title: Mucosal immunization with live attenuated Francisella novicida U112ΔiglB protects against pulmonary F. tularensis SCHU S4 in the Fischer 344 rat model.
abstract: The need for an efficacious vaccine against Francisella tularensis is a consequence of its low infectious dose and high mortality rate if left untreated. This study sought to characterize a live attenuated subspecies novicida-based vaccine strain (U112ΔiglB) in an established second rodent model of pulmonary tularemia, namely the Fischer 344 rat using two distinct routes of vaccination (intratracheal [i.t.] and oral). Attenuation was verified by comparing replication of U112ΔiglB with wild type parental strain U112 in F344 primary alveolar macrophages. U112ΔiglB exhibited an LD(50)>10(7) CFU compared to the wild type (LD(50) = 5 × 10(6) CFU i.t.). Immunization with 10(7) CFU U112ΔiglB by i.t. and oral routes induced antigen-specific IFN-γ and potent humoral responses both systemically (IgG2a>IgG1 in serum) and at the site of mucosal vaccination (respiratory/intestinal compartment). Importantly, vaccination with U112ΔiglB by either i.t. or oral routes provided equivalent levels of protection (50% survival) in F344 rats against a subsequent pulmonary challenge with ~25 LD(50) (1.25 × 10(4) CFU) of the highly human virulent strain SCHU S4. Collectively, these results provide further evidence on the utility of a mucosal vaccination platform with a defined subsp. novicida U112ΔiglB vaccine strain in conferring protective immunity against pulmonary tularemia.
authors.affiliation: South Texas Center for Emerging Infectious Disease and Center of Excellence in Infection Genomics, University of Texas at San Antonio, San Antonio, Texas, United States of America.
authors.forename: Aimee L
authors.initials: AL
authors.lastname: Signarovitz
authors.forename: Heather J
authors.initials: HJ
authors.lastname: Ray
authors.forename: Jieh-Juen
authors.initials: JJ
authors.lastname: Yu
authors.forename: M N
authors.initials: MN
authors.lastname: Guentzel
authors.forename: James P
authors.initials: JP
authors.lastname: Chambers
authors.forename: Karl E
authors.initials: KE
authors.lastname: Klose
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Arulanandam
mesh_terms: D000284:Administration, Oral; D000818:Animals; D001428:Bacterial Vaccines / Q000008:administration & dosage / Q000276:immunology; D004195:Disease Models, Animal; D005604:Francisella tularensis / Q000276:immunology / Q000472:pathogenicity; D006801:Humans; D018928:Immunity, Mucosal / Q000276:immunology; D007114:Immunization; D007371:Interferon-gamma / Q000276:immunology; D051379:Mice; D051381:Rats; D011916:Rats, Inbred F344; D013045:Species Specificity; D014406:Tularemia / Q000235:genetics / Q000276:immunology / Q000382:microbiology / Q000517:prevention & control; D014613:Vaccines, Attenuated / Q000008:administration & dosage*
chemical_list: D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated; D007371:Interferon-gamma