antibodies against marinobacter algicola and salmonella typhimurium flagellins do not cross-neutralize tlr5 activation抗体marinobacter algicola和鼠伤寒沙门氏菌鞭毛蛋白不cross-neutralize tlr5激活.pdf

Antibodies against Marinobacter algicola and Salmonella typhimurium Flagellins Do Not Cross-Neutralize TLR5 Activation 1 2 1 3 1 Raul Terron-Exposito , Benoit Dudognon , Inmaculada Galindo , Jose I. Quetglas , Julio M. Coll , 1 1 Jose M. Escribano , Eduardo Gomez-Casado * ´ ´ 1 Department of Biotechnology, Instituto Nacional de Investigacion y Tecnologıa Agraria y Alimentaria, INIA, Madrid, Spain, 2 Alternative Gene Expression S. L. (ALGENEX ´ S. L.), Madrid, Spain, 3 Division of Gene Therapy, Centro de Investigacion en Medicina Aplicada, CIMA, Pamplona, Spain Abstract Flagellins evoke strong innate and adaptive immune responses. These proteins may play a key role as radioprotectors, exert antitumoral activity in certain types of tumor and reduce graft-versus-host disease in allogeneic hematopoietic stem cell transplant recipients. Notwithstanding, flagellins are highly immunogenic, and repeated use leads to their neutralization by systemic antibodies. This neutralization is not prevented by using functional deleted flagellins. These observations led us to explore the possibility of preventing initial neutralization by means of another functional flagellin that does not belong to common pathogenic bacteria but that has the capacity to activate TLR5. Here we characterized the functional capacity of the two-phase Marinobacter algicola (MA)-derived flagellins (F and FR) as systemic and mucosal adjuvants and compared their performance with that of Sal