Immune Response Characterization after Controlled Infection with Lyophilized Shigella sonnei 53G
Kristen A. Clarkson, Robert W. Frenck, Michelle Dickey, Akamol E. Suvarnapunya, Lakshmi Chandrasekaran, Hailey P. Weerts, Christopher D. Heaney, Monica McNeal, Kate Detizio, Susan Parker, Amy Hoeper, A. Louis Bourgeois, Chad K. Porter, Malabi M. Venkatesan, Robert W. Kaminski
Abstract
Correlate(s) of immunity have yet to be defined for shigellosis. As previous disease protects against subsequent infection in a serotype-specific manner, investigating immune response profiles pre- and postinfection provides an opportunity to identify immune markers potentially associated with the development of protective immunity and/or with a reduced risk of developing shigellosis postchallenge. This study is the first to report such an extensive characterization of the immune response after challenge with S. sonnei 53G. Results demonstrate an association of progression to shigellosis with robust intestinal inflammatory and mucosal gut-homing responses. An important finding in this study was the association of elevated Shigella LPS-specific serum IgA and memory B cell IgA responses at baseline with reduced risk of disease. The increased baseline IgA responses may contribute to the lack of dose response observed in the study and suggests that IgA responses should be further investigated as potential correlates of immunity.