Immunogenicity of Clostridium difficile DNA-based vaccine in an aging mouse model

Abstract

Event Abstract Back to Event Immunogenicity of Clostridium difficile DNA-based vaccine in an aging mouse model Mariana E. Bernui1*, Scott Baliban1, Jeffrey Jacobson1 and Michele Kutzler1 1 Drexel University College of Medicine, Department of Medicine; Department of Microbiology and Immunology, United States Clostridium difficile infection (CDI) is a major source of morbidity and mortality in the United States, costing our healthcare system ~ $1.1 billion/year. CDI has led to a doubling of mortality with greater than 90% of these deaths occurring in individuals >85yrs. There is a significant correlation between advanced age and risk of recurrent CDI. Protection against severe Clostridium difficile-associated disease and reduction of recurrent CDI is mediated by host antibody responses against the toxins of C. difficile. The goal of our study is to determine the immunogenicity of a DNA based anti-toxin vaccine in an aging mouse model. Thus, young (4 mo.) and old (>18mo.) mice were immunized with our optimized DNA vaccine encoding toxin A and toxin B receptor-binding domain of Clostridium difficile (A-RBD; B-RBD). Day 12 after the first immunization the younger mice had significantly higher IgG titers against A-RBD than older mice, with 25 ug/ul versus 5 ug/ul anti-toxin serum IgG. However 10 days post second immunization the old and young mice had comparable IgG titers of approximately 500 ug/ul IgG against A-RBD. Interestingly, anti toxin B-RBD IgG responses in older mice remained statistically lower when compared to young following the second immunization (1000 ug/ul vs 2000 ug/ul). We also observe differences in anti-toxin IgG and IgA in fecal extracts post immunization between aged and young mice. These data suggest that our DNA vaccine platform is able to generate an antibody response against C. difficile toxin-based DNA vaccines in older mice but defects in vaccine priming may be occurring leading to lower titers. Two weeks post second immunization, mice were euthanized and their cellular response to the DNA vaccine was analyzed. Using flow and ELISpot assays, higher frequencies of CD4+/CD44+ (activated) T cells were detected in older mice than in the younger cohorts. Finally, we observed a higher frequency of toxin-specific CD4+ T cells that secrete pro-inflammatory cytokines (IFN-g, IL2) and Th2 cytokines (IL4, IL10) in older mice, supporting the notion of a deleterious “inflamm-aging” response. These data warrant further study of the mechanism by which lower vaccine priming or inflammation in aged mice lead to lower titers of anti-toxin vaccine responses. Keywords: Clostridium difficile, immunosenescence, immunization in elderly, aging mouse model, immune response in aging Conference: 15th International Congress of Immunology (ICI), Milan, Italy, 22 Aug - 27 Aug, 2013. Presentation Type: Abstract Topic: Translational immunology and immune intervention Citation: Bernui ME, Baliban S, Jacobson J and Kutzler M (2013). Immunogenicity of Clostridium difficile DNA-based vaccine in an aging mouse model. Front. Immunol. Conference Abstract: 15th International Congress of Immunology (ICI). doi: 10.3389/conf.fimmu.2013.02.00914 Copyright: The abstracts in this collection have not been subject to any Frontiers peer review or checks, and are not endorsed by Frontiers. They are made available through the Frontiers publishing platform as a service to conference organizers and presenters. The copyright in the individual abstracts is owned by the author of each abstract or his/her employer unless otherwise stated. Each abstract, as well as the collection of abstracts, are published under a Creative Commons CC-BY 4.0 (attribution) licence (https://creativecommons.org/licenses/by/4.0/) and may thus be reproduced, translated, adapted and be the subject of derivative works provided the authors and Frontiers are attributed. For Frontiers’ terms and conditions please see https://www.frontiersin.org/legal/terms-and-conditions. Received: 27 Jun 2013; Published Online: 22 Aug 2013. * Correspondence: Dr. Mariana E Bernui, Drexel University College of Medicine, Department of Medicine; Department of Microbiology and Immunology, Philadelphia, PA, United States, mariana.bernui@gmail.com Login Required This action requires you to be registered with Frontiers and logged in. To register or login click here. Abstract Info Abstract The Authors in Frontiers Mariana E Bernui Scott Baliban Jeffrey Jacobson Michele Kutzler Google Mariana E Bernui Scott Baliban Jeffrey Jacobson Michele Kutzler Google Scholar Mariana E Bernui Scott Baliban Jeffrey Jacobson Michele Kutzler PubMed Mariana E Bernui Scott Baliban Jeffrey Jacobson Michele Kutzler Related Article in Frontiers Google Scholar PubMed Abstract Close Back to top Javascript is disabled. Please enable Javascript in your browser settings in order to see all the content on this page.