Sutter Gerd, Staib Caroline
GSF - Institut f. Molekulare Virologie, Trogerstr. 4b, 81675 München, Germany.
Curr Drug Targets Infect Disord. 2003 Sep;3(3):263-71. doi: 10.2174/1568005033481123.
Vaccinia viruses engineered to express foreign genes are powerful vectors for production of recombinant proteins. Originating from highly efficacious vaccines securing world-wide eradication of smallpox, the most appealing use of vaccinia vectors is to serve as vaccine delivery system for heterologous antigens. Concerns about the safety of vaccinia virus have been addressed by the development of vectors based on attenuated viruses. One of them, modified vaccinia virus Ankara (MVA) can be considered as current vaccinia virus strain of choice for clinical investigation. Historical development and use of MVA as vaccine against smallpox allowed to establish an extraordinary safety profile. MVA can be used under conditions of biosafety level 1 because of its avirulence and its deficiency to productively grow in human cells. In recent years significant progress has been made with regard to the development of MVA vector technologies. Compared to replication competent vaccinia viruses, MVA provides similar levels of recombinant gene expression even in nonpermissive cells. In animal models, MVA vaccines have been found immunogenic and protective against various infectious agents including immunodeficiency viruses, influenza, parainfluenza, measles virus, flaviviruses, or plasmodium parasites. By now first data from clinical trials are becoming available. In this article we briefly review history of MVA and state-of-the art technologies with regard to generation of recombinant MVA vaccines, and describe the progress to develop MVA vector vaccines against important infectious diseases.
经过基因工程改造以表达外源基因的痘苗病毒是生产重组蛋白的强大载体。痘苗病毒起源于确保全球根除天花的高效疫苗，其最具吸引力的用途是作为异源抗原的疫苗递送系统。基于减毒病毒的载体的开发解决了对痘苗病毒安全性的担忧。其中之一，改良痘苗病毒安卡拉株（MVA）可被视为目前临床研究中首选的痘苗病毒株。MVA作为天花疫苗的历史发展和应用使其具有非凡的安全特性。由于其无毒力且在人类细胞中无法有效生长，MVA可在生物安全1级条件下使用。近年来，MVA载体技术的发展取得了重大进展。与具有复制能力的痘苗病毒相比，即使在非允许细胞中，MVA也能提供相似水平的重组基因表达。在动物模型中，已发现MVA疫苗具有免疫原性，并能预防包括免疫缺陷病毒、流感、副流感、麻疹病毒、黄病毒或疟原虫寄生虫在内的多种感染因子。到目前为止，来自临床试验的首批数据已经可用。在本文中，我们简要回顾了MVA的历史以及重组MVA疫苗生产的最新技术，并描述了开发针对重要传染病的MVA载体疫苗的进展。
