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首页> 外文期刊>Vaccine >Comparison of egg and high yielding MDCK cell-derived live attenuated influenza virus for commercial production of trivalent influenza vaccine: In vitro cell susceptibility and influenza virus replication kinetics in permissive and semi-permissivecells
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Comparison of egg and high yielding MDCK cell-derived live attenuated influenza virus for commercial production of trivalent influenza vaccine: In vitro cell susceptibility and influenza virus replication kinetics in permissive and semi-permissivecells

机译:商业生产三价流感疫苗的蛋和高产MDCK细胞减毒活流感病毒的比较:允许和半允许细胞的体外细胞敏感性和流感病毒复制动力学

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摘要

Currently MedImmune manufactures cold-adapted (ca) live, attenuated influenza vaccine (LAW) from specific-pathogen free (SPF) chicken eggs. Difficulties in production scale-up and potential exposure of chicken flocks to avian influenza viruses especially in the event of a pandemic influenza outbreak have prompted evaluation and development of alternative non-egg based influenza vaccine manufacturing technologies. As part of MedImmune's effort to develop the live attenuated influenza vaccine (LAIV) using cell culture production technologies we have investigated the use of high yielding, cloned MDCK cells as a substrate for vaccine production by assessing host range and virus replication of influenza virus produced from both SPF egg and MDCK cell production technologies. In addition to cloned MDCK cells the indicator cell lines used to evaluate the impact of producing LAIV in cells on host range and replication included two human cell lines: human lung carcinoma (A549) cells and human muco-epidermoid bronchiolar carcinoma (NCI H292) cells. The influenza viruses used to infect the indicators cell lines represented both the egg and cell culture manufacturing processes and included virus strains that composed the 2006-2007 influenza seasonal trivalent vaccine (A/New Caledonia/20/99 (H1N1), A/Wisconsin/67/05 (H3N2) and B/Malaysia/2506/04). Results from this study demonstrate remarkable similarity between influenza viruses representing the current commercial egg produced and developmental MDCK cell produced vaccine production platforms. MedImmune's high yielding cloned MDCK cells used for the cell culture based vaccine production were highly permissive to both egg and cell produced ca attenuated influenza viruses. Both the A549 and NCI H292 cells regardless of production system were less permissive to influenza A and B viruses than the MDCK cells. Irrespective of the indicator cell line used the replication properties were similar between egg and the cell produced influenza viruses. Based on these study results we conclude that the MDCK cell produced and egg produced vaccine strains are highly comparable.
机译:目前,MedImmune从不含特定病原体(SPF)的鸡蛋中生产冷适应(ca)的减毒活流感疫苗(LAW)。生产规模扩大的困难以及鸡群可能暴露于禽流感病毒中,特别是在大流行性流感爆发的情况下,已经促使人们评估和开发替代的非蛋类流感疫苗制造技术。作为MedImmune使用细胞培养生产技术开发减毒活流感疫苗(LAIV)的努力的一部分,我们通过评估宿主范围和从中产生的流感病毒的病毒复制,研究了高产量克隆的MDCK细胞作为疫苗生产底物的用途。 SPF卵和MDCK细胞生产技术。除克隆的MDCK细胞外,用于评估细胞内LAIV产生对宿主范围和复制的影响的指示细胞系包括两种人类细胞系:人类肺癌(A549)细胞和人类粘液表皮样细支气管癌(NCI H292)细胞。用于感染指标细胞系的流感病毒代表卵和细胞培养物的制造过程,并且包括组成2006-2007年流感季节性三价疫苗的病毒株(A / New Caledonia / 20/99(H1N1),A / Wisconsin / 67/05(H3N2)和B /马来西亚/ 2506/04)。这项研究的结果表明,代表当前商业鸡蛋生产的流感病毒与发展中的MDCK细胞生产的疫苗生产平台之间具有显着相似性。 MedImmune的高产量克隆MDCK细胞用于基于细胞培养的疫苗生产,对鸡蛋和细胞产生的减毒流感病毒高度允许。不论生产系统如何,A549和NCI H292细胞都比MDCK细胞对甲型和乙型流感病毒的容许率低。不管使用何种指示细胞系,卵与细胞产生的流感病毒之间的复制特性都是相似的。根据这些研究结果,我们得出结论,MDCK细胞产生的卵和卵产生的疫苗株具有高度的可比性。

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