Evidence map›Paper›PMID 33531570›Full record

ArticleScientific reports2021

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

Alla Amcheslavsky, Aaron L Wallace, Monir Ejemel, Qi Li, Conor T McMahon, Matteo Stoppato, Serena Giuntini, Zachary A Schiller, Jessica R Pondish, Jacqueline R Toomey and 9 more

Open access · goldAbstract read
In one paragraph

Article in Scientific reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
6.3field-weighted citation impact, top 3% 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

22 citing papers in PubMed, 36 citations in OpenAlex.

  1. Article
  2. Resurfacing promotes antibacterial activity of a lipid A-binding nanobody.Proceedings of the National Academy of Sciences of the United States of America · 2025
    Article
  3. Review
  4. Review
  5. Article
  6. Single-Domain Antibodies-Novel Tools to Study and Treat Allergies.International journal of molecular sciences · 2024
    Review
  7. Article
  8. Article
  9. Review
  10. Article
  11. Article
  12. Review
  13. Article
  14. Nanobodies: Robust miniprotein binders in biomedicine.Advanced drug delivery reviews · 2023
    Review
  15. Article
  16. Protective effects of α-terpineol andFrontiers in veterinary science · 2023
    Article
  17. Article
  18. Article
  19. Article
  20. Review
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

19 authors at 4 institutions in 2 countries.

Alla AmcheslavskyMassBiologics, University of Massachusetts Medical School, 460 Walk Hill Road, Boston, MA, USA.
Aaron L WallaceMassBiologics, University of Massachusetts Medical School, 460 Walk Hill Road, Boston, MA, USA.
Monir EjemelMassBiologics, University of Massachusetts Medical School, 460 Walk Hill Road, Boston, MA, USA.
Qi LiMassBiologics, University of Massachusetts Medical School, 460 Walk Hill Road, Boston, MA, USA.
Conor T McMahonDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Matteo StoppatoMassBiologics, University of Massachusetts Medical School, 460 Walk Hill Road, Boston, MA, USA.
Serena GiuntiniMassBiologics, University of Massachusetts Medical School, 460 Walk Hill Road, Boston, MA, USA.
Zachary A SchillerMassBiologics, University of Massachusetts Medical School, 460 Walk Hill Road, Boston, MA, USA.
Jessica R PondishMassBiologics, University of Massachusetts Medical School, 460 Walk Hill Road, Boston, MA, USA.
Jacqueline R ToomeyMassBiologics, University of Massachusetts Medical School, 460 Walk Hill Road, Boston, MA, USA.
Ryan M SchneiderMassBiologics, University of Massachusetts Medical School, 460 Walk Hill Road, Boston, MA, USA.
Jordan MeisingerMassBiologics, University of Massachusetts Medical School, 460 Walk Hill Road, Boston, MA, USA.
Raimond HeukersQVQ Holdings BV, Utrecht, The Netherlands.
Andrew C KruseDepartment of Biological Chemistry and Molecular Pharmacology, Blavatnik Institute, Harvard Medical School, Boston, MA, USA.
Eileen M BarryCenter for Vaccine Development, University of Maryland School of Medicine, Baltimore, MD, USA.
Brian G PierceUniversity of Maryland Institute for Bioscience and Biotechnology Research, Rockville, MD, USA.
Mark S KlempnerMassBiologics, University of Massachusetts Medical School, 460 Walk Hill Road, Boston, MA, USA.
Lisa A CavaciniMassBiologics, University of Massachusetts Medical School, 460 Walk Hill Road, Boston, MA, USA.
Yang WangMassBiologics, University of Massachusetts Medical School, 460 Walk Hill Road, Boston, MA, USA. Yang.Wang@umassmed.edu.
University of Massachusetts Chan Medical School · USHarvard University · USUniversity of Maryland, Baltimore · USQserve Group (Netherlands) · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

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.

Indexed as

AnimalsAntibodies, BacterialAntibodies, NeutralizingCaco-2 CellsCamelids, New WorldCross ProtectionDiarrheaDisease Models, AnimalDrug DesignEnterotoxigenic Escherichia coliEpitope MappingEpitopesEscherichia coli InfectionsEscherichia coli ProteinsEscherichia coli VaccinesFimbriae ProteinsAntibodies, BacterialAntibodies, NeutralizingCfaE protein, E coliEpitopesEscherichia coli ProteinsEscherichia coli VaccinesFimbriae ProteinsImmunoconjugatesSingle-Domain Antibodies

Identifiers

PMID33531570
PMCPMC7854682
OpenAlexW3126792280

What OpenQuestion holds

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Registered trials

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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.