Strategy may improve seasonal flu vaccines

Colorized electron micrograph of H1N1 influenza virus particles.NIAID

Flu viruses constantly change, or mutate, as they circulate in nature. Seasonal influenza vaccines need to be updated each year to match new emerging strains. Scientists monitor flu strains circulating around the globe to predict which 3 or 4 strains will be most prevalent during the next flu season. To allow enough time for the vaccine to be made, the strains must be selected more than 6 months before the influenza season begins. Sometimes, an unexpected strain predominates or emerges too late to be included in the vaccine. This happened during the 2014-2015 flu season. That season’s vaccine was less than 20% effective at protecting against influenza infection.

A research team led by Dr. Yoshihiro Kawaoka at the University of Wisconsin-Madison developed a strategy to predict flu mutations before they occur in nature by simulating viral evolution in the laboratory. Their work was funded in part by NIH’s National Institute of Allergy and Infectious Diseases (NIAID). The approach was described in the June 2016 issue of Nature Microbiology.

The scientists obtained samples of naturally occurring human H1N1 and H3N2 influenza viruses from different flu seasons. They generated variants of these viruses by making random mutations in the virus surface protein hemagglutinin (HA). Seasonal flu vaccines are currently developed and evaluated in part based on their ability to induce production of antibodies against HA.

The researchers mixed these mutated virus collections with antibodies targeting the flu viruses the study began with. Mutations in some strains allowed the virus to replicate despite the presence of the antibodies. These viral strains continued to replicate and mutate. If such changes occurred during natural infections, vaccinated people might not have the right antibodies to fight the mutated strains.

The scientists mapped the mutational patterns of the viruses by using a process called antigenic cartography. This mapping revealed that the laboratory-developed mutations matched how these viruses evolved in nature.

To test whether the lab-developed viruses could avoid detection by the immune system, the researchers tested mutated H1N1 viruses in mice and ferrets immunized against naturally occurring H1N1 influenza. Nearly all the viruses replicated efficiently in the immunized animals.

This laboratory-based approach could help researchers predict which viruses have the potential to cause future epidemics, and thus guide which strains to include in seasonal flu vaccines. “This is the first demonstration that one can accurately anticipate in the lab future seasonal influenza strains,” Kawaoka says.