Study to Evaluate Immunogenicity of the Hepatitis B Antigen of the GSK Biologicals' Candidate Malaria Vaccine (257049)

Concentrations, by enzyme-linked immunosorbent assay (ELISA), were presented as geometric mean concentrations (GMCs), and expressed in milli-international units per milliliter (mIU/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (\>=) 10 mIU/mL. A decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following partial or complete retesting/reanalysis, for each RTS,S Regimen A, B, C and each Engerix B Regimen A and B study groups.

Time frame: At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity measures were available.

Concentrations, by enzyme-linked immunosorbent assay (ELISA), were presented as geometric mean concentrations (GMCs), and expressed in milli-international units per milliliter (mIU/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (\>=) 10 mIU/mL. A decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following partial or complete retesting/reanalysis, with study groups pooled by primary vaccine administered (RTS,S vs Engerix-B).

Time frame: At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity measures were available.

A seroprotected subject was defined as a subject with anti-HBs antibody titers greater than or equal to (\>=) the cut-off of 10 mili-international units per mililiter (mIU/mL). A decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following partial or complete retesting/reanalysis, with study groups pooled by primary vaccine administered (RTS,S vs Engerix -B).

Time frame: At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity measures were available.

Anti-CS antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and presented as geometric mean concentrations (GMCs) expressed in ELISA units per milliliter (EL.U/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (\>=) 0.5 EL.U/mL. The table shows results for each RTS,S Regimen A, B & C, and for each Engerix B Regimen A & B study groups. No anti-CS results are available for the time point 24 months post Dose 3 (Month 26) because the quantity of serum available for the anti-CS assay was insufficient for many samples.

Time frame: At Month 14, aka at 12 months post Dose 3 of RTS,S vaccine or Engerix-B

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity measures were available.

Anti-CS antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and presented as geometric mean concentrations (GMCs) expressed in ELISA units per milliliter (EL.U/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (\>=) 0.5 EL.U/mL. The table shows results for each RTS,S Regimen A, B & C, and for each Engerix B Regimen A & B study groups.

Time frame: At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity measures were available.

Anti-CS antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and presented as geometric mean concentrations (GMCs) expressed in ELISA units per milliliter (EL.U/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (\>=) 1.9 EL.U/mL. The table shows results for each RTS,S Regimen A, B & C, and for each Engerix B Regimen A & B study groups.

Time frame: At Months 38 and 50, aka 36 and 48 months post Dose 3 of RTS,S vaccine or Engerix-B

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity measures were available.

Concentrations, by enzyme-linked immunosorbent assay (ELISA), were presented as geometric mean concentrations (GMCs), and expressed in milli-international units per milliliter (mIU/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (\>=) 10 mIU/mL. A decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following partial or complete retesting/reanalysis. Results presented are for each RTS,S Regimen A, B & C, and for each Engerix B Regimen A & B study groups.

Time frame: At Months 14 and 26, aka at 12 and 24 months post Dose 3 of RTS,S vaccine or Engerix-B

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity measures were available.

Concentrations, by enzyme-linked immunosorbent assay (ELISA), were presented as geometric mean concentrations (GMCs), and expressed in milli-international units per milliliter (mIU/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (\>=) 10 mIU/mL. A decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following partial or complete retesting/reanalysis. Results presented are for the study groups receiving the RTS,S vaccine, pooled by vaccine lot, that is, for the RTS,S Lot 1, RTS,S Lot 2, and RTS,S Lot 3 groups, as defined below.

Time frame: At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity measures were available.

Concentrations, by enzyme-linked immunosorbent assay (ELISA), were presented as geometric mean concentrations (GMCs), and expressed in milli-international units per milliliter (mIU/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (\>=) 10 mIU/mL. A decrease in the specificity of the anti-HBs ELISA assay had been observed in some studies for low levels of antibody (10-100 mIU/mL). The table shows updated results following partial or complete retesting/reanalysis. Results presented are for each RTS,S Regimen A, B & C, and for each Engerix B Regimen A & B study groups.

Time frame: At Months 38, 50 and 51, aka 36 and 48 months post Dose 3 of RTS,S vaccine or Engerix-B and one month post the Month 50 booster dose of Engerix-B

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity measures were available.

Anti-PD antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and expressed as geometric mean concentrations (GMCs), in ELISA units per milliliter (EL.U/mL). The cut-off of the assay was the seropositivity cut-off value of greater than or equal to 100 EL.U/mL. This outcome concerns the subjects who received the RTS,S or Engerix -B vaccine co-administered with Synflorix. Results presented are for the study groups pooled by co-administration, that is, for the RTS,S Regimen A and Engerix -B Regimen A groups.

Time frame: At Month 17, aka one month post the Month 16 booster dose of Synflorix

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity measures were available.

Anti-PD antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and expressed as geometric mean concentrations (GMCs), in ELISA units per milliliter (EL.U/mL). The cut-off of the assay was the seropositivity cut-off value of greater than or equal to 100 EL.U/mL. This outcome concerns the subjects who received the RTS,S or Engerix-B vaccine co-administered with Synflorix. Results presented are for the study groups pooled by co-administration, that is, for the RTS,S Regimen A and Engerix-B Regimen A groups.

Time frame: At Month 3, aka at one month post Dose 3 of Synflorix

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity measures were available.

Anti-Rotavirus (anti-RV) antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and expressed as geometric mean concentrations (GMCs). The cut-off of the assay was the seropositive cut-off value of greater than or equal to (\>=) 20 units per milliliter (U/mL). This outcome measure was assessed in subjects who were administered Rotarix as part of an EPI regimen, with and without RTS,S vaccine co-administration. This outcome concerns the subjects who received the RTS,S or Engerix-B vaccine co-administered with Rotarix. Results presented are for the study groups pooled by RTS,S or Engerix-B vaccine co-administration, that is, for the RTS,S Regimen B and Engerix-B Regimen B groups.

Time frame: At Month 3, aka one month post Dose 2 of Rotarix

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity measures were available.

The antibodies against BPT assessed were against pertussis toxoid (anti-PT), against filamentous haemagglutinin (anti-FHA), and against pertactin (anti-PRN). Concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and expressed as geometric mean concentrations (GMCs), in ELISA units per milliliter (EL.U/mL). The cut-off of the assay was the seropositivity cut-off value of greater than or equal to (\>=) 5 EL.U/mL. The table shows results for study groups pooled by primary vaccine administered (RTS,S vs Engerix -B)

Time frame: At Day 0 and at Month 3 (one month post Dose 3 of Infanrix-Hib)

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity measures were available.

Anti-HBs RF1 antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and presented as geometric mean concentrations (GMCs) expressed in ELISA units per milliliter (EL.U/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (\>=) 33 EL.U/mL. The table shows results for each RTS,S Regimen A, B & C, and for each Engerix B Regimen A & B study groups.

Time frame: At Month 3, aka at one month post Dose 3 of RTS,S vaccine or Engerix-B

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity measures were available.

Anti-HBs RF1 antibody concentrations were determined by enzyme-linked immunosorbent assay (ELISA) and presented as geometric mean concentrations (GMCs) expressed in ELISA units per milliliter (EL.U/mL). The assay cut-off was the seropositivity cut-off value of greater than or equal to (\>=) 33 EL.U/mL. The table shows results for each RTS,S Regimen A, B & C, and for each Engerix B Regimen A & B study groups.

Time frame: At Month 51, aka one month post the Month 50 booster dose of Engerix-B

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity measures were available.

A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or a reported adverse event of specific interest such as seizures occurring within a 30-day period of vaccination, immune-mediated disorders, and specific autoimmune diseases. A fatal SAE was defined as a SAE resulting in the death of the study subject.

Time frame: From Day 0 to Month 26

Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or a reported adverse event of specific interest such as seizures occurring within a 30-day period of vaccination, immune-mediated disorders, and specific autoimmune diseases. A fatal SAE was defined as a SAE resulting in the death of the study subject.

Time frame: From Day 0 to Month 8

Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or a reported adverse event of specific interest such as seizures occurring within a 30-day period of vaccination, immune-mediated disorders, and specific autoimmune diseases. A fatal SAE was defined as a SAE resulting in the death of the study subject.

Time frame: Within the 30-day follow-up periods (Days 0-29) after vaccination with RTS,S vaccine or Engerix-B

Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

A serious adverse event (SAE) was defined as any untoward medical occurrence that resulted in death, was life-threatening, required hospitalization or prolongation of existing hospitalization, resulted in disability/incapacity or a reported adverse event of specific interest such as seizures occurring within a 30-day period of vaccination, immune-mediated disorders, and specific autoimmune diseases. A fatal SAE was defined as a SAE resulting in the death of the study subject. A related SAE was defined as a SAE assessed by the investigator as being causally related to vaccination.

Time frame: From Day 0 up to Study End (Month 51)

Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

A potential immune mediated disorder (pIMD) was defined as an event about which concerns arose that vaccination may have interfered with immunological self-tolerance of the subjects. IMDs assessed included among others neuroinflammatory disorders (such as optic neuritis, multiple sclerosis, or encephalitis), musculoskeletal disorders (such as cutaneous lupus, rheumatoid arthritis, juvenile arthritis, or psoriatic arthropathy), gastrointestinal disorders (ulcerative colitis and ulcerative proctitis, celiac disease), metabolic diseases (such as autoimmune thyroiditis, or diabetes Mellitus Type 1, Addison's disease), skin disorders (such as psoriasis or vitiligo), and other disorders such as vasculitis, pernicious anemia, or, sarcoidosis.

Time frame: From Day 0 to Month 26

Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

A potential immune mediated disorder (pIMD) was defined as an event about which concerns arose that vaccination may have interfered with immunological self-tolerance of the subjects. IMDs assessed included among others neuroinflammatory disorders (such as optic neuritis, multiple sclerosis, or encephalitis), musculoskeletal disorders (such as cutaneous lupus, rheumatoid arthritis, juvenile arthritis, or psoriatic arthropathy), gastrointestinal disorders (ulcerative colitis and ulcerative proctitis, celiac disease), metabolic diseases (such as autoimmune thyroiditis, or diabetes Mellitus Type 1, Addison's disease), skin disorders (such as psoriasis or vitiligo), and other disorders such as vasculitis, pernicious anemia, or, sarcoidosis.

Time frame: From Day 0 to Month 8

Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

A potential immune mediated disorder (pIMD) was defined as an event about which concerns arose that vaccination may have interfered with immunological self-tolerance of the subjects. IMDs assessed included among others neuroinflammatory disorders (such as optic neuritis, multiple sclerosis, or encephalitis), musculoskeletal disorders (such as cutaneous lupus, rheumatoid arthritis, juvenile arthritis, or psoriatic arthropathy), gastrointestinal disorders (ulcerative colitis and ulcerative proctitis, celiac disease), metabolic diseases (such as autoimmune thyroiditis, or diabetes Mellitus Type 1, Addison's disease), skin disorders (such as psoriasis or vitiligo), and other disorders such as vasculitis, pernicious anemia, or, sarcoidosis.

Time frame: From Day 0 up to Study End (Month 51)

Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Assessed solicited general symptoms were fever, irritability/fussiness, drowsiness, and loss of appetite. Fever was defined as axillary temperature higher than (\>) 37.5 degrees Celsius (°C). Analysis for this outcome was performed solely for the 7-days follow-up periods following the primary vaccination with RTS,S vaccine or Engerix-B (at Day 0, and Months 1 and 2). Data presented are those for any occurrence of the assessed solicited general symptoms, that is, the occurrences of these symptoms regardless of their intensity grade or relationship to vaccination.

Time frame: Within the 7-day follow-up period (Days 0-6) after administration of Dose (D) 1, 2 and 3, respectively, with RTS,S or Engerix-B vaccine

Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available and who had their symptom sheets filled-in.

Assessed solicited local symptoms were pain, redness and swelling at the site of injection. All solicited local symptoms assessed were considered by the investigator as causally related to the study vaccination. Analysis for this outcome was performed solely for the 7-days follow-up periods following the primary vaccination with RTS,S vaccine or Engerix-B (at Day 0, and Months 1 and 2). Data presented are those for any occurrence of the assessed solicited local symptoms, that is, the occurrences of these symptoms regardless of their intensity grade.

Time frame: Within the 7-day follow-up period (Days 0-6) after administration of Dose (D) 1, 2 and 3, respectively, with RTS,S or Engerix-B vaccine

Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available and who had their symptom sheets filled-in.

An unsolicited AE was defined as an untoward medical occurrence in a patient or clinical investigation subject, temporally associated with use of a medicinal product, whether or not considered related to the medicinal product) 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.

Time frame: Within the 30-day follow-up periods (Days 0-29) after vaccination with RTS,S vaccine or Engerix-B

Population: The analysis was performed on the Total Vaccinated cohort, which included all vaccinated subjects for whom data were available.

Antibody concentrations were measured by GSK assay, and expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The pneumococcal vaccine serotypes assessed were the serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. The cut-off of the assay, by GSK assay, was greater than or equal to (\>=) 0.2 μg/mL. This corresponds to the standard ELISA value of 0.35 μg/mL. This outcome concerns the subjects who received the RTS,S or Engerix -B vaccine co-administered with Synflorix. Results presented are for the study groups pooled by co-administration, that is, for the RTS,S Regimen A and Engerix -B Regimen A groups.

Time frame: At Month 17, aka one month post the Month 16 booster dose of Synflorix

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity measures were available.

Antibody concentrations were measured by enzyme-linked immunosorbent assay (ELISA), and expressed as geometric mean concentrations (GMCs), in micrograms per milliliter (µg/mL). The pneumococcal vaccine serotypes assessed were the serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. The cut-off of the assay, by GSK assay, was greater than or equal to (\>=) 0.2 µg/mL. This corresponds to the standard ELISA value of 0.35 μg/mL. This outcome concerns the subjects who received the RTS,S or Engerix-B vaccine co-administered with Synflorix. Results presented are for the study groups pooled by co-administration, that is, for the RTS,S Regimen A and Engerix-B Regimen A groups.

Time frame: At Month 3, aka at one month post Dose 3 of Synflorix

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity measures were available.

The pneumococcal vaccine serotypes assessed were the serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Streptococcus pneumoniae opsonophagocytic activity was presented as the dilution of serum (opsonic titer) able to sustain 50 % killing of live pneumococci under the assay conditions, expressed as geometric mean titers (GMTs). The cut-off of the assay was an opsonic dilution \>= 8. This outcome concerns the subjects who received the RTS,S or Engerix -B vaccine co-administered with Synflorix . Results presented are for the study groups pooled by co-administration, that is, for the RTS,S Regimen A and Engerix -B Regimen A groups.

Time frame: At Month 17, aka one month post the Month 16 booster dose of Synflorix

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity measures were available.

The pneumococcal vaccine serotypes assessed were the serotypes 1, 4, 5, 6B, 7F, 9V, 14, 18C, 19F and 23F. Streptococcus pneumoniae opsonophagocytic activity was presented as the dilution of serum (opsonic titer) able to sustain 50 % killing of live pneumococci under the assay conditions, expressed as geometric mean titers (GMTs). The cut-off of the assay was an opsonic dilution \>= 8. This outcome concerns the subjects who received the RTS,S or Engerix-B vaccine co-administered with Synflorix. Results presented are for the study groups pooled by co-administration, that is, for the RTS,S Regimen A and Engerix-B Regimen A groups.

Time frame: At Month 3, aka at one month (1M) post Dose 3 of Synflorix

Population: The analysis was performed on the According-to-Protocol cohort for immunogenicity, which included all evaluable subjects (i.e. those meeting all eligibility criteria, complying with the procedures and intervals defined in the protocol, with no elimination criteria during the study) for whom data concerning immunogenicity measures were available.