Superior antimalarial immunity after vaccination with late liver stage-arresting genetically attenuated parasites.
Superior antimalarial immunity after vaccination with late liver stage-arresting genetically attenuated parasites.
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DOI：
10.1016/j.chom.2011.05.008
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发表时间：
2011-06-16
影响因子：
30.3
通讯作者：
Harty JT
中科院分区：
文献类型：
--
作者：
Butler NS;Schmidt NW;Vaughan AM;Aly AS;Kappe SH;Harty JT
虽然亚单位疫苗在临床试验中显示出部分功效，但辐射减毒子孢子（RAS）仍然是人类疫苗接种者抗疟原虫感染的灭菌保护的“金标准”。通过基因缺失设计的遗传减毒寄生虫（GAP）可以克服产生RAS所需的广泛随机DNA损伤引起的免疫原性和复制的变异性，以在肝脏发育期间的定义点进行阻滞。在这里，我们证明的原则，后期肝脏阶段逮捕GAP诱导更大和更广泛的CD8 T细胞的反应，提供上级保护近交系和远交系小鼠相比，RAS或早期逮捕GAP免疫。当通过预防相关的皮内或皮下途径给药时，晚期肝脏阻滞GAP还产生高水平的跨阶段和跨物种保护和完全保护。总的来说，我们的研究结果强调了肝晚期阻滞GAP作为广泛保护性下一代减毒活疟疾疫苗的潜在效用，并支持其作为鉴定抗原以产生跨阶段保护的强大模型的潜力。
While subunit vaccines have shown partial efficacy in clinical trials, radiation-attenuated-sporozoites (RAS) remain the “gold-standard” for sterilizing protection against Plasmodium-infection in human vaccinees. The variability in immunogenicity and replication introduced by the extensive, random DNA damage necessary to generate RAS could be overcome by genetically attenuated parasites (GAP) designed via gene deletion to arrest at defined points during liver-stage development. Here, we demonstrate the principle that late-liver-stage arresting GAP induce larger and broader CD8 T cell responses that provide superior protection in inbred and outbred mice compared to RAS or early-arresting GAP immunizations. Late-liver-stage arresting GAP also engender high-levels of cross-stage and cross-species protection and complete protection when administered by translationally-relevant intradermal or subcutaneous routes. Collectively, our results underscore the potential utility of late-liver stage arresting GAP as broadly protective next-generation live-attenuated malaria vaccines and support their potential as a powerful model for identifying antigens to generate cross-stage protection.
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影响因子：
64.5
作者：
Kaech, SM;Hemby, S;Ahmed, R
通讯作者：
Ahmed, R
影响因子：
3.6
作者：
Aly, Ahmed S. I.;Mikolajczak, Sebastian A.;Rivera, Hilda Silva;Camargo, Nelly;Jacobs-Lorena, Vanessa;Labaied, Mehdi;Coppens, Isabelle;Kappe, Stefan H. I.
通讯作者：
Kappe, Stefan H. I.
影响因子：
6.7
作者：
Cockburn IA;Chen YC;Overstreet MG;Lees JR;van Rooijen N;Farber DL;Zavala F
通讯作者：
Zavala F
影响因子：
15.9
作者：
Crompton, Peter D.;Pierce, Susan K.;Miller, Louis H.
通讯作者：
Miller, Louis H.
DOI：
10.4269/ajtmh.1975.24.397
发表时间：
1975-01-01
影响因子：
3.3
作者：
CLYDE, DF;MCCARTHY, VC;WOODWARD, WE
通讯作者：
WOODWARD, WE