Understanding immune response to flu virus key to developing new treatments

June 25, 2018 by Beth Staples, University of Maine
UMaine scientists, from left, Con Sullivan, Carol Kim and Paul Millard, believe novel treatments that are independent of vaccine effectiveness are vital. They’ll utilize a $435,166 award from the National Institutes of Health to examine the immune response to flu infection. Credit: University of Maine

This past flu season in Maine was the worst in at least five years, according to the Centers for Disease Control, with 9,018 reported cases, 82 deaths and 1,750 hospitalizations.

Each year in the United States, 21,000–49,000 people die due to seasonal flu and its complications, and 95,000–172,000 people are hospitalized, according to CDC estimates.

Because it's difficult to predict year-to-year effectiveness of , University of Maine scientists believe novel treatments that are independent of vaccine effectiveness are vital.

The Bill & Melinda Gates Foundation concurs. One of its "Grand Challenges"—initiatives that foster innovation to solve global health and development problems—is a call to develop a universal vaccine to end the pandemic threat. This challenge was issued this year, the 100-year anniversary of the 1918 flu pandemic that killed an estimated 50 million people on Earth.

To develop effective new treatments, a better understanding of the to the infection is needed, say Carol Kim, professor of microbiology; Paul Millard, associate professor of chemical and biological engineering; and Con Sullivan, assistant research professor of molecular and biomedical sciences.

Toward that end, the UMaine team will utilize a $435,166 award from the National Institutes of Health (NIH) to examine the immune response to flu infection, as well as factors that control optimum antiviral activity.

Influenza A virus infections originate in epithelial cells (sometimes called safety shields) that line the respiratory tract. Symptoms of the virus frequently include fever, chills, a cough, sore throat, muscle aches and a runny nose. At times, the contagious infection can become systemic, resulting in multi-organ failure and death.

During an infection, a person's innate antiviral immune response is activated, which initiates a feedforward loop leading to the recruitment of excess neutrophils, or .

The neutrophils, or first responders, play a key role in a person's immune response to bacterial and fungal infections. The influx of white blood cells is crucial to eliminate the flu virus. But the influx also can trigger a dangerous hyperinflammatory response, sepsis, for example—that damages multiple organ systems and can result in death.

The UMaine team will look for the so-called immunologic tipping point between infection elimination and a hyperinflammatory response that results in organ failure and death. The researchers also will explore mechanisms for reducing hyperinflammatory responses initiated by viral infections.

Kim, Millard and Sullivan will use from the UMaine Zebrafish Facility as flu virus models. The freshwater fish is nearly transparent in the larval stage, has a similar genetic structure to humans and, like people, is a vertebrate with the same major organs and tissues.

Zebrafish and humans also respond to infections and vaccinations in similar ways and zebrafish neutrophils have many similarities to human neutrophils.

UMaine scientists have used zebrafish for health-related research since 1999, when Kim established the Zebrafish Facility in Hitchner Hall with state and federal funds. The facility's 1,100 tanks can hold as many as 36,800 zebrafish.

In 2014, The Kim Lab was the first to develop the human influenza infection model in zebrafish, which is documented in the journal Disease Models and Mechanisms.

"The emergence of strains of influenza virus with the potential for causing widespread disease of pandemic proportions is a real concern," says Kim. "In the zebrafish, we have a powerful model system to help us understand the infection process and immune response to human diseases such as influenza."

The NIH also believes the development of a universal influenza vaccine is a high priority. Its National Institute of Allergy and Infectious Diseases is interested in learning from researchers using novel flu virus models—including zebrafish—"that more closely mimic human immune responses to influenza or vaccination."

Explore further: Study finds flu ravages muscles of zebrafish with muscular dystrophy

Related Stories

Study finds flu ravages muscles of zebrafish with muscular dystrophy

October 26, 2017
This time of year, doctors often recommend flu shots for people who are young, old, pregnant or immunocompromised.

Study establishes zebrafish as a model for flu study

October 1, 2014
In the ongoing struggle to prevent and manage seasonal flu outbreaks, animal models of influenza infection are essential to gaining better understanding of innate immune response and screening for new drugs. A research team ...

Data gathering can't prevent a new influenza pandemic

March 22, 2018
Commenting on a new BBC Four programme, Contagion, presenting the results of an on-going citizen-scientist experiment investigating how a new influenza pandemic might spread across the UK, influenza expert Dr. Jeremy Rossman ...

Reconstructed 1918 influenza virus has yielded key insights, scientists say

September 11, 2012
The genetic sequencing and reconstruction of the 1918 influenza virus that killed 50 million people worldwide have advanced scientists' understanding of influenza biology and yielded important information on how to prevent ...

Nanoparticle vaccine offers universal protection against influenza A viruses, study finds

January 24, 2018
Researchers have developed a universal vaccine to combat influenza A viruses that produces long-lasting immunity in mice and protects them against the limitations of seasonal flu vaccines, according to a study led by Georgia ...

Virulence factor made by influenza virus is potential target for vaccine drug development

August 14, 2017
A new study describes how NS1, a protein produced by influenza A viruses, suppresses the body's immune responses to viral infection. Researchers present the potential to develop a live attenuated vaccine based on an engineered ...

Recommended for you

Defense against intestinal infection in organism is affected by prostaglandin E2

November 15, 2018
The treatment of intestinal infections caused by some strains of the bacterium Escherichia coli, present in unsanitized or contaminated foods, may have a new ally.

No link between 'hypoallergenic' dogs and lower risk of childhood asthma

November 15, 2018
Growing up with dogs is linked to a lower risk of asthma, especially if the dogs are female, a new study from Karolinska Institutet and Uppsala University in Sweden shows. However, the researchers found no relation between ...

Researchers finds better ways to improve the chances of survival of children with a rare immune deficiency

November 15, 2018
An international study published in the journal Blood by researchers led by Dr. Elie Haddad, a pediatric immunologist and researcher at CHU Sainte-Justine and professor at Université de Montréal, highlights the urgent need ...

Human Cell Atlas study reveals maternal immune system modifications in early pregnancy

November 14, 2018
The first Human Cell Atlas study of early pregnancy in humans has shown how the function of the maternal immune system is affected by cells from the developing placenta. Researchers from the Wellcome Sanger Institute, Newcastle ...

Researchers identify factors behind inflammation in immunodeficiency patients

November 14, 2018
Oregon State University researchers have discovered two key factors behind the intestinal inflammation that plagues people suffering from a disorder that affects their immune system.

New antibody breakthrough to lead the fight against cancer

November 14, 2018
Scientists at the University of Southampton have developed a new antibody that could hold the key to unlocking cancer's defence against the body's immune system.


Please sign in to add a comment. Registration is free, and takes less than a minute. Read more

Click here to reset your password.
Sign in to get notified via email when new comments are made.