Schistosoma mansoni infection induces plasmablast and plasma cell death in the bone marrow and accelerates the decline of host vaccine responses

PLoS Pathog. 2022 Feb 14;18(2):e1010327. doi: 10.1371/journal.ppat.1010327. eCollection 2022 Feb.

Abstract

Schistosomiasis is a potentially lethal parasitic disease that profoundly impacts systemic immune function in chronically infected hosts through mechanisms that remain unknown. Given the immunoregulatory dysregulation experienced in infected individuals, this study examined the impact of chronic schistosomiasis on the sustainability of vaccine-induced immunity in both children living in endemic areas and experimental infections in mice. Data show that chronic Schistosoma mansoni infection impaired the persistence of vaccine specific antibody responses in poliovirus-vaccinated humans and mice. Mechanistically, schistosomiasis primarily fostered plasmablast and plasma cell death in the bone marrow and removal of parasites following praziquantel treatment reversed the observed cell death and partially restored vaccine-induced memory responses associated with increased serum anti-polio antibody responses. Our findings strongly suggest a previously unrecognized mechanism to explain how chronic schistosomiasis interferes with an otherwise effective vaccine regimen and further advocates for therapeutic intervention strategies that reduce schistosomiasis burden in endemic areas prior to vaccination.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow
  • Cell Death
  • Mice
  • Plasma Cells
  • Schistosoma mansoni
  • Schistosomiasis mansoni*
  • Schistosomiasis*
  • Vaccines* / therapeutic use

Substances

  • Vaccines

Grants and funding

This project is part of the EDCTP2 program supported by the European Union, through grant number TMA2016CDF-1571, with support from grant FLR\R1\191058 of the FLAIR Fellowship Program, a partnership between the African Academy of Sciences and the Royal Society funded by the UK Government’s Global Challenges Research Fund, and the Poliomyelitis research Foundation of South Africa (Grant Nr 18/19) to JKN. FM is a recipient of a Ph.D. fellowship from the South African National Research Foundation (NRF) and funding assistance from the Univer-sity of Cape Town (UCT) and the Poliomyelitis Research Foundation of South Africa (PRF). SDK is a former recipient of a PhD fellowship from the International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town component, and was a fellow of the Royal Society of Tropical Medicine and Hygiene (RSTMH) small grant supported by the National Institute for Health Research (NIHR) grant number (RSTMH\2019\12837708) and a Postdoctoral fellow within a UK Royal So-ciety FLAIR-funded grant (FLR\R1\191058) at the time of the present work. FB is funded by the International Centre for Genetic Engineering and Biotechnology, Cape Town component; the South African National Research Foundation and Medical Research Council with further support from CIDRI-Africa (grant No 203135/Z/16/Z). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.