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A Universal Flu Vaccine

08/04/2015
Sarah C.P. Williams
Adding sialylated antibodies to a typical vaccine might confer broader, longer-lasting immunity when it comes to influenza
and other viruses. How? Find out...
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Researchers have discovered that whether or not one region of an antibody has been studded with sialic acid determines
how the antibody reacts with immune cells and the breadth of immunity that antibody confers. The finding could lead to new,
longer-lasting vaccines for influenza or other viruses.
Flu vaccines are typically only effective in 50 to 60 percent of the population, and we wanted to know what could predict
that effectiveness, said Taia Wang, a clinical investigator at Rockefeller University and first author of the new paper
published in Cell. What turned out to correlate really well was the level of sialic acid.
Wang and her colleagues made this discovery while studying the
Fc region of antibodies generated in response to a flu vaccine.
While one end of an antibody interacts with the antigens in a
vaccine, the opposing Fc region binds to immune cells to
coordinate a longer-lasting immune memory of the antigen.
Sometimes, sialic acid is added to these Fc regions, changing
their interactions with B cells. Over the course of their studies, the
scientists noticed that the more sialylated the Fc regions in a
patients antibodies are, the more memory B cells there are in their
blood, and the better the protection of the vaccine against the flu.
The team wondered whether adding already-sialylated antibodies
to the antigens present in a vaccine would help boost its
effectiveness. So they tested this theory in mice, giving some
animals a normal vaccine and others a mixture of vaccine and
antibodies with a sialylated Fc region. The groups of mice had
equal protection against the flu strain theyd been vaccinated for,
but the mice that also received the antibodies were protected
against other strains of the flu as well.
Ultimately, with more sialic acid, that means B cells with higher
affinity, Wang explained. That breadth would mean multiple years
of immunity instead of just one.
Wang suspects that the sialylated Fc region causes B cells to
recognize more areas of flu antigens. Its a very basic
immunology finding that could be transferred to many other
systems, Wang added. Maybe RSV [respiratory syncytial virus]
or HIV.
Reference
Wang, T.T., Maamary, J., Tan, G.S., Bournazos, S., et al. (2015)
Anti-HA Glycoforms Drive B Cell Affinity Selection and Determine
Influenza Vaccine Efficacy. Cell. 162, 1-10.

The sialylation of anti-influenza antibodies leads to

immunoglobulin G molecules with broader
recognition of the flu virus. Credit: Wang, et al. Cell.

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