PNEUMOCELL - Conjugated Pneumococcal Vaccination in Patients With Immunoglobulin G-deficiency

Study Overview
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Brief Summary
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The aim is to study the immune response to conjugated pneumococcal vaccination (Prevenar13) in Immunoglobulin G-deficient patients and healthy controls. Our hypothesis is that the antibody response will be impaired in patients as compared with controls. In contrast, we postulate that the cellular immune response will be intact.

Detailed Description
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Ten patients with Immunoglobulin G1 and/or Immunoglobulin G2 deficiency will be enrolled together with 10 age and sex- matched controls. Blood-samples will be drawn at base-line and after 1, 2 and 4 weeks post-vaccination. Serum will be analyzed for opsonophagocytic antibodies. Peripheral blood monocytic cells (PBMCs) will be isolated, frozen and later analyzed for all time-points simultaneously. PBMCs will be stimulated with vaccine-antigens for 3-5 days and cellular activation markers will be measured together with cytokines (Interferon-gamma, Interleukin (IL)-5, IL-13, IL-10, IL-17, IL-22). In addition, levels of antimicrobial peptides in nasal fluid will be measured at baseline and after 4 weeks post-vaccination.

Official Title
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PNEUMOCELL - Conjugated Pneumococcal Vaccination in Patients With Immunoglobulin G-deficiency

Conditions
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IgG Deficiency

Intervention / Treatment
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* Biological: Prevenar13


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Immunoglobulin gamma-deficiency: Immunoglobulin gamma 1-deficiency < 2,8 g/L and/or Immunoglobulin gamma 2-deficiency < 1,15 g/L Age 18-65 Exclusion Criteria: Immunoglobulin gamma-substitution for 6 months prior to study inclusion Prevenar7 or Prevenar13 given prior to study inclusion. Pneumovax given during a 2 year period prior to study inclusion Pregnancy or planning to become pregnant during the study period (4 weeks) Taking part in another clinical study involving drugs or vaccinations during the study period (4 weeks). Taking systemic steroids, Non steroidal anti inflammatory drugs (NSAID) or immunosuppressive drugs. Being allergic to any substance in the vaccine. Acute and ongoing disease with high fever. Thrombocytopenia (< 100x109/L). Coagulopathy Breastfeeding a baby The healthy controls should not have any disease with effects on the immune-system

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: IgG-deficient patients<br>Prevenar13 | Biological: Prevenar13<br> <br> |
| Active Comparator: Healthy controls<br>Prevenar13 | Biological: Prevenar13<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in opsonophagocytic antibodies | Titers of opsonophagocytic antibodies will be measured at baseline and 4 weeks post-vaccination. Titers from 4 weeks post-vaccination will be compared with baseline-levels. | 4 weeks post-vaccination, change from baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in cellular immunity | PBMCs will be collected and stimulated with vaccine-antigens. Cellular activation markers and cytokine release will be measured and results from 4 weeks post-vaccination will be compared with baseline-levels. | 4 weeks post-vaccination, change from baseline | 
| Change in antimicrobial peptides | Levels of AMPs in nasal fluid will be measured at 0 and 4 weeks post-vaccination. Results from 4 weeks will be compared with base-line levels. | 4 weeks post-vaccination, change from baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Opsonophagocytic antibodies, Cellular immunity, Vaccine immunity, Antimicrobial peptides