Immunization with virus-like particles of enterovirus 71 elicits potent immune responses and protects mice against lethal, challenge
Immunization with virus-like particles of enterovirus 71 elicits potent immune responses and protects mice against lethal, challenge
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DOI：
10.1016/j.vaccine.2008.01.058
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发表时间：
2008-03-28
期刊：
影响因子：
5.5
通讯作者：
Hu, Yu-Chen
中科院分区：
文献类型：
--
作者：
Chung, Yao-Chi;Ho, Mei-Shang;Hu, Yu-Chen
肠道病毒71型(EV71)是手足口病季节性流行的病原体，在幼儿中引起暴发，并导致大量死亡。为了开发疫苗，我们生产并纯化了在外观、衣壳结构和蛋白质组成上与正宗病毒相似的EV71病毒样颗粒(VLP)。在这项研究中，我们进一步评估了VLP作为疫苗的潜力，通过比较纯化的VLP、变性的VLP和热灭活的EV71病毒诱导的体液和细胞免疫应答。EV71VLP免疫BALB/c小鼠后，可产生较高的总免疫球蛋白滴度和中和滴度，诱导产生强烈的体液免疫应答。VLP免疫小鼠脾细胞有明显的细胞增殖，刺激后产生高水平的干扰素-γ、IL-2和IL-4，提示VLP免疫可诱导Th1和Th2免疫应答。更重要的是，母鼠的VLP免疫为新生小鼠提供了保护(存活率高达%)，使其免受致死(1000LD50)病毒的攻击。与VLP免疫相比，变性VLP和热灭活EV71诱导的总免疫球蛋白和细胞免疫应答水平相当，但对新生小鼠的中和效价和保护作用较弱。这些数据共同表明了保留VLP结构的重要性，并暗示了VLP作为疫苗预防EV71感染的潜力。(C)2008爱思唯尔有限公司。保留所有权利。
Enterovirus 71 (EV71) is an etiologic agent responsible for seasonal epidemics of hand-foot-and-mouth disease and causes outbreaks with significant mortality among young children. To develop the vaccine, we have produced and purified the EV71 virus-like particle (VLP) that resembles the authentic virus in appearance, capsid structure and protein composition. In this study, we further evaluated the potential of VLP as a vaccine by comparing the humoral and cellular immune responses elicited by the purified VLP, denatured VLP and heat-inactivated EV71 virus. After immunization of BALB/c mice, EV71 VLP induced potent and tong-tasting humoral immune responses as evidenced by the high total IgG titer and neutralization titer. The splenocytes collected from the VLP-immunized mice exhibited significant cell proliferation and produced high levels of IFN-gamma, IL-2 and IL-4 after stimulation, indicating the induction of Th1 and Th2 immune responses by VLP immunization. More importantly, the VLP immunization of mother mice conferred protection (survival rate up to 89%) to neonatal mice against the Lethal (1000 LD50) viral challenge. Compared with the VLP immunization, immunization with denatured VLP and heat-inactivated EV71 elicited tower neutralization titers and conferred less effective protection to newborn mice, although they induced comparable Levels of total IgG and cellular immune responses. These data collectively indicate the importance of the preservation of VLP structure and implicate the potential of VLP as a vaccine to prevent EV71 infection. (C) 2008 Elsevier Ltd. All rights reserved.