Researchers look to antibodies to improve flu vaccines

February 4, 2020

Antibodies that were previously overlooked may hold the key to a better flu vaccine.

A previously overlooked antibody may offer the key to more effective flu vaccines, according to a new report.

The study, published in Science, detailed the almost accidental discovery of an antibody that could boost flu vaccine efficacy. According to the report, flu vaccines are currently developed to stimulate the body's creation of antibodies against hemagglutinin (HA). Hemagglutinin is a surface protein on the flu virus, but this protein often mutates with the evolution of flu viruses, requiring revaccination with seasonal flu vaccines each year.

In this study, however, researchers investigated a different surface protein, neuraminidase (NA), which doesn't mutate as often as hemagglutinin protein. Previous research has indicated that antibodies impacting neuraminidase proteins may offer broader protection against different flu strains, leading to better protection and less severe illness for patients who still become infected by the flu virus after vaccination. Researchers note that the mechanism behind this is similar to that of Tamiflu, which works by inactivating neuraminidase.

Florian Krammer, PhD, a professor of vaccinology at the Icahn School of Medicine at Mount Sinai, says neuraminidase has been overlooked in the past, but this study shows that it has significant potential.

"These antibodies guide us to a region of the virus that is conserved and a target for protective immune responses," Krammer says. "We can now try to develop vaccination strategies to specifically target this region."

The research team began testing how various monoclonal antibodies bound to neuraminidase after it was noticed as part of a separate study that a patient infected with the H3N2 influenza strain was developing antibodies to a protein other than hemagglutinin. Forty-five monoclonal antibodies were studied by the team, and three were found to bind to the neuraminidase protein on the H3N2 virus. As the team expanded their investigation, they found that these same three antibodies also bound themselves to the neuraminidase protein on other strains of the flu virus, as well.

One antibody in particular-1G01-bound to neuraminidase on all of the flu viruses tested, according to the report.

The next step for the researchers was to see whether these antibodies could protect against the flu, and if they could be used as a treatment. Mice were used to test the antibodies against both influenza A and B, and the study reveals that the antibodies were successful in protecting the mice against both strains. Even at lethal doses of the influenza virus, the mice were able to survive the infection and recover after treatment with the 1G01 antibodies, the study reveals. The mice were also infected with a lethal dose of the H3N2 virus, and treated with low doses of the antibody days later. All the mice recovered, according to the study.

Krammer says the results of this study offer hope that the antibodies could be used to improve the efficacy of flu vaccines overall.

"The monoclonal antibodies that we discovered could be developed into therapeutics," Krammer says. "We might be able to develop improved vaccines through antibody-guided vaccine design. Both will be valuable tools to protect patients from getting influenza virus infections or improve their outcomes if they are already infected."

While research has only been done in mouse models so far, Krammer says it may be possible to develop therapeutics based on these antibodies in the future. Research teams are actively working on making this happen, but it could take some time, he says.

"Most efforts that are currently underway to develop better influenza virus vaccines focus on the viral hemagglutinin or on internal proteins," Krammer says. "Our work shows that the neurominidase is a very valuable target as well, which might be used to develop broadly protective or universal influenza virus vaccines."