Sequential Versus Simultaneous Pneumococcal Vaccination in Elderly: Immunological Memory and Antibody Levels

Study Overview
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Brief Summary
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The purpose of the present study is to compare the immunological response of pneumococcal serotype specific B-cells, the humoral immune response and safety after sequential vaccination versus simultaneous vaccination with 13-valent pneumococcal conjugate vaccine (PCV13) and 23-valent polysaccharide vaccine (PPV23) versus single vaccination with PPV23 in a prospective, randomized controlled monocentric head-to head clinical study in elderly. The hypothesis of this study is that simultaneous vaccination with PCV13 and PPV23 might achieve an improved immune-response compared to sequential vaccination or single vaccination. Adults >=60 years without previous pneumococcal vaccination will be randomized in three groups and receive either PCV13 on day 0 plus PPV23 6 months later (sequential vaccination) or they receive PCV13 plus PPV23 simultaneous on day 0 (simultaneous vaccination) or they receive PPV23 on day 0 (single vaccination). Blood will be taken for pneumococcal serotype-specific B-memory cells against four vaccine-serotypes (ST), included in PCV13 and PPV23, vaccine-serotype 3 (ST3), vaccine-serotype 14 (ST14), vaccine-serotype 19A (ST19A) and vaccine-serotype 23F (ST23F) at visit 1, 2,4,5,7 and 8 and for antibody levels against the 12 vaccine-serotypes included in PCV13 and PPV23 at visit 1, 3, 4, 6, 7 and 8 in all three groups. Adverse events will be recorded for 28 days after each vaccination.

Official Title
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Sequential Versus Simultaneous Vaccination With Pneumococcal Conjugate Vaccine (Prevenar 13) and Pneumococcal Polysaccharide Vaccine (Pneumovax 23) in Elderly: Immunological Memory and Antibody Levels

Conditions
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Pneumococcal Infections

Intervention / Treatment
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* Drug: PCV13
* Drug: PPV23


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Unvaccinated adults >= 60 years Written informed consent Exclusion Criteria: Hypersensitivity against substances included in both vaccines Previous pneumococcal vaccination Pneumonia within the last two months Active infection Autoimmune disease Ongoing or planned immunosuppressive therapy (including corticosteroid treatment with prednisolon equivalent dose >= 5 mg/d) Active malignant disease Drug abuse or alcoholic abuse Expectation of life < 2 years Coagulation disorders Burns or injury on the injection site Plegia or paresis of extremity where injection is planned Shock parallel participation in other clinical trial with intervention Infusion of blood products within the last half year

Ages Eligible for Study
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Minimum Age: 60 Years

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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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Sequential vaccination PCV13 and PPV23<br>PCV13 0.5 ml intramuscular injection once on day 0 PPV23 0.5 ml intramuscular injection once 6 months later | Drug: PCV13<br>* Intramuscular injection of 13-valent pneumococcal conjugate vaccine once<br>* Other names: Prevenar 13;Drug: PPV23<br>* Intramuscular injection of 23-valent pneumococcal polysaccharide vaccine once<br>* Other names: Pneumovax (MSD);|
| Experimental: Simultaneous vaccination PCV13 and PPV23<br>PCV13 0.5ml intramuscular injection once on day 0 followed by PPV23 0.5ml intramuscular injection on day 0 | Drug: PCV13<br>* Intramuscular injection of 13-valent pneumococcal conjugate vaccine once<br>* Other names: Prevenar 13;Drug: PPV23<br>* Intramuscular injection of 23-valent pneumococcal polysaccharide vaccine once<br>* Other names: Pneumovax (MSD);|
| Active Comparator: Single vaccinationPPV23<br>PPV23 0.5ml intramuscular injection on day 0 | Drug: PPV23<br>* Intramuscular injection of 23-valent pneumococcal polysaccharide vaccine once<br>* Other names: Pneumovax (MSD);|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune response of B-memory cells | Change of immune response of B memory cells against 4 pneumococcal serotypes ST3,ST14,ST19A und ST23F compared to day 0 will be determined by multiparameter flow cytometry. Pneumococcal specific B-cells will be identified by labeling with fluorochrome-coupled polysaccharide antigen, B-memory cells will be identified by expression of characteristic membrane proteins and quantified. | 27-28 weeks after first vaccination | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Immune response of B-memory cells | Change immune response of B memory cells against 4 pneumococcal serotypes ST3,ST14,ST19A und ST23F compared to day 0 will be determined by multiparameter flow cytometry. Pneumococcal specific B-cells will be identified by labeling with fluorochrome-coupled polysaccharide antigen, B-memory cells will be identified by expression of characteristic membrane proteins and quantified. | 1-2 weeks, 26 weeks, 52 weeks, 104 weeks | 
| Humoral immune response | Change of serotype-specific immunoglobulin G concentrations against 12 pneumococcal vaccine-serotypes included in both vaccines PCV13 and PPV23 compared to day 0 | 4 weeks, 26 weeks, 30 weeks, 52 weeks, 104 weeks | 
| Safety (Adverse events and serious adverse events) | Adverse events and serious adverse events | 28 days after each vaccination | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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conjugate vaccine, polysaccharide vaccine