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Maintained partial protection against Streptococcus pneumoniae despite B‐cell depletion in mice vaccinated with a pneumococcal glycoconjugate vaccine

Ercoli, G; Ramos‐Sevillano, E; Pearce, E; Ragab, S; Goldblatt, D; Weckbecker, G; Brown, JS; (2021) Maintained partial protection against Streptococcus pneumoniae despite B‐cell depletion in mice vaccinated with a pneumococcal glycoconjugate vaccine. Clinical & Translational Immunology , 11 (1) 10.1002/cti2.1366. (In press). Green open access

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Abstract

Objectives: Anti-CD20 monoclonal antibody therapy rapidly depletes > 95% of CD20+ B cells from the circulation. B-cell depletion is an effective treatment for autoimmune disease and B-cell malignancies but also increases the risk of respiratory tract infections. This effect on adaptive immunity could be countered by vaccination. We have used mouse models to investigate the effects of B-cell depletion on pneumococcal vaccination, including protection against infection and timing of vaccination in relation to B-cell depletion. // Methods: C57BL/6 female mice were B-cell depleted using anti-CD20 antibody and immunized with two doses of Prevnar-13 vaccine either before or after anti-CD20 treatment. B-cell repertoire and Streptococcus pneumoniae–specific IgG levels were measured using whole-cell ELISA and flow cytometry antibody-binding assay. Protection induced by vaccination was assessed by challenging the mice using a S. pneumoniae pneumonia model. // Results: Antibody responses to S. pneumoniae were largely preserved in mice B-cell depleted after vaccination resulting in full protection against pneumococcal infections. In contrast, mice vaccinated with Prevnar-13 while B cells were depleted (with > 90% reduction in B-cell numbers) had decreased circulating anti–S. pneumoniae IgG and IgM levels (measured using ELISA and flow cytometry antibody binding assays). However, some antibody responses were maintained, and, although vaccine-induced protection against S. pneumoniae infection was impaired, septicaemia was still prevented in 50% of challenged mice. // Conclusions: This study showed that although vaccine efficacy during periods of profound B-cell depletion was impaired some protective efficacy was preserved, suggesting that vaccination remains beneficial.

Type: Article
Title: Maintained partial protection against Streptococcus pneumoniae despite B‐cell depletion in mice vaccinated with a pneumococcal glycoconjugate vaccine
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/cti2.1366
Publisher version: https://doi.org/10.1002/cti2.1366
Language: English
Additional information: © 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: B-cell depletion; CD20; immunity; Streptococcus pneumoniae; vaccination
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Medical Sciences > Div of Medicine > Respiratory Medicine
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Population Health Sciences > UCL GOS Institute of Child Health > Infection, Immunity and Inflammation Dept
URI: https://discovery.ucl.ac.uk/id/eprint/10141683
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