Anti-CfaE nanobodies provide broad cross-protection against major pathogenic enterotoxigenic Escherichia coli strains, with implications for vaccine design
| العنوان: | Anti-CfaE nanobodies provide broad cross-protection against major pathogenic enterotoxigenic Escherichia coli strains, with implications for vaccine design |
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| المؤلفون: | Mark S. Klempner, Matteo Stoppato, Alla Amcheslavsky, Jessica R. Pondish, Jordan Meisinger, Monir Ejemel, Ryan Schneider, Aaron Wallace, Qi Li, Yang Wang, Jacqueline R. Toomey, Raimond Heukers, Serena Giuntini, Lisa A. Cavacini, Eileen M. Barry, Zachary A. Schiller, Conor McMahon, Brian G. Pierce, Andrew C. Kruse |
| المصدر: | Scientific Reports, Vol 11, Iss 1, Pp 1-15 (2021) Scientific Reports |
| بيانات النشر: | Nature Portfolio, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Immunoconjugates, Cross Protection, medicine.disease_cause, Epitope, Epitopes, Mice, 0302 clinical medicine, Enterotoxigenic Escherichia coli, 030212 general & internal medicine, Hyperimmune Bovine Colostrum, Escherichia coli Infections, Vaccines, Multidisciplinary, biology, Escherichia coli Vaccines, Drug discovery, Escherichia coli Proteins, Antibodies, Bacterial, Infectious diseases, Medicine, Fimbriae Proteins, Antibody, Camelids, New World, Biotechnology, Diarrhea, medicine.drug_class, Science, Monoclonal antibody, Article, 03 medical and health sciences, medicine, Animals, Humans, Single-Domain Antibodies, Antibodies, Neutralizing, Virology, Bacterial adhesin, Disease Models, Animal, 030104 developmental biology, Epitope mapping, Infectious disease (medical specialty), Drug Design, biology.protein, Caco-2 Cells, Bacterial infection, Epitope Mapping |
| الوصف: | Enterotoxigenic 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. |
| اللغة: | English |
| تدمد: | 2045-2322 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::078cfdfd96ee937b4c593bb60c08d2bbTest https://doaj.org/article/8c71423749de4016b747f5338a446935Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....078cfdfd96ee937b4c593bb60c08d2bb |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20452322 |
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