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dc.contributor.authorAmcheslavsky, Alla
dc.contributor.authorWallace, Aaron L
dc.contributor.authorEjemel, Monir
dc.contributor.authorLi, Qi
dc.contributor.authorMcMahon, Conor T
dc.contributor.authorStoppato, Matteo
dc.contributor.authorGiuntini, Serena
dc.contributor.authorSchiller, Zachary A
dc.contributor.authorPondish, Jessica R
dc.contributor.authorToomey, Jacqueline R
dc.contributor.authorSchneider, Ryan M
dc.contributor.authorMeisinger, Jordan
dc.contributor.authorHeukers, Raimond
dc.contributor.authorKruse, Andrew C
dc.contributor.authorBarry, Eileen M
dc.contributor.authorPierce, Brian G
dc.contributor.authorKlempner, Mark S
dc.contributor.authorCavacini, Lisa A
dc.contributor.authorWang, Yang
dc.date.accessioned2021-02-19T20:25:32Z
dc.date.available2021-02-19T20:25:32Z
dc.date.issued2021-02-02
dc.identifier.urihttp://hdl.handle.net/10713/14731
dc.description.abstractEnterotoxigenic Escherichia coli (ETEC) is estimated to cause approximately 380,000 deaths annually during sporadic or epidemic outbreaks worldwide. Development of vaccines against ETEC is very challenging due to the vast heterogeneity of the ETEC strains. An effective vaccines would have to be multicomponent to provide coverage of over ten ETEC strains with genetic variabilities. There is currently no vaccine licensed to prevent ETEC. Nanobodies are successful new biologics in treating mucosal infectious disease as they recognize conserved epitopes on hypervariable pathogens. Cocktails consisting of multiple nanobodies could provide even broader epitope coverage at a lower cost compared to monoclonal antibodies. Identification of conserved epitopes by nanobodies can also assist reverse engineering of an effective vaccine against ETEC. By screening nanobodies from immunized llamas and a naïve yeast display library against adhesins of colonization factors, we identified single nanobodies that show cross-protective potency against eleven major pathogenic ETEC strains in vitro. Oral administration of nanobodies led to a significant reduction of bacterial colonization in animals. Moreover, nanobody-IgA fusion showed extended inhibitory activity in mouse colonization compared to commercial hyperimmune bovine colostrum product used for prevention of ETEC-induced diarrhea. Structural analysis revealed that nanobodies recognized a highly-conserved epitope within the putative receptor binding region of ETEC adhesins. Our findings support further rational design of a pan-ETEC vaccine to elicit robust immune responses targeting this conserved epitope. © 2021, The Author(s).en_US
dc.description.urihttps://doi.org/10.1038/s41598-021-81895-0en_US
dc.language.isoenen_US
dc.publisherSpringer Natureen_US
dc.relation.ispartofScientific Reportsen_US
dc.subjectanti-CfaE nanobodiesen_US
dc.subject.meshEnterotoxigenic Escherichia colien_US
dc.subject.meshSingle-Domain Antibodiesen_US
dc.subject.meshEscherichia coli Vaccinesen_US
dc.titleAnti-CfaE nanobodies provide broad cross-protection against major pathogenic enterotoxigenic Escherichia coli strains, with implications for vaccine design.en_US
dc.typeArticleen_US
dc.identifier.doi10.1038/s41598-021-81895-0
dc.identifier.pmid33531570
dc.source.volume11
dc.source.issue1
dc.source.beginpage2751
dc.source.endpage
dc.source.countryEngland


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