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Glycobiology. 2014 Jul;24(7):619-37. doi: 10.1093/glycob/cwu027. Epub 2014 Apr 11.

Immunization with recombinantly expressed glycan antigens from Schistosoma mansoni induces glycan-specific antibodies against the parasite.

Glycobiology

Nina Salinger Prasanphanich, Anthony E Luyai, Xuezheng Song, Jamie Heimburg-Molinaro, Msano Mandalasi, Megan Mickum, David F Smith, A Kwame Nyame, Richard D Cummings

Affiliations

  1. Emory University Glycomics Center, 4024 O. Wayne Rollins Research Building, 1510 Clifton Rd., Atlanta, GA 30322, USA.
  2. Department of Natural Sciences, University of Maryland Eastern Shore, Princess Anne, MD 21853, USA.
  3. Department of Biochemistry, Emory University School of Medicine, O. Wayne Rollins Research Center, 1510 Clifton Road, Suite 4001, Atlanta, GA 30322, USA.
  4. Emory University Glycomics Center, 4024 O. Wayne Rollins Research Building, 1510 Clifton Rd., Atlanta, GA 30322, USA Department of Biochemistry, Emory University School of Medicine, O. Wayne Rollins Research Center, 1510 Clifton Road, Suite 4001, Atlanta, GA 30322, USA [email protected].

PMID: 24727440 PMCID: PMC4038251 DOI: 10.1093/glycob/cwu027

Abstract

Schistosomiasis caused by infection with parasitic helminths of Schistosoma spp. is a major global health problem due to inadequate treatment and lack of a vaccine. The immune response to schistosomes includes glycan antigens, which could be valuable diagnostic markers and vaccine targets. However, no precedent exists for how to design vaccines targeting eukaryotic glycoconjugates. The di- and tri-saccharide motifs LacdiNAc (GalNAcβ1,4GlcNAc; LDN) and fucosylated LacdiNAc (GalNAcβ1,4(Fucα1-3)GlcNAc; LDNF) are the basis for several important schistosome glycan antigens. They occur in monomeric form or as repeating units (poly-LDNF) and as part of a variety of different glycoconjugates. Because chemical synthesis and conjugation of such antigens is exceedingly difficult, we sought to develop a recombinant expression system for parasite glycans. We hypothesized that presentation of parasite glycans on the cell surface would induce glycan-specific antibodies. We generated Chinese hamster ovary (CHO) Lec8 cell lines expressing poly-LDN (L8-GT) and poly-LDNF (L8-GTFT) abundantly on their membrane glycoproteins. Sera from Schistosoma mansoni-infected mice were highly cross-reactive with the cells and with cell-surface N-glycans. Immunizing mice with L8-GT and L8-GTFT cells induced glycan-specific antibodies. The L8-GTFT cells induced a sustained booster response, with antibodies that bound to S. mansoni lysates and recapitulated the exquisite specificity of the anti-parasite response for particular presentations of LDNF antigen. In summary, this recombinant expression system promotes successful generation of antibodies to the glycans of S. mansoni, and it can be adapted to study the role of glycan antigens and anti-glycan immune responses in many other infections and pathologies.

© The Author 2014. Published by Oxford University Press. All rights reserved. For permissions, please e-mail: [email protected].

Keywords: LDNF; cellular engineering; glyco-conjugate; helminth; schistosome

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