10 January 2018

Goodbye, flu?

The first universal DNA vaccine against all strains of the influenza virus has been created

Yulia Vorobyova, Vesti, based on UW Medicine: Promise seen in one-and-done approach to combat flu

Doctors, biologists and pharmacists have been trying to create a universal flu vaccine for a long time. It's not so easy to do this, because virus strains are constantly mutating, which means that you can't do without geneticists.

A team led by Professor Deborah Fuller from the University of Washington School of Medicine hopes that the new study will bring scientists closer to creating a vaccine that will protect patients from all strains of the flu virus, even if they change genetically over time.

Only a DNA vaccine is capable of this: unlike conventional drugs that cause the entire body to generate an immune response at once, a DNA vaccine inserts the genetic code into cells, orienting them to produce an antigen that will trigger an immune response.

In this case, the antiviral DNA vaccine will cause human cells to produce antigens, as well as enhance the work of antibodies and T cells (immune cells) to fight the pathogen.

Such a DNA vaccine will be the first drug in a completely new line of vaccines, which Fuller hopes will expand over time. Such funds are simply necessary, and the problem of flu vaccination is at the forefront. According to the US Centers for Disease Control and Prevention, twice as many people have had the flu in America alone this year than last year.

Deborah Fuller's lab is developing a DNA vaccine using the genetic components of the influenza virus. Researchers choose "conservative" components that do not change over time. If the vaccine affects them, even in the case of gene drift or other changes in the strains, its effect will remain effective, the authors explain.

So far, the first version of the vaccine contains DNA encoding proteins of four different strains of the influenza A virus. These proteins cause a strong immune response to each individual strain. In addition, the vaccine includes DNA encoding a protein that is highly conserved, and as a result, its effect extends to different strains of the virus.

To increase the power of the immune response, the researchers resorted to fusion: plasmids (small DNA molecules) of E.coli bacteria (E. coli), as well as the DNA of the hepatitis B virus were added to the vaccine. These components contribute to the production of antigens that cause a strong immune response.

During tests of the vaccine on macaques, experts found that after three doses, the drug began to generate a powerful immune response against each of the four "declared" flu strains. But, more importantly, the cellular response also extended to strains "not specified in the task conditions", that is, the vaccine turned out to be really universal. Moreover, the protection was 100%.

Fuller explains that the vaccine will be administered to patients through the skin, but not with the usual syringe, but through a gene gun. Such a device will be able to inject the substance directly into the skin cells. Then these cells will start the production of antibodies and T-cells in the body, which will begin to fight the pathogen.

According to the researchers, the advantages of the new type of vaccines are obvious. Firstly, this is a fundamentally different action: the drug helps the body to find infected cells and destroy them more effectively. Secondly, tests on primates showed that the reaction of T cells occurred so quickly that the animals simply did not have time to get sick. This effect is observed due to the directed action of the DNA vaccine: first of all, T-cells were sent to the lungs, where the greatest number of pathogens accumulate.

In addition, the production of DNA vaccines is relatively inexpensive, as well as fast: it takes an average of three months, whereas classic drugs are produced for about nine months.

A universal vaccine will also save patients from having to get annual flu shots. And if a new pandemic strain of the virus suddenly appears, the DNA vaccine, thanks to its rapid action, will be able to prevent a nationwide epidemic.

The authors also note that according to the same principles, more effective vaccines can be created against other viral infections – for example, the Zika virus.

However, it will probably take several more years from the first encouraging results to the moment when the new vaccine appears in commercial production. Various trials and improvements of the vaccine are ahead.

A more detailed description of the "holy grail" of physicians is contained in an article published in the publication PLOS One (Multigenic DNA vaccine induces protective cross-reactive T cell responses against heterologous influenza virus in nonhuman primates).

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