title: Pilin Vaccination Stimulates Weak Antibody Responses and Provides No Protection in a C57Bl/6 Murine Model of AcuteClostridium difficileInfection.
abstract: Clostridium difficileis the leading cause of nosocomial infections in the United States, adding billions of dollars per year to health care costs. A vaccine targeted against the bacterium would be extremely beneficial in decreasing the morbidity and mortality caused byC. difficile-associated disease; a vaccine directed against a colonization factor would hinder the spread of the bacterium as well as prevent disease. Type IV pili (T4Ps) are extracellular appendages composed of protein monomers called pilins. They are involved in adhesion and colonization in a wide variety of bacteria and archaea, and are putative colonization factors inC. difficile. We hypothesized that vaccinating mice with pilins would lead to generation of anti-pilin antibodies, and would protect againstC. difficilechallenge. We found that immunizing C57Bl/6 mice with various pilins, whether combined or as individual proteins, led to low anti-pilin antibody titers and no protection uponC. difficilechallenge. Passive transfer of anti-pilin antibodies led to high serum anti-pilin IgG titers, but to undetectable fecal anti-pilin IgG titers and did not protect against challenge. The low antibody titers observed in these experiments may be due to the particular strain of mice used. Further experiments, possibly with a different animal model ofC. difficileinfection, are needed to determine if an anti-T4P vaccine would be protective againstC. difficileinfection.
authors.affiliation: Department of Medicine, Division of Infectious Disease, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Grace A
authors.initials: GA
authors.lastname: Maldarelli
authors.affiliation: Department of Medicine, Division of Infectious Disease, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Hanover
authors.initials: H
authors.lastname: Matz
authors.affiliation: Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, Maryland, USA.
authors.forename: Si
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, Maryland, USA.
authors.forename: Kevin
authors.initials: K
authors.lastname: Chen
authors.affiliation: Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, Maryland, USA.
authors.forename: Therwa
authors.initials: T
authors.lastname: Hamza
authors.affiliation: Department of Pathology and Laboratory Medicine, VAMHCS, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Harris G
authors.initials: HG
authors.lastname: Yfantis
authors.affiliation: Department of Microbial Pathogenesis, University of Maryland Dental School, Baltimore, Maryland, USA.
authors.forename: Hanping
authors.initials: H
authors.lastname: Feng
authors.affiliation: Department of Medicine, Division of Infectious Disease, University of Maryland School of Medicine, Baltimore, Maryland, USA.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Donnenberg
keywords: Antibody generation; Clostridium difficile; Mouse model; Passive immunization; Type IV pilins