Center for Infectious Diseases and Vaccinology, Biodesign Institute, Arizona State University, Tempe, AZ 85287-5401.
Animal Parasitic Diseases Laboratory, the Agricultural Research Service, USDA, Beltsville, MD 20705-2359.
Avian Dis. 2020 Sep 1;64(3):254-268. doi: 10.1637/aviandiseases-D-19-00159.
A programmed self-destructive Salmonella vaccine delivery system was developed to facilitate efficient colonization in host tissues that allows release of the bacterial cell contents after lysis to stimulate mucosal, systemic, and cellular immunities against a diversity of pathogens. Adoption and modification of these technological improvements could form part of an integrated strategy for cost-effective control and prevention of infectious diseases, including those caused by parasitic pathogens. Avian coccidiosis is a common poultry disease caused by Eimeria. Coccidiosis has been controlled by medicating feed with anticoccidial drugs or administering vaccines containing low doses of virulent or attenuated Eimeria oocysts. Problems of drug resistance and nonuniform administration of these Eimeria resulting in variable immunity are prompting efforts to develop recombinant Eimeria vaccines. In this study, we designed, constructed, and evaluated a self-destructing recombinant attenuated Salmonella vaccine (RASV) lysis strain synthesizing the Eimeria tenella SO7 antigen. We showed that the RASV lysis strain χ11791(pYA5293) with a ΔsifA mutation enabling escape from the Salmonella-containing vesicle (or endosome) successfully colonized chicken lymphoid tissues and induced strong mucosal and cell-mediated immunities, which are critically important for protection against Eimeria challenge. The results from animal clinical trials show that this vaccine strain significantly increased food conversion efficiency and protection against weight gain depression after challenge with 105E. tenella oocysts with concomitant decreased oocyst output. More importantly, the programmed regulated lysis feature designed into this RASV strain promotes bacterial self-clearance from the host, lessening persistence of vaccine strains in vivo and survival if excreted, which is a critically important advantage in a vaccine for livestock animals. Our approach should provide a safe, cost-effective, and efficacious vaccine to control coccidiosis upon addition of additional protective Eimeria antigens. These improved RASVs can also be modified for use to control other parasitic diseases infecting other animal species.
一种可编程的自毁型沙门氏菌疫苗传递系统被开发出来，以促进在宿主组织中的有效定植，使细菌细胞内容物在裂解后释放，从而刺激黏膜、全身和细胞免疫，以抵抗多种病原体。采用和改进这些技术进步可以成为一种具有成本效益的控制和预防传染病的综合策略的一部分，包括由寄生虫病原体引起的传染病。禽球虫病是一种常见的家禽疾病，由艾美耳球虫引起。球虫病已通过在饲料中添加抗球虫药物或接种含有低剂量强毒或减毒艾美耳球虫卵囊的疫苗来控制。抗药性问题和这些艾美耳球虫的不均匀管理导致免疫效果不一致，这促使人们努力开发重组艾美耳球虫疫苗。在这项研究中，我们设计、构建和评估了一种自毁型重组减毒沙门氏菌疫苗（RASV）裂解株，该裂解株合成了柔嫩艾美耳球虫 SO7 抗原。我们表明，带有 ΔsifA 突变的 RASV 裂解株 χ11791(pYA5293)能够逃避含有沙门氏菌的囊泡（或内体），成功定植于鸡淋巴组织，并诱导强烈的黏膜和细胞介导免疫，这对于抵抗艾美耳球虫的挑战至关重要。动物临床试验的结果表明，该疫苗株显著提高了饲料转化率，减轻了 105E 的柔嫩艾美耳球虫卵囊攻毒后的体重减轻，同时降低了卵囊产量。更重要的是，设计到这种 RASV 株中的程序性调控裂解特征促进了细菌从宿主中的自我清除，减少了疫苗株在体内的持续存在和如果排泄时的存活，这对于家畜疫苗来说是一个至关重要的优势。我们的方法应提供一种安全、具有成本效益和有效的疫苗，以在添加额外的保护性艾美耳球虫抗原的情况下控制球虫病。这些改良的 RASV 也可以被修饰用于控制感染其他动物物种的其他寄生虫病。
