Polysaccharide Antibody Response Study

NCT02429531 — Phase 4, Completed, 200 participants, Universitaire Ziekenhuizen KU Leuven

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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

Registry	NCT02429531, acronym PARS
Status	Completed
Phase	Phase 4
Study type	Interventional; non randomized, single group, masking: none, diagnostic
Enrollment	200 (Actual)
Sponsor	Universitaire Ziekenhuizen KU Leuven (Other); collaborators: KU Leuven
Conditions	Specific Polysaccharide Antibody Deficiency
Interventions	Pneumovax 23 (Sanofi Pasteur MSD), Typhim Vi (Sanofi Pasteur MSD) (Biological)
Dates	start 2015-10-01, primary completion 2018-08-01, completion 2018-08-01, first posted 2015-04-29, last updated 2024-07-15
Locations	1 site in Belgium

-Summary

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.

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+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.

+Arms and interventions

Arm	Type	Interventions	Description
Healthy controls	Experimental	Biological: Pneumovax 23 (Sanofi Pasteur MSD); Biological: Typhim Vi (Sanofi Pasteur MSD)	Healthy volunteers who consented to participate in the study will be immunized with both Pneumovax 23 and Typhim Vi .
Patients	Experimental	Biological: Pneumovax 23 (Sanofi Pasteur MSD); Biological: Typhim Vi (Sanofi Pasteur MSD)	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 .

Pneumovax 23 (Sanofi Pasteur MSD) (Biological): Intramuscular injection of Pneumovax 23 vaccine (0.5 ml).
Typhim Vi (Sanofi Pasteur MSD) (Biological): Intramuscular injection of Typhim Vi vaccine (0.5 ml).

+Outcome measures

Primary outcomes

Typhim Vi response specific anti-Vi IgG as measured by ELISA [3-4 weeks]: specific anti-Vi IgG as measured by ELISA
Pneumovax 23 response specific pneumococcal polysaccharide IgG as measured by ELISA [3-4 weeks]: specific pneumococcal polysaccharide IgG as measured by ELISA

Secondary outcomes

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

+Eligibility

Sex: All, ages: 18 Months to 55 Years, accepts healthy volunteers

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

+Locations (1)

Facility	City	Country	Status
UZ Leuven	Leuven	Belgium

+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. PMID 25516411

+Investigators

Isabelle Meyts, MD, PhD, Principal investigator, UZ Leuven