由活重组减毒沙门氏菌疫苗株递送的鼠疫耶尔森菌多种抗原可引发针对鼠疫的保护性免疫。
Multiple antigens of Yersinia pestis delivered by live recombinant attenuated Salmonella vaccine strains elicit protective immunity against plague.
作者信息
Sanapala Shilpa, Rahav Hannah, Patel Hetal, Sun Wei, Curtiss Roy
机构信息
Center for Infectious Disease and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
Center for Infectious Disease and Vaccinology, The Biodesign Institute, Arizona State University, Tempe, AZ 85287, USA.
出版信息
Vaccine. 2016 May 5;34(21):2410-2416. doi: 10.1016/j.vaccine.2016.03.094. Epub 2016 Apr 6.
Abstract
Based on our improved novel Salmonella vaccine delivery platform, we optimized the recombinant attenuated Salmonella typhimurium vaccine (RASV) χ12094 to deliver multiple Yersinia pestis antigens. These included LcrV196 (amino acids, 131-326), Psn encoded on pYA5383 and F1 encoded in the chromosome, their synthesis did not cause adverse effects on bacterial growth. Oral immunization with χ12094(pYA5383) simultaneously stimulated high antibody titers to LcrV, Psn and F1 in mice and presented complete protection against both subcutaneous (s.c.) and intranasal (i.n.) challenges with high lethal doses of Y. pestis CO92. Moreover, no deaths or other disease symptoms were observed in SCID mice orally immunized with χ12094(pYA5383) over a 60-day period. Therefore, the trivalent S. typhimurium-based live vaccine shows promise for a next-generation plague vaccine.
摘要
基于我们改进的新型沙门氏菌疫苗递送平台，我们优化了重组减毒鼠伤寒沙门氏菌疫苗（RASV）χ12094，以递送多种鼠疫耶尔森菌抗原。这些抗原包括LcrV196（氨基酸131 - 326）、pYA5383编码的Psn和染色体中编码的F1，它们的合成不会对细菌生长造成不利影响。用χ12094(pYA5383)进行口服免疫可同时刺激小鼠体内针对LcrV、Psn和F1产生高抗体滴度，并对高致死剂量的鼠疫耶尔森菌CO92的皮下（s.c.）和鼻内（i.n.）攻击提供完全保护。此外，在60天的时间里，用χ12094(pYA5383)口服免疫的SCID小鼠未观察到死亡或其他疾病症状。因此，基于鼠伤寒沙门氏菌的三价活疫苗有望成为下一代鼠疫疫苗。
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