Comparative analysis of antibody induction and protection against influenza virus infection by DNA immunization with HA, HAe, and HA1 in mice
Comparative analysis of antibody induction and protection against influenza virus infection by DNA immunization with HA, HAe, and HA1 in mice
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DOI：
10.1007/s00705-013-1878-1
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发表时间：
2014-04-01
影响因子：
2.7
通讯作者：
Chen, Ze
中科院分区：
文献类型：
--
作者：
Chen, Jianjun;Liu, Qian;Chen, Ze
质粒DNA疫苗被认为是控制流感的灭活流感病毒疫苗的替代品。以血凝素(HA)-、血凝素外结构域(HAe)-或血凝素亚单位1 （HA1）为基础的疫苗接种可刺激动物的保护性免疫。本研究的目的是比较它们在DNA疫苗接种后诱导抗体反应和保护小鼠免受流感病毒感染的能力。构建了A/California/07/2009甲型流感病毒全长HA、HAe或HA1的三个表达载体，并设计了三个动物实验：(i)用30 μ g高压电穿孔（100 V） HA、HAe或HA1 DNA疫苗免疫BALB/c小鼠两次，增强后3周，用致死剂量的病毒攻毒。（ii）免疫和攻毒与实验1相同，但采用低压电穿孔（10 V）。（iii）小鼠用50 μ g DNA免疫1次，1周后攻毒。从抗体滴度、存活率、体重变化和肺病毒滴度等方面评价三种DNA疫苗的免疫原性效果。在所有三个实验中，HA和HAe诱导的抗体和中和滴度都高于HA1。在实验ii和iii中，用小鼠适应的致死性同源病毒攻击后，HA和HAe都降低了肺洗液中的病毒滴度，或者比HA1提供了更好的减肥保护。因此，当用作DNA疫苗时，HA1诱导的免疫反应比HA或HAe低。当面临大流行性流感的威胁时，我们的数据应该对选择最佳候选疫苗有价值。
Plasmid DNA vaccines are considered alternatives to inactivated influenza virus vaccines to control influenza. Vaccination with a hemagglutinin (HA)-, HA ectodomain (HAe)-, or HA subunit 1 (HA1)-based vaccine can stimulate protective immunity in animals. The aim of this study was to compare their capacity to induce an antibody response and protection against influenza virus infection in mice after DNA vaccination. We constructed three expression vectors encoding full-length HA, HAe, or HA1 of the A/California/07/2009 influenza A virus and designed three animal experiments: (i) BALB/c mice were immunized twice with 30 mu g of the HA, HAe, or HA1 DNA vaccine with high-voltage electroporation (100 V), and 3 weeks after boosting, they were challenged with a lethal dose of virus. (ii) Immunization and challenge were as in experiment i, but with low-voltage electroporation (10 V). (iii) Mice were immunized once with 50 mu g of DNA and challenged 1 week later. The immunogenic effects of the three DNA vaccines were evaluated in terms of antibody titer, survival rate, bodyweight change, and lung viral titer. In all three experiments, both HA and HAe induced higher antibody and neutralization titers than HA1. Following challenge with a lethal mouse-adapted homologous virus, both HA and HAe reduced the viral titers in lung washes or offered better protection from weight loss than HA1 in experiments ii and iii. Thus, HA1 induces a lower immune response than HA or HAe when used as a DNA vaccination. Our data should be valuable in choosing the optimal candidate vaccine when faced with the threat of pandemic influenza.