Evidence map›Paper›PMID 24202178›Full record

ArticleThe Journal of biological chemistry2013

Stepwise engineering of heterodimeric single domain camelid VHH antibodies that passively protect mice from ricin toxin.

David J Vance, Jacqueline M Tremblay, Nicholas J Mantis, Charles B Shoemaker

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers.

0numbers the graph read from it
0cells of the map it votes in
56citing papers in PubMed
4.1field-weighted citation impact, top 6% 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

56 citing papers in PubMed, 75 citations in OpenAlex.

  1. Article
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  6. Article
  7. The Search for Antidotes Against Ricin.Mini reviews in medicinal chemistry · 2024
    Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. Structure-guided design of a potentFrontiers in microbiology · 2023
    Article
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  15. Article
  16. Review
  17. Article
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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

4 authors at 2 institutions in 1 country.

David J VanceFrom the Division of Infectious Disease, Wadsworth Center, New York State Department of Health, Albany, New York 12208 and.
Jacqueline M Tremblay
Nicholas J Mantis
Charles B Shoemaker
New England Disabled Sports · USWadsworth Center · US

Funding

Treatments for Nipah Virus InfectionU54AI057159 · NIAID · HARVARD UNIVERSITY (MEDICAL SCHOOL) · PI KIRCHHAUSEN, TOMAS · 2003 to 2013
$113.7M
Ricin toxin: Neutralizing antibodies and vaccine designR03AI097688 · NIAID · WADSWORTH CENTER · PI MANTIS, NICHOLAS J. · 2012 to 2013
$136k
NIAID NIH HHS AI097688NIAID NIH HHS R03 AI097688NIAID NIH HHS U54 AI057159NIAID NIH HHS U54-AI057159
6 · The paper itself

Abstract

In an effort to engineer countermeasures for the category B toxin ricin, we produced and characterized a collection of epitopic tagged, heavy chain-only antibody VH domains (VHHs) specific for the ricin enzymatic (RTA) and binding (RTB) subunits. Among the 20 unique ricin-specific VHHs we identified, six had toxin-neutralizing activity: five specific for RTA and one specific for RTB. Three neutralizing RTA-specific VHHs were each linked via a short peptide spacer to the sole neutralizing anti-RTB VHH to create VHH "heterodimers." As compared with equimolar concentrations of their respective monovalent monomers, all three VHH heterodimers had higher affinities for ricin and, in the case of heterodimer D10/B7, a 6-fold increase in in vitro toxin-neutralizing activity. When passively administered to mice at a 4:1 heterodimer:toxin ratio, D10/B7 conferred 100% survival in response to a 10 × LD50 ricin challenge, whereas a 2:1 heterodimer:toxin ratio conferred 20% survival. However, complete survival was achievable when the low dose of D10/B7 was combined with an IgG1 anti-epitopic tag monoclonal antibody, possibly because decorating the toxin with up to four IgGs promoted serum clearance. The two additional ricin-specific heterodimers, when tested in vivo, provided equal or greater passive protection than D10/B7, thereby warranting further investigation of all three heterodimers as possible therapeutics.

Indexed as

Immunization, PassiveAmino Acid SequenceAnimalsAntibody AffinityBinding Sites, AntibodyCamelids, New WorldFemaleMiceMice, Inbred BALB CMolecular Sequence DataProtein EngineeringProtein MultimerizationRicinSingle-Domain AntibodiesRicinSingle-Domain AntibodiesAntibody EngineeringImmunologyImmunotherapyMouseToxinsVHH

Identifiers

PMID24202178
PMCPMC3868766
OpenAlexW2052375392

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.