Antigenic evolution and immunity to influenza
Why does the influenza vaccine fail? In spite of substantial efforts to vaccinate, influenza epidemics remain a major public health threat. In the US, the currently licensed vaccines are very safe, but only partially effective at protecting from infection. Though efficacy rates vary with age of the subjects and virus strains, estimates of protection range from 10-70%. As our abilities to study influenza viruses at the molecular level increase, and the costs to do so decrease, there are more reports of a significant degree of sequence diversity in the viruses that circulate seasonally. This raises the possibility that some of the vaccine failures may be due to antigenic drift in the viruses. Unfortunately, there are few (to no) studies that have assayed the virus sequences and antigenicity, and the specificity or function of the antibodies and memory B cells present in the subject who is infected.
As part of our surveillance activities, we will collect and analyze the viruses causing infections and match these to the individual’s antibody and B cell responses present before infection or at the time illness begins. We will also study the impact of infections versus vaccination on the responding B cell and immunoglobulin (Ig) specificity and function, including development of memory. We will also use in vitro approaches that drive antigenic drift in prototypical seasonal influenza viruses to better understand how differences in immune profiles affect virus evolution. To take this further, we propose to use the information from circulating viruses and antibody/B cell specificity to develop computational tools that analyze and predict human immune responses to influenza. We will use these models to both better understand human immunity to flu, but to also simulate how prior immunity affects immune responses to various immunization strategies.
Our goal is to develop approaches to immunization that produce more broadly cross-reactive and even “universal” immunity to flu. To accomplish these lofty goals, we have assembled a team of the very best immunologists, virologists, computational biologists, and clinical investigators who will work together on this project using cutting edge technologies. These studies have the potential to change the way we think about influenza immunity and vaccination, and create a better understanding of immune protection and virus selection.