Evidence map›Paper›PMID 27274048›Full record

ArticleProceedings of the National Academy of Sciences of the United States of America2016

Outer membrane vesicles displaying engineered glycotopes elicit protective antibodies.

Linxiao Chen, Jenny L Valentine, Chung-Jr Huang, Christine E Endicott, Tyler D Moeller, Jed A Rasmussen, Joshua R Fletcher, Joseph M Boll, Joseph A Rosenthal, Justyna Dobruchowska and 7 more

Open access · greenAbstract read
In one paragraph

Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 82 papers.

0numbers the graph read from it
0cells of the map it votes in
82citing papers in PubMed
11.7field-weighted citation impact, top 1% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

82 citing papers in PubMed, 137 citations in OpenAlex.

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22 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 3 institutions in 1 country.

Linxiao ChenRobert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853;ORCID 0000-0002-8063-9001
Jenny L ValentineRobert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853;
Chung-Jr HuangRobert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853;
Christine E EndicottRobert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853;
Tyler D MoellerRobert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853;
Jed A RasmussenDepartment of Microbiology, University of Iowa, Iowa City, IA 52242;
Joshua R FletcherGenetics Program, University of Iowa, Iowa City, IA 52242;
Joseph M BollDepartment 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;
Joseph A RosenthalNancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853;
Justyna DobruchowskaComplex Carbohydrate Research Center, The University of Georgia, Athens, GA 30602.
Zhirui WangComplex Carbohydrate Research Center, The University of Georgia, Athens, GA 30602.
Christian HeissComplex Carbohydrate Research Center, The University of Georgia, Athens, GA 30602.
Parastoo AzadiComplex Carbohydrate Research Center, The University of Georgia, Athens, GA 30602.
David PutnamRobert 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;
M Stephen TrentDepartment 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;
Bradley D JonesDepartment of Microbiology, University of Iowa, Iowa City, IA 52242; Genetics Program, University of Iowa, Iowa City, IA 52242;
Matthew P DeLisaRobert 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; md255@cornell.edu.
Cornell University · USUniversity of Georgia · USUniversity of Iowa · US

Funding

Virology and Smallpox VaccinationsU54AI057160 · NIAID · WASHINGTON UNIVERSITY · PI OLDSTONE, MICHAEL B · 2003 to 2013
$80.9M
Studies of the capsular-like antigen of F. tularensisP01AI044642 · NIAID · UNIVERSITY OF IOWA · PI NAUSEEF, WILLIAM M. · 1999 to 2014
$18.2M
PREDOCTORAL TRAINING PROGRAM IN GENETICST32GM008629 · NIGMS · UNIVERSITY OF IOWA · PI EBERL, DANIEL F · 1997 to 2021
$4.1M
MODIFICATION OF HELICOBACTER PYLORI LIPOPOLYSACCHARIDESR01AI064184 · NIAID · UNIVERSITY OF TEXAS AT AUSTIN · PI TRENT, MICHAEL STEPHEN · 2006 to 2015
$3.4M
The Outer Surface of Vibrio CholeraeR01AI076322 · NIAID · UNIVERSITY OF TEXAS AT AUSTIN · PI TRENT, MICHAEL STEPHEN · 2008 to 2017
$3.2M
Engineering Escherichia coli for glycosylation of complex human proteinsR44GM088905 · NIGMS · GLYCOBIA, INC. · PI FISHER, ADAM CHARLES · 2011 to 2012
$1.6M
Engineered Outer Membrane Vesicles as DNA Vaccine Delivery VehiclesR21EB005669 · NIBIB · CORNELL UNIVERSITY · PI PUTNAM, DAVID A · 2006 to 2007
$398k
The Outer Surface of Vibrio choleraeR56AI076322 · NIAID · UNIVERSITY OF TEXAS AT AUSTIN · PI TRENT, MICHAEL STEPHEN · 2013 to 2013
$384k
Humanizing N-linked glycosylation in Escherichia coliR43GM088905 · NIGMS · GLYCOBIA, INC. · PI FISHER, ADAM CHARLES · 2009 to 2009
$116k
Solving a Novel Multidrug Resistance Puzzle: Complete Loss of LipooligosaccharideF32GM113488 · NIGMS · UNIVERSITY OF TEXAS AT AUSTIN · PI BOLL, JOSEPH MICHAEL · 2015 to 2016
$109k
NIAID NIH HHS P01 AI044642NIAID NIH HHS R01 AI064184NIAID NIH HHS R01 AI076322NIAID NIH HHS R56 AI076322NIAID NIH HHS U54 AI057160NIBIB NIH HHS R21 EB005669NIGMS NIH HHS R43 GM088905NIGMS NIH HHS R44 GM088905NIGMS NIH HHS T32 GM008629
6 · The paper itself

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.

Indexed as

AnimalsAntibodies, BacterialBacterial VaccinesEscherichia coliFemaleFrancisella tularensisGlycosylationHumansMiceMice, Inbred BALB CO AntigensTransport VesiclesTularemiaVaccinationAntibodies, BacterialBacterial VaccinesO Antigensanti-glycan antibodiesglycanglycoconjugate vaccinehumoral immune responseO-antigen polysaccharide

Identifiers

PMID27274048
PMCPMC4932928
OpenAlexW2411905403

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.