Specific anti-glycan antibodies are sustained during and after parasite clearance in Schistosoma japonicum-infected rhesus macaques

PLoS Negl Trop Dis. 2017 Feb 2;11(2):e0005339. doi: 10.1371/journal.pntd.0005339. eCollection 2017 Feb.

Abstract

Background: Human immunity to Schistosoma infection requires many years of exposure, and multiple infections and treatments to develop. Unlike humans, rhesus macaques clear an established schistosome infection naturally at the same time acquiring immunity towards re-infection. In macaques, schistosome egg production decreases after 8 weeks post-infection and by week 22, physiological impairment of the worm caused by unclarified antibody-mediated processes is observed. Since strong antibody responses have been observed against schistosome glycan antigens in human and animal infections, we here investigate if anti-glycan antibodies are associated with immunity against schistosome infections in macaques.

Methods: We used a microarray containing a large repertoire of glycoprotein- and glycolipid-derived glycans from different schistosome life stages to analyse anti-glycan serum IgG and IgM from S. japonicum-infected macaques during the course of infection and self-cure. We also used an in vitro schistosomula assay to investigate whether macaque sera containing anti-glycan antibodies can kill schistosomula.

Conclusions/significance: Antibody responses towards schistosome glycans at week 4 post-infection were dominated by IgM while IgG was high at week 8. The profound increase in IgG was observed mainly for antibodies towards a large subset of glycans that contain (multi-)fucosylated terminal GalNAcβ1-4GlcNAc (LDN), and Galβ1-4(Fucα1-3)GlcNAc (LeX) motifs. In general, glycans with a higher degree of fucosylation gave rise to stronger antibody responses than non-fucosylated glycans. Interestingly, even though many IgG and IgM responses had declined by week 22 post-infection, IgG towards O-glycans with highly fucosylated LDN motifs remained. When incubating macaque serum with schistosomula in vitro, schistosomula death was positively correlated with the duration of infection of macaques; macaque serum taken 22 weeks post-infection caused most schistosomula to die, suggesting the presence of potentially protective antibodies. We hypothesize that IgGs against highly fucosylated LDN motifs that remain when the worms deteriorate are associated with infection clearance and the resistance to re-infection in macaques.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Helminth / immunology*
  • Antigens, Helminth / immunology
  • Antigens, Helminth / metabolism
  • Glycoproteins / immunology
  • Glycoproteins / metabolism
  • Glycosylation
  • Humans
  • Immunoglobulin G / immunology
  • Macaca mulatta
  • Polysaccharides / immunology*
  • Schistosoma japonicum / immunology*
  • Schistosoma japonicum / metabolism
  • Schistosomiasis japonica / immunology*
  • Schistosomiasis japonica / parasitology

Substances

  • Antibodies, Helminth
  • Antigens, Helminth
  • Glycoproteins
  • Immunoglobulin G
  • Polysaccharides

Grants and funding

The research leading to these results has received funding from European Union’s Seventh Framework Programme (FP7/2007-2013) under grant agreement number 242107, as well as from the European Union's Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreements number 642870 (ETN-Immunoshape). We acknowledge funding by the Spanish Ministry of Economy and Competiveness, MINECO (CTQ2014-58779-R). Additionally, funding was received from the National Natural Science Foundation of China (http://www.nsfc.gov.cn/) under agreement number 31100637 and the Natural Science Foundation of Shanghai (http://www.stcsm.gov.cn/) under agreement number 15ZR1444330. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.