Combined deficient response to polysaccharide-based and protein-based vaccines predicts a severe clinical phenotype

Maaike Cockx^{1

2}, Filomeen Haerynck^{3

4}, Levi Hoste^{3

4}, Rik Schrijvers^{1

5}, Jutte Van der Werff Ten Bosch⁶, Doreen Dillaerts¹, Debby Thomas^{2

7}, Heidi Schaballie⁸, Giorgia Bucciol⁸, Wiert Robberechts⁶, Dina Patel⁹, Guy Berbers¹⁰, Isabelle Desombere¹¹, Nick Geukens², Isabelle Meyts^{8

12}, Xavier Bossuyt^{1

2

13}

Affiliations

¹ Department of Microbiology, Immunology and Transplantation, University of Leuven, Leuven, Belgium.
² PharmAbs, The KU Leuven Antibody Center, University of Leuven, Leuven, Belgium.
³ Department of Internal Medicine and Pediatrics, Center for Primary Immunodeficiency, PID research lab, Ghent University, Ghent, Belgium.
⁴ Department of Pediatric Pulmonology and Immunology, University Hospital Ghent, Ghent, Belgium.
⁵ Department of General Internal Medicine, University Hospitals Leuven, Leuven, Belgium.
⁶ Department of Pediatrics, University Hospital Brussels, Brussels, Belgium.
⁷ Laboratory for Therapeutic and Diagnostic Antibodies, University of Leuven, Leuven, Belgium.
⁸ Department of Pediatrics, Division of Primary Immunodeficiencies, University Hospitals Leuven, Leuven, Belgium.
⁹ UK NEQAS Immunology, Immunochemistry & Allergy, Northern General Hospital, Sheffield, UK.
¹⁰ National Institute for Public Health and the Environment, Centre for Infectious Disease Control, Bilthoven, The Netherlands.
¹¹ Department of Infectious Diseases in Humans, Laboratory Immune Response, Sciensano, Brussels, Belgium.
¹² Department of Microbiology, Immunology and Transplantation, Laboratory for Inborn Errors of Immunity, University of Leuven, Leuven, Belgium.
¹³ Laboratory of Clinical and Diagnostic Immunology, Leuven, Belgium.

PMID: 37731388
DOI: 10.1515/cclm-2023-0626

Combined deficient response to polysaccharide-based and protein-based vaccines predicts a severe clinical phenotype

Maaike Cockx et al. Clin Chem Lab Med. 2023.

. 2023 Sep 21;62(1):138-149.

doi: 10.1515/cclm-2023-0626. Print 2024 Jan 26.

Authors

Affiliations

¹ Department of Microbiology, Immunology and Transplantation, University of Leuven, Leuven, Belgium.
² PharmAbs, The KU Leuven Antibody Center, University of Leuven, Leuven, Belgium.
³ Department of Internal Medicine and Pediatrics, Center for Primary Immunodeficiency, PID research lab, Ghent University, Ghent, Belgium.
⁴ Department of Pediatric Pulmonology and Immunology, University Hospital Ghent, Ghent, Belgium.
⁵ Department of General Internal Medicine, University Hospitals Leuven, Leuven, Belgium.
⁶ Department of Pediatrics, University Hospital Brussels, Brussels, Belgium.
⁷ Laboratory for Therapeutic and Diagnostic Antibodies, University of Leuven, Leuven, Belgium.
⁸ Department of Pediatrics, Division of Primary Immunodeficiencies, University Hospitals Leuven, Leuven, Belgium.
⁹ UK NEQAS Immunology, Immunochemistry & Allergy, Northern General Hospital, Sheffield, UK.
¹⁰ National Institute for Public Health and the Environment, Centre for Infectious Disease Control, Bilthoven, The Netherlands.
¹¹ Department of Infectious Diseases in Humans, Laboratory Immune Response, Sciensano, Brussels, Belgium.
¹² Department of Microbiology, Immunology and Transplantation, Laboratory for Inborn Errors of Immunity, University of Leuven, Leuven, Belgium.
¹³ Laboratory of Clinical and Diagnostic Immunology, Leuven, Belgium.

PMID: 37731388
DOI: 10.1515/cclm-2023-0626

Abstract

Objectives: Antibody response on polysaccharide- and protein-based vaccines is useful to test B cell functionality. As only few studies have explored the value of studying immune response to both vaccines, we evaluated the clinical value of anti-polysaccharide and anti-protein Luminex-based multiplex assays in context of primary immunodeficiency (PID) diagnosis.

Methods: A 10-plex Luminex-based assay detecting antibodies to ten pneumococcal polysaccharide (PnPS) serotypes [present in unconjugated Pneumovax, not in 13-valent pneumococcal conjugated vaccine (PCV)] and a 5-plex assay detecting antibodies to five protein antigens (present in DTap/Tdap) were clinically validated in healthy individuals (n=99) and in retrospective (n=399) and prospective (n=108) patient cohorts. Clinical features of individuals with impaired response to PnPS and/or proteins were compared to those with normal response.

Results: Antigen-specific antibody thresholds were determined in healthy individuals. Individuals with impaired anti-PnPS responses and deficient immunoglobulin levels suffered more from autoimmune diseases and had lower B cell levels compared to individuals with impaired anti-PnPS response with normal immunoglobulin levels. Individuals with combined impaired response to PnPS and proteins showed more severe clinical manifestations compared to individuals with isolated impaired response to PnPS or proteins. Eight of the 11 individuals with severely impaired responses to both PnPS and proteins had common variable immunodeficiency. Evaluation of the anti-PnPS response to four serotypes not contained in 20-valent PCV was comparable to evaluation to ten serotypes not contained in 13-valent PCV.

Conclusions: Multiplexed assessment of anti-PnPS and anti-protein responses combined with immunoglobulin quantification provides useful clinical information to support PID diagnosis.

Keywords: DTaP/Tdap vaccine; PCV15/20; Pneumovax; multiplex assays; pneumococcal polysaccharides; primary immunodeficiency diagnosis.

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References

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1. Bonilla, FA. Update: vaccines in primary immunodeficiency. J Allergy Clin Immunol 2018;141:474–81. https://doi.org/10.1016/j.jaci.2017.12.980 . - DOI

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Combined deficient response to polysaccharide-based and protein-based vaccines predicts a severe clinical phenotype

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Combined deficient response to polysaccharide-based and protein-based vaccines predicts a severe clinical phenotype

Authors

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Abstract

References

MeSH terms

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LinkOut - more resources

Full Text Sources

Research Materials