Lafontaine Eric R, Chen Zhenhai, Huertas-Diaz Maria Cristina, Dyke Jeremy S, Jelesijevic Tomislav P, Michel Frank, Hogan Robert J, He Biao
Department of Infectious Diseases, University of Georgia College of Veterinary Medicine, Athens, GA 30602, USA.
Department of Veterinary Biosciences and Diagnostic Imaging, University of Georgia College of Veterinary Medicine, Athens, GA 30602, USA.
Vaccine X. 2018 Dec 22;1:100002. doi: 10.1016/j.jvacx.2018.100002. eCollection 2019 Apr 11.
and are the causative agents of glanders and melioidosis, respectively. There is no vaccine to protect against these highly-pathogenic and intrinsically antibiotic-resistant bacteria, and there is concern regarding their use as biological warfare agents. For these reasons, and are classified as Tier 1 organisms by the U.S. Federal Select Agent Program and the availability of effective countermeasures represents a critical unmet need.
Vaccines (subunit and vectored) containing the surface-exposed passenger domain of the conserved autotransporter protein BatA were administered to BALB/c mice and the vaccinated animals were challenged with lethal doses of wild-type and strains via the aerosol route. Mice were monitored for signs of illness for a period of up to 40 days post-challenge and tissues from surviving animals were analyzed for bacterial burden at study end-points.
A single dose of recombinant Parainfluenza Virus 5 (PIV5) expressing BatA provided 74% and 60% survival in mice infected with and , respectively. Vaccination with PIV5-BatA also resulted in complete bacterial clearance from the lungs and spleen of 78% and 44% of animals surviving lethal challenge with , respectively. In contrast, all control animals vaccinated with a PIV5 construct expressing an irrelevant antigen and infected with were colonized in those tissues.
Our study indicates that the autotransporter BatA is a valuable target for developing countermeasures against and and demonstrates the utility of the PIV5 viral vaccine delivery platform to elicit cross-protective immunity against the organisms.
[细菌名称1]和[细菌名称2]分别是鼻疽和类鼻疽的病原体。目前尚无针对这些高致病性且具有内在抗生素抗性的细菌的疫苗,人们担心它们会被用作生物战剂。出于这些原因,[细菌名称1]和[细菌名称2]被美国联邦选择制剂计划列为1级生物制剂,开发有效的应对措施是一个关键的未满足需求。
将含有保守的自转运蛋白BatA表面暴露的乘客结构域的疫苗(亚单位疫苗和载体疫苗)接种到BALB/c小鼠体内,然后通过气溶胶途径用致死剂量的野生型[细菌名称1]和[细菌名称2]菌株对接种疫苗的动物进行攻击。在攻击后长达40天的时间内监测小鼠的疾病症状,并在研究终点分析存活动物组织中的细菌负荷。
单剂量表达BatA的重组副流感病毒5(PIV5)分别使感染[细菌名称1]和[细菌名称2]的小鼠存活率达到74%和60%。用PIV5-BatA疫苗接种还分别使78%和44%在致死性攻击中存活的动物的肺部和脾脏中的细菌被完全清除。相比之下,所有接种表达无关抗原的PIV5构建体并感染[细菌名称1]的对照动物在这些组织中都被细菌定植。
我们的研究表明,自转运蛋白BatA是开发针对[细菌名称1]和[细菌名称2]的应对措施的有价值靶点,并证明了PIV5病毒疫苗递送平台在引发针对这些生物的交叉保护性免疫方面的效用。