Why T cell vaccines could be the key to long-term immunity amid the rise of COVID

Vaccine administration has moved on to the third dose or ‘booster shot’ to combat the third wave of COVID-19 cases by elevating antibody levels.

the focus is back on antibodies that are To develop In a body that has been given both shots of the anti-Covid vaccine.

Omicron has been reported to evade immunity and has thirty-seven mutations, making it potentially highly transmissible compared to other variants.

Antibodies play an important role in fighting virus And are important to stop the coronavirus infecting our cells.

While these additional jabs maintain good protection against severe COVID, it is estimated that people receiving the third dose of the Pfizer vaccine may increase their immunity against the development of COVID symptoms (of any degree) in the ten weeks following their booster. Will see protection reduced from 75% to 45%. ,

Scientists have questioned whether topping up of antibodies is sustainable only to see them soon fade away.

Antibodies are just one part of our complex and interconnected immune system. In particular, it is probably time we focused on T cells.

In this article Professor Sheena Cruickshank in Biomedical Sciences at the University of Manchester explains why T cell vaccines may be the key to long-term immunity.

How do different immune cells work?

When the body is infected, such as by a virus, it responds by producing white blood cells called lymphocytes. The main types are B cells, which make antibodies, and T cells, which either support B cell antibody production or act as killer cells to destroy viruses.

Some T cells and B cells also become long-lasting memory cells that know what to do if they meet the same infection again.

B cells and T cells “see” the virus in different ways. Normally, B cells recognize the outside shape of the virus, making antibodies that will lock onto them (like two jigsaw pieces that meet).

T cells instead recognize the bits of amino acids that make up the virus, including bits that can normally be found inside it.

Every virus has many unique characteristics, both inside and out. A person’s immune response can create different types of T cells and B cells that target a whole range of these characteristics among them. This is sometimes called the “width of the response”.

A good breadth of response has many different lymphocytes that see different parts of the virus, making it very difficult to completely hide from the virus.

Omicron worried many researchers because a key part of its external structure that is targeted by antibodies—the spike protein (in red in the photo above)—is heavily mutated, allowing antibodies to bind to the virus and neutralize it. capacity is reduced.

However, because T cells focus on other parts of the virus, such mutations may not prevent them from recognizing it.

Indeed, early data, which is still awaiting review, suggests this is the case. This is reassuring, as the virus’s spike protein has changed greatly during pandemics, suggesting that it may have always mutated far beyond the reach of antibodies.

However, T cells should be less sensitive to viral mutations. T cells designed to fight COVID also appear to last longer in the human body than antibodies.

But do T cells have a stronger effect?

We already know much about the important role of T cells in other viral infections. This knowledge suggests that, against COVID, a good T cell response is needed not only to help B cells produce antibodies, but also to make killer T cells that can widely recognize the coronavirus. , can protect in many ways.

Evidence directly on COVID and T cells is still being collected. However, it is gradually becoming clear that T cells play a larger role in COVID.

Research has shown that generating broadly reactive T cells that recognize a range of viral characteristics is associated with a stronger response against disease. Generating a particularly good amount of broadly reactive killer T cells makes COVID less severe.

Conversely, a poor T cell response is associated with worse outcomes for patients. In fact, some people who have had severe covid have been found to have persistent defects in their T cell response.

A common feature of the many studies demonstrating the effectiveness of T cells in COVID is the need for a wide breadth of response – the presence of T cells (and B cells) that recognize many of the characteristics of the virus. It is believed that this may be the key to experiencing minor illness.

This breadth can extend even further especially with this coronavirus. The COVID virus is a betacoronavirus, and there are many betacoronaviruses that already infect us, including those that cause the common cold.

The shared features between these cold-causing viruses and COVID may mean that the T cells we already had against colds are now protecting us from COVID. Evidence for this in both adults and children is being uncovered.

What does this mean for vaccines?

Many vaccines designed to date, including Moderna, Pfizer and AstraZeneca, have focused on just one major target on the coronavirus: its spike protein. These vaccines have been very effective in producing antibodies. They also stimulate the T cell response to the spike.

But now that we understand more about the role of T cells, the importance of the broad T cell response, and the issue of antibody depletion, perhaps we should focus on generating T cells and targeting more than just one protein in our vaccine strategies. But refocusing should be considered. ,

Work is underway in this direction. Early trials of vaccines that can trigger more broadly reactive helper and killer T cell responses, and several other T cell vaccines are also entering trials.

These T cell vaccines could be the key to boosting existing immunity and providing long-term protection against serious illness from various types of COVID-19. If so, they will be a bigger part of the world living more safely with COVID.

(with inputs from PTI)