Universal flu vaccines can be one step closer and provide long-term protection against influenza

A bad year for the flu Tens of thousands Deaths in the United States Get vaccinated You can protect you from the flu, but you have to shoot every year to catch up Changing virus To replenish Short-lived immunity provided by the vaccine.. Vaccine efficacy also depends on the correct prediction of which strain is most common in a particular season.

For these reasons, a one-time universal vaccine that provides sustained immunity over multiple seasons of influenza and protects against a variety of strains has been a long-term goal for scientists.

Researchers are now one step closer to achieving that goal. Scientists have recently completed the first human trial of a vaccine created by recombinant genetic engineering, tricking the immune system into attacking some of the viruses that don’t change very quickly and are common to different strains. It was.

I am a microbiologist Interested in infectious diseases,And, I Seasonal influenza pandemic for several years.. I am excited about this news. This news could be a turning point in the quest for a universal influenza vaccine. This is all the mechanics.

Biology of the invading influenza virus

Like the virus that causes COVID-19, influenza viruses have a protein shell covered with a lipid membrane. Penetrating the membrane are multiple copies of the three proteins. Hemagglutinin, HA for short. Neuraminidase, NA for short; and matrix protein, M2.

It’s a property of HA and NA proteins Distinguish between different strains of virus. You’ve probably heard of stocks like H1N1 and H3N2, both of which Infects Americans this year..

The HA molecule is shaped like a flower bud and has a stem and a head. When someone inhales the virus, The tip of the head of the HA molecule binds To receptors on the surface of cells that line the human respiratory tract.

This first binding is very important because it induces the cells to swallow the virus. Once inside, the virus begins to work to replicate its own genetic material.However, the enzyme that copies that single-strand RNA Very sloppyYou can leave two or three mistakes called mutations. With all new copies..

Sometimes the genetic changes are so dramatic that the progeny virus does not survive. At other times, they are the beginning of a new strain of influenza.based on Virus samples collected from all over the worldThe influenza virus, which arrives a year later, has about 7 new mutations in the HA gene and 4 new mutations in the NA gene compared to the previous year’s virus. These differences are a big part of why the same flu vaccine is not so effective from one year to the next.

Fighting the flu infection

When infected with the flu virus, the immune system produces antibodies to prevent it. Most of these antibodies interact with HA heads Prevents viruses from invading cells.

However, the strong reaction has its downsides. The immune response to the virus’s head is so intense that little attention is paid. Other parts of the virus.. That is, even if the rest of the virus is the same, the immune system is not ready to prevent future infections by viruses with different HA heads.

Because current influenza vaccines are inactivated versions of the influenza virus, they also work by inducing antibodies that target the HA head. And that’s why each version of the vaccine usually works only for specific strains. However, as influenza spreads, rapid genetic alterations can produce new versions of HA heads that evade vaccine-induced antibodies. These newly resistant viruses will be ineffective even with this season’s vaccine.

The stem of the HA molecule is much more genetically stable than the head. Also, the HA stems of various influenza strains are much more similar than the area of ​​the head.

Therefore, the obvious way to protect people from various influenza strains is to use only HA stalks in the vaccine. Unfortunately, vaccination with headless stems alone does not seem to prevent infection.

Scientists are currently pursuing some Various solutions to this problem..

New type of influenza vaccine

A team of scientists led by Florian Kramer Completed the first human being at Ikarn Medical College on Mount Sinai Clinical trial What they want is a universal flu vaccine.

Researchers use recombinant genetic technology Influenza virus containing “chimeric” HA protein – Basically, a patchwork quilt constructed from fragments of various influenza strains.

Volunteer Clinical trial I received two vaccinations every three months. The first dose consisted of an inactivated H1N1 virus with the original HA stalk, but in the head of the avian influenza virus. Vaccination with this virus elicited a mild antibody response to the outpatient head and a strong response to the stem. This pattern meant that the subject’s immune system had never encountered the head, but had seen stems from previous influenza vaccinations or infections.

The second vaccination consisted of the same H1N1 virus, but used HA heads of different bird viruses. This dose again elicited a mild antibody response to the new head, but was further boosted in response to HA stalks. After each vaccine, the subject’s stem antibody concentration averaged about eight times the initial level.

Researchers have found that even if the vaccine is based on the HA stalks of the H1N1 virus strain, the antibodies it induces also react with the HA stalks of other strains. In lab tests, antibodies from vaccinated volunteers attacked the H2N2 virus. 1957 Asian cold pandemic H9N2 virus that the CDC considers Concerns about future outbreaks.. The antibody did not respond to the stems of the more distantly related H3 virus strains.

The antibody reaction also lasted for a long time. A year and a half later, the volunteers still had antibodies in their blood that were about four times higher than they were at the start of the study.

Because this was Phase 1 clinical trial Testing only side effects (minimum), researchers exposed vaccinated people to the flu and did not test whether new antibodies were protecting them.

However, they injected the mice with the serum of the subjects containing the antibodies to see if they could protect them from the flu virus. One month after receiving the booster shot, taking serum shots from volunteers with high antibody levels resulted in 95 health status of mice after virus exposure compared to mice that received serum from unvaccinated volunteers. % Improved. Even mice that received serum from vaccinated volunteers one year after the start of the study had about 30% less disease.

These results Vaccination with chimeric influenza proteins has been shown to be able to provide long-term immunity to several different strains of influenza virus.Scientists need to Continue optimizing this approach Therefore, it works with different types and strains of influenza. However, the success of this first human experiment means that one day it may be released from the flu in one shot.

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