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A bad year for the flu can mean tens of thousands of deaths in the United States Getting the vaccine may protect you from the flu, but you need to get the vaccine every year to catch up with the evolving virus and to boost immunity over time. duration of the vaccine. provides. The effectiveness of the vaccine also depends on correct predictions of the most common strains in a given season.
For these reasons, a single universal vaccine that would provide long-lasting immunity over several influenza seasons and protect against a variety of strains has been a long-term goal for scientists.
Researchers are now on the verge of achieving this goal. Scientists recently completed the first human trial of a vaccine created by recombinant genetic technology to trick the immune system into attacking a part of the virus that doesn’t change so quickly and is common among different strains.
I am a microbiologist interested in infectious diseases and have followed the epidemic of seasonal influenza for several years. I am excited about this news, which could mark the turning point in the quest for a universal influenza vaccine. Here is how it all works.
Biology of the invasive influenza virus
Like the virus that causes COVID-19, the influenza virus has a protein envelope covered by a lipid membrane. Sticking through the membrane are multiple 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 United States this year.
The HA molecule is shaped like a flower bud, with a stem and a head. After someone inhales the virus, the tip of the head of the HA molecule binds to a receptor on the surface of cells that line a person’s airways.
This initial binding is crucial because it induces the cell to engulf the virus. Once inside, the virus goes to work by replicating its own genetic material. But the enzyme that copies its single-stranded RNA is very sloppy; it can leave two or three errors, called mutations, in each new copy.
Sometimes the genetic changes are so drastic that the offspring viruses do not survive; other times, they are the start of new influenza strains. Based on viral samples collected from around the world, influenza virus that arrives one year will have about seven new mutations in the HA gene and four in the NA gene compared to virus of the year. previous. These differences go a long way in explaining why the same influenza vaccine will not be as effective from year to year.
Fighting an influenza infection
When infected with the influenza virus, your immune system makes antibodies to repel it. Most of these antibodies interact with the HA head and prevent the virus from entering your cells.
But there is a downside to this strong reaction. Because the immune response to the head of the virus is so vigorous, it pays little attention to other parts of the virus. This means that your immune system is not ready to fend off any future infection with a virus that has a different HA head, even if the rest of the virus is the same.
Current influenza vaccines are inactivated versions of the influenza virus and therefore also work by inducing targeted antibodies to the HA head. And that’s why each version of the vaccine usually only works against a particular strain. But, as the flu spreads, the rapid pace of genetic change can produce new versions of the HA head that will escape the antibodies induced by the vaccine. These newly resistant viruses will then render even the current season’s vaccine ineffective.
The stem part of the HA molecule is much more genetically stable than the head. And the HA stems of different flu strains look a lot more alike than their head regions.
So an obvious way to protect people from different strains of influenza would be to use only the HA stem in a vaccine. Unfortunately, vaccination with just a headless rod does not appear to prevent infection.
Scientists are currently researching several different solutions to this problem.
A new type of flu vaccine
A team of scientists led by Florian Krammer of the Icahn School of Medicine at Mount Sinai have just completed the first human clinical trial of what they hope will be a universal influenza vaccine.
Researchers used recombinant genetic technology to create influenza viruses with “chimeric” HA proteins – essentially a patchwork quilt constructed from pieces of different flu strains.
The clinical trial volunteers received two vaccinations three months apart. The first dose consisted of an inactivated H1N1 virus with its stem of HA origin but the head part of an avian influenza virus. Vaccination with this virus induced a mild antibody response to the foreign head, and a robust response to the stem. This pattern meant that the subjects’ immune systems had never encountered the head before, but had seen the backbone of previous flu vaccinations or infections.
The second vaccination consisted of the same H1N1 virus but with an HA head of a different avian virus. This dose elicited, again, a slight antibody response against the new head, but another boost in response to the HA rod. After each dose of vaccine, the subjects’ stem antibody concentrations were on average about eight times higher than their initial levels.
The researchers found that although the vaccine was based on the HA stalk of the H1N1 virus strain, the antibodies it elicited also reacted to the HA stems of other strains. In lab tests, antibodies from vaccinated volunteers attacked the H2N2 virus that caused the 1957 Asian flu pandemic and the H9N2 virus that the CDC considers of concern for future epidemics. The antibodies did not react to the stem of the more distant H3 viral strain.
The antibody response also lasted a long time; after a year and a half, the volunteers still had about four times the concentration of anti-HA antibodies in their blood than at the start of the trial.
Since this was a Phase 1 clinical trial to test only for side effects (which were minimal), the researchers did not expose the vaccinated people to the flu to test whether their new antibodies protected them.
However, they injected the subjects’ blood serum, which contains the antibodies, into mice to see if it would protect them against the flu virus. Obtaining a dose of serum taken from volunteers one month after receiving the booster vaccine, when antibody levels were high, led the mice to be 95% healthier after exposure to the virus than the mice that received blood serum from unvaccinated volunteers. Even the mice that received serum from vaccinated volunteers one year after the start of the trial were about 30% less sick.
These results show that vaccination with a chimeric influenza protein can confer lasting immunity to several different strains of influenza virus. Scientists will need to continue optimizing this approach so that it works for different types and strains of influenza. But the success of this first human trial means that one day you can receive just one vaccine and, finally, be free from the flu.
[The Conversation’s science, health and technology editors pick their favorite stories. Weekly on Wednesdays.]
This article is republished from The Conversation, a nonprofit 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.
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