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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2011-1-6
pubmed: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, FcR?(-/-), Fc?RI(-/-), Fc?RIII(-/-), and (Fc?RI, Fc?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?RIII for in vivo immune protection but other anti-M2e IgG isotypes can rescue Fc?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?RI, Fc?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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1550-6606
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
186
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1022-31
pubmed:meshHeading
pubmed-meshheading:21169548-Animals, pubmed-meshheading:21169548-Cell Death, pubmed-meshheading:21169548-Cytotoxicity, Immunologic, pubmed-meshheading:21169548-Disease Models, Animal, pubmed-meshheading:21169548-Female, pubmed-meshheading:21169548-Immunization, Passive, pubmed-meshheading:21169548-Immunoglobulin G, pubmed-meshheading:21169548-Influenza A virus, pubmed-meshheading:21169548-Influenza Vaccines, pubmed-meshheading:21169548-Lymphocyte Depletion, pubmed-meshheading:21169548-Macrophages, Alveolar, pubmed-meshheading:21169548-Mice, pubmed-meshheading:21169548-Mice, Inbred BALB C, pubmed-meshheading:21169548-Mice, Inbred C57BL, pubmed-meshheading:21169548-Mice, Knockout, pubmed-meshheading:21169548-Orthomyxoviridae Infections, pubmed-meshheading:21169548-Protein Interaction Domains and Motifs, pubmed-meshheading:21169548-Receptors, Fc, pubmed-meshheading:21169548-Receptors, IgG, pubmed-meshheading:21169548-Viral Matrix Proteins
pubmed:year
2011
pubmed:articleTitle
Universal vaccine based on ectodomain of matrix protein 2 of influenza A: Fc receptors and alveolar macrophages mediate protection.
pubmed:affiliation
Department for Molecular Biomedical Research, Flanders Institute of Biotechnology (VIB), B-9052 Ghent, Belgium.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural