Why We Can’t ‘Boost’ Our Way Out of the COVID-19 Pandemic in the Long Term – The Wire Science

woman receive booster A snapshot of a COVID-19 vaccine at Taipei Main Station, Taiwan, January 24, 2022. Photo: REUTERS/Ann Wang/FILE PHOTO


  • mRNA vaccines have failed to provide long-term protective immunity against superinfection: the cases of COVID-19 infection that occur in fully vaccinated people.
  • Even second boosters will not protect for long from superinfection, so it has become necessary to retool existing vaccines to extend protection.
  • Some researchers also believe that repeated or continued exposure to foreign particles in an infectious agent may cause immune “exhaustion.”
  • While current vaccines are effective in preventing severe disease, the next phase of vaccine development will need to focus on stimulating a long-term antibody response.

With yet another COVID-19 booster available to the at-risk population of the United States, many people are finding themselves wondering what the endgame is.

The mRNA vaccines currently in use in the United States against COVID-19 have successfully prevented 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 from being hospitalized.

However, vaccines have failed to provide long-term protective immunity against superinfections – cases of COVID-19 infections that occur in fully vaccinated people.

For this reason, the Centers for Disease Control and Prevention recently approved a second booster dose for individuals 50 years of age or older and people who are immunocompromised. Other countries including Israel, the United Kingdom and South Korea have also agreed to a second boost.

But it is becoming increasingly clear that the second booster does not provide long-term protection against superinfection. As a result, it will be necessary to retool existing vaccines to increase the duration of protection in order to help end the epidemic.

As immunologists study the immune response to infection and other threats, we are trying to better understand the immunity elicited by the COVID-19 booster vaccine.

Long-term immune activation

It’s kind of a medical mystery: Why do mRNA vaccines prevent the dangerous form of COVID-19 but aren’t so great at protecting against superinfection? Understanding this concept is critical to stopping new infections and controlling the epidemic.

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

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

However, if not enough antibodies are produced, the virus can escape and infect the host cells. When this happens, the immune system activates what are known as killer T cells. These cells can recognize and destroy virus-infected cells immediately after infection, thus preventing the virus from reproducing and causing the infection to spread.

Thus, there is increasing evidence that antibodies may help prevent superinfection while killer T cells provide protection from the acute form of the disease.

Why booster shots?

B cells and T cells are unique in that, after they make 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 mount a rapid response when they encounter the same infectious agent. Because of these memory cells, some vaccines against diseases like smallpox provide protection for decades.

But with some vaccines, such as hepatitis, it is necessary to give multiple doses of the vaccine to boost the immune response. This is because the first or second dose is not sufficient to stimulate strong antibodies or to maintain the response of memory B and T cells.

This boosting or amplification of the immune response helps increase the number of B cells and T cells that can respond to the infectious agent. The boost also stimulates the memory response, thus providing long-term immunity against re-infection.

COVID vaccine boosters

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

This diminished protection even after the third dose is what prompted the Centers for Disease Control and Prevention to endorse the fourth round of the COVID-19 vaccine — called the second booster — for immunocompromised people 50 and older.

However, a recent preliminary study from Israel that had not yet been peer-reviewed showed that the second booster did not enhance the immune response, but did restore the diminished immune response seen during the third dose. Also, the second booster offered little additional protection against COVID-19 when compared to the initial three doses.

So, while a second booster certainly provides a small benefit to the most vulnerable by extending immune protection for a few months, there has been significant confusion about what it means to have a fourth injection available to the general population.

Frequent boosting and fatigue of the immune system

In addition to the inability of current COVID-19 vaccines to provide long-term immunity, some researchers believe that repeated or continued exposure to foreign particles contained in an infectious agent may cause immunity to be ‘depleted’.

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

Evidence also indicates that in severe cases of COVID-19, killer T cells may show immune depletion and thus be unable to mount a robust immune response. Whether repeated COVID-19 vaccine boosters can cause similar T-cell depletion likely needs further study.

The role of adjuvants in enhancing vaccine-induced immunity

Another reason why mRNA vaccines fail to produce a sustained antibody and memory response may be related to components called adjuvants. Conventional vaccines such as those for diphtheria and tetanus use adjuvants to boost the immune response. These are compounds that activate the innate immunity made up of cells known as macrophages. These are specialized cells that assist T cells and B cells, which eventually lead to a stronger antibody response.

Because mRNA-based vaccines are a relatively new class of vaccines, they do not include traditional adjuvants. Current mRNA vaccines used in the United States rely on small balls of lipids called lipid nanoparticles to deliver mRNA. These lipid molecules can act as adjuvants, but it remains to be seen how precisely these molecules affect the long-term immune response. Whether the failure of current COVID-19 vaccines to trigger a robust long-lived antibody response is related to the adjuvants in current formulations remains to be explored.

While current vaccines are highly effective in preventing severe disease, the next phase of vaccine development will need to focus on how to trigger a long-term antibody response that would last for at least a year, making it likely that COVID-19 vaccines will last. . It becomes an annual snapshot.

Prakash Nagarkatti and Mitzi Nagarkatti are both professors of pathology, microbiology, and immunology at the University of South Carolina.

This article has been republished from Conversation.

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