Influenza virus evolution precludes long lasting natural or vaccine induced immunity to IAV, and is the cause of yearly vaccine reformulation. Antigenic variation in the hemagglutinin (HA) glycoprotein is the sine qua non of human influenza A viruses (IAVs). Despite its importance, we have only a limited understanding of the molecular mechanisms underlying influenza virus evolution in vivo. To study virus changes in the context of natural in vivo transmission, we aim to set up a guinea pig transmission model of influenza virus infection. We have recently shown that many of the HA mutations that occur during viral passage in mice result in alterations in HA receptor affinity. We are following these changes in a natural model of influenza transmission and also examining modifications that may occur in the viral NA because the NA and HA must work together to enable viral entry and release from cells.

Project Start
Project End
Budget Start
Budget End
Support Year
Fiscal Year
Total Cost
Indirect Cost
Zip Code
Li, Gui-Mei; Chiu, Christopher; Wrammert, Jens et al. (2012) Pandemic H1N1 influenza vaccine induces a recall response in humans that favors broadly cross-reactive memory B cells. Proc Natl Acad Sci U S A 109:9047-52
O'Donnell, Christopher D; Vogel, Leatrice; Wright, Amber et al. (2012) Antibody pressure by a human monoclonal antibody targeting the 2009 pandemic H1N1 virus hemagglutinin drives the emergence of a virus with increased virulence in mice. MBio 3:
Wrammert, Jens; Koutsonanos, Dimitrios; Li, Gui-Mei et al. (2011) Broadly cross-reactive antibodies dominate the human B cell response against 2009 pandemic H1N1 influenza virus infection. J Exp Med 208:181-93
Khurana, Surender; Verma, Nitin; Yewdell, Jonathan W et al. (2011) MF59 adjuvant enhances diversity and affinity of antibody-mediated immune response to pandemic influenza vaccines. Sci Transl Med 3:85ra48