Insight on how to build a better flu vaccine
New approach enables scientists to see how immune system responds to vaccination

Date:
August 31, 2020
Source:
Washington University School of Medicine
Summary:
Repeated exposure to influenza viruses may undermine the
effectiveness of the annual flu vaccine. A team of researchers
has developed an approach to assess whether a vaccine activates
the kind of immune cells needed for long-lasting immunity against
new influenza strains. The findings could aid efforts to design
an improved flu vaccine.



FULL STORY ==========================================================================
Flu season comes around like clockwork every year, and sooner or later
everyone gets infected. The annual flu shot is a key part of public
health efforts to control the flu, but the vaccine's effectiveness is notoriously poor, falling somewhere from 40% to 60% in a typical year.


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A growing body of evidence suggests that a history of exposure to
influenza virus might be undermining the effectiveness of the annual flu vaccine. Partial immunity developed during prior flu seasons -- either
through natural infection or vaccination -- might interfere with the
body's response to a new vaccine, such that vaccination mainly boosts
the recognition of prior influenza strains but does little to create
the ability to fight new strains.

Now, a team led by researchers at Washington University School of Medicine
in St. Louis has developed an approach to assess whether a vaccine
activates the kind of immune cells needed for long-lasting immunity
against new influenza strains. Using this technique, the researchers
showed that the flu vaccine is capable of eliciting antibodies that
protect against a broad range of flu viruses, at least in some people. The findings, published Aug. 31 in the journal Nature, could aid efforts to
design an improved flu vaccine that provides protection not only against
old influenza viruses but also new ones.

"Every year, about half of the U.S. adult population gets vaccinated
against influenza," said senior author Ali Ellebedy, PhD, an assistant professor of pathology and immunology at Washington University. "It's
necessary for public health, but it's also incredibly expensive and inefficient. What we need is a one-and-done influenza shot, but we are
not there yet. Anything that helps us understand how immunity develops
in the context of prior exposures would be important as we try to make a
better vaccine." The key to long-lasting immunity lies in lymph nodes, minuscule organs of the immune system positioned throughout the body. Easy
to miss in healthy people, lymph nodes become swollen and tender during
an infection as immune cells busily interact and multiply within them.

The first time a person is exposed to a virus -- either by infection
or vaccination -- immune cells capture the virus and bring it to the
nearest lymph node. There, the virus is presented to so-called nai"ve
B cells, causing them to mature and start producing antibodies to fight
the infection. Once the virus is successfully routed, most of the immune
cells that take part in the battle die off, but a few continue circulating
in the blood as long-lived memory B cells.



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The second time a person is exposed to a virus, memory B cells quickly reactivate and start producing antibodies again, bypassing naive B
cells. This rapid response quickly builds protection for people who
have been reinfected with the exact same strain of virus, but it's not
ideal for people who have received a vaccine designed to build immunity
against a slightly different strain, as in the annual flu vaccine.

"If our influenza vaccine targets memory cells, those cells will respond
to the parts of the virus that haven't changed from previous influenza strains," Ellebedy said. "Our goal is to get our immune system up to
date with the new strains of influenza, which means we want to focus the
immune response on the parts of the virus that are different this year."
To get decades-long immunity against the new strains, the flu strains
from the vaccine need to be taken to the lymph nodes, where they can be
used to train a new set of nai"ve B cells and induce long-lived memory
B cells specifically tailored to recognize the unique features of the
vaccine strains.

To find out what happens inside lymph nodes after influenza vaccination, Ellebedy enlisted the help of co-authors Rachel Presti, MD, PhD, an
associate professor of medicine, and Sharlene Teefey, MD, a professor of radiology at Washington University. Presti led a team at the Infectious
Disease Clinical Research Unit that coordinated the sampling of blood and
lymph nodes from healthy volunteers before and after vaccination. Guided
by ultrasound imaging, Teefey carefully extracted so-called germinal
centers that hold immune cells from underarm lymph nodes of eight healthy, young volunteers vaccinated with the 2018-19 quadrivalent influenza
vaccine. That vaccine was designed to protect against four different
strains of influenza virus. The immune cells were extracted at one, two,
four and nine weeks after vaccination.

Ellebedy and colleagues - including co-senior authors Steven Kleinstein,
PhD, a professor of pathology at Yale University School of Medicine, and
Andrew Ward, PhD, a professor of integrative structural and computational biology at Scripps Research Institute, as well as co-first authors
Jackson Turner, PhD, a postdoctoral researcher who works with Ellebedy,
Julian Zhou, a graduate student in Kleinstein's lab, and Julianna Han,
PhD, a postdoctoral scholar who works with Ward -- analyzed the immune
cells in the germinal centers to find the ones that had been activated
by vaccination.

In three volunteers, both memory B cells and nai"ve B cells in the lymph
nodes responded to the vaccine strains, indicating that the vaccine
had initiated the process of inducing long-lasting immunity against the
new strains.

"Our study shows that the influenza vaccine can engage both kinds of cells
in the germinal centers, but we still don't know how often that happens," Ellebedy said. "But given that influenza vaccine effectiveness hovers
around 50%, it probably doesn't happen as often as we would like. That
brings up the importance of promoting strategies to boost the germinal
centers as a step toward a universal influenza vaccine."

========================================================================== Story Source: Materials provided by
Washington_University_School_of_Medicine. Original written by Tamara
Bhandari. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Turner JS, Zhou JQ, Han J, Schmitz AJ, Rizk AA, Alsoussi WB,
Lei T, Amor
M, McIntire KM, Meade P, Strohmeier S, Brent RI, Richey ST, Haile
A, Yang YR, Klebert MK, Suessen T, Teefey S, Presti RM, Krammer F,
Kleinstein SH, Ward AB, Ellebedy AH. Human germinal centres engage
memory and nai"ve B cells after influenza vaccination. Nature,
Aug. 31, 2020 DOI: 10.1038/ s41586-020-2711-0 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2020/08/200831112347.htm

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