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

Autor: Ercoli G; Centre for Inflammation and Tissue Repair UCL Respiratory Division of Medicine University College Medical School Rayne Institute London UK., Ramos-Sevillano E; Centre for Inflammation and Tissue Repair UCL Respiratory Division of Medicine University College Medical School Rayne Institute London UK., Pearce E; Department of Immunobiology UCL Great Ormond Street Institute of Child Health NIHR Biomedical Research Centre London UK., Ragab S; Department of Immunobiology UCL Great Ormond Street Institute of Child Health NIHR Biomedical Research Centre London UK., Goldblatt D; Department of Immunobiology UCL Great Ormond Street Institute of Child Health NIHR Biomedical Research Centre London UK., Weckbecker G; Novartis Institute for BioMedical Research Novartis Basel Switzerland., Brown JS; Centre for Inflammation and Tissue Repair UCL Respiratory Division of Medicine University College Medical School Rayne Institute London UK.
Jazyk: angličtina
Zdroj: Clinical & translational immunology [Clin Transl Immunology] 2021 Dec 28; Vol. 11 (1), pp. e1366. Date of Electronic Publication: 2021 Dec 28 (Print Publication: 2022).
DOI: 10.1002/cti2.1366
Abstrakt: 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.
Competing Interests: GW was employed by the company Novartis Institute for BioMedical Research. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
(© 2021 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.)
Databáze: MEDLINE
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