Retargeting pre-existing human antibodies to a bacterial pathogen with an alpha-Gal conjugated aptamer
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| 024 | 7 | 0 | |a 10.1007/s00109-015-1280-4 |2 doi |
| 035 | |a (NATIONALLICENCE)springer-10.1007/s00109-015-1280-4 | ||
| 245 | 0 | 0 | |a Retargeting pre-existing human antibodies to a bacterial pathogen with an alpha-Gal conjugated aptamer |h [Elektronische Daten] |c [Sascha Kristian, John Hwang, Bradley Hall, Emma Leire, John Iacomini, Robert Old, Uri Galili, Charles Roberts, Kary Mullis, Mike Westby, Victor Nizet] |
| 520 | 3 | |a 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. 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. | |
| 540 | |a Springer-Verlag Berlin Heidelberg, 2015 | ||
| 690 | 7 | |a Aptamer |2 nationallicence | |
| 690 | 7 | |a Galactose-α-1,3-galactosyl-β-1,4- N -acetyl-glucosamine |2 nationallicence | |
| 690 | 7 | |a α-Gal |2 nationallicence | |
| 690 | 7 | |a Anti-Gal |2 nationallicence | |
| 690 | 7 | |a Antibiotic therapy |2 nationallicence | |
| 690 | 7 | |a Drug development |2 nationallicence | |
| 690 | 7 | |a Antibodies |2 nationallicence | |
| 690 | 7 | |a Group A Streptococcus |2 nationallicence | |
| 690 | 7 | |a M protein |2 nationallicence | |
| 690 | 7 | |a Phagocytosis |2 nationallicence | |
| 700 | 1 | |a Kristian |D Sascha |u Altermune Technologies, LLC, Irvine, CA, USA |4 aut | |
| 700 | 1 | |a Hwang |D John |u BS/MS Program, Division of Biological Sciences, University of California San Diego (UCSD), La Jolla, CA, USA |4 aut | |
| 700 | 1 | |a Hall |D Bradley |u Altermune Technologies, LLC, Irvine, CA, USA |4 aut | |
| 700 | 1 | |a Leire |D Emma |u Department of Pediatrics, University of California San Diego (UCSD), La Jolla, CA, USA |4 aut | |
| 700 | 1 | |a Iacomini |D John |u Sackler School of Biomedical Sciences Programs in Immunology and Genetics, Department of Development, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA, USA |4 aut | |
| 700 | 1 | |a Old |D Robert |u Loxbridge Research, The Royal Institution of Great Britain, London, UK |4 aut | |
| 700 | 1 | |a Galili |D Uri |u Department of Surgery, University of Massachusetts Medical School, Worcester, MA, USA |4 aut | |
| 700 | 1 | |a Roberts |D Charles |u Altermune Technologies, LLC, Irvine, CA, USA |4 aut | |
| 700 | 1 | |a Mullis |D Kary |u Altermune Technologies, LLC, Irvine, CA, USA |4 aut | |
| 700 | 1 | |a Westby |D Mike |u Altermune Technologies, LLC, Irvine, CA, USA |4 aut | |
| 700 | 1 | |a Nizet |D Victor |u Department of Pediatrics, University of California San Diego (UCSD), La Jolla, CA, USA |4 aut | |
| 773 | 0 | |t Journal of Molecular Medicine |d Springer Berlin Heidelberg |g 93/6(2015-06-01), 619-631 |x 0946-2716 |q 93:6<619 |1 2015 |2 93 |o 109 | |
| 856 | 4 | 0 | |u https://doi.org/10.1007/s00109-015-1280-4 |q text/html |z Onlinezugriff via DOI |
| 898 | |a BK010053 |b XK010053 |c XK010000 | ||
| 900 | 7 | |a Metadata rights reserved |b Springer special CC-BY-NC licence |2 nationallicence | |
| 908 | |D 1 |a research-article |2 jats | ||
| 949 | |B NATIONALLICENCE |F NATIONALLICENCE |b NL-springer | ||
| 950 | |B NATIONALLICENCE |P 856 |E 40 |u https://doi.org/10.1007/s00109-015-1280-4 |q text/html |z Onlinezugriff via DOI | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Kristian |D Sascha |u Altermune Technologies, LLC, Irvine, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Hwang |D John |u BS/MS Program, Division of Biological Sciences, University of California San Diego (UCSD), La Jolla, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Hall |D Bradley |u Altermune Technologies, LLC, Irvine, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Leire |D Emma |u Department of Pediatrics, University of California San Diego (UCSD), La Jolla, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Iacomini |D John |u Sackler School of Biomedical Sciences Programs in Immunology and Genetics, Department of Development, Molecular and Chemical Biology, Tufts University School of Medicine, Boston, MA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Old |D Robert |u Loxbridge Research, The Royal Institution of Great Britain, London, UK |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Galili |D Uri |u Department of Surgery, University of Massachusetts Medical School, Worcester, MA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Roberts |D Charles |u Altermune Technologies, LLC, Irvine, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Mullis |D Kary |u Altermune Technologies, LLC, Irvine, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Westby |D Mike |u Altermune Technologies, LLC, Irvine, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 700 |E 1- |a Nizet |D Victor |u Department of Pediatrics, University of California San Diego (UCSD), La Jolla, CA, USA |4 aut | ||
| 950 | |B NATIONALLICENCE |P 773 |E 0- |t Journal of Molecular Medicine |d Springer Berlin Heidelberg |g 93/6(2015-06-01), 619-631 |x 0946-2716 |q 93:6<619 |1 2015 |2 93 |o 109 | ||