NOVEL APPROACH TO DESIGN GLYCOPEPTIDES BASED ON O-SPECIFIC POLYSACCHARIDE OF SHIGELLA FLEXNERI SEROTYPE 2A

摘要

Both intestinal secretory IgA (SIgA) and serum IgG specific for the O-antigen(O-Ag), thepolysaccharide part of the bacterial lipopolysaccharide (LPS) are elicitedupon Shigellainfection, the causative agent of bacillary dysentery. We have addressed herethe protectiverole of the anti-LPS IgG response, using the marine model of pulmonaryinfection. Uponintraperitoneal (i.p.) immunization writh killed Shigella flexneri 2abacteria, mice were shownto elicit a serum, but not a local, anti-LPS IgG response that conferred onlypartial protectionagainst intranasal (i.n.) challenge with the homologous virulent strain.However. miceintranasally administered with, prior to in challenge, an anti-LPS IgGpolyclonal serum fromi.p. immunized mice, showed a significant antibody dose-dependent decrease ofthe lung-bacterial load in comparison to mice that received preimmune serum. Usingmarinemonoclonal antibodies (mAbs) of the G isotype (mIgG) representative of thedifferent IgGsubclasses and specific for serotype-specific determinants on the O-Ag, weshowed that eachIgG subclass exhibited a similar serotype-specific protective capacity, withsignificantreduction of the lung-bacterial load and of subsequent inflammation and tissuedestruction. Incontrast, different subclasses of mIgG specific for the invasins IpaB or IpaCdid riot conferprotection. In conclusion, the IgG-mediated systemic response to serotype-specificdeterminants contributes to protection against homologous Shigella infection,if the effectorsare present locally at the time of mucosal infection.