout 
Minor editorial and document 
formatting revisions 
Minor, therefore, have not been 
summarized 
Section 1.1 Synopsis, Section 3 
Objective and Endpoints, 
Section 8.1.2 Laboratory 
Assays, Table 13 Tertiary 
Endpoints-Statistical Analyses 
Table 1 Schedule of 
Assessments 
Added that out-of-window 
vaccinations are not allowed 
To provide clarity and avoid 
potential protocol deviations 
Table 2 Interval between Visits 
The intervals between a few 
visits were updated. 
To provide flexibility and avoid 
protocol deviations arising due to 
out of window visits 
Table 5 Study Holding Rules 
Some of the events were 
reworded 
To provide clarity 
Section 7.3 Participant 
Discontinuation/Withdrawal 
from the Study 
Section 8.1.1 Biological 
Samples 
Clarification added on taking 
immunogenicity sample and 
safety follow-up for participant 
discontinued due to AE 
To avoid protocol deviations 
arising from taking 
immunogenicity samples from 
discontinued participants observed 
in Stage 1 due to lack of clarity in 
the current protocol. 
Section 8.1.2 Laboratory assay 
Clarified that Prothrombin time 
will not be done in Stage 2 
Prothrombin time cannot be 
performed in the Malawi site. 
CCI

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Section # and Name 
Description of Change 
Brief Rationale 
Section 8.2.1.1 Collection of 
Demographic Data, 
Medical/Vaccination History, 
and Physical Examination 
Justification for collection of 
race (ethnic background) data 
was added 
Collection of race (ethnic 
background) data is necessary to 
assess and monitor the diversity of 
the trial participants and the impact 
of race (ethnic background) on the 
trial endpoints 
Section 9.7 Internal Safety 
Review Committee 
Update in timing for iSRC #5 
review 
Updated to ensure data review #5 
occurs before start of the 3rd doses 
administration in Stage 2 and to 
avoid protocol deviations (ie, 
having subjects receiving 3rd doses 
in Stage 2 outside the allowed time 
interval). All safety data collected 
28 days after 2nd administrations of 
remaining 84 participants in 
Stage 2 will still be evaluated as 
described in Table 14 (blinded 
instream monitoring). 
Appendix 2 Regulatory, 
Ethical, and Study Oversight 
Considerations 
Clarification on Data 
protection, Data quality 
assurance, and Source 
documents 
Additional requirement for GDPR 
compliance in accordance with the 
latest GSK protocol template 
Appendix 7 Grading scales for 
hematology and biochemistry 
safety laboratory assessments 
Updated Stage 2 grading scale  
Updated to reflect ranges adjusted 
between DAIDS and local Malawi 
laboratory ranges. 
Appendix 8 Protocol 
Amendment History 
The summary of changes 
related to previous amendment 
(Amendment 1) moved to 
Appendix 8 
In compliance with the template 
used for writing this protocol 
 

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TABLE OF CONTENTS 
TITLE PAGE .................................................................................................. 1 
PROTOCOL AMENDMENT SUMMARY OF CHANGES TABLE ....... 3 
TABLE OF CONTENTS ............................................................................... 5 
LIST OF TABLES .......................................................................................... 9 
LIST OF FIGURES ...................................................................................... 10 
1.0 
PROTOCOL SUMMARY ............................................................... 11 
1.1 
Synopsis .................................................................................. 11 
1.2 
Schema ................................................................................... 20 
1.3 
Schedule of Activities ............................................................ 21 
2.0 
INTRODUCTION............................................................................. 29 
2.1 
Study Rationale ..................................................................... 29 
2.2 
Background ........................................................................... 30 
2.3 
Benefit/Risk Assessment ....................................................... 32 
2.3.1 
Risk Assessment ....................................................... 32 
2.3.2 
Risk Mitigation Strategies ........................................ 33 
2.3.3 
Benefit Assessment .................................................. 34 
2.3.4 
Overall Benefit/Risk Conclusion .............................. 34 
3.0 
OBJECTIVES AND ENDPOINTS ................................................. 35 
4.0 
STUDY DESIGN ............................................................................... 39 
4.1 
Overall Design ....................................................................... 39 
4.1.1 
Stage 1 ...................................................................... 39 
4.1.2 
Stage 2 ...................................................................... 41 
4.2 
Scientific Rationale for Study Design .................................. 44 
4.2.1 
Choice of Comparator Vaccines ............................... 45 
4.2.2 
Rationale for Blinding .............................................. 46 
4.3 
Justification for Dose ............................................................ 46 
4.4 
End of Study Definition ........................................................ 47 
4.5 
Study Holding Criteria ......................................................... 47 
4.5.1 
Study Holding Rules ................................................. 47 
4.5.1.1 
Risk Assessment Curves for Holding 
Rules Cutoff Definition .......................... 50 
5.0 
STUDY POPULATION ................................................................... 53 
5.1 
Inclusion Criteria .................................................................. 53 

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5.2 
Exclusion Criteria ................................................................. 54 
5.2.1 
Medical Conditions .................................................. 54 
5.2.2 
Prior/Concomitant Therapy ...................................... 54 
5.2.3 
Prior/Concurrent Clinical Study Experience ............ 55 
5.2.4 
Other Exclusions ...................................................... 55 
5.3 
Lifestyle Considerations ....................................................... 56 
5.4 
Screen Failures ...................................................................... 56 
5.5 
Criteria for Temporarily Delaying Enrollment/Study 
Intervention Administration ................................................ 57 
6.0 
STUDY INTERVENTION AND CONCOMITANT THERAPY 57 
6.1 
Study Intervention(s) Administered .................................... 57 
6.2 
Preparation, Handling, Storage, and Accountability ........ 62 
6.3 
Measures to Minimize Bias: Randomization and Blinding
................................................................................................. 62 
6.3.1 
Participant Identification .......................................... 62 
6.3.2 
Intervention Allocation to the Participant ................ 62 
6.3.3 
Blinding and Unblinding .......................................... 63 
6.3.3.1 
Emergency Unblinding ........................... 63 
6.3.3.2 
Unblinding Prior to Regulatory Reporting 
of SAEs ................................................... 63 
6.4 
Study Intervention Compliance ........................................... 64 
6.4.1 
Treatment Strategy ................................................... 64 
6.4.2 
Warnings and Precautions ........................................ 64 
6.5 
Dose Modification ................................................................. 65 
6.6 
Continuing Access to Study Intervention After the End of 
the Study ................................................................................ 65 
6.7 
Treatment of Overdose ......................................................... 65 
6.8 
Concomitant Therapy ........................................................... 65 
7.0 
DISCONTINUATION OF STUDY INTERVENTION AND 
PARTICIPANT DISCONTINUATION/WITHDRAWAL .......... 66 
7.1 
Discontinuation of Study Intervention ................................ 66 
7.2 
Contraindications to Subsequent Study Intervention(s) 
Administration ...................................................................... 66 
7.3 
Participant Discontinuation/Withdrawal from the Study 67 
7.4 
Lost to Follow-up .................................................................. 68 
8.0 
STUDY ASSESSMENTS AND PROCEDURES ........................... 68 
8.1 
Immunogenicity Assessments .............................................. 69 
8.1.1 
Biological Samples ................................................... 69 
8.1.2 
Laboratory Assays .................................................... 70 
8.2 
Safety Assessments ................................................................ 73 
8.2.1 
Pre-intervention Administration Procedures ............ 73 
8.2.1.1 
Collection of Demographic Data, 
Medical/Vaccination History, and 
Physical Examination ............................. 73 

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8.2.1.2 
Pregnancy ............................................... 73 
8.2.2 
Clinical Safety Laboratory Assessments .................. 74 
8.3 
Adverse Events ...................................................................... 74 
8.3.1 
Time Period and Frequency for Collecting AE and 
SAE Information ...................................................... 74 
8.3.2 
Method of Detecting AEs and SAEs ........................ 75 
8.3.2.1 
Clinically Significant Abnormal 
Laboratory Findings ............................... 75 
8.3.3 
Regulatory Reporting Requirements for SAEs ........ 75 
8.3.4 
Treatment of Adverse Events ................................... 76 
8.3.5 
Solicited Adverse Events .......................................... 76 
8.3.6 
Participant Card ........................................................ 76 
8.3.7 
Medical Device Deficiencies .................................... 76 
8.3.7.1 
Detection, Follow-up, and Prompt 
Reporting of Medical Device Deficiency
 ................................................................ 77 
8.3.7.2 
Regulatory Reporting of Medical Device 
Deficiency When Used as Combination 
Product .................................................... 77 
8.4 
Pharmacokinetics and Pharmacodynamics ........................ 77 
8.5 
Study Procedures During Special Circumstances ............. 78 
8.6 
Genetic Testing ...................................................................... 78 
9.0 
STATISTICAL CONSIDERATIONS ............................................ 78 
9.1 
Statistical Hypotheses ........................................................... 78 
9.2 
Sample Size Determination .................................................. 79 
9.3 
Populations for Analyses ...................................................... 79 
9.4 
Statistical Analyses................................................................ 80 
9.4.1 
Primary Endpoints .................................................... 80 
9.4.2 
Secondary Endpoints ................................................ 82 
9.4.3 
Tertiary Endpoints .................................................... 84 
9.5 
Missing Data .......................................................................... 85 
9.6 
Interim Analyses ................................................................... 85 
9.6.1 
Sequence of Analyses ............................................... 85 
9.6.2 
Statistical Considerations ......................................... 86 
9.7 
Internal Safety Review Committee...................................... 86 
10.0 
REFERENCES .................................................................................. 89 
11.0 
APPENDICES ................................................................................... 92 
Appendix 1 
Abbreviations .......................................................... 92 
Appendix 2 
Regulatory, Ethical, and Study Oversight 
Considerations ....................................................................... 98 
Regulatory and Ethical Considerations ................................... 98 
Adequate Resources ................................................................ 98 
Financial Disclosure................................................................ 99 
Informed Consent Process ...................................................... 99 

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Data Protection........................................................................ 99 
Administrative Structure ....................................................... 100 
Medical Monitor ................................................................... 100 
Dissemination of Clinical Study Data................................... 101 
Data Quality Assurance ........................................................ 101 
Source Documents ................................................................ 102 
Study and Study Center Closure ........................................... 103 
Publication Policy ................................................................. 103 
Appendix 3 
Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting .......... 104 
Appendix 4 
Contraceptive Guidance and Collection of 
Pregnancy Information ...................................................... 112 
Definitions............................................................................. 112 
Contraception Guidance........................................................ 112 
Collection of Pregnancy Information.................................... 114 
Appendix 5 
Genetics ................................................................. 115 
Appendix 6 
Definition of Medical Device AE, Adverse Device 
Effect (ADE), Serious Adverse Device Effect (SADE) and 
Unanticipated SADE (USADE) ......................................... 116 
Definitions of a Medical Device AE ..................................... 116 
Definition of Medical Device SAE, SADE and USADE ..... 116 
Recording and Reporting of Medical Device AE, ADEs, 
SADEs, and USADE .............................................. 117 
Reporting of Medical Device Deficiencies for Associated 
Person ..................................................................... 117 
Appendix 7 
Grading Scales for Hematology and Biochemistry 
Safety Laboratory Assessments ......................................... 118 
Appendix 8 
Protocol Amendment History .............................. 120 
Appendix 9 
Signature of Investigator ..................................... 124 
 

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LIST OF TABLES 
Table 1 
Schedule of Activities ............................................................. 21 
Table 2 
Intervals Between Study Visits ............................................... 29 
Table 3 
Study Objectives and Endpoints ............................................. 35 
Table 4 
Study Groups, Intervention, and Blinding .............................. 42 
Table 5 
Study Holding Rules ............................................................... 49 
Table 6 
Study Interventions Administered (Investigational Vaccines)
................................................................................................. 58 
Table 7 
Study Interventions Administered (Comparator and Control 
Vaccines)................................................................................. 60 
Table 8 
Biological Sample ................................................................... 70 
Table 9 
Laboratory Assays .................................................................. 71 
Table 10 
Analysis Sets ........................................................................... 79 
Table 11 
Primary Endpoints-Statistical Analyses .................................. 81 
Table 12 
Secondary Endpoints-Statistical Analyses .............................. 82 
Table 13 
Tertiary Endpoints-Statistical Analyses .................................. 84 
Table 14 
Summary of the iSRC Reviews* ............................................ 88 
Table 15 
Time points for Blinded Instream Monitoring ........................ 88 
Table 16 
Study Administrative Structure............................................. 100 
Table 17 
Solicited Events to be Collected ........................................... 106 
Table 18 
Intensity Scales for Solicited Events..................................... 107 
Table 19 
Stage 1 – Adults (Europe) ..................................................... 118 
Table 20 
Stage 2 – Adults (Africa) ...................................................... 119 
 

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LIST OF FIGURES 
Figure 1 
Study Schema.......................................................................... 20 
Figure 2 
Blinded Review: Safety Holding Rules 1a, 1b, 1c, 1d.1 and 2c 
After 10, 21, 40 and 105 Participants ..................................... 50 
Figure 3 
Unblinded Review: Safety Holding Rules 1d.2 After 4, 9, 16 
and 45 Participants .................................................................. 51 
Figure 4 
Unblinded Review: Safety Holding Rules 2a and 2b After 4 
and 16 Participants .................................................................. 52 
 

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1.0 PROTOCOL SUMMARY 
1.1 
Synopsis 
Protocol Title: A Phase 1/2a, observer-blind, randomized, controlled, two-stage, 
multi-country study to evaluate the safety, reactogenicity, and immune response of the 
trivalent vaccine against invasive nontyphoidal Salmonella (iNTS) and Typhoid Fever in 
healthy European and African adults 
Short Title: A study to evaluate safety, reactogenicity, and immune response of GVGH 
iNTS-TCV vaccine against invasive nontyphoidal Salmonella and Typhoid Fever 
Rationale: 
GlaxoSmithKline Biologicals SA (GSK) Vaccines Institute for Global Health (GVGH), 
with the support of Combating Antibiotic Resistant Bacteria-X (CARB-X), is developing 
a new candidate trivalent vaccine (GVGH iNTS-typhoid conjugate vaccine [TCV]) 
against Salmonella Typhimurium (S. Typhimurium), Salmonella Enteritidis 
(S. Enteritidis), and Salmonella Typhi. GVGH iNTS-TCV is based on the previously 
developed GVGH monovalent TCV and bivalent S. Typhimurium and S. Enteritidis 
vaccine, using the generalized modules for membrane antigens (GMMA) -platform 
technology. The newly developed vaccine, GVGH iNTS-TCV vaccine, is new but its 
components are not new as the iNTS vaccine is already in development by GVGH while 
TCV is registered by Indian vaccine manufacturer Biological E in India and World 
Health Organization prequalified. 
This candidate vaccine targets diseases of major importance for African populations. 
Until now, there is no vaccine for iNTS or TCV widely used in Africa. However, 
safety/effectiveness studies are ongoing in Africa to support TCV introduction, which is 
backed by the Global Alliance for Vaccines and Immunization. 
The estimated death toll from these diseases combined was 90 000 deaths in sub-Saharan 
Africa in 2019. 
The purpose of the current trial is to evaluate the safety, reactogenicity, and the 
immunogenicity of the primary response induced by this vaccine. The current clinical 
trial will evaluate the GVGH iNTS-TCV candidate vaccine for the first time in humans in 
European adults (Stage 1). Following Stage 1, the same vaccine will be evaluated in 
African adults as part of Stage 2 of the trial. 

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Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
• 
To evaluate the safety and 
reactogenicity profile of 
GSK Vaccines Institute for 
Global Health (GVGH) 
invasive nontyphoidal 
Salmonella-typhoid 
conjugate vaccine (iNTS-
TCV) vaccine in healthy 
European/African adults 
• 
Number of participants in Europe/Stage 1 with solicited 
administration site and systemic events during 7 days after each 
study intervention administration (ie, on the day of study 
intervention administration and the 6 subsequent days) occurring at 
Day 1, Day 57, and Day 169, by study intervention group 
• 
Number of participants in Europe/Stage 1 with unsolicited adverse 
events (AEs) during 28 days after each study intervention 
administration (ie, on the day of study intervention administration 
and the 27 subsequent days) occurring at Day 1, Day 57, and Day 
169, by study intervention group 
• 
Number of participants in Europe/Stage 1 with serious adverse 
events (SAEs) from first study intervention administration (Day 1) 
to 28 days after third study intervention administration (Day 197), 
by study intervention group 
• 
Number of participants in Europe/Stage 1 with AEs/SAEs leading 
to withdrawal from the study and/or withholding doses of study 
intervention, from first study intervention administration up to 28 
days after third study intervention administration (Day 1 to Day 
197), by study intervention group 
• 
Number of participants in Europe/Stage 1 with deviations from 
normal or baseline values for hematological, renal, and hepatic 
panels test results at 7 days after each study intervention 
administration (Day 8, Day 64, and Day 176) and at 28 days after 
each study intervention administration (Day 29, Day 85, and Day 
197), by study intervention group 
• 
Number of participants in Africa/Stage 2 with solicited 
administration site and systemic events during 7 days after each 
study intervention administration (ie, on the day of study 
intervention administration and the 6 subsequent days) occurring at 
Day 1, Day 57, and Day 169, by study intervention group 
• 
Number of participants in Africa/Stage 2 with unsolicited AEs 
during 28 days after each study intervention administration (ie, on 
the day of study intervention administration and the 27 subsequent 
days) occurring at Day 1, Day 57, and Day 169, by study 
intervention group 
• 
Number of participants in Africa/Stage 2 with SAEs from first 
study intervention administration (Day 1) to 28 days after third 
study intervention administration (Day 197), by study intervention 
group 
• 
Number of participants in Africa/Stage 2 with AEs/SAEs leading to 
withdrawal from the study and/or withholding doses of study 
intervention, from first study intervention administration up to 28 
days after third study intervention administration (Day 1 to Day 
197), by study intervention group 
• 
Number of participants in Africa/Stage 2 with deviations from 
normal or baseline values for hematological, renal, and hepatic 

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Objectives 
Endpoints 
panel test results at 7 days after each study intervention 
administration (Day 8, Day 64, and Day 176) and at 28 days after 
each study intervention administration (Day 29, Day 85, and Day 
197), by study intervention group 
Secondary 
• 
To evaluate the long-term 
safety profile of GVGH 
iNTS-TCV vaccine in 
healthy European/African 
adults 
• 
Number of participants with any SAE from 28 days after third 
study intervention administration (Day 197) up to Day 337, per 
study intervention group in Stage 1/Stage 2. 
• 
Number of participants with AEs/SAEs leading to withdrawal from 
the study, from 28 days after third study intervention administration 
(Day 197) up to Day 337, by study intervention group in Stage 
1/Stage 2. 
• 
To evaluate the 
immunogenicity profile of 
GVGH iNTS-TCV vaccine 
in healthy European adults 
• 
Anti-serotype specific immunoglobulin (Ig) G* geometric mean 
concentrations (GMCs), in participants in Europe/Stage 1, as 
determined by enzyme-linked immunosorbent assay (ELISA), 
before each study intervention administration (Day 1, Day 57, and 
Day 169) and 28 days after each study intervention administration 
(Day 29, Day 85 and Day 197), for each study intervention group 
and between groups ratios 
• 
Anti-serotype specific IgG* within-participant geometric mean 
ratios (GMRs), in participants in Europe/Stage 1, as determined by 
ELISA at 28 days after each study intervention administration 
compared to each study intervention administration baseline (Day 
29 versus Day 1, Day 85 versus Day 57 and Day 197 versus Day 
169) 
* Anti- Salmonella Typhi (S. Typhi) Vi antigen (Ag) total IgG, 
Anti-Salmonella Typhimurium (S. Typhimurium) O Ag total IgG, 
Anti-Salmonella Enteritidis (S. Enteritidis) O Ag total IgG will be tested. 
• 
To evaluate seroresponse 
with the GVGH iNTS-
TCV vaccine after each 
study intervention 
administration in healthy 
European adults 
• 
Number of participants in Europe/Stage 1 achieving, for each Ag, 
at least a 4-fold** rise in Anti-serotype specific IgG* antibody 
concentration 28 days after each study intervention administration 
(Day 29, Day 85, and Day 197) compared to first study intervention 
administration baseline (Day 1), as measured by ELISA, by study 
intervention group 
• 
Number of participants in Europe/Stage 1 with Anti-S. Typhi Vi Ag 
IgG antibody concentrations equivalent to ≥4.3 µg/mL***, before 
each study intervention administration (Day 1, Day 57, and Day 
169) and 28 days after each study intervention administration (Day 
29, Day 85, and Day 197), as measured by ELISA, by study 
intervention group 
* Anti-S. Typhi Vi Ag total IgG, Anti-S. Typhimurium O Ag total IgG, 
Anti-S. Enteritidis O Ag total IgG will be tested 
** 4-fold is considered clinically meaningful measure of seroconversion 
in the absence of an established correlate of protection. 
*** 4.3 µg/mL threshold is clinically meaningful as accepted by World 
Health Organization (WHO) as immunological protection threshold for 
Vi containing typhoid vaccines and has been used in previous studies for 
registration of these vaccines 

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Objectives 
Endpoints 
• 
To evaluate the 
immunogenicity profile of 
GVGH iNTS-TCV vaccine 
in healthy African adults 
• 
Anti-serotype specific IgG* GMC, in participants in Africa/Stage 2, 
as determined by ELISA, before each study intervention 
administration (Day 1, Day 57, and Day 169) and 28 days after 
each study intervention administration (Day 29, Day 85, and Day 
197), for each study intervention group and between-groups ratios 
• 
Anti-serotype specific IgG* within-participant GMRs, in 
participants in Africa/Stage 2, as determined by ELISA at 28 days 
after each study intervention administration compared to each study 
intervention administration baseline (Day 29 versus Day 1, Day 85 
versus Day 57, and Day 197 versus Day 169) 
* Anti-S. Typhi Vi Ag total IgG, Anti-S. Typhimurium O Ag total IgG, 
Anti-S. Enteritidis O Ag total IgG will be tested. 
• 
To evaluate seroresponse 
with the GVGH iNTS-
TCV vaccine after each 
study intervention 
administration in healthy 
African adults 
• 
Number of participants in Africa/Stage 2 achieving, for each Ag, at 
least a 4-fold** rise in Anti-serotype specific IgG* antibody 
concentration 28 days after each study intervention administration 
(Day 29, Day 85, and Day 197) compared to first study intervention 
administration baseline (Day 1), as measured by ELISA, by study 
intervention group 
• 
Number of participants in Africa/Stage 2 with Anti-S. Typhi Vi Ag 
IgG* antibody concentrations equivalent to ≥4.3 µg/mL***, before 
each study intervention administration (Day 1, Day 57, and Day 
169) and 28 days after each study intervention administration (Day 
29, Day 85, and Day 197), as measured by ELISA, by study 
intervention group 
* Anti-S. Typhi Vi Ag total IgG, Anti-S. Typhimurium O Ag total IgG, 
Anti-S. Enteritidis O Ag total IgG will be tested 
** 4-fold is considered clinically meaningful measure of seroconversion 
in the absence of an established correlate of protection. 
*** 4.3 µg/mL threshold is clinically meaningful as accepted by WHO 
as immunological protection threshold for Vi containing typhoid 
vaccines and has been used in previous studies for registration of these 
vaccines 
Tertiary 
CCI

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Objectives 
Endpoints 
Overall Design: 
This is a Phase 1/2a, observer-blind, randomized, dose-escalation, controlled, 
multi-country, two-staged, and staggered study including 9 groups. 
The study will be conducted overall (both Stage 1 and Stage 2) with approximately 
155 healthy adult participants (18 to 50 years of age). The healthy European adults will 
be randomly assigned to 1 of the groups indicated for Stage 1. The healthy African adults 
will be randomly assigned to 1 of the groups indicated for Stage 2. Each group will 
receive 2 of the 11 study interventions at each administration, except for the 
Control_Stage 2 group which will receive 4 study interventions (a different active 
comparator at each administration time point together with saline). 
Each participant will receive 1 randomly selected intramuscular study intervention per 
arm on Day 1, Day 57, and Day 169. 
CCI

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Stage 1 
Stage 1 (Europe) will follow a 2-step staggered design, leading in with low doses of all 
the study interventions, in a dose-escalation manner. The sentinel approach will be 
followed for the first 10 participants each in Step 1 and Step 2, in which only 
1 participant will be treated daily. This will be done to ensure maximum safety of the 
participants. 
In Step 1, 10 healthy European adults, randomized in a 2:2:1 ratio, will receive: 
• The low dose of the candidate iNTS-TCV vaccine and concomitant saline to be 
administered in different arms, or 
• Separate administration of low doses of iNTS-GMMA and TCV vaccines in different 
arms, or 
• Placebo and saline in different arms. 
The 10 sentinel participants in Step 1 will receive the first study intervention on 
consecutive days and a telephonic safety follow-up call will be performed on the next 
day. If the participants have any complaints, they will be invited to the study site for an 
evaluation of the possible adverse events (AEs) and holding rules, prior to administration 
of study intervention in the next participant. If the Investigator becomes aware of a 
holding rule being met, he/she must suspend administration of the study intervention and 
inform the Sponsor’s delegate immediately who will in-turn inform the Sponsor. 
The internal Safety Review Committee (iSRC) will review all safety data collected up to 
7 days after the first study intervention in Step 1. Step 2 will only commence if there is a 
favorable safety assessment during this review. 
In Step 2, 40 healthy European adults will be randomized in a 2:2:1 ratio. A staggered 
approach will be followed for the first 10 sentinel participants and these participants will 
be followed up with a safety follow-up call on the next day of administration of study 
intervention. If the participants have any complaints, they will be invited to the study site 
for an evaluation of the AEs and holding rules, prior to administration of study 
intervention in the next participant. If the Investigator becomes aware of a holding rule 
being met, he/she must suspend administration of the study intervention and inform the 
Sponsor’s delegate immediately who will in-turn inform the Sponsor. The remainder of 
the 30 participants will receive the study intervention in a sequential (at least 60 minutes 
apart) manner. The participants in Step 2 will receive: 
• The full dose of the candidate iNTS-TCV vaccine and concomitant saline to be 
administered in different arms, or 
• Separate administration of full doses of iNTS-GMMA and TCV vaccines in different 
arms, or 
• Placebo and saline in different arms. 
For the trial to proceed to Stage 2, a favorable evaluation of all available safety data by the 
iSRC following the first and second study intervention administrations (up to 28 days 
after second administration) in Step 2 of Stage 1 will be required. In case a No-Go 

CONFIDENTIAL 
216152 (INTS GMMA GVGH-002) (H08_01TP) 
Protocol Amendment 2 Final 
08 June 2023 
17 
decision is made, the study will be terminated at the end of Stage 1 and there will be no 
further administration of the study intervention in Step 2. 
Stage 2 
In Stage 2 (Africa), a total of 105 healthy African adults, randomized in a 3:3:1 ratio, will 
receive: 
• The full dose of the candidate iNTS-TCV vaccine and concomitant saline to be 
administered in different arms, or 
• Separate administration of full doses of iNTS-GMMA and TCV vaccines in different 
arms, or 
• MenACWY (Menveo) and saline for the first administration, TdaP (Boostrix) and 
saline for the second administration and Typhoid Vi polysaccharide vaccine (Typhim 
Vi) and saline for the third administration in different arms. This is the 
Control_Stage 2 Group. 
The first 21 participants in Stage 2 will initially be recruited with administration 
proceeding sequentially, at least 60 minutes apart. These participants will be followed up 
with a safety follow-up call on the next day of administration of study intervention. If the 
participants have any complaints, they will be invited to the study site for an evaluation 
of the possible adverse events (AEs) and holding rules, prior to administration of study 
intervention in the next participant. If the Investigator becomes aware of a holding rule 
being met, he/she must suspend administration of the study intervention and inform the 
Sponsor’s delegate immediately who will in-turn inform the Sponsor. All safety data 
from these participants up to 7 days after the first administration of the study intervention 
will be reviewed by the iSRC and the recruitment of the remaining 84 participants in 
Stage 2 will only commence if there is a positive evaluation by the iSRC. The study 
interventions will be administered in parallel in the remaining 84 participants. 
All 155 participants (Stage 1 and Stage 2) will be closely observed for a minimum of 
60 minutes after each study intervention administration, before leaving the facilities. The 
Investigator will decide if the participant should be observed for more than 60 minutes 
after each study intervention administered, if required. 
An internal GSK Safety Review Team (SRT) and iSRC will also be involved in the 
safety oversight for this study. 
Number of Investigators and Study Centers: 
The trial will be conducted in 2 sites, each with a different Principal Investigator. 
Number of Participants: 
A total of 155 participants are planned to be randomized to achieve at least 133 evaluable 
participants. 

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216152 (INTS GMMA GVGH-002) (H08_01TP) 
Protocol Amendment 2 Final 
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18 
Treatment Groups and Duration: 
The treatment groups in Stage 1 are: 
• iNTS-TCV low dose: the low dose of the candidate iNTS-TCV vaccine and 
concomitant saline to be administered in different arms, 
• iNTS-GMMA and TCV low doses: separate administration of low doses of 
iNTS-GMMA and TCV vaccines in different arms, 
• Placebo: placebo and saline in different arms, 
• iNTS-TCV full dose: the full dose of the candidate iNTS-TCV vaccine and 
concomitant saline to be administered in different arms, 
• iNTS-GMMA and TCV full doses: separate administration of full doses of 
iNTS-GMMA and TCV vaccines in different arms. 
The treatment groups in Stage 2 are: 
• iNTS-TCV full dose: the full dose of the candidate iNTS-TCV vaccine and 
concomitant saline to be administered in different arms, 
• iNTS-GMMA and TCV full doses: separate administration of full doses of 
iNTS-GMMA and TCV vaccines in different arms, 
• Control: MenACWY (Menveo) and saline for the first administration, TdaP (Boostrix) 
and saline for the second administration and Typhim Vi and saline for the third 
administration in different arms. 
Each participant will be part of this trial for approximately 13 months (from the 
Screening starting 28 days before first study intervention administration and until 
6 months after third study intervention administration). 
Statistical Methods: 
A total of 155 participants are planned to be randomized to achieve at least 133 evaluable 
participants. The following analysis sets are being included in the study: 
• Enrolled Set: Participants who were randomized or received study intervention or 
underwent a post-screening procedure. The allocation in a group is based on the 
administered intervention. 
• Exposed Set (ES): All participants who received at least 1 dose of the study 
intervention. The allocation in a group is based on the administered intervention. 
• Full Analysis Set (FAS): All participants who received at least 1 dose of the study 
intervention and have post-dose immunogenicity data. The allocation in a group is 
based on the randomized intervention. The FAS for immunogenicity will be defined 
by time point. 
• Per Protocol Set (PPS): All eligible participants who received all doses as per protocol, 
have immunogenicity results post-dose, complied with dosing/blood draw intervals, 
without intercurrent conditions that may interfere with immunogenicity and without 
prohibited concomitant medication/vaccination. The PPS for immunogenicity will be 
defined by time point. 

CONFIDENTIAL 
216152 (INTS GMMA GVGH-002) (H08_01TP) 
Protocol Amendment 2 Final 
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• Unsolicited Safety Set: All participants who received at least 1 dose of the study 
intervention (ES) that report unsolicited AEs/report not having unsolicited AEs. The 
allocation in a group is based on the administered intervention. 
• Solicited Safety Set: All participants who received at least 1 dose of the study 
intervention (ES) who have solicited safety data. The allocation in a group is based on 
the administered intervention. 
The analysis on primary objective will be based on the Solicited, Unsolicited, and 
Exposed Sets. The analysis on secondary and tertiary objectives will be based on the PPS 
for immunogenicity. If, in any study group and at any time point, the percentage of 
vaccinated participants with serological results excluded from the PPS for analysis of 
immunogenicity is 10% or more, a second-line analysis based on the FAS for 
immunogenicity will be performed to complement the PPS analysis. 
A group-unblinded interim analysis for immunogenicity will be performed 28 days after 
the second administration in all study participants in Stage 2 to support the preparation 
for future studies. The final analysis will be performed after all data from Stage 1 and 
Stage 2 are available. All analyses before unblinding the study team will be conducted on 
data as clean as possible. 
Data Monitoring Committee: Yes 
An internal GSK SRT and an iSRC will be involved in the trial. 
The SRT is a GSK Central Committee responsible for ongoing assessment of the 
benefit/risk balance of the product. In addition, a separate iSRC will be established to 
monitor safety and to specifically recommend continuation of subsequent steps of the 
study based on the safety results. The iSRC, which will be comprised of 
study-independent GSK members and an external expert in clinical development, will 
review unblinded data at predefined time points during the study. Ad hoc safety 
evaluations by the iSRC may be called at any time if there are any suspected safety 
concerns. 

CONFIDENTIAL 
216152 (INTS GMMA GVGH-002) (H08_01TP) 
Protocol Amendment 2 Final 
08 June 2023 
20 
1.2 
Schema 
Figure 1 
Study Schema 
 

CONFIDENTIAL 
216152 (INTS GMMA GVGH-002) (H08_01TP) 
Protocol Amendment 2 Final 
08 June 2023 
21 
1.3 
Schedule of Activities 
Table 1 
Schedule of Activities 
Epoch 
Screeni
ng 
First study intervention administration 
Second study intervention 
administration 
Third study intervention administration 
Type of contact 
Screeni
ng Visit 
Visit 
1 
(First 
adm, 
A1) 
Sentinel 
Safety 
phone 
contact 
Reminde
r phone 
contact1 
Home 
visit2 
Visit 
2 
Visit 
3 
Visit 4 
(Second 
adm, A2)3 
Remind
er 
phone 
contact1 
Home 
visit2 
Visit 
5 
Visit 
6 
Visit 7  
(Third 
adm, 
A3)3 
Remind
er 
phone 
contact1 
Home 
visit2 
Visit 
8 
Visit 
9 
Visit 10 
(Safety 
phone 
contact) 
Time points 
Day -28 
to 
Day −1  
Day 1 Day 2 
Day 4 
Day 2 
to 
Day 7 
Day 
8 
Day 
29 
Day 57 
Day 60 
Day 58 
to 
Day 63 
Day 
64 
Day 
85 
Day 
169  
Day 
172 
Day 
170 to 
Day 
175 
Day 
176  
Day 
197 
Day 
337 
Sampling time points 
 
Pre-
A1 
 
 
 
Post
-A1 
Post-
A1 
Pre-A2 
 
 
Post
-A2 
Post
-A2 Pre-A3 Post-A3  
Post
-A3 
Post
-A3 Post-A3 
Informed consent 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Check inclusion/exclusion 
criteria 
● 
● 
 
 
 
 
 
● 
 
 
 
 
● 
 
 
 
 
Collect demographic data ● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Medical and vaccination 
history  
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Physical examination  
● 
● 
 
 
 
 
 
● 
 
 
 
 
● 
 
 
 
 
Symptom directed 
physical examination  
 
 
 
 
 
○ 
○ 
 
 
 
○ 
○ 
 
 
○ 
○ 
 
Vital sign assessment 
● 
● 
 
 
 
● 
 
● 
 
 
● 
 
● 
 
● 
 
 
Body temperature* before 
study intervention 
administration 
 
● 
 
 
 
 
 
● 
 
 
 
 
● 
 
 
 
 

CONFIDENTIAL 
216152 (INTS GMMA GVGH-002) (H08_01TP) 
Protocol Amendment 2 Final 
08 June 2023 
22 
Epoch 
Screeni
ng 
First study intervention administration 
Second study intervention 
administration 
Third study intervention administration 
Type of contact 
Screeni
ng Visit 
Visit 
1 
(First 
adm, 
A1) 
Sentinel 
Safety 
phone 
contact 
Reminde
r phone 
contact1 
Home 
visit2 
Visit 
2 
Visit 
3 
Visit 4 
(Second 
adm, A2)3 
Remind
er 
phone 
contact1 
Home 
visit2 
Visit 
5 
Visit 
6 
Visit 7  
(Third 
adm, 
A3)3 
Remind
er 
phone 
contact1 
Home 
visit2 
Visit 
8 
Visit 
9 
Visit 10 
(Safety 
phone 
contact) 
Time points 
Day -28 
to 
Day −1  
Day 1 Day 2 
Day 4 
Day 2 
to 
Day 7 
Day 
8 
Day 
29 
Day 57 
Day 60 
Day 58 
to 
Day 63 
Day 
64 
Day 
85 
Day 
169  
Day 
172 
Day 
170 to 
Day 
175 
Day 
176  
Day 
197 
Day 
337 
Sampling time points 
 
Pre-
A1 
 
 
 
Post
-A1 
Post-
A1 
Pre-A2 
 
 
Post
-A2 
Post
-A2 Pre-A3 Post-A3  
Post
-A3 
Post
-A3 Post-A3 
Height** and weight 
measurements 
● 
○ 
 
 
 
○ 
○ 
○ 
 
 
○ 
○ 
○ 
 
○ 
○ 
 
Check contraindications 
and warnings, and 
precautions to study 
intervention 
administration 
○ 
○ 
 
 
 
 
 
○ 
 
 
 
 
○ 
 
 
 
 
Study group allocation 
 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Check criteria for 
temporary delay for 
enrollment and study 
intervention 
administration 
○ 
○ 
 
 
 
 
 
○ 
 
 
 
 
○ 
 
 
 
 
Urine pregnancy test  
● 
● 
 
 
 
 
 
● 
 
 
 
 
● 
 
 
 
 
Study intervention 
administration$ 
 
● 
 
 
 
 
 
● 
 
 
 
 
● 
 
 
 
 

CONFIDENTIAL 
216152 (INTS GMMA GVGH-002) (H08_01TP) 
Protocol Amendment 2 Final 
08 June 2023 
23 
Epoch 
Screeni
ng 
First study intervention administration 
Second study intervention 
administration 
Third study intervention administration 
Type of contact 
Screeni
ng Visit 
Visit 
1 
(First 
adm, 
A1) 
Sentinel 
Safety 
phone 
contact 
Reminde
r phone 
contact1 
Home 
visit2 
Visit 
2 
Visit 
3 
Visit 4 
(Second 
adm, A2)3 
Remind
er 
phone 
contact1 
Home 
visit2 
Visit 
5 
Visit 
6 
Visit 7  
(Third 
adm, 
A3)3 
Remind
er 
phone 
contact1 
Home 
visit2 
Visit 
8 
Visit 
9 
Visit 10 
(Safety 
phone 
contact) 
Time points 
Day -28 
to 
Day −1  
Day 1 Day 2 
Day 4 
Day 2 
to 
Day 7 
Day 
8 
Day 
29 
Day 57 
Day 60 
Day 58 
to 
Day 63 
Day 
64 
Day 
85 
Day 
169  
Day 
172 
Day 
170 to 
Day 
175 
Day 
176  
Day 
197 
Day 
337 
Sampling time points 
 
Pre-
A1 
 
 
 
Post
-A1 
Post-
A1 
Pre-A2 
 
 
Post
-A2 
Post
-A2 Pre-A3 Post-A3  
Post
-A3 
Post
-A3 Post-A3 
Recording of 
administered study 
intervention number 
 
○ 
 
 
 
 
 
○ 
 
 
 
 
○ 
 
 
 
 
Distribution of participant 
pDiary 
 
○4 
 
 
 
 
 
○4 
 
 
 
 
○4 
 
 
 
 
Safety phone call/Home 
visit to sentinel 
participants in Steps 1 and 
2 of Stage 1 and in Stage 
2, one day post-study 
intervention 
administration to check 
for any holding rule 
events or SAEs 
 
 
● 
 
●7 
 
 
 
 
 
 
 
 
 
 
 
 
Phone contact/Home visit 
for pDiary card 
completion reminder 
 
 
 
● 
● 
 
 
 
● 
● 
 
 
 
● 
● 
 
 
 
Return of pDiaries 
 
 
 
 
 
○5 
 
 
 
 
○5 
 
 
 
○5 
 
 

CONFIDENTIAL 
216152 (INTS GMMA GVGH-002) (H08_01TP) 
Protocol Amendment 2 Final 
08 June 2023 
24 
Epoch 
Screeni
ng 
First study intervention administration 
Second study intervention 
administration 
Third study intervention administration 
Type of contact 
Screeni
ng Visit 
Visit 
1 
(First 
adm, 
A1) 
Sentinel 
Safety 
phone 
contact 
Reminde
r phone 
contact1 
Home 
visit2 
Visit 
2 
Visit 
3 
Visit 4 
(Second 
adm, A2)3 
Remind
er 
phone 
contact1 
Home 
visit2 
Visit 
5 
Visit 
6 
Visit 7  
(Third 
adm, 
A3)3 
Remind
er 
phone 
contact1 
Home 
visit2 
Visit 
8 
Visit 
9 
Visit 10 
(Safety 
phone 
contact) 
Time points 
Day -28 
to 
Day −1  
Day 1 Day 2 
Day 4 
Day 2 
to 
Day 7 
Day 
8 
Day 
29 
Day 57 
Day 60 
Day 58 
to 
Day 63 
Day 
64 
Day 
85 
Day 
169  
Day 
172 
Day 
170 to 
Day 
175 
Day 
176  
Day 
197 
Day 
337 
Sampling time points 
 
Pre-
A1 
 
 
 
Post
-A1 
Post-
A1 
Pre-A2 
 
 
Post
-A2 
Post
-A2 Pre-A3 Post-A3  
Post
-A3 
Post
-A3 Post-A3 
pDiaries transcription by 
Investigator or delegate  
 
 
 
 
 
● 
 
 
 
 
● 
 
 
 
● 
 
 
 
Laboratory Assessments 
 
Blood sampling for safety 
screening (hematology 
panel, biochemistry, viral 
serologic analyses and 
HLA-B27 testing***) (up 
to 15 mL)  
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sampling for safety 
laboratory assays 
(hematology panel and 
biochemistry analyses) 
(up to 10 mL) 
 
● 
 
 
 
● 
● 
● 
 
 
● 
● 
● 
 
● 
● 
 
Urinalysis 
● 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Blood sampling for 
antibody determination 
(approximately 10 mL)# 
 
● 
 
 
 
 
● 
● 
 
 
 
● 
● 
 
 
● 
 

CONFIDENTIAL 
216152 (INTS GMMA GVGH-002) (H08_01TP) 
Protocol Amendment 2 Final 
08 June 2023 
25 
Epoch 
Screeni
ng 
First study intervention administration 
Second study intervention 
administration 
Third study intervention administration 
Type of contact 
Screeni
ng Visit 
Visit 
1 
(First 
adm, 
A1) 
Sentinel 
Safety 
phone 
contact 
Reminde
r phone 
contact1 
Home 
visit2 
Visit 
2 
Visit 
3 
Visit 4 
(Second 
adm, A2)3 
Remind
er 
phone 
contact1 
Home 
visit2 
Visit 
5 
Visit 
6 
Visit 7  
(Third 
adm, 
A3)3 
Remind
er 
phone 
contact1 
Home 
visit2 
Visit 
8 
Visit 
9 
Visit 10 
(Safety 
phone 
contact) 
Time points 
Day -28 
to 
Day −1  
Day 1 Day 2 
Day 4 
Day 2 
to 
Day 7 
Day 
8 
Day 
29 
Day 57 
Day 60 
Day 58 
to 
Day 63 
Day 
64 
Day 
85 
Day 
169  
Day 
172 
Day 
170 to 
Day 
175 
Day 
176  
Day 
197 
Day 
337 
Sampling time points 
 
Pre-
A1 
 
 
 
Post
-A1 
Post-
A1 
Pre-A2 
 
 
Post
-A2 
Post
-A2 Pre-A3 Post-A3  
Post
-A3 
Post
-A3 Post-A3 
PBMC extraction for 
monoclonal antibodies 
generation for Stage 2 
participants only 
(approximately 50 mL) 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
● 
 
Malaria Rapid Diagnostic 
Test6 
○ 
○ 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
Safety assessments 
Record any concomitant 
medications/vaccinations 
● 
● 
 
 
 
● 
● 
● 
 
 
● 
● 
● 
 
● 
● 
 
Record any intercurrent 
medical conditions  
 
● 
 
 
 
● 
● 
● 
 
 
● 
● 
● 
 
● 
● 
 
Recording of solicited 
AEs in pDiary (Days 1 to 
7 post-administration)  
 
○4 
 
 
○4 
 
 
○4 
 
○4 
 
 
○4 
○4 
 
 
 
Transcription of solicited 
AEs in the eCRF by the 
Investigator or delegate 
 
● 
 
 
 
● 
 
● 
 
 
● 
 
● 
 
● 
 
 

CONFIDENTIAL 
216152 (INTS GMMA GVGH-002) (H08_01TP) 
Protocol Amendment 2 Final 
08 June 2023 
26 
Epoch 
Screeni
ng 
First study intervention administration 
Second study intervention 
administration 
Third study intervention administration 
Type of contact 
Screeni
ng Visit 
Visit 
1 
(First 
adm, 
A1) 
Sentinel 
Safety 
phone 
contact 
Reminde
r phone 
contact1 
Home 
visit2 
Visit 
2 
Visit 
3 
Visit 4 
(Second 
adm, A2)3 
Remind
er 
phone 
contact1 
Home 
visit2 
Visit 
5 
Visit 
6 
Visit 7  
(Third 
adm, 
A3)3 
Remind
er 
phone 
contact1 
Home 
visit2 
Visit 
8 
Visit 
9 
Visit 10 
(Safety 
phone 
contact) 
Time points 
Day -28 
to 
Day −1  
Day 1 Day 2 
Day 4 
Day 2 
to 
Day 7 
Day 
8 
Day 
29 
Day 57 
Day 60 
Day 58 
to 
Day 63 
Day 
64 
Day 
85 
Day 
169  
Day 
172 
Day 
170 to 
Day 
175 
Day 
176  
Day 
197 
Day 
337 
Sampling time points 
 
Pre-
A1 
 
 
 
Post
-A1 
Post-
A1 
Pre-A2 
 
 
Post
-A2 
Post
-A2 Pre-A3 Post-A3  
Post
-A3 
Post
-A3 Post-A3 
Recording of unsolicited 
AEs (Days 1 to 28 
post-administration) 
 
○ 
 
 
 
○ 
 
○ 
 
 
○ 
 
○ 
 
○ 
 
 
Transcription of 
unsolicited AEs in the 
eCRF by the Investigator 
or delegate 
 
● 
 
 
 
● 
● 
● 
 
 
● 
● 
● 
 
● 
● 
 
Safety surveillance 
including vital sign and 
body temperature 
measurements 
(60 minutes 
post-administration) 
 
● 
 
 
 
 
 
● 
 
 
 
 
● 
 
 
 
 
Recording of SAEs 
 
● 
 
 
 
● 
● 
● 
 
 
● 
● 
● 
 
● 
● 
● 
Recording of pregnancies   
● 
 
 
 
● 
● 
● 
 
 
● 
● 
● 
 
● 
● 
 
Recording of AEs leading 
to withdrawal 
 
● 
 
 
 
● 
● 
● 
 
 
● 
● 
● 
 
● 
● 
● 

CONFIDENTIAL 
216152 (INTS GMMA GVGH-002) (H08_01TP) 
Protocol Amendment 2 Final 
08 June 2023 
27 
Epoch 
Screeni
ng 
First study intervention administration 
Second study intervention 
administration 
Third study intervention administration 
Type of contact 
Screeni
ng Visit 
Visit 
1 
(First 
adm, 
A1) 
Sentinel 
Safety 
phone 
contact 
Reminde
r phone 
contact1 
Home 
visit2 
Visit 
2 
Visit 
3 
Visit 4 
(Second 
adm, A2)3 
Remind
er 
phone 
contact1 
Home 
visit2 
Visit 
5 
Visit 
6 
Visit 7  
(Third 
adm, 
A3)3 
Remind
er 
phone 
contact1 
Home 
visit2 
Visit 
8 
Visit 
9 
Visit 10 
(Safety 
phone 
contact) 
Time points 
Day -28 
to 
Day −1  
Day 1 Day 2 
Day 4 
Day 2 
to 
Day 7 
Day 
8 
Day 
29 
Day 57 
Day 60 
Day 58 
to 
Day 63 
Day 
64 
Day 
85 
Day 
169  
Day 
172 
Day 
170 to 
Day 
175 
Day 
176  
Day 
197 
Day 
337 
Sampling time points 
 
Pre-
A1 
 
 
 
Post
-A1 
Post-
A1 
Pre-A2 
 
 
Post
-A2 
Post
-A2 Pre-A3 Post-A3  
Post
-A3 
Post
-A3 Post-A3 
Recording of SAEs 
related to study 
participation, or to a 
concurrent GSK 
medication/vaccine 
● 
● 
 
 
 
● 
● 
● 
 
 
● 
● 
● 
 
● 
● 
● 
Study Conclusion 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
 
● 
Abbreviations: adm = administration; AE = Adverse event; eCRF = electronic case report form; GSK = GlaxoSmithKline Biologicals SA; Pre-A1 = pre-first study 
intervention administration; Post-A1 = post-first study intervention administration; Pre-A2 = pre-second study intervention administration; Post-A2 = post-second 
study intervention administration; Pre-A3 = pre-third study intervention administration; Post-A3 = post-third study intervention administration; 
pDiary = paper diary; PBMC = peripheral blood mononuclear cells; RDT = rapid diagnostic test; SAE = Serious adverse event. 
Note: The double-line border following Day 169 indicates the analyses which will be performed on all data obtained up to Day 169. 
● A study procedure that requires documentation in the individual eCRF. 
○ A study procedure that does not require documentation in the individual eCRF. 
* The preferred location for measuring temperature will be the axilla. Fever is defined as body temperature ≥38.0°C/100.4°F. 
** Height will be measured only at Screening. 
*** HLA-B27 testing will be done in Stage 1 only. 
# An additional 20 mL for assay development will be taken in Stage 1 on Day 85 from the participants who have given specific consent. 
$ Out-of-window vaccination is not allowed.  
1 For literate participants in Europe/Africa only 

CONFIDENTIAL 
216152 (INTS GMMA GVGH-002) (H08_01TP) 
Protocol Amendment 2 Final 
08 June 2023 
28 
2 For illiterate participants in Africa only 
3 The pre 2nd and 3rd vaccination screening in Malawi could take more than a day, necessitating additional site visits but not more than 72 hours prior to the actual 
receipt of the vaccination.  
4 For illiterate participants, pDiary cards will be completed by the site field worker. 
5 For illiterate participants, pDiary cards can be returned by the field worker at the end of the 7 days after administration. 
6 For Malawi (Stage 2) only, subjects who test positive for malaria at Screening will be temporarily excluded (even if asymptomatic) and enrollment/first vaccination 
delayed until a negative malaria highly sensitive RDT is available. Treatment will also be provided for such prospective participants at the Investigator’s discretion 
according to local guideline. For subsequent vaccinations, malaria RDT testing will only be performed if participants have symptoms suggestive of malaria. 
7 Home visit for safety follow-up will take place only on Day 2. 

CONFIDENTIAL 
216152 (INTS GMMA GVGH-002) (H08_01TP) 
Protocol Amendment 2 Final 
08 June 2023 
29 
Table 2 
Intervals Between Study Visits 
Interval 
Planned visit 
interval  
Allowed interval range 
Screening (Day −28) → Visit 1 (Day 1) 
Up to 28 days* 
Up to 28 days* 
Visit 1 (Day 1) → Visit 2 (Day 8) 
7 days 
7-10 days 
Visit 1 (Day 1) → Reminder phone call 1 
(Day 4) 
3 days 
1-3 days 
Visit 1 (Day 1) → Visit 3 (Day 29) 
28 days 
28-33# days** 
Visit 1 (Day 1) → Visit 4 (Day 57) 
56 days 
52-62 days** 
Visit 4 (Day 57) → Visit 5 (Day 64) 
7 days 
7-10 days 
Visit 4 (Day 57) → Reminder phone call 2 
(Day 60) 
3 days 
1-3 days 
Visit 4 (Day 57) → Visit 6 (Day 85) 
28 days 
28-33# days** 
Visit 4 (Day 57) → Visit 7 (Day 169) 
112 days 
110-126 days** 
Visit 4 (Day 57) → Visit 7 (Day 169) 
112 days 
110-140$ days** 
Visit 7 (Day 169) → Visit 8 (Day 176) 
7 days 
7-10 days 
Visit 7 (Day 169) → Reminder phone call 3 
(Day 172) 
3 days 
1-3 days 
Visit 7 (Day 169) → Visit 9 (Day 197) 
28 days 
28-33# days** 
Visit 7 (Day 169) → Visit 10 (Day 337) 
168 days 
154-182 days 
* Screening evaluations may be completed up to 28 days before Visit 1 (Day 1). Site staff should allow 
enough time between the Screening Visit and Visit 1 to receive and review hematology/biochemical 
results. If screening laboratory tests are performed within 3 days of vaccination, it would not be 
necessary to repeat them pre-vaccination for the first study intervention administration. 
** Visits out of the allowed interval can lead to elimination from the Per Protocol Set for analysis of 
immunogenicity. 
$ Interval range will only be applicable for Stage 2 participants in Malawi. 
# Under special circumstances, eg, during coronavirus disease 2019 pandemic, the length of interval 
between visits for the collection of biological samples or for the vaccine administration may be extended 
to 38 days. 
2.0 INTRODUCTION 
2.1 
Study Rationale 
GlaxoSmithKline Biologicals SA (GSK) Vaccines Institute for Global Health (GVGH), 
with the support of Combating Antibiotic Resistant Bacteria-X (CARB-X), is developing 
a new candidate trivalent nontyphoidal Salmonella-generalized modules for membrane 
antigens (GMMA) vaccine (GVGH invasive nontyphoidal Salmonella-typhoid conjugate 
vaccine [iNTS-TCV]) against Salmonella Typhimurium (S. Typhimurium), Salmonella 
Enteritidis (S. Enteritidis), and Salmonella Typhi (S. Typhi). GVGH iNTS-TCV is based 

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on the previously developed GVGH monovalent TCV and bivalent S. Typhimurium and 
S. Enteritidis vaccine, using the GMMA-platform technology. The newly developed 
vaccine, GVGH iNTS-TCV vaccine, is new but its components are not new as iNTS 
vaccine is already in development by GVGH while TCV is registered in India and World 
Health Organization (WHO) prequalified. 
This candidate vaccine targets diseases of major importance for African populations. The 
death toll from these diseases combined was 90 000 deaths in sub-Saharan Africa (sSA) 
in 2019 [IHME, 2021]. Until now, there is no vaccine for iNTS or TCV widely used in 
Africa. However, safety/effectiveness studies are ongoing in Africa to support TCV 
introduction, which is backed by the Global Alliance for Vaccines and Immunization. 
The purpose of the current trial is to evaluate the safety and the immunogenicity of the 
primary response induced by this vaccine both in European and African adults. The 
current clinical trial will evaluate the GVGH iNTS-TCV candidate vaccine for the first 
time in humans in European adults (Stage 1). Following Stage 1, the same vaccine will be 
evaluated in African adults as part of Stage 2 of the trial. The details of the study 
objectives and endpoints are mentioned in Table 3. 
2.2 
Background 
Invasive nontyphoidal Salmonella disease is an important neglected and poverty-related 
disease [Balasubramanian, 2019; Feasey, 2012], primarily in resource-poor settings of 
sSA. In sSA, iNTS is one of the most common causes of bacteremia and reflects a major 
public health and socioeconomic burden. Infection with iNTS has been reported in sSA 
since the 1980s as a cause of child febrile illness and bacteremia, but often misdiagnosed 
as malaria [Feasey, 2012]. An estimated 59 100 iNTS deaths with more than half of them 
in children <5 years of age and a 14.5% case fatality rate have been reported in 2017 
[Collaborators GBDN-TSID, 2019]. The iNTS disease causative agents are associated 
with increasing antimicrobial resistance (AMR) and are classified by the WHO as high 
priority pathogens for developing new antibiotics. The most common African S. Enterica 
serovars associated with iNTS disease are S. Enteritidis and S. Typhimurium, accounting 
for >90% of iNTS cases in sSA [Reddy, 2010]. 
Infants and young children aged 9 to 24 months and human immunodeficiency virus 
infected individuals of all ages are most affected [Balasubramanian, 2019]. The number 
of cases per year were estimated around 535 000 in 2017, of which >400 000 were in sSA 
[Collaborators GBDN-TSID, 2019]. The iNTS cases have been reported across Africa, 
demonstrating that disease and mortality is a widespread threat throughout the continent 
[Uche, 2017]. The population-based surveillance study Typhoid Surveillance in Africa 
Program revealed among all bacteremia an overall iNTS prevalence of 17% in 10 sSA 
countries and 13 different sentinel sites [Marks, 2017]. 

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Fluoroquinolone-resistant Salmonella species are included in the WHO 
antibiotic-resistant high priority pathogens for Research and Development of new 
antibiotics. Specifically, African iNTS causative isolates show a concerning increase and 
high level of AMR with a high percentage of strains associated with multidrug resistance 
[Aldrich, 2019; Feasey, 2015; Kariuki, 2019; Puyvelde, 2019]. The only current 
intervention for iNTS disease is treatment by antibiotics. Resistance against the first-line 
antimicrobials ampicillin, chloramphenicol, and trimethoprim/sulfamethoxazole and 
multidrug resistance to all three agents among iNTS isolates is common in sSA. 
Furthermore, the emergence of iNTS strains resistant to fluoroquinolones, azithromycin, 
and third generation cephalosporins is posing a further challenge to clinical management 
of the disease in resource-limited settings where the few remaining effective 
antimicrobials are too expensive or unavailable. 
There is no licensed human vaccine against iNTS and currently no preventive 
intervention. 
GSK is developing a 2-component (ie, STmGMMA and SEnGMMA) GMMA-based 
candidate vaccine, invasive nontyphoidal Salmonella-generalized modules for membrane 
antigens (iNTS-GMMA), for the prevention of iNTS disease caused by S. Typhimurium 
and S. Enteritidis in infants from 6 weeks of age. 
The GMMA-technology is a novel vaccine platform based on bacterial outer membranes 
used to deliver the O antigen (Ag) portion of lipopolysaccharide (LPS) of 
S. Typhimurium and S. Enteritidis as active moieties [Lanzilao, 2015]. 
The GMMA are outer membrane particles (also known as blebs or exosomes), which are 
spontaneously released from Gram-negative bacteria. The bacteria are genetically 
manipulated to increase blebbing and reduce endotoxicity mainly associated with lipid A 
portion of LPS molecules. GMMA consist of LPS, outer membrane proteins, outer 
membrane lipids (eg, phospholipids), and enclosed periplasmic proteins 
[Benedetto, 2017; Maggiore, 2016]. 
S. Enteritidis O Ag and S. Typhimurium O Ag are structurally similar, sharing the same 
trisaccharide repeating unit of the O Ag backbone (mannose – rhamnose – galactose), 
with the mannose bearing abequose in S. Typhimurium and tyvelose in S. Enteritidis. The 
GSK 2-component vaccine is composed of STmGMMA and SEnGMMA derived 
respectively from genetically modified S. Typhimurium and S. Enteritidis bacteria that 
each produce high-yield of outer membrane exosomes with a detoxified LPS. 
The GMMA-production strains have been named NVGH2157 (S. Enteritidis) and 
NVGH2363 (S. Typhimurium). The GMMA (Drug Substances) produced from these 
strains are called SEnGMMA (also referred to as 2157-GMMA) and STmGMMA (also 
referred to as 2363-GMMA), respectively. 
 
 
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The development of an iNTS vaccine combined with TCV is a straightforward approach 
to sustainability of a much-needed neglected iNTS vaccine. The iNTS-TCV would 
potentially prevent approximately 70 000 deaths per year in sSA and help limit the spread 
of AMR bacteria. 
2.3 
Benefit/Risk Assessment 
2.3.1 
Risk Assessment 
During the current trial, there may be risks related to the blood sampling (eg, bruising and 
pain at the blood draw site). 
The iNTS-TCV candidate vaccine is yet to be tested in humans. 
Of the 3 iNTS-TCV vaccine components, the BioE-TCV has been licensed in India since 
January 2020 and WHO Prequalified in December 2020. It was well tolerated during 
clinical trials in 6-month-old to 64-year-old participants and has a safety profile similar to 
other injectable vaccines. 
The GSK GMMA-technology has been applied to a candidate vaccine against Shigella 
Sonnei. The S. Sonnei candidate vaccine 1790GAHB has been tested in two Phase 1, an 
extension study, Phase 2a and Phase 2b clinical studies and was shown to be 
immunogenic and well tolerated in healthy European, African, and US adults 
[Launay, 2017; Launay, 2019; Obiero, 2017; Robert, 2021; Frenck, 2021]. 
The human data on BioE-TCV and iNTS-GMMA (trials with BioE-TCV and 
iNTS-GMMA are being conducted in parallel with the current trial), will de-risk the 
development of the iNTS-TCV candidate vaccine. 
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Based on GSK’s preclinical data produced with other antigens, co-formulation of GMMA 
and TCV is unlikely to adversely impact on the antibody response induced by each 
component. 
As for any vaccine administered intramuscularly, local reactions such as injection site 
pain, injection site redness, and injection site swelling may occur within days after 
administration. Injection of saline does not usually cause side effects other than the ones 
known for any injection (eg, local pain, injection site reactions, muscle pain). 
More detailed information about the known and expected benefits and risks and 
reasonably expected AEs related to iNTS-TCV may be found in the current Investigator’s 
Brochure (IB). 
Detailed information about the known and expected benefits and risks and expected AEs 
of Menveo, Boostrix, and Typhoid Vi polysaccharide vaccine (Typhim Vi) can be found 
in their respective Prescribing Information/Package Insert/ Summary of Product 
Characteristics (SmPC). 
Coronavirus Disease 2019 
During special circumstances (eg, coronavirus disease 2019 [COVID-19] pandemic), the 
specific guidance from local public health and other competent authorities regarding the 
protection of individuals’ welfare must be applied. 
2.3.2 
Risk Mitigation Strategies 
For the safety of the participants, the protocol has incorporated various risk mitigation 
measures, including sentinel approach (refer to Section 4.1), staggered administration of 
study intervention (refer to Section 4.1), study holding criteria (refer to Section 4.5), 
appropriate inclusion and exclusion criteria (refer to Section 5.1 and Section 5.2), 
checking contraindications to study intervention (refer to Section 7.2), and close 
monitoring of participants after administration of study intervention. 
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All study activities at the study center will be performed by trained clinical staff 
authorized by the study Investigator.  
After the administration of study intervention, all participants will be observed for a 
minimum of 60 minutes, with medical attention available in case of anaphylaxis. 
The blinded monitoring of study data will be performed by the Sponsor’s 
designee/Contract Research Organization (IQVIA). 
Additional safety monitoring will be performed by an internal GSK Safety Review Team 
(SRT) and an internal Safety Review Committee (iSRC). 
The Sponsor will immediately notify the Principal Investigator if any additional safety or 
toxicology information becomes available during the study. 
This study will be performed in compliance with the protocol, International Council for 
Harmonisation (ICH) Good Clinical Practice (GCP) and applicable regulatory 
requirements. Aspects of the study concerned with the investigational medicinal 
product(s) will meet the requirements of European Union – Good Manufacturing 
Practice. 
2.3.3 
Benefit Assessment 
By receiving iNTS-TCV, the participants may be protected against iNTS and typhoid 
fever. 
By receiving the comparator vaccines, the participants are expected to be protected 
against meningococcal disease (Menveo), tetanus, diphtheria, and pertussis (Boostrix), 
and typhoid (Typhim Vi). 
All participants will undergo a physical medical examination at the first study visit; these 
evaluations, made by skilled and trained clinical staff, may potentially provide valuable 
knowledge about the participant’s health. In case the study staff discovers any medical 
condition, the participant may be referred to the local healthcare system, in case any 
abnormalities/diseases are observed. 
The participants will contribute to the process of developing therapies in an area of unmet 
need. They may also help provide valuable data, about the tolerability and 
immunogenicity of the investigational vaccine and about its potential ability to provide 
clinical protection against iNTS and typhoid fever. 
2.3.4 
Overall Benefit/Risk Conclusion 
Considering the measures taken to minimize possible risks to the participants in this 
study, the potential risks associated with the study interventions and study assessments 
are balanced by the potential benefits that may be provided to the participants. 

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3.0 OBJECTIVES AND ENDPOINTS 
Table 3 
Study Objectives and Endpoints 
Objectives 
Endpoints 
Primary 
• 
To evaluate the safety and 
reactogenicity profile of 
GSK Vaccines Institute for 
Global Health (GVGH) 
invasive nontyphoidal 
Salmonella-typhoid 
conjugate vaccine (iNTS-
TCV) vaccine in healthy 
European/African adults 
• 
Number of participants in Europe/Stage 1 with solicited 
administration site and systemic events during 7 days after each 
study intervention administration (ie, on the day of study 
intervention administration and the 6 subsequent days) occurring at 
Day 1, Day 57, and Day 169, by study intervention group 
• 
Number of participants in Europe/Stage 1 with unsolicited adverse 
events (AEs) during 28 days after each study intervention 
administration (ie, on the day of study intervention administration 
and the 27 subsequent days) occurring at Day 1, Day 57, and Day 
169, by study intervention group 
• 
Number of participants in Europe/Stage 1 with serious adverse 
events (SAEs) from first study intervention administration (Day 1) 
to 28 days after third study intervention administration (Day 197), 
by study intervention group 
• 
Number of participants in Europe/Stage 1 with AEs/SAEs leading 
to withdrawal from the study and/or withholding doses of study 
intervention, from first study intervention administration up to 28 
days after third study intervention administration (Day 1 to Day 
197), by study intervention group 
• 
Number of participants in Europe/Stage 1 with deviations from 
normal or baseline values for hematological, renal, and hepatic 
panels test results at 7 days after each study intervention 
administration (Day 8, Day 64, and Day 176) and at 28 days after 
each study intervention administration (Day 29, Day 85, and Day 
197), by study intervention group 
• 
Number of participants in Africa/Stage 2 with solicited 
administration site and systemic events during 7 days after each 
study intervention administration (ie, on the day of study 
intervention administration and the 6 subsequent days) occurring at 
Day 1, Day 57, and Day 169, by study intervention group 
• 
Number of participants in Africa/Stage 2 with unsolicited AEs 
during 28 days after each study intervention administration (ie, on 
the day of study intervention administration and the 27 subsequent 
days) occurring at Day 1, Day 57, and Day 169, by study 
intervention group 
• 
Number of participants in Africa/Stage 2 with SAEs from first 
study intervention administration (Day 1) to 28 days after third 
study intervention administration (Day 197), by study intervention 
group 
• 
Number of participants in Africa/Stage 2 with AEs/SAEs leading to 
withdrawal from the study and/or withholding doses of study 
intervention, from first study intervention administration up to 28 
days after third study intervention administration (Day 1 to Day 
197), by study intervention group 

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Objectives 
Endpoints 
• 
Number of participants in Africa/Stage 2 with deviations from 
normal or baseline values for hematological, renal, and hepatic 
panel test results at 7 days after each study intervention 
administration (Day 8, Day 64, and Day 176) and at 28 days after 
each study intervention administration (Day 29, Day 85, and Day 
197), by study intervention group 
Secondary 
• 
To evaluate the long-term 
safety profile of GVGH 
iNTS-TCV vaccine in 
healthy European/African 
adults 
• 
Number of participants with any SAE from 28 days after third 
study intervention administration (Day 197) up to Day 337, per 
study intervention group in Stage 1/Stage 2. 
• 
Number of participants with AEs/SAEs leading to withdrawal from 
the study, from 28 days after third study intervention administration 
(Day 197) up to Day 337, by study intervention group in Stage 
1/Stage 2. 
• 
To evaluate the 
immunogenicity profile of 
GVGH iNTS-TCV vaccine 
in healthy European adults 
• 
Anti-serotype specific immunoglobulin (Ig) G* geometric mean 
concentrations (GMCs), in participants in Europe/Stage 1, as 
determined by enzyme-linked immunosorbent assay (ELISA), 
before each study intervention administration (Day 1, Day 57, and 
Day 169) and 28 days after each study intervention administration 
(Day 29, Day 85 and Day 197), for each study intervention group 
and between groups ratios 
• 
Anti-serotype specific IgG* within-participant geometric mean 
ratios (GMRs), in participants in Europe/Stage 1, as determined by 
ELISA at 28 days after each study intervention administration 
compared to each study intervention administration baseline (Day 
29 versus Day 1, Day 85 versus Day 57 and Day 197 versus Day 
169) 
* Anti- Salmonella Typhi (S. Typhi) Vi antigen (Ag) total IgG, 
Anti-Salmonella Typhimurium (S. Typhimurium) O Ag total IgG, 
Anti-Salmonella Enteritidis (S. Enteritidis) O Ag total IgG will be tested. 
• 
To evaluate seroresponse 
with the GVGH iNTS-
TCV vaccine after each 
study intervention 
administration in healthy 
European adults 
• 
Number of participants in Europe/Stage 1 achieving, for each Ag, 
at least a 4-fold** rise in Anti-serotype specific IgG* antibody 
concentration 28 days after each study intervention administration 
(Day 29, Day 85, and Day 197) compared to first study intervention 
administration baseline (Day 1), as measured by ELISA, by study 
intervention group 
• 
Number of participants in Europe/Stage 1 with Anti-S. Typhi Vi Ag 
IgG antibody concentrations equivalent to ≥4.3 µg/mL***, before 
each study intervention administration (Day 1, Day 57, and Day 
169) and 28 days after each study intervention administration (Day 
29, Day 85, and Day 197), as measured by ELISA, by study 
intervention group 
* Anti-S. Typhi Vi Ag total IgG, Anti-S. Typhimurium O Ag total IgG, 
Anti-S. Enteritidis O Ag total IgG will be tested 
** 4-fold is considered clinically meaningful measure of seroconversion 
in the absence of an established correlate of protection. 
*** 4.3 µg/mL threshold is clinically meaningful as accepted by World 
Health Organization (WHO) as immunological protection threshold for 

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Objectives 
Endpoints 
Vi containing typhoid vaccines and has been used in previous studies for 
registration of these vaccines 
• 
To evaluate the 
immunogenicity profile of 
GVGH iNTS-TCV vaccine 
in healthy African adults 
• 
Anti-serotype specific IgG* GMC, in participants in Africa/Stage 2, 
as determined by ELISA, before each study intervention 
administration (Day 1, Day 57, and Day 169) and 28 days after 
each study intervention administration (Day 29, Day 85, and Day 
197), for each study intervention group and between-groups ratios 
• 
Anti-serotype specific IgG* within-participant GMRs, in 
participants in Africa/Stage 2, as determined by ELISA at 28 days 
after each study intervention administration compared to each study 
intervention administration baseline (Day 29 versus Day 1, Day 85 
versus Day 57, and Day 197 versus Day 169) 
* Anti-S. Typhi Vi Ag total IgG, Anti-S. Typhimurium O Ag total IgG, 
Anti-S. Enteritidis O Ag total IgG will be tested. 
• 
To evaluate seroresponse 
with the GVGH iNTS-
TCV vaccine after each 
study intervention 
administration in healthy 
African adults 
• 
Number of participants in Africa/Stage 2 achieving, for each Ag, at 
least a 4-fold** rise in Anti-serotype specific IgG* antibody 
concentration 28 days after each study intervention administration 
(Day 29, Day 85, and Day 197) compared to first study intervention 
administration baseline (Day 1), as measured by ELISA, by study 
intervention group 
• 
Number of participants in Africa/Stage 2 with Anti-S. Typhi Vi Ag 
IgG* antibody concentrations equivalent to ≥4.3 µg/mL***, before 
each study intervention administration (Day 1, Day 57, and Day 
169) and 28 days after each study intervention administration (Day 
29, Day 85, and Day 197), as measured by ELISA, by study 
intervention group 
* Anti-S. Typhi Vi Ag total IgG, Anti-S. Typhimurium O Ag total IgG, 
Anti-S. Enteritidis O Ag total IgG will be tested 
** 4-fold is considered clinically meaningful measure of seroconversion 
in the absence of an established correlate of protection. 
*** 4.3 µg/mL threshold is clinically meaningful as accepted by WHO 
as immunological protection threshold for Vi containing typhoid 
vaccines and has been used in previous studies for registration of these 
vaccines 
Tertiary 
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Objectives 
Endpoints 
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4.0 STUDY DESIGN 
4.1 
Overall Design 
This is a Phase 1/2a, observer-blind, randomized, dose-escalation, controlled, 
multi-country, two-staged, staggered study including 9 groups. 
The full dose of the TCV component is the licensed dose of the TCV vaccine, while the 
full dose of both iNTS components have been tested in repeat-dose toxicology studies in 
rabbits and were well tolerated. The details of the selected doses are provided in 
Section 4.3. 
The study will be conducted overall (both Stage 1 and Stage 2) with approximately 
155 healthy adult participants (18 to 50 years of age). The healthy European adults will 
be randomly assigned to 1 of the groups indicated for Stage 1 (refer to Section 4.1.1). The 
healthy African adults will be randomly assigned to 1 of the groups indicated for Stage 2 
(refer to Section 4.1.2). 
Each group will receive 2 of the 11 study interventions at each administration, except for 
the Control_Stage 2 group which will receive 4 study interventions (a different active 
comparator at each administration time point together with saline) (Table 4). 
Each participant will receive 1 randomly selected intramuscular (IM) study intervention 
per arm on Day 1, Day 57, and Day 169. Each participant will be part of this trial for 
approximately 13 months (from the Screening starting 28 days before first study 
intervention administration and until 6 months after third study intervention 
administration). 
The primary completion date of the study will be at Visit 9 (Day 197), 28 days after the 
third study intervention. An extended safety follow-up will be performed until 6 months 
after the third study intervention administration (Day 337) for collection of SAEs. 
Table 1 shows the full schedule of activities (SoA) for Stages 1 and 2 and the details of 
the intervals between study visits are as shown in Table 2. 
4.1.1 
Stage 1 
Stage 1 (Europe) will follow a 2-step staggered design, leading in with low doses of all 
the study interventions, in a dose-escalation manner. The sentinel approach will be 
followed for the first 10 participants each in Step 1 and Step 2, in which only 
1 participant will be treated daily. This will be done to ensure maximum safety of the 
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In Step 1, 10 healthy European adults, randomized in a 2:2:1 ratio, will receive: 
• 
The low dose of the candidate iNTS-TCV vaccine and concomitant saline to be 
administered in different arms, or 
• 
Separate administration of low doses of iNTS-GMMA and TCV vaccines in different 
arms, or 
• 
Placebo and saline in different arms. 
The 10 sentinel participants in Step 1 will receive the first study intervention on 
consecutive days and a telephonic safety follow-up call will be performed on the next 
day. If the participants have any complaints, they will be invited to the study site for an 
evaluation of the possible AEs and holding rules, prior to administration of study 
intervention in the next participant. If the Investigator becomes aware of a holding rule 
being met, he/she must suspend administration of the study intervention and inform the 
Sponsor’s delegate immediately who will in-turn inform the Sponsor. 
The iSRC will review all safety data collected up to 7 days after the first study 
intervention in Step 1. Step 2 will only commence if there is a favorable safety 
assessment during this review. 
In Step 2, 40 healthy European adults will be randomized in a 2:2:1 ratio. A staggered 
approach will be followed for the first 10 sentinel participants and these participants will 
be followed up with a safety follow-up call on the next day of administration of study 
intervention. If the participants have any complaints, they will be invited to the study site 
for an evaluation of the AEs and holding rules, prior to administration of study 
intervention in the next participant. If the Investigator becomes aware of a holding rule 
being met, he/she must suspend administration of the study intervention and inform the 
Sponsor’s delegate immediately who will in-turn inform the Sponsor. The remainder of 
the 30 participants will receive the study intervention in a sequential (at least 60 minutes 
apart) manner. The participants in Step 2 will receive: 
• 
The full dose of the candidate iNTS-TCV vaccine and concomitant saline to be 
administered in different arms, or 
• 
Separate administration of full doses of iNTS-GMMA and TCV vaccines in different 
arms, or 
• 
Placebo and saline in different arms. 
For the trial to proceed to Stage 2, a favorable evaluation of all available safety data by 
the iSRC following the first and second study intervention administrations (up to 28 days 
after second administration) in Step 2 of Stage 1 will be required. In case a No-Go 
decision is made, the study will be terminated at the end of Stage 1 and there will be no 
further administration of the study intervention in Step 2. 

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4.1.2 
Stage 2 
In Stage 2 (Africa), a total of 105 healthy African adults, randomized in a 3:3:1 ratio, will 
receive: 
• 
The full dose of the candidate iNTS-TCV vaccine and concomitant saline to be 
administered in different arms, or 
• 
Separate administration of full doses of iNTS-GMMA and TCV vaccines in different 
arms, or 
• 
MenACWY (Menveo) and saline for the first administration, TdaP (Boostrix) and 
saline for the second administration and Typhim Vi and saline for the third 
administration in different arms. This is the Control_Stage 2 group. 
The first 21 participants in Stage 2 will initially be recruited with administration 
proceeding sequentially, at least 60 minutes apart. These participants will be followed up 
with a safety follow-up call on the next day of administration of study intervention. If the 
participants have any complaints, they will be invited to the study site for an evaluation 
of the possible AEs and holding rules, prior to administration of study intervention in the 
next participant. If the Investigator becomes aware of a holding rule being met, he/she 
must suspend administration of the study intervention and inform the Sponsor’s delegate 
immediately who will in-turn inform the Sponsor. All safety data from these participants 
up to 7 days after the first administration of the study intervention will be reviewed by the 
iSRC and the recruitment of the remaining 84 participants in Stage 2 will only commence 
if there is a positive evaluation by the iSRC. The study interventions will be administered 
in parallel in the remaining 84 participants. 
All 155 participants (Stage 1 and Stage 2) will be closely observed for a minimum of 
60 minutes after each study intervention administration, before leaving the facilities. The 
Investigator will decide if the participant should be observed for more than 60 minutes 
after each study intervention administered, if required. 

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Table 4 
Study Groups, Intervention, and Blinding 
Study groups 
Number of 
participants 
Age 
(Min-
Max) 
Study 
interventions 
first 
administration 
Study 
interventions 
second 
administration 
Study 
interventions 
third 
administration 
Blinding 
Visit 
1→Visit 
10 
(Observer
-blind)* 
Stage 1 
(50 
participants) 
 
Step 1  
(10 
participants) 
1 
Invasive nontyphoidal 
Salmonella-typhoid 
conjugate vaccine 
(iNTS-TCV) low dose 
4 
18 – 
50 
years 
iNTS-TCV low 
dose 
iNTS-TCV low 
dose 
iNTS-TCV low 
dose 
X 
Saline 
Saline 
Saline 
2 
Invasive nontyphoidal 
Salmonella-generalized 
modules for membrane 
antigens vaccine (iNTS-
GMMA) and Typhoid 
conjugate vaccine (TCV) 
low doses 
4 
18 - 
50 
years 
iNTS-GMMA 
low dose 
iNTS-GMMA 
low dose 
iNTS-GMMA 
low dose 
X 
TCV low dose 
TCV low dose 
TCV low dose 
3 Placebo_Step 1 
2 
18 – 
50 
years 
Placebo 
Placebo 
Placebo 
X 
Saline 
Saline 
Saline 
Step 2 
(40 participants
) 
4 iNTS-TCV full dose_1 
16 
18 – 
50 
years 
iNTS-TCV full 
dose 
iNTS-TCV full 
dose 
iNTS-TCV full 
dose 
X 
Saline 
Saline 
Saline 
5 iNTS-GMMA and TCV full 
doses_1 
16 
18 - 
50 
years 
iNTS-GMMA 
full dose 
iNTS-GMMA 
full dose 
iNTS-GMMA 
full dose 
X 
TCV full dose 
TCV full dose 
TCV full dose 
6 Placebo_Step 2 
8 
18 – 
50 
years 
Placebo 
Placebo 
Placebo 
X 
Saline 
Saline 
Saline 

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Study groups 
Number of 
participants 
Age 
(Min-
Max) 
Study 
interventions 
first 
administration 
Study 
interventions 
second 
administration 
Study 
interventions 
third 
administration 
Blinding 
Visit 
1→Visit 
10 
(Observer
-blind)* 
Stage 2 (105 participants) 
7 iNTS-TCV full dose_2 
45 
18 – 
50 
years 
iNTS-TCV full 
dose 
iNTS-TCV full 
dose 
iNTS-TCV full 
dose 
X 
Saline 
Saline 
Saline 
8 iNTS-GMMA and TCV full 
doses_2 
45 
18 - 
50 
years 
iNTS-GMMA 
full dose 
iNTS-GMMA 
full dose 
iNTS-GMMA 
full dose 
X 
TCV full dose 
TCV full dose 
TCV full dose 
9 Control_Stage 2 
15 
18 – 
50 
years 
Menveo 
Boostrix 
Typhim Vi 
X 
Saline 
Saline 
Saline 
* The Sponsor representatives are unblinded after Visit 9 is completed for all subjects. 

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Blood samples will be collected: 
• 
For selected hematology, biochemistry, viral serologic analyses, and human 
leukocyte antigen B27 (HLA-B27) testing, as part of the Screening. HLA-B27 
testing will be done in Stage 1 only. 
• 
For selected hematology and biochemistry analyses, before each study intervention 
administration and at 7 and 28 days after each study intervention administration, 
from all participants. 
• 
For immunological assays, before and 28 days after each study intervention 
administration, from each randomized participant. 
• 
An additional 20 mL for assay development will be taken in Stage 1 on Day 85 from 
the participants who have given specific consent. 
• 
For peripheral blood mononuclear cells extraction for monoclonal antibodies 
generation at Visit 9 (for Stage 2 only) 
Data will be collected through standardized electronic Case Report Forms (eCRFs). The 
collection of solicited administration site and systemic events will be done through a 
participant paper diary (pDiary). 
An internal GSK SRT and iSRC will be involved in the safety oversight for this study. 
Safety precautions such as study design with staggered enrollment, stepwise 
dose-escalation (Figure 1), limited dosing, and study holding rules have been predefined 
to ensure maximum safety of the participants. Refer to Section 9.7 for detailed 
description of safety monitoring. 
Details of the formulations of investigational and active comparator vaccines are 
indicated in Table 6 and Table 7, respectively. 
4.2 
Scientific Rationale for Study Design 
The European Medicine Agency’s “Guideline on strategies to identify and mitigate risks 
for first-in-human (FIH) clinical trials with investigational medicinal products; 
(EMEA/CHMP/SWP/28367/07 Rev 1)”, is intended to assist Sponsors in the transition 
from nonclinical to early clinical development. It outlines factors influencing risk to be 
considered in the nonclinical testing strategy and designs of FIH clinical studies or 
investigational medicinal products. This guideline applies to all new chemical and 
biological investigational medicinal products except gene and cell therapy products. This 
guideline also applies to relevant Clinical Trial Authorization applications submitted in 
accordance with Directive 2001/20/EC (EU No 536/2014). 
The study is designed in 2 stages to allow for the evaluation of the vaccine safety and 
immunogenicity across 2 geographic locations. This allows an assessment of the vaccine 
in both low and high endemicity settings and evaluate the potential impact of 
environmental exposure on the vaccine immune response. The first stage of the trial 

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which is the First Time in Human part of the trial is designed with the required safety 
measures to serve as risk mitigation (refer to Section 2.3.2). The vaccination schedule is 
selected based on the number of doses expected to be immunogenic in the target 
population for primary immunization with the vaccine if eventually licensed (ie, young 
infants from 6 weeks of age). The specific time points are selected to allow integration 
with existing Expanded Programme on Immunization schedules in the target regions for 
the vaccine (ie, 6 weeks, 14 weeks, and 9 months of age). Evaluating the safety of three 
doses in adults will allow the eventual testing of the same number of doses in the target 
population. 
4.2.1 
Choice of Comparator Vaccines 
For the adults in Europe, a placebo will be used. The placebo will be the diluent for the 
study intervention (iNTS-TCV and iNTS-GMMA) to obtain the low dose. It has been 
used in past GVGH-managed trials and in many licensed vaccines without any safety 
concerns. For the population in Europe, it is important to compare the reactogenicity of 
the candidate vaccine against a placebo to objectively assess its safety profile. 
A saline solution is used in this study to ensure adequate blinding and to also ensure an 
appropriate comparison of the study arms based on the effects of the vaccine components 
(all participants to receive an equal amount of alum). 
For the adults in Stage 2 in Africa, Menveo and Boostrix have been used as comparators 
in a previous study conducted in Kenya during the development of the S. Sonnei 
1790GAHB vaccine [Obiero, 2017]. Menveo is indicated for active immunization to 
prevent invasive meningococcal disease caused by Neisseria meningitidis serogroups A, 
C, Y and W-135. The vaccine contains no preservative or adjuvant. Meningitis being 
prevalent in Malawi, administering a dose of Menveo will provide some benefits to the 
participants. Boostrix provides protection against tetanus, diphtheria, and pertussis. It can 
be administered as a booster in this age population. Typhim Vi is licensed for the 
prevention of typhoid fever in individuals from 2 years of age, however it is also not 
routinely administered to adults in Malawi. In the typhoid-endemic region of Malawi, 
providing a dose of Typhim Vi will provide some benefits to the participants. 
The separate administration of the iNTS-GMMA and TCV vaccines as comparators is to 
allow for the evaluation of the vaccines’ immunogenicity as a combination (trivalent) 
vaccine and as separate vaccines, evaluate the likelihood of interference of iNTS-GMMA 
with the immunogenicity of TCV vaccines, and vice versa, and aid the planning of future 
development of either a combination trivalent vaccine or a bivalent iNTS-GMMA 
vaccine. 

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4.2.2 
Rationale for Blinding 
Because of the difference in the presentation of the investigational vaccine and the 
comparator vaccines, ie, the difference in the labeling of the vaccine vials and the 
difference in the appearance of the diluent presentation, double blinding is not possible. 
The study will be conducted in an observer-blind manner. Refer to the definitions of 
double blinding and observer-blind in Appendix 1 and refer to Section 6.3.3 for details. 
When all data up to Day 85 in Stage 2 are available, a group-unblinded interim statistical 
analysis for immunogenicity will be performed. This analysis may lead to the unblinding 
of the study team with respect to some participants. A statistician will be unblinded for 
the analysis. 
The remaining study personnel will stay blinded until study end (Day 337 in Stage 2). 
The Investigator and the participants will not have access to the treatment allocation up to 
study end (Day 337 in Stage 2). 
4.3 
Justification for Dose 
• 
In preclinical studies, 
 
 
 The TCV component of the vaccine is already licensed 
by Biological E with good immunogenicity demonstrated in populations aged 
6 months to 64 years. 
 
 
 There was also no signal of interference between the different 
components of the vaccine in the animal experiments. 
• 
The highest dose of the iNTS-TCV vaccine to be used in this trial was tested in a 
repeated-dose toxicology study in rabbits and it concluded that based on the findings 
from the study, 4 IM administrations of the vaccine at 2-week intervals to New 
Zealand White rabbits were well tolerated with no evidence of systemic toxicity. 
Additionally, the vaccine-related changes were mild in severity and likely 
represented a physiological reaction following the immune stimulation in response to 
the vaccine candidate. 
Lower starting doses will be used for the first stage of the trial before escalating to the 
full dose to mitigate any potential risks related to dose increases. 
The selected full dose of the TCV component is the dose of the licensed TCV vaccine, 
while the full dose of both iNTS components have been tested in repeat-dose toxicology 
studies in rabbits and were well tolerated. Two doses will be tested, 
 dilutions of 
the full doses (low dose) of all study interventions and the full doses of all the study 
interventions. The licensed TCV is 25 µg in 0.5 mL dose and in the absence of a 
commercial diluent, it is most feasible to achieve the fractional low dose of 
 mL, 
 
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. The selected low dose will be 
used as a safety lead-in before testing the full dose in the FIH stage of this trial and will 
allow an initial assessment of the vaccine immunogenicity using a lower antigen content. 
The alum component is the same as has been tested in previous trials with GMMA 
vaccines and will be the same irrespective of the dose-level. 
4.4 
End of Study Definition 
A participant is considered to have completed the study if he/she returns for the last 
visit/contact or is available for the last scheduled procedure/contact as described in the 
protocol. 
The end of study (EoS) is defined as the date of the Last Subject Last Visit (LSLV) or 
date of last testing results released, whichever comes last. In the latter, EoS must be 
achieved no later than 8 months after LSLV. 
4.5 
Study Holding Criteria 
4.5.1 
Study Holding Rules 
Holding rules will be introduced to ensure a well-controlled exposure to the 
investigational candidate vaccine and to prevent participants from being exposed to any 
unnecessary safety risks in this FIH study. The holding rules will point attention to safety 
signals and indicate requirements for formal committee reviews that will decide whether 
additional participants can be exposed to the study intervention if particular criteria are 
met. Study holding rules are defined in Table 5. 
Holding rule 1 and 2c (threshold ≥1) will be assessed by the Investigator on a continuous 
basis irrespective of the number of enrolled participants and meeting any of these holding 
rules will trigger a hold of study intervention administration irrespective of number of 
enrolled participants and/or timing of the event relative to study intervention 
administration. Holding rule 2 (2a-b) and 1d.2 in Stage 2 (threshold ≥2) will be assessed 
during the safety evaluations on blinded or unblinded data. 
These holding rules have been written under the assumption that the safety data from all 
participants will be available. If the data from some participants are not available (eg, in 
case a participant is lost to follow-up), then the holding rules will be assessed on a 
pro-rata basis. 
If the Investigator becomes aware of a holding rule being met, he/she must suspend 
administration of the study intervention and inform the Sponsor’s delegate immediately 
(holding rules 1a-d and 2c). 
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However, for the other holding rules (1d.2 in Stage 2, 2a and 2b) which have a threshold 
>2, the Investigator will inform the Sponsor’s delegate immediately, without suspending 
the administration of the study intervention. 
The Sponsor’s delegate will inform the Investigator if holding rules 1d.2 in Stage 2 and 
2a-b are met. 
The following communication sequence must be followed: 
• 
The concerned site staff has to put study intervention administration on hold. 
• 
The concerned site staff must immediately inform IQVIA CRA and Medical Monitor 
(contact details will be provided in a separate document) via email and phone 
communication who will in-turn inform the GVGH Study Responsible Project 
Physician. 
• 
All informed site staff will confirm to their local contact that action has been taken 
providing appropriate documentation to GVGH through the IQVIA CRA and 
Medical Monitor. 
• 
GSK will further evaluate the case with the iSRC and GSK Global Safety Board and 
will take the decision to stop or to restart the study intervention administration. 
GVGH project physician will inform the IQVIA project lead of the decision and the 
rationale for the decision and all site staff will be informed about that final decision 
by IQVIA project lead. 

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Table 5 
Study Holding Rules 
 
Events 
Number or % of 
participants needed to 
pause administration 
of study intervention 
Stage 1 
Step 1 and 
Step 2 
Stage 2 
1a 
Death or any life-threatening SAE regardless of causality 
≥1 
≥1 
1b 
Any non-life-threatening SAE that cannot be reasonably attributed to 
another cause other than study intervention administration 
≥1 
≥1 
1c 
Any withdrawal from the study (by Investigator or participant 
request) following a Grade 3 AE that cannot be reasonably attributed 
to another cause other than study intervention administration 
≥1 
≥1 
1d.1 
Any administration site or general solicited event leading to 
hospitalization, 
OR 
Necrosis at the injection site, 
each within the 7-day (Days 1 to 7) post-administration period 
≥1 
≥1 
1d.2 
Fever >40°C (104°F) within the 7-day (Days 1 to 7) post-
administration period 
≥1 
≥2 
2a 
Any Grade 3 solicited administration site event (lasting 48 h or more) 
in an investigational group, within the 7-day (Days 1 to 7) 
post-administration period 
≥2 
NA 
2b 
Any Grade 3 solicited general AE (lasting 48 h or more) in an 
investigational group, within the 7-day (Days 1 to 7) post-
administration period 
≥2 
NA 
2c 
Any Grade 3 unsolicited AE in an investigational group, that can be 
reasonably attributed to the study intervention administration, within 
the 7-day (Days 1 to 7) post-administration period or 
Any Grade 3 abnormality in prespecified hematological or 
biochemical laboratory parameters in an investigational group within 
the 7-day (Days 1 to 7) post-administration period 
≥1 
NA 
Abbreviations: AE = adverse event; h = hours; SAE = serious adverse event; NA = not applicable 

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4.5.1.1 
Risk Assessment Curves for Holding Rules Cutoff Definition 
Figure 2 
Blinded Review: Safety Holding Rules 1a, 1b, 1c, 1d.1 and 2c After 10, 
21, 40 and 105 Participants 
 
Figure 2 illustrates the following: 
• 
With 10 participants, each holding rule 1a-d.1, and 2c has more than 90% chance of 
not being met for study intervention administration with a true incidence rate below 
1% and has more than 65% chance of being met for study intervention 
administration with a true incidence rate above 10%. 
• 
With 21 participants, each holding rule 1a-d.1 has more than 80% chance of not 
being met for study intervention administration with a true incidence rate below 1% 
and has more than 65% chance of being met for study intervention administration 
with a true incidence rate above 4.8%. 
• 
With 40 participants, each holding rule 1a-d.1, and 2c has more than 70% chance of 
not being met for study intervention administration with a true incidence rate below 
1% and has more than 65% chance of being met for study intervention 
administration with a true incidence rate above 2.5%. 
• 
With 105 participants, each holding rule 1a-d.1 has more than 90% chance of not 
being met for study intervention administration with a true incidence rate below 1% 
and has more than 88% chance of being met for study intervention administration 
with a true incidence rate above 2.0%. 

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Figure 3 
Unblinded Review: Safety Holding Rules 1d.2 After 4, 9, 16 and 45 
Participants 
 
Figure 3 illustrates the following: 
• 
With 4 participants in administration cohort, holding rule 1d.2 has more than 90% 
chance of not being met for study intervention administration with a true incidence 
rate below 2.5% and has more than 68% chance of being met with a true incidence 
rate above 25%. 
• 
With 9 participants in administration cohort, holding rule 1d.2 has more than 90% 
chance of not being met for study intervention administration with a true incidence 
rate below 6% and has more than 63% chance of being met for study intervention 
administration with a true incidence rate above 22.2%. 
• 
With 16 participants in administration cohort, holding rule 1d.2 has more than 85% 
chance of not being met for study intervention administration with a true incidence 
rate below 1% and has more than 65% chance of being met with a true incidence rate 
above 6.2%. 
• 
With 45 participants in administration cohort, holding rule 1d.2 has more than 80% 
chance of not being met for study intervention administration with a true incidence 
rate below 2% and has more than 60% chance of being met with a true incidence rate 
above 4.4%. 

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Figure 4 
Unblinded Review: Safety Holding Rules 2a and 2b After 4 and 16 
Participants 
 
Figure 4 illustrates the following: 
• 
With 4 participants in administration cohort, each holding rule 2a and 2b has more 
than 90% chance of not being met for study intervention administration with a true 
incidence rate below 14% and has more than 69% chance of being met for study 
intervention administration with a true incidence rate above 50%. 
• 
With 16 participants in administration cohort, each holding rule 2a and 2b has more 
than 90% chance of not being met for study intervention administration with a true 
incidence rate below 3% and has more than 61% chance of being met for study 
intervention administration with a true incidence rate above 12.5%. 

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5.0 STUDY POPULATION 
Prospective approval of protocol deviations to recruitment and enrollment criteria, also 
known as protocol waivers or exemptions, is not permitted. 
5.1 
Inclusion Criteria 
All participants must satisfy ALL the following criteria at the entry of the trial: 
• 
Participants, who, in the opinion of the Investigator, can and will comply with the 
requirements of the protocol (eg, completion of the pDiary cards, return for 
follow-up visits). 
• 
Written or witnessed/thumb printed informed consent obtained from the participant 
prior to performance of any study-specific procedure. 
• 
Healthy participants as established by medical history, clinical examination, and 
laboratory assessment. 
• 
Participant satisfying screening requirements. 
• 
A male or female between and including 18 and 50 years of age at the time of the 
first study intervention administration. 
• 
Female participants of nonchildbearing potential may be enrolled in the study. 
Nonchildbearing potential is defined as pre-menarche, current bilateral tubal ligation 
or occlusion, hysterectomy, bilateral ovariectomy, or post-menopause. 
• 
Female participants of childbearing potential may be enrolled in the trial if the 
participant: 
− 
Has practiced adequate contraception (as indicated in Appendix 4) for 1 month 
prior to study intervention administration, and 
− 
Has a negative pregnancy test on the day of study intervention administration, 
and 
− 
Has agreed to continue adequate contraception during the entire treatment period 
and for 1 month after completion of the study intervention administration series. 
• 
Blood sample for simultaneous follicle-stimulating hormone (FSH) and estradiol 
levels may be collected at the discretion of the Investigator to confirm 
non-reproductive potential according to local laboratory reference range. 
• 
Genetic testing for HLA-B27 will be performed at Screening and only participants 
with a negative result will be allowed to participate in the study*. 
*Only for Stage 1 
• 
For Malawi (Stage 2), the participant lives in Blantyre and has agreed to remain in 
Blantyre for the study duration. 

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5.2 
Exclusion Criteria 
Participants will be excluded from the trial if any of the following criteria apply: 
5.2.1 
Medical Conditions 
• 
Known exposure to S. Typhi and nontyphoidal Salmonella confirmed by blood 
culture during the period starting 3 years prior to first study intervention 
administration confirmed using past medical history. 
• 
History of any reaction or hypersensitivity associated with any component of the 
study interventions. 
• 
Any confirmed or suspected immunosuppressive or immunodeficient condition, 
based on medical history and physical examination (no laboratory testing required). 
• 
Acute or chronic, clinically significant pulmonary, cardiovascular, hepatic, or renal 
functional abnormality, as determined by physical examination or laboratory 
screening tests (Appendix 7). 
• 
Recurrent history or uncontrolled neurological disorders or seizures. 
• 
Any clinically significant* hematological and/or biochemical laboratory 
abnormality. 
* The Investigator should use his/her clinical judgment to decide which abnormalities are 
clinically significant from the panel of tests in the list of safety assays (Table 9). 
• 
Clinical conditions representing a contraindication to IM injections and/or blood 
draws. 
• 
Any behavioral or cognitive impairment or psychiatric disease that in the opinion of 
the Investigator, may interfere with the participant’s ability to participate in the 
study. 
• 
Confirmed positive COVID-19 polymerase chain reaction or lateral flow test during 
the period starting 28 days before the first administration of study vaccines (Day −28 
to Day 1). 
• 
Acute or chronic illness which may be severe enough to preclude participation. 
• 
Any other clinical condition that, in the opinion of the Investigator, might pose 
additional risk to the participant due to participation in the study. 
• 
All medical conditions will be assessed by the Investigator who may use his/her 
discretion to decide if the participant meets the exclusion criteria. 
5.2.2 
Prior/Concomitant Therapy 
• 
History of receiving any typhoid vaccine (Ty21a, Vi capsular polysaccharide, or 
TCV) in the participant’s life. 
• 
History of receiving any investigational iNTS or GMMA vaccines in the 
participant’s life. 

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• 
Use of any investigational or non-registered product (drug, vaccine, or medical 
device) other than the study interventions during the period beginning 30 days 
(Days −30 to 1) before the first dose of study interventions, or their planned use 
during the study period. 
• 
A vaccine not foreseen by the study protocol administered during the period starting 
at 14 days before the first dose and ending 28 days after the last dose of study 
interventions administration*, with the exception of flu vaccines or COVID-19 
vaccine. 
*In case emergency mass vaccination for an unforeseen public health threat (eg, a 
pandemic) is recommended and/or organized by public health authorities outside the 
routine immunization program, the time period described above can be reduced if, 
necessary for that vaccine, provided it is used according to the local governmental 
recommendations and that the Sponsor is notified accordingly. 
When regulations allow, the recommended time intervals for administration of these 
vaccines are at least 7 days before or 7 days after (at least 14 days before or 14 days after 
in case of live vaccines) each dose of study intervention administration. 
• 
Administration of long-acting immune-modifying drugs at any time during the study 
period (eg, infliximab). 
• 
Administration of immunoglobulins and/or any blood products or plasma derivatives 
during the period starting 3 months before the administration of the first dose of 
study interventions or planned administration during the study period. 
• 
Chronic administration (defined as more than 14 days in total) of 
immunosuppressants or other immune-modifying drugs during the period starting 
3 months prior to the first study intervention dose(s). For corticosteroids, this will 
mean prednisone equivalent ≥20 mg/day for adult participants. Inhaled and topical 
steroids are allowed. 
5.2.3 
Prior/Concurrent Clinical Study Experience 
• 
Concurrently participating in another clinical trial, at any time during the study 
period, in which the participant has been or will be exposed to an investigational or a 
non-investigational intervention (vaccine and drug). 
5.2.4 
Other Exclusions 
• 
Pregnant or lactating female 
• 
Female planning to become pregnant or planning to discontinue contraceptive 
precautions 

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• 
History of/current chronic alcohol consumption and/or drug abuse. This will be 
decided at the discretion of the Investigator. Chronic alcohol consumption is defined 
as one or more of the following: 
− 
A prolonged period of frequent and heavy alcohol use 
− 
The inability to control drinking once it has begun 
− 
Physical dependence manifested by withdrawal symptoms when the individual 
stops using alcohol 
− 
Tolerance or the need to use increasing amounts of alcohol to achieve the same 
effects 
− 
A variety of social and/or legal problems arising from alcohol use. 
• 
Any study personnel or their immediate dependents, family, or household members. 
5.3 
Lifestyle Considerations 
There are no lifestyle restrictions in this trial. 
5.4 
Screen Failures 
Screen failures are defined as participants who consent to participate in the clinical study 
but are not subsequently randomly assigned to study intervention. A minimal set of 
screen failure information is required to ensure transparent reporting of screen failure 
participants to meet the Consolidated Standards of Reporting Trials publishing 
requirements and to respond to queries from regulatory authorities. Minimal information 
includes demography, screen failure details, eligibility criteria, and any SAE. 
Individuals who do not meet the criteria for participation in this study due to 
hematological/biochemical values out of normal range which are expected to be 
temporary (screen failure) may be rescreened at a later date. Rescreened participants 
should not be assigned the same participant number as for the initial screening. 
Rescreening will follow the same process as the initial screening. 

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5.5 
Criteria for Temporarily Delaying Enrollment/Study Intervention 
Administration 
Enrollment/study intervention administration may be postponed within the permitted time 
interval until transient conditions cited below are resolved: 
• 
Participants with hematological/biochemical values out of normal range (and deemed 
clinically significant by the Investigator) as per the latest available test result, which 
are expected to be temporary may be rescreened/re-dosed at a later date within the 
allowed time interval (The latest laboratory results will be used to assess eligibility 
for second and third study intervention administration). 
• 
Acute disease or fever at the time of enrollment and/or study intervention 
administration.  
• 
Refer to the SoA (Table 1) for definition of fever and preferred location for 
measuring temperature in this study. 
• 
Participants with a minor illness (such as mild diarrhea, mild upper respiratory 
infection) without fever may be enrolled and/or dosed at the discretion of the 
Investigator. 
• 
Use of antipyretics and/or analgesics and/or antibiotics within 3 days prior to study 
intervention administration. 
• 
Participants with a positive COVID-19 test in the 14 days before a planned study 
intervention administration will be allowed to receive the study intervention at least 
14 days after the date of their first positive COVID-19 test. 
6.0 STUDY INTERVENTION AND CONCOMITANT 
THERAPY 
Study intervention is defined as any investigational treatment(s), marketed product(s), 
placebo, or medical device(s) intended to be administered to a participant according to 
the study protocol. 
6.1 
Study Intervention(s) Administered 
Please refer to Table 6 and Table 7. 
 

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Table 6 
Study Interventions Administered (Investigational Vaccines) 
Study 
intervention 
name: 
iNTS-TCV low dose 
iNTS-GMMA low dose 
TCV low 
dose 
iNTS-TCV 
full dose 
iNTS-GMMA full dose 
TCV full 
dose 
Study 
intervention 
formulation: 
Presentation: 
Suspension 
for injection 
(vial) 
Suspension for 
injection (vial) 
Suspension 
for injection 
(vial) 
Suspension 
for injection 
(vial) 
Suspension for 
injection (vial) 
Solution for 
injection 
(vial) 
Suspension for 
injection (vial) 
Suspension for 
injection (vial) 
Suspension 
for injection 
(vial) 
Solution for 
injection 
(vial) 
Type: 
Study 
Study 
Study 
Study 
Study 
Study 
Product 
category: 
Biologic product 
Biologic product 
Biologic 
product 
Biologic 
product 
Biologic product 
Biologic 
product 
Route of 
administration: 
Intramuscular use 
Intramuscular use 
Intramuscular 
use 
Intramuscular 
use 
Intramuscular use 
Intramuscular 
use 
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Study 
intervention 
name: 
iNTS-TCV low dose 
iNTS-GMMA low dose 
TCV low 
dose 
iNTS-TCV 
full dose 
iNTS-GMMA full dose 
TCV full 
dose 
Administration 
site: 
Location: 
Deltoid 
Deltoid 
Deltoid 
Deltoid 
Deltoid 
Deltoid 
Directionality: 
Upper 
Upper 
Upper 
Upper 
Upper 
Upper 
Laterality: 
Random 
Random 
Random 
Random 
Random 
Random 
Number of 
doses to be 
administered: 
3 
3 
3 
3 
3 
3 
Volume to be 
administered: 
Packaging and 
labeling: 
SPM 
Manufacturer: 
GSK 
GSK 
Biological E GSK 
GSK 
Biological E 
Abbreviations: 
; GMMA = generalized modules for membrane antigens; GSK = GlaxoSmithKline Biologicals SA ; 
iNTS-GMMA = invasive nontyphoidal Salmonella-generalized modules for membrane antigens; iNTS-TCV = invasive nontyphoidal Salmonella-typhoid conjugate 
vaccine; 
 ; TCV = typhoid conjugate vaccine 
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Table 7 
Study Interventions Administered (Comparator and Control Vaccines) 
Study intervention 
name: 
Menveo 
Boostrix 
Typhim Vi 
Placebo 
Saline 
Study intervention 
formulation: 
Presentation: 
Powder for 
solution for 
injection (vial) 
Solution for solution for 
injection (vial) 
Suspension for injection (syringe) 
Solution for injection 
(syringe) 
Suspension for 
injection (vial) 
Solution for 
injection 
(ampoule) 
Type: 
Control 
Control 
Control 
Control 
Control 
Product category: 
Biologic product 
Combination product 
Combination product Drug 
Drug 
Route of 
administration: 
Intramuscular use 
Intramuscular use 
Intramuscular use 
Intramuscular use Intramuscular 
use 
Administration site: 
Location: 
Deltoid 
Deltoid 
Deltoid 
Deltoid 
Deltoid 
Directionality: 
Upper 
Upper 
Upper 
Upper 
Upper 
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Study intervention 
name: 
Menveo 
Boostrix 
Typhim Vi 
Placebo 
Saline 
Laterality: 
Random 
Random 
Random 
Random 
Random 
Number of doses to 
be administered: 
1 
1 
1 
3 
3 
Volume to be 
administered: 
Packaging, labeling 
and TM: 
SPM 
Manufacturer: 
GSK 
GSK 
Sanofi Pasteur 
GSK 
Hameln Pharma 
Abbreviations : 
 
 
GSK = GlaxoSmithKline Biologicals SA ; 
 
 
 
 
 
CCI
CCI
CCI

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6.2 
Preparation, Handling, Storage, and Accountability 
The study interventions must be stored in a secured place within the temperature range 
specified on the study intervention’s label. The storage temperature should be 
continuously monitored and recorded with a calibrated (if not validated) temperature 
monitoring device(s). 
Only authorized study personnel should be allowed access to the study interventions. 
Storage conditions will be assessed by a Sponsor’s delegate study contact during prestudy 
activities. Refer to the Study Reference Manual for more details on storage and handling 
of the study interventions. 
6.3 
Measures to Minimize Bias: Randomization and Blinding 
6.3.1 
Participant Identification 
Participant identification numbers will be assigned by the study center sequentially to the 
participants who have consented to participate in the trial, according to the range of 
participant identification numbers allocated to the study center. 
6.3.2 
Intervention Allocation to the Participant 
Allocation of the participant to a study group at the study center will be performed using 
envelopes prior to first study intervention administration, according to a randomization 
schedule generated prior to the study by an independent statistician. 
In Stage 1 (Europe), Step 1, 10 healthy European adults, randomized in a 2:2:1 ratio, will 
receive: 
• 
The low dose of the candidate iNTS-TCV vaccine and concomitant saline to be 
administered in different arms, or 
• 
Separate administration of low doses of iNTS-GMMA and TCV vaccines in different 
arms, or 
• 
Placebo and saline in different arms. 
In Stage 1 (Europe), Step 2, 40 healthy European adults, randomized in a 2:2:1 ratio, will 
receive: 
• 
The full dose of the candidate iNTS-TCV vaccine and concomitant saline to be 
administered in different arms, or 
• 
Separate administration of full doses of iNTS-GMMA and TCV vaccines in different 
arms, or 
• 
Placebo and saline in different arms. 

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In Stage 2 (Africa), a total of 105 healthy African adults, randomized in a 3:3:1 ratio, will 
receive: 
• 
The full dose of the candidate iNTS-TCV vaccine and concomitant saline to be 
administered in different arms, or 
• 
Separate administration of full doses of iNTS-GMMA and TCV vaccines in different 
arms, or 
• 
MenACWY (Menveo) and saline for the first administration, TdaP (Boostrix) and 
saline for the second administration and Typhim Vi and saline for the third 
administration in different arms. 
6.3.3 
Blinding and Unblinding 
Data will be collected in an observer-blind manner. By observer-blind, it is meant that 
during the course of the study, the vaccine recipient and those responsible for the 
evaluation of any study endpoint (eg, safety and reactogenicity) will all be unaware of 
which study intervention was administered. 
To do so, vaccine preparation and administration will be done by authorized medical 
personnel who will not participate in any of the study clinical evaluations. 
The laboratory in charge of the laboratory testing will be blinded to the treatment, and 
codes will be used to link the participant and study (without any link to the treatment 
attributed to the participant) to each sample. 
6.3.3.1 
Emergency Unblinding 
Unblinding a participant’s individual study intervention number should occur ONLY in 
case of a medical emergency when this information is essential for the clinical 
management or welfare of the participant. 
In case of emergency, the Investigator can have unrestricted, immediate, and direct 
access to the participant’s study intervention information via emergency envelopes. 
A physician other than the Investigator (eg, an emergency room physician) or 
participant/participant’s care giver or family member may also request emergency access 
to the participant’s study intervention information either via the Investigator or 
Investigator’s back up (preferred option). 
6.3.3.2 
Unblinding Prior to Regulatory Reporting of SAEs 
GSK policy requires unblinding of any unexpected SAE which is attributable/suspected 
to be attributable to the study intervention(s), prior to regulatory reporting. GSK Global 
Safety is responsible for unblinding the study intervention assignment within the 
timeframes defined for expedited reporting of SAEs. 

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In addition, GSK Global Safety staff may unblind the intervention assignment for any 
participant with a Suspected Unexpected Serious Adverse Reaction (SUSAR) or a SAE 
that is fatal or life-threatening. For SAEs requiring expedited reporting to 1 or more 
regulatory agencies, a copy of the report containing participant’s intervention assignment 
may be sent to investigators in accordance with local regulations and/or GSK policy. 
6.4 
Study Intervention Compliance 
When participants are dosed at the site, they will receive study intervention directly from 
the Investigator or designee, under medical supervision. The date and time when each 
dose is administered in the clinic will be recorded in the source documents. 
6.4.1 
Treatment Strategy 
The clinical staff is responsible for the ongoing safety and wellbeing of the participants 
while they are in the study center. There is a warning system to alert the clinical staff to 
any area in the center where a participant may need medical attention. In the case of an 
emergency, epinephrine, ventilation balloon, and defibrillation material are available on 
site and the site staff is trained on a regular basis in cardiopulmonary resuscitation. There 
is a physician on site during the working hours of the center. Outside working hours, a 
site physician can be reached by phone for medical questions related to the study. In 
addition, if necessary, the clinical staff can contact further on-call physicians or public 
emergencies services in the event of a serious medical event. Equipment and emergency 
drugs are available to treat common medical emergencies that might occur in the 
Phase 1/2a vaccine study. 
Participants will be observed by trained research staff in the research clinic rooms after 
vaccination for at least 60 minutes. This procedure is to mitigate the very low risk of any 
immediate reaction to study intervention administration. In Stage 2 in Malawi, the 3A 
research clinic rooms are situated directly opposite to a respiratory high dependency unit 
at Queen Elizabeth Central Hospital. In the unlikely event that a participant became 
unwell after vaccination, they would be transported to this ward, for treatment and close 
monitoring. The study will also have an emergency/anaphylaxis kit available at the study 
visit clinic room itself, in order to be able to react immediately. A safety information 
leaflet will be provided. 
6.4.2 
Warnings and Precautions 
As this is the first administration of the study intervention to man, all effects cannot be 
reliably predicted. The preclinical data suggest an acceptable safety profile. 
Warnings and precautions to administration of study interventions must be checked at 
each visit with planned administration of study intervention. 
Refer to the approved product label/package insert for marketed products. 

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6.5 
Dose Modification 
Not applicable. 
6.6 
Continuing Access to Study Intervention After the End of the 
Study 
During the study conclusion visit, the Investigator will ask each participant if they are 
interested in participating in a long-term study. If a participant is not interested in joining 
the long-term study, the reason for refusal will be documented, when available, in the 
participant’s eCRF. 
The Investigator is encouraged to share the immunological assay results of 
non-responders with the study participants. 
6.7 
Treatment of Overdose 
Not applicable. 
6.8 
Concomitant Therapy 
At each study visit/contact, the Investigator or his/her delegate should question the 
participant about all medications/products taken, and vaccinations received by the 
participant. 
The following concomitant medication(s)/product(s)/vaccine(s) must be recorded in the 
eCRF: 
• 
All concomitant medication associated with an AE, including vaccines/products, 
except vitamins and dietary supplements, administered after the first dose of study 
intervention (Day 1 to Day 197). 
• 
All concomitant medication leading to discontinuation of the study intervention or 
elimination from the analysis, including products/vaccines. 
• 
All concomitant medication which may explain/cause/be used to treat an SAE 
including vaccines/products (refer to Section 8.3.4). These must also be recorded in 
the Expedited AEs report. For further details related to AEs, please refer to 
Section 8.3 and Appendix 3. 
• 
Prophylactic medication (ie, medication administered in the absence of any symptom 
and in anticipation of a reaction to the vaccination). 
• 
The IQVIA Clinical Research Associate should be contacted if there are any 
questions regarding concomitant or prior therapy. 

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7.0 DISCONTINUATION OF STUDY INTERVENTION 
AND PARTICIPANT 
DISCONTINUATION/WITHDRAWAL 
7.1 
Discontinuation of Study Intervention 
If a participant who does not meet enrollment criteria is inadvertently enrolled, that 
participant must be discontinued from study treatment and the Sponsor or Sponsor 
designee must be contacted. An exception may be granted in rare circumstances for 
which there is a compelling safety reason to allow the participant to continue. In these 
rare cases, the Investigator must obtain documented approval from the Sponsor or 
Sponsor designee to allow the participant to continue in the study. 
In case of premature discontinuation of the study intervention, the primary reason for 
premature discontinuation of the study intervention will be documented on the eCRF as 
follows: 
• 
Adverse event requiring expedited reporting to Sponsor 
• 
Unsolicited non-serious adverse event  
• 
Solicited adverse event 
• 
Not willing to be vaccinated 
• 
Other (specify) 
Participants who discontinue study treatment will not be replaced. 
7.2 
Contraindications to Subsequent Study Intervention(s) 
Administration 
The eligibility for subsequent study intervention administration must be confirmed before 
administering any additional dose. 
Participants who meet any of the criteria listed below or criteria listed in Sections 5.2.1 
and 5.2.2 should not receive additional doses of any study intervention. Such participants 
should be encouraged to continue other study procedures, at the Investigator’s discretion. 
All relevant criteria for discontinuation of study intervention administration must be 
recorded in the eCRF. 
• 
Participants who experience any SAE judged to be possibly or probably related to 
study intervention or non-study concomitant vaccine/product, including 
hypersensitivity reactions. 
• 
Participants who develop any new condition which, in the opinion of the 
Investigator, may pose additional risk to the participant if he/she continues to 
participate in the study. 
• 
Suspected or confirmed anaphylaxis following the administration of study 
intervention(s). 

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• 
Any condition that in the judgment of the Investigator would make intramuscular 
injection unsafe. 
For contraindications to administered marketed study vaccines, refer to their approved 
product label/package insert. 
Please also refer to Appendix 3 for further details about discontinuations due to AEs. 
7.3 
Participant Discontinuation/Withdrawal from the Study 
• 
A participant may withdraw from the study at any time at his/her own request or may 
be withdrawn at any time at the discretion of the Investigator for safety, behavioral, 
compliance, or administrative reasons. 
• 
If the participant withdraws consent for disclosure of future information, the Sponsor 
may retain and continue to use any data collected before such a withdrawal of 
consent. 
• 
If a participant withdraws from the study, he/she may request destruction of any 
samples taken and not tested, and the Investigator must document this in the study 
center study records. 
• 
All data and samples collected up to and including the date of withdrawal of/last 
contact with the participant will be included in the study analyses. 
• 
Participants who are withdrawn from the study because of AEs/SAEs must be clearly 
distinguished from participants who are withdrawn for other reasons. Investigator 
will follow participants who are withdrawn from the study due to an AE/SAE until 
the event is resolved. 
• 
Should a participant request or decide to withdraw from the study, all efforts must be 
made to complete and report the observations as thoroughly as possible up to the 
date of withdrawal. Participants withdrawing due to an AE should be followed up 
according to the follow-up visit. 
• 
Immunogenicity samples should not be taken from participants that are discontinued 
from the study due to AEs or other reason. Safety follow-up should be continued for 
the participants discontinued due to AE. 
• 
Participants who voluntarily withdraw are termed dropouts. Dropouts and 
participants withdrawn due to protocol violations will not be replaced. 
The primary reason for study withdrawal will be documented in the eCRF. 
Adverse events requiring expedited reporting to GSK (refer to the Appendix 3) 
• 
Unsolicited non-serious adverse events 
• 
Solicited adverse event 
• 
Withdrawal by participant, not due to an adverse event* 
• 
Migrated/Moved from the study area 
• 
Lost to follow-up 
• 
Sponsor study termination 

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• 
Other (specify) 
Participants withdrawn due to an AE will not be replaced. 
*If a participant is withdrawn from the study because the participant has withdrawn 
consent and the reason for withdrawal was provided, the Investigator must document this 
reason in the eCRF. 
Participants who are withdrawn from the study because of AEs/SAEs, must be clearly 
distinguished from participants who are withdrawn for other reasons. Investigator will 
follow participants who are withdrawn from the study due to an AE/SAE until the event 
is resolved. 
7.4 
Lost to Follow-up 
A participant will be considered lost to follow-up if he or she repeatedly fails to return for 
scheduled visits and is unable to be contacted by the study center. 
The following actions must be taken if a participant fails to return to the clinic for a 
required study visit: 
• 
The study center must attempt to contact the participant and reschedule the missed 
visit as soon as possible and counsel the participant on the importance of maintaining 
the assigned visit schedule and ascertain whether or not the participant wishes to 
and/or should continue in the study. 
• 
Before a participant is deemed lost to follow-up, the Investigator or designee must 
make every effort to regain contact with the participant (where possible, 3 telephone 
calls and, if necessary, a certified letter to the participant’s last known mailing 
address or local equivalent methods). These contact attempts should be documented 
in the participant’s medical record. 
• 
Should the participant continue to be unreachable, he/she will be considered to have 
withdrawn from the study. 
8.0 STUDY ASSESSMENTS AND PROCEDURES 
Protocol waivers or exemptions are only permitted when necessary for the management 
of immediate safety concerns for the participant. 
Immediate safety concerns should be discussed with the Sponsor as soon as they occur or 
when the study team becomes aware of them. The purpose of this communication is to 
determine if the participant(s) should discontinue the study intervention. 
Study procedures and their timing are summarized in the SoA (refer to Section 1.3). 
All screening evaluations must be completed, and the results reviewed before confirming 
that potential participants meet all eligibility criteria. 

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The Investigator will maintain a log of all participants screened. All relevant information, 
such as confirmation of eligibility and reasons for screening failure will be mentioned in 
this screening log. 
The Study Reference Manual provides the Investigator and study center personnel with 
detailed administrative and technical information that does not impact the participant 
safety. 
8.1 
Immunogenicity Assessments 
8.1.1 
Biological Samples 
Biological samples will be used for research planned in the protocol and for purposes 
related to the improvement, development and quality assurance of the laboratory tests 
described in this protocol or in future protocols part of the same development plan. The 
details of samples for immunogenicity assessments are shown in Table 8. 
Findings in this or future studies may make it desirable to use samples acquired in this 
study for research not planned in this protocol. In this case, all participants in countries 
where this is allowed will be asked to give consent to allow GSK or a contracted partner, 
to use the samples for further research. The further research will be subjected to prior 
Institutional Review Boards (IRB)/Independent Ethics Committees (IEC) approval, if 
required by local legislation. 
Information on further research and its rationale can be obtained from GSK. 
Sample testing will be done in accordance with the recorded consent of the individual 
participant. No immunogenicity sample should be taken from participants that are 
discontinued or withdrawn from the study due to AEs or other reason. 
By default, collected samples will be stored for a maximum of 20 years. This storage 
period begins when the last participant performs the last study visit. This timeline can be 
adapted based on local laws, regulations or guidelines requiring different timeframes or 
procedures. In all cases, the storage period should be aligned with participant’s consent. 
These additional requirements must be formally communicated to, discussed, and agreed 
with GSK. 

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Table 8 
Biological Sample 
Sample type  
Quantity  
Unit  Time 
point  
Participants sampled 
Blood for 
serum 
preparation 
 
Approximately 10 mL/Visit for 
antibody determination; approximately 
15 mL/Visit for safety screening; up to 
10 mL/Visit for pre/post-vaccination 
safety assays 
mL 
As 
scheduled 
(refer to 
Figure 1 
and Table 
1) 
All participants in 
Stage 1 and Stage 2 
Approximately 20 mL/Visit for assay 
development 
 
 
Only participants in 
Stage 1 who have 
given specific consent 
for this collection 
 
 
Blood for 
PBMC 
preparation 
Approximately 50 mL/Visit for PBMC 
extraction for monoclonal antibodies 
generation 
All participants in 
Stage 2 
Abbreviation: PBMC = peripheral blood mononuclear cells 
8.1.2 
Laboratory Assays 
All laboratory testing will be performed using characterized and fit-for-purpose qualified 
assays as indicated in Table 9 at GVGH laboratory or in a laboratory designated by 
GVGH. 

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Table 9 
Laboratory Assays 
Assay type 
System 
Sampling time points 
Component 
Method 
Unit of 
measure 
Number of 
participants 
Humoral 
Immunity 
(Antibody 
determination) 
Serum 
Stage 1 
Days 1, 29, 57, 85, 169 and 
197 
Stage 2 
Days 1, 29, 57, 85, 169 and 
197 
Anti-S. Typhi Vi Ag total IgG 
ELISA 
EU/mL# 
50 (Stage 1) 
105 (Stage 2) 
Anti-S. Typhimurium O Ag total IgG 
EU/mL 
Anti-S. Enteritidis O Ag total IgG 
EU/mL 
Clinical Safety 
 
Whole 
blood 
Screening: Day -28 to 
Day -1 
Stage 1 
Days 1, 8, 29, 57, 64, 85, 
169, 176 and 197 
Stage 2 
Days 1, 8, 29, 57, 64, 85, 
169, 176 and 197 
 
Leukocytes (white blood cells) 
  Eosinophils 
  Basophils 
  Neutrophils 
  Monocytes 
  Lymphocytes 
Erythrocytes (red blood cells)s 
  Hemoglobin 
  Hematocrits 
  Platelets 
  Prothrombin times, ** 
Hematology 
panel 
 
155 (Screening) 
50 (Stage 1) 
105 (Stage 2) 
Serum/ 
whole 
blood 
Screening: Day -28 to 
Day -1 
Stage 1 
Total bilirubins 
Aspartic Aminotransferase 
Alanine Aminotransferase 
γ-Glutamyl Transferases 
Biochemistry 
 
155 (Screening) 
50 (Stage 1) 
105 (Stage 2) 
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Assay type 
System 
Sampling time points 
Component 
Method 
Unit of 
measure 
Number of 
participants 
Days 1, 8, 29, 57, 64, 85, 
169, 176 and 197 
Stage 2 
Days 1, 8, 29, 57, 64, 85, 
169, 176 and 197 
Lactic Dehydrogenases 
Alkaline Phosphatases 
Total Proteinss 
Glycosylated hemoglobin (HbA1c)s 
Urea/Blood Urea Nitrogen 
Creatinine 
Sodiums 
Potassiums 
Serum 
Screening: Day -28 to 
Day -1 
HBsAg 
HCV antibodies 
HIV antibodies 
Serology for 
virology 
 
155 (Screening) 
 
Urine 
Screening: Day -28 to 
Day -1 
Stage 1: Days 1, 57 and 169 
Stage 2: Days 1, 57 and 169 
Human chorionic gonadotropin 
Pregnancy 
test 
 
NK (Stage 1) 
NK (Stage 2) 
Urine 
Screening 
Urinalysis 
Dipstick 
 
155 (Screening) 
Serum 
Screening 
Human leukocyte antigen B27* 
PCR 
 
50 (Stage 1, Screening) 
Abbreviations: Ab = Antibody; 
; IgG = Immunoglobulin G; EU = ELISA Units; ELISA = enzyme-linked immunosorbent assay; 
GVGH = GlaxoSmithKline Biological SA Vaccines Institute for Global Health; HBsAg = hepatitis B surface antigen; HCV = hepatitis C virus; HIV = human 
immunodeficiency virus; NK = Not Known; PCR = polymerase chain reaction; S = test performed only during Screening period; 
; 
 
# The IgG against Vi antigen will be determined using GVGH ELISA and the results will be presented in EU/mL unit, which may be further converted to µg/mL, 
based on correlation with concentration of the standard calibrated against the international standard/another standard already calibrated. 
* The assay will be performed by the site laboratory, or a laboratory designated by the site. In case of participant rescreening, this test should not be repeated since the 
result is not expected to change in the participant lifetime. 
**Prothrombin time will only be applicable for Stage 1 participants. 
 
CCI
CCI
CCI

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8.2 
Safety Assessments 
The primary safety endpoints will assess the occurrence of laboratory abnormal values, 
solicited administration site and systemic events 7 days following each study intervention 
administration, unsolicited AEs which occur within 28 days after each study intervention 
administration and SAEs throughout the study duration. The occurrence of withdrawals 
due to AEs will also be assessed throughout the study duration. Currently, there are no 
AEs of special interest foreseen in this study. 
Grading of laboratory values will be based on the US Food & Drug Administration 
Guidance for Industry “Toxicity Grading Scale for Healthy Adults and Adolescent 
Volunteers Enrolled in Preventive Vaccine Clinical Trials” [US Department of Health 
and Human Services, 2007] and Division of AIDS Table for Grading the Severity of 
Adult AEs [US Department of Health and Human Services, 2017]. Refer to Appendix 7. 
Planned time points for all safety assessments are provided in the SoA (Table 1). 
8.2.1 
Pre-intervention Administration Procedures 
8.2.1.1 
Collection of Demographic Data, Medical/Vaccination History, and 
Physical Examination 
Demographic data such as age in years, sex, and race (ethnic background) will be 
collected from each participant. Collection of sex and race (ethnic background) data is 
necessary to assess and monitor the diversity of the trial participants, and to determine if 
the trial participants are truly representative of the impacted population and the impact of 
race (ethnic background) on the trial endpoints. Medical history should be collected, and 
it should be verified that none of exclusion criteria related to medical and vaccination 
history (refer to Section 5.2) are met. Vaccine history will be recorded for each 
participant. Physical examination will be performed for each participant. Physical 
examination includes assessment of body temperature (axillary) and resting vital signs 
(systolic/diastolic blood pressure, heart rate, and respiratory rate). On days of 
vaccination, body temperature and vital signs will be measured before and 60 minutes 
after vaccination. If the Investigator determines that the participant’s health on the day of 
the study intervention administration temporarily precludes dosing, the visit will be 
rescheduled. 
8.2.1.2 
Pregnancy 
• 
Details of all pregnancies in female participants will be collected after the start of 
study treatment and 1 month after completion of the last study intervention 
administration. 

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• 
If a pregnancy is reported, the Investigator should inform the Sponsor within 
24 hours of learning of the pregnancy and should follow the procedures outlined in 
Appendix 4. 
• 
Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, 
congenital anomalies, ectopic pregnancy) are considered SAEs. 
Generally, follow-up will be no longer than 6 to 8 weeks after the estimated delivery 
date. Pregnancy termination will be reported regardless of fetal status (presence or 
absence of anomalies) or indication for procedure. 
8.2.2 
Clinical Safety Laboratory Assessments 
All laboratory testing will be performed at GVGH laboratory or in a laboratory 
designated by GVGH. Please refer to Table 9 for the list of clinical laboratory safety 
assessments required by the protocol. 
The Investigator may perform additional tests, if considered essential for the participant’s 
safety. 
8.3 
Adverse Events 
The definitions of an AE or SAE can be found in Appendix 3. 
Adverse events will be reported by the participant (or, when appropriate, by a caregiver, 
surrogate, or the participant's legally authorized representative). 
The Investigator and any designees are responsible for detecting, documenting, and 
recording events that meet the definition of an AE or SAE and remain responsible for 
following up AEs that are serious, considered related to the study treatment or study 
procedures, or that caused the participant to discontinue the study intervention (refer to 
Section 7.0). For further details, please refer to Appendix 3. 
8.3.1 
Time Period and Frequency for Collecting AE and SAE Information 
The definition of an AE or SAE are provided in Appendix 3. All initial SAEs will be 
recorded and reported to the Sponsor or designee immediately, without undue delay but 
not later than within 24 hours of obtaining knowledge, as indicated in Appendix 3. The 
SAEs will be reported for every participant throughout the study until study end 
(Day −28 to Day 337). 
The Investigator or designee will record and immediately report all SAEs in screened and 
enrolled participants to the Sponsor or designee via the Expedited AE Reporting Form. 
Reporting should, under no circumstances, occur later than 24 hours after the Investigator 
becomes aware of an SAE. The Investigator will submit any updated SAE data to the 
Sponsor within 24 hours of it being available. 

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Investigators are not obligated to actively seek AE or SAE after conclusion of the study 
participation. However, if the Investigator learns of any SAE, including a death, at any 
time after a participant has been discharged from the study, and he/she considers the 
event to be reasonably related to the study treatment or study participation, the 
Investigator must promptly notify Sponsor or Sponsor’s delegate. 
8.3.2 
Method of Detecting AEs and SAEs 
The methods for detecting and recording AEs and SAEs, and the assessment of AE/SAE 
intensity, causality, and outcome are provided in Appendix 3. 
Care will be taken not to introduce bias when detecting AEs and/or SAEs. Open-ended 
and non-leading verbal questioning of the participant is the preferred method to inquire 
about AE occurrences. 
After the initial AE/SAE report, the Investigator is required to proactively follow each 
participant at subsequent visits/contacts. All SAEs will be followed until resolution, 
stabilization, the event is otherwise explained, or the participant is lost to follow-up. 
Further information on follow-up procedures is given in Appendix 3. 
8.3.2.1 
Clinically Significant Abnormal Laboratory Findings 
The Investigator must review the laboratory report, document that he/she did so, and 
record any clinically relevant changes occurring during the study in the AE section of the 
eCRF. Clinically significant abnormal laboratory findings are those which are not 
associated with an underlying disease, unless judged by the Investigator to be more 
severe than expected for the participant's condition. 
All clinically significant abnormal laboratory test values reported during the study will be 
repeated until the values return to normal/baseline, or until they are no longer considered 
significantly abnormal by the Investigator. 
If such values do not return to normal/baseline after an interval judged reasonable by the 
Investigator, the etiology of the abnormal value should be identified, and the Sponsor 
notified. 
8.3.3 
Regulatory Reporting Requirements for SAEs 
Once the Investigator or designee becomes aware that a study participant has experienced 
an SAE, they or designated study staff must report it to Sponsor’s delegate immediately, 
no later than 24 hours of obtaining knowledge, using an electronic Expedited AE Report 
in the eCRF. The Investigator will provide an assessment of causality at the time of the 
initial report, as defined in the Appendix 3. New or updated information will be recorded 
on the originally completed form with all changes signed and dated by the Investigator 
and reported to IQVIA within 24 hours. This is essential for meeting GSK legal 

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obligations and ethical responsibilities for the participant’s safety and the safety of a 
study intervention under clinical investigation. 
For COVID-19-related SAEs, reports should be submitted following routine procedures 
for SAEs. Local regulatory requirements and GSK’s policy for the preparation of an 
Investigator safety report for SUSARs must be followed. These reports will be forwarded 
to investigators as necessary. 
GSK has a legal responsibility to notify both the local regulatory authority and other 
regulatory agencies about the safety of a study intervention under clinical investigation. 
GSK and IQVIA will comply with country-specific requirements related to safety 
reporting to the regulatory authority, IRB, and investigators. 
8.3.4 
Treatment of Adverse Events 
Any medication administered for the treatment of an SAE should be recorded in the 
Expedited AE Report. 
8.3.5 
Solicited Adverse Events 
The solicited administration site and systemic events that will be collected during the 
7-day follow-up period after each administration (ie, from Day 1 to Day 7, from Day 57 
to Day 63, and from Day 169 to Day 175) are presented in Table 17. 
The intensity of the solicited AEs will be assessed as described in Table 18. 
8.3.6 
Participant Card 
The Investigator or Investigator’s designee must provide the participants with a 
“participant card” containing information about the clinical study. The participants will 
be instructed to keep the participant card in their possession at all times throughout the 
study. In an emergency, this card serves to inform the responsible attending 
physician/family member that the participant is in a clinical study and that relevant 
information may be obtained by contacting the Investigator or his/her backup. 
8.3.7 
Medical Device Deficiencies 
Some of the comparator control vaccines used in this study are combination products 
constituted of a biologic product in a medical device (pre-filled syringes). Refer to 
Appendix 1 for the definition of combination product and medical device deficiency and 
Appendix 6 for further details. 

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8.3.7.1 
Detection, Follow-up, and Prompt Reporting of Medical Device 
Deficiency 
The Investigator is responsible for the detection, documentation, and prompt reporting of 
any medical device deficiency occurring during the study to Sponsor or Sponsor’s 
delegate. This applies to any medical device provided for the conduct of the study. 
Device deficiencies will be reported to Sponsor or Sponsor’s delegate within 24 hours 
after the Investigator determines that the event meets the protocol definition of a device 
deficiency. 
The Investigator will ensure that follow-up includes any additional investigations to 
elucidate the nature and/or related of the device deficiency to the incident. Follow-up 
applies to all participants, including those who discontinue study intervention or the 
study. 
New or updated information will be recorded on the originally completed form with all 
changes signed and dated by the Investigator and reported to Sponsor or Sponsor’s 
delegate within 24 hours. 
Medical device deficiencies and any associated AE/SAEs for associated person (ie, 
spouse, caregiver, site staff) will also be collected. The associated person will be 
provided with a safety reporting information and authorization letter. 
Follow-up applies to all participants, including those who discontinue study intervention 
or the study, and associated persons. 
8.3.7.2 
Regulatory Reporting of Medical Device Deficiency When Used as 
Combination Product 
The Investigator will promptly report all device deficiencies occurring with any medical 
device provided for use in the study to Sponsor or Sponsor’s delegate. Sponsor or 
Sponsor’s delegate has a legal responsibility to notify appropriate regulatory authorities 
and other entities about safety information linked to medical devices being used in 
clinical studies. 
The Investigator, or responsible person according to local requirements (eg, the head of 
the medical institution), will comply with the applicable local regulatory requirements 
relating to the reporting of device deficiencies to the IRB/IEC. 
8.4 
Pharmacokinetics and Pharmacodynamics 
Pharmacokinetics and pharmacodynamic parameters are not evaluated in this study. 

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8.5 
Study Procedures During Special Circumstances 
During special circumstances (eg, COVID-19 pandemic), the specific guidance from 
local public health and other competent authorities regarding the protection of 
individuals’ welfare must be followed. For the duration of such special circumstances, the 
following measures may be implemented for enrolled participants: 
• 
Safety follow-up may be made by a phone call, other means of virtual contact, or 
home visit, if appropriate. 
• 
Visits for suspected AEs may take place in a different location* other than the study 
center or at participant’s home. If this is not feasible, then the medical evaluation of 
AEs may take place through remote visit with documentation of symptoms by other 
means of communication (eg, phone call or videoconference), if possible. Refer to 
Appendix 1 for the definition of remote visit. 
• 
Biological samples may be collected at a different location* other than the study 
center or at participant’s home. Biological samples should not be collected if they 
cannot be processed in a timely manner or appropriately stored until the intended 
use. 
• 
COVID-19 test will be performed pre and post-study intervention administration on 
participants with symptoms or clinical suspicion of COVID-19, as per the 
Investigator’s discretion. 
*Note: It is the Investigator’s responsibility to identify an alternate location. The 
Investigator should ensure that this alternate location meets ICH GCP requirements, such 
as adequate facilities to perform study procedures, appropriate training of the staff, and 
documented delegation of responsibilities in this location. This alternate location may 
need to be covered by proper insurance for the conduct of study on participants by 
Investigator and study center staff other than the designated study center. 
8.6 
Genetic Testing 
Based on advice from Belgian CA (FAHMP), to minimize any risk of autoimmune 
reactions, and spondyloses specifically, blood samples collected for safety during 
Screening in stage 1 will undergo sampling for HLA-B27 genetic marker and only 
prospective participants who are found to be negative for HLA-B27 will be included in 
the study [McColl, 2000; Ekman, 2000; Zeidler, 2021]. Refer to Appendix 5 for details. 
9.0 STATISTICAL CONSIDERATIONS 
9.1 
Statistical Hypotheses 
No formal statistical hypotheses are to be tested. 

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9.2 
Sample Size Determination 
A total of 155 participants are planned to be randomized to achieve at least 133 evaluable 
participants in the Per Protocol analysis set for immunogenicity, assuming a 12% dropout 
rate for each group. Participants who withdraw from the study will not be replaced. 
No confirmatory objectives are planned in this trial; however, the sample size was chosen 
to allow an exploratory comparison of immunogenicity 28 days after the third 
administration in Stage 2 (Day 197), between participants receiving full dose of candidate 
iNTS-TCV vaccine and separate full doses of iNTS-GMMA and TCV vaccines, with 
respect to Anti-S. Typhi Vi Ag total IgG, Anti-S. Typhimurium O Ag total IgG, 
Anti-S. Enteritidis O Ag total IgG. 
9.3 
Populations for Analyses 
For purposes of analysis, the analysis sets in Table 10 are defined. 
Table 10 
Analysis Sets 
Analysis Set 
Description 
Enrolled Set  
Participants who were randomized or received study intervention or 
underwent a post-screening procedure. Note that as per Good Clinical 
Practice, an enrolled participant should have completed the informed 
consent process and participants should be eligible before initiating 
any study procedure. The allocation in a group is based on the 
administered intervention. 
Exposed Set (ES) 
All participants who received at least 1 dose of the study intervention. 
The allocation in a group is based on the administered intervention. 
Full Analysis Set (FAS) 
All participants who received at least 1 dose of the study intervention 
and have post-dose immunogenicity data. The allocation in a group is 
based on the randomized intervention. The FAS for immunogenicity 
will be defined by time point. 
Per Protocol Set (PPS) 
All eligible participants who received all doses as per protocol, had 
immunogenicity results post-dose, complied with dosing/blood draw 
intervals, without intercurrent conditions that may interfere with 
immunogenicity and without prohibited concomitant 
medication/vaccination. The PPS for immunogenicity will be defined 
by time point. 
Unsolicited Safety Set 
All participants who received at least 1 dose of the study intervention 
(ES) that report unsolicited adverse events (AEs)/report not having 
unsolicited AEs. The allocation in a group is based on the 
administered intervention. 
Solicited Safety Set 
All participants who received at least 1 dose of the study intervention 
(ES) who have solicited safety data. The allocation in a group is based 
on the administered intervention. 
If the participant meets one of the criteria mentioned below or ones listed in the 
Section 7.2, he/she may be eliminated from per protocol analysis. 

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• 
Use of any investigational or non-registered product (drug or vaccine) other than the 
study vaccine(s) used during the study period. 
• 
Use of immunosuppressants or other immune-modifying drugs administered 
chronically (ie, more than 14 days in total) during the study period. For 
corticosteroids, this will mean prednisone 20 mg/day (for adult participants), or 
equivalent. Inhaled and topical steroids are allowed. 
• 
Use of any long-acting immune-modifying drugs administered at any time during the 
study period (eg, infliximab). 
• 
Use of any vaccine not foreseen by the study protocol administered during the entire 
period of participant’s study participation, with the exception of flu vaccines, 
COVID-19 vaccines, and vaccines administered routinely according to the national 
immunization program. 
• 
Use of any Immunoglobulins and/or any blood products administered during the 
study period. 
• 
Any drug and/or alcohol abuse. 
• 
Occurrence of a condition that has the capability of altering their immune response 
(ie, varicella) or are confirmed to have an alteration of their initial immune status. 
• 
Occurrence of a serious chronic or progressive disease according to judgment of the 
Investigator (eg, neoplasm, insulin dependent diabetes, cardiac, renal, or hepatic 
disease). 
• 
Occurrence of any malignancy or lymphoproliferative disorder. 
• 
Occurrence of any confirmed or suspected immunosuppressive or immunodeficient 
condition, based on physical examination. 
• 
Unblinding after any study intervention has been performed. 
• 
Other details to be included in the Statistical Analysis Plan. 
9.4 
Statistical Analyses 
The Statistical Analysis Plan will be developed and finalized before database lock and 
will describe the participant analysis sets to be included in the analyses, and procedures 
for accounting for missing, unused, and spurious data. This section is a summary of the 
planned statistical analyses of the primary and secondary endpoints. 
9.4.1 
Primary Endpoints 
The analysis on primary objective will be based on the Solicited, Unsolicited, and 
Exposed Sets, as indicated in Table 11. 

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Table 11 
Primary Endpoints-Statistical Analyses 
Endpoint 
Statistical Analysis Methods 
Primary 
safety 
• 
The number and percentage of participants with at least 1 solicited 
administration site and systemic event during the 7-day follow-up period will 
be tabulated by group after each study intervention administration and 
overall. The same calculations will be performed for symptoms rated as 
Grade 3. 
• 
The number and percentage of participants with at least 1 unsolicited adverse 
event (AE) during the 28-day follow-up period will be tabulated by group 
after each study intervention administration and overall. The same 
calculations will be performed for symptoms rated as Grade 3. 
• 
The percentage of doses associated with at least 1 solicited administration 
site and systemic event during the 7-day follow-up period will be tabulated 
for the overall administration course. The same calculations will be 
performed for symptoms rated as Grade 3. 
• 
The percentage of doses associated with at least 1 unsolicited AE during the 
28-day follow-up period will be tabulated for the overall administration 
course. The same calculations will be performed for symptoms rated as 
Grade 3. 
• 
The number and percentage of participants reporting each individual solicited 
administration site (ie, injection site pain, erythema [redness], swelling) and 
systemic event (ie, fever [temperature ≥38.0°C], headache, myalgia, 
arthralgia, fatigue; any Grade and Grade 3) during the 7-day solicited 
follow-up period after each study intervention administration and by group 
will be tabulated. The percentage of doses associated with each individual 
solicited administration site and systemic event will be tabulated for the 
overall administration course. 
• 
Occurrence of fever will be reported as number and percentages of 
participants reporting temperature ≥38°C in 0.5°C cumulative increments 
during the 7-day follow-up period. This will be tabulated for each group after 
each dose. 
• 
The number and percentage of participants with at least 1 reported 
unsolicited AE during the 28-day follow-up period after each study 
intervention administration and by group, as classified by the Medical 
Dictionary for Regulatory Activities (MedDRA) preferred term, by system 
organ class and by group will be tabulated. The same tabulation will be 
performed for Grade 3 unsolicited AEs and for unsolicited AEs according to 
relationship to study intervention administration. 
• 
The number and percentage of participants reporting serious AEs (SAEs) and 
AEs/SAEs leading to withdrawal from the study and/or withholding doses of 
study intervention, collected from first study intervention administration up 
to 28 days after third study intervention administration (Day 1 to Day 197) 
will be tabulated. The detailed listings will also be produced. 
• 
For each group, for hematological, renal, and hepatic panel test results at 
7 days after each study intervention administration (Day 8, Day 64, and 
Day 176) and at 28 days after each study intervention administration 
(Day 29, Day 85, and Day 197), and for other tests at baseline: 
- 
The percentage of participants having hematological, renal, and hepatic 
results below or above the laboratory normal ranges will be tabulated by 
time point. 

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Endpoint 
Statistical Analysis Methods 
- 
The maximum Grade from Day 1 until the end of the participant’s 
participation will be tabulated. 
The verbatim reports of unsolicited symptoms will be reviewed by a physician and the 
signs and symptoms will be coded according to the MedDRA Dictionary for AE 
Terminology. 
9.4.2 
Secondary Endpoints 
The analysis on secondary objectives will be based on the Per Protocol Set (PPS) for 
immunogenicity, as shown in Table 12. If, in any study group and at any time point, the 
percentage of vaccinated participants with serological results excluded from the PPS for 
analysis of immunogenicity is 10% or more, a second-line analysis based on the Full 
Analysis Set (FAS) for immunogenicity will be performed to complement the PPS 
analysis. 
Table 12 
Secondary Endpoints-Statistical Analyses 
Endpoint 
Statistical Analysis Methods 
Secondary 
immunogenicity 
For each study group with participants in Europe, for each sampling time point, and 
for each antigen*, the following statistics will be computed: 
• 
Unadjusted GMCs with 95% CI of anti-serotype specific IgG* before and 
28 days after each study intervention administration as measured by 
in-house ELISA. 
• 
Unadjusted within-participant GMRs with 95% CI at 28 days after each 
study intervention administration compared to each study intervention 
administration baseline of anti-serotype specific IgG* as measured by 
in-house ELISA. 
• 
The number and percentage of participants with at least a 4-fold increase in 
Anti-serotype specific IgG* antibody concentration 28 days after each 
study intervention administration compared to first study intervention 
administration baseline, with 95% CI as measured by in-house ELISA. 
• 
The number and percentage of participants with Anti-S. Typhi Vi Ag IgG 
antibody concentrations equivalent to ≥4.3 µg/mL, before and 28 days after 
each study intervention administration, with 95% CI as measured by 
in-house ELISA. 
• 
Unadjusted between-group ratio of GMC with 95% CI between iNTS-TCV 
groups and iNTS-GMMA and TCV groups will be computed for each 
anti-serotype specific IgG*, visit, and administration. 
For each study group with participants in Africa, for each sampling time point, and 
for each antigen*, the following statistics will be computed: 
• 
Unadjusted GMCs with 95% CI of anti-serotype specific IgG* before and 
28 days after each study intervention administration as measured by 
in-house ELISA. 
• 
Unadjusted within-participant GMRs with 95% CI at 28 days after each 
study intervention administration compared to each study intervention 
administration baseline of anti-serotype specific IgG* as measured by 
in-house ELISA. 

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Endpoint 
Statistical Analysis Methods 
• 
The number and percentage of participants with at least a 4-fold increase in 
Anti-serotype specific IgG* antibody concentration 28 days after each 
study intervention administration compared to first study intervention 
administration baseline, with exact 95% CI as measured by in-house 
ELISA. 
• 
The number and percentage of participants with Anti-S. Typhi Vi Ag IgG 
antibody concentrations equivalent to ≥4.3 µg/mL, before and 28 days after 
each study intervention administration, with 95% CI as measured by in-
house ELISA. 
• 
Unadjusted between-group ratio of GMC with 95% CI between iNTS-TCV 
groups and iNTS-GMMA and TCV groups will be computed for each 
anti-serotype specific IgG*, visit, and administration. 
* Anti-S. Typhi Vi Ag total IgG, Anti-S. Typhimurium O Ag total IgG, 
Anti-S. Enteritidis O Ag total will be tested. 
The GMCs, GMRs, and ratio of GMC along with 95% CIs will be obtained by 
exponentiating (base 10) the means and the lower and upper limits of the 95% CIs of 
the log-transformed values (base 10). 
For the between-group assessments, the ANOVA model will be fitted based on the 
participants having a result at both the baseline and the considered time point. 
Immunogenicity data from full dose group in Europe will be pooled with those from 
full dose group in Africa if p-value associated to parameter for Center*Treatment 
interaction from ANOVA model ≥0.10 (ie, suggesting that impact of treatment on 
immunogenicity endpoint does not depend on center). 
In that case, GMC, GMRs, and ratio of GMC will be calculated for entire full dose 
group (ie, Europe + Africa) adjusted by center. ANOVA model will include both 
vaccine group and center group as fixed effects, and adjusted GMC, GMRs, and 
ratio of GMC will be derived by exponential transformation of the corresponding 
group contrast in the model. 
A sensitivity analysis will be performed pooling Europe and Africa data and 
adjusting treatment effect for center variable, regardless of the center*treatment 
associated p-value. 
A second sensitivity analysis will be performed pooling Europe and Africa and 
adjusting treatment effect for race variable. 
Finally, subgroup analysis will be performed by race. 
Secondary 
Safety 
The number and percentage of participants reporting SAEs from 28 days after third 
study intervention administration (Day 197) up to Day 337 will be tabulated by 
study intervention group in Stage 1/Stage 2. 
Number of participants with AEs/SAEs leading to withdrawal from the study, from 
28 days after third study intervention administration (Day 197) up to Day 337, by 
study intervention group in Stage 1/Stage 2. 
Abbreviations: Ag = Antigen; ANOVA = analysis of variance; CI = confidence intervals; 
ELISA = enzyme-linked immunosorbent assay; GMC = geometric mean concentrations; GMR = geometric 
mean ratios; iNTS-GMMA = invasive nontyphoidal Salmonella-generalized modules for membrane 
antigens; iNTS-TCV = invasive nontyphoidal Salmonella-typhoid conjugate vaccine; SAE = serious 
adverse event; S. Typhi = Salmonella Typhi; S. Typhimurium = Salmonella Typhimurium; TCV = typhoid 
conjugate vaccine 

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9.4.3 
Tertiary Endpoints 
The analysis on tertiary objective will be based on the PPS for immunogenicity, as 
described in Table 13. If, in any study group and at any time point, the percentage of 
vaccinated participants with serological results excluded from the PPS for analysis of 
immunogenicity is 10% or more, a second-line analysis based on the FAS for 
immunogenicity will be performed to complement the PPS analysis. 
Table 13 
Tertiary Endpoints-Statistical Analyses 
CCI

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9.5 
Missing Data 
Data from participants who withdraw from the study, including AEs and any follow-up, 
will be included in the analyses of primary, secondary, and tertiary outcomes. Missing 
data will not be imputed. 
9.6 
Interim Analyses 
A group-unblinded interim analysis for immunogenicity will be performed 28 days after 
the second administration in all study participants in Stage 2 in order to support the 
preparation for future studies. 
9.6.1 
Sequence of Analyses 
All analyses before unblinding will be conducted on data as clean as possible. 
The sequence of interim and final analyses will be the following: 
a. 
A group-unblinded interim analysis will be performed for all immunogenicity data 
accumulated up to 28 days after second intervention (Day 85) administration in 
Stage 2. At this point, the statistician will be unblinded for the analysis (ie, will have 
access to individual participant treatment assignments). The remaining study 
personnel will stay blinded (ie, will not have access to the individual participant 
treatment assignment) until Day 197. It is possible however, due to limited sample 
size, that unblinding occurs for a few participants having as specific AE or SAE (eg, 
an AE/SAE occurring only in a single group). Therefore, anyone having access to the 
analysis of Day 85 could become unblinded regarding those specific cases. The study 
will be considered as a single-blind from this point onwards. Results from 
immunogenicity analysis in Stage 2, and if applicable, in participants receiving the 
full dose in Stage 1/Step 2 will help with the design and approach in subsequent 
studies. No individual listings or data with the participants identifying information 
will be disseminated. The investigators and the participants will not have access to 
the treatment allocation up to study end (Day 337). 
b. After unblinding of the Sponsor personnel (partial observer-blind), an analysis on all 
data up to and including Day 197 (Visit 9) will be performed and individual listings 
will be generated. Data collected during the extended safety follow-up period will be 
analyzed after Day 337. 
c. 
A final CSR will be produced after the analysis after Visit 9 in Stage 2 and the 
analysis after Day 337 will be included in an integrated CSR to be written after. 

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9.6.2 
Statistical Considerations 
Comparative analyses will be exploratory and should be interpreted with caution 
considering that there is no adjustment for multiplicity and that the study is not powered 
for such comparisons. 
9.7 
Internal Safety Review Committee 
An iSRC will be established to monitor the safety of participants throughout the trial and, 
more specifically, to recommend whether proceeding from low dose in Stage 1/Step 1 to 
the full dose in Stage 1/Step 2 is permissible, based on the accumulated safety data. They 
will also recommend proceeding the clinical testing of the vaccine in African participants 
in Stage 2 based on the post-primary safety results in Stage 1 (iSRC #3). The iSRC will 
include study-independent GSK members and an external, non-GSK clinical 
development expert to ensure an unbiased assessment. 
Planned safety data reviews are specified in Figure 1 and in Table 14. After the reviews, 
if no safety signal is observed, the favorable outcome of the safety evaluations will be 
documented and provided in a written way, authorizing the Investigator to start the 
administration of the subsequent dose of study intervention to participants, as well as 
enrollment and study intervention administration to the remaining participants in the next 
step of the study, as described in the protocol. If a safety signal is observed during the 
safety evaluations or if any of the holding rules are met, the iSRC Chair (or his/her 
representative) is responsible for the urgent communication to GVGH PP, including the 
rationale for the decision to put the study intervention administration on hold or not. 
The IQVIA study project lead will be accountable for notifying all investigators of the 
decision whether to suspend, modify or continue the conduct of the study on all groups or 
on selected groups. 
In Stage 1/Step 1, there will be a sequential approach in which the 10 sentinel participants 
will receive the first low dose of the study interventions on consecutive days. The 
sentinel participants will receive a safety phone call for safety surveillance on the day 
following first study intervention administration (Day 2), before proceeding with 
administration of study intervention in subsequent participants. If the Investigator 
becomes aware of a holding rule being met, he/she must suspend administration of the 
study intervention and inform the Sponsor’s delegate immediately. 
In Step 2, a second sentinel of 10 participants vaccinated on consecutive days. They will 
receive a phone call for safety surveillance on the day following the first study 
intervention administration (Day 2), before proceeding with study intervention 
administration in the subsequent participants. The remaining 30 participants will be 
vaccinated at least 60 minutes apart. 

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Likewise, in Stage 2, the first 21 participants will receive the study interventions 
sequentially, at least 60 minutes apart, with a safety phone call/home Visit the day after 
administration for safety surveillance. 
All 155 participants in the study (Stage 1 and Stage 2) will be closely monitored at the 
site for at least 60 minutes post-administration for safety surveillance. 
Seven days after the first study intervention administration in the low dose cohort 
(Step 1) in Stage 1 is completed, an iSRC will receive a summary of all available safety 
data (solicited administration site events and systemic events, unsolicited AEs and SAEs) 
and listings of hematology and blood chemistry test values obtained following the first 
study intervention administration (baseline and 7 days after study intervention 
administration). Based on evaluation of the safety data (review #1, Table 14), the iSRC 
will make a recommendation, as to whether the next stage of the trial (Stage 1/Step 2), 
when the administration of the full dose of the study interventions to the study 
participants, should start. 
Seven days after all participants in Stage 1/Step 1 have received their second study 
intervention, there will be an iSRC review of all safety data collected up to day 7 after 
second administration (Day 64) in Step 1 (review #2, Table 14). If there is no safety 
concern with any of the investigational groups, the second study intervention 
administration in Stage 1/Step 2 can commence. 
There will be another iSRC data review 28 days after the second administration in 
Stage 1/Step 2 (review #3, Table 14). In the case of a favorable review, recruitment of 
participants in Stage 2 in Africa can commence. 
All the participants in Stage 1 will complete the trial according to the schedule. A final 
safety evaluation of all data collected in Stage 1 will be performed once the study is 
completed. 
The first 21 participants in Stage 2 will receive the study interventions sequentially, 
60 minutes apart, with a follow-up safety phone call/home Visit conducted one day after 
the first administration to identify any safety concerns in the participants who received 
the study interventions. The Investigator will proceed with study interventions 
administration in the subsequent study participant only in the case that there is no safety 
concern in the previous participant who received the study interventions. If the 
Investigator becomes aware of a holding rule being met, he/she must suspend 
administration of the study intervention and inform the Sponsor’s delegate immediately. 
Seven days after the first administration of the study interventions of the first 
21 participants in Stage 2, there will be an iSRC to review all available safety data 
collected (review #4, Table 14). Following this, in the event of a positive safety review, 
the 84 remaining participants will receive the study interventions in parallel. 

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A last iSRC review analysis for safety will be performed 28 days after second 
administration in the first 21 participants in Stage 2 to allow the third study intervention 
administration of all participants in Stage 2 and to support preparation for future studies 
(review #5, Table 14). 
A summary of the planned unblinded iSRC reviews for the trial are presented in Table 
14. In case of any safety concerns, ad hoc iSRC reviews may be called.  
Instream blinded monitoring will also be performed by the internal GSK Safety Review 
Team (SRT); details of these blinded data reviews for the trial are presented in Table 15. 
Table 14 
Summary of the iSRC Reviews* 
iSRC # 
Timing of Safety Evaluation 
Subsequent Activities 
1 
7 days after first administration with 
low dose of 10 sentinel participants in 
Step 1 (Stage 1) 
First administration with full dose of 
40 participants in Step 2 (Stage 1)  
2 
7 days after second administration with 
low dose of 10 sentinel participants in 
Step 1 (Stage 1) 
Second administration with full dose of 
40 participants in Step 2 (Stage 1) 
3 
28 days after second administration 
with full dose of 40 participants in Step 
2 (Stage 1) 
First administration with full dose of first 
21 participants in Stage 2  
4 
7 days after first administration of first 
21 participants in Stage 2 
First administration of remaining 
84 participants in Stage 2 
5 
28 days after second administration in 
the first 21 participants in Stage 2  
Third administration with full dose of 
all participants in Stage 2 
Abbreviation: iSRC= Internal Safety Review Committee 
* All available safety data will be cumulatively reviewed at each safety evaluation. 
Table 15 
Time points for Blinded Instream Monitoring 
Stage # 
Instream Monitoring 
Stage 1 
(Steps 1 and 2) 
All cumulative data (all subjects) up to 7 days post-first vaccination 
All cumulative data (all subjects) up to 7 days post-second vaccination 
All cumulative data (all subjects) up to 7 days post-third vaccination  
Stage 2 
All cumulative data (all subjects) up to 7 days post-first vaccination of the additional 
84 subjects 
All cumulative data (all subjects) up to 28 days post-first vaccination of the additional 
84 subjects 
All cumulative data (all subjects) up to 7 days post-second vaccination of the first 
21 subjects 
All cumulative data (all subjects) up to 28 days post-second vaccination of the 
additional 84 subjects 

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10.0 REFERENCES 
Aldrich, C, Hartman H, Feasey N, et al. Emergence of phylogenetically diverse and 
fluoroquinolone resistant Salmonella Enteritidis as a cause of invasive nontyphoidal 
Salmonella disease in Ghana. PLoS Negl Trop Dis. 2019;13(6):e0007485. 
Balasubramanian R, Im J, Lee JS, et al. The global burden and epidemiology of 
invasive non-typhoidal Salmonella infections. Hum Vaccin Immunother. 
2019;15(6):1421-26. 
Benedetto GD, Alfini R, Cescutti P, et al. Characterization of O-antigen delivered by 
Generalized Modules for Membrane Antigens (GMMA) vaccine candidates against 
nontyphoidal Salmonella', Vaccine. 2017;35(3): 419-26. 
Butler NR, Voyce MA, Burland WL, Hilton MJ. Advantages of aluminium hydroxide 
adsorbed combined diphtheria, tetanus, and pertussis vaccines for the immunization 
of infants. Br Med J. 1969;1(5645):633-6. 
Ekman P, Kirveskari J, Granfors K. Modification of disease outcome in salmonella-
infected patients by HLA-B27. Arthritis Rheum. 2000; 43(7):1527-34. 
Feasey NA, Dougan G, Kingsley RK, Heyderman RS, Gordon MA. Invasive 
non-typhoidal salmonella disease: an emerging and neglected tropical disease in 
Africa. Lancet. 2012;379(9835): 2489-99. 
Feasey NA, Masesa C, Jassi C, et al. Three Epidemics of Invasive Multidrug-
Resistant Salmonella Bloodstream Infection in Blantyre, Malawi, 1998-2014. Clin 
Infect Dis, 2015;61 Suppl 4(Suppl 4):S363-71. 
Frenck Jr. RW, Conti V, Ferruzi P, et al. Efficacy, safety, and immunogenicity of the 
Shigella Sonnei 1790GAHB GMMA candidate vaccine: Results from a phase 2b 
randomized, placebo-controlled challenge study in adults. EClinicalMedicine. 2021 
Aug 13;39:101076. 
Garçon N, Stern PL, Cunningham AL. Understanding modern vaccines: perspectives 
in vaccinology. Amsterdam: Elsevier;2011. 
GBD 2017 Non-typhoidal Salmonella Invasive Disease Collaborators. The global 
burden of non-typhoidal salmonella invasive disease: a systematic analysis for the 
Global Burden of Disease Study 2017. Lancet Infect Dis. 2019;19(12):1312-24. 
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Kariuki S, Mbae C, Onsare R, et al. Multidrug-resistant Nontyphoidal Salmonella 
Hotspots as Targets for Vaccine Use in Management of Infections in Endemic 
Settings. Clin Infect Dis. 2019;68(Suppl 1): S10-S15. 
Kawahara M, Kato-Negishi M. Link between Aluminum and the Pathogenesis of 
Alzheimer's Disease: The Integration of the Aluminum and Amyloid Cascade 
Hypotheses. Int J Alzheimers Dis. 2011:276393. 
Lanzilao L, Stefanetti G, Saul A, MacLennan CA, Micoli , Rondini S. Strain 
Selection for Generation of O-Antigen-Based Glycoconjugate Vaccines against 
Invasive Nontyphoidal Salmonella Disease. PLoS One. 2015;10(10):e0139847. 
Launay O, Lewis DJM, Anemona A, et al. Safety Profile and Immunologic 
Responses of a Novel Vaccine Against Shigella Sonnei Administered 
Intramuscularly, Intradermally and Intranasally: Results From Two Parallel 
Randomized Phase 1 Clinical Studies in Healthy Adult Volunteers in Europe. 
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Launay O, Ndiaye AGW, Conti V, et al. Booster Vaccination With GVGH Shigella 
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Unvaccinated Healthy European Adults: Results From a Phase 1 Clinical Trial. Front 
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sub-Saharan Africa: a multicentre population-based surveillance study. Lancet Glob 
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McColl GJ, Diviney MB, Holdsworth RF, et al. HLA-B27 expression and reactive 
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Adults from a Shigellosis-Endemic Country. Front Immunol. 2017;8:1884. 
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2015 and Beyond. Vaccines (Basel). 2015;3(2):320-43. 
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Puyvelde SV, Pickard D, Vandelannoote K, et al. An African Salmonella 
Typhimurium ST313 sublineage with extensive drug-resistance and signatures of host 
adaptation. Nat Commun. 2019;10(1):4280. 
Reddy EA, Shaw AV, Crump JA. Community-acquired bloodstream infections in 
Africa: a systematic review and meta-analysis. Lancet Infect Dis. 2010;10(6):417-32. 
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Shigella Sonnei 1790GAHB GMMA candidate vaccine: Results from a phase 2b 
randomized, placebo-controlled challenge study in adults. EClinicalMedicine. 
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Factors and Case Fatality Rates of Invasive Nontyphoidal Salmonella (iNTS) Disease 
in Africa (1966 to 2014). PLoS Negl Trop Dis. 2017;11(1):e0005118. 
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(FDA) Center for Biologics Evaluation and Research. Guidance for Industry-Toxicity 
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11.0 APPENDICES 
Appendix 1 
Abbreviations 
Abbreviation 
Definition 
ADE 
Adverse device effect 
AE 
Adverse event 
Ag 
Antigen 
AMR 
Antimicrobial resistance 
CFR 
Code of Federal Regulations 
CI 
Confidence interval 
COVID-19 
Coronavirus disease 2019 
eCRF 
Electronic case report form 
DAIDS 
Division of AIDS 
EoS 
End of study 
ES 
Exposed Set 
FAS 
Full Analysis Set 
FIH 
First-in-human 
FSH 
Follicle-stimulating hormone 
GCP 
Good Clinical Practice 
GMMA 
Generalized modules for membrane antigens 
GSK 
GlaxoSmithKline Biologicals SA 
GVGH 
GSK Vaccines Institute for Global Health 
HLA-B27 
Human leukocyte antigen B27 
HRT 
Hormonal replacement therapy 
IB 
Investigator’s Brochure 
ICF 
Informed consent form 
ICH 
International Council for Harmonisation 
IEC 
Independent Ethics Committee 
Ig 
Immunoglobulin 
IM 
Intramuscular 

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Abbreviation 
Definition 
iNTS 
Invasive nontyphoidal Salmonella 
IRB 
Institutional Review Boards 
iSRC 
Internal Safety Review Committee 
LPS 
Lipopolysaccharides 
LSLV 
Last subject last visit 
PPS 
Per Protocol Set 
S. Enteritidis 
Salmonella Enteritidis 
S. Typhi 
Salmonella Typhi 
S. Typhimurium 
Salmonella Typhimurium 
SADE 
Serious adverse device effect 
SAE 
Serious adverse event 
SmPC 
Summary of Product Characteristics 
SoA 
Schedule of Activities 
SRT 
Safety Review Team 
sSA 
Sub-Saharan Africa 
SUSAR 
Suspected Unexpected Serious Adverse Reactions 
TCV 
Typhoid conjugate vaccine 
Typhim Vi 
Typhoid Vi polysaccharide vaccine 
USADE 
Unanticipated serious adverse device effect 
WHO 
World Health Organization 
WOCBP 
Woman of childbearing potential 

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Glossary of Terms 
Adverse event: 
Any untoward medical occurrence in a patient or clinical 
investigation participant, temporally associated with the 
use of a medicinal product, whether or not considered 
related to the medicinal product. 
An adverse event can therefore be any unfavorable and 
unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) 
temporally associated with the use of a medicinal 
product. For marketed medicinal products, this also 
includes failure to produce expected benefits (ie, lack of 
efficacy), abuse or misuse. 
Blinding: 
A procedure in which 1 or more parties to the trial are 
kept unaware of the intervention assignment in order to 
reduce the risk of biased study outcomes. The level of 
blinding is maintained throughout the conduct of the 
trial, and only when the data are cleaned to an acceptable 
level of quality will appropriate personnel be unblinded 
or when required in case of a serious adverse event 
In an observer-blind study, the participant, the site, and 
Sponsor personnel involved in the clinical evaluation of 
the participants are blinded while other study personnel 
may be aware of the treatment assignment.  
Certified copy: 
A copy (irrespective of the type of media used) of the 
original record that has been verified (ie, by a dated 
signature or by generation through a validated process) 
to have the same information, including data that 
describe the context, content, and structure, as the 
original. 
Combination product: 
Combination product comprises any combination of 
− 
drug 
− 
device 
− 
biological product 
Each drug, device and biological product included in a 
combination product is a constituent part.  
Eligible: 
Qualified for enrollment into the study based upon strict 
adherence to inclusion/exclusion criteria. 
Enrollment: 
The process of registering a participant into a clinical 
study by assigning participant identification number 
after signing the informed consent form. 

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Essential documents: 
Documents which individually and collectively permit 
evaluation of the conduct of a study and the quality of 
the data produced. 
Evaluable: 
Meeting all eligibility criteria, complying with the 
procedures defined in the protocol, and, therefore, 
included in the per protocol analysis. 
First act of recruitment: 
The study start date is the date on which the clinical 
study will be open for recruitment of participants and the 
first participant will sign the informed consent form. 
GSK Vaccines Institute 
for Global Health 
(GVGH): 
A GSK-owned company, part of the GSK Global Health 
Program, committed to develop vaccines for major 
neglected diseases of impoverished communities. 
Intervention: 
Term used throughout the clinical study to denote a set 
of investigational product(s) or marketed product(s) or 
placebo intended to be administered to a participant. 
Intervention number: 
A number identifying an intervention to a participant, 
according to intervention allocation. 
Invasive medical device: 
A device which, in whole or in part, penetrates inside the 
body, either through a body orifice or through the 
surface of the body. 
Investigational 
vaccine/product: 
A pharmaceutical form of an active ingredient being 
tested in a clinical trial, including a product with a 
marketing authorization when used in a way different 
from the approved form, or when used for an 
unapproved indication, or when used to gain further 
information about an approved use. 
Synonym: Investigational Medicinal Product 
Investigator: 
A person responsible for the conduct of the clinical trial 
at a trial site. If a trial is conducted by a team of 
individuals at a trial site, the Investigator is the 
responsible leader of the team and may be called the 
Principal Investigator. 
The Investigator can delegate trial-related duties and 
functions conducted at the trial site to qualified 
individual or party to perform those trial-related duties 
and functions. 
Medical device deficiency: A device deficiency is an inadequacy of a medical 
device with respect to its identity, quality, durability, 
reliability, safety, or performance. Device deficiencies 
include malfunctions, use errors and information 
supplied by the manufacturer. 

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Participant: 
Term used throughout the protocol to denote an 
individual who has been contacted to participate or who 
participates in the clinical study as a recipient of the 
study intervention (vaccine(s)/product(s)/control). 
Synonym: subject 
Participant number: 
A unique identification number assigned to each 
participant who consents to participate in the study. 
Primary completion date: 
The date that the final participant was examined or 
received an intervention for the purpose of final 
collection of data for all primary outcomes, whether the 
clinical trial was concluded according to the prespecified 
protocol or was terminated. 
Protocol amendment: 
The ICH defines a protocol amendment as: ‘A written 
description of a change(s) to or formal clarification of a 
protocol.’ GSK further details this to include a change to 
an approved protocol that affects the safety of 
participants, scope of the investigation, study design, or 
scientific integrity of the study. 
Randomization: 
Process of random attribution of intervention to 
participants to reduce selection bias. 
Remote visit: 
This term refers to the visit conducted in the place other 
than the study site. 
Safety Review Team: 
This team lead by safety comprises of core 
representatives from GSK Global Safety, clinical, 
epidemiology, regulatory, and statistics departments, 
who are also part of the study team. For this study, the 
team is responsible for reviewing observed safety 
concerns based on blinded safety data. 
Solicited event: 
Events to be recorded as endpoints in the clinical study. 
The presence/occurrence/intensity of these events is 
actively solicited from the participant or an observer 
during a specified follow-up period following study 
intervention administration. 
Source data: 
All information in original records and certified copies 
of original records of clinical findings, observations, or 
other activities in a clinical trial necessary for the 
reconstruction and evaluation of the trial. Source data 
are contained in source documents (original records or 
certified copies). 
Source documents: 
Original legible documents, data, and records (eg, 
hospital records, clinical and office charts, laboratory 
notes, memoranda, participants' diaries or evaluation 
checklists, pharmacy dispensing records, recorded data 

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from automated instruments, copies or transcriptions 
certified after verification as being accurate copies, 
microfiches, photographic negatives, microfilm or 
magnetic media, x-rays, participant files, and records 
kept at the pharmacy, laboratories and at medico-
technical departments involved in the clinical trial). 
Study intervention: 
Any investigational or marketed product(s) or placebo 
intended to be administered to a participant during the 
study. 
Study monitor: 
An individual assigned by the Sponsor and responsible 
for assuring proper conduct of clinical studies at 1 or 
more investigational sites. 
Unsolicited adverse event: 
Any AE reported in addition to those solicited during the 
clinical study. Also, any ‘solicited’ symptom with onset 
outside the specified period of follow-up for solicited 
symptoms will be reported as an unsolicited adverse 
event. 

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Appendix 2 
Regulatory, Ethical, and Study Oversight 
Considerations 
Regulatory and Ethical Considerations 
• 
This study will be conducted in accordance with the protocol and with the following: 
− 
Consensus ethical principles derived from international guidelines including the 
Declaration of Helsinki and Council for International Organizations of Medical 
Sciences International Ethical Guidelines. 
− 
Applicable ICH GCP Guidelines. 
− 
Applicable laws and regulations. 
• 
The protocol, protocol amendments, informed consent form (ICF), IB, and other 
relevant documents (eg, advertisements) must be submitted to an IRB/IEC by the 
Investigator and reviewed and approved by the IRB/IEC before the study is initiated. 
• 
Any amendments to the protocol will require IRB/IEC and regulatory authority 
approval, when applicable, before implementation of changes made to the study 
design, except for changes necessary to eliminate an immediate hazard to 
participants. 
• 
The Investigator will be responsible for the following: 
− 
Providing written summaries of the status of the study to the IRB/IEC annually 
or more frequently in accordance with the requirements, policies, and 
procedures established by the IRB/IEC. 
− 
Notifying the IRB/IEC of SAEs or other significant safety findings as required 
by IRB/IEC procedures. 
− 
Providing oversight of the conduct of the study at the study center and 
adherence to requirements of 21 Code of Federal Regulations (CFR), ICH 
guidelines, the IRB/IEC, European regulation 536/2014 for clinical studies (if 
applicable), and all other applicable local regulations. 
• 
After reading the protocol, each Investigator will sign the protocol signature page 
and send a copy of the signed page to the Sponsor or representative (Appendix 9). 
The study will not start at any study center at which the Investigator has not signed 
the protocol. 
Adequate Resources 
The Investigator is responsible for supervising any individual or party to whom the 
Investigator delegates study-related duties and functions conducted at the study center. 
If the Investigator/institution retains the services of any individual or party to perform 
study-related duties and functions, the Investigator/institution should ensure this 
individual, or party is qualified to perform those study-related duties and functions and 

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should implement procedures to ensure the integrity of the study-related duties and 
functions performed and any data generated. 
Financial Disclosure 
Investigators and sub-Investigators will provide the Sponsor with sufficient, accurate 
financial information as requested to allow the Sponsor to submit complete and accurate 
financial certification or disclosure statements to the appropriate regulatory authorities. 
Investigators are responsible for providing information on financial interests during the 
course of the study and for 1 year after completion of the study. 
Informed Consent Process 
• 
The Investigator or his/her representative will explain the nature of the study to the 
participant or his/her legally authorized representative and answer all questions 
regarding the study. 
• 
Participants must be informed that their participation is voluntary. Participants will 
be required to sign a statement of informed consent that meets the requirements of 21 
CFR 50, local regulations, ICH guidelines, Health Insurance Portability and 
Accountability Act requirements, where applicable, and the IRB/IEC or study center. 
• 
The medical record must include a statement that written informed consent was 
obtained before the participant was entered in the study and the date the written 
consent was obtained. The authorized person obtaining the informed consent must 
also sign the ICF. 
• 
Participants must be re-consented to the most current version of the ICF(s) during 
their participation in the study. 
• 
A copy of the ICF(s) must be provided to the participant or the participant’s legally 
authorized representative. 
For participants who are rescreened, participants are required to sign a new ICF, only if 
there are changes to the original ICF. If there are no changes to the original ICF, 
participants should confirm that they still agree to be part of the study. This information 
should be captured in the participant source document. 
Data Protection 
The Sponsor must keep coded data from clinical studies for a minimum of 30 years after 
the end of the study to ensure the validity of the research. This will also be the case if a 
participant stopped study participation prematurely. The Sponsor will also keep coded 
data, where needed because of legal action or an investigation involving the Sponsor. 
The contract between Sponsor and study sites specifies responsibilities of the parties 
related data protection, including handling of data security breaches and respective 
communication and cooperation of the parties. 

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Information technology systems used to collect, process, and store study-related data are 
secured by technical and organizational security measures designed to protect such data 
against accidental or unlawful loss, alteration, or unauthorized disclosure or access. 
Sponsor or Sponsor’s delegate are contractually bound to protect participant coded data. 
GSK will protect participant coded data and will only share it as described in the ICF. 
Participants will be assigned a unique identifier by the Sponsor or Sponsor’s delegate. 
Any participant records or datasets transferred to the Sponsor or Sponsor’s delegate will 
contain only the identifier. Name and any other information which would identify the 
participant will not be transferred. 
The participants must be informed that: 
• 
Their personal study-related data will be used by the Sponsor in accordance with 
local data protection law. 
• 
Their medical records may be examined by Clinical Quality Assurance auditors or 
other authorized personnel appointed by the Sponsor, by appropriate IRB/IEC 
members, and by inspectors from regulatory authorities. 
• 
Sponsor or Sponsor’s delegate will ensure protection of the personal data of the 
Investigator and site staff which is collected within the framework of and for the 
purpose of the study, in accordance with the Data Privacy Notice that will be sent to 
the site staff. 
The participants must be notified about their rights regarding the use of their personal 
data in accordance with the data privacy section of the ICF. 
Administrative Structure 
The details of administrative structure are provided in Table 16. 
Table 16 
Study Administrative Structure 
Function 
Responsible Organization 
Clinical Supply Management, Quality Assurance 
Auditing 
GSK 
Laboratory Assessments 
GSK 
Randomization, Blinding, unblinding 
IQVIA 
Study Operations Management, Medical 
Monitoring, Study Master File 
IQVIA 
Biostatistics, Medical Writing 
IQVIA 
Medical Monitor 
Refer to Study Reference Manual 

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Dissemination of Clinical Study Data 
The key design elements of this protocol and results summaries will be posted on 
www.ClinicalTrials.gov, https://pactr.samrc.ac.za, and/or GSK Clinical Study Register in 
compliance with applicable regulations/GSK policy. GSK will aim to register protocols 
summaries prior to study start and target results summaries submission within 12 months 
of primary/study completion date. Where external regulations require earlier disclosure, 
GSK will follow those timelines. 
Where required by regulation, summaries will also be posted on applicable national or 
regional clinical study registers. 
Where required by applicable regulatory requirements, an Investigator signatory will be 
identified for the approval of the study report, and provided reasonable access to 
statistical tables, figures, and relevant reports. GSK will also provide the Investigator 
with the full summary of the study results. The Investigator is encouraged to share the 
summary results with the study participants, as appropriate. 
Sponsor or Sponsor’s delegate will provide the Investigator with the randomization codes 
for their site only after completion of the full statistical analysis. 
GSK intends to make anonymized patient-level data from this study available to external 
researchers for scientific analyses or to conduct further research that can help advance 
medical science or improve patient care. This helps ensure the data provided by study 
participants are used to maximum effect in the creation of knowledge and understanding. 
Data Quality Assurance 
The Investigator should maintain a record of the location(s) of their respective essential 
documents, including source documents (refer to Appendix 1 for definitions of essential 
and source documents). The document storage system used during the study and for 
archiving (irrespective of the type of media used) should provide for document 
identification, version history, search, and retrieval. 
Essential study documents may be added or removed where justified (in advance of study 
initiation) based on their importance and relevance to the study. When a copy is used to 
replace an original document (eg, source documents, eCRF), the copy should fulfill the 
requirements for certified copies (refer to Appendix 1 for the definition of a certified 
copy). 
All participant data related to the study will be recorded on printed or eCRF unless 
transmitted to GSK/IQVIA electronically (eg, laboratory data). The Investigator is 
responsible for verifying that data entries are accurate and correct by physically or 
electronically signing the eCRF. 

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The Investigator must maintain adequate and accurate source documents and study 
records that include all pertinent observations on each of the site’s study participants 
(refer to Appendix 1 for the definition of source documents) that supports information 
entered in the eCRF. 
The Investigator must permit study-related monitoring, audits, IRB review, and 
regulatory agency inspections and provide direct access to source documents or certified 
copies for such review and inspection. 
IQVIA is responsible for the data management of this study including quality checking of 
the source data (refer to Appendix 1 for the definition of source data). 
Study monitors will perform ongoing source data verification to confirm that data entered 
in the eCRF by authorized site personnel are attributable, legible, contemporaneous, 
original, accurate, and complete. Changes to source data must be traceable, not obscure 
the original entry, and be fully explained if necessary (eg, via an audit trail). The safety 
and rights of participants must be protected, and the study conducted in accordance with 
the currently approved protocol and any other study agreements, ICH GCP, and all 
applicable regulatory requirements. 
Quality tolerance limits will be predefined to identify systematic issues that can impact 
participant safety and/or the reliability of study results. 
Study records and source documents pertaining to the conduct of this study, including 
signed ICFs, must be retained by the Investigator for 25 years from issuance of the final 
CSR/equivalent summary unless local regulations or institutional policies require a longer 
retention period. No records may be destroyed during the retention period without the 
written approval of GSK. No records may be transferred to another location or party 
without written notification to GSK. 
Source Documents 
Source documents provide evidence to establish the existence of the participant and 
substantiate the integrity of collected data. The Investigator should maintain a record of 
the location(s) of their source documents. 
Data transcribed into the eCRF from source documents must be consistent with those 
source documents; any discrepancies must be explained. The Investigator may need to 
request previous medical records or transfer records, depending on the study. Also, 
current medical records must be available. 
The Sponsor or designee will perform monitoring to confirm that data entered in the 
eCRF by authorized site personnel are accurate, complete, and verifiable from source 
documents; that the safety and rights of participants are being protected; and that the 

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study is being conducted in accordance with the currently approved protocol and any 
other study agreements, ICH GCP, and all applicable regulatory requirements. 
Definitions of what constitutes source data and documents can be found in Appendix 1. 
Study and Study Center Closure 
The first act of recruitment is the date of the first participant enrollment and is considered 
the study start date. 
GSK/IQVIA reserves the right to close the study center or terminate the study at any time 
for any reason. Study centers will be closed upon study completion. A study center is 
considered closed when all required documents and study supplies have been collected 
and a study center closure visit has been performed. 
The Investigator may initiate study center closure at any time, provided there is 
reasonable cause and sufficient notice is given in advance of the intended termination. 
Reasons for the early closure of a study center may include but are not limited to: 
• 
Failure of the Investigator to comply with the protocol, the requirements of the IRB 
or local health authorities, GSK’s procedures, or GCP guidelines 
• 
Inadequate recruitment of participants by the Investigator 
• 
Discontinuation of further study intervention development 
• 
Total number of participants included earlier than expected 
If the study is prematurely terminated or suspended, GSK/IQVIA shall promptly inform 
the investigators, the IRBs, and the regulatory authorities of the reason for termination or 
suspension, as specified by the applicable regulatory requirements. The Investigator shall 
promptly inform the participants and should assure appropriate participant therapy and/or 
follow-up. 
Publication Policy 
GSK aims to submit for publication the results of the study in searchable, peer reviewed 
scientific literature within 18 months from LSLV studies and follows authorship and 
other guidance from the International Committee of Medical Journal Editors. 

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Appendix 3 
Adverse Events: Definitions and Procedures for 
Recording, Evaluating, Follow-up, and Reporting 
Definition of AE 
AE Definition 
• 
An AE is any untoward medical occurrence in a patient or participant, temporally associated with 
the use of study treatment, whether or not considered related to the study treatment. 
Note: An AE can therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the use of study 
treatment. 
 
Events Meeting the AE Definition  
• 
Significant or unexpected worsening or exacerbation of the condition/indication under study. 
• 
Any abnormal laboratory test results (hematology, clinical chemistry, or urinalysis) or other safety 
assessments (eg, electrocardiogram, radiological scans, vital signs measurements), including those 
that worsen from baseline, considered clinically significant in the medical and scientific judgment 
of the Investigator (ie, not related to progression of underlying disease). 
• 
Exacerbation of a chronic or intermittent pre-existing condition including either an increase in 
frequency and/or intensity of the condition. 
• 
New conditions detected or diagnosed after study treatment administration even though it may have 
been present before the start of the study. 
• 
Signs, symptoms, or the clinical sequelae of a suspected drug, disease or other interaction. 
• 
Signs, symptoms, or the clinical sequelae of a suspected overdose of either study treatment or a 
concomitant medication. Overdose per se will not be reported as an AE/SAE unless it is an 
intentional overdose taken with possible suicidal/self-harming intent. Such overdoses should be 
reported regardless of sequelae. 
• 
Signs or symptoms temporally associated with administration of the study intervention. 
• 
Signs, symptoms that require medical attention (eg, hospital stays, physician visits and emergency 
room visits). 
• 
Significant failure of an expected pharmacologic or biological action. 
• 
Pre- or post- intervention events that occur as a result of protocol-mandated procedures (ie, 
invasive procedures, modification of participant’s previous therapeutic regimen). 
• 
The signs, symptoms, and/or clinical sequelae resulting from lack of efficacy will be reported as 
AE or SAE if they fulfill the definition of an AE or SAE. 
 

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Events NOT Meeting the AE Definition  
• 
Any clinically significant abnormal laboratory findings or other abnormal safety assessments which 
are associated with the underlying disease, unless judged by the Investigator to be more severe than 
expected for the participant’s condition. 
• 
Pre-existing conditions or signs and/or symptoms present in a participant before the first dose of 
study intervention. These events will be recorded in the medical history section of the eCRF. 
• 
Situations in which an untoward medical occurrence did not occur (eg, social and/or convenience 
admission to a hospital). 
• 
Anticipated day-to-day fluctuations of pre-existing disease(s) or condition(s) present or detected at 
the start of the study that do not worsen. 
• 
Hospitalization for elective treatment of a pre-existing condition (known or diagnosed before 
signing the informed consent) that did not worsen from baseline. 
Definition of SAE 
An SAE is defined as any untoward medical occurrence that, at any dose: 
a) Results in death 
b) Is life-threatening 
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. 
c) Requires inpatient hospitalization or prolongation of existing hospitalization 
In general, hospitalization signifies that the participant has been detained (usually involving at least an 
overnight stay) at the hospital or emergency ward for observation and/or treatment that would not have 
been appropriate in the physician’s office or outpatient setting. Complications that occur during 
hospitalization are AEs. If a complication prolongs hospitalization or fulfills any other serious criteria, 
the event is serious. When in doubt as to whether “hospitalization” occurred or was necessary, the AE 
should be considered serious. 
Hospitalization for elective treatment of a pre-existing condition that did not worsen from baseline is not 
considered an AE. 
d) Results in persistent disability/incapacity 
• 
The term disability means a substantial disruption of a person’s ability to conduct normal life 
functions. 
• 
This definition is not intended to include experiences of relatively minor medical significance such 
as uncomplicated headache, nausea, vomiting, diarrhea, influenza, and accidental trauma (eg, 
sprained ankle) which may interfere with or prevent everyday life functions but do not constitute a 
substantial disruption. 
e) Abnormal pregnancy outcomes (eg, spontaneous abortion, fetal death, stillbirth, congenital 
anomalies, ectopic pregnancy) 

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f) 
Other situations: 
• 
Medical or scientific judgment should be exercised in deciding whether SAE reporting is 
appropriate in other situations such as important medical events that may not be immediately life-
threatening or result in death or hospitalization but may jeopardize the participant or may require 
medical or surgical intervention to prevent 1 of the other outcomes listed in the above definition. 
These events should usually be considered serious. 
Examples of such events include invasive or malignant cancers, intensive treatment in an emergency 
room or at home for allergic bronchospasm, blood dyscrasias or convulsions that do not result in 
hospitalization, or development of drug dependency or drug abuse. 
Solicited Events 
Events to be recorded as endpoints in the clinical study. The 
presence/occurrence/intensity of these events is actively solicited from the participant or 
an observer during a specified follow-up period following study intervention 
administration. 
Table 17 
Solicited Events to be Collected 
Solicited administration site events 
Pain at administration site 
Redness at administration site 
Swelling at administration site 
Solicited systemic events 
Fever 
Headache 
Myalgia 
Arthralgia 
Fatigue 
Participants will be instructed to measure and record the axilla temperature in the 
evening. If additional temperature measurements are taken at other times of the day, 
participants will be instructed to record the highest temperature in the pDiary card. 
Unsolicited Events 
Any AE reported in addition to those solicited during the clinical study. Also, any 
‘solicited’ symptom with onset outside the specified period of follow-up for solicited 
symptoms will be reported as unsolicited AEs. Unsolicited events will be collected for 
28 days after each study intervention administration (ie, Day 1 to Day 28, Day 57 to 
Day 84 and Day 169 to Day 196). 
An unsolicited AEs is an AEs that was not included in a list of solicited events using a 
Participant pDiary. Unsolicited events must have been spontaneously communicated by a 

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participant who has signed the informed consent. Unsolicited AEs include both serious 
and non-serious AEs. 
Potential unsolicited AEs may be medically attended (ie, symptoms or illnesses requiring 
a hospitalization, or an emergency room visit, or visit to/by a health care provider). The 
participants will be instructed to contact the site as soon as possible to report medically 
attended event(s), as well as any events that, though not medically attended, are of 
participant’s concern. Detailed information about reported unsolicited AEs will be 
collected by qualified site personnel and documented in the participant’s records. 
Unsolicited AEs that are not medically attended or perceived as a concern by the 
participant will be collected during an interview with the participants and by review of 
available medical records at the next visit. 
COVID-19 Cases 
Diagnosis of COVID-19 should be made in accordance with the WHO COVID-19 Case 
Definitions [WHO, 2020]. Cases should be categorized as AEs (unsolicited or AEs 
leading to withdrawal) or SAEs, and routine procedures for recording, evaluation, 
follow-up, and reporting of AEs and SAEs should be followed in accordance with the 
time period set out in the protocol. 
Assessment of Intensity 
The intensity of the following solicited events will be assessed as described: 
Table 18 
Intensity Scales for Solicited Events 
Event 
Intensity 
grade 
Parameter 
Pain at administration site 
0 
None 
1 (Mild) 
Mild: Any pain neither interfering with nor 
preventing normal everyday activities. 
2 (Moderate) 
Moderate: Painful when limb is moved and 
interferes with everyday activities. 
3 (Severe) 
Severe: Significant pain at rest. Prevents normal 
everyday activities. 
Redness and swelling at 
administration site (Greatest 
surface diameter in mm) 
0 
<20 mm 
1 (Mild) 
≥20 mm to ≤50 mm 
2 (Moderate) 
>50 mm to ≤100 mm 
3 (Severe) 
>100 mm 
Temperature* in °C 
0 
<38.0°C 
1 (Mild) 
≥38.0°C to <39.0°C 
2 (Moderate) 
≥39.0°C to ≤40.0°C 

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Event 
Intensity 
grade 
Parameter 
3 (Severe) 
>40.0°C 
Headache 
0 
None 
1 (Mild) 
Headache that is easily tolerated 
2 (Moderate) 
Headache that interferes with normal activity 
3 (Severe) 
Headache that prevents normal activity 
Myalgia 
0 
None 
1 (Mild) 
Myalgia present but does not interfere with 
activity 
2 (Moderate) 
Myalgia that interferes with normal activity 
3 (Severe) 
Myalgia that prevents normal activity 
Arthralgia 
0 
None 
1 (Mild) 
Arthralgia present but does not interfere with 
activity 
2 (Moderate) 
Arthralgia that interferes with normal activity 
3 (Severe) 
Arthralgia that prevents normal activity 
Fatigue 
0 
Normal 
1 (Mild) 
Fatigue that is easily tolerated 
2 (Moderate) 
Fatigue that interferes with normal activity 
3 (Severe) 
Fatigue that prevents normal activity 
*Refer to the Schedule of Activities (Table 1) for the definition of fever and the preferred location for 
temperature measurement. 
The Investigator will assess the maximum intensity that occurred over the duration of the 
event for all unsolicited AEs (including SAEs) recorded during the study. The assessment 
will be based on the Investigator’s clinical judgment. 
The intensity should be assigned to one of the following categories: 
1 (mild) 
= 
An AE which is easily tolerated by the participant, causing minimal 
discomfort, and not interfering with everyday activities. 
2 (moderate) 
= 
An AE which is sufficiently discomforting to interfere with normal everyday 
activities. 
3 (severe) 
= 
An AE which prevents normal, everyday activities 
An AE that is assessed as Grade 3 (severe) should not be confused with an SAE. Grade 3 
is a category used for rating the intensity of an event; and both AEs and SAEs can be 
assessed as Grade 3. 
Assessment of Causality 
The Investigator must assess the relationship between study intervention and the 
occurrence of each unsolicited AE/SAE using clinical judgment. Where several different 

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interventions were administered, the Investigator should specify, when possible, if the 
unsolicited AE/SAE could be causally related to a specific intervention. When a causal 
relationship to a specific study intervention cannot be determined, the Investigator should 
indicate the unsolicited AE/SAE to be related to all interventions. 
Alternative possible causes, such as the natural history of underlying disease, 
concomitant therapy, other risk factors, and the temporal relationship of the event to the 
study intervention will be considered and investigated. The Investigator will also consult 
the IB and/or SmPC to assist in making his/her assessment. 
Causality should be assessed by the Investigator using the following question: 
Is there a reasonable possibility that the unsolicited AE may have been caused by the 
study intervention? 
YES 
NO  
There is a reasonable possibility that the study intervention contributed to the AE. 
There is no reasonable possibility that the AE is causally related to the administration of the 
study intervention. There is other, more likely causes and administration of the study 
intervention is not suspected to have contributed to the AE. 
If an event meets the criteria to be determined ‘serious’, additional examinations/tests 
will be performed by the Investigator to determine ALL possible contributing factors for 
each SAE. 
Possible contributing factors include: 
• 
Medical history. 
• 
Other medication. 
• 
Protocol required procedure. 
• 
Other procedure not required by the protocol. 
• 
Lack of efficacy of the study intervention, if applicable. 
• 
An error in study intervention administration. 
• 
Other cause (specify). 
There may be situations when an SAE has occurred, and the Investigator has minimal 
information to include in the initial report to GSK. However, it is very important to 
record an assessment of causality for every event before submitting the Expedited AEs 
Report to GSK. 
The causality assessment is 1 of the criteria used when determining regulatory reporting 
requirements. The Investigator may change his/her opinion of causality after receiving 
additional information and update the SAE information accordingly. 
Assessment of Outcomes 
The Investigator will assess the outcome of all unsolicited AEs (including SAEs) 
recorded during the study as: 

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• 
Recovered/resolved. 
• 
Recovering/resolving. 
• 
Not recovered/not resolved. 
• 
Recovered with sequelae/resolved with sequelae. 
• 
Fatal (SAEs only) 
Medically Attended Visits 
For each solicited and unsolicited AE the participant experiences, the participant will be 
asked if the participant received medical attention (defined as hospitalization, or an 
otherwise unscheduled visit to or from medical personnel for any reason, including 
emergency room visits). This information will be recorded in the in the pDiary/source 
documents and in the eCRF/Expedited Adverse Events Report as applicable. 
Reporting, Follow-up, and Assessments of AE and/or SAE 
AE and SAE Recording 
All AEs and SAEs should be recorded into the appropriate section of the eCRF, irrespective of intensity 
or whether or not they are considered intervention-related. 
The participant will be instructed to contact the Investigator immediately should the participants 
manifest any signs or symptoms they perceive as serious. 
When an AE/SAE occurs, it is the responsibility of the Investigator to review all documentation (eg, 
hospital progress notes, laboratory, and diagnostics reports) relative to the event. The Investigator will 
then record all relevant information regarding an AE/SAE in the eCRF. The Investigator is not allowed 
to send photocopies of the participant’s medical records to either the Sponsor or IQVIA instead of 
appropriately completing the eCRF. However, there may be instances when copies of medical records 
for certain cases are requested by the Sponsor or IQVIA. In this instance, all participant identifiers will 
be blinded on the copies of the medical records prior to submission to the Sponsor or IQVIA. 
The Investigator will attempt to establish a diagnosis pertaining to the event based on signs, symptoms, 
and/or other clinical information. In such cases, the diagnosis should be documented as the AE/SAE and 
not the individual signs/symptoms. 
 
Follow-up of AEs and SAEs 
After the initial AE/SAE or any other event of interest for the study, the Investigator is required to 
proactively follow each participant at subsequent visits/contacts. All SAEs will be followed until the 
event is resolved, stabilized, or otherwise explained or the participant is lost to follow-up. Other non-
serious AEs must be followed until the last contact or until the participant is lost to follow-up. 
Follow-up During the Study 
AEs documented at a previous visit/contact and defined as not recovered/not resolved or 
recovering/resolving will be reviewed at subsequent visits/contacts until the last visit/contact of the 
participant. If the participant dies during participation in the study or during a recognized follow-up 
period, IQVIA will be provided with any available post-mortem findings, including histopathology. 
Follow-up After the Participant is Discharged from the Study 
The Investigator will provide any new or updated relevant information on previously reported SAE to 
IQVIA using electronic Expedited AE Report as applicable. The Investigator is obliged to perform or 

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arrange for the conduct of supplemental clinical examinations/tests and/or evaluations to elucidate the 
nature and/or causality of the AE or SAE as fully as possible. 
Updating of SAE Information After Removal of Write Access to the Participant’s eCRF 
When additional SAE information is received after removal of write access to the participant’s eCRF, 
new or updated information should be recorded on the appropriate paper report, with all changes signed 
and dated by the Investigator. 
 
Events Requiring Expedited Reporting to Sponsor’s Delegate 
• 
Once an Investigator becomes aware that an SAE has occurred in a study participant, the 
Investigator or Investigator’s designee must complete information in the electronic Expedited AE 
Report WITHIN 24 HOURS. The report will always be completed as thoroughly as possible with 
all available details of the event. The report allows to specify that the event is serious or non-
serious. 
• 
Even if the Investigator does not have all information regarding an SAE, the report should still be 
completed within 24 hours. Once additional relevant information is received, the report should be 
updated WITHIN 24 HOURS. The Investigator will always provide an assessment of causality at 
the time of the initial report. 
• 
The Investigator will be required to confirm the review of the SAE causality by ticking the 
“reviewed” box in the electronic Expedited AE Report within 72 hours of submission of the SAE. 
 
SAE Reporting to IQVIA via an Electronic Data Collection Tool 
• 
The primary mechanism for reporting an SAE to IQVIA will be the electronic data collection tool. 
• 
If the electronic system is unavailable for more than 24 hours, then the study center will use paper 
Expedited AE Report. 
• 
The study center will enter the SAE data into the electronic system as soon as it becomes available. 
• 
After the study is completed at a given study center, the electronic data collection tool will be taken 
off-line to prevent the entry of new data or changes to existing data. 
• 
If a study center receives a report of a new SAE from a participant or receives updated data on a 
previously reported SAE after the electronic data collection tool has been taken off-line, then the 
study center can report this information on a paper Expedited AE Report or by phone. 
• 
Contacts of SAE reporting can be found in the Study Reference Manual. 
 

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Appendix 4 
Contraceptive Guidance and Collection of Pregnancy 
Information 
Definitions 
Woman of Childbearing Potential (WOCBP) 
A woman is considered fertile following menarche and until becoming postmenopausal 
unless permanently sterile (see below). 
Women in the following categories are not considered WOCBP 
1. Premenarchal 
2. Premenopausal female with 1 of the following: 
a) Documented hysterectomy. 
b) Documented bilateral salpingectomy. 
c) Documented bilateral oophorectomy. 
Note: Documentation can come from the study center personnel’s: review of the 
participant’s medical records, medical examination, or medical history 
interview. 
3. Postmenopausal female: 
a) A postmenopausal state is defined as no menses for 12 months without an 
alternative medical cause. A high FSH level in the postmenopausal range may 
be used to confirm a postmenopausal state in women not using hormonal 
contraception or hormonal replacement therapy (HRT). However, in the absence 
of 12 months of amenorrhea, a single FSH measurement is insufficient. 
b) Females on HRT and whose menopausal status is in doubt will be required to 
use 1 of the non-estrogen hormonal highly effective contraception methods if 
they wish to continue their HRT during the study. Otherwise, they must 
discontinue HRT to allow confirmation of postmenopausal status before study 
enrollment. 
Contraception Guidance 
Female participants 
Female participants of childbearing potential are eligible to participate if they agree to 
use a highly effective method of contraception consistently and correctly as described in 
the table below. 

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Highly Effective Contraceptive Methods 
Highly Effective Contraceptive Methods That Are User Dependenta 
Failure rate of <1% per year when used consistently and correctly.  
Combined (estrogen and progestogen containing) hormonal contraception associated with inhibition of 
ovulation 
• 
Oral. 
• 
Intravaginal. 
• 
Transdermal. 
Progestogen only hormonal contraception associated with inhibition of ovulation 
• 
Oral. 
• 
Injectable.  
Highly Effective Methods That Are User Independenta  
• 
Implantable progestogen only hormonal contraception associated with inhibition of ovulation 
• 
Intrauterine device (IUD). 
• 
Intrauterine hormone-releasing system (IUS). 
• 
Bilateral tubal occlusion. 
Male partner sterilization prior to the female participant’s entry into the study, and this male is the sole 
partner for that participant, 
(The information on the male sterility can come from the site personnel’s review of the participant’s 
medical records; medical examination and/or semen analysis, or medical history interview provided by her 
or her partner). 
Vasectomized partner 
A vasectomized partner is a highly effective birth control method provided that the partner is the sole male 
sexual partner of the WOCBP and the absence of sperm has been confirmed. If not, an additional highly 
effective method of contraception should be used.  
Sexual abstinence 
Sexual abstinence is considered a highly effective method only if defined as refraining from heterosexual 
intercourse during the entire period of risk associated with the study treatment. The reliability of sexual 
abstinence needs to be evaluated in relation to the duration of the study and the preferred and usual lifestyle 
of the participant.  
NOTES:  
a Typical use failure rates may differ from those when used consistently and correctly. Use should be 
consistent with local regulations regarding the use of contraceptive methods for subjects participating in 
clinical studies. 

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Collection of Pregnancy Information 
Female Participants who Become Pregnant 
• 
The Investigator will collect pregnancy information on any female participant who 
becomes pregnant while participating in this study. Information will be recorded on 
the appropriate form and submitted to the Sponsor’s delegate within 24 hours of 
learning of a participant’s pregnancy. The participant will be followed to determine 
the outcome of the pregnancy. The Investigator will collect follow-up information on 
the participant and the neonate and the information will be forwarded to the Sponsor. 
Generally, follow-up will not be required for longer than 6 to 8 weeks beyond the 
estimated delivery date. Any termination of pregnancy will be reported, regardless of 
fetal status (presence or absence of anomalies) or indication for the procedure. 
• 
While pregnancy itself is not considered to be an AE or SAE, any pregnancy 
complication or elective termination of a pregnancy will be reported as an AE or 
SAE. A spontaneous abortion is always considered to be an SAE and will be 
reported as such. 
• 
Any post-study pregnancy related SAE considered reasonably related to the study 
treatment by the Investigator will be reported to the Sponsor as described in 
Section 8.3.3. While the Investigator is not obligated to actively seek this 
information in former participants, he or she may learn of an SAE through 
spontaneous reporting. 
• 
Any female participant who becomes pregnant while participating in the study will 
discontinue study intervention or be withdrawn from the study. 

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Appendix 5 
Genetics  
In Stage 1 only, genetic testing for HLA-B27 will be performed at Screening and only 
participants with a negative result will be allowed to participate in the study. The assay 
will be performed by the local site laboratory, or a laboratory designated by the site. In 
case of participant rescreening, this test should not be repeated since the result is not 
expected to change in the participant lifetime. 
 

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Appendix 6 
Definition of Medical Device AE, Adverse Device 
Effect (ADE), Serious Adverse Device Effect (SADE) 
and Unanticipated SADE (USADE) 
Definitions of a Medical Device AE 
• 
Medical device AE is any untoward medical occurrence, in a clinical study 
participant, users, or other persons, temporally associated with the use of study 
intervention whether considered related to a medical device or not. An AE can 
therefore be any unfavorable and unintended sign (including an abnormal laboratory 
finding), symptom, or disease (new or exacerbated) temporally associated with the 
use of a medical device. This definition includes events related to the medical device 
or comparator and events related to the procedures involved. 
• 
An ADE is an AE related to the use of a medical device. This definition includes any 
AE resulting from: 
− 
insufficient or inadequate instructions for use (ie, user error), or 
− 
any malfunction of a medical device, or 
− 
intentional misuse of the medical device. 
Definition of Medical Device SAE, SADE and USADE 
A medical device SAE is any serious adverse event that: 
Led to death  
Led to serious deterioration in the health of the participant, that either resulted in: 
• 
A life-threatening illness or injury. 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. 
• 
A permanent impairment of a body structure or a body function. 
• 
Inpatient or prolonged hospitalization. Planned hospitalization for a pre-existing condition, or 
a procedure required by the protocol, without serious deterioration in health, is not considered 
an SAE. 
• 
Medical or surgical intervention to prevent life-threatening illness or injury or permanent 
impairment to a body structure or a body function. 
Led to fetal distress, fetal death or a congenital abnormality or birth defect 
Is a suspected transmission of any infectious agent via a medicinal product  
Serious Adverse Device Effect (SADE) definition 
A SADE is defined as an adverse device effect that has resulted in any of the consequences characteristic 
of a serious adverse event. 
Any device deficiency that might have led to an SAE if appropriate action had not been taken or 
circumstances had been less fortunate. 

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Unanticipated SADE (USADE) definition 
An USADE (also identified as UADE in US Regulations 21 CFR 813.3), is a serious adverse device 
effect that by its nature, incidence, severity, or outcome has not been identified in the current version of 
the IB. 
Recording and Reporting of Medical Device AE, ADEs, SADEs, and USADE 
• 
Any device deficiency must be reported to Sponsor or Sponsor’s delegate within 
24 hours after the Investigator determines that the event meets the definition of a 
device deficiency. 
• 
Refer to paper ‘Medical device or combination product with device 
deficiency/incident report form’ for details on transmission of this information to the 
Sponsor. 
• 
Sponsor or Sponsor’s delegate will review all device deficiencies, determine, and 
document in writing whether they could have led to an SAE. These device 
deficiencies will be reported to the regulatory authorities and IRBs/IECs as required 
by national regulations. 
• 
If required or in case of any issues refer to the general safety contacts for SAE/AE 
reporting. 
Reporting of Medical Device Deficiencies for Associated Person 
• 
If an Associated Person (eg, spouse, caregiver, site staff etc.) experiences a device 
deficiency, the medical device deficiency information, and any associated AE/SAE 
information will be reported to GSK. The associated person will be provided with 
the safety reporting information and authorization to contact physician letter. 
• 
If follow-up information is required, authorization to contact physician (or other 
licensed medical practitioner) must be signed to obtain consent. 
• 
Medical device deficiencies should be reported using the medical device deficiency 
report form. 
• 
Sponsor will review all device deficiencies and determine and document in writing 
whether they could have led to an SAE. These device deficiencies will be reported to 
the regulatory authorities and IRBs/IECs as required by national regulations. 
• 
Contacts for Medical Device Deficiency reporting can be found in the medical 
device deficiency report form. 

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Appendix 7 
Grading Scales for Hematology and Biochemistry 
Safety Laboratory Assessments 
The details of grading scales are provided in Table 19 and Table 20. 
Table 19 
Stage 1 – Adults (Europe) 
Laboratory test 
Mild 
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially 
life--threatening 
(Grade 4) 
Creatinine – mg/dL (male) 
>1.17 – 1.7 
>1.7 – 2.0 
>2.0 – 2.5 
>2.5 or requires 
dialysis 
Creatinine – mg/dL (female) 
>0.96 – 1.7 
>1.7 – 2.0 
>2.0 – 2.5 
>2.5 or requires 
dialysis 
Liver Function Tests –ALT, 
AST 
increase by factor 
≥1.1 – 2.5 × 
ULN 
>2.5 – 5.0 × 
ULN 
>5.0 – 10 × 
ULN 
>10 × ULN 
Hemoglobin (female) - g/dL 
11.0 – <11.8 
9.5 – <11.0 
8.0 – <9.5 
<8.0 
Hemoglobin (female/male) 
change from baseline value - 
g/dL  
Any decrease – 
1.5 
>1.5 – 2.0 
>2.0 – 5.0 
>5.0 
Hemoglobin (male) - g/dL  
12.5 – <12.9 
10.5 – <12.5 
8.5 – <10.5 
<8.5 
WBC Increase - cell/mm3  
>9300 – 15000 
>15000 – 
20000 
>20000 – 
25000 
>25000 
WBC Decrease - cell/mm3  
2500 – <3650 
1500 – <2500 
1000 – 
<1500 
<1000 
Platelets Decreased - 
cell/mm3 (male) 
125000 – 
<149000 
100000 – 
<125000 
25000 – 
<100000 
<25000 
Platelets Decreased – 
cell/mm3 (female) 
125000 – 
<171000 
100000 – 
<125000 
25000 – 
<100000 
<25000 
Neutrophils Decrease - 
cell/mm3 
1500 – <1573 
1000 – <1500 
500 – 
<1000 
<500 
Lymphocytes decrease 
cell/mm3 
750 - <1133 
500 - <750 
250 - <500 
<250 
Eosinophils 
Cell/mm3 
>273 - 1500 
>1500 - 5000 
>5000 
Hypereosinophilic 
Abbreviations: ALT=alanine aminotransferase; AST = aspartate aminotransferase; ULN=upper limit of 
normal; WBC=white blood cell 
The grading scale has been adapted from the Food and Drug Administration (FDA) Guidance for Industry- 
Toxicity Grading Scale for Healthy Adult and Adolescent Volunteers Enrolled in Preventive Vaccine 
Clinical Trials [US Department of Health and Human Services, 2007] and adjusted considering local 
reference ranges provided by the site. Parameters not included in the FDA grading scales will not be 
graded; their assessment will be based on laboratory reference ranges and medical judgment. 

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Table 20 
Stage 2 – Adults (Africa) 
Laboratory test 
 
Mild  
(Grade 1) 
Moderate 
(Grade 2) 
Severe 
(Grade 3) 
Potentially 
life- 
threatening 
(Grade 4) 
Creatinine  
≥1.1 – 1.3 x ULN 
>1.3 – 1.8 x 
ULN OR 
Increase to 
1.3 to <1.5 
x 
participant’s 
baseline 
>1.8 – <3.5 x 
ULN OR 
Increase to 
1.5 to <2.0 
x 
participant’s 
baseline 
≥3.5 x ULN 
OR 
Increase of 
≥2.0 x 
participant’s 
baseline 
Liver Function 
Tests –ALT, 
AST 
≥1.25 – <2.5 x ULN 
2.5 – <5.0 x 
ULN 
5.0 – <10.0 x 
ULN 
≥10.0 x ULN 
Hemoglobin 
(female) - g/dL 
9.5 – <11.4 
8.5 – <9.5 
6.5 – < 8.5 
<6.5 
Hemoglobin 
(male) - g/dL  
10.0 – <11.4 
9.0 – <10.0 
7.0 – <9.0 
<7.0 
WBC Decrease - 
cell/mm3 
(male/female) 
2000 – <2400 
1500 – <2000 
1000 – <1500 
<1000 
Platelets 
Decreased - 
cell/mm3 
(male/female) 
100000 – <117000 
50000 – 
<100000 
25000 – 
<50000 
<25000 
Neutrophils 
Decrease - 
cell/mm3 
(male/female) 
700 – <750 
600 – <700 
400 – <600 
<400 
Lymphocytes 
decrease 
cell/mm3 
(male/female) 
600 – <830 
500 – <600 
350 – <500 
<350 
Abbreviations: ALT=alanine aminotransferase; AST=aspartate aminotransferase; ULN=upper limit of 
normal; WBC=white blood cell. The grading scale has been adapted from the Division of AIDS 
(DAIDS) Table for Grading the Severity of Adult and Pediatric Adverse Events [US Department of 
Health and Human Services, 2017] and adjusted considering local normal ranges provided by the site. 
Parameters not included in the DAIDS grading scales will not be graded and their assessment will be 
based on laboratory normal ranges and medical judgment. 

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Appendix 8 
Protocol Amendment History 
The Protocol Amendment Summary of Changes Table for the current amendment is 
located directly before the Table of Contents (TOC). 
Amendment 1 (12 August 2022) 
This amendment is considered to be substantial based on the criteria set forth in 
Article 10(a) of Directive 2001/20/EC of the European Parliament and the Council of the 
European Union. 
Overall Rationale for the Amendment: 
The original protocol has been amended to include the suggestions from the Belgium site 
Ethics Committee, and remove exploratory tertiary endpoints related to Stage 2 blood 
sampling that can no longer be performed and as such are no longer applicable and to 
correct inconsistencies in the protocol.  
Section # and Name 
Description of Change 
Brief Rationale 
Throughout 
Minor editorial and document formatting 
revisions 
Minor, therefore, 
have not been 
summarized 
Section 1.0 Protocol Synopsis, 
Section 3.0 Objectives and 
Endpoints, Section 1.3 
Schedule of Activities Table 1 
Schedule of Activities, 
Section 8.1.2 Laboratory 
Assays, Section 9.4.1 Primary 
Endpoints, Table 11 Primary 
Endpoints-Statistical Analyses 
The primary endpoints were updated. 
In the Original Protocol, the reporting 
duration of AEs/SAEs leading to withdrawal 
from the study and/or withholding doses of 
study intervention was mentioned up to the 
study end (Day 1 to Day 337). This duration 
was updated to 28 days after third study 
intervention administration (Day 1 to 
Day 197) in Protocol Amendment 1. 
To differentiate 
between the active 
follow-up duration 
from Day 1 to Day 
197 and long-term 
safety follow-up 
duration from 
Day 197 to Day 337. 
Section 1.0 Protocol Synopsis, 
Section 3.0 Objectives and 
Endpoints, Section 1.3 
Schedule of Activities Table 1 
Schedule of Activities, 
Section 8.1.2 Laboratory 
Assays, Section 9.4.1 Primary 
Endpoints, Section 9.4.2 
Secondary Endpoints Table 12 
Secondary Endpoints-Statistical 
Analyses 
In the Protocol Amendment 1, a new 
secondary endpoint was added to include 
number of participants with AEs/SAEs 
leading to withdrawal from the study from 
28 days after third study intervention 
administration (Day 197) up to Day 337. 
To differentiate 
between the active 
follow-up duration 
from Day 1 to Day 
197 and long-term 
safety follow-up 
duration from 
Day 197 to Day 337. 
Section 1.0 Protocol Synopsis, 
Section 3.0 Objectives and 
Endpoints, Section 1.3 
Schedule of Activities Table 1 
Schedule of Activities, 
Section 8.1.2 Laboratory 
Assays Table 9 Laboratory 
Assays, Section 9.4.3 Tertiary 
Tertiary endpoints were updated to reflect the 
subset of visits from each group instead of 
subset of randomly selected participants from 
each group. 
It was clarified that immunogenicity samples 
from different groups will be considered for 
different antibody components. 
To maximize the 
number of samples 
to be tested for 
functionality of 
antibodies, by 
sampling all 
participants but 
limiting the time 

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Section # and Name 
Description of Change 
Brief Rationale 
Endpoints Table 13 Tertiary 
Endpoints-Statistical Analyses 
points to the most 
relevant ones 
Section 1.0 Protocol Synopsis, 
Section 3.0 Objectives and 
Endpoints, Section 1.3 
Schedule of Activities Table 1 
Schedule of Activities, 
Section 4.1.2 Stage 2, Section 
8.1.1 Biological Samples Table 
8 Biological Sample, Section 
9.4.3 Tertiary Endpoints, 
Appendix 5 Genetics 
Flow cytometry, cytokines and gene 
expression for Stage 2 have been removed. 
The following endpoints or information 
related to these endpoints were deleted: 
• 
S. Typhimurium-specific lymphocyte 
populations in randomly selected 
participants from each group in 
Africa/Stage 2 before each study 
intervention administration (Day 1, 
Day 57, and Day 169), 7 days after 
each study intervention 
administration (Day 8, Day 64, and 
Day 176) and 28 days after each 
study intervention administration 
(Day 29, Day 85, and Day 197)  
• 
Quantify cytokines produced 
following vaccination using a 
Luminex multiplex cytokine assay 
before each study intervention 
administration (Day 1, Day 57, and 
Day 169) and 7 days after each study 
intervention administration (Day 8, 
Day 64, and Day 176)  
• 
Characterize gene expression with 
ribonucleic acid-sequencing in all 
participants in Stage 2 before each 
study intervention administration 
(Day 1, Day 57, and Day 169) and 7 
days after each study intervention 
administration (Day 8, Day 64, and 
Day 176) 
The specified 
analysis is no longer 
feasible at the site as 
earlier planned 
Section 1.0 Synopsis, Section 
1.3 Schedule of Activities 
Table 1 Schedule of Activities, 
Section 4.1.2 Stage 2 
Statement about safety follow-up call in Stage 
2 was added. 
To clarify that the 
sentinels in Stage 2 
will also be 
followed up with a 
safety phone call, 
similar to Stage 1 
participants. 
Section 1.3 Schedule of 
Activities Table 1 Schedule of 
Activities, Section 4.1.2 
Stage 2 
Statement about 7-day post-dose sample for 
antibody determination was deleted.  
To correct an error 
which was 
introduced in the 
Original Protocol. 
CCI

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Section # and Name 
Description of Change 
Brief Rationale 
Section 1.3 Schedule of 
Assessments Table 2 Intervals 
Between Study Visits 
The last study interval was updated from 
Visit 9 (Day 197) → Visit 10 (Day 337) to 
Visit 7 (Day 169) → Visit 10 (Day 337). 
For consistency and 
relevancy. 
Section 1.3 Schedule of 
Activities Table 1 Schedule of 
Activities 
Information about Home visit was added. 
To clarify that a 
home visit may be 
performed in 
Stage 2 to assist 
illiterate participants 
in completing the 
diary cards and 
same will be 
included in the 
eCRFs. 
Section 1.3 Schedule of 
Activities Table 1 Schedule of 
Activities, Section 4.1.2 
Stage 2, Section 5.1 Inclusion 
Criteria, Section 8.6 Genetic 
Testing, Appendix 5 Genetics 
It was clarified that HLA-B27 testing will be 
done in Stage 1 only. 
The HLA test was 
added in the 
Original Protocol 
based on advice 
from Belgian 
authorities. 
This is removed for 
Stage 2 now due to 
unavailability of 
HLA-B27 test in 
Malawi and based 
on the feedback 
from Malawi PI that 
genetic testing is not 
favored by Malawi 
EC. 
Section 1.1 Synopsis, 
Section 4.1.2 Stage 2 
It was clarified that, if the participants have 
any complaints, they will be invited to the 
study site for an evaluation of the possible 
AEs and holding rules, prior to administration 
of study intervention in the next participant. If 
the Investigator becomes aware of a holding 
rule being met, he/she must suspend 
administration of the study intervention and 
inform the Sponsor’s delegate immediately 
who will in-turn inform the Sponsor. 
To provide further 
details and ensure 
that holding rules 
are applied 
promptly, if needed. 
Section 4.1.2 Stage 2 Table 4 
Study groups, Intervention, and 
Blinding 
It was clarified that the Sponsor 
representatives are unblinded after Visit 9 are 
completed for all subjects. 
For clarity 
Section 4.4 End of Study 
Definition 
The end of study information (in case where 
the end of study would be the date of last 
testing results revealed) was updated to be 
achieved no later than 8 months after last 
subject last visit instead of 6 months after 
third study intervention administration. 
To adhere to the 
applicable 
guidelines, since 
these guidelines 
consider last subject 
last visit as the 
criteria for the end 
of study  
Section 6.0 Study Intervention 
The title was updated from Study Intervention 
to Study Intervention and Concomitant 
To reflect that this 
section also includes 

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Section # and Name 
Description of Change 
Brief Rationale 
and Concomitant Therapy 
Therapy. 
information about 
concomitant 
medications 
Section 6.1 Study 
Intervention(s) Administered 
Table 7 Study Interventions 
Administered (Comparator and 
Control Vaccines) 
The presentation for Saline was updated to 
“ampoule” from “vial” 
To rectify an earlier 
error 
Section 6.3.3.1 Emergency 
Unblinding 
Sponsor helpdesk contact is removed, because 
CRO’s (IQVIA) randomization system will be 
used in the study. 
To facilitate prompt 
access by the 
Investigator in case 
emergency 
unblinding is 
required 
Section 8.6 Genetic Testing 
It was clarified that based on advice from 
Belgian CA (FAHMP), to minimize any risk 
of autoimmune reactions, and spondyloses 
specifically, blood samples collected for 
safety during Screening in Stage 1 will 
undergo sampling for HLA-B27 genetic 
marker and only prospective participants who 
are found to be negative for HLA-B27 will be 
included in the study. 
Rationale added for 
rationale for 
including only 
participants negative 
for HLA B27, in 
Stage 1 
Section 10.0 references 
New references have been added. 
To provide the 
background for 
newly added 
information in the 
document 
Appendix 2 Regulatory, 
Ethical, and Study Oversight 
Considerations 
It was added that the Sponsor must keep 
coded data from clinical studies for a 
minimum of 30 years after the end of the 
study to ensure the validity of the research. 
This will also be the case if a participant 
stopped study participation prematurely. The 
Sponsor will also keep coded data, where 
needed because of legal action or an 
investigation involving the Sponsor. 
Based on the request 
for Belgian site 
Ethics Committee 
Throughout 
Minor editorial and document formatting 
revisions 
To improve the 
quality of the 
document 
 

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Appendix 9 
Signature of Investigator 
PROTOCOL TITLE: A Phase 1/2a, observer-blind, randomized, controlled, two-stage, 
multi-country study to evaluate the safety, reactogenicity and immune response of the 
trivalent vaccine against invasive nontyphoidal Salmonella (iNTS) and Typhoid Fever in 
healthy European and African adults 
PROTOCOL NO: 
216152 (INTS-GMMA GVGH-002) (H08_01TP) 
VERSION:  
 
Protocol Amendment 2 Final  
This protocol is a confidential communication of Sponsor. I confirm that I have read this 
protocol, I understand it, and I will work according to this protocol. I will also work 
consistently with the ethical principles that have their origin in the Declaration of 
Helsinki and that are consistent with Good Clinical Practices and the applicable laws and 
regulations. Acceptance of this document constitutes my agreement that no unpublished 
information contained herein will be published or disclosed without prior written 
approval from the Sponsor. 
Instructions to the Investigator: Please SIGN and DATE this signature page. PRINT your 
name, title, and the name of the study center in which the study will be conducted. Return 
the signed copy to IQVIA. 
 
I have read this protocol in its entirety and agree to conduct the study accordingly: 
 
Signature of Investigator:  
__________________________ Date: ________ 
Printed Name: ___________________________ 
Investigator Title: ___________________________ 
 
Name/Address of Center:  
___________________________ 
 
 
 
 
 
___________________________ 
 
 
 
 
 
___________________________ 
 

Signature Page for  216152 TMF-16201956 v1.0
Signature Page for TMF-16201956 v1.0
Reason for signing: Approved
Name:
Role: Approver
Date of signature: 09-Jun-2023 14:09:40 GMT+0000
PPD