Evidence map›Paper›PMID 26530460›Full record

ArticlePharmaceutical research2016

In Vivo Toxicity and Immunological Characterization of Detoxified Recombinant Botulinum Neurotoxin Type A.

Easwaran Ravichandran, Pavithra Janardhanan, Kruti Patel, Stephen Riding, Shuowei Cai, Bal Ram Singh

Abstract read
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In one paragraph

Article in Pharmaceutical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.

0numbers the graph read from it
0cells of the map it votes in
14citing papers in PubMed
–field-weighted citation impact
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

14 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Novel Native and Engineered Botulinum Neurotoxins.Handbook of experimental pharmacology · 2021
    Review
  8. Article
  9. Review
  10. Article
  11. Article
  12. Article
  13. Review
  14. Article
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

6 authors.

Easwaran RavichandranDepartment of Chemistry and Biochemistry, University of Massachusetts Dartmouth, 285 Old Westport Road, North Dartmouth, Massachusetts, 02747, USA.
Pavithra JanardhananDepartment of Chemistry and Biochemistry, University of Massachusetts Dartmouth, 285 Old Westport Road, North Dartmouth, Massachusetts, 02747, USA.
Kruti PatelDepartment of Chemistry and Biochemistry, University of Massachusetts Dartmouth, 285 Old Westport Road, North Dartmouth, Massachusetts, 02747, USA.
Stephen RidingDepartment of Chemistry and Biochemistry, University of Massachusetts Dartmouth, 285 Old Westport Road, North Dartmouth, Massachusetts, 02747, USA.
Shuowei CaiDepartment of Chemistry and Biochemistry, University of Massachusetts Dartmouth, 285 Old Westport Road, North Dartmouth, Massachusetts, 02747, USA.
Bal Ram SinghDepartment of Chemistry and Biochemistry, University of Massachusetts Dartmouth, 285 Old Westport Road, North Dartmouth, Massachusetts, 02747, USA. bsingh@inads.org.

Funding

Botulinum Neurotoxin Trafficking and Tissue Distribution with Mouse Body ImagingR03AI103868 · NIAID · UNIVERSITY OF MASSACHUSETTS DARTMOUTH · PI SINGH, BAL RAM · 2013 to 2014
$147k
NIAID NIH HHS R03AI103868PHS HHS 1U01A1078070-01
6 · The paper itself

Abstract

purposeA double-mutant E224A/E262A full-length botulinum neurotoxin (BoNT) Type A with structural similarity to native BoNT/A but lacking the endopeptidase activity provides an ideal surrogate for testing pharmacokinetics and immunochemical characteristics of BoNT.

methodsWe determined lethality (LD50) of deactivated recombinant botulinum neurotoxin (drBoNT/A) to be 24.0 μg by intraperitoneal route (i.p). The polypeptide drBoNT/A labeled with near infra-red dye 800 (NIR 800) was used to examine its distribution to different organs using whole body imaging when administered to mice via intravenous (i.v) or i.p route. Also, drBoNT/A was used to evaluate its immunogenicity in Balb/C mice model.

resultsdrBoNT/A was found to be highly immunogenic when tested under various in vivo conditions in Balb/C mice model. For the first time we have demonstrated that a full length 150 kDa drBoNT/A, by administering via inhalation route in mice model, has evoked both circulating immunoglobulin levels of IgG and secretory IgA at the mucosal surface. The immunoglobulin levels were sufficient enough to protect against the challenge dose of native BoNT toxin in mice model. Tissue distribution of drBoNT/A seems to be similar to that of native toxin.

conclusionsBased on the characteristics described in this report this nontoxic holotoxin protein will assist us to explore the window of opportunity available for therapeutic treatment in case of unnatural poisoning, and also it can be an effective vaccine candidate.

Indexed as

AnimalsAntibody FormationBotulinum Toxins, Type ACell Line, TumorFemaleImmunoglobulin A, SecretoryImmunoglobulin GMiceMice, Inbred BALB CRecombinant ProteinsTissue DistributionBotulinum Toxins, Type AImmunoglobulin A, SecretoryImmunoglobulin GRecombinant ProteinsbotulinumClostridiumdeactivated neurotoxindrug deliverymicrospheremucosal vaccinetoxicityvaccine

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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.