title: Recombinant attenuated Listeria monocytogenes vaccine expressing Francisella tularensis IglC induces protection in mice against aerosolized Type A F. tularensis.
abstract: Fransicella tularensis, the causative agent of tularemia, is in the top category (Category A) of potential agents of bioterrorism. To develop a safer vaccine against aerosolized F. tularensis, we have employed an attenuated Listeria monocytogenes, which shares with F. tularensis an intracellular and extraphagosomal lifestyle, as a delivery vehicle for F. tularensis antigens. We constructed recombinant L. monocytogenes (rLm) vaccines stably expressing seven F. tularensis proteins including IglC (rLm/iglC), and tested their immunogenicity and protective efficacy against lethal F. tularensis challenge in mice. Mice immunized intradermally with rLm/iglC developed significant cellular immune responses to F. tularensis IglC as evidenced by lymphocyte proliferation and CD4+ and CD8+ T-cell intracellular expression of interferon gamma. Moreover, mice immunized with rLm/iglC were protected against lethal challenge with F. tularensis LVS administered by the intranasal route, a route chosen to mimic airborne infection, and, most importantly, against aerosol challenge with the highly virulent Type A F. tularensis SchuS4 strain.
authors.affiliation: Division of Infectious Diseases, Department of Medicine, 37-121 Center for Health Sciences, School of Medicine, University of California - Los Angeles, 10833 Le Conte Avenue, Los Angeles, CA 90095-1688, United States.
authors.forename: Qingmei
authors.initials: Q
authors.lastname: Jia
authors.forename: Bai-Yu
authors.initials: BY
authors.lastname: Lee
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Clemens
authors.forename: Richard A
authors.initials: RA
authors.lastname: Bowen
authors.forename: Marcus A
authors.initials: MA
authors.lastname: Horwitz
mesh_terms: D000281:Administration, Intranasal; D000818:Animals; D000942:Antigens, Bacterial / Q000235:genetics / Q000276:immunology*; D001428:Bacterial Vaccines / Q000235:genetics* / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D049109:Cell Proliferation; D015169:Colony Count, Microbial; D005604:Francisella tularensis / Q000235:genetics / Q000276:immunology*; D007271:Injections, Intradermal; D007371:Interferon-gamma / Q000096:biosynthesis; D008089:Listeria monocytogenes / Q000235:genetics*; D008099:Liver / Q000382:microbiology; D008168:Lung / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D013154:Spleen / Q000382:microbiology; D016019:Survival Analysis; D014406:Tularemia / Q000276:immunology / Q000517:prevention & control*; D014613:Vaccines, Attenuated / Q000235:genetics / Q000276:immunology; D014614:Vaccines, Synthetic / Q000235:genetics / Q000276:immunology
chemical_list: D000942:Antigens, Bacterial; D001428:Bacterial Vaccines; D014613:Vaccines, Attenuated; D014614:Vaccines, Synthetic; D007371:Interferon-gamma