Cross-clade protective immune responses to influenza viruses with H5N1 HA and NA elicited by an influenza virus-like particle.
Cross-clade protective immune responses to influenza viruses with H5N1 HA and NA elicited by an influenza virus-like particle.
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DOI：
10.1371/journal.pone.0001501
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发表时间：
2008-01-30
期刊：
影响因子：
3.7
通讯作者：
Ross TM
中科院分区：
文献类型：
--
作者：
Bright RA;Carter DM;Crevar CJ;Toapanta FR;Steckbeck JD;Cole KS;Kumar NM;Pushko P;Smith G;Tumpey TM;Ross TM
疫苗接种是应对季节性或大流行性流感爆发威胁的一种经济有效的对策。为了满足改进流感疫苗和鸡蛋生产替代品的需求，我们设计了一种流感病毒样颗粒 (VLP)，作为新一代非鸡蛋或非哺乳动物细胞培养的候选疫苗。我们使用昆虫细胞从杆状病毒表达系统中产生了一种非感染性重组 VLP 疫苗，来自具有大流行潜力的甲型流感 H5N1 进化枝 1 和进化枝 2 分离株。以一剂或两剂方案给小鼠施用 VLP，并将免疫反应与重组血凝素 (rHA) 诱导的免疫反应进行比较。分析了体液和细胞反应。接种 VLP 的小鼠可以免受表达 H5N1 HA 和 NA 的致命重配病毒的攻击，无论 H5N1 进化枝与疫苗是同源还是异源。然而，接种 rHA 的小鼠在受到异变分支病毒攻击后表现出明显的体重减轻和死亡。 VLP 诱导的死亡保护作用与攻击前 HAI 滴度或细胞介导的 HA 或 M1 反应无关，因为接种疫苗的小鼠具有低至不可检测的跨进化枝 HAI 抗体或对流感抗原的细胞反应，仍然免受致命病毒攻击。然而，与 rHA 疫苗相比，抗体与 HA 结合的明显关联率与保护作用相关，并且使用 VLP 可以增强抗体结合率，特别是在鼻内递送时。这是第一份描述使用从进化枝 2 分离株制备的 H5N1 VLP 疫苗的报告。结果表明，非复制型病毒样颗粒可有效引发针对新出现的 H5N1 流感分离株的蛋白质的更广泛的跨进化枝保护性免疫反应，从而产生潜在的人类大流行性流感候选疫苗，可以储存以备 H5N1 流感爆发时使用。
Vaccination is a cost-effective counter-measure to the threat of seasonal or pandemic outbreaks of influenza. To address the need for improved influenza vaccines and alternatives to egg-based manufacturing, we have engineered an influenza virus-like particle (VLP) as a new generation of non-egg or non-mammalian cell culture-based candidate vaccine. We generated from a baculovirus expression system using insect cells, a non-infectious recombinant VLP vaccine from both influenza A H5N1 clade 1 and clade 2 isolates with pandemic potential. VLPs were administered to mice in either a one-dose or two-dose regimen and the immune responses were compared to those induced by recombinant hemagglutinin (rHA). Both humoral and cellular responses were analyzed. Mice vaccinated with VLPs were protected against challenge with lethal reassortant viruses expressing the H5N1 HA and NA, regardless if the H5N1 clade was homologous or heterologous to the vaccine. However, rHA-vaccinated mice showed considerable weight loss and death following challenge with the heterovariant clade virus. Protection against death induced by VLPs was independent of the pre-challenge HAI titer or cell-mediated responses to HA or M1 since vaccinated mice, with low to undetectable cross-clade HAI antibodies or cellular responses to influenza antigens, were still protected from a lethal viral challenge. However, an apparent association rate of antibody binding to HA correlated with protection and was enhanced using VLPs, particularly when delivered intranasally, compared to rHA vaccines. This is the first report describing the use of an H5N1 VLP vaccine created from a clade 2 isolate. The results show that a non-replicating virus-like particle is effective at eliciting a broadened, cross-clade protective immune response to proteins from emerging H5N1 influenza isolates giving rise to a potential pandemic influenza vaccine candidate for humans that can be stockpiled for use in the event of an outbreak of H5N1 influenza.
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影响因子：
3.7
作者：
Bower, JF;Green, TD;Ross, TM
通讯作者：
Ross, TM
DOI：
10.1001/jama.295.8.joc60020
发表时间：
2006-02-22
影响因子：
120.7
作者：
Bright, RA;Shay, DK;Klimov, AI
通讯作者：
Klimov, AI
DOI：
10.1073/pnas.96.15.8597
发表时间：
1999-07-20
影响因子：
11.1
作者：
Flynn, KJ;Riberdy, JM;Doherty, PC
通讯作者：
Doherty, PC
影响因子：
5.4
作者：
Gao, WT;Soloff, AC;Gambotto, A
通讯作者：
Gambotto, A
影响因子：
12.7
作者：
Asahi-Ozaki, Y;Yoshikawa, T;Sata, T
通讯作者：
Sata, T