Live Attenuated Francisella novicida Vaccine Protects against Francisella tularensis Pulmonary Challenge in Rats and Non-human Primates

PLoS Pathogens

Julie Wilder¹  Michelle Valderas¹  Robert L. Sherwood¹  C. Rick Lyons²  Aimee L. Cunningham³  Jesse Q. Nguyen³  Jieh-Juen Yu³  Jeffrey R. Barker³  Karl E. Klose³  Bernard P. Arulanandam³  Ping Chu³ 

[1] Applied Life Sciences & Toxicology, Lovelace Respiratory Research Institute, Albuquerque, New Mexico, United States of America;Infectious Disease Research Center, Colorado State University, Fort Collins, Colorado, United States of America;South Texas Center for Emerging Infectious Diseases and Department of Biology, University of Texas San Antonio, San Antonio, Texas, United States of America

关键词: Vaccination;    immunization;    Francisella tularensis;    Macaque;    Tularemia;    Vaccines;    Francisella;    Antibodies;    Enzyme-linked immunoassays;   

DOI  :  10.1371/journal.ppat.1004439

学科分类：生物科学（综合）

来源: Public Library of Science

【 摘 要 】

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.

【 授权许可】

CC BY