Evidence map›Paper›PMID 25940316›Full record

ArticleJournal of molecular medicine (Berlin, Germany)2015

Retargeting pre-existing human antibodies to a bacterial pathogen with an alpha-Gal conjugated aptamer.

Sascha A Kristian, John H Hwang, Bradley Hall, Emma Leire, John Iacomini, Robert Old, Uri Galili, Charles Roberts, Kary B Mullis, Mike Westby and 1 more

Open access · bronzeAbstract read
In one paragraph

Article in Journal of molecular medicine (Berlin, Germany), 2015. 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
3.5field-weighted citation impact, top 7% 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, 33 citations in OpenAlex.

  1. Article
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  5. Review
  6. Article
  7. Aptamers: precision tools for diagnosing and treating infectious diseases.Frontiers in cellular and infection microbiology · 2024
    Review
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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

11 authors at 5 institutions in 2 countries.

Sascha A KristianAltermune Technologies, LLC, Irvine, CA, USA.
John H Hwang
Bradley Hall
Emma Leire
John Iacomini
Robert Old
Uri Galili
Charles Roberts
Kary B Mullis
Mike Westby
Victor Nizet
Royal Institution of Great Britain · GBUniversity of California, San Diego · USTufts University · USUniversity of Massachusetts Chan Medical School · USUniversity of Montana · US

Funding

GAS Switch from Colonizing Bacterium to Invasive PathogenR01AI077780 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI NIZET, VICTOR · 2008 to 2019
$3.8M
Mechanisms of the M protein in group A Streptococcus virulenceR01AI096837 · NIAID · UNIVERSITY OF CALIFORNIA, SAN DIEGO · PI GHOSH, PARTHO, NIZET, VICTOR · 2011 to 2015
$2.7M
Using natural antibodies to improve vaccinesR01AI083459 · NIAID · TUFTS UNIVERSITY BOSTON · PI IACOMINI, JOHN J · 2010 to 2014
$2.2M
NIAID NIH HHS 1R01AI083459-06NIAID NIH HHS R01 AI077780NIAID NIH HHS R01 AI083459NIAID NIH HHS R01 AI096837
6 · The paper itself

Abstract

unlabelledThe ever-increasing threat of multi-drug resistant bacterial infections has spurred renewed interest in alternative approaches to classical antibiotic therapy. In contrast to other mammals, humans do not express the galactose-α-1,3-galactosyl-β-1,4-N-acetyl-glucosamine (α-Gal) epitope. As a result of exposure of humans to α-Gal in the environment, a large proportion of circulating antibodies are specific for the trisaccharide. In this study, we examine whether these anti-Gal antibodies can be recruited and redirected to exert anti-bacterial activity. We show that a specific DNA aptamer conjugated to an α-Gal epitope at its 5' end, herein termed an alphamer, can bind to group A Streptococcus (GAS) bacteria by recognition of a conserved region of the surface-anchored M protein. The anti-GAS alphamer was shown to recruit anti-Gal antibodies to the streptococcal surface in an α-Gal-specific manner, elicit uptake and killing of the bacteria by human phagocytes, and slow growth of invasive GAS in human whole blood. These studies provide a first in vitro proof of concept that alphamers have the potential to redirect pre-existing antibodies to bacteria in a specific manner and trigger an immediate antibacterial immune response. Further validation of this novel therapeutic approach of applying α-Gal technology in in vivo models of bacterial infection is warranted. KEY MESSAGES: . α-Gal-tagged aptamers lead to GAS opsonization with anti-Gal antibodies. . α-Gal-tagged aptamers confer phagocytosis and killing of GAS cells by human phagocytes. . α-Gal-tagged aptamers reduces replication of GAS in human blood. . α-Gal-tagged aptamers may have the potential to be used as novel passive immunization drugs.

Indexed as

AcetylglucosamineAnimalsAnti-Bacterial AgentsAntibodies, BacterialAptamers, NucleotideBase SequenceDrug DiscoveryEpitopesHumansMolecular Sequence DataPhagocytosisStreptococcal InfectionsStreptococcusAcetylglucosamineAnti-Bacterial AgentsAntibodies, BacterialAptamers, NucleotideEpitopes

Identifiers

PMID25940316
PMCPMC4469262
OpenAlexW2090842328

What OpenQuestion holds

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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.