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GENTAUR BULGARIA
53 Iskar Str. 1191 Kokalyane, Sofia
Tel 0035924682280
Fax 0035929830072
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9, rue Lagrange, 75005 Paris
Tel 01 43 25 01 50
Fax 01 43 25 01 60
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GmbH Marienbongard 20
52062 Aachen Deutschland
Tel (+49) 0241 56 00 99 68
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GENTAUR Ltd.
Howard Frank Turnberry House
1404-1410 High Road
Whetstone London N20 9BH
Tel 020 3393 8531
Fax 020 8445 9411
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GENTAUR Poland Sp. z o.o.
ul. Grunwaldzka 88/A m.2
81-771 Sopot, Poland
Tel 058 710 33 44
Fax 058 710 33 48
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GENTAUR Nederland BV
Kuiper 1
5521 DG Eersel Nederland
Tel 0208-080893
Fax 0497-517897
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GENTAUR SRL IVA IT03841300167
Piazza Giacomo Matteotti, 6, 24122 Bergamo
Tel 02 36 00 65 93
Fax 02 36 00 65 94
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Tel 0911876558
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Genprice Inc, Logistics
547, Yurok Circle
San Jose, CA 95123
Phone/Fax:
(408) 780-0908
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GENPRICE Inc. invoicing/ accounting:
6017 Snell Ave, Suite 357
San Jose, CA. 96123
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Modified Antibodies Trigger Immune Response, Point to Novel Vaccine Design Strategies
In an approach with the potential to aid therapeutic vaccine development, Whitehead Institute scientists have shown that enzymatically modified antibodies can be used to generate highly targeted, potent responses from cells of the immune system.
The approach, referred to as "sortagging," relies on the bacterial enzyme sortase A to modify antibodies to carry various payloads, such as peptides, fluorophores, lipids, fluorophores, and proteins. In this case, the scientists, whose findings are reported online this week in theProceedings of the National Academy of Sciences, attached a variety of small antigens to an antibody directed at the surface of key immune cells. Through sortagging, the scientists were quickly able to prepare various antibody-antigen fusions and to deliver the antigens to their intended targets and track them as the immune cells mounted their intricate responses.
"Sortagging is remarkably specific and efficient," says Lee Kim Swee, a researcher in the lab of Whitehead Member Hidde Ploegh. "We were able to create 50 different constructs (antibody-protein attachments), which wouldn't have been feasible if we had relied on the more traditional approach of genetic fusion."
Swee and colleagues tested the approach in a mouse model of herpes virus, sortagging 19 known viral epitopes to a cell-specific antibody. They created a vaccine cocktail and immunized a group of mice. Upon subsequent re-exposure to the virus, vaccinated mice showed a 10-fold reduction in the amount of circulating virus.
"This is proof of principle that one could in fact use sortagging on antibodies to easily attach a tailored set of antigens, toward which the immune system can be educated," Swee says. "This technique also helps us understand how to design better antibody-based vaccines."
For paper co-author Carla Guimaraes, sortagging's value is bolstered by its flexibility. She likens it to "playing with Legos," because it allows "you to mix and match" proteins of diverse shapes, sizes, and functions. The process can be used, for example, to attach the relatively large green fluorescent protein (GFP) to antibodies without hindering GFP's desirable fluorescing activity or the binding of the conveying antibody to its intended target.
"Imagination is really your only limitation," says Guimaraes, who is also a postdoctoral researcher in the Ploegh lab. "You could for example, use sortase to attach a toxin to an antibody and use that antibody to deliver the toxin to specific cells." Such an approach, she notes, would be an appealing strategy for developing better-tolerated cancer therapies.
Hidde Ploegh's primary affiliation is with Whitehead Institute for Biomedical Research, where his laboratory is located and all his research is conducted. He is also a professor of biology at Massachusetts Institute of Technology.