Polysaccharide Antibody Response Study

Study Overview
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Brief Summary
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Specific polysaccharide antibody deficiency (SPAD) is a primary immunodeficiency characterized by a deficient antibody production to capsular polysaccharides with normal total immunoglobulin levels. Patients suffer from recurrent ear-nose and throat infections and lung infections. SPAD can also occur as part of a primary immunodeficiency affecting other components of the immune system. Diagnosis of SPAD is hampered by difficulties with the interpretation of the Pneumovax 23 antibody response. The purpose of this study is to assess the diagnostic value of the Typhim Vi antibody response and allohemagglutinin titers as an alternative to the Pneumovax 23 response to detect polysaccharide specific antibody deficiency.

Detailed Description
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Healthy controls (n = 100) and patients with suspected SPAD (n = 100) will be immunized with both Pneumovax 23 and Typhim Vi (age 18 months - 55 years). Analyses of anti-pneumococcal polysaccharide antibodies and anti-Vi antibodies are performed before and 3-4 weeks after vaccination. Also bloodgroup and anti-A/anti-B are assessed. Relevant clinical information (ENT infections, lung infections, bronchiectasis, invasive infections) is obtained from the patient file and history and is noted in a Case Report Form. The diagnostic performance of Typhim Vi response and allohemagglutinins will be analyzed by calculating sensitivity, specificity, predictive values, likelihood ratios and Receiver Operating Characteristic curves for Typhim Vi and allohemagglutinins using pneumococcal antibody response as the reference standard. The association between low Typhim Vi response or low allohemagglutinins and clinical signs of polysaccharide antibody deficiency will be studied by multiple logistic regression.

Official Title
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The Polysaccharide Antibody Response Study: Typhim Vi Response and Allohemagglutinins Versus Pneumovax 23 Vaccine Response in the Diagnosis of Specific Polysaccharide Antibody Deficiency

Conditions
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Specific Polysaccharide Antibody Deficiency

Intervention / Treatment
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* Biological: Pneumovax 23 (Sanofi Pasteur MSD)
* Biological: Typhim Vi (Sanofi Pasteur MSD)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Assessment of polysaccharide antibody response is indicated for the clinical care of the patient (not for healthy volunteers) Informed consent given Exclusion Criteria: History of serious adverse reaction to a vaccine Vaccination with Typhim Vi or Pneumovax 23 in 5 years prior to the study (Potential) pregnancy

Ages Eligible for Study
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Minimum Age: 18 Months
Maximum Age: 55 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: Diagnostic
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Healthy controls<br>Healthy volunteers who consented to participate in the study will be immunized with both Pneumovax 23 and Typhim Vi . | Biological: Pneumovax 23 (Sanofi Pasteur MSD)<br>* Intramuscular injection of Pneumovax 23 vaccine (0.5 ml).<br>Biological: Typhim Vi (Sanofi Pasteur MSD)<br>* Intramuscular injection of Typhim Vi vaccine (0.5 ml).<br>|
| Experimental: Patients<br>Patients presenting for immune evaluation because of recurrent ENT/lung infection or invasive infection with encapsulated bacteria, in whom evaluation of pneumococcal antibody response is indicated, will be immunized with both Pneumovax 23 and Typhim Vi . | Biological: Pneumovax 23 (Sanofi Pasteur MSD)<br>* Intramuscular injection of Pneumovax 23 vaccine (0.5 ml).<br>Biological: Typhim Vi (Sanofi Pasteur MSD)<br>* Intramuscular injection of Typhim Vi vaccine (0.5 ml).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Typhim Vi response specific anti-Vi IgG as measured by ELISA | specific anti-Vi IgG as measured by ELISA | 3-4 weeks | 
| Pneumovax 23 response specific pneumococcal polysaccharide IgG as measured by ELISA | specific pneumococcal polysaccharide IgG as measured by ELISA | 3-4 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| allohemaglutinin titer as measured by column agglutination | bloodgroup, anti-A, anti-B IgG and IgM as measured by column agglutination | 1 day | 
| ENT infections (number of ENT infections obtained by history and medical file) | number of ENT infections obtained by history and medical file | 12 months before inclusion untill inclusion | 
| pneumonia (number of lung infections, confirmed on chest radiography, obtained by history and medical file) | number of lung infections, confirmed on chest radiography, obtained by history and medical file | 5 years before inclusion untill inclusion | 
| invasive infections (number and infection site of invasive infections obtained by history and medical file) | number and infection site of invasive infections obtained by history and medical file | 5 years before inclusion untill inclusion | 
| bronchiectasis (presence or absence of bronchiectasis (diagnosed by high resolution CT) obtained by history and medical file) | presence or absence of bronchiectasis (diagnosed by high resolution CT) obtained by history and medical file | 5 years before inclusion untill inclusion | 
| adverse effects | vaccine related adverse effects | 4 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Pneumovax 23, Typhim Vi, allohemagglutinins