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An Influenza A Vaccine Based on Tetrameric Ectodomain of Matrix Protein 2.
- Source :
-
Journal of Biological Chemistry . 4/25/2008, Vol. 283 Issue 17, p11382-11387. 6p. 5 Color Photographs, 10 Graphs. - Publication Year :
- 2008
-
Abstract
- Matrix protein 2 (M2) of influenza A is a tetrameric type III membrane protein that functions as a proton-selective channel. The extracellular domain (M2e) has remained nearly invariable since the first human influenza strain was isolated in 1933. By linking a modified form of the leucine zipper of the yeast transcription factor GCN4 to M2e, we obtained a recombinant tetrameric protein, M2e-tGCN4. This protein mimics the quaternary structure of the ectodomain of the natural M2 protein. M2e-tGCN4 was purified, biochemically characterized, and used to immunize BALB/c mice. High M2e-specific serum IgG antibody titers were obtained following either intraperitoneal or intranasal administration. Immunized mice were protected fully against a potentially lethal influenza A virus challenge. Antibodies raised by M2e-tGCN4 immunization specifically bound to the surface of influenza-infected cells and to an M2-ex- pressing cell line. Using a M2e peptide competition enzyme- linked immunosorbent assay with M2-expressing cells as target, we obtained evidence that M2e-tGCN4 induces antibodies that are specific for the native tetrameric M2 ectodomain. Therefore, fusion of an oligomerization domain to the extracellular part of a transmembrane protein allows it to mimic the natural quaternary structure and can promote the induction of oligomer-specific antibodies. [ABSTRACT FROM AUTHOR]
- Subjects :
- *INFLUENZA A virus
*VACCINATION
*INFLUENZA viruses
*MEMBRANE proteins
*PROTEINS
Subjects
Details
- Language :
- English
- ISSN :
- 00219258
- Volume :
- 283
- Issue :
- 17
- Database :
- Academic Search Index
- Journal :
- Journal of Biological Chemistry
- Publication Type :
- Academic Journal
- Accession number :
- 32037161
- Full Text :
- https://doi.org/10.1074/jbc.M800650200