Codelivery of improved immune complex and virus-like particle vaccines containing Zika virus envelope domain III synergistically enhances immunogenicity
Codelivery of improved immune complex and virus-like particle vaccines containing Zika virus envelope domain III synergistically enhances immunogenicity
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DOI：
10.1016/j.vaccine.2020.02.089
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发表时间：
2020-04-16
期刊：
影响因子：
5.5
通讯作者：
Mason, Hugh S.
中科院分区：
文献类型：
--
作者：
Diamos, Andrew G.;Pardhe, Mary D.;Mason, Hugh S.
寨卡病毒(ZIKV)的再次出现对健康构成了重大威胁，特别是由于其对胎儿发育的风险，因此需要安全有效的疫苗来保护孕妇。寨卡病毒包膜结构域III(ZE3)被认为是一种安全有效的候选疫苗，但其免疫原性较差。我们之前的研究表明，植物制造的重组免疫复合物(RIC)疫苗是提高弱抗原免疫原性的一个强大平台。在这项研究中，我们改变了RIC平台上的抗原融合位置，以适应与免疫球蛋白重链(N-RIC)的N-末端融合，从而使更广泛的抗原范围，导致RIC的表达比正常的C-末端融合(C-RIC)提高了40%。这两种类型的含有ZE3的RICS在工厂中被有效地组装，并通过简单的一步纯化纯化到95%的同源性。ZE3RICS与补体受体C1q强结合，并诱导出与ZIKV中和相关的ZE3特异性抗体滴度。当N-RIC或C-RIC与显示ZE3的植物产生的乙肝核心(HBC)病毒样颗粒(VLP)共同递送时，仅在两剂无佐剂的情况下，该组合诱导的抗体滴度(>；1,000,000)是RICS或VLP单独递送的5倍，并更强地中和ZIKV。这些发现表明，需要自由N末端以获得最佳抗原展示的抗原现在可以与RIC系统一起使用，植物制成的RICS和VLP是针对ZE3的高效疫苗。因此，RIC平台可以更普遍地应用于更广泛种类的抗原。(C)2020爱思唯尔有限公司。保留所有权利。
Zika virus (ZIKV) reemergence poses a significant health threat especially due to its risks to fetal development, necessitating safe and effective vaccines that can protect pregnant women. Zika envelope domain III (ZE3) has been identified as a safe and effective vaccine candidate, however it is poorly immunogenic. We previously showed that plant-made recombinant immune complex (RIC) vaccines are a robust platform to improve the immunogenicity of weak antigens. In this study, we altered the antigen fusion site on the RIC platform to accommodate N-terminal fusion to the IgG heavy chain (N-RIC), and thus a wider range of antigens, with a resulting 40% improvement in RIC expression over the normal C-terminal fusion (C-RIC). Both types of RICs containing ZE3 were efficiently assembled in plants and purified to >95% homogeneity with a simple one-step purification. Both ZE3 RICs strongly bound complement receptor C1q and elicited strong ZE3-specific antibody titers that correlated with ZIKV neutralization. When either N-RIC or C-RIC was codelivered with plant-produced hepatitis B core (HBc) virus-like particles (VLP) displaying ZE3, the combination elicited 5-fold greater antibody titers (>1,000,000) and more strongly neutralized ZIKV than either RICs or VLPs alone, after only two doses without adjuvant. These findings demonstrate that antigens that require a free N-terminus for optimal antigen display can now be used with the RIC system, and that plant-made RICs and VLPs are highly effective vaccines targeting ZE3. Thus, the RIC platform can be more generally applied to a wider variety of antigens. (C) 2020 Elsevier Ltd. All rights reserved.