Cold chain and virus-free chloroplast-made booster vaccine to confer immunity against different poliovirus serotypes
Cold chain and virus-free chloroplast-made booster vaccine to confer immunity against different poliovirus serotypes
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DOI：
10.1111/pbi.12575
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发表时间：
2016-11-01
影响因子：
13.8
通讯作者：
Daniell, Henry
中科院分区：
文献类型：
--
作者：
Chan, Hui-Ting;Xiao, Yuhong;Daniell, Henry
世卫组织建议在2016年4月之前在全球范围内完全停用2型口服脊髓灰质炎疫苗（OPV），代之以至少一剂灭活脊髓灰质炎病毒疫苗（IPV）。然而，IPV的高成本、有限供应、持续循环的疫苗衍生脊髓灰质炎病毒传播以及后续加强剂的需求仍然没有得到解决。为了满足这一关键需求，报道了一种新的策略，即在单次IPV剂量后低成本无冷链植物制造的病毒蛋白1（VP 1）亚单位口服加强疫苗。VP 1基因的密码子优化增强了叶绿体中的表达50倍。与IPV注射的较低IgG 1或可忽略的伊加滴度相比，在用IPV单次引发后用植物来源的佐剂口服加强在植物细胞中表达的VP 1显著增加了VP 1-IgG 1和VP 1-伊加滴度。伊加在根除脊髓灰质炎方面发挥着关键作用，因为它通过受污染的水或下水道系统传播。使用两剂IPV和植物细胞口服加强剂观察到针对所有三种脊髓灰质炎病毒Sabin血清型的中和抗体滴度（类似于3.17-10.17 log（2）滴度）和血清阳性（70-90%），但单剂IPV导致中和效果较差。在环境温度下储存的表达VP 1的冻干植物细胞保持了效力并无限期地保留了抗原折叠/组装，从而消除了目前所有疫苗所需的冷链。用这种加强疫苗替代OPV以及FDA批准的抗原和佐剂的临床翻译的下一步进行了讨论。
The WHO recommends complete withdrawal of oral polio vaccine (OPV) type 2 by April 2016 globally and replacing with at least one dose of inactivated poliovirus vaccine (IPV). However, high-cost, limited supply of IPV, persistent circulating vaccine-derived polioviruses transmission and need for subsequent boosters remain unresolved. To meet this critical need, a novel strategy of a low-cost cold chain-free plant-made viral protein 1 (VP1) subunit oral booster vaccine after single IPV dose is reported. Codon optimization of the VP1 gene enhanced expression by 50-fold in chloroplasts. Oral boosting of VP1 expressed in plant cells with plant-derived adjuvants after single priming with IPV significantly increased VP1-IgG1 and VP1-IgA titres when compared to lower IgG1 or negligible IgA titres with IPV injections. IgA plays a pivotal role in polio eradication because of its transmission through contaminated water or sewer systems. Neutralizing antibody titres (similar to 3.17-10.17 log(2) titre) and seropositivity (70-90%) against all three poliovirus Sabin serotypes were observed with two doses of IPV and plant-cell oral boosters but single dose of IPV resulted in poor neutralization. Lyophilized plant cells expressing VP1 stored at ambient temperature maintained efficacy and preserved antigen folding/assembly indefinitely, thereby eliminating cold chain currently required for all vaccines. Replacement of OPV with this booster vaccine and the next steps in clinical translation of FDA-approved antigens and adjuvants are discussed.