Journal article
Outer membrane vesicles displaying engineered glycotopes elicit protective antibodies
Proceedings of the National Academy of Sciences - PNAS, Vol.113(26), pp.E3609-E3618
06/28/2016
DOI: 10.1073/pnas.1518311113
PMCID: PMC4932928
PMID: 27274048
Abstract
The O-antigen polysaccharide (O-PS) component of lipopolysaccharides on the surface of gram-negative bacteria is both a virulence factor and a B-cell antigen. Antibodies elicited by O-PS often confer protection against infection; therefore, O-PS glycoconjugate vaccines have proven useful against a number of different pathogenic bacteria. However, conventional methods for natural extraction or chemical synthesis of O-PS are technically demanding, inefficient, and expensive. Here, we describe an alternative methodology for producing glycoconjugate vaccines whereby recombinant O-PS biosynthesis is coordinated with vesiculation in laboratory strains of Escherichia coli to yield glycosylated outer membrane vesicles (glycOMVs) decorated with pathogen-mimetic glycotopes. Using this approach, glycOMVs corresponding to eight different pathogenic bacteria were generated. For example, expression of a 17-kb O-PS gene cluster from the highly virulent Francisella tularensis subsp. tularensis (type A) strain Schu S4 in hypervesiculating E. coli cells yielded glycOMVs that displayed F. tularensis O-PS. Immunization of BALB/c mice with glycOMVs elicited significant titers of O-PS-specific serum IgG antibodies as well as vaginal and bronchoalveolar IgA antibodies. Importantly, glycOMVs significantly prolonged survival upon subsequent challenge with F. tularensis Schu S4 and provided complete protection against challenge with two different F. tularensis subsp. holarctica (type B) live vaccine strains, thereby demonstrating the vaccine potential of glycOMVs. Given the ease with which recombinant glycotopes can be expressed on OMVs, the strategy described here could be readily adapted for developing vaccines against many other bacterial pathogens.
Details
- Title: Subtitle
- Outer membrane vesicles displaying engineered glycotopes elicit protective antibodies
- Creators
- Linxiao Chen - University of Iowa, Mechanical EngineeringJenny L Valentine - Cornell UniversityChung-Jr Huang - Cornell UniversityChristine E Endicott - Cornell UniversityTyler D Moeller - Cornell UniversityJed A Rasmussen - Department of Microbiology, University of Iowa, Iowa City, IA 52242Joshua R Fletcher - Genetics Program, University of Iowa, Iowa City, IA 52242Joseph M Boll - The University of Texas at AustinJoseph A Rosenthal - Cornell UniversityJustyna Dobruchowska - Complex Carbohydrate Research Center, The University of Georgia, Athens, GA 30602Zhirui Wang - University of GeorgiaChristian Heiss - Complex Carbohydrate Research Center, The University of Georgia, Athens, GA 30602Parastoo Azadi - Complex Carbohydrate Research Center, The University of Georgia, Athens, GA 30602David Putnam - Cornell UniversityM Stephen Trent - The University of Texas at AustinBradley D Jones - University of Iowa, Microbiology and ImmunologyMatthew P DeLisa - Cornell University
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.113(26), pp.E3609-E3618
- DOI
- 10.1073/pnas.1518311113
- PMID
- 27274048
- PMCID
- PMC4932928
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Grant note
- R56 AI076322 / NIAID NIH HHS F32 GM113488 / NIGMS NIH HHS T32 GM008629 / NIGMS NIH HHS R44 GM088905 / NIGMS NIH HHS R01 AI064184 / NIAID NIH HHS P01 AI044642 / NIAID NIH HHS R21 EB005669 / NIBIB NIH HHS R01 AI076322 / NIAID NIH HHS R43 GM088905 / NIGMS NIH HHS U54 AI057160 / NIAID NIH HHS
- Language
- English
- Date published
- 06/28/2016
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984206855302771
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