Flu vaccine's effectiveness can be improved, new findings suggest

November 15, 2016

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, research that suggests that the conventional flu vaccine can be improved. The findings were reported in the journal Nature Medicine on Nov. 7.

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.
-end-
This research received funding from the Clayton Foundation for Research, the National Institutes of Health and the Department of Defense through a contract from the Defense Threat Reduction Agency.

University of Texas at Austin

Related Immune System Articles from Brightsurf:

How the immune system remembers viruses
For a person to acquire immunity to a disease, T cells must develop into memory cells after contact with the pathogen.

How does the immune system develop in the first days of life?
Researchers highlight the anti-inflammatory response taking place after birth and designed to shield the newborn from infection.

Memory training for the immune system
The immune system will memorize the pathogen after an infection and can therefore react promptly after reinfection with the same pathogen.

Immune system may have another job -- combatting depression
An inflammatory autoimmune response within the central nervous system similar to one linked to neurodegenerative diseases such as multiple sclerosis (MS) has also been found in the spinal fluid of healthy people, according to a new Yale-led study comparing immune system cells in the spinal fluid of MS patients and healthy subjects.

COVID-19: Immune system derails
Contrary to what has been generally assumed so far, a severe course of COVID-19 does not solely result in a strong immune reaction - rather, the immune response is caught in a continuous loop of activation and inhibition.

Immune cell steroids help tumours suppress the immune system, offering new drug targets
Tumours found to evade the immune system by telling immune cells to produce immunosuppressive steroids.

Immune system -- Knocked off balance
Instead of protecting us, the immune system can sometimes go awry, as in the case of autoimmune diseases and allergies.

Too much salt weakens the immune system
A high-salt diet is not only bad for one's blood pressure, but also for the immune system.

Parkinson's and the immune system
Mutations in the Parkin gene are a common cause of hereditary forms of Parkinson's disease.

How an immune system regulator shifts the balance of immune cells
Researchers have provided new insight on the role of cyclic AMP (cAMP) in regulating the immune response.

Read More: Immune System News and Immune System Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.