Why you can’t get out of the COVID-19 pandemic in the long run | Health

With yet another COVID-19 booster available to vulnerable people in the United States, many are wondering what the final game will be.

The mRNA vaccine currently used in the United States for COVID-19 has been very successful in preventing hospitalization and death. The Commonwealth Fund recently reported that the vaccine alone killed more than 2 million people and prevented more than 17 million people from being hospitalized in the United States alone.

However, the vaccine has failed to provide long-term protective immunity to prevent breakthrough infections, cases of COVID-19 infection that occur in fully vaccinated people.

For this reason, the US Centers for Disease Control and Prevention recently approved a second booster shot for individuals over the age of 50 and people with immunodeficiency. Other countries, including Israel, the United Kingdom and South Korea, have also approved the second booster.

However, it is becoming increasingly clear that the second booster does not provide long-term protection against breakthrough infections. As a result, existing vaccines need to be modified to extend the protection period in order to end the pandemic.

As an immunologist studying the immune response to infectious diseases and other threats, he seeks to better understand vaccine booster-induced immunity against COVID-19.

Activates long-term immunity

It’s a bit of a medical mystery: why is the mRNA vaccine so successful in preventing the serious form of COVID-19, but not so good in protecting it from breakthrough infections? Understanding this concept is important for stopping new infections and controlling pandemics.

COVID-19 infections are unique in that the majority of people who recover from mild to moderate symptoms have few serious illnesses that can lead to hospitalization or death.

Understanding how the immune system works in mild and severe forms of COVID-19 is also important in the process of developing more targeted vaccines.

When people are first exposed to SARS-CoV-2 (the virus that causes COVID-19) or a vaccine against COVID-19, the immune system activates two major types of immune cells, called B cells and T cells. .. B cells produce Y-shaped protein molecules called antibodies. Antibodies bind to peplomer proteins that project onto the surface of the virus. This will prevent the virus from invading the cells and ultimately the infection.

However, if sufficient antibodies are not produced, the virus can escape and infect the host cell. When this happens, the immune system activates what is known as killer T cells. These cells recognize and destroy cells infected with the virus immediately after infection, preventing the virus from replicating and spreading widely.

Therefore, there is increasing evidence that killer T cells provide protection against severe forms of disease, while antibodies may help prevent breakthrough infections.

Why booster shot?

B cells and T cells are unique in that they are converted to memory cells after they initiate the first immune response. Unlike antibodies, memory cells can stay in the human body for decades and can initiate a rapid reaction when the same infectious pathogen is encountered. It is because of such memory cells that some vaccines against diseases such as smallpox provide protection for decades.

However, certain vaccines, such as hepatitis, require multiple vaccinations to boost the immune response. This is because the first or second dose is not sufficient to induce strong antibodies or maintain memory B and T cell responses.

This enhancement or amplification of the immune response helps increase the number of B and T cells that can respond to infectious pathogens. Boost also provokes a memory response, thereby providing long-term immunity to reinfection.

COVID vaccine booster

A third dose (or first boost) of the COVID-19 vaccine was very effective in preventing severe forms of COVID-19, but protection against infection lasted less than 4-6 months.

Because of the reduced protection after the third dose, the CDC approved a fourth dose of the COVID-19 vaccine, called the second booster, for people with immunodeficiency and those over the age of 50.

However, a recent preliminary study from Israel that has not yet been peer-reviewed shows that the second booster did not further boost the immune response, only recovering the reduced immune response seen during the third dose. Was shown. Also, the second booster provided little additional protection against COVID-19 when compared to the first three doses.

Therefore, the second booster certainly brings a small benefit to the most vulnerable people by extending immune protection for several months, but what does the availability of the fourth shot mean to the general public? There was a lot of confusion about.

Frequent boosting and immune exhaustion

In addition to the inability of current COVID-19 vaccines to provide long-term immunity, some researchers have found that frequent or constant exposure to foreign molecules found in infectious pathogens can cause “depletion” of immunity. I think there is.

Such phenomena are widely reported in HIV infection and cancer. In such cases, the T cells constantly “see” foreign molecules, which can be worn down and unable to get rid of cancer or HIV in the body.

Evidence also suggests that in severe cases of COVID-19, killer T cells may indicate immune depletion and therefore cannot initiate a strong immune response. Whether repeated COVID-19 vaccine boosters can cause similar T cell depletion may require further research.

The role of an adjuvant to enhance vaccine-induced immunity Another reason why mRNA vaccines have failed to elicit persistent antibodies and memory responses may be related to a component called an adjuvant. Traditional vaccines such as diphtheria and tetanus use adjuvants to boost the immune response. These are compounds that activate innate immunity consisting of cells known as macrophages. These are specialized cells that help T and B cells and ultimately elicit a stronger antibody response.

Since mRNA-based vaccines are a relatively new class of vaccines, they do not contain traditional adjuvants. Current mRNA vaccines used in the United States rely on small spheres of fat called lipid nanoparticles to deliver mRNA. Although these lipid molecules can act as adjuvants, it is not yet known how accurately these molecules affect the long-term immune response. And it has not yet been investigated whether the current COVID-19 vaccine’s inability to elicit a potent long-lived antibody response is associated with an adjuvant in existing formulations.

Current vaccines are very effective in preventing serious diseases, but the next phase of vaccine development should focus on how to elicit a long-lived antibody response that lasts at least one year, the COVID-19 vaccine. Will be the annual shot.

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