Research Progress in Vero Cell-based Influenza Vaccine

doi:10.13560/j.cnki.biotech.bull.1985.2022-0238

Abstract

Abstract:

The prevention of influenza is one of the most severe challenges faced by mankind. Influenza vaccine inoculation is the key of preventing influenza. There are limitations in the traditional production process of influenza vaccine due to its dependence on chicken embryo, and the production of large-scale influenza vaccine is gradually transferred from chicken embryo to mammalian cells. Currently, MDCK, Vero and PER.C6 cell lines can be used for influenza vaccine development. Vero cells have non-tumogenesis within a certain range of generations and been used in the production of a variety of human viral vaccines. It is the cell line recommended by WHO that is widely used in the production of human and animal virial vaccines, however, there is still challenges in the Vero cell-based influenza vaccine production. This paper reviews the research of influenza vaccine, the comprehensive comparison of cell-based influenza vaccine and the difficulties faced by Vero cells in the production of influenza vaccine, aiming to provide reference for the development of cell-based influenza vaccine.

Key words: influenza, Vero cell, vaccine, suspension culture

MA Fang-fang, KANG Bi-jing, MA Chun-ying, LIU Zhen-bin, YANG Di, QIAO Zi-lin, WANG Ming-ming, MA Zhong-ren, WANG Jia-min. Research Progress in Vero Cell-based Influenza Vaccine[J]. Biotechnology Bulletin, 2022, 38(12): 137-143.

Figures/Tables 6

References 33

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商品名称 Name of product	制造商 Manufacturer	疫苗类型 Vaccine type	佐剂 Adjuvant	接种量Pre-sentation/mL	适用人群 Applicable people	每种疫苗每剂所含HA/病毒数HA or virus count for each vaccine virus（per dose）	汞（硫柳汞）含量 Mercury（from thimerosal）
Afluria	Seqirus	四价灭活疫苗	无	0.25	6-35 个月	7.5 μg/0.25 mL 15 μg/0.5 mL	-
				0.5	≥3 岁		-
				5.0	≥6 个月（needle/syringe） 18-64 岁（jet injector）		24.5 μg/0.5 mL
Fluarix	GlaxoSmithKline	四价灭活疫苗	无	0.5	≥6 个月	15 μg/0.5 mL	-
FluLaval	GlaxoSmithKline	四价灭活疫苗	无	0.5	≥6 个月	15 μg/0.5 mL	-
Fluzone	Sanofi Pasteur	四价灭活疫苗	无	0.5	≥6 个月	15 μg/0.5 mL	-
				0.5	≥6 个月
				5.0	≥6 个月
Fluzone High-Dose	Sanofi Pasteur	高剂量四价灭活疫苗	无	0.7	≥65 岁	60 μg/0.7 mL	-
Fluad	Seqirus	四价灭活疫苗	MF59	0.5	≥65 岁	15 μg/0.5 mL	-
Fluad	Seqirus	三价灭活疫苗	MF59	0.5	≥65 岁	15 μg/0.5 mL	-

商品名称 Name of product	制造商 Manufacturer	疫苗类型 Vaccine type	佐剂 Adjuvant	接种量Pre-sentation/mL	适用人群 Applicable people	每种疫苗每剂所含HA/病毒数HA or virus count for each vaccine virus（per dose）	汞（硫柳汞）含量 Mercury（from thimerosal）
Afluria	Seqirus	四价灭活疫苗	无	0.25	6-35 个月	7.5 μg/0.25 mL 15 μg/0.5 mL	-
				0.5	≥3 岁		-
				5.0	≥6 个月（needle/syringe） 18-64 岁（jet injector）		24.5 μg/0.5 mL
Fluarix	GlaxoSmithKline	四价灭活疫苗	无	0.5	≥6 个月	15 μg/0.5 mL	-
FluLaval	GlaxoSmithKline	四价灭活疫苗	无	0.5	≥6 个月	15 μg/0.5 mL	-
Fluzone	Sanofi Pasteur	四价灭活疫苗	无	0.5	≥6 个月	15 μg/0.5 mL	-
				0.5	≥6 个月
				5.0	≥6 个月
Fluzone High-Dose	Sanofi Pasteur	高剂量四价灭活疫苗	无	0.7	≥65 岁	60 μg/0.7 mL	-
Fluad	Seqirus	四价灭活疫苗	MF59	0.5	≥65 岁	15 μg/0.5 mL	-
Fluad	Seqirus	三价灭活疫苗	MF59	0.5	≥65 岁	15 μg/0.5 mL	-

生产厂家 Manufacturer	疫苗类型 Vaccine type	毒株 Strain	细胞基质 Cell substrate	培养方式 Cultivating way	商品名称 Name of product
Solvay	三价亚单位疫苗	A/H1N1、A/H3N2、一种乙型毒株	MDCK 细胞	无血清微载体贴壁培养	Influvac
Novartis	单价灭活疫苗	A/H1N1	MDCK细胞	-	Celtura
Novartis	三价亚单位疫苗	A/H1N1、A/H3N2、一种乙型毒株	MDCK细胞	无血清悬浮培养	Flucelvax
Seqirus	四价流感疫苗	A/H1N1，A/H3N2，B Yamagata，B Victoria	MDCK细胞	-	Flucelvax
Baxter	单价灭活疫苗	A/ H1N1或A/H5N1	Vero 细胞	微载体无血清培养	Celvapan
Baxter	三价灭活疫苗	A/H1N1、A/H3N2、一种乙型毒株	Vero 细胞	微载体无血清培养	Preflucel
Sanofi Pasteur	单价灭活疫苗	H7N1	PER.C6细胞	-	-

生产厂家 Manufacturer	疫苗类型 Vaccine type	毒株 Strain	细胞基质 Cell substrate	培养方式 Cultivating way	商品名称 Name of product
Solvay	三价亚单位疫苗	A/H1N1、A/H3N2、一种乙型毒株	MDCK 细胞	无血清微载体贴壁培养	Influvac
Novartis	单价灭活疫苗	A/H1N1	MDCK细胞	-	Celtura
Novartis	三价亚单位疫苗	A/H1N1、A/H3N2、一种乙型毒株	MDCK细胞	无血清悬浮培养	Flucelvax
Seqirus	四价流感疫苗	A/H1N1，A/H3N2，B Yamagata，B Victoria	MDCK细胞	-	Flucelvax
Baxter	单价灭活疫苗	A/ H1N1或A/H5N1	Vero 细胞	微载体无血清培养	Celvapan
Baxter	三价灭活疫苗	A/H1N1、A/H3N2、一种乙型毒株	Vero 细胞	微载体无血清培养	Preflucel
Sanofi Pasteur	单价灭活疫苗	H7N1	PER.C6细胞	-	-

细胞名称 Name of cell	培养方式 Cultivating way	有无血清 Presence of serum	毒株 Strain	最高增殖密度 Maximum proliferation density/（Cells·mL^-1）	血凝滴度 Degree of HA/ （lgHAU·100 μL^-1）	病毒感染性滴度 Titer of viral infectivity/ （lgHAU·100 μL^-1）
MDCK细胞	微载体Cytodex 1悬浮培养	有	H5N1（A /Vietnam /1194 /2004-NIB RG-14）	0.8 × 10⁷	2.9	8.64-9.22
Vero 细胞	微载体 Cytodex 1悬浮培养	有	H1N1（A/PR/8 /34）	-	2.6	7.83-7.88
Vero 细胞	微载体 Cytodex3 悬浮培养	无	A/Vietnam/1203 /2004和 A/Indonesia /05 /2005	2.73 × 10⁶	2.70-3.01	8.6-9.0
MDCK细胞	全悬浮培养	无	H1N1	5.97×10⁶	3.88	10.34
MDCK细胞	半灌注全悬浮培养	-	H1N1（A/PR/8/34）	6 × 10⁷	4.5	10