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Retargeting pre-existing human antibodies to a bacterial pathogen with an alpha-Gal conjugated aptamer
- Source :
- Journal of Molecular Medicine. 93:619-631
- Publication Year :
- 2015
- Publisher :
- Springer Science and Business Media LLC, 2015.
-
Abstract
- The 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. • 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.
- Subjects :
- Aptamer
Phagocytosis
Molecular Sequence Data
Article
Epitope
Acetylglucosamine
Microbiology
Epitopes
Immune system
Streptococcal Infections
Drug Discovery
Animals
Humans
Genetics (clinical)
Base Sequence
biology
Streptococcus
Aptamers, Nucleotide
Antibodies, Bacterial
In vitro
Anti-Bacterial Agents
Antibody opsonization
Immunization
biology.protein
Molecular Medicine
Antibody
Subjects
Details
- ISSN :
- 14321440 and 09462716
- Volume :
- 93
- Database :
- OpenAIRE
- Journal :
- Journal of Molecular Medicine
- Accession number :
- edsair.doi.dedup.....89e4c18c47d7c949b60d24012e930b91
- Full Text :
- https://doi.org/10.1007/s00109-015-1280-4