C - Chemistry – Metallurgy – 07 – K
Patent
C - Chemistry, Metallurgy
07
K
C07K 2/00 (2006.01) A61K 31/702 (2006.01) A61K 31/715 (2006.01) A61K 35/74 (2006.01) A61K 39/112 (2006.01) A61K 47/42 (2006.01) A61K 47/48 (2006.01) C07H 3/00 (2006.01) C07K 7/06 (2006.01) C07K 9/00 (2006.01) C07K 14/195 (2006.01) C07K 16/12 (2006.01) C08B 37/00 (2006.01)
Patent
CA 2434685
Both intestinal secretory IgA (SIgA) and serum IgG specific for the O-antigen (O-Ag), the polysaccharide part of the bacterial lipopolysaccharide (LPS) are elicited upon Shigella infection, the causative agent of bacillary dysentery. We have addressed here the protective role of the anti-LPS IgG response, using the marine model of pulmonary infection. Upon intraperitoneal (i.p.) immunization writh killed Shigella flexneri 2a bacteria, mice were shown to elicit a serum, but not a local, anti-LPS IgG response that conferred only partial protection against intranasal (i.n.) challenge with the homologous virulent strain. However. mice intranasally administered with, prior to in challenge, an anti-LPS IgG polyclonal serum from i.p. immunized mice, showed a significant antibody dose-dependent decrease of the lung- bacterial load in comparison to mice that received preimmune serum. Using marine monoclonal antibodies (mAbs) of the G isotype (mIgG) representative of the different IgG subclasses and specific for serotype-specific determinants on the O-Ag, we showed that each IgG subclass exhibited a similar serotype-specific protective capacity, with significant reduction of the lung-bacterial load and of subsequent inflammation and tissue destruction. In contrast, different subclasses of mIgG specific for the invasins IpaB or IpaC did riot confer protection. In conclusion, the IgG-mediated systemic response to serotype- specific determinants contributes to protection against homologous Shigella infection, if the effectors are present locally at the time of mucosal infection.
Baleux Francoise
Belot Frederic
Grandjean Cyrille
Mulard Laurence
Phalipon Armelle
Baleux Francoise
Belot Frederic
Grandjean Cyrille
Mulard Laurence
Phalipon Armelle
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