An inactivated West Nile Virus vaccine derived from a chemically synthesized cDNA system

被引:19
作者
Orlinger, Klaus K. [1 ]
Holzer, Georg W. [1 ]
Schwaiger, Julia [1 ]
Mayrhofer, Josef [1 ]
Schmid, Karl [1 ]
Kistner, Otfried [1 ]
Barrett, P. Noel [1 ]
Falkner, Falko G. [1 ]
机构
[1] Baxter Biosci, Biomed Res Ctr, A-2304 Orth, Austria
关键词
West Nile Virus; Gene synthesis; Vaccine; BORNE ENCEPHALITIS-VIRUS; INFECTIOUS CLONE; JAPANESE ENCEPHALITIS; RNA; TYPE-2; CONSTRUCTION; FLAVIVIRUS; GENOME; ELEMENTS;
D O I
10.1016/j.vaccine.2010.02.092
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
A cDNA comprising the complete genome of West Nile Virus (WNV) was generated by chemical synthesis using published sequence data, independent of any preformed viral components The synthetic WNV, produced by transfection of in vitro transcribed RNA Into cell culture, exhibited undistinguishable biological properties compared to the corresponding animal-derived wild-type virus No differences were found concerning viral growth in mammalian and insect cell lines and concerning expression of viral proteins in cells There were also no significant differences in virulence in mice following intranasal challenge After immunizations of mice with experimental vaccines derived from the synthetic and wildtype viruses, protection from lethal challenge was achieved with similar amounts of antigen. Both vaccine preparations also Induced comparable levels of neutralizing antibodies in mice In addition, the synthetic approach turned out to be very accurate, since the rescued WNV genome contained no undesired mutations Thus, the first flavivirus based on chemical gene synthesis was indistinguishable from the parent virus This demonstrates that virus isolates from animal sources are dispensable to derive seed viruses for vaccine production or research (C) 2010 Elsevier Ltd All rights reserved
引用
收藏
页码:3318 / 3324
页数:7
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