AI Article Synopsis

  • Influenza virus continues to pose a significant threat due to its ability to change and avoid detection by vaccines, known as antigenic drift.
  • Researchers have isolated a human monoclonal antibody, MEDI8852, that effectively targets all influenza A hemagglutinin subtypes and shows better effectiveness compared to other antibodies.
  • MEDI8852 has been shown to work well in animal studies, providing a promising approach for immunotherapy against influenza infections in humans.

Article Abstract

Influenza virus remains a threat because of its ability to evade vaccine-induced immune responses due to antigenic drift. Here, we describe the isolation, evolution, and structure of a broad-spectrum human monoclonal antibody (mAb), MEDI8852, effectively reacting with all influenza A hemagglutinin (HA) subtypes. MEDI8852 uses the heavy-chain VH6-1 gene and has higher potency and breadth when compared to other anti-stem antibodies. MEDI8852 is effective in mice and ferrets with a therapeutic window superior to that of oseltamivir. Crystallographic analysis of Fab alone or in complex with H5 or H7 HA proteins reveals that MEDI8852 binds through a coordinated movement of CDRs to a highly conserved epitope encompassing a hydrophobic groove in the fusion domain and a large portion of the fusion peptide, distinguishing it from other structurally characterized cross-reactive antibodies. The unprecedented breadth and potency of neutralization by MEDI8852 support its development as immunotherapy for influenza virus-infected humans.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4967455PMC
http://dx.doi.org/10.1016/j.cell.2016.05.073DOI Listing

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