PRIMING WITH RECOMBINANT INFLUENZA-VIRUS FOLLOWED BY ADMINISTRATION OF RECOMBINANT VACCINIA VIRUS INDUCES CD8+ T-CELL-MEDIATED PROTECTIVE IMMUNITY AGAINST MALARIA
PRIMING WITH RECOMBINANT INFLUENZA-VIRUS FOLLOWED BY ADMINISTRATION OF RECOMBINANT VACCINIA VIRUS INDUCES CD8+ T-CELL-MEDIATED PROTECTIVE IMMUNITY AGAINST MALARIA
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DOI：
10.1073/pnas.90.11.5214
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发表时间：
1993-06-01
影响因子：
11.1
通讯作者：
ZAVALA, F
中科院分区：
文献类型：
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作者：
LI, SQ;RODRIGUES, M;ZAVALA, F
表达外源抗原的活载体已被用来诱导对几种病原体的免疫。然而，对于强毒的鼠类疟疾寄生虫约氏疟原虫，使用表达该寄生虫环子孢子蛋白的重组痘苗病毒、伪狂犬病病毒或沙门氏菌未能诱导保护。我们构建了一种表达约氏疟原虫环子孢子蛋白表位的重组流感病毒，该表位可被CD8+T细胞识别，并证明该载体可诱导针对该外源表位的I类主要组织相容性复合体限制性细胞毒T细胞。用这种重组流感病毒免疫小鼠，然后用表达整个环子孢子蛋白的重组痘苗病毒免疫小鼠，可以诱导对子孢子诱导的疟疾的保护性免疫。免疫顺序似乎是至关重要的，因为注射重组痘苗病毒的初级疫苗，然后注射重组流感病毒的加强疫苗，都不能产生保护作用。这些重组病毒的免疫保护作用主要是由CD8+T细胞介导的，因为抗CD8单抗处理会使小鼠丧失抗疟疾免疫。使用不同的活载体作为引发剂和加强剂，对免疫应答有协同作用，并可能代表一种有效的一般策略，以诱导对微生物病原体关键抗原的保护性免疫应答。
Live vectors expressing foreign antigens have been used to induce immunity against several pathogens. However, for the virulent rodent malaria parasite Plasmodium yoelii, the use of recombinant vaccinia virus, pseudorabies virus, or Salmonella, expressing the circumsporozoite protein of this parasite, failed to induce protection. We generated a recombinant influenza virus expressing an epitope from the circumsporozoite protein of P. yoelii known to be recognized by CD8+ T cells and demonstrated that this vector induced class I major histocompatibility complex-restricted cytotoxic T cells against this foreign epitope. Immunization of mice with this recombinant influenza virus, followed by a recombinant vaccinia virus expressing the entire circumsporozoite protein, induced protective immunity against sporozoite-induced malaria. The sequence of immunization appears to be crucial, since a primer injection with recombinant vaccinia virus, followed by a booster injection with recombinant influenza virus, failed to induce protection. The protection induced by immunization with these recombinant viruses is mostly mediated by CD8+ T cells, as treatment of mice with anti-CD8 monoclonal antibody abolishes the anti-malarial immunity. The use of different live vectors for primer and booster injections has a synergistic effect on the immune response and might represent an effective general strategy for eliciting protective immune responses to key antigens of microbial pathogens.