If Only Santa Would be Real…When Are We Going to Have a Universal Flu Vaccine?

 

By Jesica Levingston Mac leod, PhD

Wouldn’t it be great if the answer to that question was “next year” (yep, only a 1 month wait). Sadly, besides all the astonishing efforts of various researchers groups we are just entering the clinical studies that might lead towards a safe and effective vaccine.

Probably you already heard about the antigenic mismatch with the current vaccine (for the strain H3N2): this means that the strains used in the vaccine could potentially not completely cover one or more of the seasonal influenza virus varieties. Therefore, if you got the flu shot, you might get sick anyways.

The concept behind the universal vaccine is to bypass the antigenic mismatch problem and other issues related with the way in which the vaccines are formulated nowadays. As Drs. Natali Pica and Peter Palese explained last year (Pica et al. 2013), the vaccines are prepared year by year with the aim to protect against the virus strains that are predicted to circulate in the next period. But, and there is always a “but” in predictions, an unexpected mutation in the virus not contemplated in the vaccine production, could conclude in a pandemic.

The clue came from thinking outside of the box, and breaking with the traditional dogmas in flu vaccine production. When you get infected with the influenza virus, your immune system targets the head domain of the HA (Hemagglutinin) protein, so the current vaccine production approach was to aim for this antigen. The bad news is that this domain changes every year. The flu vaccines are based on inactivated viruses , when you receive this vaccine, you will generate antibodies to fight these specific HA proteins. In Dr. Palese’s lab they are focus on regions of influenza HA protein that are highly conserved across virus subtypes, like the stalk domain of the HA protein. Also, he is engineering different HA chimeras. This strategy has been really successful, showing protection in animal models (mice and ferrets), and the vaccines were approved to go to clinical trial next year. This universal vaccine offered good protection for pandemics H5N1 and H7N9 influenza viruses.

Another strategy, published in Nature Medicine (Sridhar et al.) reports that targeting conserved core proteins using virus-specific CD8+ T cells (lymphocytes or white blood cells with a vital role in the immune system) could provide a draft for a universal influenza vaccine. But… even the scientists implicated in the research were not very positive about how long is going to take to translate this technique to the “outside the lab” world.

The third strategy is coming from an Italian group (Vitelli et al. 2013), and this potential universal influenza vaccine is been tested in animal models by the FDA.  This vaccine uses as a vector the virus PanAd3 (it was isolated from a great ape), which carries 2 genes that express proteins conserved among a variety of influenza viruses. The 2 viral proteins, the matrix protein (M1) and the nucleoprotein (NP), could be expressed for the human cells infected with the recombinant PanAd3 virus and immunize the patient against different influenza viruses.

Other entrepreneurial ideas are blooming around the world in order to solver the “influenza virus infection” problem. The influenza virus kills around 500,000 people annually worldwide (WHO), and affects very negatively the life of other hundreds of thousands. In fact, I do not know anybody who did not got the flu at least ones, I encourage to try to find somebody who was never sick with flu symptoms. This points out how universal this problem is and therefore it should get an universal solution soon.