Though current vaccines reduce the impact of influenza, IAV remains a major human pathogen with an enormous global and domestic impact, causing 30,000 deaths per year in the USA and economic costs totaling tens of billions dollars each year in the USA. Despite its remarkable impact on public health, we have only a limited understanding of the molecular mechanisms underlying its ability to evade the immune response. Antigenic drift precludes long lasting natural or vaccine induced immunity to IAV, and is the cause of yearly vaccine reformulation. Despite its remarkable impact on public health, we have only a limited understanding of the molecular mechanisms underlying antigenic drift. We are examining the changes in the structure and function of the influenza HA that provide an advantage in the face of the host neutralizing antibody response.

Project Start
Project End
Budget Start
Budget End
Support Year
3
Fiscal Year
2010
Total Cost
$562,832
Indirect Cost
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State
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Frank, Gregory M; Angeletti, Davide; Ince, William L et al. (2015) A Simple Flow-Cytometric Method Measuring B Cell Surface Immunoglobulin Avidity Enables Characterization of Affinity Maturation to Influenza A Virus. MBio 6:e01156
Altman, Meghan O; Bennink, Jack R; Yewdell, Jonathan W et al. (2015) Lamprey VLRB response to influenza virus supports universal rules of immunogenicity and antigenicity. Elife 4:
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Whittle, James R R; Wheatley, Adam K; Wu, Lan et al. (2014) Flow cytometry reveals that H5N1 vaccination elicits cross-reactive stem-directed antibodies from multiple Ig heavy-chain lineages. J Virol 88:4047-57
Brooke, Christopher B; Ince, William L; Wrammert, Jens et al. (2013) Most influenza a virions fail to express at least one essential viral protein. J Virol 87:3155-62
Graber, Tyson E; Hébert-Seropian, Sarah; Khoutorsky, Arkady et al. (2013) Reactivation of stalled polyribosomes in synaptic plasticity. Proc Natl Acad Sci U S A 110:16205-10
Yewdell, Jonathan W (2013) To dream the impossible dream: universal influenza vaccination. Curr Opin Virol 3:316-21
Ince, William L; Gueye-Mbaye, Aissatou; Bennink, Jack R et al. (2013) Reassortment complements spontaneous mutation in influenza A virus NP and M1 genes to accelerate adaptation to a new host. J Virol 87:4330-8
Brooke, Christopher B; Yewdell, Jonathan W (2013) Host versus flu: antibodies win a round? Nat Struct Mol Biol 20:245-6

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