title: Immunization with Outer Membrane Vesicles Displaying Designer Glycotopes Yields Class-Switched, Glycan-Specific Antibodies.
abstract: The development of antibodies against specific glycan epitopes poses a significant challenge due to difficulties obtaining desired glycans at sufficient quantity and purity, and the fact that glycans are usually weakly immunogenic. To address this challenge, we leveraged the potent immunostimulatory activity of bacterial outer membrane vesicles (OMVs) to deliver designer glycan epitopes to the immune system. This approach involved heterologous expression of two clinically important glycans, namely polysialic acid (PSA) and Thomsen-Friedenreich antigen (T antigen) in hypervesiculating strains of non-pathogenic Escherichia coli. The resulting glycOMVs displayed structural mimics of PSA or T antigen on their surfaces, and induced high titers of glycan-specific IgG antibodies following immunization in mice. In the case of PSA glycOMVs, serum antibodies potently killed Neisseria meningitidis serogroup B (MenB), whose outer capsule is PSA, in a serum bactericidal assay. These findings demonstrate the potential of glycOMVs for inducing class-switched, humoral immune responses against glycan antigens.
authors.affiliation: Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Jenny L
authors.initials: JL
authors.lastname: Valentine
authors.affiliation: Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Linxiao
authors.initials: L
authors.lastname: Chen
authors.affiliation: College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Emily C
authors.initials: EC
authors.lastname: Perregaux
authors.affiliation: Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Kevin B
authors.initials: KB
authors.lastname: Weyant
authors.affiliation: Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA.
authors.forename: Joseph A
authors.initials: JA
authors.lastname: Rosenthal
authors.affiliation: Complex Carbohydrate Research Center, The University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA.
authors.forename: Christian
authors.initials: C
authors.lastname: Heiss
authors.affiliation: Complex Carbohydrate Research Center, The University of Georgia, 315 Riverbend Road, Athens, GA 30602, USA.
authors.forename: Parastoo
authors.initials: P
authors.lastname: Azadi
authors.affiliation: Glycobia Inc., 33 Thornwood Drive, Ithaca, NY 14850, USA.
authors.forename: Adam C
authors.initials: AC
authors.lastname: Fisher
authors.affiliation: Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA; College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA.
authors.forename: David
authors.initials: D
authors.lastname: Putnam
authors.affiliation: Centers for Cancer and Immunobiology and Vaccine Development, Children's Hospital Oakland Research Institute, Oakland, CA 94609, USA.
authors.forename: Gregory R
authors.initials: GR
authors.lastname: Moe
authors.affiliation: Glycobia Inc., 33 Thornwood Drive, Ithaca, NY 14850, USA.
authors.forename: Judith H
authors.initials: JH
authors.lastname: Merritt
authors.affiliation: Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA; College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA; Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA. Electronic address: md255@cornell.edu.
authors.forename: Matthew P
authors.initials: MP
authors.lastname: DeLisa
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology*; D000937:Antigen-Antibody Reactions; D000942:Antigens, Bacterial / Q000276:immunology*; D001425:Bacterial Outer Membrane Proteins / Q000276:immunology*; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D005260:Female; D007114:Immunization; D017578:Immunoglobulin Class Switching; D051379:Mice; D008807:Mice, Inbred BALB C; D038541:Neisseria meningitidis, Serogroup B / Q000276:immunology*; D011134:Polysaccharides / Q000737:chemistry / Q000276:immunology*
chemical_list: D000907:Antibodies, Bacterial; D000942:Antigens, Bacterial; D001425:Bacterial Outer Membrane Proteins; D000939:Epitopes; D011134:Polysaccharides