Chen Jianjun, Liu Qian, Chen Quanjiao, Xiong Chaochao, Yao Yanfeng, Wang Huadong, Wang Hanzhong, Chen Ze
Center for Emerging Infectious Diseases, Wuhan Institute of Virology, Chinese Academy of Sciences, Wuhan, Hubei, China,
Arch Virol. 2014 Apr;159(4):689-700. doi: 10.1007/s00705-013-1878-1. Epub 2013 Oct 17.
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 μg 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 μg 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.
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。用基于血凝素(HA)、HA胞外域(HAe)或HA亚基1(HA1)的疫苗进行接种可刺激动物产生保护性免疫。本研究的目的是比较DNA疫苗接种后它们在小鼠中诱导抗体反应和预防流感病毒感染的能力。我们构建了三种表达载体,分别编码A/加利福尼亚/07/2009甲型流感病毒的全长HA、HAe或HA1,并设计了三个动物实验:(i)用30μg的HA、HAe或HA1 DNA疫苗对BALB/c小鼠进行两次高压电穿孔(100V)免疫,加强免疫3周后,用致死剂量的病毒进行攻击。(ii)免疫和攻击与实验i相同,但采用低压电穿孔(10V)。(iii)小鼠用50μg DNA免疫一次,1周后进行攻击。根据抗体滴度、存活率、体重变化和肺病毒滴度评估三种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均高于HA1。在用致死性小鼠适应同源病毒攻击后,在实验ii和iii中,HA和HAe均降低了肺灌洗液中的病毒滴度,或比HA1提供了更好的体重减轻保护。因此,当用作DNA疫苗时,HA1诱导的免疫反应低于HA或HAe。在面临大流行性流感威胁时,我们的数据对于选择最佳候选疫苗应该是有价值的。