Journal article
Increase in Incidence of Clostridium Difficile infection in aged models and effective DNA vaccine strategies for the prevention of disease
The Journal of immunology (1950), v 198(1_Supplement)
01 May 2017
Abstract
Abstract Clostridium difficile–associated disease (CDAD) constitutes a large majority of nosocomial diarrhea cases in industrialized nations and is mediated by the effects of two secreted toxins, toxin A (TcdA) and toxin B (TcdB). Key toxin-neutralizing epitopes have been discovered within the carboxy-terminal receptor-binding domain (RBD) of the toxins, which has generated interest in developing the RBD as a vaccine target. The elderly mount an impaired humoral response to C. difficile toxins leading to more severe and recurrent disease; however, it has yet to be determined what underlying mechanisms lead to lower anti-toxin titers, thus higher incidence of severe and recurrent disease. While numerous platforms have been studied, very few data describe the potential of DNA vaccination against CDAD. We immunized C57BL/6 mice with plasmids encoding the RBD from TcdA and TcdB intramuscularly followed by in vivo electroporation. Vaccination induced significant levels of anti-RBD antibodies within the serum and feces that could neutralize toxins in an in vitro cytotoxicity assay. Aged animals had lower endpoint and anti-toxin neutralization titers, but aged mice still elicited functional antibody post vaccination. Both young and aged immunized mice were protected following orogastric challenge with strains of C. difficile spores that were homologous (VPI 10463; n=10/10) and heterologous (hypervirulent UK1; n=4/8) strains to our vaccine antigens. These data demonstrate the robust immunogenicity and efficacy of a TcdA/B RBD-based DNA vaccine in preclinical young adult and aged models of acute toxin-associated disease.
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Details
- Title
- Increase in Incidence of Clostridium Difficile infection in aged models and effective DNA vaccine strategies for the prevention of disease
- Creators
- Michele A. Kutzler - Drexel University
- Publication Details
- The Journal of immunology (1950), v 198(1_Supplement)
- Publisher
- American Association of Immunologists (AAI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Infectious Diseases (and HIV Medicine)
- Other Identifier
- 991020550346404721