Mucosal Antibodies to the C Terminus of Toxin A Prevent Colonization of Clostridium difficile

• Published in: Infection and immunity Vol. 85; no. 4
• Main Authors: Hong, Huynh A, Hitri, Krisztina, Hosseini, Siamand, Kotowicz, Natalia, Bryan, Donna, Mawas, Fatme, Wilkinson, Anthony J, van Broekhoven, Annie, Kearsey, Jonathan, Cutting, Simon M
• Format: Journal Article
• Language: English
• Published: United States American Society for Microbiology 01-04-2017
• Subjects: Animals; Antibodies, Bacterial - immunology; Bacillus subtilis; Bacterial Toxins - chemistry; Bacterial Toxins - immunology; Cell Line; Clostridioides difficile - immunology; Clostridium difficile; Clostridium Infections - immunology; Clostridium Infections - microbiology; Clostridium Infections - prevention & control; Cricetinae; Cross Reactions; Enterotoxins - chemistry; Enterotoxins - immunology; Humans; Immunity, Mucosal; Immunization; Immunoglobulin A, Secretory - immunology; Mice; Microbial Immunity and Vaccines; Mucous Membrane - immunology; Mucous Membrane - microbiology; Peptide Fragments - immunology; Protein Interaction Domains and Motifs - immunology; Spores, Bacterial - immunology; oral vaccines; colonization; Clostridium difficile; immune exclusion; mucosal immunity
• ISSN: 0019-9567; 1098-5522
• DOI: 10.1128/IAI.01060-16

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