Details about broadly neutralizing antibodies provide insights for universal flu vaccine

New research from an immunology team at the University of Chicago may shed light on the challenges of developing a universal flu vaccine that would provide long-lasting and broad protection against influenza viruses.

The study, published October 22 in Immunity, explores the behavior of polyreactive antibodies -- antibodies that are capable of binding to more than one distinct antigen -- in an effort to understand their role against influenza viruses. The researchers identified that broadly neutralizing antibodies are commonly polyreactive and are preferentially induced by novel and pandemic-level influenza viruses.

The research is inspired by the limited efficacy of the annual flu vaccine, which must be adjusted each year to provide the best protection against commonly circulating strains of the virus, and why it so rarely induces broadly neutralizing antibodies.

"For whatever reason, when we are exposed to the flu virus, the antibody response mounted targets the parts of the virus that want to change, so you have to get vaccinated every year to keep up," said Jenna Guthmiller, PhD, a postdoctoral fellow at the University of Chicago. "But there are some parts of the virus that don't change. So why doesn't the seasonal flu vaccine produce antibodies that target those?"

This study has implications for the development of a universal flu vaccine that can elicit broadly neutralizing antibodies and that would only need be administered once or twice during a person's lifetime, instead of every year.

These polyreactive antibodies, like all antibodies, are produced by the body's B cells. When a person receives their annual flu vaccine, B cells will bind to the inactivated virus and begin generating antibodies against it, preparing the body to fight off the pathogen if it encounters the live flu virus in the environment.

This vaccine-induced immune response tends to produce very specific antibodies that target those frequently-changing epitopes on the surface of the virus, in contrast to broadly neutralizing antibodies that can identify the conserved regions that are the same every year.

The new study found that these polyreactive antibodies tend to bind to the portions of the flu virus that are conserved, and that they are preferentially produced when the body encounters a novel flu strain. Importantly, their unique ability to bind to more than one antigen is potentially due to their flexibility; the antibodies themselves can slightly adjust their conformation, allowing them to imperfectly bind to multiple similarly-shaped antigens.

This means that polyreactive antibodies are broadly neutralizing due to their ability to attach to and block the portions of influenza virus that are similar across strains and from year to year. Polyreactive antibodies are therefore ideal candidates for developing a universal flu vaccine -- one that can not only protect against common annual strains, but also novel influenza viruses, like the H1N1 strain seen during the 2009 pandemic.