ABSTRACT
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.
Subject(s)
Bacterial Vaccines/immunology , Clostridioides difficile/immunology , Enterocolitis, Pseudomembranous/prevention & control , Membrane Glycoproteins/immunology , Adjuvants, Immunologic/administration & dosage , Animals , Antibodies, Bacterial/blood , Cell Wall Skeleton/administration & dosage , Cholera Toxin/administration & dosage , Cholera Toxin/immunology , Cord Factors/administration & dosage , Cricetinae , Enterocolitis, Pseudomembranous/immunology , Female , Immunoglobulin A/blood , Immunoglobulin G/blood , Lipid A/administration & dosage , Lipid A/analogs & derivatives , Mesocricetus , Mice , Mice, Inbred BALB C , Survival AnalysisABSTRACT
Clostridium difficile is a major cause of antibiotic-associated diarrhoea and the primary cause of pseudomembraneous colitis in hospitalised patients. We assessed the protective effect of anti-surface layer protein (SLP) antibodies on C. difficile infection in a lethal hamster challenge model. Post-challenge survival was significantly prolonged in the anti-SLP treated group compared with control groups (P=0.0281 and P=0.0283). The potential mechanism of action of the antiserum was shown to be through enhancement of C. difficile phagocytosis. This report indicates that anti-SLP antibodies can modulate the course of C. difficile infection and may therefore merit closer investigation for use as constituents of multi-component vaccines against C. difficile associated diarrhoea.
