Chan Hui-Ting, Xiao Yuhong, Weldon William C, Oberste Steven M, Chumakov Konstantin, Daniell Henry
Department of Biochemistry, School of Dental Medicine, University of Pennsylvania, Philadelphia, PA, USA.
Centers for Disease Control and Prevention, Atlanta, GA, USA.
Plant Biotechnol J. 2016 Nov;14(11):2190-2200. doi: 10.1111/pbi.12575. Epub 2016 Jun 1.
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 (~3.17-10.17 log 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.
世界卫生组织建议在2016年4月前在全球范围内完全停用2型口服脊髓灰质炎疫苗（OPV），并用至少一剂灭活脊髓灰质炎病毒疫苗（IPV）取而代之。然而，IPV成本高昂、供应有限、疫苗衍生脊髓灰质炎病毒持续循环传播以及后续加强免疫的需求等问题仍未得到解决。为满足这一关键需求，本文报道了一种新策略，即在单剂IPV接种后使用低成本、无需冷链的植物源病毒蛋白1（VP1）亚单位口服加强疫苗。VP1基因的密码子优化使叶绿体中的表达提高了50倍。与IPV注射后较低的IgG1滴度或可忽略不计的IgA滴度相比，在单剂IPV初免后用植物源佐剂对植物细胞中表达的VP1进行口服加强免疫，显著提高了VP1-IgG1和VP1-IgA滴度。由于IgA可通过受污染的水或下水道系统传播，因此在根除脊髓灰质炎方面发挥着关键作用。两剂IPV和植物细胞口服加强免疫后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（约3.17 - 10.17对数滴度）和血清阳性率（70 - 90%），但单剂IPV导致中和效果不佳。表达VP1的冻干植物细胞在室温下储存可保持效力并无限期保存抗原折叠/组装，从而消除了目前所有疫苗所需的冷链。本文还讨论了用这种加强疫苗替代OPV以及FDA批准的抗原和佐剂临床转化的后续步骤。
