TY - JOUR
T1 - Active immunization of hamsters against Clostridium difficile infection using surface-layer protein
AU - Ní Eidhin, Déirdre B.
AU - O'Brien, Julie B.
AU - McCabe, Matthew S.
AU - Athié-Morales, Verónica
AU - Kelleher, Dermot P.
PY - 2008/3
Y1 - 2008/3
N2 - Clostridium difficile is the leading cause of infectious antibiotic-associated diarrhoea, particularly among the elderly. Its surface-layer protein (SLP) was tested as a vaccine component in a series of immunization and challenge experiments with Golden Syrian hamsters, combined with different systemic and mucosal adjuvants. Some regimens were also tested in a nonchallenge BALB/c mouse model, enabling closer monitoring of the immune response. None of the regimens conferred complete protection in the hamster model, and antibody stimulation was variable within regimens, and generally modest or poor. Mice displayed stronger antibody responses to SLP compared with hamsters. Two hamsters of five given SLP with Ribi (monophosphoryl lipid A and synthetic trehalose dicorynomycolate) survived the challenge, as did two of three given SLP with Ribi and cholera toxin. This modest trend to protection is interpreted with caution, because the survivors had low anti-SLP serum antibody titres. The hamsters were an outbred line, and subject to more genetic variability than inbred animals; however, BALB/c mice also showed strongly variable antibody responses. There is a clear need for better adjuvants for single-component vaccines, particularly for mucosal delivery. The hamster challenge model may need to be modified to be useful in active immunization experiments with SLP.
AB - Clostridium difficile is the leading cause of infectious antibiotic-associated diarrhoea, particularly among the elderly. Its surface-layer protein (SLP) was tested as a vaccine component in a series of immunization and challenge experiments with Golden Syrian hamsters, combined with different systemic and mucosal adjuvants. Some regimens were also tested in a nonchallenge BALB/c mouse model, enabling closer monitoring of the immune response. None of the regimens conferred complete protection in the hamster model, and antibody stimulation was variable within regimens, and generally modest or poor. Mice displayed stronger antibody responses to SLP compared with hamsters. Two hamsters of five given SLP with Ribi (monophosphoryl lipid A and synthetic trehalose dicorynomycolate) survived the challenge, as did two of three given SLP with Ribi and cholera toxin. This modest trend to protection is interpreted with caution, because the survivors had low anti-SLP serum antibody titres. The hamsters were an outbred line, and subject to more genetic variability than inbred animals; however, BALB/c mice also showed strongly variable antibody responses. There is a clear need for better adjuvants for single-component vaccines, particularly for mucosal delivery. The hamster challenge model may need to be modified to be useful in active immunization experiments with SLP.
KW - Adjuvants
KW - Clostridium difficile
KW - Hamster model
KW - Surface-layer protein
KW - Vaccine
UR - http://www.scopus.com/inward/record.url?scp=39049167109&partnerID=8YFLogxK
U2 - 10.1111/j.1574-695X.2007.00363.x
DO - 10.1111/j.1574-695X.2007.00363.x
M3 - Article
C2 - 18093141
AN - SCOPUS:39049167109
SN - 0928-8244
VL - 52
SP - 207
EP - 218
JO - FEMS Immunology and Medical Microbiology
JF - FEMS Immunology and Medical Microbiology
IS - 2
ER -