[sale0303]

The flu season this year started too early in some parts of the northern hemisphere, and many people are literally scrambling to get their annual vaccine. This ritual, however, could become history.

The Properties of Influenza Virus

Influenza, or simply “flu” is a very common seasonal infectious disease of birds and mammals. It is caused by Influenza viruses that belong to Orthomyxoviridae family. All influenza viruses are divided to two groups, A and B. These are RNA viruses, which means that RNA is their genetic material. Common symptoms of the infection are: chills, fever, sore throat, muscle pains, headache (often severe), coughing, weakness/fatigue and general discomfort.

This illness is not dangerous for healthy people, although the severely diseased chronic patients may experience alteration of their symptoms and in that case, this infection might become even life threatening. There are three to five millions of severe cases of influenza reported per one year, and about 500000 deaths. According to the World Health Organization: "Every winter, tens of millions of people get the flu. Most are only ill and out of work for a week, yet the elderly are at a higher risk of death from the illness. We know the worldwide death toll exceeds a few hundred thousand people a year, but even in developed countries the numbers are uncertain, because medical authorities don't usually verify who actually died of influenza and who died of a flu-like illness."

Although there are many influenza vaccines today, they are not always effective due to abilities of this virus to quickly change its properties from season to season. It is a real challenge to produce highly effective, long lasting influenza vaccine, mostly because it is most commonly occurred pandemic disease.

New flu vaccine could be made of information RNA (mRNA), the genetic material that controls the production of proteins. Unlike its precursors, the new vaccine could last a lifetime and it would be possible to produce it quickly enough to stop the pandemic.

How Do We Get Immunity?

We become immune to the specific strain of flu when our system learns to recognize a key protein called HA and NA, which is located on the surface of the virus. This can happen either because we have caught the virus and found a way to win that particular type of influenza, or because we have received one of the standard vaccines, which contains a large amount of attenuated viral particles.

However, the flu is constantly evolving, so the viral proteins also change and our immunity to influenza doesn’t transfer from one to the next season. For each season, a new vaccine must be produced. Most influenza vaccines are grown in chicken eggs or cell cultures, a process that takes approximately six months to finish.

This delay means that the World Health Organization has to predict months before the virus appear, which type of the virus has the best chance to be one that will circle the world next winter. Pharmaceutical industry then creates a new vaccine based on WHO recommendations. Of course, these recommendations may be wrong, or worse - when a completely new virus causes a pandemic, its first wave can be completed before any vaccine is ready.

mRNA Vaccine Advantages

However, there may be a solution. mRNA, which controls the production of HA and NA of influenza virus, can be produced in great amounts in a few weeks, says Lothar Stitz from Friedrich-Lofler Institute in Germany. This mRNA can be stored in frozen dry powder which is not necessary to freeze, unlike most vaccines that must be kept refrigerated.

mRNA vaccine is producted by the immune cells, and then transferred to the protein. These proteins the body then recognizes as foreign, causing the immune response. The immune system will further identify proteins if it encounters a virus, allowing the fight against this type of flu.

Similar vaccines are made of DNA with the code for proteins of influenza. However, DNA vaccines may never be approved because of concerns that they could be incorporated into human DNA, thus disrupting gene regulation.

This risk, however, does not exist when it comes to the mRNA, because it can not become a part of the genome. For this reasons, "RNA probably has advantages over DNA when it comes to safety," said Jaze Bjarne Bogen from the University of Oslo in Norway, working on DNA vaccines.
Test RNA vaccines have failed, as they were quickly destroyed in the blood. But "Curevac" company from Tubingen in Germany, found a protein called protamine, which binds to RNA and protects it, which is applied in the mRNA vaccine against prostate cancer and lung cancer, which has already been tested on humans.

Preclinical Experiments

"Amazing, mRNA vaccine has never actually been tested against infectious diseases," said Stitch. His team used Curevac's process of creating durable mRNA vaccines for common types of human flu, and the H5N1 avian influenza. In tests in mice, ferrets, and pigs, the vaccine has very quickly increased antiviral antibody levels.

This has also triggered an immune response that does not involve antibodies, but active blood cells such as T cells, ie. cytotoxic T lymphocyte to destroy the pathogen. The vaccines which are made only of proteins do not cause this kind of reaction.

The fact that both types of responses were obtained simultaneously eliminates the infection more quickly, and may also protect from the flu for a long time, as long as the cells are recognizing the flu virus, and even after the viruses are evolved to avoid antibodies.

A universal flu vaccine, however, will stimulate the immunity against proteins that are common to all flu viruses, but that virus usually hides from the immune system. Stitch’s team made the mRNA vaccine of such type of protein of ordinary seasonal flu virus. The vaccine not only protects animals from this type of influenza, but also from the H5N1, the bird flu.

Vaccines that protect against all types of influenza could be possibly received during childhood, as well as vaccines against other diseases. Meanwhile, Stitch is also working on the mRNA vaccine against rabies. "We think that the mRNA could provide an excellent platform against viral, bacterial and fungal diseases," he said.