Tularemia是一种高度传染性疾病,由感染土拉氏杆菌(Ft)引起,一种致病性细胞内革兰阴性细菌,感染多种动物,导致人类严重疾病和死亡,让它成为公众健康问题。疫苗是预防暴aremia的最有效方法。然而,由于安全问题,到目前为止还没有食品和药物管理局(FDA)批准的Ft疫苗。在这里,Ft的三种膜蛋白,Tul4,OmpA,还有FopA,和分子伴侣,DnaK,使用多因子保护性抗原平台鉴定为潜在的保护性抗原。此外,重组DnaK,福帕,和Tul4蛋白疫苗引发高水平的IgG抗体,但不能抵御攻击.相比之下,保护性免疫是由编码Tul4,OmpA的复制缺陷型人5型腺病毒(Ad5)引起的,福帕,和DnaK蛋白(Ad5-Tul4,Ad5-OmpA,Ad5-FopA,和Ad5-DnaK)单次免疫后,所有基于Ad5的疫苗都刺激了Th1偏向的免疫反应。此外,使用prime-boost策略的Ad5-Tul4的肌内和鼻内疫苗接种有效地消除了Ft肺,脾脏和肝脏定植,并提供近80%的保护,对抗Ft活疫苗株(LVS)的鼻内攻击。只有肌肉内,不是鼻内疫苗,Ad5-Tul4保护小鼠免受腹膜内攻击。这项研究提供了对由亚基或腺病毒载体疫苗提供的针对Ft的保护性免疫的全面比较,并表明用Ad5-Tul4进行粘膜疫苗接种可能产生针对粘膜感染的理想保护功效。而肌肉内接种疫苗对腹膜内暴aremia提供了更大的整体保护。
Tularemia is a highly contagious disease caused by infection with Francisella tularensis (Ft), a pathogenic intracellular gram-negative bacterium that infects a wide range of animals and causes severe disease and death in people, making it a public health concern. Vaccines are the most effective way to prevent tularemia. However, there are no Food and Drug Administration (FDA)-approved Ft vaccines thus far due to safety concerns. Herein, three membrane proteins of Ft, Tul4, OmpA, and FopA, and a molecular chaperone, DnaK, were identified as potential protective antigens using a multifactor protective antigen platform. Moreover, the recombinant DnaK, FopA, and Tul4 protein vaccines elicited a high level of IgG antibodies but did not protect against challenge. In contrast, protective immunity was elicited by a replication-defective human type 5 adenovirus (Ad5) encoding the Tul4, OmpA, FopA, and DnaK proteins (Ad5-Tul4, Ad5-OmpA, Ad5-FopA, and Ad5-DnaK) after a single immunization, and all Ad5-based vaccines stimulated a Th1-biased immune response. Moreover, intramuscular and intranasal vaccination with Ad5-Tul4 using the prime-boost strategy effectively eliminated Ft lung, spleen and liver colonization and provided nearly 80% protection against intranasal challenge with the Ft live vaccine strain (LVS). Only intramuscular, not intranasal vaccination, with Ad5-Tul4 protected mice from intraperitoneal challenge. This study provides a comprehensive comparison of protective immunity against Ft provided by subunit or adenovirus-vectored vaccines and suggests that mucosal vaccination with Ad5-Tul4 may yield desirable protective efficacy against mucosal infection, while intramuscular vaccination offers greater overall protection against intraperitoneal tularemia.