Influenza nucleoprotein delivered with aluminium salts protects mice from an influenza A virus that expresses an altered nucleoprotein sequence.

Influenza nucleoprotein delivered with aluminium salts protects mice from an influenza A virus that expresses an altered nucleoprotein sequence.
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DOI:
10.1371/journal.pone.0061775
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发表时间:
2013
期刊:
影响因子:
3.7
通讯作者:
Marrack P
Marrack P
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Macleod MK;David A;Jin N;Noges L;Wang J;Kappler JW;Marrack P

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流感病毒对保护性免疫提出了严峻的挑战。这种病毒善于改变其表面蛋白,这些蛋白是中和抗体的目标。因此,每年都必须开发新的疫苗来对抗当前的再循环菌株。一种通用的流感疫苗,可以引发识别病毒保守部分的特定记忆细胞,可以证明对每年的流感变种和新出现的潜在大流行毒株都有效。这种疫苗必须含有安全有效的佐剂,可用于所有年龄段的个体。我们研究了用来自A型流感PR8株的核蛋白接种的小鼠对病毒攻击的保护作用,该蛋白在病毒亚型中高度保守。用普遍使用的安全佐剂(由不溶性铝盐组成)递送的核蛋白接种疫苗,提供针对表达相同或改变形式的核蛋白的病毒的保护。这种保护与感染后早期感染动物肺中存在核蛋白特异性CD8 T细胞相关。相比之下,与明矾和解毒的LPS佐剂,单磷酰脂质A,提供了一些保护同源病毒株,但没有保护流感病毒感染表达的变异核蛋白的NP免疫。总之,这些数据指向所有甲型流感亚型的疫苗解决方案。
Influenza virus poses a difficult challenge for protective immunity. This virus is adept at altering its surface proteins, the proteins that are the targets of neutralizing antibody. Consequently, each year a new vaccine must be developed to combat the current recirculating strains. A universal influenza vaccine that primes specific memory cells that recognise conserved parts of the virus could prove to be effective against both annual influenza variants and newly emergent potentially pandemic strains. Such a vaccine will have to contain a safe and effective adjuvant that can be used in individuals of all ages. We examine protection from viral challenge in mice vaccinated with the nucleoprotein from the PR8 strain of influenza A, a protein that is highly conserved across viral subtypes. Vaccination with nucleoprotein delivered with a universally used and safe adjuvant, composed of insoluble aluminium salts, provides protection against viruses that either express the same or an altered version of nucleoprotein. This protection correlated with the presence of nucleoprotein specific CD8 T cells in the lungs of infected animals at early time points after infection. In contrast, immunization with NP delivered with alum and the detoxified LPS adjuvant, monophosphoryl lipid A, provided some protection to the homologous viral strain but no protection against infection by influenza expressing a variant nucleoprotein. Together, these data point towards a vaccine solution for all influenza A subtypes.
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