Analysis: Recalls are crucial, but revamped COVID vaccines will be key to ending the pandemic

With another COVID-19 reminder available for vulnerable populations in the United States, many people are wondering what the endgame will be.

The mRNA vaccines currently used in the United States against COVID-19 have been very successful in preventing hospitalization and death. The Commonwealth Fund recently reported that in the United States alone, vaccines have prevented more than 2 million people from dying and more than 17 million hospitalizations.

However, vaccines have 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 Centers for Disease Control and Prevention recently approved a second booster shot for people 50 and older and people with compromised immune systems. Other countries, including Israel, the United Kingdom and South Korea, have also approved a second booster.

However, it has become increasingly clear that the second booster does not provide long-lasting protection against breakthrough infections. As a result, it will be necessary to retool existing vaccines to increase the duration of protection to help end the pandemic.

As immunologists studying the immune response to infections and other threats, we are trying to better understand the immunity induced by the COVID-19 vaccine booster.

Activate longer term immunity

It’s a bit of a medical mystery: why are mRNA vaccines so good at preventing the severe form of COVID-19, but not so good at protecting against emerging infections? Understanding this concept is key to stopping new infections and controlling the pandemic.

COVID-19 infection is unique in that the majority of people who catch it recover with mild to moderate symptoms, while a small percentage contract the severe illness that can lead to hospitalization and death.

Understanding how our immune system works during mild and severe forms of COVID-19 is also important for 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 for COVID-19, the immune system activates two key types of immune cells, called B cells and T. B cells produce Y-shaped protein molecules called antibodies. The antibodies bind to the protruding spike protein on the surface of the virus. This prevents the virus from entering a cell and ultimately prevents it from causing an infection.

However, if not enough antibodies are produced, the virus can escape and infect host cells. When this happens, the immune system activates what are called killer T cells. These cells can recognize virus-infected cells immediately after infection and destroy them, thereby preventing the virus from replicating and causing widespread infection.

Thus, there is growing evidence that antibodies can help prevent breakthrough infections while killer T cells offer protection against the severe form of the disease.

Why booster shots?

B cells and T cells are unique in that after mounting an initial immune response, they are converted into memory cells. Unlike antibodies, memory cells can stay in a person’s body for decades and can react quickly when they encounter the same infectious agent. It is thanks to these memory cells that certain vaccines against diseases such as smallpox provide protection for decades.

But with some vaccines, such as hepatitis, multiple doses of a vaccine are needed to stimulate the immune response. Indeed, the first or second dose is not sufficient to induce robust antibodies or to maintain the memory B and T cell response.

This stimulation, or amplification of the immune response, helps to increase the number of B cells and T cells that can respond to the infectious agent. Stimulation also triggers the memory response, thereby providing prolonged immunity against reinfection.

COVID vaccine reminders

While the third dose – or first booster – of COVID-19 vaccines was highly effective in preventing the severe form of COVID-19, the protection offered against infection lasted less than four to six months.

This reduced protection even after the third dose is what led the CDC to approve the fourth COVID-19 vaccine — called the second booster — for immunocompromised people and those age 50 and older.

However, a recent preliminary study from Israel which has yet to be peer-reviewed showed that the second booster did not boost the immune response further, but merely restored the waning immune response seen with the third dose. . Additionally, the second booster provided little additional protection against COVID-19 compared to the initial three doses.

So while the second booster certainly offers a small benefit to the most vulnerable people by prolonging immune protection for a few months, there has been considerable confusion about what the availability of the fourth vaccine means for the general population.

Frequent boost and immune depletion

In addition to the inability of current COVID-19 vaccines to provide long-term immunity, some researchers believe that frequent or constant exposure to foreign molecules present in an infectious agent may cause immune “exhaustion.”

Such a phenomenon has been widely reported with HIV infection and cancer. In these cases, because T cells “see” foreign molecules all the time, they can wear out and fail to rid the body of cancer or HIV.

Evidence also suggests that in severe cases of COVID-19, killer T cells may exhibit immune exhaustion and therefore be unable to mount a strong immune response. Whether repeated boosters of the COVID-19 vaccine can cause similar T-cell depletion is a possibility that requires further study.

Role of adjuvants in boosting vaccine-induced immunity

Another reason why mRNA vaccines have failed to induce a sustained antibody and memory response may be related to ingredients called adjuvants. Traditional vaccines such as those against diphtheria and tetanus use adjuvants to stimulate the immune response. These are compounds that activate innate immunity made up of cells called macrophages. They are specialized cells that help T cells and B cells, ultimately inducing a stronger antibody response.

Because mRNA vaccines are a relatively new class of vaccines, they do not include traditional adjuvants. The mRNA vaccines currently used in the United States rely on small balls of fat called lipid nanoparticles to deliver mRNA. These lipid molecules can act as adjuvants, but how precisely these molecules affect the long-term immune response remains to be seen. And whether the failure of current COVID-19 vaccines to elicit a strong, long-lasting antibody response is related to adjuvants in existing formulations remains to be explored.

While current vaccines are highly effective at preventing serious disease, the next phase of vaccine development will need to focus on how to elicit a long-lasting antibody response that would last at least a year, making COVID vaccines likely -19 become an annual hit.

This article is republished from The Conversation under a Creative Commons license. Read the original article.


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