Polysaccharide Antibody Response Study (PARS)

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

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.

Study Overview

• Status: Completed
• Conditions: Specific Polysaccharide Antibody Deficiency
• Intervention / Treatment: Biological: Pneumovax 23 (Sanofi Pasteur MSD); Biological: Typhim Vi (Sanofi Pasteur MSD)

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 200
• Phase: Phase 4

Contacts and Locations

Study Locations

• Belgium
  • Leuven, Belgium, 3000
    • UZ Leuven

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 year to 55 years (Child, Adult)
• Accepts Healthy Volunteers: Yes

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Non-Randomized
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Healthy controls; 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); Intramuscular injection of Pneumovax 23 vaccine (0.5 ml).; Biological: Typhim Vi (Sanofi Pasteur MSD); Intramuscular injection of Typhim Vi vaccine (0.5 ml).
Experimental: Patients; 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); Intramuscular injection of Pneumovax 23 vaccine (0.5 ml).; Biological: Typhim Vi (Sanofi Pasteur MSD); Intramuscular injection of Typhim Vi vaccine (0.5 ml).

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Universitaire Ziekenhuizen KU Leuven
• Collaborators: KU Leuven
• Investigators: Principal Investigator: Isabelle Meyts, MD, PhD, UZ Leuven

Publications and helpful links

General Publications

• Schaballie H, Vermeulen F, Verbinnen B, Frans G, Vermeulen E, Proesmans M, De Vreese K, Emonds MP, De Boeck K, Moens L, Picard C, Bossuyt X, Meyts I. Value of allohaemagglutinins in the diagnosis of a polysaccharide antibody deficiency. Clin Exp Immunol. 2015 May;180(2):271-9. doi: 10.1111/cei.12571.

Study record dates

Study Major Dates

• Study Start: October 1, 2015
• Primary Completion (Actual): August 1, 2018
• Study Completion (Actual): August 1, 2018

Study Registration Dates

• First Submitted: February 19, 2015
• First Submitted That Met QC Criteria: April 23, 2015
• First Posted (Estimated): April 29, 2015

Study Record Updates

• Last Update Posted (Actual): July 15, 2024
• Last Update Submitted That Met QC Criteria: July 11, 2024
• Last Verified: July 1, 2024

More Information

Terms related to this study

• Keywords: Pneumovax 23; Typhim Vi; allohemagglutinins
• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Immunologic Factors; Heptavalent Pneumococcal Conjugate Vaccine
• Other Study ID Numbers: S57605