Antibodies are not required to a protective immune response against dengue virus elicited in a mouse encephalitis model

Antibodies are not required to a protective immune response against dengue virus elicited in a mouse encephalitis model
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DOI:
10.1016/j.virol.2015.10.006
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发表时间:
2016-01-01
期刊:
影响因子:
3.7
通讯作者:
de Souza Ferreira, Luis Carlos
de Souza Ferreira, Luis Carlos
中科院分区:
医学3区
文献类型:
--
作者:
Amorim, Jaime Henrique;dos Santos Alves, Rubens Prince;de Souza Ferreira, Luis Carlos

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产生中和抗体被认为是控制登革病毒(DENV)感染的先决条件。然而,T淋巴细胞也被证明在保护性免疫状态中是重要的。为了研究体液和细胞免疫应答在DENV免疫中的贡献,我们使用了一种实验模型,其中使用非致死性DENV 2毒株(ACS 46)颅内致敏Balb/C小鼠,所述小鼠产生针对致死性DENV 2毒株(JHA 1)的保护性免疫。引发的小鼠产生了主要针对非结构蛋白的免疫特异性抗体和CD 8(+)T细胞应答。来自受保护小鼠的免疫血清不赋予用JHA 1菌株攻击的幼稚小鼠被动保护。相比之下,CD 4(+)和CD 8(+)T淋巴细胞的耗竭显著降低了用JHA 1菌株攻击的ACS 46致敏小鼠的存活率。总的来说,本研究中提出的结果表明,靶向非结构蛋白的细胞免疫应答是开发登革热疫苗的一种有前途的方法。(C)2015 Elsevier Inc. All rights reserved.
Generating neutralizing antibodies have been considered a prerequisite to control dengue virus (DENV) infection. However, T lymphocytes have also been shown to be important in a protective immune state. In order to investigate the contribution of both humoral and cellular immune responses in DENV immunity, we used an experimental model in which a non-lethal DENV2 strain (ACS46) is used to intracranially prime Balb/C mice which develop protective immunity against a lethal DENV2 strain (JHA1). Primed mice generated envelope-specific antibodies and CD8(+) T cell responses targeting mainly non-structural proteins. Immune sera from protected mice did not confer passive protection to naive mice challenged with the JHA1 strain. In contrast, depletion of CD4(+) and CD8(+) T lymphocytes significantly reduced survival of ACS46-primed mice challenged with the JHA1 strain. Collectively, results presented in this study show that a cellular immune response targeting non-structural proteins are a promising way in vaccine development against dengue. (C) 2015 Elsevier Inc. All rights reserved.