Deciphering the protective role of adaptive immunity to CHIKV/IRES a novel candidate vaccine against Chikungunya in the A129 mouse model.
Deciphering the protective role of adaptive immunity to CHIKV/IRES a novel candidate vaccine against Chikungunya in the A129 mouse model.
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DOI：
10.1016/j.vaccine.2013.05.059
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发表时间：
2013-07-18
期刊：
影响因子：
5.5
通讯作者：
Osorio, Jorge E.
中科院分区：
文献类型：
--
作者：
Chu, Haiyan;Das, Subash C.;Fuchs, Jeremy F.;Suresh, M.;Weaver, Scott C.;Stinchcomb, Dan T.;Partidos, Charalambos D.;Osorio, Jorge E.
基孔肯雅病毒（CHIKV）是一种蚊媒甲病毒，最近在非洲重新出现，并蔓延到印度洋岛屿、印度次大陆和东南亚。病毒携带者也向西半球输入了CHIKV病毒，这突出了CHIKV病毒在公共卫生中的重要性。除了可持续数月或数年的关节炎疾病的巨大负担外，流行病学研究估计病死率约为0.1%，主要来自老年患者的神经系统疾病。目前还没有获得许可的疫苗或有效的疗法来预防或治疗人类CHIKV感染。我们开发了一种奇kv活疫苗（CHIKV/IRES），它在小鼠模型中高度减毒但具有免疫原性，并且不能在蚊子细胞中复制。在这项研究中，我们试图破译由CHIKV/IRES引发的适应性免疫在抵抗野生型CHIKV感染中的作用。单剂量疫苗有效激活T细胞，在免疫后第10天达到扩增高峰，并诱导CD4+和CD8+ T细胞在CHIKV/IRES再刺激后产生IFN-γ、TNF-α和IL-2。CHIKV/ ires免疫CD4+或CD8+ T细胞的过继转移不具有抵抗CHIKV- lr攻击的保护作用。相比之下，抗chikv /IRES免疫血清被动免疫提供了保护，并建立了最低保护性中和抗体滴度的相关性。总的来说，我们的研究结果证明了CHIKV/IRES疫苗的免疫原性潜力，并强调了中和抗体在预防急性CHIKV感染方面发挥的重要作用。
Chikungunya virus (CHIKV), a mosquito-borne alphavirus, recently re-emerged in Africa and spread to islands in the Indian Ocean, the Indian subcontinent, and to South East Asia. Viremic travelers have also imported CHIKV to the Western hemisphere highlighting the importance of CHIKV in public health. In addition to the great burden of arthralgic disease, which can persist for months or years, epidemiologic studies have estimated case-fatality rates of ~0.1%, principally from neurologic disease in older patients. There are no licensed vaccines or effective therapies to prevent or treat human CHIKV infections. We have developed a live CHIKV vaccine (CHIKV/IRES) that is highly attenuated yet immunogenic in mouse models, and is incapable of replicating in mosquito cells. In this study we sought to decipher the role of adaptive immunity elicited by CHIKV/IRES in protection against wild-type CHIKV infection. A single dose of vaccine effectively activated T cells with an expansion peak on day 10 post immunization and elicited memory CD4+ and CD8+ T cells that produced IFN-γ, TNF-α and IL-2 upon restimulation with CHIKV/IRES. Adoptive transfer of CHIKV/IRES-immune CD4+ or CD8+ T cells did not confer protection against wtCHIKV-LR challenge. By contrast, passive immunization with anti-CHIKV/IRES immune serum provided protection, and a correlate of a minimum protective neutralizing antibody titer was established. Overall, our findings demonstrate the immunogenic potential of the CHIKV/IRES vaccine and highlight the important role that neutralizing antibodies play in protection against an acute CHIKV infection.
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影响因子：
11.1
作者：
Kam, Yiu-Wing;Lum, Fok-Moon;Teo, Teck-Hui;Lee, Wendy W. L.;Simarmata, Diane;Harjanto, Sumitro;Chua, Chong-Long;Chan, Yoke-Fun;Wee, Jin-Kiat;Chow, Angela;Lin, Raymond T. P.;Leo, Yee-Sin;Le Grand, Roger;Sam, I-Ching;Tong, Joo-Chuan;Roques, Pierre;Wiesmueller, Karl-Heinz;Renia, Laurent;Roetzschke, Olaf;Ng, Lisa F. P.
通讯作者：
Ng, Lisa F. P.
DOI：
10.1093/infdis/jis033
发表时间：
2012-04-01
期刊：
The Journal of infectious diseases
影响因子：
--
作者：
Kam YW;Simarmata D;Chow A;Her Z;Teng TS;Ong EK;Rénia L;Leo YS;Ng LF
通讯作者：
Ng LF
DOI：
10.1016/j.trstmh.2004.03.013
发表时间：
2005-02-01
影响因子：
2.2
作者：
Laras, K;Sukri, NC;Corwin, AL
通讯作者：
Corwin, AL
影响因子：
6.7
作者：
Plante K;Wang E;Partidos CD;Weger J;Gorchakov R;Tsetsarkin K;Borland EM;Powers AM;Seymour R;Stinchcomb DT;Osorio JE;Frolov I;Weaver SC
通讯作者：
Weaver SC
影响因子：
4.4
作者：
Hoarau, Jean-Jacques;Bandjee, Marie-Christine Jaffar;Gasque, Philippe
通讯作者：
Gasque, Philippe