Immunogenicity of Clostridium difficult DNA-based vaccine in an aging mouse model (VAC7P.959)

Clostridium difficile infection (CDI) is a major source of morbidity and mortality, costing our healthcare system ~ $1 billion/year. Over 90% of CDI-related deaths occur in individuals >85yrs. Protection against severe C. difficile-associated disease and recurrent CDI is mediated by host antibody responses against C. difficile toxins. Our goal is to determine the immunogenicity of a DNA based anti-toxin vaccine in an aging mouse model. Young (4 mo.) and old (>18mo.) mice were immunized with our optimized DNA vaccine encoding toxin A and toxin B receptor-binding domain of C. 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 (25 ug/ul vs. 5 ug/ul anti-toxin serum IgG). However 10 days post second immunization the both groups had comparable IgG titers (~500 ug/ul IgG) against A-RBD. Anti toxin B-RBD IgG responses in older mice remained lower when compared to young following the second immunization. This suggests our DNA vaccine platform can generate an antibody response against C. difficile toxin in older mice but defects in vaccine priming may be occurring leading to lower titers. Day 14 post second immunization, mice cellular responses were analyzed. Higher frequencies of CD4+/CD44+ (activated) T cells and toxin-specific CD4+ T cells secreting pro-inflammatory cytokines (IFN-gamma, IL2) and Th2 cytokines (IL4, IL10) were generated in older mice.