University of Texas at Austin
The UT Austin team suggests that quadrivalent influenza vaccines
-- which are currently recommended by the Centers for Disease Control and
Prevention to protect against four virus strains and which may cost more for
consumers and health insurers to use -- 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 paper.
The team evaluated the serum antibody repertoire in young adults
before and after seasonal flu vaccination. Every year, influenza infections
cause more than 5 million cases of severe illness, resulting in approximately
half a million deaths globally and posing a threat of another pandemic.
The UT Austin team discovered that after vaccination, only about
40 percent of the influenza-specific antibodies were elicited directly in
response to the vaccine.
The remaining 60 percent 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 percent 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.
