Universal Vaccine Based on Ectodomain of Matrix Protein 2 of Influenza A: Fc Receptors and Alveolar Macrophages Mediate Protection
Universal Vaccine Based on Ectodomain of Matrix Protein 2 of Influenza A: Fc Receptors and Alveolar Macrophages Mediate Protection
复制标题
DOI：
10.4049/jimmunol.0902147
复制
发表时间：
2011-01-15
影响因子：
4.4
通讯作者：
Saelens, Xavier
中科院分区：
文献类型：
--
作者：
El Bakkouri, Karim;Descamps, Francis;Saelens, Xavier
甲型流感病毒基质蛋白2（M2 e）的胞外域是通用甲型流感疫苗的一个有吸引力的靶点：M2 e序列在流感病毒亚型中高度保守，诱导的体液抗M2 e免疫在动物模型中保护免受致死性流感病毒攻击。M2 e候选疫苗的I期临床研究已经完成。然而，由M2 e-载体疫苗接种诱导的免疫保护的体内机制尚不清楚。使用野生型、FcR γ（-/-）、Fc γ RI-/-、Fc γ RIII-/-和（Fc γ RI、Fc γ RIII）（-/-）小鼠的被动免疫实验，我们在本研究中报告Fc受体对于抗M2 e IgG介导的免疫保护至关重要。M2 e特异性IgG 1同种型Ab显示需要功能性Fc γ RIII用于体内免疫保护，但其他抗M2 e IgG同种型可使Fc γ RIII-/-小鼠免于致死性攻击。使用条件性细胞耗竭方案，我们还证明了肺泡巨噬细胞（AM）在体液M2 e特异性免疫保护中起着至关重要的作用。此外，我们表明，野生型AM过继转移到（Fc γ RI，Fc γ RIII）（-/-）小鼠恢复被动转移的抗M2 e IgG的保护。我们得出结论，AM和Fc受体依赖性消除甲型流感病毒感染的细胞是必不可少的保护抗M2 e IgG。免疫学杂志，2011，186：1022-1031。
The ectodomain of matrix protein 2 (M2e) of influenza A virus is an attractive target for a universal influenza A vaccine: the M2e sequence is highly conserved across influenza virus subtypes, and induced humoral anti-M2e immunity protects against a lethal influenza virus challenge in animal models. Clinical phase I studies with M2e vaccine candidates have been completed. However, the in vivo mechanism of immune protection induced by M2e-carrier vaccination is unclear. Using passive immunization experiments in wild-type, FcR gamma(-/-), Fc gamma RI-/-, Fc gamma RIII-/-, and (Fc gamma RI, Fc gamma RIII)(-/-) mice, we report in this study that Fc receptors are essential for anti-M2e IgG-mediated immune protection. M2e-specific IgG1 isotype Abs are shown to require functional Fc gamma RIII for in vivo immune protection but other anti-M2e IgG isotypes can rescue Fc gamma RIII-/- mice from a lethal challenge. Using a conditional cell depletion protocol, we also demonstrate that alveolar macrophages (AM) play a crucial role in humoral M2e-specific immune protection. Additionally, we show that adoptive transfer of wild-type AM into (Fc gamma RI, Fc gamma RIII)(-/-) mice restores protection by passively transferred anti-M2e IgG. We conclude that AM and Fc receptor-dependent elimination of influenza A virus-infected cells are essential for protection by anti-M2e IgG. The Journal of Immunology, 2011, 186: 1022-1031.