A virus-like particle based bivalent vaccine confers dual protection against enterovirus 71 and coxsackievirus A16 infections in mice
A virus-like particle based bivalent vaccine confers dual protection against enterovirus 71 and coxsackievirus A16 infections in mice
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基于病毒样颗粒的二价疫苗可为小鼠提供针对肠道病毒 71 和柯萨奇病毒 A16 感染的双重保护
DOI：
10.1016/j.vaccine.2014.06.025
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发表时间：
2014-07-23
期刊：
影响因子：
5.5
通讯作者：
Huang, Zhong
中科院分区：
文献类型：
--
作者：
Ku, Zhiqiang;Liu, Qingwei;Huang, Zhong
肠道病毒71型（EV71）和柯萨奇病毒A16型（CA16）是导致亚太地区流行的手足口病的罪魁祸首，在幼儿中造成大量发病率和死亡率。这两种病毒的共同循环和共同感染突出了同时开发针对这两种病毒的疫苗的重要性和紧迫性。本文报道了由EV71和CA16病毒样颗粒（VLPs）组成的二价联合疫苗的免疫原性和保护效果。我们发现，单价EV71或CA16- vlps诱导的血清抗体对同型病毒表现出有效的中和作用，但对异型病毒几乎没有作用，而针对二价疫苗制剂的抗血清能够有效地中和EV71和CA16，这表明在诱导病毒特异性中和抗体的能力方面，两种抗原之间不存在免疫干扰。单价VLP疫苗的被动免疫保护小鼠免受同型病毒的攻击，但对异型感染不起作用。令人惊讶的是，在单特异性抗ca16 VLP血清被动转移的小鼠中观察到疾病的抗体依赖性增强（ADE），随后用EV71攻毒。相比之下，二价VLP疫苗对EV71或CA16的致命攻击具有充分的保护作用，从而消除了ADE的可能性。综上所述，我们的研究结果首次表明，二价VLP方法代表了一种安全有效的EV71和CA16疫苗策略。(C) 2014 Elsevier Ltd.版权所有。
Enterovirus 71(EV71) and coxsackievirus A16 (CA16) are responsible for hand, foot and mouth disease which has been prevalent in Asia-Pacific regions, causing significant morbidity and mortality in young children. Co-circulation of and co-infection by both viruses underscores the importance and urgency of developing vaccines against both viruses simultaneously. Here we report the immunogenicity and protective efficacy of a bivalent combination vaccine comprised of EV71 and CA16 virus-like particles (VLPs). We show that monovalent EV71- or CA16-VLPs-elicited serum antibodies exhibited potent neutralization effect on the homotypic virus but little or no effect on the heterotypic one, whereas the antisera against the bivalent vaccine formulation were able to efficiently neutralize both EV71 and CA16, indicating there is no immunological interference between the two antigens with respect to their ability to induce virus-specific neutralizing antibodies. Passive immunization with monovalent VLP vaccines protected mice against a homotypic virus challenge but not heterotypic infection. Surprisingly, antibody-dependent enhancement (ADE) of disease was observed in mice passively transferred with mono-specific anti-CA16 VLP sera and subsequently challenged with EV71. In contrast, the bivalent VLP vaccine conferred full protection against lethal challenge by either EV71 or CA16, thus eliminating the potential of ADE. Taken together, our results demonstrate for the first time that the bivalent VLP approach represents a safe and efficacious vaccine strategy for both EV71 and CA16. (C) 2014 Elsevier Ltd. All rights reserved.