Huang Bao-Ying, Wang Xiu-Ping, Wang Wen-Ling, Hu Wei, Gao Qiang, Tan Wen-Jie, Ruan Li
National Institute for Viral Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing 100052 ,China.
Bing Du Xue Bao. 2011 May;27(3):265-73.
To investigate the seasonal influenza split vaccine's immune protective effectiveness against the homologous and heterogonous subtypes of influenza A virus challenge and the relationship between the protective effectiveness and hemagglutination inhibition (HI) antibody titer in mice. Two components of H1N1 and H3N2 in Chinese 2008-2009 seasonal influenza spilt vaccine, were derived from vaccine strain A/Brisbane/59/2007 (H1N1)-like virus and A/Brisbane/10/2007 (H3N2)-like virus respectively, and were used to immune BALB/c mice. Firstly, different doses of the vaccines were used to immunize mice and the HA immunization dosage that can induce the HI antibody titer of 40 in mice was identified; Secondly, H1N1 vaccine immunized mice were challenged with different doses of influenza virus mouse adaptation strains of A/Brisbane/59/2007 (H1N1)-like virus (MA) (referred to as A1 virus, well matched-strain in the homologous subtype) and A/Purto Rico/8/34 (H1N1) (referred to as PR8 virus, poor matched-strain in the homologous subtype) respectively, and H3N2 vaccine immunized mice were challenged with H1N1 influenza virus of A1 strain (Heterogonous subtype), body weight changes and survival rates were observed to explore the immune protective effectiveness of influenza split vaccine against the homologous and heterogonous subtypes of influenza A virus in mice. Results indicated that HI antibody titers were elevated as the HA protein immunization dosages increased from 0.15 microg, 0.5 microg, 1.5 microg, 5 microg to 15 microg in mice, and 1.5 microg HA of the seasonal influenza split vaccine could induced HI antibody titer of 40 in mice; 3LD50, 10LD50, 30LD50, 100LD50, 300LD50,1000LD50 and 3000LD50 of influenza virus strain A1 were used to challenge the H1N1 immunization mice, 1.5 microg HA of H1N1 vaccine could 100% protect mice against challenge with 1000LD50 of matched and homologous subtype of influenza virus strains A1, mice immunized with 15 microg HA of H1N1 vaccine even could 100% protect mice against challenge with 3000LD50 of influenza virus strains A1; but mice immunized with both the 1.5 microg and 15 microg HA of H1N1 vaccine were all sacrificed when challenged with 3LD50 of the mismatched and homologous subtype of influenza virus strain PR8, and mice immunized with the high dosage of 15 microg HA of H3N2 vaccine also were all sacrificed when challenged with 3LD50 of the heterogonous subtype of influenza virus strain A1. These results suggest that 1.5 microg HA of seasonal influenza split vaccine could induced HI antibody titer of 40 after one dose in mice, this dosage of HA can effectively protect mice against matched homologous subtype of influenza virus strain, but hardly to protect mice against mismatched homologous or heterogonous subtype of influenza virus strain. These results provide materials for the establishment of influenza vaccine evaluation system based on seasonal influenza vaccine.
探讨季节性流感裂解疫苗对甲型流感病毒同源和异源亚型攻击的免疫保护效果以及保护效果与血凝抑制(HI)抗体滴度之间的关系。中国2008 - 2009年季节性流感裂解疫苗中的H1N1和H3N2两种成分,分别来源于疫苗株A/ Brisbane/59/2007(H1N1)- 样病毒和A/ Brisbane/10/2007(H3N2)- 样病毒,并用于免疫BALB/c小鼠。首先,用不同剂量的疫苗免疫小鼠,确定能诱导小鼠HI抗体滴度达到40的HA免疫剂量;其次,用H1N1疫苗免疫的小鼠分别用不同剂量的甲型流感病毒鼠适应株A/ Brisbane/59/2007(H1N1)- 样病毒(MA)(称为A1病毒,同源亚型中匹配良好的毒株)和A/ Purto Rico/8/34(H1N1)(称为PR8病毒,同源亚型中匹配不佳的毒株)进行攻击,用H3N2疫苗免疫的小鼠用A1株H1N1流感病毒(异源亚型)进行攻击,观察体重变化和存活率,以探讨流感裂解疫苗对小鼠甲型流感病毒同源和异源亚型的免疫保护效果。结果表明,随着HA蛋白免疫剂量从0.15μg、0.5μg、1.5μg、5μg增加到15μg,小鼠的HI抗体滴度升高,季节性流感裂解疫苗1.5μg HA可诱导小鼠HI抗体滴度达到40;用流感病毒株A1的3LD50、10LD50、30LD50、100LD50、300LD50、1000LD50和3000LD50攻击H1N1免疫小鼠,1.5μg HA的H1N1疫苗可100%保护小鼠免受1000LD50匹配的同源亚型流感病毒株A1的攻击,用15μg HA的H1N1疫苗免疫的小鼠甚至可100%保护小鼠免受3000LD50流感病毒株A1的攻击;但用1.5μg和15μg HA的H1N1疫苗免疫的小鼠在用3LD50不匹配的同源亚型流感病毒株PR8攻击时全部死亡,并在用3LD50异源亚型流感病毒株A1攻击时,用高剂量15μg HA的H3N2疫苗免疫的小鼠也全部死亡。这些结果表明,季节性流感裂解疫苗1.5μg HA在小鼠单次给药后可诱导HI抗体滴度达到40,该剂量的HA能有效保护小鼠免受匹配的同源亚型流感病毒株的攻击,但几乎不能保护小鼠免受不匹配的同源或异源亚型流感病毒株的攻击。这些结果为基于季节性流感疫苗建立流感疫苗评价体系提供了材料。