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Sci Immunol. 2019 Nov 1;4(41). pii: eaay6125. doi: 10.1126/sciimmunol.aay6125.

Incomplete genetic reconstitution of B cell pools contributes to prolonged immunosuppression after measles.

Author information

1
Department of Human Genetics, Wellcome Sanger Institute, Cambridge, UK. vp5@sanger.ac.uk c.a.russell@amc.uva.nl.
2
Veterinary Medicine Division, Paul-Ehrlich-Institut, Federal Institute for Vaccines and Biomedicines and DZIF TTU Emerging Infections, Langen, Germany.
3
Bioinformatics Institute, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.
4
Laboratory of Applied Evolutionary Biology, Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands.
5
Department of Viroscience, Postgraduate School of Molecular Medicine, Erasmus MC, University Medical Centre Rotterdam, Rotterdam, Netherlands.
6
Institute for Research in Biomedicine, Università della Svizzera Italiana, Bellinzona, Switzerland.
7
Department of Human Genetics, Wellcome Sanger Institute, Cambridge, UK.
8
Department of Medicine, Division of Infectious Diseases, Imperial College Faculty of Medicine, Wright Fleming Institute, St Mary's Campus, London, UK.
9
Kymab Ltd., The Bennet Building, Babraham Research Campus, Cambridge, UK.
10
Laboratory of Applied Evolutionary Biology, Department of Medical Microbiology, Academic Medical Center, University of Amsterdam, Amsterdam, Netherlands. vp5@sanger.ac.uk c.a.russell@amc.uva.nl.

Abstract

Measles is a disease caused by the highly infectious measles virus (MeV) that results in both viremia and lymphopenia. Lymphocyte counts recover shortly after the disappearance of measles-associated rash, but immunosuppression can persist for months to years after infection, resulting in increased incidence of secondary infections. Animal models and in vitro studies have proposed various immunological factors underlying this prolonged immune impairment, but the precise mechanisms operating in humans are unknown. Using B cell receptor (BCR) sequencing of human peripheral blood lymphocytes before and after MeV infection, we identified two immunological consequences from measles underlying immunosuppression: (i) incomplete reconstitution of the naïve B cell pool leading to immunological immaturity and (ii) compromised immune memory to previously encountered pathogens due to depletion of previously expanded B memory clones. Using a surrogate model of measles in ferrets, we investigated the clinical consequences of morbillivirus infection and demonstrated a depletion of vaccine-acquired immunity to influenza virus, leading to a compromised immune recall response and increased disease severity after secondary influenza virus challenge. Our results show that MeV infection causes changes in naïve and memory B lymphocyte diversity that persist after the resolution of clinical disease and thus contribute to compromised immunity to previous infections or vaccinations. This work highlights the importance of MeV vaccination not only for the control of measles but also for the maintenance of herd immunity to other pathogens, which can be compromised after MeV infection.

PMID:
31672862
DOI:
10.1126/sciimmunol.aay6125

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