Strategy introduces stable components of flu virus for long-lasting, DNA-enhanced protection

January 5, 2018 by Barbara Clements, University of Washington
The vaccine strategy introduces stable components of flu virus to the body's dermal layer to spur universal, and long-lasting DNA-enhanced protection. Credit: ThinkStock

Getting a flu shot every year can be a pain. One UW Medicine researcher is hoping to make the yearly poke a thing of the past with the development of a universal vaccine that would protect from all strains of influenza virus, even as the viruses genetically shape-shift from year to year.

The research in Deborah Fuller's lab uses a DNA to instruct the individual's own skin cells to produce antigens and induce antibodies and T cell responses to fight the infection. Her most recent research on this effort was published today in PLOS ONE.

"Relatively speaking, DNA vaccination is the new kid on the block with regard to the types of vaccines," said Fuller, a professor in the Department of Microbiology at the University of Washington School of Medicine. This year, U.S. medical professionals expect a challenging flu season, with 7,000 confirmed cases reported nationwide by the end of November – double the number from last year at the same time, according to the Centers for Disease Control and Prevention.

The DNA vaccine in Fuller's lab was engineered by using genetic components of – the conserved areas – which do not change. This is one way Fuller's DNA vaccine gets around the genetic drift, or changes, that occur in influenza from year to year, and challenge clinicians who combat the disease.

It is also administered through the epidermis with a "gene gun" device that injects the DNA vaccine directly into the skin cells. The cells then produce the and prompts the body to create antibodies and T-cells to fight infection.

"With the immunized groups, we found that using this conserved component of the virus gave them 100 percent protection against a previous circulating influenza virus that didn't match the vaccine," Fuller said. "This was very exciting for us."

The vaccine developed by Fuller's lab takes a different approach to attacking the influenza virus within the body. Instead of simply repelling the virus, as on-the-market vaccines do now, this vaccine seeks out infected cells and kills them. The T-cell responses against the virus were so swift and complete in the tested non-human primates that they simply did not get sick, she said. Fuller's team also was able to direct the T-cells to go to the lungs first, where much of the damage of an influenza infection occurs.

Another advantage: This approach requires production time of about three months, whereas it typically takes about nine months to produce the U.S.-approved vaccine for a flu season that begins in December (in the United States) and runs through February.

Fuller firmly believes this is the new direction of .

"We've been working essentially with the same vaccine (techniques) over the last 40 years. It's been a shake-and-bake vaccine: You produce the virus, you kill the virus, you inject it. Now it's time for vaccines to go through an overhaul, and this includes the ."

A "universal" vaccine would eliminate the need for yearly flu vaccinations and could be on-hand for rapid deployment should a deadly pandemic strain of the virus emerge.

The idea of a DNA-based vaccine might also pose a mechanism for vaccines for other viruses, such as Zika, and for possible pandemic outbreaks which might emerge in the future, she said.

But don't expect the vaccine in Fuller's lab to appear on the drugstore shelves anytime soon. It can take five to 10 years from the time a vaccine shows promising results in the lab to commercial availability.

A deeper look into this research:

In the Fuller lab, senior research scientist, Jim Fuller, engineered a vaccine that contained DNA coding for viral proteins from four different influenza A strains. These proteins, called HA, are targeted by standard vaccines and are known to trigger a strong immune response to each individual strain. In addition, the vaccine included DNA for a protein that is highly conserved and, thus, shared across different strains of virus.

Because DNA vaccines often fail to generate a strong immune response, the researchers sought to boost the vaccine's effectiveness by fusing the DNA for some of the antigens with DNA proteins from a bacteria, a toxin from E. Coli, and protein from the hepatitis B that are known to be antigens that elicit a strong immune response.

In an animal study in cynomolgus macaques, researchers in the Fuller lab, Drs. Merika Treants Koday and Jolie Leonard, found that after three doses, the DNA vaccine generated a strong antibody response against each of the flu strains it targeted. Antibodies bind to and help clear microbial invaders, preventing an infection from taking hold or reducing its severity.

More importantly, the vaccine triggered a strong cellular immune response that was effective not only against the strains covered by the vaccine but also strains that were not.

Deborah Fuller was the co-inventor of the gene gun used in this research, and co-founded Orlance, Inc. a startup which is working on engineering a clinical version of the DNA vaccine delivery system and commercializing it for vaccines, including .

Explore further: H3N2 mutation in last year's flu vaccine responsible for lowered efficacy

More information: Merika T. Koday et al. Multigenic DNA vaccine induces protective cross-reactive T cell responses against heterologous influenza virus in nonhuman primates, PLOS ONE (2017). DOI: 10.1371/journal.pone.0189780

Related Stories

H3N2 mutation in last year's flu vaccine responsible for lowered efficacy

November 6, 2017
The low efficacy of last year's influenza vaccine can be attributed to a mutation in the H3N2 strain of the virus, a new study reports. Due to the mutation, most people receiving the egg-grown vaccine did not have immunity ...

Team develops new broadly protective vaccines for H3N2 influenza

November 2, 2017
A collaborative research and development partnership between researchers at the University of Georgia and Sanofi Pasteur, the largest influenza vaccine manufacturer in the world, has resulted in the identification of a vaccine ...

Experts discuss Influenza vaccine challenges and opportunities

November 30, 2017
In a New England Journal of Medicine perspective, experts from the National Institute of Allergy and Infectious Diseases (NIAID), part of the National Institutes of Health, and the World Health Organization (WHO) Collaborating ...

Experts say flu season could be severe this year

September 22, 2017
If last year's active flu season and this year's severe season in the Southern Hemisphere is any indication of what flu season will look like across the country beginning this fall, then it's important to get vaccinated soon ...

Will this year's flu shot be as weak as last season's?

November 8, 2017
(HealthDay)—Lots of people came down with influenza last year despite getting a flu shot—and researchers can't promise this season's vaccine will be any more effective.

Live attenuated flu vaccine not effective for children in 2015-16

August 10, 2017
(HealthDay)—During the 2015 to 2016 season, influenza vaccines reduced the risk of influenza illness, but the live attenuated vaccine was ineffective among children 2 to 17 years of age, according to a study published in ...

Recommended for you

Implantable islet cells come with their own oxygen supply

April 25, 2018
Since the 1960s, researchers have been interested in the possibility of treating type 1 diabetes by transplanting islet cells—the pancreatic cells that are responsible for producing insulin when blood glucose concentration ...

'Incompatible' donor stem cells cure adult sickle cell patients

April 25, 2018
Doctors at the University of Illinois Hospital have cured seven adult patients of sickle cell disease, an inherited blood disorder primarily affecting the black community, using stem cells from donors previously thought to ...

Research explains link between exercise and appetite loss

April 24, 2018
Ever wonder why intense exercise temporarily curbs your appetite? In research described in today's issue of PLOS Biology, Albert Einstein College of Medicine researchers reveal that the answer is all in your head—more specifically, ...

Mammary stem cells challenge costly bovine disease

April 24, 2018
Mastitis is the most expensive disease in the dairy industry. Each clinical case can cost a dairy farmer more than $400 and damages both the cow's future output as well as her comfort.

Fruit fly study identifies new gene linked to aortic aneurysms

April 24, 2018
An interdisciplinary team of researchers has identified a new gene linked to human aortic aneurysms. By combining comprehensive genetic studies in the fruit fly, dataset searches and analysis of diseased human aortic tissue, ...

Scientists manipulate 'satellite cells' to speed healing

April 24, 2018
Muscle aches and pains, whether from stretching, strenuous exercise or just normal wear and tear, can put a crimp in your day, a limp in your step and be an actual pain in the neck. But no matter the severity, stem cells ...


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.