The Journal of immunology (1950), 2011-01, Vol.186 (2), p.1022-1031
2011
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- Autor(en) / Beteiligte
- Titel
- Universal vaccine based on ectodomain of matrix protein 2 of influenza A: Fc receptors and alveolar macrophages mediate protection
- Ist Teil von
- The Journal of immunology (1950), 2011-01, Vol.186 (2), p.1022-1031
- Ort / Verlag
- United States
- Erscheinungsjahr
- 2011
- Quelle
- MEDLINE
- Beschreibungen/Notizen
- 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, FcRγ(-/-), FcγRI(-/-), FcγRIII(-/-), and (FcγRI, FcγRIII)(-/-) 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 FcγRIII for in vivo immune protection but other anti-M2e IgG isotypes can rescue FcγRIII(-/-) 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 (FcγRI, FcγRIII)(-/-) 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 0022-1767eISSN: 1550-6606DOI: 10.4049/jimmunol.0902147Titel-ID: cdi_proquest_miscellaneous_904463498
- Format
- –
- Schlagworte
- Animals, Cell Death - genetics, Cell Death - immunology, Cytotoxicity, Immunologic, Disease Models, Animal, Female, Immunization, Passive, Immunoglobulin G - metabolism, Immunoglobulin G - toxicity, Influenza A virus, Influenza A virus - genetics, Influenza A virus - immunology, Influenza Vaccines - genetics, Influenza Vaccines - immunology, Influenza Vaccines - therapeutic use, Lymphocyte Depletion - methods, Macrophages, Alveolar - immunology, Macrophages, Alveolar - pathology, Macrophages, Alveolar - virology, Mice, Mice, Inbred BALB C, Mice, Inbred C57BL, Mice, Knockout, Orthomyxoviridae Infections - immunology, Orthomyxoviridae Infections - pathology, Orthomyxoviridae Infections - prevention & control, Protein Interaction Domains and Motifs - genetics, Protein Interaction Domains and Motifs - immunology, Receptors, Fc - deficiency, Receptors, Fc - physiology, Receptors, Fc - therapeutic use, Receptors, IgG - deficiency, Receptors, IgG - metabolism, Receptors, IgG - physiology, Viral Matrix Proteins - genetics, Viral Matrix Proteins - immunology, Viral Matrix Proteins - therapeutic use