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Supplementation of Influenza Split Vaccines with Conserved M2 Ectodomains Overcomes Strain-Specificity and Provides Long-term Cross Protection

tetano

Editor, Senior Moderator
Mol Ther. 2014 Mar 4. doi: 10.1038/mt.2014.33. [Epub ahead of print]
Supplementation of Influenza Split Vaccines with Conserved M2 Ectodomains Overcomes Strain-Specificity and Provides Long-term Cross Protection.
Kim MC1, Lee YN2, Ko EJ2, Lee JS2, Kwon YM2, Hwang HS2, Song JM3, Song BM4, Lee YJ4, Choi JG4, Kang HM4, Quan FS5, Compans RW6, Kang SM2.
Author information
Abstract

Current influenza vaccines do not provide good protection against antigenically different influenza A viruses. As an approach to overcome strain-specificity of protection, this study demonstrates significantly improved long-term cross protection by supplementing split vaccines with a conserved molecular target, a repeat of the influenza M2 ectodomain (M2e) expressed on virus-like particles (M2e5x VLPs) in a membrane-anchored form. Intramuscular immunization with H1N1 split vaccine (A/California/07/2009) supplemented with M2e5x VLPs induced M2e specific humoral and cellular immune responses, and shaped the host responses to the vaccine in the direction of T helper type 1 responses inducing dominant IgG2a isotype antibodies as well as IFN-? producing cells in systemic and mucosal sites. Upon lethal challenge, M2e5x VLP-supplemented vaccination lowered lung viral loads and induced long-term cross protection against H3N2 or H5N1 subtype influenza viruses over 12 months. M2e antibodies, CD4 T cells, and CD8 T-cells were found to contribute to improving heterosubtypic cross protection. In addition, improved cross protection by supplemented vaccination with M2e5x VLPs was mediated via Fc receptors. The results support evidence that supplementation with M2e5x VLPs is a promising approach for overcoming the limitation of strain-specific protection by current influenza vaccination.Molecular Therapy (2014); doi:10.1038/mt.2014.33.

PMID:
24590045
[PubMed - as supplied by publisher]

http://www.ncbi.nlm.nih.gov/pubmed/24590045
 
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