Department of Anesthesia, University of California San Francisco, San Francisco, California 94143, USA.
Microbiol Immunol. 2009 Nov;53(11):587-94. doi: 10.1111/j.1348-0421.2009.00165.x.
Virulent P. aeruginosa strains express PcrV, one of the translocational components of the type III secretion system. PcrV has been reported to be a protective antigen against lethal P. aeruginosa infection. The PcrV region, which contributes to protective immunity against P. aeruginosa infection, was investigated by using genetically engineered, truncated PcrV proteins and affinity-purified anti-PcrV antibodies against the truncated PcrV proteins. The efficacy of active and passive immunization against PcrV was tested in mice with cyclophosphamide-induced immunosuppression by intraabdominal challenge of P. aeruginosa. Active immunization with either full-length PcrV1-294 or PcrV139-294 significantly improved the survival of mice infected with P. aeruginosa, while PcrV139-258, PcrV139-234, PcrV197-294, and PcrV261-294 were not protective. These results suggest that an effective PcrV vaccine needs to contain not only the Mab166 epitope (PcrV144-257) but also the carboxyl terminal tail of PcrV. In the case of passive immunization, administration of affinity-purified anti-PcrV IgG against either PcrV1-294 or PcrV139-258 showed significantly higher efficacy against lethal P. aeruginosa infection than did original anti-PcrV IgG and Mab166. The increased efficacy of affinity-purified anti-PcrV IgG implies that more potent anti-PcrV strategies are possible. The results of this study are crucial to the development of an effective PcrV vaccine for active immunization and to an appropriate blocking anti-PcrV antibody against P. aeruginosa infection in humans.
毒力型铜绿假单胞菌菌株表达 III 型分泌系统的转位成分之一 PcrV。已有报道称 PcrV 是一种针对致死性铜绿假单胞菌感染的保护性抗原。本研究通过使用基因工程构建的、截断的 PcrV 蛋白和针对截断的 PcrV 蛋白的亲和纯化的抗 PcrV 抗体，研究了有助于对铜绿假单胞菌感染产生保护性免疫的 PcrV 区域。通过腹腔内铜绿假单胞菌攻击，用环磷酰胺诱导免疫抑制的小鼠来检测针对 PcrV 的主动和被动免疫的功效。全长 PcrV1-294 或 PcrV139-294 的主动免疫显著提高了感染铜绿假单胞菌的小鼠的存活率，而 PcrV139-258、PcrV139-234、PcrV197-294 和 PcrV261-294 则没有保护作用。这些结果表明，有效的 PcrV 疫苗不仅需要包含 Mab166 表位（PcrV144-257），还需要包含 PcrV 的羧基末端尾部。在被动免疫的情况下，针对 PcrV1-294 或 PcrV139-258 的亲和纯化的抗 PcrV IgG 的给药显示出对致死性铜绿假单胞菌感染的显著更高功效，优于原始抗 PcrV IgG 和 Mab166。亲和纯化的抗 PcrV IgG 的功效增加意味着可能存在更有效的抗 PcrV 策略。本研究的结果对于开发针对铜绿假单胞菌感染的主动免疫的有效 PcrV 疫苗以及针对人类铜绿假单胞菌感染的适当阻断抗 PcrV 抗体至关重要。
