Oyarzún Patricio, Kobe Bostjan
a Biotechnology Center, Facultad de Ingeniería y Tecnología, Universidad San Sebastián , Concepción , Chile.
b School of Chemistry and Molecular Biosciences, Institute for Molecular Bioscience and Australian Infectious Diseases Research Center, University of Queensland , Brisbane , Australia.
Hum Vaccin Immunother. 2016 Mar 3;12(3):763-7. doi: 10.1080/21645515.2015.1094595.
Novel vaccination approaches based on rational design of B- and T-cell epitopes - epitope-based vaccines - are making progress in the clinical trial pipeline. The epitope-focused recombinant protein-based malaria vaccine (termed RTS,S) is a next-generation approach that successfully reached phase-III trials, and will potentially become the first commercial vaccine against a human parasitic disease. Progress made on methods such as recombinant DNA technology, advanced cell-culture techniques, immunoinformatics and rational design of immunogens are driving the development of these novel concepts. Synthetic recombinant proteins comprising both B- and T-cell epitopes can be efficiently produced through modern biotechnology and bioprocessing methods, and can enable the induction of large repertoires of immune specificities. In particular, the inclusion of appropriate CD4+ T-cell epitopes is increasingly considered a key vaccine component to elicit robust immune responses, as suggested by results coming from HIV-1 clinical trials. In silico strategies for vaccine design are under active development to address genetic variation in pathogens and several broadly protective "universal" influenza and HIV-1 vaccines are currently at different stages of clinical trials. Other methods focus on improving population coverage in target populations by rationally considering specificity and prevalence of the HLA proteins, though a proof-of-concept in humans has not been demonstrated yet. Overall, we expect immunoinformatics and bioprocessing methods to become a central part of the next-generation epitope-based vaccine development and production process.
基于B细胞和T细胞表位合理设计的新型疫苗接种方法——即基于表位的疫苗——正在临床试验阶段取得进展。以表位为重点的重组蛋白基疟疾疫苗（称为RTS,S）是一种成功进入III期试验的下一代方法，并有可能成为第一种针对人类寄生虫病的商业疫苗。重组DNA技术、先进细胞培养技术、免疫信息学和免疫原合理设计等方法取得的进展推动了这些新概念的发展。包含B细胞和T细胞表位的合成重组蛋白可通过现代生物技术和生物加工方法高效生产，并能诱导产生大量免疫特异性。特别是，正如来自HIV-1临床试验的结果所表明的，纳入适当的CD4+T细胞表位越来越被视为引发强大免疫反应的关键疫苗成分。疫苗设计的计算机策略正在积极开发中，以应对病原体的基因变异，目前几种具有广泛保护作用的“通用”流感和HIV-1疫苗正处于不同的临床试验阶段。其他方法则通过合理考虑HLA蛋白的特异性和流行率来提高目标人群的覆盖率，不过尚未在人体中得到概念验证。总体而言，我们预计免疫信息学和生物加工方法将成为下一代基于表位的疫苗开发和生产过程的核心部分。
