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 found that single amino acid substitutions in the HA can escape antibody neutralization by a combination of antigenic alterations and altered specificity for host sialic acids.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Intramural Research (Z01)
Project #
1Z01AI001055-01
Application #
7732703
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
1
Fiscal Year
2008
Total Cost
$547,150
Indirect Cost
City
State
Country
United States
Zip Code
Yewdell, Jonathan W; Ince, William L (2013) Greasing the SCIDs for universal flu antibodies. Cell Host Microbe 14:7-8
Das, Suman R; Hensley, Scott E; Ince, William L et al. (2013) Defining influenza A virus hemagglutinin antigenic drift by sequential monoclonal antibody selection. Cell Host Microbe 13:314-23
Hensley, Scott E; Yewdell, Jonathan W (2009) Que sera, sera: evolution of the swine H1N1 influenza A virus. Expert Rev Anti Infect Ther 7:763-8
Yewdell, Jonathan W (2008) How to succeed in science: a concise guide for young biomedical scientists. Part I: taking the plunge. Nat Rev Mol Cell Biol 9:413-6
Yewdell, Jonathan W (2008) How to succeed in science: a concise guide for young biomedical scientists. Part II: making discoveries. Nat Rev Mol Cell Biol 9:491-4