Immunological Memory Against Pneumococcus Induced by 3 Infant PCV 13 Vaccination Schedules

Study Overview
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Brief Summary
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The purpose of this study is to evaluate the establishment of immunological memory between the 3 different infant vaccination schedules with the 13-valent pneumococcal conjugate vaccine (PCV13) currently in use. We aim to determine the optimal schedule for the establishment of antigen-specific memory B-cell pool, which may serve as a correlate for longevity of immunological memory against vaccine serotypes. Moreover, we will study the transcriptome profiles expressed by peripheral lymphocytes during each immune response in an attempt to reveal immunological mechanisms beyond the antibody and circulating B cells level.

Official Title
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The Establishment of Serotype-specific Immunological Memory Against Pneumococcus by a 3+1 Versus a 2+1 or 3+0 Infant PCV13 Vaccination Schedule

Conditions
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Immunogenicity, Vaccine, Immunologic Memory

Intervention / Treatment
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* Biological: 13-valent pneumococcal conjugate vaccine (PCV13)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 2-15 months of age Exclusion Criteria: previously recorded allergy to PCV intravenous immunoglobulin (IVIG) given within the previous 6 months primary or secondary immunodeficiency any chronic medical condition

Ages Eligible for Study
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Minimum Age: 2 Months
Maximum Age: 15 Months

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| 3+1<br>Healthy infants will receive 4 doses of the 13-valent pneumococcal conjugate vaccine (PCV13) at 2,4,6 and 12 months of age and blood and serum collection pre- dose, 7 days post- (only blood) and 28 days post- last dose. | Biological: 13-valent pneumococcal conjugate vaccine (PCV13)<br>* Vaccination with PCV13<br>* Other names: Prevenar13;|
| 3+0<br>Healthy infants will receive 3 doses of the 13-valent pneumococcal conjugate vaccine (PCV13) at 2,4 and 6 months of age and blood and serum collection pre- dose, 7 days post- (only blood) and 28 days post- last dose. | Biological: 13-valent pneumococcal conjugate vaccine (PCV13)<br>* Vaccination with PCV13<br>* Other names: Prevenar13;|
| 2+1<br>Healthy infants will receive 3 doses of the 13-valent pneumococcal conjugate vaccine (PCV13) at 2,4 and 12 months of age and blood and serum collection pre- dose, 7 days post- (only blood) and 28 days post- last dose. | Biological: 13-valent pneumococcal conjugate vaccine (PCV13)<br>* Vaccination with PCV13<br>* Other names: Prevenar13;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| immunoglobulin G (IgG) antibody serum titers (measured by ELISA) | measurement of IgG antibody titers in serum pre- and post- last dose of PCV13 | 28 days post last vaccine dose | 
| switched immunoglobulin G (swIgG) B memory cell response (measured by flow cytometry) | phenotype characterisation of swIgG memory B cells pre- and post- last dose of PCV13 | 28 days post last vaccine dose | 
| immunoglobulin M (IgM) B memory cell response (measured by flow cytometry) | phenotype characterisation of IgM memory B cells pre- and post- last dose of PCV13 | 28 days post last vaccine dose | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Transcriptional profile of Peripheral Blood Mononuclear Cells (PBMC) in response to PCV13 (measured by RNA-Sequencing) | transcriptome analysis of PBMCs pre- and post last dose of PCV13 on a cohort of patients | 7 days post last vaccine dose |