A Deleted Deletion Site in a New Vector Strain and Exceptional Genomic Stability of Plaque-Purified Modified Vaccinia Ankara(MVA)  

作　　者：Ingo Jordan Deborah Horn Kristin Thiele Lars Haag Katharina Fiddeke Volker Sandig 

机构地区：[1]ProBioGen AG.Herbert-Bayer-StraBe 8,13086 Berlin,Germany [2]Sartorius Stedim Cellca GmbH.Erwin-Rentschler-Str 21,88471 Laupheim,Germany [3]Vironova AB,Giivlegatan 22,11330 Stockholm,Sweden [4]Department of Laboratory Medicine,Karolinska Universitetsjukhuset i Huddinge,14152 Huddinge,Sweden

出　　处：《Virologica Sinica》2020年第2期212-226,共15页中国病毒学（英文版）

基　　金：Part of this work was financially supported by the EU FP7 Grant FLUNIVAC(Project-ID 602604).

摘　　要：Vectored vaccines based on highly attenuated modified vaccinia Ankara(MVA) are reported to be immunogenic, tolerant to pre-existing immunity, and able to accommodate and stably maintain very large transgenes. MVA is usually produced on primary chicken embryo fibroblasts, but production processes based on continuous cell lines emerge as increasingly robust and cost-effective alternatives. An isolate of a hitherto undescribed genotype was recovered by passage of a nonplaque-purified preparation of MVA in a continuous anatine suspension cell line(CR.pIX) in chemically defined medium.The novel isolate(MVA-CR19) replicated to higher infectious titers in the extracellular volume of suspension cultures and induced fewer syncytia in adherent cultures. We now extend previous studies with the investigation of the point mutations in structural genes of MVA-CR19 and describe an additional point mutation in a regulatory gene. We furthermore map and discuss an extensive rearrangement of the left telomer of MVA-CR19 that appears to have occurred by duplication of the right telomer. This event caused deletions and duplications of genes that may modulate immunologic properties of MVACR19 as a vaccine vector. Our characterizations also highlight the exceptional genetic stability of plaque-purified MVA:although the phenotype of MVA-CR19 appears to be advantageous for replication, we found that all genetic markers that differentiate wildtype and MVA-CR19 are stably maintained in passages of recombinant viruses based on either wildtype or MVA-CR.

关 键 词：Modified vaccinia Ankara(MVA) MVA-CR19 CR.pIX Suspension cell line Vaccine production Genome stability 

分 类 号：R392[医药卫生—免疫学]