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
2
Fiscal Year
2009
Total Cost
$541,176
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:
Brooke, Christopher B; Ince, William L; Wei, Jiajie et al. (2014) Influenza A virus nucleoprotein selectively decreases neuraminidase gene-segment packaging while enhancing viral fitness and transmissibility. Proc Natl Acad Sci U S A 111:16854-9
Magadán, Javier G; Altman, Meghan O; Ince, William L et al. (2014) Biogenesis of influenza a virus hemagglutinin cross-protective stem epitopes. PLoS Pathog 10:e1004204
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Yu, Cheng-Rong; Dambuza, Ivy M; Lee, Yong-Jun et al. (2013) STAT3 regulates proliferation and survival of CD8+ T cells: enhances effector responses to HSV-1 infection, and inhibits IL-10+ regulatory CD8+ T cells in autoimmune uveitis. Mediators Inflamm 2013:359674
Yewdell, Jonathan W; Spiro, David J; Golding, Hana et al. (2013) Getting to the heart of influenza. Sci Transl Med 5:191ed8
Magadan, Javier G; Khurana, Surender; Das, Suman R et al. (2013) Influenza a virus hemagglutinin trimerization completes monomer folding and antigenicity. J Virol 87:9742-53
Yewdell, Jonathan W; Ince, William L (2013) Greasing the SCIDs for universal flu antibodies. Cell Host Microbe 14:7-8
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

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