Preparation and verification of tetravalent influenza virus subunit vaccine

doi:10.3877/cma.j.issn.1674-1358.2019.06.013

Abstract

Abstract:

Objective

To prepare the 4-valent influenza virus subunit vaccine.

Methods

Four strains of virus were inoculated into the allantoic cavity of healthy chicken embryo which were 9 to 11 days old. After incubated at 33-35 ℃ for 48-72 h, the embryos were cooled and the allantoic fluid was harvested. Following virus inactivation, lysis and purification, sterilization and filtration were applied to prepare a monovalent vaccine stock solution; polyacrylamide gel electrophoresis (SDS-PAGE) was used to analyze the purity. The harvested four monovalent stocks are mixed to prepare a tetravalent influenza virus subunit vaccine. Finally, the finished product vaccine was fully verified according to the Pharmacopoeia of the People’s Republic of China (2015 edition).

Results

The tetravalent influenza virus subunit vaccine was successfully prepared, among which hemagglutinin accounted for 91.4% of the total protein. The hemagglutinin of the four vaccine strains were H1N1 for 30 μg/ml, H3N2 for 34 μg/ml, B1 for 36 μg/ml, and B2 for 30 μg/ml, respectively.

Conclusion

The four-valent influenza subunit vaccine produced meets the requirements of production and verification.

Key words: Tetravalent influenza virus subunit vaccine, Influenza, Vaccine, Type B influenza virus

Ning Chen, Xuefeng Li, Zhaojing Xu, Rui Yao, Chengmai Ruan. Preparation and verification of tetravalent influenza virus subunit vaccine[J]. Chinese Journal of Experimental and Clinical Infectious Diseases(Electronic Edition), 2019, 13(06): 524-527.

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References 22

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项目	《中华人民共和国药典》标准	检定结果
鉴别试验	抗原性与推荐毒株相一致	一致
外观	为微乳白色液体且无异物	微乳白色液体且无异物
装量	不低于标示量	0.56～0.59 ml
pH值	6.80～8.00	7.20
蛋白质含量	≥ 400 μg/ml且不超过疫苗中血凝素含量的4.50倍	272 μg/ml
血凝素含量	每毫升中各型流感病毒毒株血凝素含量应为配置量的80%～120%	H1N1：30 μg/ml；H3N2：34 μg/ml；B1：36 μg/ml；B2：30 μg/ml
卵清蛋白含量	不高于300 ng/ml	196 ng/ml
无菌检查	无菌	无菌生长
异常毒性检查	健存，体重增加	符合规定
细菌内毒素检查	不高于20 EU/ml	符合规定
游离甲醛含量	不超过40 μg/ml	21 μg/ml
渗透压摩尔浓度	符合通则0632要求	261 mOsmol/kg

项目	《中华人民共和国药典》标准	检定结果
鉴别试验	抗原性与推荐毒株相一致	一致
外观	为微乳白色液体且无异物	微乳白色液体且无异物
装量	不低于标示量	0.56～0.59 ml
pH值	6.80～8.00	7.20
蛋白质含量	≥ 400 μg/ml且不超过疫苗中血凝素含量的4.50倍	272 μg/ml
血凝素含量	每毫升中各型流感病毒毒株血凝素含量应为配置量的80%～120%	H1N1：30 μg/ml；H3N2：34 μg/ml；B1：36 μg/ml；B2：30 μg/ml
卵清蛋白含量	不高于300 ng/ml	196 ng/ml
无菌检查	无菌	无菌生长
异常毒性检查	健存，体重增加	符合规定
细菌内毒素检查	不高于20 EU/ml	符合规定
游离甲醛含量	不超过40 μg/ml	21 μg/ml
渗透压摩尔浓度	符合通则0632要求	261 mOsmol/kg

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