Abstract
New therapies are needed to prevent and treat Clostridium difficile infection and to limit the rise in antibiotic resistance. Besides toxins, several surface components have been characterized as colonization factors and have been shown as immunogenic. This review will focus on passive and active immunization strategies targeting C. difficile surface components to combat C. difficile. Concerning passive immunization, the first strategies used antisera raised against the entire bacterium to prevent infection in the hamster model. Then, surface components such as the flagellin and the S-layer proteins were used for immunization and the passive transfer of antibodies was protective in animal models. Passive immunotherapy with polyvalent immunoglobulins was used in humans and bovine immunoglobulin concentrates were evaluated in clinical trials. Concerning active immunization, vaccine assays targeting surface components were tested mainly in animal models, mouse models of colonization and hamster models of infection. Bacterial extracts, spore proteins and surface components of vegetative cells such as cell wall proteins, flagellar proteins, and polysaccharides were used as vaccine targets. Vaccine assays were performed by parenteral and mucosal routes of immunization. Both gave promising results and pave the way to development of new vaccines.
Highlights
Clostridium difficile is involved in a wide spectrum of diseases from mild post-antibiotic diarrhea to pseudomembranous colitis (PMC) that can be severe and lead to complications such as toxic megacolon, septic shock, and death (Rupnik et al, 2009)
While neutralizing toxins can prevent clinical signs, an immunotherapy targeting surface components aims to prevent the first step of C. difficile pathogenesis gut colonization
Several assays of vaccine targeting surface components of C. difficile vegetative cells and spores have been performed in animal models
Summary
Clostridium difficile is involved in a wide spectrum of diseases from mild post-antibiotic diarrhea to pseudomembranous colitis (PMC) that can be severe and lead to complications such as toxic megacolon, septic shock, and death (Rupnik et al, 2009). In humans it is difficult to pinpoint the role of the immune response in the susceptibility to CDI because of the accumulation of risk factors in immunodeficient patients such as multiple antibiotic treatments (Fisher et al, 2014). Several studies showed that the intensity of the specific host immune response to C. difficile exposure is a key factor in CDI outcome. Promising results in the decrease of CDI and recurrences, vaccines and passive immunotherapies targeting toxins do not appear to prevent C. difficile gut colonization, and further dissemination of spores in the environment. Another approach to prevent CDI and recurrences is to directly target the bacterium by developing immunotherapeutic strategies specific for C. difficile surface components. A better knowledge of C. difficile pathogenesis has shed light on several components involved in intestinal colonization
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