Takada Ayato, Matsushita Sachiko, Ninomiya Ai, Kawaoka Yoshihiro, Kida Hiroshi
Division of Virology, Department of Microbiology and Immunology, Institute of Medical Science, University of Tokyo, Tokyo, 108-8639, Japan.
Vaccine. 2003 Jul 4;21(23):3212-8. doi: 10.1016/s0264-410x(03)00234-2.
It has been known that influenza A virus infection induces a cross-protective immunity against infection by viruses with different subtypes of viral envelope proteins, hemagglutinin (HA) and neuraminidase (NA). This heterosubtypic immunity is generally mediated by cytotoxic T lymphocytes (CTL) reactive to specific epitopes in the viral internal proteins, such as nucleoprotein and matrix protein. By contrast, immunization with inactivated virus antigens has been thought to be unable to generate heterosubtypic immunity, since inactivated antigens do not usually induce CTL responses. However, we show that intranasal immunization with formalin-inactivated intact virus, but not ether-split vaccines, induced a broad spectrum of heterosubtypic protective immunity in mice. The protection may be mediated by the mucosal immune response, most likely secretory IgA antibodies to the viral proteins. This approach may overcome limitations in the efficacy of inactivated influenza vaccines and confer potent immunity to humans against viruses with new pandemic potential.
已知甲型流感病毒感染可诱导针对具有不同亚型病毒包膜蛋白（血凝素（HA）和神经氨酸酶（NA））的病毒感染的交叉保护性免疫。这种异源亚型免疫通常由对病毒内部蛋白（如核蛋白和基质蛋白）中特定表位有反应的细胞毒性T淋巴细胞（CTL）介导。相比之下，用灭活病毒抗原进行免疫一直被认为无法产生异源亚型免疫，因为灭活抗原通常不会诱导CTL反应。然而，我们发现，用福尔马林灭活的完整病毒经鼻内免疫，而非醚裂解疫苗，可在小鼠中诱导广泛的异源亚型保护性免疫。这种保护可能由黏膜免疫反应介导，很可能是针对病毒蛋白的分泌型IgA抗体。这种方法可能克服灭活流感疫苗效力的局限性，并赋予人类针对具有新大流行潜力病毒的强大免疫力。
