Mutated, Defenseless Virus Could Lead to Universal Flu Vaccine

The unpredictability of seasonal influenza has researchers looking for a "universal" vaccine against all strains of the virus. | Flickr/ peigov/ CC BY-NC-ND 2.0]

A mutant influenza A virus generated by scientists at the University of California, Los Angeles may pave the way to a universal treatment for the flu. Highlighting their findings in a new study published January 18 in Science, researchers demonstrate how their mutant virus may help overcome key challenges of flu vaccination, including the need to accurately predict which kind of influenza is most prevalent in a given season.

"Because the variations of seasonal influenza viruses and pandemics can be unpredictable, current vaccines may not provide effective protection against them. A universal vaccine can potentially provide broad protection against various types of influenza virus, so even if predictions are wrong, the vaccine will still be effective," said Yushen Du, a Ph.D. student at the department of molecular and medical pharmacology at UCLA, and lead author of the study.

In the U.S., this year's flu season has been moderately severe, with seven influenza-associated pediatric deaths in the first week of January alone. In the same week, the proportion of individuals seeing their health care provider for influenza-like illness rose to 5.8%, above the national baseline of 2.2%.

According to the CDC , the H3N2 influenza virus — an especially troublesome strain — has predominated the season so far. While vaccines targeting the H3N2 type have been prepared (the CDC strongly recommends the use of both vaccines and antiviral drugs this season), it is difficult to gauge how effective the seasonal flu vaccine will be until the season is over.

The flu virus is notorious for its ability to evade the immune system by quickly and cleverly mutating portions of its genome. If a vaccine targets the correct seasonal strain, but that virus has already mutated to evade the body's defense, the vaccine will not work.

An effective flu vaccine must also be safe — not an easy feat. The nature of a vaccine is to deliver inactivated and essentially weaker versions of viruses — sometimes only comprised of the viral proteins or toxins that trigger protective responses from the immune system. The design is necessary for ensuring that the patient does not get a full-blown and potentially dangerous infection from the vaccine, but scientists are concerned that this engineered weakness means vaccines do not sufficiently prepare the immune system against viruses encountered in real life.

With these hurdles to overcome, new strategies for flu vaccination are urgently needed. Du and colleagues approached this problem with a unique lens, concentrating on portions of the influenza virus that are not normally the target when developing flu vaccines.

They scoured whole genomes of influenza A viruses, identifying genes that allow the virus to escape one of the body's primary immune defense mechanisms — type 1 interferon (IFN-1) function. They targeted and mutated multiple IFN-1-regulating genes to combine into one virus that would be hyper-sensitive to IFN-1.

"A universal vaccine can potentially provide broad protection against various types of influenza virus, so even if predictions are wrong, the vaccine will still be effective. "

Yushen Du

Mice and ferrets inoculated with this virus produced higher amounts of IFN-1, eventually leading to potent immunity against recurrent infection by multiple types of influenza A, including H1N1 and H3N2 subtypes. The authors found that the vaccine performed well on a variety of measures, including survival rates and immune system responses.

"With this approach, the safety and efficacy requirement of vaccines can potentially be achieved simultaneously," said Du. The mutant virus exhibited several of the desired properties for viruses used in influenza vaccines, including replicating well in the laboratory, while remaining harmless to the animals.

Because IFN-1 is involved in many different protective pathways, Du believes their approach can be broadly applied to develop vaccines against a wide range of viruses.

"We are extending the study to influenza B virus, and designing other test screens to further improve the safety and efficacy of this vaccine candidate," said Du. "We are also thinking about performing large-scale animal testing before moving to clinical trials of the current vaccine strain," she added.