Study in Healthy Adults to Evaluate Gene Activation After Vaccination With GlaxoSmithKline (GSK) Biologicals' Candidate Tuberculosis (TB) Vaccine GSK 692342

Phase 2

Completed

Conditions: Tuberculosis

Interventions: Biological: GSK Biologicals' investigational TB vaccine GSK 692342

Registration Number: NCT01669096

Lead Sponsor: GlaxoSmithKline

Brief Summary: The purpose of this study is to assess the safety and immunogenicity of two doses of the TB vaccine administered according to a 0, 1 month schedule. In, addition, blood samples collected at different time points after vaccination will be analysed to see when exactly genes are activated by the vaccine using an assay called mRNA expression profiling. The different methods for mRNA expression profiling using whole blood samples versus Peripheral Blood Mononuclear cell(s) (PBMCs), will also be compared.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 20

Inclusion Criteria

Subjects who, in the opinion of the investigator, can and will comply with the requirements of the protocol.
A male or female between, and including, 18 and 50 years of age at the time of obtaining informed consent.
Written informed consent obtained from the subject.
Healthy subjects as established by medical history and clinical examination before entering into the study.
Known BCG vaccination or presence of a BCG scar.
Seronegative for human immunodeficiency virus-1.
Female of non-childbearing potential may be enrolled in the study.
Female subjects of childbearing potential may be enrolled in the study, if the subject:
- has practiced adequate contraception for 30 days prior to vaccination, and
- has a negative pregnancy test on the day of screening and the day of first vaccination, and
- has agreed to continue adequate contraception during the entire treatment period and for 2 months after completion of the vaccination series.

Exclusion Criteria

Use of any investigational or non-registered product (drug or vaccine) other than the study vaccine within 30 days preceding the first dose of study vaccine, or planned use during the study period.
Chronic administration (defined as more than 14 days in total) of immunosuppressants or other immune-modifying drugs within six months prior to the first vaccine dose (for corticosteroids, this will mean prednisone ≥ 20 mg/day or equivalent). Inhaled and topical steroids are allowed.
Administration of long-acting immune-modifying drugs starting 2 years before the first dose and planned administration during the study.
Planned administration/administration of a vaccine/product not foreseen by the study protocol within the period starting 30 days before the first dose of study vaccine and ending at the last study visit.
Concurrently participating in another clinical study, at any time during the study period, in which the subject has been or will be exposed to an investigational or a non-investigational vaccine/product (pharmaceutical product or device).
History of TB disease.
History of any reaction or hypersensitivity likely to be exacerbated by any component of the vaccine.
Any confirmed or suspected immunosuppressive or immunodeficient condition, based on medical history and physical examination.
QuantiFERON® TB Gold positive test result.
History of medically confirmed autoimmune disease.
Administration of immunoglobulins and/or any blood products within the 3 months preceding the first dose of study vaccine or planned administration during the study period.
History of any reaction of hypersensitivity likely to be exacerbated by any component of the vaccine.
Pregnant or lactating female.
Female planning to become pregnant or planning to discontinue contraceptive precautions.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
GSK 692342 Group	GSK Biologicals' investigational TB vaccine GSK 692342	Healthy male and female subjects, between and including 18 to 50 years of age, who received 2 doses of GSK 692342 vaccine administered intramuscularly in the deltoid region of the arm, at Days 0 and 30.

Primary Outcome Measures

Name	Time	Method
Frequency of M72 Fusion Protein Specific Cluster of Differentiation CD4+/CD8+ T Cells Expressing at Least Two Different Immune Markers	At Day 60 post-Dose 2	Among immune markers expressed were interleukin-2 (IL-2) and/or tumour necrosis factor-alpha (TNF-α) and/or interferon-gamma (IFN-γ) and/or cluster of differentiation 40-ligand \[CD40-L\] and/or IL-13 and/or IL-17. The analysis of cytokines expression was performed by flow cytometry using intracellular cytokine staining (ICS) on frozen peripheral blood mononuclear cell (PBMCs).
Concentration of Specific Interferon Gamma (IFN-γ) Antibodies Secreted in Serum Samples	At Day 47 post-Dose 2	Antibody concentrations are presented as geometric mean concentrations (GMCs), expressed in femtogram per milliliter (fg/mL), as assessed by cytometric bead array (CBA) assay. The reference seropositivity cut-off value was equal to or above (≥) 7047 fg/mL.
Frequency of Mycobacterium Tuberculosis Fusion Protein (M72) Specific Cluster of Differentiation CD4+/CD8+ T Cells Expressing at Least Two Different Immune Markers	At Day 0 prior to Dose 1	Among immune markers expressed were interleukin-2 (IL-2) and/or tumour necrosis factor-alpha (TNF-α) and/or interferon-gamma (IFN-γ) and/or cluster of differentiation 40-ligand (CD40-L) and/or IL-13 and/or IL-17. The analysis of cytokines expression was performed by flow cytometry using intracellular cytokine staining (ICS) on frozen peripheral blood mononuclear cell (PBMCs).
Frequency of M72 Specific Cluster of Differentiation CD4+ T Cells Expressing Any Combination of Immune Markers (M1 to M 14)	At Day 0 prior -Dose 1	Expressed immune markers combinations for CD4+ T cells included CD40-L, IL-2, TNF-α, IFN-γ, IL-17 and IL-13, as follows: M1=CD4.CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(+); M2=CD4.CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(-); M3=CD4.CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(+); M4=CD4.CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(-); M5=CD4.CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(+); M6=CD4.CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(-); M7=CD4.CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(+); M8=CD4.CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(-); M9=CD4.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(+); M10=CD4.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(-); M11=CD4.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(+); M12=CD4.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(-); M13=CD4.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(+); M14=CD4.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(-).
Frequency of M72 Specific Cluster of Differentiation CD4+ T Cells Expressing Any Combination of Immune Markers (M15 to M28)	At Day 0 prior-Dose 1	Expressed immune markers combinations for CD4+ T cells included CD40-L, IL-2, TNF-α, IFN-γ, IL-17 and IL-13, as follows: M15=CD4.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(+); M16=CD4.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(-); M17=CD4.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(+); M18=CD4.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(-); M19=CD4.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(+); M20=CD4.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(-); M21=CD4.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(+); M22=CD4.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(-); M23=CD4.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(+); M24=CD4.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(-); M25=CD4.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(+); M26=CD4.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(-); M27=CD4.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(+); M28=CD4.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(-).
Frequency of M72 Specific Cluster of Differentiation CD4+ T Cells Expressing Any Combination of Immune Markers (M29 to M42)	At Day 0 prior - Dose 1	Expressed immune markers combinations for CD4+ T cells included CD40-L, IL-2, TNF-α, IFN-γ, IL-17 and IL-13, as follows: M29=CD4.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(+); M30=CD4.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(-); M31=CD4.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(+); M32=CD4.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(-); M33=CD4.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(+); M34=CD4.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(-); M35=CD4.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(+); M36=CD4.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(-); M37=CD4.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(+); M38=CD4.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(-); M39=CD4.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(+); M40=CD4.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(-); M41=CD4.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(-); M42=CD4.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(+).
Frequency of M72 Specific Cluster of Differentiation CD4+ T Cells Expressing Any Combination of Immune Markers (M43 to M56)	At Day 0 (prior- Dose 1)	Expressed immune markers combinations for CD4+ T cells included CD40-L, IL-2, TNF-α, IFN-γ, IL-17 and IL-13, as follows: M43=CD4.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(-); M44=CD4.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(+); M45=CD4.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(-); M46=CD4.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(+); M47=CD4.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(-); M48=CD4.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(+); M49=CD4.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(+); M50=CD4.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(-); M51=CD4.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(+); M52=CD4.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(-); M53=CD4.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(+); M54=CD4.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(-); M55=CD4.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(+); M56=CD4.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(-).
Frequency of M72 Specific Cluster of Differentiation CD4+ T Cells Expressing Any Combination of Immune Markers (M57 to M63)	At Day 0 (prior to Dose 1)	Expressed immune markers combinations for CD4+ T cells included CD40-L, IL-2, TNF-α, IFN-γ, IL-17 and IL-13, as follows: M57=CD4.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(+); M58=CD4.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(-); M59=CD4.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(+); M60=CD4.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(-); M61=CD4.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(+); M62=CD4.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(-); M63=CD4.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(+).
Frequency of M72 Specific Cluster of Differentiation CD4+ T Cells Expressing Any Combination of Immune Markers, Post Dose 2 (M1 to M14)	At Day 60 post-Dose 2	Expressed immune markers combinations for CD4+ T cells included CD40-L, IL-2, TNF-α, IFN-γ, IL-17 and IL-13, as follows: M1=CD4.CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(+); M2=CD4.CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(-); M3=CD4.CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(+); M4=CD4.CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(-); M5=CD4.CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(+); M6=CD4.CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(-); M7=CD4.CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(+); M8=CD4.CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(-); M9=CD4.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(+); M10=CD4.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(-); M11=CD4.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(+); M12=CD4.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(-); M13=CD4.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(+); M14=CD4.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(-).
Frequency of M72 Specific Cluster of Differentiation CD4+ T Cells Expressing Any Combination of Immune Markers, Post Dose 2 (M15 to M28)	At Day 60 post - Dose 2	Expressed immune markers combinations for CD4+/CD8+ T cells included CD40-L, IL-2, TNF-α, IFN-γ, IL-17 and IL-13, as follows: M15=CD4.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(+); M16=CD4.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(-); M17=CD4.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(+); M18=CD4.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(-); M19=CD4.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(+); M20=CD4.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(-); M21=CD4.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(+); M22=CD4.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(-); M23=CD4.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(+); M24=CD4.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(-); M25=CD4.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(+); M26=CD4.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(-); M27=CD4.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(+); M28=CD4.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(-).
Frequency of M72 Specific Cluster of Differentiation CD4+ T Cells Expressing Any Combination of Immune Markers, Post Dose 2 (M29 to M42)	At Day 60 post Dose 2	Expressed immune markers combinations for CD4+ T cells included CD40-L, IL-2, TNF-α, IFN-γ, IL-17 and IL-13, as follows: M29=CD4.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(+); M30=CD4.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(-); M31=CD4.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(+); M32=CD4.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(-); M33=CD4.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(+); M34=CD4.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(-); M35=CD4.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(+); M36=CD4.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(-); M37=CD4.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(+); M38=CD4.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(-); M39=CD4.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(+); M40=CD4.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(-); M41=CD4.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(-); M42=CD4.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(+).
Frequency of M72 Specific Cluster of Differentiation CD8+ T Cells Expressing Any Combination of Immune Markers (M1 to M14)	At Day 0 prior-Dose 1	Expressed immune markers combinations for CD8+ T cells included CD40-L, IL-2, TNF-α, IFN-γ, IL-17 and IL-13, as follows: M1=CD8.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(-); M2=CD8.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(+); M3=CD8.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(-); M4=CD8.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(+); M5=CD8.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(-); M6=CD8.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(+); M7=CD8.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(-); M8=CD8.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(+); M9=CD8.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(-); M10=CD8.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(+); M11=CD8.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(-); M12=CD8.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(+); M13=CD8.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(-); M14=CD8.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(+).
Frequency of M72 Specific Cluster of Differentiation CD8+ T Cells Expressing Any Combination of Immune Markers (M15 to M28)	At Day 0 prior -Dose 1	Expressed immune markers combinations for CD8+ T cells included CD40-L, IL-2, TNF-α, IFN-γ, IL-17 and IL-13, as follows: M15=CD8.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(-); M16=CD8.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(+); M17=CD8.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(-); M18=CD8.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(+); M19=CD8.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(-); M20=CD8.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(+); M21=CD8.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(-); M22=CD8.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(+); M23=CD8.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(-); M24=CD8.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(+); M25=CD8.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(-); M26=CD8.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(+); M27=CD8.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(-); M28=CD8.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(+).
Frequency of M72 Specific Cluster of Differentiation CD4+ T Cells Expressing Any Combination of Immune Markers,Post Dose 2 (M43 to M56)	At Day 60 (post-Dose 2)	Expressed immune markers combinations for CD4+ T cells included CD40-L, IL-2, TNF-α, IFN-γ, IL-17 and IL-13, as follows: M43=CD4.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(-); M44=CD4.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(+); M45=CD4.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(-); M46=CD4.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(+); M47=CD4.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(-); M48=CD4.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(+); M49=CD4.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(+); M50=CD4.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(-); M51=CD4.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(+); M52=CD4.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(-); M53=CD4.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(+); M54=CD4.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(-); M55=CD4.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(+); M56=CD4.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(-).
Frequency of M72 Specific Cluster of Differentiation CD4+ T Cells Expressing Any Combination of Immune Markers, Post Dose 2 (M57 to M63)	At Day 60 post- Dose 2	Expressed immune markers combinations for CD4+ T cells included CD40-L, IL-2, TNF-α, IFN-γ, IL-17 and IL-13, as follows: M57=CD4.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(+); M58=CD4.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(-); M59=CD4.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(+); M60=CD4.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(-); M61=CD4.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(+); M62=CD4.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(-); M63=CD4.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(+).
Frequency of M72 Specific Cluster of Differentiation CD8+ T Cells Expressing Any Combination of Immune Markers (M29 to M42)	At Day 0 prior- Dose 1	Expressed immune markers combinations for CD8+ T cells included CD40-L, IL-2, TNF-α, IFN-γ, IL-17 and IL-13, as follows: M29=CD8.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(-); M30=CD8.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(+); M31=CD8.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(-); M32=CD8.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(+); M33=CD8.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(-); M34=CD8.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(+); M35=CD8.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(-); M36=CD8.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(+); M37=CD8.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(-); M38=CD8.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(+); M39=CD8.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(-); M40=CD8.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(+); M41=CD8.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(-); M42=CD8.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(+).
Frequency of M72 Specific Cluster of Differentiation CD8+ T Cells Expressing Any Combination of Immune Markers (M43 to M56)	At Day 0 prior to Dose 1	Expressed immune markers combinations for CD8+ T cells included CD40-L, IL-2, TNF-α, IFN-γ, IL-17 and IL-13, as follows: M43=CD8.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(-); M44=CD8.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(+); M45=CD8.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(-); M46=CD8.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(+); M47=CD8.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(-); M48=CD8.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(+); M49=CD8.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(-); M50=CD8.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(+); M51=CD8_CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(+); M52=CD8_CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(-); M53=CD8_CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(+); M54=CD8_CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(-); M55=CD8_CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(+); M56=CD8_CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(-).
Frequency of M72 Specific Cluster of Differentiation CD8+ T Cells Expressing Any Combination of Immune Markers (M57 to M63)	At Day 0 (prior to Dose 1)	Expressed immune markers combinations for CD8+ T cells included CD40-L, IL-2, TNF-α, IFN-γ, IL-17 and IL-13, as follows: M57=CD8_CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(+); M58=CD8_CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(-); M59=CD8_CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(+); M60=CD8_CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(-); M61=CD8_CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(+); M62=CD8_CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(-); M63=CD8_CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(+).
Frequency of M72 Specific Cluster of Differentiation CD8+ T Cells Expressing Any Combination of Immune Markers, Post Dose 2 (M1 to M14)	At Day 60 post-Dose 2	Expressed immune markers combinations for CD8+ T cells included CD40-L, IL-2, TNF-α, IFN-γ, IL-17 and IL-13, as follows: M1=CD8.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(-); M2=CD8.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(+); M3=CD8.CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(-); M4=CD8.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(+); M5=CD8.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(-); M6=CD8.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(+); M7=CD8.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(-); M8=CD8.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(+); M9=CD8.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(-); M10=CD8.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(+); M11=CD8.CD40L(+)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(-); M12=CD8.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(+); M13=CD8.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(-); M14=CD8.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(+).
Frequency of M72 Specific Cluster of Differentiation CD8+ T Cells Expressing Any Combination of Immune Markers, Post Dose 2 (M15 to M28)	At Day 60 post -Dose 2	Expressed immune markers combinations for CD8+ T cells included CD40-L, IL-2, TNF-α, IFN-γ, IL-17 and IL-13, as follows: M15=CD8.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(-); M16=CD8.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(+); M17=CD8.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(-); M18=CD8.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(+); M19=CD8.CD40L(+)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(-); M20=CD8.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(+); M21=CD8.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(-); M22=CD8.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(+); M23=CD8.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(-); M24=CD8.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(+); M25=CD8.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(-); M26=CD8.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(+); M27=CD8.CD40L(-)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(-); M28=CD8.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(+).
Frequency of M72 Specific Cluster of Differentiation CD8+ T Cells Expressing Any Combination of Immune Markers, Post Dose 2 (M29 to M42)	At Day 60 post- Dose 2	Expressed immune markers combinations for CD8+ T cells included CD40-L, IL-2, TNF-α, IFN-γ, IL-17 and IL-13, as follows: M29=CD8.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(-); M30=CD8.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(+); M31=CD8.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(-); M32=CD8.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(+); M33=CD8.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(-); M34=CD8.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(+); M35=CD8.CD40L(-)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(-); M36=CD8.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(+); M37=CD8.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(-); M38=CD8.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(+); M39=CD8.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(-); M40=CD8.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(+); M41=CD8.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(-); M42=CD8.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(+).
Frequency of M72 Specific Cluster of Differentiation CD8+ T Cells Expressing Any Combination of Immune Markers, Post Dose 2 (M43 to M56)	At Day 60 post-Dose 2	Expressed immune markers combinations for CD8+ T cells included CD40-L, IL-2, TNF-α, IFN-γ, IL-17 and IL-13, as follows: M43=CD8.CD40L(-)+IL-2(-)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(-); M44=CD8.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(+); M45=CD8.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(-); M46=CD8.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(+); M47=CD8.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(-); M48=CD8.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(+); M49=CD8.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(-); M50=CD8.CD40L(-)+IL-2(-)+TNF-α(-)+IFN-γ(-)+IL-17(-)+IL-13(+); M51=CD8_CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(+); M52=CD8_CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(+)+IL-13(-); M53=CD8_CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(+); M54=CD8_CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(+)+IL-17(-)+IL-13(-); M55=CD8_CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(+); M56=CD8_CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(+)+IL-13(-).
Frequency of M72 Specific Cluster of Differentiation CD8+ T Cells Expressing Any Combination of Immune Markers, Post Dose 2 (M57 to M63)	At Day 60 post Dose 2	Expressed immune markers combinations for CD8+ T cells included CD40-L, IL-2, TNF-α, IFN-γ, IL-17 and IL-13, as follows: M57=CD8_CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(+); M58=CD8_CD40L(+)+IL-2(+)+TNF-α(+)+IFN-γ(-)+IL-17(-)+IL-13(-); M59=CD8_CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(+); M60=CD8_CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(+)+IL-13(-); M61=CD8_CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(+); M62=CD8_CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(+)+IL-17(-)+IL-13(-); M63=CD8_CD40L(+)+IL-2(+)+TNF-α(-)+IFN-γ(-)+IL-17(+)+IL-13(+).
Number of Subjects With Serious Adverse Events (SAEs)	During the entire study period (from Day 0 to Month 7)	SAEs assessed include medical occurrences that result in death, are life-threatening, require hospitalization or prolongation of hospitalization or result in disability/incapacity.
Number of Subjects With Any and Grade 3 Solicited Local Symptoms	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses	Assessed solicited local symptoms were pain, redness and swelling. Any = occurrence of the symptom regardless of intensity grade. Grade 3 pain = pain that prevented normal activity. Grade 3 redness/swelling = redness/swelling spreading beyond 50 millimeters (mm) of injection site.
Number of Subjects With Any, Grade 3 and Related Solicited General Symptoms	During the 7-day (Days 0-6) post-vaccination period following each dose and across doses	Assessed solicited general symptoms were Fatigue, Gastrointestinal symptoms, Headache, Malaise, Myalgia and Fever \[defined as axillary temperature equal to or above (≥) 37.5 degrees Celsius (°C)\]. Any = incidence of any particular symptom regardless of intensity grade. Grade 3 = incidence of a particular symptom that prevented normal, everyday activity. Grade 3 fever = axillary temperature above (\>) 39.5 °C. Related = general symptom assessed by the investigator as causally related to the study vaccination.
Number of Subjects With Unsolicited Adverse Events (AEs)	During the 30-day (Days 0-29) post-vaccination period	An unsolicited AE covers any untoward medical occurrence in a clinical investigation subject temporally associated with the use of a medicinal product, whether or not considered related to the medicinal product and reported in addition to those solicited during the clinical study and any solicited symptom with onset outside the specified period of follow-up for solicited symptoms. Any was defined as the occurrence of any unsolicited AE regardless of intensity grade or relation to vaccination. Grade 3 AE = an AE which prevented normal, everyday activities. Related AE = an AE assessed by the investigator as causally related to the study vaccination.
Number of Subjects With Potential Immune-Mediated Disease(s) (pIMDs)	During the entire study period (From Day 0 to Month 7)	pIMDs are a subset of AEs that include autoimmune diseases and other inflammatory and/or neurologic disorders of interest which may or may not have an autoimmune aetiology.