title: Live attenuated Francisella novicida vaccine protects against Francisella tularensis pulmonary challenge in rats and non-human primates.
abstract: Francisella tularensis causes the disease tularemia. Human pulmonary exposure to the most virulent form, F. tularensis subsp. tularensis (Ftt), leads to high morbidity and mortality, resulting in this bacterium being classified as a potential biothreat agent. However, a closely-related species, F. novicida, is avirulent in healthy humans. No tularemia vaccine is currently approved for human use. We demonstrate that a single dose vaccine of a live attenuated F. novicida strain (Fn iglD) protects against subsequent pulmonary challenge with Ftt using two different animal models, Fischer 344 rats and cynomolgus macaques (NHP). The Fn iglD vaccine showed protective efficacy in rats, as did a Ftt iglD vaccine, suggesting no disadvantage to utilizing the low human virulent Francisella species to induce protective immunity. Comparison of specific antibody profiles in vaccinated rat and NHP sera by proteome array identified a core set of immunodominant antigens in vaccinated animals. This is the first report of a defined live attenuated vaccine that demonstrates efficacy against pulmonary tularemia in a NHP, and indicates that the low human virulence F. novicida functions as an effective tularemia vaccine platform.
authors.affiliation: South Texas Center for Emerging Infectious Diseases and Department of Biology, University of Texas San Antonio, San Antonio, Texas, United States of America.
authors.forename: Ping
authors.initials: P
authors.lastname: Chu
authors.affiliation: South Texas Center for Emerging Infectious Diseases and Department of Biology, University of Texas San Antonio, San Antonio, Texas, United States of America.
authors.forename: Aimee L
authors.initials: AL
authors.lastname: Cunningham
authors.affiliation: South Texas Center for Emerging Infectious Diseases and Department of Biology, University of Texas San Antonio, San Antonio, Texas, United States of America.
authors.forename: Jieh-Juen
authors.initials: JJ
authors.lastname: Yu
authors.affiliation: South Texas Center for Emerging Infectious Diseases and Department of Biology, University of Texas San Antonio, San Antonio, Texas, United States of America.
authors.forename: Jesse Q
authors.initials: JQ
authors.lastname: Nguyen
authors.affiliation: South Texas Center for Emerging Infectious Diseases and Department of Biology, University of Texas San Antonio, San Antonio, Texas, United States of America.
authors.forename: Jeffrey R
authors.initials: JR
authors.lastname: Barker
authors.affiliation: Infectious Disease Research Center, Colorado State University, Fort Collins, Colorado, United States of America.
authors.forename: C Rick
authors.initials: CR
authors.lastname: Lyons
authors.affiliation: Applied Life Sciences & Toxicology, Lovelace Respiratory Research Institute, Albuquerque, New Mexico, United States of America.
authors.forename: Julie
authors.initials: J
authors.lastname: Wilder
authors.affiliation: Applied Life Sciences & Toxicology, Lovelace Respiratory Research Institute, Albuquerque, New Mexico, United States of America.
authors.forename: Michelle
authors.initials: M
authors.lastname: Valderas
authors.affiliation: Applied Life Sciences & Toxicology, Lovelace Respiratory Research Institute, Albuquerque, New Mexico, United States of America.
authors.forename: Robert L
authors.initials: RL
authors.lastname: Sherwood
authors.affiliation: South Texas Center for Emerging Infectious Diseases and Department of Biology, University of Texas San Antonio, San Antonio, Texas, United States of America.
authors.forename: Bernard P
authors.initials: BP
authors.lastname: Arulanandam
authors.affiliation: South Texas Center for Emerging Infectious Diseases and Department of Biology, University of Texas San Antonio, San Antonio, Texas, United States of America.
authors.forename: Karl E
authors.initials: KE
authors.lastname: Klose
mesh_terms: D000818:Animals; D001428:Bacterial Vaccines / Q000276:immunology*; D005604:Francisella tularensis; D016056:Immunodominant Epitopes / Q000276:immunology*; D008252:Macaca fascicularis; D051379:Mice; D023421:Models, Animal; D011916:Rats, Inbred F344; D014406:Tularemia / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control; D014611:Vaccination; D014613:Vaccines, Attenuated / Q000276:immunology
chemical_list: D001428:Bacterial Vaccines; D016056:Immunodominant Epitopes; D014613:Vaccines, Attenuated