Mucosal Antibodies to the C Terminus of Toxin A Prevent Colonization of Clostridium difficile.
Mucosal immunity is considered important for protection againstClostridium difficileinfection (CDI). We show that in hamsters immunized withBacillus subtilisspores expressing a carboxy-terminal segment (TcdA26-39) ofC. difficiletoxin A, no colonization occurs in protected animals when challenged withC. difficilestrain 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 TcdA26-39expressed on theB. subtilisspore surface, cross-react with a number of seemingly unrelated proteins expressed on the vegetative cell surface or spore coat ofC. difficileThese include two dehydrogenases, AdhE1 and LdhA, as well as the CdeC protein that is present on the spore. Anti-TcdA26-39mucosal antibodies obtained following immunization with recombinantB. subtilisspores were able to reduce the adhesion ofC. difficileto mucus-producing intestinal cells. This cross-reaction is intriguing yet important since it illustrates the importance of mucosal immunity for complete protection against CDI.
School of Biological Sciences, Royal Holloway University of London, Egham, Surrey, United Kingdom.
Huynh A
HA
Hong
School of Biological Sciences, Royal Holloway University of London, Egham, Surrey, United Kingdom.
Krisztina
K
Hitri
School of Biological Sciences, Royal Holloway University of London, Egham, Surrey, United Kingdom.
Siamand
S
Hosseini
SporeGen Ltd., School of Biological Sciences, Royal Holloway University of London, Egham, Surrey, United Kingdom.
Natalia
N
Kotowicz
The National Institute for Biological Standards and Control, Mimms, Potters Bar, Hertfordshire, United Kingdom.
Donna
D
Bryan
The National Institute for Biological Standards and Control, Mimms, Potters Bar, Hertfordshire, United Kingdom.
Fatme
F
Mawas
Structural Biology Laboratory, Department of Chemistry, University of York, York, United Kingdom.
Anthony J
AJ
Wilkinson
Q-Biologicals NV, Zwijnaarde, Belgium.
Annie
A
van Broekhoven
Leads to Development, Paris, France.
Jonathan
J
Kearsey
School of Biological Sciences, Royal Holloway University of London, Egham, Surrey, United Kingdom s.cutting@rhul.ac.uk.
Simon M
SM
Cutting
D000818:Animals; D000907:Antibodies, Bacterial / Q000276:immunology; D001427:Bacterial Toxins / Q000737:chemistry / Q000276:immunology*; D002460:Cell Line; D016360:Clostridioides difficile / Q000276:immunology*; D003015:Clostridium Infections / Q000276:immunology* / Q000382:microbiology* / Q000517:prevention & control; D006224:Cricetinae; D003429:Cross Reactions; D004768:Enterotoxins / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D018928:Immunity, Mucosal; D007114:Immunization; D007071:Immunoglobulin A, Secretory / Q000276:immunology*; D051379:Mice; D009092:Mucous Membrane / Q000276:immunology* / Q000382:microbiology*; D010446:Peptide Fragments / Q000276:immunology; D054730:Protein Interaction Domains and Motifs / Q000276:immunology*; D013171:Spores, Bacterial / Q000276:immunology
D000907:Antibodies, Bacterial; D001427:Bacterial Toxins; D004768:Enterotoxins; D007071:Immunoglobulin A, Secretory; D010446:Peptide Fragments; C041348:tcdA protein, Clostridium difficile
Clostridium difficile; colonization; immune exclusion; mucosal immunity; oral vaccines