Kiseleva I V, Isakova I N, Larionova N V, Oleĭnik E S, Rudenko L G
Zh Mikrobiol Epidemiol Immunobiol. 2007 Nov-Dec(6):40-5.
Reassortant strains for modern live influenza vaccines are prepared using growing chicken embryos. It is very important to switch manufacture of influenza vaccines from chicken embryos to cell cultures, especially due to the threat of future pandemic, when there will be need of big quantities of vaccine for immunization of all age groups. Efficacy of production of reassortant strains with 6:2 vaccine formulation of genome (6 internal genes from the donor of attenuation and 2 genes coding external antigens--hemagglutinin and neuraminidase--from epidemic strain) in MDCK cell culture, using standard techniques employed for production of the vaccine in chicken embryos, was studied. It was shown that yield frequency of aforementioned reassortants of influenza A viruses did not exceed 5.7% whereas in chicken embryos vaccine 6:2 reassortants were isolated with frequency of 4%. For influenza B viruses, yield of 6:2 reassortants in growing chicken embryos exceeded 67% whereas in MDCK cell culture we were unable to produce clones with required genome composition. Thus, existing method while effective for production of vaccine reassortants in chicken embryos is low effective for isolation of 6:2 reassortants in MDCK cell culture. Fundamentally new techniques are needed for production of reassortant strains for live influenza vaccine in cell culture.
现代流感活疫苗的重配毒株是通过在鸡胚中培养制备的。将流感疫苗的生产从鸡胚转向细胞培养非常重要,特别是考虑到未来大流行的威胁,届时将需要大量疫苗为所有年龄组进行免疫接种。本研究采用在鸡胚中生产疫苗的标准技术,研究了在MDCK细胞培养中使用基因组6:2疫苗配方(6个内部基因来自减毒供体,2个基因编码来自流行毒株的外部抗原——血凝素和神经氨酸酶)生产重配毒株的效果。结果表明,上述甲型流感病毒重配体的产生频率不超过5.7%,而在鸡胚疫苗中,6:2重配体的分离频率为4%。对于乙型流感病毒,在生长的鸡胚中6:2重配体的产量超过67%,而在MDCK细胞培养中,我们无法产生具有所需基因组组成的克隆。因此,现有方法虽然在鸡胚中生产疫苗重配体有效,但在MDCK细胞培养中分离6:2重配体的效率较低。在细胞培养中生产流感活疫苗的重配毒株需要全新的技术。