Adenovirus-based vaccination against Clostridium difficile toxin A allows for rapid humoral immunity and complete protection from toxin A lethal challenge in mice.
Clostridium difficile associated diarrhea (CDAD) is a critical public health problem worldwide with over 300,000 cases every year in the United States alone. Clearly, a potent vaccine preventing the morbidity and mortality caused by this detrimental pathogen is urgently required. However, vaccine efforts to combat C. difficile infections have been limited both in scope as well as to efficacy, as such there is not a vaccine approved for use against C. difficile to date. In this study, we have used a highly potent Adenovirus (Ad) based platform to create a vaccine against C. difficile. The Ad-based vaccine was able to generate rapid and robust humoral as well as cellular (T-cell) immune responses in mice that correlated with provision of 100% protection from lethal challenge with C. difficile toxin A. Most relevant to the clinical utility of this vaccine formulation was our result that toxin A specific IgGs were readily detected in plasma of Ad immunized mice as early as 3 days post vaccination. In addition, we found that several major immuno-dominant T cell epitopes were identified in toxin A, suggesting that the role of the cellular arm in protection from C. difficile infections may be more significant than previously appreciated. Therefore, our studies confirm that an Adenovirus based-C. difficile vaccine could be a promising candidate for prophylactic vaccination both for use in high risk patients and in high-risk environments.
Department of Microbiology and Molecular Genetics, College of Osteopathic Medicine, Michigan State University, East Lansing, MI 48824, United States.
Sergey S
SS
Seregin
Yasser A
YA
Aldhamen
David P W
DP
Rastall
Sarah
S
Godbehere
Andrea
A
Amalfitano
D000256:Adenoviridae / Q000235:genetics* / Q000276:immunology; D000818:Animals; D000992:Antitoxins / Q000097:blood*; D001427:Bacterial Toxins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D003015:Clostridium Infections / Q000517:prevention & control; D004195:Disease Models, Animal; D004337:Drug Carriers / Q000008:administration & dosage*; D004768:Enterotoxins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000276:immunology*; D018984:Epitopes, T-Lymphocyte / Q000276:immunology; D007111:Immunity, Cellular; D007074:Immunoglobulin G / Q000097:blood; D051379:Mice; D008807:Mice, Inbred BALB C; D011041:Poisoning / Q000517:prevention & control; D016019:Survival Analysis; D014611:Vaccination / Q000379:methods*
D000992:Antitoxins; D001427:Bacterial Toxins; D001428:Bacterial Vaccines; D004337:Drug Carriers; D004768:Enterotoxins; D018984:Epitopes, T-Lymphocyte; D007074:Immunoglobulin G; C041348:tcdA protein, Clostridium difficile