A bad year for flu could mean tens of thousands of deaths in the US. Being vaccinated can protect you from the flu, but you should be given the opportunity to catch up with the changing virus each year and to supplement the short-lived immunity of the vaccine. provide. The effectiveness of the vaccine also depends on correct predictions about which strains are most common in a given season.
For these reasons, scientists are a long-term target for universal vaccines that will provide lasting immunity over several flu seasons and protect against a variety of strains.
Researchers are now one step closer to reaching the target. Scientists recently completed the first human experiment with a vaccine created by recombinant genetic technology to deceive the immune system into attacking a part of the virus that does not change as quickly and that is common among different strains.
I am a microbiologist interested in infectious diseases, and I have been following the seasonal flu epidemic for several years. I’m excited about this news, which could be the turning point in the pursuit of a universal flu vaccine. Here’s how it all works.
Biology of the invasive influenza virus
Like the virus that causes COVID-19, the flu virus has a protein shell that is covered by a lipid membrane. Through the membrane pass several copies of three types of proteins: hemagglutinin, abbreviated as HA; neuraminidase, abbreviated as NA; and the matrix protein, M2.
It is the properties of the HA and NA proteins that distinguish the different strains of the virus. You’ve probably heard of strains like H1N1 and H3N2, both of which infect people in the US this year.
The HA molecule is a bit like a flower bud, with a stem and a head. Once someone inhales the virus, the tip of the HA molecule’s head binds to a receptor on the surface of the cells that leads through the person’s respiratory tract.
This initial binding is crucial because it causes the cell to swallow the virus. Once it enters, the virus begins to replicate its own genetic material. But the enzyme that copies the single-stranded RNA is very sloppy; it can leave two or three errors, called mutations, in each new instance.
Sometimes the genetic changes are so drastic that the progeny viruses do not survive; other times it is the beginning of new flu strains. Based on viral samples collected from around the world, the one-year-old flu virus will have approximately seven new mutations in the gene for HA and four in the gene for NA compared to the previous year’s virus. These differences are a big part of the reason why the same flu vaccine from one year to the next will not be as effective.
Fighting a flu infection
If you are infected with the flu virus, your immune system produces antibodies to ward it off. Most of these antibodies interact with the HA head and prevent the virus from entering your cells.
But there is a downside to the strong response. Because the immune response to the head of the virus is so strong, it pays little attention to other parts of the virus. This means that your immune system is not prepared to ward off any future infection with a virus with a different HA head, even though the rest of the virus is identical.
Current flu vaccines are inactivated versions of the flu virus and therefore also work by causing antibodies directed at the HA head. And therefore, each version of the vaccine usually only works against a specific strain. But as the flu spreads, the rapid pace of genetic change could yield new versions of the HA head that will evade the antibodies caused by the vaccine. These newly resistant viruses will make even the current season’s vaccine ineffective.
The stem portion of the HA molecule is much more genetically stable than the head. And HA stems from different flu strains are much more alike than their main regions.
So, an obvious way to protect people from various flu strains is to just use the HA stem in a vaccine. Unfortunately, vaccination with only a headless stem can not prevent infection.
Scientists are currently working on various solutions to this problem.
A new type of flu vaccine
A team of scientists led by Florian Krammer at the Icahn School of Medicine on Mount Sinai has just completed the first human clinical trial that they believe will be a universal flu vaccine.
The researchers use recombinant genetic technology to create flu viruses with ‘chimeric’ HA proteins – essentially a patchwork quilt built from different flu strains.
Volunteers for the clinical trial received two vaccinations, separated by three months. The first dose consisted of an inactivated H1N1 virus with its original HA stem but the head portion of a bird flu virus. Vaccination with this virus caused a mild antibody response to the foreign head and a strong reaction to the stalk. This pattern meant that the subjects’ immune systems had never encountered the head before, but that the stem of previous vaccination or flu infections had been seen.
The second vaccination consists of the same H1N1 virus, but with an HA head from another bird virus. This dose again elicited a mild antibody response to the new head, but a further boost in response to the HA steal. After each vaccine dose, the subject’s antibody concentration was approximately eight times higher than their initial levels.
Researchers have found that although the vaccine is based on the HA stem of the H1N1 virus strain, the antibodies it elicits also respond to HA stems from other strains. In laboratory tests, the antibodies of vaccinated volunteers attacked the H2N2 virus that caused the Asian flu pandemic in 1957 and the H9N2 virus, which the CDC considers worrying about future outbreaks. The antibodies do not respond to the stealing of the more related H3 viral strain.
The antibody response also lasted a long time; after one and a half years, the volunteers still had about four times the concentration of antibodies against the HA stem in their blood as when the trial began.
Since it was a phase 1 clinical trial that was only tested for adverse effects (which were minimal), the researchers did not vaccinate people exposed to the flu to test whether their new antibodies protected them.
They did inject the blood serum of the subjects, which contained the antibodies, into mice to see if it would protect them from the flu virus. The acquisition of a serum serum from volunteers one month after receiving the booster shot, when the antibody level was high, resulted in mice after exposure to viruses being 95% healthier than mice receiving blood serum from non-vaccinated volunteers. . Even the mice that received serum collected from vaccinated volunteers a year after the start of the trial were about 30% less sick.
These results show that vaccination with a chimeric influenza protein can provide long-lasting immunity to different strains of the influenza virus. Scientists will need to continue to optimize this approach so that it can be used for different types of boundaries. But the success of this first human trial means that you may one day get a single chance and finally be free from the flu.
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This article was published from The Conversation, a non-profit news site dedicated to sharing ideas from academic experts. It was written by: Patricia L. Foster, Indiana University.
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Patricia L. Foster is affiliated with the Union of Concerned Scientists and Concerned Scientists at Indiana University.