Anti-CfaE nanobodies provide broad cross-protection against major pathogenic enterotoxigenic Escherichia coli strains, with implications for vaccine design

Autor: 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
Jazyk: angličtina
Rok vydání: 2021
Předmět:
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
Zdroj: Scientific Reports, Vol 11, Iss 1, Pp 1-15 (2021)
Scientific Reports
ISSN: 2045-2322
Popis: 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.
Databáze: OpenAIRE
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