Long-term Follow-up Study to Assess Antibody Persistence in Children Previously Vaccinated With Four Doses of Pneumococcal Conjugate Vaccine in Primary Vaccination Study (105553) and Booster Vaccination Study (107046)
Trial Snapshot
- Phase
- Phase 3
- Status
- Completed
- Sponsor
- GlaxoSmithKline
- Enrollment
- 524
- Locations
- 6
- Primary Endpoint
- Number of Subjects With Anti-vaccine Pneumococcal Serotypes Antibody Concentrations ≥ the Cut-off [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)]
Study Overview
Brief Summary
This protocol posting deals with objectives & outcome measures of the extension phase up to 48-50 months post booster vaccination, to assess long-term antibody persistence in children at around 30, 42 and 66 months of age, who received previously 4 doses of pneumococcal conjugate vaccine. The objectives & outcome measures of the primary phase are presented in a separate protocol posting (NCT number = 00307554). This Protocol posting has been updated in order to comply with the FDA AA (Sep 2007).
Detailed Description
This study consists in a serological follow-up study to evaluate persistence 12, 24 and 48 months after the booster vaccination study (107046). No study vaccines will be administered within this study.
Study Design
- Study Type
- Interventional
- Allocation
- Non Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Prevention
- Masking
- None
Eligibility Criteria
- Ages
- 28 Months to 32 Months (Child)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Male or female between, and including, 28-30 months of age at the time of first blood sampling.
- •Subjects who previously participated in the 105553 and 107046 studies and who received a full four dose regimen of pneumococcal conjugate vaccine during the primary and booster studies.
- •Subjects for whom the investigator believes that their parents/guardians can and will comply with the requirements of the protocol.
- •Written informed consent, covering visits 1, 2 and 3, obtained from the parent or guardian of the subject.
- •Free of obvious health problems as established by medical history and clinical examination before entering into the study.
Exclusion Criteria
- •Chronic administration of immunosuppressants or other immune-modifying drugs within 6 months prior to the blood sampling
- •Administration of any additional pneumococcal vaccine since end of 107046 study.
- •Use of any investigational or non-registered product (drug or vaccine) within 30 days preceding the blood sampling.
- •Administration of immunoglobulins and/or any blood products less than 6 months prior to blood sampling.
- •Any confirmed or suspected immunosuppressive or immunodeficient condition since the end of the 107046 study, based on medical history and physical examination.
Arms & Interventions
Synflorix + Infanrix + Havrix and/or Varilrix Group
This group consisted of subjects primed with Synflorix vaccine in the 10PN-PD-DIT-001 (1105553) and 007 (107046) studies. In 105553 study, subjects had been primed with 3 doses of Synflorix vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In 107046 study, subjects had received a booster dose of Synflorix vaccine at 12-18 months of age co-administered with Infanrix hexa vaccine. In this study, in the Year 4 (111347 study), subjects received at Month 48 (4 years post Dose 1 in study 105553) one additional dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix) and/or against varicella (a single dose of Varilrix).
Intervention: GSK1024805A (Biological)
Synflorix + Infanrix + Havrix and/or Varilrix Group
This group consisted of subjects primed with Synflorix vaccine in the 10PN-PD-DIT-001 (1105553) and 007 (107046) studies. In 105553 study, subjects had been primed with 3 doses of Synflorix vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In 107046 study, subjects had received a booster dose of Synflorix vaccine at 12-18 months of age co-administered with Infanrix hexa vaccine. In this study, in the Year 4 (111347 study), subjects received at Month 48 (4 years post Dose 1 in study 105553) one additional dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix) and/or against varicella (a single dose of Varilrix).
Intervention: Havrix (Biological)
Prevenar + Infanrix + Havrix and/or Varilrix Group
This group consisted of subjects vaccinated with Prevenar vaccine in the 10PN-PD-DIT-001 (105553) and 007 (107046) studies. In 105553 study, subjects had been primed with 3 doses of Prevenar vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In 107046 study, subjects had received a booster dose at 12-18 months of age of Prevenar vaccine co-administered with Infanrix hexa vaccine. In this study, in the Year 4 111347 study, subjects had received at Month 48 (4 years post Dose 1 in study 105553) one dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix and/or against varicella (a single dose of Varilrix).
Intervention: Prevenar (Biological)
Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
This group consisted of subjects vaccinated with Prevenar and Synflorix vaccines in the 10PN-PD-DIT-001 (105553) and 10PN-PD-DIT-007 (107046) studies. In 105553 study, subjects had been primed with 3 doses Prevenar vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In the 107046 study, subjects had received at 12-18 months of age a booster dose of Synflorix vaccine co-administered with Infanrix hexa vaccine. In this study, in the Year 4 (111347 study), subjects had received at Month 48 (4 years post Dose 1 in study 105553) one additional dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix and/or against varicella (a single dose of Varilrix).
Intervention: GSK1024805A (Biological)
Unprimed Group
This group consisted of subjects between, and including, 64-68 months of age at the time of additional vaccination (primed subjects) or dose 1 (unprimed subjects), and for whom the investigator believed that their parents/guardians could and would comply with the requirements of the protocol. Subjects were not previously vaccinated with any pneumococcal vaccine and received 2 doses of Synflorix vaccine at 64-68 and 66-70 months of age (at Day 0 and Month 2).
The Unprimed Group was added only in Year 4 of the study.
Intervention: GSK1024805A (Biological)
Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
This group consisted of subjects vaccinated with Prevenar and Synflorix vaccines in the 10PN-PD-DIT-001 (105553) and 10PN-PD-DIT-007 (107046) studies. In 105553 study, subjects had been primed with 3 doses Prevenar vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In the 107046 study, subjects had received at 12-18 months of age a booster dose of Synflorix vaccine co-administered with Infanrix hexa vaccine. In this study, in the Year 4 (111347 study), subjects had received at Month 48 (4 years post Dose 1 in study 105553) one additional dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix and/or against varicella (a single dose of Varilrix).
Intervention: Varilrix (Biological)
Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
This group consisted of subjects vaccinated with Prevenar and Synflorix vaccines in the 10PN-PD-DIT-001 (105553) and 10PN-PD-DIT-007 (107046) studies. In 105553 study, subjects had been primed with 3 doses Prevenar vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In the 107046 study, subjects had received at 12-18 months of age a booster dose of Synflorix vaccine co-administered with Infanrix hexa vaccine. In this study, in the Year 4 (111347 study), subjects had received at Month 48 (4 years post Dose 1 in study 105553) one additional dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix and/or against varicella (a single dose of Varilrix).
Intervention: Havrix (Biological)
Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
This group consisted of subjects vaccinated with Prevenar and Synflorix vaccines in the 10PN-PD-DIT-001 (105553) and 10PN-PD-DIT-007 (107046) studies. In 105553 study, subjects had been primed with 3 doses Prevenar vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In the 107046 study, subjects had received at 12-18 months of age a booster dose of Synflorix vaccine co-administered with Infanrix hexa vaccine. In this study, in the Year 4 (111347 study), subjects had received at Month 48 (4 years post Dose 1 in study 105553) one additional dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix and/or against varicella (a single dose of Varilrix).
Intervention: Infanrix hexa (Biological)
Prevenar + Synflorix + Infanrix + Havrix and/or Varilrix
This group consisted of subjects vaccinated with Prevenar and Synflorix vaccines in the 10PN-PD-DIT-001 (105553) and 10PN-PD-DIT-007 (107046) studies. In 105553 study, subjects had been primed with 3 doses Prevenar vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In the 107046 study, subjects had received at 12-18 months of age a booster dose of Synflorix vaccine co-administered with Infanrix hexa vaccine. In this study, in the Year 4 (111347 study), subjects had received at Month 48 (4 years post Dose 1 in study 105553) one additional dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix and/or against varicella (a single dose of Varilrix).
Intervention: Prevenar (Biological)
Prevenar + Infanrix + Havrix and/or Varilrix Group
This group consisted of subjects vaccinated with Prevenar vaccine in the 10PN-PD-DIT-001 (105553) and 007 (107046) studies. In 105553 study, subjects had been primed with 3 doses of Prevenar vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In 107046 study, subjects had received a booster dose at 12-18 months of age of Prevenar vaccine co-administered with Infanrix hexa vaccine. In this study, in the Year 4 111347 study, subjects had received at Month 48 (4 years post Dose 1 in study 105553) one dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix and/or against varicella (a single dose of Varilrix).
Intervention: Varilrix (Biological)
Prevenar + Infanrix + Havrix and/or Varilrix Group
This group consisted of subjects vaccinated with Prevenar vaccine in the 10PN-PD-DIT-001 (105553) and 007 (107046) studies. In 105553 study, subjects had been primed with 3 doses of Prevenar vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In 107046 study, subjects had received a booster dose at 12-18 months of age of Prevenar vaccine co-administered with Infanrix hexa vaccine. In this study, in the Year 4 111347 study, subjects had received at Month 48 (4 years post Dose 1 in study 105553) one dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix and/or against varicella (a single dose of Varilrix).
Intervention: Havrix (Biological)
Prevenar + Infanrix + Havrix and/or Varilrix Group
This group consisted of subjects vaccinated with Prevenar vaccine in the 10PN-PD-DIT-001 (105553) and 007 (107046) studies. In 105553 study, subjects had been primed with 3 doses of Prevenar vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In 107046 study, subjects had received a booster dose at 12-18 months of age of Prevenar vaccine co-administered with Infanrix hexa vaccine. In this study, in the Year 4 111347 study, subjects had received at Month 48 (4 years post Dose 1 in study 105553) one dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix and/or against varicella (a single dose of Varilrix).
Intervention: Infanrix hexa (Biological)
Synflorix + Infanrix + Havrix and/or Varilrix Group
This group consisted of subjects primed with Synflorix vaccine in the 10PN-PD-DIT-001 (1105553) and 007 (107046) studies. In 105553 study, subjects had been primed with 3 doses of Synflorix vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In 107046 study, subjects had received a booster dose of Synflorix vaccine at 12-18 months of age co-administered with Infanrix hexa vaccine. In this study, in the Year 4 (111347 study), subjects received at Month 48 (4 years post Dose 1 in study 105553) one additional dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix) and/or against varicella (a single dose of Varilrix).
Intervention: Varilrix (Biological)
Synflorix + Infanrix + Havrix and/or Varilrix Group
This group consisted of subjects primed with Synflorix vaccine in the 10PN-PD-DIT-001 (1105553) and 007 (107046) studies. In 105553 study, subjects had been primed with 3 doses of Synflorix vaccine at 2, 3 and 4 months of age co-administered with Infanrix related vaccines. In 107046 study, subjects had received a booster dose of Synflorix vaccine at 12-18 months of age co-administered with Infanrix hexa vaccine. In this study, in the Year 4 (111347 study), subjects received at Month 48 (4 years post Dose 1 in study 105553) one additional dose of Synflorix vaccine. In addition, subjects were also offered vaccination against hepatitis A (2 doses of Havrix) and/or against varicella (a single dose of Varilrix).
Intervention: Infanrix hexa (Biological)
Outcomes
Primary Outcomes
Number of Subjects With Anti-vaccine Pneumococcal Serotypes Antibody Concentrations ≥ the Cut-off [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)]
Time Frame: At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT-007)
A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Analysis was performed using the 22F-inhibition Enzyme-linked immunosorbent assay (ELISA), using 0.05 μg/mL as seropositivity cut off.
Number of Subjects With Anti-vaccine Pneumococcal Serotypes Antibody Concentrations Greater Than or Equal to (≥) the Cut-off [Follow-up Period: Persistence Analysis in Year 1 (111345 Sub-study)]
Time Frame: At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007)
A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Analysis was performed using the 22F-inhibition Enzyme-linked immunosorbent assay (ELISA), using 0.05 microgram per milliliter (µg/mL) as seropositivity cut off.
Number of Subjects With Anti-vaccine Pneumococcal Serotypes Antibody Concentrations ≥ the Cut-off [Follow-up Period: Persistence Analysis in Year 2 (111346 Sub-study)]
Time Frame: At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT-007)
A seropositive subject was a subject whose antibody concentration was greater than or equal to (≥) the cut-off value. Analysis was performed using the 22F-inhibition Enzyme -linked immunosorbent assay (ELISA), using 0.05 μg/mL as seropositivity cut off.
Secondary Outcomes
- Antibody Concentrations Against Pneumococcal Serotypes [Follow-Up Period: Persistence Analysis in Year 1 (111345 Sub-study)](At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007))
- Antibody Concentrations Against Pneumococcal Serotypes [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 Sub-study)](For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination))
- Antibody Concentrations Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and - 19A) - Follow-Up Period: Persistence Analysis in Year 2 (111346 Sub-study)(At Year 2 (Y2) (post booster vaccination administrated in study 10PN-PDDIT- 007))
- Antibody Concentrations Against Pneumococcal Serotypes [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)](At Year 4 (Y4) (post booster vaccination administered in study 10PN-PDDIT- 007))
- Antibody Concentrations Against Pneumococcal Serotypes [Follow-Up Period: Persistence Analysis in Year 2 (111346 Sub-study)](At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT-007))
- Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 Sub-study)](For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination))
- Antibody Concentrations Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and - 19A) [Follow-up Period: Persistence Analysis in Year 1 (111345 Sub-study)](At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007))
- Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes [Follow-Up Period: Persistence Analysis in Year 2 (111346 Sub-study)](At Year 2 (Y2) (post booster vaccination administrated in study 10PN-PD-DIT-007))
- Opsonophagocytic Activity (OPA) Titers Against Crossreactive Pneumococcal Serotypes 6A and 19 A [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)](At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT-007))
- Antibody Concentrations to Protein D (Anti-PD) - Follow-up Period: Persistence Analysis in Year 2 (111346 Sub-study)(At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT- 007))
- Number of Seropositive Subjects for Opsonophagocytic Activity Against Pneumococcal Serotypes [Follow-up Period: Persistence Analysis in Year 1 (111345 Sub-study)](At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007))
- Number of Seropositive Subjects for Opsonophagocytic Activity Against Pneumococcal Serotypes [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)](At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT-007))
- Number of Seropositive Subjects for Opsonophagocytic Activity Against Pneumococcal Cross-reactive Serotypes 6A and 19A [Follow-up Period: Persistence Analysis in Year 1 (111345 Sub-study)](At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007))
- Number of Seropositive Subjects for Anti-protein D (Anti-PD) [Follow-up Period: Persistence Analysis in Year 1 (111345 Sub-study)](At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007))
- Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes [Follow-Up Period: Persistence Analysis in Year 1 (111345 Sub-study)](At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007))
- Opsonophagocytic Activity (OPA) Titers Against Crossreactive Pneumococcal Serotypes 6A and 19 A [Follow-up Period: Persistence Analysis in Year 2 (111346 Sub-study)](At Year 2 (Y2) (post booster vaccination administrated in study 10PN-PD-DIT-007))
- Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes 6A and 19A [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 Sub-study)](For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination))
- Antibody Concentrations to Protein D (Anti-PD) - Follow-up Period: Persistence Analysis in Year 1 (111345 Sub-study)(At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007))
- Number of Subjects With Serious Adverse Events (SAEs) [Follow-up Period: Vaccination Period in Year 4 (111347 Sub-study)](For primed groups: from Months 48-49 (additional vaccination period); for unprimed group: from Day 0 up to Month 3 (catch-up vaccination period))
- Number of Seropositive Subjects for Opsophagocytic Activity Against Pneumococcal Serotypes [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 Sub-study)](For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination))
- Number of Seropositive Subjects for Anti-pneumococcal Cross-reactive Serotypes 6A and 19A [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)](At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT-007))
- Opsonophagocytic Activity (OPA) Titers Against Pneumococcal Serotypes [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)](At Year 4 (Y4) (post booster vaccination administrated in study 10PN-PD-DIT-007))
- Antibody Concentrations Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and 19A) [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 Sub-study)](For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination))
- Opsonophagocytic Activity (OPA) Titers Against Crossreactive Pneumococcal Serotypes 6A and 19 A [Follow-up Period: Persistence Analysis in Year 1 (111345 Sub-study)](At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007))
- Number of Subjects With Unsolicited Adverse Events (AEs)(Within 31 days (Day 0-30) after Synflorix vaccination in Year 4 Persistence and Immunological Memory 111347 Study)
- Number of Seropositive Subjects for Opsonophagocytic Activity Against Pneumococcal Cross-reactive Serotypes 6A and 19A [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)](At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT-007))
- Number of Seropositive Subjects for Anti-protein D (Anti-PD) [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 Sub-study)](For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination))
- Number of Seropositive Subjects for Anti-vaccine Pneumococcal Serotypes Antibodies [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 Sub-study)](For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination))
- Antibody Concentrations Against Cross-reactive Pneumococcal Serotypes 6A and 19A (Anti-6A and - 19A) [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)](At Year 4 (Y4) (post booster vaccination administrated in study 10PN-PD-DIT- 007))
- Number of Seropositive Subjects for Anti-pneumococcal Cross-reactive Serotypes 6A and 19A [Follow-up Period: Persistence Analysis in Year 2 (111346 Sub-study)](At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT-007))
- Number of Seropositive Subjects for Anti-pneumococcal Cross-reactive Serotypes 6A and 19A [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 Sub-study)](For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination))
- Number of Seropositive Subjects for Opsonophagocytic Activity Against Pneumococcal Cross-reactive Serotypes 6A and 19A [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 Sub-study)](For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination))
- Number of Seropositive Subjects for Anti Protein D (Anti-PD) [Follow-up Period: Persistence Analysis in Year 2 (111345 Sub-study)](At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT-007))
- Antibody Concentrations to Protein D (Anti-PD) [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)](At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT- 007))
- Antibody Concentrations to Protein D (Anti-PD) [Follow-up Period: Immunogenicity Analysis in Year 4 (111347 Sub-study)](For primed groups: At Month 48+7 days after additional dose (D7);For unprimed group: at Day 0 (D0) (Pre-vaccination [PRE]), at Day 7 (D7) post dose 1 (of the 2-dose catch-up vaccination) and at Month 3 (M3) post dose 2 (of the 2-dose catch-up vaccination))
- Number of Subjects Reported With Solicited Local Symptoms(Within 4 days (Days 0-3) period(s) after Synflorix vaccination in Year 4 Persistence and Immunological Memory 111347 Study)
- Number of Subjects Reported With Solicited General Symptoms(Within 4 days (Days 0-3) period(s) after Synflorix vaccination in Year 4 Persistence and Immunological Memory 111347 Study)
- Number of Subjects With Serious Adverse Events (SAEs) Related to Study Procedures [Follow-up Period: Year 1 (111345 Sub-study)](During Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007) i.e. for each primed subject: from the time the subject was enrolled in the 111345 study until he/she completed the same study (approximatively 12 months))
- Number of Subjects With Serious Adverse Events (SAEs) Related to Study Procedures [(Follow-up Period: Year 2 (111346 Sub-study) Until Year 4 (111347 Sub-study)](From Year (Y) 2 to Y4 FU visit (post booster vaccination administered in 10PN-PD-DIT-007) i.e. for each subject(S): when S was enrolled in 111346 study until S completed the same study visit or the 111347 study visit (range of 1 to 3 years for each S)))
- Number of Seropositive Subjects for Opsonophagocytic Activity Against Pneumococcal Serotypes [Follow-up Period: Persistence Analysis in Year 2 (111346 Sub-study)](At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT-007))
- Number of Seropositive Subjects for Anti-pneumococcal Cross-reactive Serotypes 6A and 19A [Follow-up Period: Persistence Analysis in Year 1 (111345 Sub-study)](At Year 1 (Y1) (post booster vaccination administered in study 10PN-PD-DIT-007))
- Number of Seropositive Subjects for Opsonophagocytic Activity Against Pneumococcal Cross-reactive Serotypes 6A and 19A [Follow-up Period: Persistence Analysis in Year 2 (111346 Sub-study)](At Year 2 (Y2) (post booster vaccination administered in study 10PN-PD-DIT-007))
- Number of Seropositive Subjects for Anti-protein D (Anti-PD) [Follow-up Period: Persistence Analysis in Year 4 (111347 Sub-study)](At Year 4 (Y4) (post booster vaccination administered in study 10PN-PD-DIT-007))