Zika virus-like particle (VLP) based vaccine.
Zika virus-like particle (VLP) based vaccine.
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DOI：
10.1371/journal.pntd.0005608
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发表时间：
2017-05
影响因子：
3.8
通讯作者：
Galarza JM
中科院分区：
文献类型：
--
作者：
Boigard H;Alimova A;Martin GR;Katz A;Gottlieb P;Galarza JM
新出现的蚊子传播的寨卡病毒构成了一个重大的公共挑战，因为它能够导致重大的出生缺陷和神经系统疾病。性传播的影响尚不清楚，但引起了对病毒传播的进一步关注。目前还没有具体的治疗方法或疫苗，因此开发安全有效的疫苗至关重要。在这里，我们描述了一种通过共表达结构蛋白（CprME）和非结构蛋白（NS 2B/NS 3）组装寨卡病毒样颗粒（VLP）的新策略，并证明了它们作为疫苗的有效性。VLP在哺乳动物细胞的悬浮培养物中产生，并自组装成与寨卡病毒非常相似的颗粒，如电子显微镜研究所示。我们测试了各种VLP疫苗，并将它们与用作参考的灭活寨卡病毒（In-ZIKV）的类似组合物进行了比较。VLP免疫引起高滴度的抗体，如In-ZIKV对照一样。然而，在小鼠中，VLP疫苗刺激比In-ZIKV疫苗的可比制剂显著更高的病毒中和抗体滴度。使用更高的VLP剂量并添加佐剂，VLP疫苗引起的血清中和活性得到增强，达到的中和滴度大于2015年在巴西从寨卡感染中恢复的患者血清中检测到的中和滴度。VLP疫苗和In-ZIKV之间中和水平的差异表明化学灭活对E蛋白内的中和表位具有有害影响。这沿着VLP疫苗不能引起感染，使其成为疫苗开发的优选候选物。寨卡病毒是一种新出现的蚊媒感染，目前尚无疫苗或特定治疗方法来对抗和控制其快速传播和有害影响。这项工作描述了一种开发基于病毒样颗粒（VLP）的寨卡疫苗的新策略，并在小鼠模型中测试时显示了其有效性。VLP是寨卡病毒的非感染模拟物，因此不需要化学灭活。VLP疫苗能够保持天然表位结构，并且比灭活的寨卡病毒对照表现更好。我们的研究结果显示了快速开发安全且潜在高效的人类VLP寨卡疫苗的可行性。
The newly emerged mosquito-borne Zika virus poses a major public challenge due to its ability to cause significant birth defects and neurological disorders. The impact of sexual transmission is unclear but raises further concerns about virus dissemination. No specific treatment or vaccine is currently available, thus the development of a safe and effective vaccine is paramount. Here we describe a novel strategy to assemble Zika virus-like particles (VLPs) by co-expressing the structural (CprME) and non-structural (NS2B/NS3) proteins, and demonstrate their effectiveness as vaccines. VLPs are produced in a suspension culture of mammalian cells and self-assembled into particles closely resembling Zika viruses as shown by electron microscopy studies. We tested various VLP vaccines and compared them to analogous compositions of an inactivated Zika virus (In-ZIKV) used as a reference. VLP immunizations elicited high titers of antibodies, as did the In-ZIKV controls. However, in mice the VLP vaccine stimulated significantly higher virus neutralizing antibody titers than comparable formulations of the In-ZIKV vaccine. The serum neutralizing activity elicited by the VLP vaccine was enhanced using a higher VLP dose and with the addition of an adjuvant, reaching neutralizing titers greater than those detected in the serum of a patient who recovered from a Zika infection in Brazil in 2015. Discrepancies in neutralization levels between the VLP vaccine and the In-ZIKV suggest that chemical inactivation has deleterious effects on neutralizing epitopes within the E protein. This along with the inability of a VLP vaccine to cause infection makes it a preferable candidate for vaccine development. Zika is an emerging mosquito-borne infection for which vaccines or specific treatments are not available to combat and control its rapid dissemination and deleterious effects. This work describes a novel strategy for the development of a virus-like particle (VLP) based Zika vaccine and shows its effectiveness when tested in a murine model. VLPs are non-infections mimics of the Zika virus, thus chemical inactivation is not required. A VLP vaccine is able to maintain native epitopes structures and to perform better than an inactivated Zika virus control. Our results show feasibility for the rapid development of a safe and potentially highly effective VLP based Zika vaccine for humans.