A bad year for the flu could mean tens of thousands of deaths in the United States. Being vaccinated can protect you from the flu, but you have to get the vaccine every year to recover from the mutating virus and increase the short-lived immunity the vaccine provides. The vaccine’s effectiveness also depends on correct predictions about which strains will be most common in a given season.
For these reasons, a unique universal vaccine that provides lasting immunity for several seasons of the flu and protects against a variety of strains has been a long-term goal for scientists.
The researchers are now one step closer to reaching that target. Scientists recently completed the first human test of a vaccine created by recombinant genetic technology to trick the immune system into attacking a part of the virus that does not change so quickly and 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 am excited about this news, which could mark the turning point in the search for a universal flu vaccine. See how it all works.
Biology of the invasive flu virus
Like the virus that causes COVID-19, the flu virus has a protein layer that is covered by a lipid membrane. Crossing the membrane are several copies of three types of proteins: hemagglutinin, abbreviated 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 have probably heard of strains like H1N1 and H3N2, both infecting people in the United States this year.
The HA molecule is shaped like a flower bud, with a stem and a head. As soon as someone inhales the virus, the tip of the HA molecule’s head attaches to a receptor on the surface of the cells lining the person’s airways.
This initial binding is crucial, as it induces the cell to engulf the virus. Once inside, the virus starts to work replicating its own genetic material. But the enzyme that copies its single-stranded RNA is very sloppy; you can leave two or three errors, called mutations, in each new copy.
Sometimes, the genetic changes are so drastic that the descending viruses do not survive; other times, they are the beginning of new strains of influenza. Based on viral samples collected worldwide, the flu virus that arrives in one year will have about seven new mutations in the HA gene and four in the NA gene compared to the virus from the previous year. These differences are a big part of why the same influenza vaccine will not be as effective from year to year.
Fighting a flu infection
When infected with the flu virus, your immune system produces antibodies to ward you off. Most of these antibodies interact with the head of HA and prevent the virus from entering cells.
But there is a downside to this strong reaction. Because the immune response to the virus head is so vigorous, it pays little attention to the other parts of the virus. This means that your immune system is not prepared to prevent any future infection with a virus that has a different head of HA, even if the rest of the virus is identical.
Current flu vaccines are inactivated versions of the flu virus and therefore also work by inducing antibodies to the head of HA. And that is why each version of the vaccine generally works only against a specific strain. But as the flu spreads, the rapid rate of genetic change can produce new versions of the head of HA that will avoid antibodies induced by the vaccine. These new resistant viruses will even render 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 strains of flu are much more similar than the regions of their heads.
So an obvious way to protect people against different strains of influenza would be to use only the stalk of HA in a vaccine. Unfortunately, vaccination with just a headless rod does not seem to prevent infection.
Scientists are currently looking for several different 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 of what they hope will be a universal flu vaccine.
The researchers used recombinant genetic technology to create flu viruses with “chimeric” HA proteins – essentially a patchwork made from pieces of different flu strains.
The clinical trial volunteers 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 an avian flu virus. Vaccination with this virus induced a moderate antibody response to the foreign head and a robust response to the stem. This pattern meant that the individuals’ immune systems had never found their heads before, but had seen the stem of previous flu vaccinations or infections.
The second vaccination consisted of the same H1N1 virus, but with an HA head of a different bird virus. This dose again provoked a moderate antibody response to the new head, but an additional boost in response to the HA stem. After each dose of vaccine, the concentrations of antibodies in the individuals’ stem were on average about eight times higher than their initial levels.
The researchers found that although the vaccine was based on the HA stem of the H1N1 strain, the antibodies it produced reacted to the HA stems of other strains as well. In laboratory tests, antibodies from vaccinated volunteers attacked the H2N2 virus that caused the 1957 Asian flu pandemic and the H9N2 virus, which the CDC considers to be a concern for future outbreaks. The antibodies did not react to the stem of the most distantly related 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 antibodies to the HA stem in their blood than when the trial started.
As this was a phase 1 clinical trial only for adverse effects (which were minimal), the researchers did not expose vaccinated people to the flu to test whether their new antibodies protected them.
However, they injected the individuals’ blood serum, which contains the antibodies, into mice to see if that would protect them from the flu virus. Taking an injection of serum from volunteers one month after receiving the booster injection, when antibody levels were high, made the mice 95% healthier after exposure to the virus than those who received blood serum from volunteers. not vaccinated. Even the mice that received serum collected from vaccinated volunteers one year after the start of the test were about 30% less sick.
These results show that vaccination with a chimeric flu protein can provide long-lasting immunity to several different strains of the flu virus. Scientists will need to continue to optimize this approach so that it works for different types and strains of influenza. But the success of this first human test means that one day you can have a single injection and finally be free of the flu.
[The Conversation’s science, health and technology editors pick their favorite stories. Weekly on Wednesdays.]
This article was republished from The Conversation, a nonprofit news site dedicated to sharing ideas from academic experts. It was written by: Patricia L. Foster, Indiana University.
Read More:
Patricia L. Foster is affiliated with the Union of Concerned Scientists and Concerned Scientists at Indiana University.