Every year, influenza
infections cause more than five million cases of severe illness, resulting
in approximately half a million deaths globally and posing a threat of
another pandemic. The quadrivalent influenza vaccines are currently recommended by the Centers for Disease Control and
Prevention to protect against four virus strains.
A team of engineers and scientists at The University of Texas at
Austin is reporting new findings on how the influenza vaccine produces
antibodies that protect against disease. These findings suggest that the
conventional flu vaccine can be improved. The findings were reported in
the journal Nature Medicine
‘A new class of antibodies that are effective at offering the body protection from several influenza virus strains have been discovered by researchers.’
The UT Austin team suggests that quadrivalent influenza vaccines may not offer significant
benefits over trivalent influenza vaccines. The team also discovered a
new class of antibodies that are effective at offering the body
protection from several influenza virus strains.
The four-year project was led by George Georgiou, a professor in the
Cockrell School of Engineering and in the College of Natural Sciences.
His team includes 34 researchers from various institutions, including
the Icahn School of Medicine at Mount Sinai in New York, the National
Institutes of Health and Stanford University.
According to the study, these insights were possible because of the
team's new technology that is able to directly identify and quantify
antibodies - the protein molecules responsible for protecting our
bodies from viruses and bacteria - that are present in human blood.
Exposure to a pathogen or virus stimulates our immune systems to
generate a diverse array of antibodies, collectively known as the
antibody repertoire, that then help fend off disease. Although various
clinical tests can help determine whether a patient has antibodies that
recognize the pathogen (for example, antibodies to HIV-1 in infected
individuals), the number, molecular identities and amounts of the
different antibodies that recognize the pathogen had not been known.
This breakthrough, which provides a molecular-level analysis of the
serum antibody repertoire - called "Ig-Seq" - capitalizes on a series
of technical advances in protein and single-cell DNA sequencing
pioneered by the UT Austin team. The Ig-Seq technology is the first and
only approach able to identify antibodies and to quantify how much of
each type of antibody are present in blood or other bodily fluids.
Antibodies that are present in circulation in higher concentrations play
a more significant role in preventing disease relative to those present
at low levels.
The ability to identify and quantify antibodies is important
because it allows scientists to see how the vaccine stimulates the
immune system to induce the production of antibodies that may then
protect against infection.
"In order to develop a better vaccine, you need to have a more
precise, better understanding of the current vaccine's efficacy, and to
do that you need to identify the individual antibodies that specifically
bind to influenza, understand how they protect from disease and measure
how long they can persist in circulation," said Jiwon Lee, a Cockrell
School chemical engineering doctoral student and first author on the
The team evaluated the serum antibody repertoire in young adults
before and after seasonal flu vaccination.
The UT Austin team discovered that after vaccination, only about 40% of the influenza-specific antibodies were elicited directly in
response to the vaccine. The remaining 60% were antibodies that
were already present, the result of previous exposure to earlier
circulating viruses or vaccines.
The study also reported the discovery of a new class of antibodies
that are remarkably proficient in protecting laboratory mice against
lethal challenge by influenza yet unexpectedly do not block the virus
from infecting cells.
This finding is important because all current metrics of
influenza vaccine efficacy depend solely on the ability of serum to
block infection and do not take into account the effect of antibodies
that can protect against disease via alternate mechanisms.
The researchers also investigated the relative benefits of the
longstanding influenza vaccine composed of three different strains of
virus (trivalent) compared with the quadrivalent vaccine, which contains
four viruses. They found that about 90% of the antibodies
elicited by one of the viruses in the trivalent vaccine also bind to the
fourth virus that is now included in the newer vaccine, raising the
question of whether the adaption of the more complex quadrivalent
vaccine confers an improved health care benefit.
In a separate collaborative study led by researchers at Harvard University and also published in the same issue of Nature Medicine
Georgiou and colleagues reported that because the current flu vaccines
are produced in chicken eggs, they partly direct the human immune system
to produce antibodies toward the mutated form of the virus adapted for
better production in eggs, but not the human strain.
"The implication here is that the production of the vaccine in
eggs can detract from its utility in eliciting a protective immune
response in humans," Georgiou said.