Outer membrane vesicles displaying engineered glycotopes elicit protective antibodies

Chen, Linxiao; Valentine, Jenny L.; Huang, Chung-Jr; Endicott, Christine E.; Moeller, Tyler D.; Rasmussen, Jed A.; Fletcher, Joshua R.; Boll, Joseph M.; Rosenthal, Joseph A.; Dobruchowska, Justyna; Wang, Zhirui; Heiss, Christian; Azadi, Parastoo; Putnam, David; Trent, M. Stephen; Jones, Bradley D.; DeLisa, Matthew P.

doi:10.1073/pnas.1518311113

Outer membrane vesicles displaying engineered glycotopes elicit protective antibodies

Journal Article · Mon Jun 06 00:00:00 EDT 2016 · Proceedings of the National Academy of Sciences of the United States of America

DOI:https://doi.org/10.1073/pnas.1518311113· OSTI ID:1256136

^[1]; Valentine, Jenny L. ^[1]; Huang, Chung-Jr ^[1]; Endicott, Christine E. ^[1]; Moeller, Tyler D. ^[1]; Rasmussen, Jed A. ^[2]; Fletcher, Joshua R. ^[3]; Boll, Joseph M. ^[4]; Rosenthal, Joseph A. ^[5]; Dobruchowska, Justyna ^[6]; Wang, Zhirui ^[6]; Heiss, Christian ^[6]; Azadi, Parastoo ^[6]; Putnam, David ^[7]; Trent, M. Stephen ^[4]; Jones, Bradley D. ^[8]; DeLisa, Matthew P. ^[7]

Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853,
Department of Microbiology, University of Iowa, Iowa City, IA 52242,
Genetics Program, University of Iowa, Iowa City, IA 52242,
Department of Molecular Biosciences, The University of Texas at Austin, Austin, TX 78712,, Department of Infectious Diseases, The University of Georgia College of Veterinary Medicine, Athens, GA 30602,
Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853,
Complex Carbohydrate Research Center, The University of Georgia, Athens, GA 30602
Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853,, Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853,
Department of Microbiology, University of Iowa, Iowa City, IA 52242,, Genetics Program, University of Iowa, Iowa City, IA 52242,

Significance

Conjugate vaccines have proven to be an effective and safe strategy for reducing the incidence of disease caused by bacterial pathogens. However, the manufacture of these vaccines is technically demanding, inefficient, and expensive, thereby limiting their widespread use. Here, we describe an alternative methodology for generating glycoconjugate vaccines whereby recombinant polysaccharide biosynthesis is coordinated with vesicle formation in nonpathogenic Escherichia coli , resulting in glycosylated outer membrane vesicles (glycOMVs) that can effectively deliver pathogen-mimetic glycotopes to the immune system. An attractive feature of our approach is the fact that different plasmid-encoded polysaccharide biosynthetic pathways can be readily transformed into E. coli , enabling a “plug-and-play” platform for the on-demand creation of glycOMV vaccine candidates that carry heterologous glycotopes from numerous pathogenic bacteria.

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Sponsoring Organization:: USDOE

Grant/Contract Number:: FG02-93ER20097

OSTI ID:: 1256136

Alternate ID(s):: OSTI ID: 1349046

Journal Information:: Proceedings of the National Academy of Sciences of the United States of America, Journal Name: Proceedings of the National Academy of Sciences of the United States of America Journal Issue: 26 Vol. 113; ISSN 0027-8424

Publisher:: Proceedings of the National Academy of SciencesCopyright Statement

Country of Publication:: United States

Language:: English

References (62)

A systematic nomenclature for carbohydrate fragmentations in FAB-MS/MS spectra of glycoconjugates Domon, Bruno; Costello, Catherine E. Glycoconjugate Journal, Vol. 5, Issue 4 https://doi.org/10.1007/BF01049915	journal	January 1988
Putting endotoxin to work for us: Monophosphoryl lipid A as a safe and effective vaccine adjuvant Casella, C. R.; Mitchell, T. C. Cellular and Molecular Life Sciences, Vol. 65, Issue 20 https://doi.org/10.1007/s00018-008-8228-6	journal	August 2008
Somatic antigens of Shigella: Structure of the O-specific polysaccharide chain of the Shigella dysenteriae type 7 lipopolysaccharide Knirel, Yuriy A.; Dashunin, Vladimir V.; Shashkov, Alexander S. Carbohydrate Research, Vol. 179 https://doi.org/10.1016/0008-6215(88)84109-0	journal	August 1988
Structure of the O-antigen of Francisella tularensis strain 15 Vinogradov, Eugeny V.; Shashkov, Alexander S.; Knirel, Yuriy A. Carbohydrate Research, Vol. 214, Issue 2 https://doi.org/10.1016/0008-6215(91)80036-M	journal	July 1991
Role of lipopolysaccharide and a major outer membrane protein from Francisella tularensis in the induction of immunity against tularemia Fulop, Mark; Manchee, Richard; Titball, Richard Vaccine, Vol. 13, Issue 13 https://doi.org/10.1016/0264-410X(95)00062-6	journal	January 1995
Expression cloning of Yersinia enterocolitica 0 : 3 rfb gene cluster in Escherichia coli K12 Al-Hendy, Ayman; Toivanen, Paavo; Skurnik, Mikael Microbial Pathogenesis, Vol. 10, Issue 1 https://doi.org/10.1016/0882-4010(91)90065-I	journal	January 1991
Role of antibody to lipopolysaccharide in protection against low- and high-virulence strains of Francisella tularensis Fulop, Mark; Mastroeni, Pietro; Green, Michael Vaccine, Vol. 19, Issue 31 https://doi.org/10.1016/S0264-410X(01)00189-X	journal	August 2001
Immunology of bacterial polysaccharide antigens Weintraub, Andrej Carbohydrate Research, Vol. 338, Issue 23, p. 2539-2547 https://doi.org/10.1016/j.carres.2003.07.008	journal	November 2003
Microbial biosynthesis of designer outer membrane vesicles Baker, Jenny L.; Chen, Linxiao; Rosenthal, Joseph A. Current Opinion in Biotechnology, Vol. 29 https://doi.org/10.1016/j.copbio.2014.02.018	journal	October 2014
Engineered Bacterial Outer Membrane Vesicles with Enhanced Functionality Kim, Jae-Young; Doody, Anne M.; Chen, David J. Journal of Molecular Biology, Vol. 380, Issue 1 https://doi.org/10.1016/j.jmb.2008.03.076	journal	June 2008
Optimising the use of conjugate vaccines to prevent disease caused by Haemophilus influenzae type b, Neisseria meningitidis and Streptococcus pneumoniae Trotter, Caroline L.; McVernon, Jodie; Ramsay, Mary E. Vaccine, Vol. 26, Issue 35 https://doi.org/10.1016/j.vaccine.2008.05.073	journal	August 2008
Properties and clinical performance of vaccines containing outer membrane vesicles from Neisseria meningitidis Holst, Johan; Martin, Diana; Arnold, Richard Vaccine, Vol. 27 https://doi.org/10.1016/j.vaccine.2009.04.071	journal	June 2009
Preparation of bacterial polysaccharide–protein conjugates: Analytical and manufacturing challenges Frasch, Carl E. Vaccine, Vol. 27, Issue 46 https://doi.org/10.1016/j.vaccine.2009.06.013	journal	October 2009
B Cell Mitogenic Properties of Thymus-independent Antigens Coutinho, Antonio; MÖLler, GÖRan Nature New Biology, Vol. 245, Issue 140 https://doi.org/10.1038/newbio245012a0	journal	September 1973
Innate B cell helpers reveal novel types of antibody responses Vinuesa, Carola G.; Chang, Pheh-Ping Nature Immunology, Vol. 14, Issue 2 https://doi.org/10.1038/ni.2511	journal	January 2013
Carbohydrate vaccines: developing sweet solutions to sticky situations? Astronomo, Rena D.; Burton, Dennis R. Nature Reviews Drug Discovery, Vol. 9, Issue 4 https://doi.org/10.1038/nrd3012	journal	April 2010
New vaccine platform? Flemming, Alexandra Nature Reviews Drug Discovery, Vol. 9, Issue 3 https://doi.org/10.1038/nrd3117	journal	March 2010
T-cell–B-cell cooperation Mitchison, N. A. Nature Reviews Immunology, Vol. 4, Issue 4 https://doi.org/10.1038/nri1334	journal	April 2004
Tularaemia: bioterrorism defence renews interest in Francisella tularensis Oyston, Petra C. F.; Sjöstedt, Anders; Titball, Richard W. Nature Reviews Microbiology, Vol. 2, Issue 12 https://doi.org/10.1038/nrmicro1045	journal	December 2004
Characterization of bacteria using its O-antigen with surface-enhanced Raman scattering Osorio-Román, I. O.; Aroca, R. F.; Astudillo, J. The Analyst, Vol. 135, Issue 8 https://doi.org/10.1039/c0an00061b	journal	January 2010
Engineering N-linked protein glycosylation with diverse O antigen lipopolysaccharide structures in Escherichia coli Feldman, M. F.; Wacker, M.; Hernandez, M. Proceedings of the National Academy of Sciences, Vol. 102, Issue 8 https://doi.org/10.1073/pnas.0500044102	journal	February 2005
Substrate specificity of bacterial oligosaccharyltransferase suggests a common transfer mechanism for the bacterial and eukaryotic systems Wacker, M.; Feldman, M. F.; Callewaert, N. Proceedings of the National Academy of Sciences, Vol. 103, Issue 18 https://doi.org/10.1073/pnas.0509207103	journal	April 2006
Delivery of foreign antigens by engineered outer membrane vesicle vaccines Chen, D. J.; Osterrieder, N.; Metzger, S. M. Proceedings of the National Academy of Sciences, Vol. 107, Issue 7 https://doi.org/10.1073/pnas.0805532107	journal	January 2010
Modulating the innate immune response by combinatorial engineering of endotoxin Needham, Brittany D.; Carroll, Sean M.; Giles, David K. Proceedings of the National Academy of Sciences, Vol. 110, Issue 4 https://doi.org/10.1073/pnas.1218080110	journal	January 2013
Incorporation of Heterologous Outer Membrane and Periplasmic Proteins into Escherichia coli Outer Membrane Vesicles Kesty, Nicole C.; Kuehn, Meta J. Journal of Biological Chemistry, Vol. 279, Issue 3 https://doi.org/10.1074/jbc.M307628200	journal	October 2003
γδ T Cells Provide an Early Source of Interferon γ in Tumor Immunity Gao, Yunfei; Yang, Wancai; Pan, Meng The Journal of Experimental Medicine, Vol. 198, Issue 3 https://doi.org/10.1084/jem.20030584	journal	August 2003
Exploitation of bacterial N -linked glycosylation to develop a novel recombinant glycoconjugate vaccine against Francisella tularensis Cuccui, Jon; Thomas, Rebecca M.; Moule, Madeleine G. Open Biology, Vol. 3, Issue 5 https://doi.org/10.1098/rsob.130002	journal	May 2013
Recent developments in bacterial protein glycan coupling technology and glycoconjugate vaccine design Terra, V. S.; Mills, D. C.; Yates, L. E. Journal of Medical Microbiology, Vol. 61, Issue Pt_7 https://doi.org/10.1099/jmm.0.039438-0	journal	April 2012
Characterization of the O antigen gene cluster and structural analysis of the O antigen of Francisella tularensis subsp. tularensis Prior, J. L. Journal of Medical Microbiology, Vol. 52, Issue 10 https://doi.org/10.1099/jmm.0.05184-0	journal	October 2003
Protective B-cell epitopes of Francisella tularensis O-polysaccharide in a mouse model of respiratory tularaemia: Protective epitopes of Francisella tularensis O-antigen Lu, Zhaohua; Madico, Guillermo; Roche, Marly I. Immunology, Vol. 136, Issue 3 https://doi.org/10.1111/j.1365-2567.2012.03589.x	journal	June 2012
Release of the type I secreted alpha-haemolysin via outer membrane vesicles from Escherichia coli Balsalobre, Carlos; Silvan, Jose Manuel; Berglund, Stina Molecular Microbiology, Vol. 59, Issue 1 https://doi.org/10.1111/j.1365-2958.2005.04938.x	journal	January 2006
Elucidation of a novel Vibrio cholerae lipid A secondary hydroxy-acyltransferase and its role in innate immune recognition: Incorporation of hydroxy fatty acids into V. cholerae LPS by LpxN Hankins, Jessica V.; Madsen, James A.; Giles, David K. Molecular Microbiology, Vol. 81, Issue 5 https://doi.org/10.1111/j.1365-2958.2011.07765.x	journal	July 2011
Production of Secretory and Extracellular N-Linked Glycoproteins in Escherichia coli Fisher, Adam C.; Haitjema, Charles H.; Guarino, Cassandra Applied and Environmental Microbiology, Vol. 77, Issue 3 https://doi.org/10.1128/AEM.01901-10	journal	December 2010
Successful Protection against Tularemia in C57BL/6 Mice Is Correlated with Expansion of Francisella tularensis-Specific Effector T Cells Griffin, Amanda J.; Crane, Deborah D.; Wehrly, Tara D. Clinical and Vaccine Immunology, Vol. 22, Issue 1 https://doi.org/10.1128/CVI.00648-14	journal	November 2014
Naturally Produced Outer Membrane Vesicles from Pseudomonas aeruginosa Elicit a Potent Innate Immune Response via Combined Sensing of Both Lipopolysaccharide and Protein Components Ellis, T. N.; Leiman, S. A.; Kuehn, M. J. Infection and Immunity, Vol. 78, Issue 9 https://doi.org/10.1128/IAI.00433-10	journal	July 2010
Immunization with Salmonella enterica Serovar Typhimurium-Derived Outer Membrane Vesicles Delivering the Pneumococcal Protein PspA Confers Protection against Challenge with Streptococcus pneumoniae Muralinath, Maneesha; Kuehn, Meta J.; Roland, Kenneth L. Infection and Immunity, Vol. 79, Issue 2 https://doi.org/10.1128/IAI.00950-10	journal	November 2010
Inactivated Francisella tularensis Live Vaccine Strain Protects against Respiratory Tularemia by Intranasal Vaccination in an Immunoglobulin A-Dependent Fashion Baron, S. D.; Singh, R.; Metzger, D. W. Infection and Immunity, Vol. 75, Issue 5 https://doi.org/10.1128/IAI.01606-06	journal	February 2007
Francisella tularensis Schu S4 Lipopolysaccharide Core Sugar and O-Antigen Mutants Are Attenuated in a Mouse Model of Tularemia Rasmussen, Jed A.; Post, Deborah M. B.; Gibson, Bradford W. Infection and Immunity, Vol. 82, Issue 4 https://doi.org/10.1128/IAI.01640-13	journal	January 2014
Immunologic Memory Induced by a Glycoconjugate Vaccine in a Murine Adoptive Lymphocyte Transfer Model Guttormsen, Hilde-Kari; Wetzler, Lee M.; Finberg, Robert W. Infection and Immunity, Vol. 66, Issue 5 https://doi.org/10.1128/IAI.66.5.2026-2032.1998	journal	May 1998
Cognate Stimulatory B-Cell–T-Cell Interactions Are Critical for T-Cell Help Recruited by Glycoconjugate Vaccines Guttormsen, Hilde-Kari; Sharpe, Arlene H.; Chandraker, Anil K. Infection and Immunity, Vol. 67, Issue 12 https://doi.org/10.1128/IAI.67.12.6375-6384.1999	journal	December 1999
Purified Lipopolysaccharide from Francisella tularensis Live Vaccine Strain (LVS) Induces Protective Immunity against LVS Infection That Requires B Cells and Gamma Interferon Dreisbach, V. C.; Cowley, S.; Elkins, K. L. Infection and Immunity, Vol. 68, Issue 4 https://doi.org/10.1128/IAI.68.4.1988-1996.2000	journal	April 2000
Expression of Heterologous Antigens in Commensal Neisseria spp.: Preservation of Conformational Epitopes with Vaccine Potential O'Dwyer, C. A.; Reddin, K.; Martin, D. Infection and Immunity, Vol. 72, Issue 11 https://doi.org/10.1128/IAI.72.11.6511-6518.2004	journal	October 2004
Escherichia coli tol-pal Mutants Form Outer Membrane Vesicles Bernadac, Alain; Gavioli, Marthe; Lazzaroni, Jean-Claude Journal of Bacteriology, Vol. 180, Issue 18 https://doi.org/10.1128/JB.180.18.4872-4878.1998	journal	September 1998
Working toward the Future: Insights into Francisella tularensis Pathogenesis and Vaccine Development Pechous, R. D.; McCarthy, T. R.; Zahrt, T. C. Microbiology and Molecular Biology Reviews, Vol. 73, Issue 4 https://doi.org/10.1128/MMBR.00028-09	journal	November 2009
Pathogenicity and molecular genetics of O-specific side-chain lipopolysaccharides of Escherichia coli Valvano, Miguel A. Canadian Journal of Microbiology, Vol. 38, Issue 7 https://doi.org/10.1139/m92-117	journal	July 1992
How Bacterial Carbohydrates Influence the Adaptive Immune System Avci, Fikri Y.; Kasper, Dennis L. Annual Review of Immunology, Vol. 28, Issue 1 https://doi.org/10.1146/annurev-immunol-030409-101159	journal	March 2010
Lipopolysaccharide Endotoxins Raetz, Christian R. H.; Whitfield, Chris Annual Review of Biochemistry, Vol. 71, Issue 1 https://doi.org/10.1146/annurev.biochem.71.110601.135414	journal	June 2002
Biosynthesis and Assembly of Capsular Polysaccharides in Escherichia coli Whitfield, Chris Annual Review of Biochemistry, Vol. 75, Issue 1, p. 39-68 https://doi.org/10.1146/annurev.biochem.75.103004.142545	journal	June 2006
T Cell-Independent Antigens Type 2 Mond, James J.; Lees, Andrew; Snapper, Clifford M. Annual Review of Immunology, Vol. 13, Issue 1 https://doi.org/10.1146/annurev.iy.13.040195.003255	journal	April 1995
Biological Functions and Biogenesis of Secreted Bacterial Outer Membrane Vesicles Kulp, Adam; Kuehn, Meta J. Annual Review of Microbiology, Vol. 64, Issue 1 https://doi.org/10.1146/annurev.micro.091208.073413	journal	October 2010
Production of glycoprotein vaccines in Escherichia coli Ihssen, Julian; Kowarik, Michael; Dilettoso, Sandro Microbial Cell Factories, Vol. 9, Issue 1 https://doi.org/10.1186/1475-2859-9-61	journal	January 2010
Discovery of new biosynthetic pathways: the lipid A story Raetz, Christian R. H.; Guan, Ziqiang; Ingram, Brian O. Journal of Lipid Research, Vol. 50, Issue Supplement https://doi.org/10.1194/jlr.R800060-JLR200	journal	October 2008
Identification, Characterization and Immunogenicity of an O-Antigen Capsular Polysaccharide of Francisella tularensis Apicella, Michael A.; Post, Deborah M. B.; Fowler, Andrew C. PLoS ONE, Vol. 5, Issue 7 https://doi.org/10.1371/journal.pone.0011060	journal	July 2010
Mechanistic Insight into the TH1-Biased Immune Response to Recombinant Subunit Vaccines Delivered by Probiotic Bacteria-Derived Outer Membrane Vesicles Rosenthal, Joseph A.; Huang, Chung-Jr.; Doody, Anne M. PLoS ONE, Vol. 9, Issue 11 https://doi.org/10.1371/journal.pone.0112802	journal	November 2014
Conjugate vaccines Lockhart, Stephen Expert Review of Vaccines, Vol. 2, Issue 5 https://doi.org/10.1586/14760584.2.5.633	journal	October 2003
Adjuvant properties of meningococcal outer membrane vesicles and the use of adjuvants in Neisseria meningitidis protein vaccines Sanders, Holly; Feavers, Ian M. Expert Review of Vaccines, Vol. 10, Issue 3 https://doi.org/10.1586/erv.11.10	journal	March 2011
Vaccines based on the cell surface carbohydrates of pathogenic bacteria Jones, Christopher Anais da Academia Brasileira de Ciências, Vol. 77, Issue 2 https://doi.org/10.1590/S0001-37652005000200009	journal	June 2005
Recombinant outer membrane vesicles carrying Chlamydia muridarum HtrA induce antibodies that neutralize chlamydial infection in vitro Bartolini, Erika; Ianni, Elvira; Frigimelica, Elisabetta Journal of Extracellular Vesicles, Vol. 2, Issue 1 https://doi.org/10.3402/jev.v2i0.20181	journal	January 2013
Antibody-mediated immunity induced by engineered Escherichia coli OMVs carrying heterologous antigens in their lumen Fantappiè, Laura; de Santis, Micaela; Chiarot, Emiliano Journal of Extracellular Vesicles, Vol. 3, Issue 1 https://doi.org/10.3402/jev.v3.24015	journal	January 2014
A Novel Role for Plasmin-Mediated Degradation of Opsonizing Antibody in the Evasion of Host Immunity by Virulent, but Not Attenuated, Francisella tularensis Crane, Deborah D.; Warner, Shayna L.; Bosio, Catharine M. The Journal of Immunology, Vol. 183, Issue 7 https://doi.org/10.4049/jimmunol.0901655	journal	September 2009
Membrane Vesicles Are Immunogenic Facsimiles of Salmonella typhimurium That Potently Activate Dendritic Cells, Prime B and T Cell Responses, and Stimulate Protective Immunity In Vivo Alaniz, Robert C.; Deatherage, Brooke L.; Lara, Jimmie C. The Journal of Immunology, Vol. 179, Issue 11 https://doi.org/10.4049/jimmunol.179.11.7692	journal	November 2007
Bexsero: A multicomponent vaccine for prevention of meningococcal disease Gorringe, Andrew R.; Pajón, Rolando Human Vaccines & Immunotherapeutics, Vol. 8, Issue 2 https://doi.org/10.4161/hv.18500	journal	February 2012

Outer membrane vesicles displaying engineered glycotopes elicit protective antibodies

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Outer membrane vesicles displaying engineered glycotopes elicit protective antibodies

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