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

Age-related increase in estrogen may cause common men's hernia

October 16, 2018
An age-related increase in estrogen may be the culprit behind inguinal hernias, a condition common among elderly men that often requires corrective surgery, according to a Northwestern Medicine study was published Oct. 15 ...

New findings cast light on lymphatic system, key player in human health

October 16, 2018
Scientists at the Oklahoma Medical Research Foundation have broken new ground in understanding how the lymphatic system works, potentially opening the door for future therapies.

New model suggests cuffless, non-invasive blood pressure monitoring possible using pulse waves

October 16, 2018
A large team of researchers from several institutions in China and the U.S. has developed a model that suggests it should be possible to create a cuffless, non-invasive blood pressure monitor based on measuring pulse waves. ...

Discovery of inner ear function may improve diagnosis of hearing impairment

October 15, 2018
Results from a research study published in Nature Communications show how the inner ear processes speech, something that has until now been unknown. The authors of the report include researchers from Linköping University, ...

Team's study reveals hidden lives of medical biomarkers

October 12, 2018
What do medical biomarkers do on evenings and weekends, when they might be considered off the clock?

Widespread errors in 'proofreading' cause inherited blindness

October 12, 2018
Mistakes in "proofreading" the genetic code of retinal cells is the cause of a form of inherited blindness, retinitis pigmentosa (RP) caused by mutations in splicing factors.

0 comments

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.