Universal influenza B vaccine based on the maturational cleavage site of the hemagglutinin precursor
Universal influenza B vaccine based on the maturational cleavage site of the hemagglutinin precursor
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DOI：
10.1128/jvi.79.12.7380-7388.2005
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发表时间：
2005-06-01
影响因子：
5.4
通讯作者：
Pessi, A
中科院分区：
文献类型：
--
作者：
Bianchi, E;Liang, XP;Pessi, A
常规流感疫苗可以预防感染，但其效力取决于用于疫苗制备的毒株与人群中流行的毒株之间的抗原“匹配”程度。一种基于病毒不变区的通用流感疫苗，能够提供广泛的交叉反应保护，而不需要持续的生产更新，将解决一个主要的医疗需求。由于流感病毒类型和/或亚型（A/H3、A/H1或B）的时间和地理优势尚无法预测，因此通用疫苗（如目前使用的疫苗）应包括A型和B型流感病毒组分。然而，尽管对于甲型流感病毒有令人鼓舞的临床前数据，但是对于B流感病毒没有候选的通用疫苗。我们在此表明，基于B型流感病毒血凝素HA（0）前体的高度保守成熟裂解位点的肽缀合物疫苗，可以引发针对属于代表性非抗原性交叉反应性B型流感病毒谱系之一的病毒的致死性攻击的保护性免疫应答。我们证明HA（0）疫苗的保护作用是由抗体介导的，可能是通过效应器机制，并且保护性应答的主要部分靶向HA（0）的最保守区域，即易断裂键的P1残基和融合肽结构域。此外，我们提供了初步证据，证明该方法可以扩展到甲型流感病毒，尽管等效HA（0）缀合物不如对B流感病毒有效。
Conventional influenza vaccines can prevent infection, but their efficacy depends on the degree of antigenic "match" between the strains used for vaccine preparation and those circulating in the population. A universal influenza vaccine based on invariant regions of the virus, able to provide broadly cross-reactive protection, without requiring continuous manufacturing update, would solve a major medical need. Since the temporal and geographical dominance of the influenza virus type and/or subtype (A/H3, A/H1, or B) cannot yet be predicted, a universal vaccine, like the vaccines currently in use, should include both type A and type B influenza virus components. However, while encouraging preclinical data are available for influenza A virus, no candidate universal vaccine is available for influenza B virus. We show here that a peptide conjugate vaccine, based on the highly conserved maturational cleavage site of the HA(0) precursor of the influenza B virus hemagglutinin, can elicit a protective immune response against lethal challenge with viruses belonging to either one of the representative, non-antigenically cross-reactive influenza B virus lineages. We demonstrate that protection by the HA(0) vaccine is mediated by antibodies, probably through effector mechanisms, and that a major part of the protective response targets the most conserved region of HA(0), the P1 residue of the scissile bond and the fusion peptide domain. In addition, we present preliminary evidence that the approach can be extended to influenza A virus, although the equivalent HA(0) conjugate is not as efficacious as for influenza B virus.