Mucosal antibodies to the C terminus of toxin A prevent colonization of Clostridium difficile

TY - JOUR

T1 - Mucosal antibodies to the C terminus of toxin A prevent colonization of Clostridium difficile

AU - Hong, Huynh A.

AU - Hitri, Krisztina

AU - Hosseini, Siamand

AU - Kotowicz, Natalia

AU - Bryan, Donna

AU - Mawas, Fatme

AU - Wilkinson, Anthony J.

AU - van Broekhoven, Annie

AU - Kearsey, Jonathan

AU - Cutting, Simon M.

N1 - © 2017 American Society for Microbiology. This is an author-produced version of the published paper. Uploaded in accordance with the publisher’s self-archiving policy. Further copying may not be permitted; contact the publisher for details

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Mucosal immunity is considered important for protection against Clostridium difficile infection (CDI). We show that in hamsters immunized with Bacillus subtilis spores expressing a carboxy-terminal segment (TcdA26-39) of C. difficile toxin A, no colonization occurs in protected animals when challenged with C. difficile strain 630. In contrast, animals immunized with toxoids showed no protection and remained fully colonized. Along with neutralizing toxins, antibodies to TcdA26-39 (but not to toxoids), whether raised to the recombinant protein or to TcdA26-39 expressed on the B. subtilis spore surface, cross-react with a number of seemingly unrelated proteins expressed on the vegetative cell surface or spore coat of C. difficile. These include two dehydrogenases, AdhE1 and LdhA, as well as the CdeC protein that is present on the spore. Anti-TcdA26-39 mucosal antibodies obtained following immunization with recombinant B. subtilis spores were able to reduce the adhesion of C. difficile to mucus-producing intestinal cells. This cross-reaction is intriguing yet important since it illustrates the importance of mucosal immunity for complete protection against CDI.

AB - Mucosal immunity is considered important for protection against Clostridium difficile infection (CDI). We show that in hamsters immunized with Bacillus subtilis spores expressing a carboxy-terminal segment (TcdA26-39) of C. difficile toxin A, no colonization occurs in protected animals when challenged with C. difficile strain 630. In contrast, animals immunized with toxoids showed no protection and remained fully colonized. Along with neutralizing toxins, antibodies to TcdA26-39 (but not to toxoids), whether raised to the recombinant protein or to TcdA26-39 expressed on the B. subtilis spore surface, cross-react with a number of seemingly unrelated proteins expressed on the vegetative cell surface or spore coat of C. difficile. These include two dehydrogenases, AdhE1 and LdhA, as well as the CdeC protein that is present on the spore. Anti-TcdA26-39 mucosal antibodies obtained following immunization with recombinant B. subtilis spores were able to reduce the adhesion of C. difficile to mucus-producing intestinal cells. This cross-reaction is intriguing yet important since it illustrates the importance of mucosal immunity for complete protection against CDI.

KW - Clostridium difficile

KW - Colonization

KW - Immune exclusion

KW - Mucosal immunity

KW - Oral vaccines

UR - http://www.scopus.com/inward/record.url?scp=85016183400&partnerID=8YFLogxK

U2 - 10.1128/IAI.01060-16

DO - 10.1128/IAI.01060-16

M3 - Article

AN - SCOPUS:85016183400

SN - 0019-9567

VL - 85

JO - Infection and Immunity

JF - Infection and Immunity

IS - 4

M1 - e01060-16

ER -