Influenza‐specific IgG1+ memory B‐cell numbers increase upon booster vaccination in healthy adults but not in patients with predominantly antibody deficiency

Abstract Background Annual influenza vaccination is recommended to all individuals over 6 months of age, including predominantly antibody deficiency (PAD) patients. Vaccination responses are typically evaluated by serology, and because PAD patients are by definition impaired in generating IgG and re...

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Main Authors: Gemma E Hartley, Emily S J Edwards, Julian J Bosco, Samar Ojaimi, Robert G Stirling, Paul U Cameron, Katie Flanagan, Magdalena Plebanski, Philip Mark Hogarth, Robyn E O’Hehir, Menno C vanZelm
Format: Article
Language:English
Published: Wiley 2020-01-01
Series:Clinical & Translational Immunology
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Online Access:https://doi.org/10.1002/cti2.1199
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author Gemma E Hartley
Emily S J Edwards
Julian J Bosco
Samar Ojaimi
Robert G Stirling
Paul U Cameron
Katie Flanagan
Magdalena Plebanski
Philip Mark Hogarth
Robyn E O’Hehir
Menno C vanZelm
author_facet Gemma E Hartley
Emily S J Edwards
Julian J Bosco
Samar Ojaimi
Robert G Stirling
Paul U Cameron
Katie Flanagan
Magdalena Plebanski
Philip Mark Hogarth
Robyn E O’Hehir
Menno C vanZelm
author_sort Gemma E Hartley
collection DOAJ
description Abstract Background Annual influenza vaccination is recommended to all individuals over 6 months of age, including predominantly antibody deficiency (PAD) patients. Vaccination responses are typically evaluated by serology, and because PAD patients are by definition impaired in generating IgG and receive immunoglobulin replacement therapy (IgRT), it remains unclear whether they can mount an antigen‐specific response. Objective To quantify and characterise the antigen‐specific memory B (Bmem) cell compartment in healthy controls and PAD patients following an influenza booster vaccination. Methods Recombinant hemagglutinin (HA) from the A/Michigan/2015 H1N1 (AM15) strain with an AviTag was generated in a mammalian cell line, and following targeted biotinylation, was tetramerised with BUV395 or BUV737 streptavidin conjugates. Multicolour flow cytometry was applied on blood samples before and 28 days after booster influenza vaccination in 16 healthy controls and five PAD patients with circulating Bmem cells. Results Recombinant HA tetramers were specifically recognised by 0.5–1% of B cells in previously vaccinated healthy adults. HA‐specific Bmem cell numbers were significantly increased following booster vaccination and predominantly expressed IgG1. Similarly, PAD patients carried HA‐specific Bmem cells, predominantly expressing IgG1. However, these numbers were lower than in controls and did not increase following booster vaccination. Conclusion We have successfully identified AM15‐specific Bmem cells in healthy controls and PAD patients. The presence of antigen‐specific Bmem cells could offer an additional diagnostic tool to aid in the clinical diagnosis of PAD. Furthermore, alterations in the number or immunophenotype of HA‐specific Bmem cells post‐booster vaccination could assist in the evaluation of immune responses in individuals receiving IgRT.
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spelling doaj.art-735b1e7014794777a7f6c1fbad0307d22022-12-22T01:20:34ZengWileyClinical & Translational Immunology2050-00682020-01-01910n/an/a10.1002/cti2.1199Influenza‐specific IgG1+ memory B‐cell numbers increase upon booster vaccination in healthy adults but not in patients with predominantly antibody deficiencyGemma E Hartley0Emily S J Edwards1Julian J Bosco2Samar Ojaimi3Robert G Stirling4Paul U Cameron5Katie Flanagan6Magdalena Plebanski7Philip Mark Hogarth8Robyn E O’Hehir9Menno C vanZelm10Department of Immunology and Pathology Central Clinical School Monash University Melbourne VIC AustraliaDepartment of Immunology and Pathology Central Clinical School Monash University Melbourne VIC AustraliaThe Jeffrey Modell Diagnostic and Research Centre for Primary Immunodeficiencies Melbourne VIC AustraliaThe Jeffrey Modell Diagnostic and Research Centre for Primary Immunodeficiencies Melbourne VIC AustraliaThe Jeffrey Modell Diagnostic and Research Centre for Primary Immunodeficiencies Melbourne VIC AustraliaThe Jeffrey Modell Diagnostic and Research Centre for Primary Immunodeficiencies Melbourne VIC AustraliaDepartment of Immunology and Pathology Central Clinical School Monash University Melbourne VIC AustraliaSchool of Health and Biomedical Sciences RMIT Bundoora VIC AustraliaDepartment of Immunology and Pathology Central Clinical School Monash University Melbourne VIC AustraliaDepartment of Immunology and Pathology Central Clinical School Monash University Melbourne VIC AustraliaDepartment of Immunology and Pathology Central Clinical School Monash University Melbourne VIC AustraliaAbstract Background Annual influenza vaccination is recommended to all individuals over 6 months of age, including predominantly antibody deficiency (PAD) patients. Vaccination responses are typically evaluated by serology, and because PAD patients are by definition impaired in generating IgG and receive immunoglobulin replacement therapy (IgRT), it remains unclear whether they can mount an antigen‐specific response. Objective To quantify and characterise the antigen‐specific memory B (Bmem) cell compartment in healthy controls and PAD patients following an influenza booster vaccination. Methods Recombinant hemagglutinin (HA) from the A/Michigan/2015 H1N1 (AM15) strain with an AviTag was generated in a mammalian cell line, and following targeted biotinylation, was tetramerised with BUV395 or BUV737 streptavidin conjugates. Multicolour flow cytometry was applied on blood samples before and 28 days after booster influenza vaccination in 16 healthy controls and five PAD patients with circulating Bmem cells. Results Recombinant HA tetramers were specifically recognised by 0.5–1% of B cells in previously vaccinated healthy adults. HA‐specific Bmem cell numbers were significantly increased following booster vaccination and predominantly expressed IgG1. Similarly, PAD patients carried HA‐specific Bmem cells, predominantly expressing IgG1. However, these numbers were lower than in controls and did not increase following booster vaccination. Conclusion We have successfully identified AM15‐specific Bmem cells in healthy controls and PAD patients. The presence of antigen‐specific Bmem cells could offer an additional diagnostic tool to aid in the clinical diagnosis of PAD. Furthermore, alterations in the number or immunophenotype of HA‐specific Bmem cells post‐booster vaccination could assist in the evaluation of immune responses in individuals receiving IgRT.https://doi.org/10.1002/cti2.1199antigen‐specific memory B cellsinfluenzapredominantly antibody deficiencyvaccination
spellingShingle Gemma E Hartley
Emily S J Edwards
Julian J Bosco
Samar Ojaimi
Robert G Stirling
Paul U Cameron
Katie Flanagan
Magdalena Plebanski
Philip Mark Hogarth
Robyn E O’Hehir
Menno C vanZelm
Influenza‐specific IgG1+ memory B‐cell numbers increase upon booster vaccination in healthy adults but not in patients with predominantly antibody deficiency
Clinical & Translational Immunology
antigen‐specific memory B cells
influenza
predominantly antibody deficiency
vaccination
title Influenza‐specific IgG1+ memory B‐cell numbers increase upon booster vaccination in healthy adults but not in patients with predominantly antibody deficiency
title_full Influenza‐specific IgG1+ memory B‐cell numbers increase upon booster vaccination in healthy adults but not in patients with predominantly antibody deficiency
title_fullStr Influenza‐specific IgG1+ memory B‐cell numbers increase upon booster vaccination in healthy adults but not in patients with predominantly antibody deficiency
title_full_unstemmed Influenza‐specific IgG1+ memory B‐cell numbers increase upon booster vaccination in healthy adults but not in patients with predominantly antibody deficiency
title_short Influenza‐specific IgG1+ memory B‐cell numbers increase upon booster vaccination in healthy adults but not in patients with predominantly antibody deficiency
title_sort influenza specific igg1 memory b cell numbers increase upon booster vaccination in healthy adults but not in patients with predominantly antibody deficiency
topic antigen‐specific memory B cells
influenza
predominantly antibody deficiency
vaccination
url https://doi.org/10.1002/cti2.1199
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