Here Are 2 Possible Steps Toward A Universal Flu Vaccine

This year's harsher flu season is a not-so-gentle reminder that we really, really need a universal flu vaccine, a vaccine that works against all influenza viruses. While developing a universal vaccine is not easy scientifically and means overcoming some non-scientific challenges, could two newly published studies in the journal Science and in the journal Nature Communications be significant steps towards this Holy Grail of influenza?

This season, the flu vaccine seems to be less than 40% effective, which as you'll see is not the worst that it's been but is certainly far from perfect. Of course, as is the case with swordfighting and Polar Bear Plunges, some protection is better than nothing. So, make sure you get the flu vaccine if you haven't already.

From flu season to flu season the protection offered by the vaccine can be a bit of like a kangaroo on a pogo stick. Here are some data on the seasonal influenza vaccine effectiveness over the past twelve years from the Centers for Disease Control and Prevention (CDC):

When the vaccine is 49% effective, that means the vaccine can decrease the number of cases by 49%. As you can see, the 2010-11 season was a good one with a 60% effective vaccine. But 2004-05 and 2014-2015, not so good.  

Since it takes about 5 to 6 months to produce each year's batches of the influenza vaccine as described by the World Health Organization, flu experts have to predict in February-March what flu virus strains will be circulating by the time October and later rolls around. (This can be a bit like predicting each year during the NFL pre-season which team will end up losing to the New England Patriots in the Super Bowl.) Moreover, the flu virus can mutate along the way, further complicating the match between the vaccine and the viruses. All of this gets even more complicated when a completely new strain of the flu circulates, which is what happened in 2009, resulting in a pandemic. Different strains circulating each year and the flu viruses mutating also mean that you have to get a different flu shot every year.

You can then see how a universal vaccine, that is one that works against all influenza viruses, would be a game changer. This would help protect against new viruses never seen infecting humans before and prevent pandemics. This could do away with the guesswork that has to occur each year and boost the vaccine effectiveness to be much higher. This could also mean that you wouldn't have to get the flu shot every year, depending on how long the vaccine effect lasts. Our computational model published in the journal Influenza and Other Respiratory Viruses showed that doing so could yield substantial cost savings. Moreover, a universal flu vaccine could be our only really effective line of defense when the really, really big epidemic comes a knocking, if the culprit is a novel flu virus.

However, importance does not necessarily mean funding and the focus of the pharmaceutical industry. Vaccines don't offer high profit margins and return on investment to pharmaceutical companies compared to some other products. Big pharmaceutical companies may be doing less research and development in general these days, as Ana Swanson described for the Washington Post. And unless you've been living inside a syringe, you have probably heard that the White House has been trying to cut funding for scientific research.

Nevertheless, different research groups have tried to push forward mainly with whatever funding happens to be available from the government. To develop a universal vaccines, various researchers have focused on the parts or aspects of the flu virus that are conserved (i.e., common or remain the same) across all flu viruses.

The Science publication detailed one potential approach advanced by a team of researchers led by Ren Sun, PhD, Professor of Molecular and Medical Pharmacology and Bioengineering at the David Geffen School of Medicine at UCLA. Cells that comprise your immune system produce proteins called interferons that help regulate many aspects of your immune system response and kill invading viruses. Influenza viruses, being the sneaky b*stards that they are, have ways of suppressing the production and function of interferons, in effect disabling major parts of your defenses against influenza. Dr. Sun's team searched the genomes of influenza viruses for genetic sequences that give the viruses this ability to suppress your interferons.

After 4 years, voila: the team identified the key sequences and then introduced mutations that managed to deactivate them, resulting in a hyper–interferon-sensitive (HIS) virus. They then produced a vaccine with this HIS virus, gave the vaccine to mice, and demonstrated how such a vaccine could generate in mice an immune response that could protect against various influenza strains in mice. “By disabling these interferon-evasion functions, the engineered virus is weakened in typical hosts,” explained the study’s first author, Yushen Du. “At the same time, however, due to interferon stimulation, the engineered virus generates very strong immune responses.” Here's a video from UCLA with additional information:

The Nature Communications publication presented another possible approach from Baozhong Wang, PhD, Associate Professor at Georgia State University and his team. They've been developing very small protein particles ("nanoparticles") to stimulate the immune system to target the inner stems of the influenza virus that tends to stay the same from virus strain to virus strain and year to year rather than the heads of the virus which tend to mutate and are more likely to vary among different strains. Injecting mice with these nanoparticles seemed to protect mice against a variety of different influenza A viruses. As this Associated Press video shows, a number of research groups are targeting different portions of the stems.

Of course, mice aren't men, or women or girls or boys or infants. So both possibilities are still quite early stage. It's not yet clear which may eventually become viable vaccines and when. But this year's flu season should be a smack in the face that more urgency and investment are needed to make a universal flu vaccine a reality sooner than later.