Flu vaccines in the US are made to target a small number of viral strains based on public health experts’ predictions. Scientists hope that, one day, a universal flu vaccine will be developed that will be effective against all strains, and the findings of a new study may take researchers one step closer to this goal.
The study, published in Cell, found that chemical modifications to a specific region in antibodies could be used to improve current flu vaccines.
“We believe these results may represent a preliminary step toward a universal flu vaccine, one that is effective against a broad range of the flu viruses,” states senior author Jeffrey Ravetch, head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology at the Rockefeller University, New York.
Vaccines in the US are typically formulated to target H1 and H3 influenza A viruses along with influenza B strains predicted by experts to be prevalent during the coming flu season. If the experts’ predictions are inaccurate, however, then the vaccines are rendered ineffective.
Just this January, the Centers for Disease Control and Prevention (CDC) reported that this season’s flu vaccine was only 23% effective across all age groups, due to a large proportion of this season’s viruses being “drift variants.”
“While the conventional flu vaccine protects only against specific strains, usually three of them, our experiments show that by including modified antibodies within the vaccine it may be possible to elicit broad protection against many strains simultaneously,” explains Ravetch.
Influenza can be a dangerous illness – particularly in adults over the age of 65 and people with other health conditions. The American Lung Association state that 90% of deaths from influenza occur in adults older than 65.
It is a difficult virus for scientists to target with vaccines due to the wide variety of strains that exist, with new strains emerging regularly. Because of how elusive the virus can be, a universal vaccine represents a dream goal for scientists and has been the focus of many research projects.
The new study revolves around a new strategy involving the Fc region of antibodies – the region that connects with immune cells. The researchers, led by Taia Wang and Jad Maamary, already knew that modifying the Fc region affected how the antibodies interacted with immune cells, and so the team set out to investigate how changes to the region might improve an immune response.
Healthy volunteers were vaccinated with a seasonal flu vaccine containing an inactivated strain of the H1N1 virus – also known as swine flu. Using blood samples, the researchers tracked how the participants’ immune systems responded, looking for chemical modifications to antibodies against a surface protein.
Around a week later, the researchers noticed an increase in the number of sialylated antibodies present. Sialic acid is a molecule crucial to signaling, meaning that the presence of these antibodies indicated a positive response to the vaccine.
Experiments on cell cultures and mice revealed that sialylated Fc regions bind to a receptor protein called CD23 on specific immune cells called B cells. In turn, CD23 activates another receptor known as FcyRIIB that discourages B cells from producing low-affinity antibodies.
In short, sialylated Fc regions lead to the activation of B cells producing the highest affinity antibodies. The researchers found that this higher affinity resulted in broad protection against influenza viruses from the H1 subtype (to which H1N1 belongs).
Using this discovery, the researchers modified the H1N1 vaccine by adding sialylated antibodies against the virus’ protein. The new and improved vaccine was then tested on mice.
“When we immunized mice with just the H1 protein from one strain or with the sialylated complexes containing the same viral protein, we found both offered equal protection against the same strain of flu,” explains Maamary. “However, when we exposed them to strains expressing different versions of the H1 protein, only the sialylated immunizations offered protection.”
Wang believes the new mechanism they have uncovered could potentially be utilized to reduce the rates of morbidity and mortality attributable to seasonal influenza virus infections.
“We are now looking into applying this strategy toward improving existing vaccines; ideally, this would result in a vaccine that provides lifelong immunity against flu infections,” she states.
Earlier this year, Medical News Today reported on a study suggesting that a newly discovered class of antibodies could lead to a universal flu vaccine “within 5 years.”