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Universal vaccine based on ectodomain of matrix protein 2 of Influenza A: Fc receptors and alveolar macrophages mediate protection

(2011) JOURNAL OF IMMUNOLOGY. 186(2). p.1022-1031
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Abstract
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.
Keywords
MONOCLONAL-ANTIBODY, EXTRACELLULAR DOMAIN, M2 PROTEIN, GAMMA-RIII CD16, VIRUS-REPLICATION, MICE, INFECTION, SUBCLASS, PHAGOCYTOSIS, MICRODOMAINS

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Chicago
El Bakkouri, Karim, Francis Descamps, Marina De Filette, Anouk Smet, Els Festjens, Ashley Birkett, Nico Van Rooijen, Sjef Verbeek, Walter Fiers, and Xavier Saelens. 2011. “Universal Vaccine Based on Ectodomain of Matrix Protein 2 of Influenza A: Fc Receptors and Alveolar Macrophages Mediate Protection.” Journal of Immunology 186 (2): 1022–1031.
APA
El Bakkouri, K., Descamps, F., De Filette, M., Smet, A., Festjens, E., Birkett, A., Van Rooijen, N., et al. (2011). Universal vaccine based on ectodomain of matrix protein 2 of Influenza A: Fc receptors and alveolar macrophages mediate protection. JOURNAL OF IMMUNOLOGY, 186(2), 1022–1031.
Vancouver
1.
El Bakkouri K, Descamps F, De Filette M, Smet A, Festjens E, Birkett A, et al. Universal vaccine based on ectodomain of matrix protein 2 of Influenza A: Fc receptors and alveolar macrophages mediate protection. JOURNAL OF IMMUNOLOGY. 2011;186(2):1022–31.
MLA
El Bakkouri, Karim, Francis Descamps, Marina De Filette, et al. “Universal Vaccine Based on Ectodomain of Matrix Protein 2 of Influenza A: Fc Receptors and Alveolar Macrophages Mediate Protection.” JOURNAL OF IMMUNOLOGY 186.2 (2011): 1022–1031. Print.
@article{1187377,
  abstract     = {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.},
  author       = {El Bakkouri, Karim and Descamps, Francis and De Filette, Marina and Smet, Anouk and Festjens, Els and Birkett, Ashley and Van Rooijen, Nico and Verbeek, Sjef and Fiers, Walter and Saelens, Xavier},
  issn         = {0022-1767},
  journal      = {JOURNAL OF IMMUNOLOGY},
  keywords     = {MONOCLONAL-ANTIBODY,EXTRACELLULAR DOMAIN,M2 PROTEIN,GAMMA-RIII CD16,VIRUS-REPLICATION,MICE,INFECTION,SUBCLASS,PHAGOCYTOSIS,MICRODOMAINS},
  language     = {eng},
  number       = {2},
  pages        = {1022--1031},
  title        = {Universal vaccine based on ectodomain of matrix protein 2 of Influenza A: Fc receptors and alveolar macrophages mediate protection},
  url          = {http://dx.doi.org/10.4049/jimmunol.0902147},
  volume       = {186},
  year         = {2011},
}

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