Center of Emphasis in Infectious Diseases, Department of Molecular and Translational Medicine, Texas Tech University Health Sciences Center, El Paso, TX, USA.
Sci Rep. 2020 Mar 4;10(1):4017. doi: 10.1038/s41598-020-61103-1.
Mosquito borne viral diseases are an emerging threat as evident from the recent outbreak of Zika virus (ZIKV) as well as repeated outbreaks of Chikungunya (CHIKV), Yellow fever (YFV) and Japanese encephalitis (JEV) virus in different geographical regions. These four arboviruses are endemic in overlapping regions due to the co-prevalence of the transmitting mosquito vector species Aedes and Culex. Thus, a multivalent vaccine that targets all four viruses would be of benefit to regions of the world where these diseases are endemic. We developed a potential Virus Like Particle (VLP) based multivalent vaccine candidate to target these diseases by using stable cell lines that continuously secrete VLPs in the culture supernatants. Moreover, inclusion of Capsid in the VLPs provides an additional viral protein leading to an enhanced immune response as evident from our previous studies with ZIKV. Immunization of Balb/c mice with different combinations of Capsid protein containing VLPs either as monovalent, bivalent or tetravalent formulation resulted in generation of high levels of neutralizing antibodies. Interestingly, the potential tetravalent VLP vaccine candidate provided strong neutralizing antibody titers against all four viruses. The 293 T stable cell lines secreting VLPs were adapted to grow in suspension cultures to facilitate vaccine scale up. Our stable cell lines secreting individual VLPs provide a flexible yet scalable platform conveniently adaptable to different geographical regions as per the need. Further studies in appropriate animal models will be needed to define the efficacy of the multivalent vaccine candidate to protect against lethal virus challenge.
蚊媒病毒病是一种新出现的威胁，最近寨卡病毒 (ZIKV) 的爆发以及基孔肯雅热 (CHIKV)、黄热病 (YFV) 和日本脑炎 (JEV) 病毒在不同地理区域的反复爆发都证明了这一点。由于传播媒介蚊子 Aedes 和 Culex 的共同流行，这四种虫媒病毒在重叠区域流行。因此，针对所有四种病毒的多价疫苗将有益于这些疾病流行的世界区域。我们通过使用在培养上清液中持续分泌 VLPs 的稳定细胞系，开发了一种针对这些疾病的潜在病毒样颗粒 (VLP) 多价疫苗候选物。此外，衣壳蛋白包含在 VLPs 中提供了额外的病毒蛋白，从而导致免疫反应增强，这从我们之前对 ZIKV 的研究中可以明显看出。用不同组合的包含衣壳蛋白的 VLPs 对 Balb/c 小鼠进行免疫接种，无论是单价、双价还是四价制剂，均可产生高水平的中和抗体。有趣的是，潜在的四价 VLP 疫苗候选物对所有四种病毒都提供了强烈的中和抗体滴度。分泌 VLPs 的 293T 稳定细胞系已适应在悬浮培养中生长，以促进疫苗扩大规模。我们分泌单个 VLP 的稳定细胞系提供了一个灵活且可扩展的平台，根据需要方便地适用于不同的地理区域。需要在适当的动物模型中进行进一步研究，以确定多价疫苗候选物针对致命病毒挑战的功效。
