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Prolonged Prophylactic Protection from Botulism with a Single Adenovirus Treatment Promoting Serum Expression of a VHH-Based Antitoxin Protein

Overview of attention for article published in PLOS ONE, August 2014
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About this Attention Score

  • In the top 5% of all research outputs scored by Altmetric
  • High Attention Score compared to outputs of the same age (96th percentile)
  • High Attention Score compared to outputs of the same age and source (93rd percentile)

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6 news outlets
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1 X user
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1 patent
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2 Redditors

Citations

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31 Dimensions

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53 Mendeley
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Title
Prolonged Prophylactic Protection from Botulism with a Single Adenovirus Treatment Promoting Serum Expression of a VHH-Based Antitoxin Protein
Published in
PLOS ONE, August 2014
DOI 10.1371/journal.pone.0106422
Pubmed ID
Authors

Jean Mukherjee, Igor Dmitriev, Michelle Debatis, Jacqueline M. Tremblay, Gillian Beamer, Elena A. Kashentseva, David T. Curiel, Charles B. Shoemaker

Abstract

Current therapies for most acute toxin exposures are limited to administration of polyclonal antitoxin serum. We have shown that VHH-based neutralizing agents (VNAs) consisting of two or more linked, toxin-neutralizing heavy-chain-only VH domains (VHHs), each binding distinct epitopes, can potently protect animals from lethality in several intoxication models including Botulinum neurotoxin serotype A1 (BoNT/A1). Appending a 14 amino acid albumin binding peptide (ABP) to an anti-BoNT/A1 heterodimeric VNA (H7/B5) substantially improved serum stability and resulted in an effective VNA serum half-life of 1 to 2 days. A recombinant, replication-incompetent, adenoviral vector (Ad/VNA-BoNTA) was engineered that induces secretion of biologically active VNA, H7/B5/ABP (VNA-BoNTA), from transduced cells. Mice administered a single dose of Ad/VNA-BoNTA, or a different Ad/VNA, via different administration routes led to a wide range of VNA serum levels measured four days later; generally intravenous > intraperitoneal > intramuscular > subcutaneous. Ad/VNA-BoNTA treated mice were 100% protected from 10 LD50 of BoNT/A1 for more than six weeks and protection positively correlated with serum levels of VNA-BoNTA exceeding about 5 ng/ml. Some mice developed antibodies that inhibited VNA binding to target but these mice displayed no evidence of kidney damage due to deposition of immune complexes. Mice were also successfully protected from 10 LD50 BoNT/A1 when Ad/VNA-BoNTA was administered up to 1.5 hours post-intoxication, demonstrating rapid appearance of the protective VNA in serum following treatment. Genetic delivery of VNAs promises to be an effective method of providing prophylactic protection and/or acute treatments for many toxin-mediated diseases.

X Demographics

X Demographics

The data shown below were collected from the profile of 1 X user who shared this research output. Click here to find out more about how the information was compiled.
Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 53 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
Germany 1 2%
Unknown 52 98%

Demographic breakdown

Readers by professional status Count As %
Student > Bachelor 26 49%
Researcher 6 11%
Professor 3 6%
Student > Ph. D. Student 3 6%
Student > Postgraduate 3 6%
Other 8 15%
Unknown 4 8%
Readers by discipline Count As %
Medicine and Dentistry 33 62%
Biochemistry, Genetics and Molecular Biology 7 13%
Agricultural and Biological Sciences 3 6%
Immunology and Microbiology 3 6%
Veterinary Science and Veterinary Medicine 1 2%
Other 1 2%
Unknown 5 9%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 42. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 30 May 2023.
All research outputs
#913,308
of 24,337,175 outputs
Outputs from PLOS ONE
#12,142
of 209,797 outputs
Outputs of similar age
#9,303
of 240,845 outputs
Outputs of similar age from PLOS ONE
#309
of 4,947 outputs
Altmetric has tracked 24,337,175 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 96th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 209,797 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 15.6. This one has done particularly well, scoring higher than 94% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 240,845 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 96% of its contemporaries.
We're also able to compare this research output to 4,947 others from the same source and published within six weeks on either side of this one. This one has done particularly well, scoring higher than 93% of its contemporaries.