New approach could help curtail hospitalizations due to influenza infection

January 18, 2018, University of California, Los Angeles
UCLA scientists developed a new technique to identify and eliminate the virus's defense mechanisms. Credit: National Institute of Allergy and Infectious Diseases/NIH

More than 700,000 Americans were hospitalized due to illnesses associated with the seasonal flu during the 2014-15 flu season, according to federal estimates. A radical new approach to vaccine development at UCLA may help lower that figure for future flu seasons.

The scientists used leading-edge genomics to identify and eliminate the ' defense mechanisms, enabling them to develop a vaccine "candidate"—meaning that it must still undergo evaluation and approval by the FDA—that in animals has been proven to be safe and highly effective against influenza.

In the study, which was published in the journal Science, the engineered influenza virus induced strong immune responses in animals. While further research will be needed, the UCLA scientists are hopeful that their approach could lead to a new, more effective vaccine that can be taken as a nasal spray at home, rather than as an injection by a health professional.

"Because the variations of seasonal influenza viruses can be unpredictable, current vaccines may not provide effective protection against them," said Ren Sun, a professor of molecular and medical pharmacology at the David Geffen School of Medicine at UCLA and the study's senior author. "Previous pandemics and recent outbreaks of avian influenza highlight the need to develop vaccines that offer broader, more effective protection."

The key to the new vaccine is an understanding of the interactions between the virus and interferons, which are proteins that are critical to the body's immune response. Interferons have two main functions: one is a first line of defense to kill invading viruses very quickly; a second is to coordinate the adaptive immune responses, which provide long-lasting protection against the virus. The latter is the basis of vaccination.

"If viruses do not induce interferons, they will not be killed in the first-line defense; and without interferons, the is limited," said Sun, who also is a professor of bioengineering at the UCLA Henry Samueli School of Engineering and Applied Science. "For these reasons, viruses have evolved strategies to evade detection and limit the production of interferons by host organisms."

Sun and colleagues have spent the past four years searching the 's entire genome for its anti-interferon properties. After defining the function of every amino acid in the genome, they deactivated the sequences that prevent interferon induction, which meant that interferon production would be highly stimulated in organisms infected with the virus.

"By disabling these interferon-evasion functions, the engineered virus is weakened in typical hosts," said Yushen Du, the study's first author, who recently earned his doctorate at UCLA. "At the same time, however, due to interferon stimulation, the engineered virus generates very strong immune responses."

Sun added: "With this approach, the safety and efficacy requirement of vaccines can potentially be achieved simultaneously. In traditional vaccine development, one is usually sacrificed for the other."

Although researchers have disabled genetic sequences that block interferon before, the UCLA scientists were the first to systematically identify and eliminate multiple interferon-evasion sites at single amino acid resolution on the virus.

"Other researchers have knocked out one anti- sequence, but we knocked out eight locations by changing one amino acid at a time," Du said.

Sun and his colleagues now plan to test the in animals with two strains of before moving to clinical trials with humans. He said the approach could also be applied to developing vaccines against a wide range of other viruses.

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

More information: Y. Du el al., "Genome-wide identification of interferon-sensitive mutations enables influenza vaccine design," Science (2018). science.sciencemag.org/cgi/doi … 1126/science.aan8806

J.R. Teijaro el al., "Taking down defenses to improve vaccines," Science (2018). science.sciencemag.org/cgi/doi … 1126/science.aar5421

Related Stories

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 ...

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

January 5, 2018
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, ...

Aging impairs innate immune response to flu

December 13, 2017
Aging impairs the immune system's response to the flu virus in multiple ways, weakening resistance in older adults, according to a Yale study. The research reveals why older people are at increased risk of illness and death ...

Engineered virus has artificial amino acid allowing it to serve as a vaccine

December 2, 2016
(Medical Xpress)—A team of researchers at Peking University has developed a new type of vaccine that they claim may allow for a new approach to generating live virus vaccines which could conceivably be adapted to any type ...

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 ...

Genetic mutation could, if altered, boost flumist vaccine effectiveness, research suggests

November 28, 2017
Researchers at Johns Hopkins Bloomberg School of Public Health have discovered a genetic mutation in the FluMist intranasal flu vaccine that has the potential to be altered to enhance the vaccine's protective effect.

Recommended for you

Anticancer drug offers potential alternative to transplant for patients with liver failure

August 15, 2018
Patients suffering sudden liver failure could in the future benefit from a new treatment that could reduce the need for transplants, research published today shows.

Study shows how MERS coronavirus evolves to infect different species

August 14, 2018
In the past 15 years, two outbreaks of severe respiratory disease were caused by coronaviruses transmitted from animals to humans. In 2003, SARS-CoV (severe acute respiratory syndrome coronavirus) spread from civets to infect ...

Inching closer to a soft spot in isoniazid-resistant tuberculosis

August 14, 2018
Antibiotic-resistant tuberculosis is a public health threat. TB and other bacteria become resistant to antibiotics by evolving genetic changes over time, which they can do quite quickly because bacterial lifecycles are short. ...

Why do women get more migraines?

August 14, 2018
Research published today reveals a potential mechanism for migraine causation which could explain why women get more migraines than men. The study, in Frontiers in Molecular Biosciences, suggests that sex hormones affect ...

How long is an Ebola survivor contagious? One case is causing scientists to rethink the answer.

August 14, 2018
Surviving Ebola isn't like getting over the flu.

Link between common 'harmless' virus and cardiovascular damage

August 13, 2018
Researchers from Brighton and Sussex Medical School (BSMS) have found an unexpectedly close link between a herpes virus and the occurrence of immune cells damaging cardiovascular tissue.

2 comments

Adjust slider to filter visible comments by rank

Display comments: newest first

humy
not rated yet Jan 19, 2018
from the above link;

"...After defining the function of every amino acid in the genome..."

Err, the genome is NOT made of amino acids.
The genome is made of nucleotides.
I assume they meant the function of very amino acid that the genome codes for as opposed to being IN the genome but, that STILL doesn't make a whole lot of sense because the function of each one amino acid molecule doesn't have a readily definable function and only whole protein molecules do.
humy
not rated yet Jan 19, 2018
The 'function' of each amino acid molecule is generally only definable in the narrow current context of the exact position in the protein molecule it is in and thus its 'function' just depends on that context.
Although I am sure they didn't mean to imply so, the way this link talks about it makes it sound to me that they imply the contrary to that!

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.