title: Utilization of Fc receptors as a mucosal vaccine strategy against an intracellular bacterium, Francisella tularensis.
abstract: Numerous studies have demonstrated that targeting Ag to Fc receptors (FcR) on APCs can enhance humoral and cellular immunity. However, studies are lacking that examine both the use of FcR-targeting in generating immune protection against infectious agents and the use of FcRs in the induction of mucosal immunity. Francisella tularensis is a category A intracellular mucosal pathogen. Thus, intense efforts are underway to develop a vaccine against this organism. We hypothesized that protection against mucosal infection with F. tularensis would be significantly enhanced by targeting inactivated F. tularensis live vaccine strain (iFt) to FcRs at mucosal sites, via intranasal immunization with mAb-iFt complexes. These studies demonstrate for the first time that: 1) FcR-targeted immunogen enhances immunogen-specific IgA production and protection against subsequent infection in an IgA-dependent manner, 2) FcgammaR and neonatal FcR are crucial to this protection, and 3) inactivated F. tularensis, when targeted to FcRs, enhances protection against the highly virulent SchuS4 strain of F. tularensis, a category A biothreat agent. In summary, these studies show for the first time the use of FcRs as a highly effective vaccination strategy against a highly virulent mucosal intracellular pathogen.
authors.affiliation: Center for Immunology and Microbial Disease, Albany Medical College, Albany, NY 12208, USA.
authors.forename: Deepak B
authors.initials: DB
authors.lastname: Rawool
authors.forename: Constantine
authors.initials: C
authors.lastname: Bitsaktsis
authors.forename: Ying
authors.initials: Y
authors.lastname: Li
authors.forename: Diane R
authors.initials: DR
authors.lastname: Gosselin
authors.forename: Yili
authors.initials: Y
authors.lastname: Lin
authors.forename: Nitin V
authors.initials: NV
authors.lastname: Kurkure
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Metzger
authors.forename: Edmund J
authors.initials: EJ
authors.lastname: Gosselin
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000907:Antibodies, Bacterial / Q000096:biosynthesis / Q000276:immunology; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology*; D016207:Cytokines / Q000276:immunology / Q000378:metabolism*; D005604:Francisella tularensis / Q000276:immunology* / Q000472:pathogenicity; D018928:Immunity, Mucosal; D007117:Immunization, Secondary; D007070:Immunoglobulin A / Q000096:biosynthesis / Q000276:immunology; D007156:Immunologic Memory; D007249:Inflammation / Q000276:immunology / Q000517:prevention & control; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D008099:Liver / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D008168:Lung / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009092:Mucous Membrane / Q000276:immunology / Q000378:metabolism*; D011961:Receptors, Fc / Q000276:immunology* / Q000378:metabolism; D013154:Spleen / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014406:Tularemia / Q000276:immunology / Q000517:prevention & control*; D014611:Vaccination
chemical_list: D000907:Antibodies, Bacterial; D001428:Bacterial Vaccines; D016207:Cytokines; D007070:Immunoglobulin A; D011961:Receptors, Fc; D007371:Interferon-gamma