| First Author | El Bakkouri K | Year | 2011 |
| Journal | J Immunol | Volume | 186 |
| Issue | 2 | Pages | 1022-31 |
| PubMed ID | 21169548 | Mgi Jnum | J:168757 |
| Mgi Id | MGI:4938203 | Doi | 10.4049/jimmunol.0902147 |
| Citation | El Bakkouri K, et al. (2011) Universal vaccine based on ectodomain of matrix protein 2 of influenza A: Fc receptors and alveolar macrophages mediate protection. J Immunol 186(2):1022-31 |
| abstractText | 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, FcRgamma(-/-), FcgammaRI(-/-), FcgammaRIII(-/-), and (FcgammaRI, FcgammaRIII)(-/-) 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 FcgammaRIII for in vivo immune protection but other anti-M2e IgG isotypes can rescue FcgammaRIII(-/-) 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 (FcgammaRI, FcgammaRIII)(-/-) 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. |
