DREAMS of a universal flu vaccine that is effective against all flu strains are a step closer to becoming a reality thanks to the findings of a new study.
The study revealed that chemical modifications to a specific region in antibodies may be used to improve current flu vaccines. “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,” said senior author Prof Jeffrey Ravetch, Head of the Leonard Wagner Laboratory of Molecular Genetics and Immunology, The Rockefeller University, New York City, New York, USA.
Led by Dr Jad Maamary and Dr Taia Wang, the research team designed their study around a new strategy involving the Fc region of antibodies. They already knew that modifying the Fc region affected how the antibodies interacted with immune cells, therefore the team aimed to investigate how changes to the region may improve an immune response.
Healthy volunteers were vaccinated with a seasonal flu vaccine containing an inactivated strain of the H1N1 virus. Using blood samples, the team tracked how the subjects’ immune systems responded, looking for chemical modifications to antibodies against a surface protein. Approximately 1 week later, the researchers identified a rise in the number of sialylated antibodies present. Sialic acid is a molecule vital to signalling, thus the presence of these antibodies suggested a positive response to the vaccine.
Experiments on cell cultures and mice showed that sialylated Fc regions bind to a receptor protein called CD23 on specific immune cells (B cells). Subsequently, CD23 activates another receptor known as FcgRIIB that prevents B cells from producing low-affinity antibodies. As a result, sialylated Fc regions lead to the activation of B cells producing the highest affinity antibodies. The team found that this higher affinity resulted in extensive protection against influenza viruses from the H1 subtype (incorporating H1N1).
Consequently, the researchers modified the H1N1 vaccine by adding sialylated antibodies against the virus’ protein, and tested the new vaccine on mice. “When we immunised 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,” explained Dr Maamary. “However, when we exposed them to strains expressing different versions of the H1 protein, only the sialylated immunisations offered protection.”
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