Department of Microbiology and Immunology and Emory Vaccine Center, Emory University School of Medicine, Atlanta, GA 30322, USA.
Proc Natl Acad Sci U S A. 2011 Jan 11;108(2):757-61. doi: 10.1073/pnas.1012199108. Epub 2010 Dec 27.
Development of an influenza vaccine that provides broadly cross-protective immunity has been a scientific challenge for more than half a century. This study presents an approach to overcome strain-specific protection by supplementing conventional vaccines with virus-like particles (VLPs) containing the conserved M2 protein (M2 VLPs) in the absence of adjuvants. We demonstrate that an inactivated influenza vaccine supplemented with M2 VLPs prevents disease symptoms without showing weight loss and confers complete cross protection against lethal challenge with heterologous influenza A viruses including the 2009 H1N1 pandemic virus as well as heterosubtypic H3N2 and H5N1 influenza viruses. Cross-protective immunity was long-lived, for more than 7 mo. Immune sera from mice immunized with M2 VLP supplemented vaccine transferred cross protection to naive mice. Dendritic and macrophage cells were found to be important for this cross protection mediated by immune sera. The results provide evidence that supplementation of seasonal influenza vaccines with M2 VLPs is a promising approach for overcoming the limitation of strain-specific protection by current vaccines and developing a universal influenza A vaccine.
开发一种能提供广泛交叉保护免疫的流感疫苗，是半个多世纪以来的科学挑战。本研究提出了一种方法，通过在没有佐剂的情况下，用含有保守 M2 蛋白的病毒样颗粒（M2 VLPs）来补充传统疫苗，从而克服针对特定菌株的保护。我们证明，添加 M2 VLPs 的灭活流感疫苗能预防疾病症状，不导致体重减轻，并能完全交叉保护免受包括 2009 年 H1N1 大流行病毒在内的异源甲型流感病毒以及异亚型 H3N2 和 H5N1 流感病毒的致死性攻击。交叉保护免疫的持续时间长达 7 个月以上。用添加 M2 VLP 的疫苗免疫的小鼠的免疫血清能将交叉保护作用转移给未免疫的小鼠。发现树突状细胞和巨噬细胞对这种由免疫血清介导的交叉保护作用很重要。研究结果表明，在季节性流感疫苗中添加 M2 VLPs 是一种很有前途的方法，能克服当前疫苗针对特定菌株保护的局限性，并开发出通用的甲型流感疫苗。
