Chu Ping, Cunningham Aimee L, Yu Jieh-Juen, Nguyen Jesse Q, Barker Jeffrey R, Lyons C Rick, Wilder Julie, Valderas Michelle, Sherwood Robert L, Arulanandam Bernard P, Klose Karl E
South Texas Center for Emerging Infectious Diseases and Department of Biology, University of Texas San Antonio, San Antonio, Texas, United States of America.
Infectious Disease Research Center, Colorado State University, Fort Collins, Colorado, United States of America.
PLoS Pathog. 2014 Oct 23;10(10):e1004439. doi: 10.1371/journal.ppat.1004439. eCollection 2014 Oct.
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.
土拉弗朗西斯菌可引发兔热病。人类肺部暴露于毒性最强的菌株——土拉弗朗西斯菌土拉亚种（Ftt）会导致高发病率和死亡率，因此该细菌被列为潜在的生物威胁因子。然而，与之密切相关的新凶手弗朗西斯菌在健康人类中无致病性。目前尚无获批用于人类的兔热病疫苗。我们证明，使用两种不同的动物模型——Fischer 344大鼠和食蟹猕猴（非人灵长类动物，NHP），单剂量的减毒活新凶手弗朗西斯菌菌株（Fn iglD）疫苗可抵御随后的Ftt肺部攻击。Fn iglD疫苗在大鼠中显示出保护效力，Ftt iglD疫苗也是如此，这表明利用低人类致病性的弗朗西斯菌属物种诱导保护性免疫并无劣势。通过蛋白质组芯片比较接种疫苗的大鼠和NHP血清中的特异性抗体谱，确定了接种疫苗动物中的一组核心免疫显性抗原。这是关于一种明确的减毒活疫苗的首次报道，该疫苗在NHP中显示出对兔热病的肺部感染有效，并表明低人类致病性的新凶手弗朗西斯菌可作为一种有效的兔热病疫苗平台。
Zotero 插件
