Friedrich-Loeffler-Institute, Institute of Molecular Biology, Federal Research Institute for Animal Health, Suedufer 10, Greifswald - Insel Riems, 17493, Germany.
Expert Opin Ther Pat. 2010 Mar;20(3):447-50. doi: 10.1517/13543770903547855.
The respiratory disease influenza gives rise to severe public health concerns. During inter-pandemic periods, the constant problem of the annually recurring seasonal influenza is perpetuated by the ability of influenza viruses to alter their surface antigens continuously (antigenic drift). Therefore, vaccines eliciting broad immunity against drift variants still remain a major objective in vaccine development. The patent WO2008048984 evaluated in this article claims an approach which aims to elicit homosubtypic protection against drift variants by simultaneous vaccination with several hemagglutinins (HAs) of the same serotype. The proposed multivalent vaccine based on simultaneous administration of several HAs, the results obtained from mice immunization studies and the implications of this concept are discussed in light of their relevance to application in humans. This proof-of-principle study suggests that a multivalent HA vaccine could elicit broad protection against drifted virus variants of one HA subtype. In the future, the dependence of broad efficacy on large antigenic distances among the HAs used for immunization as well as the antigenic distance between the HAs administered to that of the challenge virus, the immunological correlates of broad efficacy, and the suitability of this concept for domestic animals and humans remain to be investigated.
流感等呼吸道疾病引起了严重的公共卫生关注。在大流行期间，流感病毒不断改变其表面抗原（抗原漂移），使得每年都会出现季节性流感这一持续存在的问题。因此，开发能够诱导针对漂移变异体产生广泛免疫的疫苗仍然是疫苗开发的主要目标。本文评估的专利 WO2008048984 提出了一种通过同时用几种同种血清型血凝素（HA）进行疫苗接种来诱导同亚型漂移保护的方法。基于同时给予几种 HA 的多价疫苗、从小鼠免疫研究中获得的结果以及这一概念的意义，根据其对人类应用的相关性进行了讨论。这项原理验证研究表明，多价 HA 疫苗可诱导针对同一 HA 亚型漂移病毒变异体的广泛保护。在未来，广泛有效性对用于免疫接种的 HA 之间的大抗原距离以及所接种 HA 与挑战病毒之间的抗原距离的依赖性、广泛有效性的免疫学相关性以及该概念在 家畜和人类中的适用性仍有待研究。
