title: CBA/J mice generate protective immunity to soluble Ag85 but fail to respond efficiently to Ag85 during natural Mycobacterium tuberculosis infection.
abstract: In CBA/J mice, susceptibility to Mycobacterium tuberculosis (M.tb) is associated with low interferon-gamma (IFN-γ) responses to antigens (Antigen 85 (Ag85) and early secreted antigenic target-6 (ESAT-6)) that have been defined as immunodominant. Here, we asked whether the failure of CBA/J mice to recognize Ag85 is a consequence of M.tb infection or whether CBA/J mice have a general defect in generating specific T-cell responses to this protein antigen. We compared CBA/J mice during primary M.tb infection, Ag85 vaccination followed by M.tb challenge, or M.tb memory immune mice for their capacity to generate Ag85-specific IFN-γ responses and to control M.tb infection. CBA/J mice did not respond efficiently to Ag85 in the context of natural infection or re-infection. In contrast, CBA/J mice could generate Ag85-specific IFN-γ responses and protective immunity when this antigen was delivered as a soluble protein. Our data indicate that although M.tb infection of CBA/J mice does not drive an Ag85 response, these mice can fully and protectively respond to Ag85 if it is delivered as a vaccine. The data from this experimental model suggest that the Ag85-containing vaccines in clinical trials should protect M.tb susceptible humans.
authors.affiliation: Center for Microbial Interface Biology, The Ohio State University, Columbus, OH, USA.
authors.forename: Gillian L
authors.initials: GL
authors.lastname: Beamer
authors.forename: Joshua
authors.initials: J
authors.lastname: Cyktor
authors.forename: David K
authors.initials: DK
authors.lastname: Flaherty
authors.forename: Paul C
authors.initials: PC
authors.lastname: Stromberg
authors.forename: Bridget
authors.initials: B
authors.lastname: Carruthers
authors.forename: Joanne
authors.initials: J
authors.lastname: Turner
mesh_terms: D000818:Animals; D000942:Antigens, Bacterial / Q000276:immunology / Q000494:pharmacology*; D004195:Disease Models, Animal; D006801:Humans; D007156:Immunologic Memory / Q000187:drug effects*; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D009169:Mycobacterium tuberculosis / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014376:Tuberculosis / Q000276:immunology* / Q000517:prevention & control*; D014611:Vaccination
chemical_list: D000942:Antigens, Bacterial; D007371:Interferon-gamma