Cell-based influenza vaccines: Progress to date

Cell-based influenza vaccines: Progress to date
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DOI:
10.2165/00003495-200868110-00002
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发表时间:
2008-01-01
期刊:
影响因子:
11.5
通讯作者:
Tannock, Gregory A.
Tannock, Gregory A.
中科院分区:
医学1区
文献类型:
--
作者:
Audsley, Jennifer M.;Tannock, Gregory A.

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人类抗流感疫苗已经有近60年的历史,直到最近,几乎完全是用在9到11天大的鸡胚尿囊腔中生长的病毒制备的。涉及鸡蛋的生产不够灵活,无法迅速扩大疫苗供应,特别是在面临即将到来的大流行时。其他问题可能来自对鸡蛋供应产生不利影响的祖禽群的感染,以及生产过程本身,在生产过程中,偶尔会由于大量病毒尿囊液的污染而导致无菌性的破坏。此外,鸡蛋培养的病毒在抗原性方面与从临床标本中分离的哺乳动物细胞系病毒有所不同。近年来,由于H5N1禽流感感染在几个亚洲国家向人类有限传播,这些关切和今后可能需要大大扩大生产能力的问题已成为焦点。近年来,一些制造商一直在寻求使用经认可的非洲绿猴肾(Vero)、Madin-Darby犬肾(MDCK)和其他细胞系的锚定依赖性和独立制剂的替代方法。已经取得了与胚胎卵相当的产量。这些改进与新技术同时发生,新技术允许细胞在不含动物血清的新合成培养基中生长,以减轻监管机构对传染性海绵状脑病传播可能性的担忧。
Human vaccines against influenza have been available for almost 60 years and, until recently, were prepared almost entirely from viruses grown in the allantoic cavity of 9- to 11-day-old embryonated chicken eggs. Manufacture involving eggs is not sufficiently flexible to allow vaccine supplies to be rapidly expanded, especially in the face of an impending pandemic. Other problems may arise from the infections of progenitor flocks that adversely affect egg supplies, and from the manufacturing process itself, where breakdowns in sterility can occur from the occasional contamination of large batches of viral allantoic fluid. In addition, egg-grown viruses exhibit differences in antigenicity from viruses isolated in mammalian cell lines from clinical specimens. These concerns and the probable need for greatly expanded manufacturing capability in the future have been brought into focus in recent years by the limited spread of H5N1 avian influenza infections to humans in several Asian countries. Alternative approaches involving the use of accredited anchorage-dependent and independent preparations of the African Green monkey kidney (Vero), Madin-Darby canine kidney (MDCK) and other cell lines have been pursued by several manufacturers in recent years. Yields comparable with those obtained in embryonated eggs have been achieved. These improvements have occurred in parallel with newer technologies that allow the growth of cells in newer synthetic media that do not contain animal serum, in order to allay the concerns of regulators about the potential for spread of transmissible spongiform encephalopathies.