Firdaus Moh Egy Rahman, Mustopa Apon Zaenal, Ekawati Nurlaili, Chairunnisa Sheila, Arifah Rosyida Khusniatul, Hertati Ai, Irawan Shasmita, Prastyowati Anika, Kusumawati Arizah, Nurfatwa Maritsa
Research Center for Genetic Engineering, National Research and Innovation Agency (BRIN), Bogor, 16911, Indonesia.
Current Address: Laboratory of Structural Virology, The International Institute of Molecular Mechanisms and Machines (IMOL), Polish Academy of Sciences, Warsaw, Poland.
J Genet Eng Biotechnol. 2023 May 24;21(1):68. doi: 10.1186/s43141-023-00514-9.
Vaccination is the one of the agendas of many countries to reduce cervical cancer caused by the Human papillomavirus. Currently, VLP-based vaccine is the most potent vaccine against HPV, which could be produced by a variety of expression systems. Our study focuses on a comparison of recombinant protein expression L1 HPV52 using two common yeasts, Pichia pastoris and Hansenula polymorpha that have been used for vaccine production on an industrial scale. We also applied bioinformatics approach using reverse vaccinology to design alternative multi-epitope vaccines in recombinant protein and mRNA types.
Our study found that P. pastoris relatively provided higher level of L1 protein expression and production efficiency compared to H. polymorpha in a batch system. However, both hosts showed self-assembly VLP formation and stable integration during protein induction. The vaccine we have designed exhibited high immune activation and safe in computational prediction. It is also potentially suitable for production in a variety of expression systems.
By monitoring the overall optimization parameter assessment, this study can be used as the basis reference for large-scale production of the HPV52 vaccine.
疫苗接种是许多国家减少人乳头瘤病毒所致宫颈癌的议程之一。目前，基于病毒样颗粒（VLP）的疫苗是针对人乳头瘤病毒最有效的疫苗，可通过多种表达系统生产。我们的研究重点是比较使用两种常用于工业规模疫苗生产的常见酵母——毕赤酵母和多形汉逊酵母来表达重组蛋白L1 HPV52。我们还应用了反向疫苗学的生物信息学方法来设计重组蛋白和mRNA类型的替代性多表位疫苗。
我们的研究发现，在分批系统中，与多形汉逊酵母相比，毕赤酵母相对能提供更高水平的L1蛋白表达和生产效率。然而，两种宿主在蛋白诱导过程中均显示出病毒样颗粒的自组装形成和稳定整合。我们设计的疫苗在计算预测中表现出高免疫激活且安全。它也可能适用于多种表达系统的生产。
通过监测整体优化参数评估，本研究可为大规模生产HPV52疫苗提供基础参考。
