Department of Microbiology, Mount Sinai School of Medicine, New York, New York, USA.
mBio. 2010 May 18;1(1):e00018-10. doi: 10.1128/mBio.00018-10.
Although highly effective in the general population when well matched to circulating influenza virus strains, current influenza vaccines are limited in their utility due to the narrow breadth of protection they provide. The strain specificity of vaccines presently in use mirrors the exquisite specificity of the neutralizing antibodies that they induce, that is, antibodies which bind to the highly variable globular head domain of hemagglutinin (HA). Herein, we describe the construction of a novel immunogen comprising the conserved influenza HA stalk domain and lacking the globular head. Vaccination of mice with this headless HA construct elicited immune sera with broader reactivity than those obtained from mice immunized with a full-length HA. Furthermore, the headless HA vaccine provided full protection against death and partial protection against disease following lethal viral challenge. Our results suggest that the response induced by headless HA vaccines is sufficiently potent to warrant their further development toward a universal influenza virus vaccine.
尽管在与流行的流感病毒株匹配良好时对一般人群非常有效，但由于其提供的保护范围狭窄，当前的流感疫苗在实用性上存在局限性。目前使用的疫苗的菌株特异性反映了它们诱导的中和抗体的高度特异性，即与血凝素（HA）的高度可变球形头部结构域结合的抗体。在此，我们描述了一种新型免疫原的构建，该免疫原包含保守的流感 HA 茎部结构域且缺乏球形头部。用这种无头 HA 构建物对小鼠进行疫苗接种可引发比用全长 HA 免疫的小鼠产生的免疫血清具有更广泛的反应性。此外，无头 HA 疫苗可完全预防死亡，并在致命性病毒攻击后部分预防疾病。我们的研究结果表明，无头 HA 疫苗诱导的反应足够有效，值得进一步开发为通用流感病毒疫苗。
