Journal article
Immunization with outer membrane vesicles displaying conserved surface polysaccharide antigen elicits broadly antimicrobial antibodies
Proceedings of the National Academy of Sciences - PNAS, Vol.115(14), pp.E3106-E3115
PNAS Plus
04/03/2018
DOI: 10.1073/pnas.1718341115
PMCID: PMC5889644
PMID: 29555731
Abstract
Many microbial pathogens produce a β-(1→6)-linked poly-N-acetyl-d-glucosamine (PNAG) surface capsule, including bacterial, fungal, and protozoan cells. Broadly protective immune responses to this single conserved polysaccharide antigen in animals are possible but only when a deacetylated poly-N-acetyl-d-glucosamine (dPNAG; <30% acetate) glycoform is administered as a conjugate to a carrier protein. Unfortunately, conventional methods for natural extraction or chemical synthesis of dPNAG and its subsequent conjugation to protein carriers can be technically demanding and expensive. Here, we describe an alternative strategy for creating broadly protective vaccine candidates that involved coordinating recombinant poly-N-acetyl-d-glucosamine (rPNAG) biosynthesis with outer membrane vesicle (OMV) formation in laboratory strains of Escherichia coli The glycosylated outer membrane vesicles (glycOMVs) released by these engineered bacteria were decorated with the PNAG glycopolymer and induced high titers of PNAG-specific IgG antibodies after immunization in mice. When a Staphylococcus aureus enzyme responsible for PNAG deacetylation was additionally expressed in these cells, glycOMVs were generated that elicited antibodies to both highly acetylated PNAG (∼95-100% acetate) and a chemically deacetylated dPNAG derivative (∼15% acetate). These antibodies mediated efficient in vitro killing of two distinct PNAG-positive bacterial species, namely S. aureus and Francisella tularensis subsp. holarctica, and mice immunized with PNAG-containing glycOMVs developed protective immunity against these unrelated pathogens. Collectively, our results reveal the potential of glycOMVs for targeting this conserved polysaccharide antigen and engendering protective immunity against the broad range of pathogens that produce surface PNAG.
Details
- Title: Subtitle
- Immunization with outer membrane vesicles displaying conserved surface polysaccharide antigen elicits broadly antimicrobial antibodies
- Creators
- Taylor C Stevenson - Cornell UniversityColette Cywes-Bentley - Harvard Medical SchoolTyler D Moeller - Cornell UniversityKevin B Weyant - Cornell UniversityDavid Putnam - Cornell UniversityYung-Fu Chang - Cornell UniversityBradley D Jones - University of Iowa, Microbiology and ImmunologyGerald B Pier - Harvard Medical SchoolMatthew P DeLisa - Cornell University
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.115(14), pp.E3106-E3115
- Publisher
- National Academy of Sciences
- Series
- PNAS Plus
- DOI
- 10.1073/pnas.1718341115
- PMID
- 29555731
- PMCID
- PMC5889644
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Grant note
- DMR-1120296 / National Science Foundation (NSF) GM088905-01 / HHS | National Institutes of Health (NIH) EY016144 / HHS | National Institutes of Health (NIH) Graduate Research Fellowship / National Science Foundation (NSF) AI044642 / HHS | National Institutes of Health (NIH) EB005669-01 / HHS | National Institutes of Health (NIH) CBET-1159581 / National Science Foundation (NSF) AI057160 / HHS | National Institutes of Health (NIH) CBET-1264701 / National Science Foundation (NSF)
- Language
- English
- Date published
- 04/03/2018
- Academic Unit
- Microbiology and Immunology
- Record Identifier
- 9984215757102771
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