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Title: Immunization with Outer Membrane Vesicles Displaying Designer Glycotopes Yields Class-Switched, Glycan-Specific Antibodies

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:
 [1] ;  [1] ;  [1] ;  [1] ;  [1] ;  [2] ;  [2] ;  [3] ;  [1] ;  [4] ;  [3] ;  [1]
  1. Cornell Univ., Ithaca, NY (United States)
  2. Univ. of Georgia, Athens, GA (United States)
  3. Glycobia Inc., Ithaca, NY (United States)
  4. Children's Hospital Oakland Research Inst., Oakland, CA (United States)
Publication Date:
Grant/Contract Number:
FG02-93ER20097
Type:
Published Article
Journal Name:
Cell Chemical Biology
Additional Journal Information:
Journal Volume: 23; Journal Issue: 6; Journal ID: ISSN 2451-9456
Publisher:
Cell Press - Elsevier
Research Org:
Univ. of Georgia, Athens, GA (United States)
Sponsoring Org:
USDOE Office of Science (SC), Basic Energy Sciences (BES) (SC-22). Chemical Sciences, Geosciences & Biosciences Division; USDOE
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES
OSTI Identifier:
1365583
Alternate Identifier(s):
OSTI ID: 1356684; OSTI ID: 1437991

Valentine, Jenny L., Chen, Linxiao, Perregaux, Emily C., Weyant, Kevin B., Rosenthal, Joseph A., Heiss, Christian, Azadi, Parastoo, Fisher, Adam C., Putnam, David, Moe, Gregory R., Merritt, Judith H., and DeLisa, Matthew P.. Immunization with Outer Membrane Vesicles Displaying Designer Glycotopes Yields Class-Switched, Glycan-Specific Antibodies. United States: N. p., Web. doi:10.1016/j.chembiol.2016.05.014.
Valentine, Jenny L., Chen, Linxiao, Perregaux, Emily C., Weyant, Kevin B., Rosenthal, Joseph A., Heiss, Christian, Azadi, Parastoo, Fisher, Adam C., Putnam, David, Moe, Gregory R., Merritt, Judith H., & DeLisa, Matthew P.. Immunization with Outer Membrane Vesicles Displaying Designer Glycotopes Yields Class-Switched, Glycan-Specific Antibodies. United States. doi:10.1016/j.chembiol.2016.05.014.
Valentine, Jenny L., Chen, Linxiao, Perregaux, Emily C., Weyant, Kevin B., Rosenthal, Joseph A., Heiss, Christian, Azadi, Parastoo, Fisher, Adam C., Putnam, David, Moe, Gregory R., Merritt, Judith H., and DeLisa, Matthew P.. 2016. "Immunization with Outer Membrane Vesicles Displaying Designer Glycotopes Yields Class-Switched, Glycan-Specific Antibodies". United States. doi:10.1016/j.chembiol.2016.05.014.
@article{osti_1365583,
title = {Immunization with Outer Membrane Vesicles Displaying Designer Glycotopes Yields Class-Switched, Glycan-Specific Antibodies},
author = {Valentine, Jenny L. and Chen, Linxiao and Perregaux, Emily C. and Weyant, Kevin B. and Rosenthal, Joseph A. and Heiss, Christian and Azadi, Parastoo and Fisher, Adam C. and Putnam, David and Moe, Gregory R. and Merritt, Judith H. and DeLisa, Matthew P.},
abstractNote = {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.},
doi = {10.1016/j.chembiol.2016.05.014},
journal = {Cell Chemical Biology},
number = 6,
volume = 23,
place = {United States},
year = {2016},
month = {6}
}