Covid: Why T-Cell Vaccines Could Hold The Key To Long-Term Immunity

Given the the Omicron variant has rapidly increased Covid infections, the focus is once again on antibodies, and rightly so.

Antibodies play a critical role in fighting viruses and are important in preventing the coronavirus from infecting our cells.

This is why some countries have mounted booster vaccination campaigns in response to recent covid surges, in order to increase antibody levels.

But there’s a problem. Antibodies against Covid do not persist as wellhence the need for reinforcements.

In fact, while these additional injections maintain good protection against severe Covid, it is estimated that people receiving a third dose of the Pfizer vaccine will see their protection against developing Covid symptoms (of any degree) drop. 75% to 45% during the 10 weeks following your booster.

Scientists have questioned whether permanently recharging antibodies, only to see them soon wane, is a sustainable strategy.

If we want to build long-lasting immunity to covid, maybe it’s time to take a fresh look at our broader immune response.

Antibodies are just one part of our intricate and intertwined immune system. Specifically, maybe it’s time we focused on T cells.

How the different immune cells work

When the body is infected, say with a virus, it responds by producing white blood cells called lymphocytes. The main types of lymphocytes are b cells, that produce antibodies, and purpose T, which support the production of B-cell antibodies or act as killer cells to destroy the virus.

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

B cells and T cells “see” the virus in different ways.

Generally speaking, B cells recognize the forms on the outside of the virus, creating antibodies that latch onto or dock with them (a bit like 2 matching puzzle pieces).

In this illustration, antibodies (in white) are seen binding to the proteins of the virus that causes Covid. (Photo: SCIENCE PHOTO LIBRARY)

However, T cells recognize fragments of the amino acids that make up the virus, including fragments that are normally found inside.

Each virus has many unique features, both inside and out. A person’s immune response can end up producing a variety of T cells and B cells that, between them, attack a wide range of those traits.

This is sometimes called “response amplitude“. A good amplitude response involves many different lymphocytes seeing different parts of the virus, which makes it very difficult for the virus to completely hide itself.

Omicron concerned many researchers because a key part of its external structure that antibodies target, the spike protein or spike (in red in the first image above), has many mutations, which reduces the ability of antibodies to bind to the virus and neutralize it.

But nevertheless, because T cells target other parts of the virus, such mutations may not prevent it from being identified.

Indeed, preliminary data, still pending peer review, suggests this is the case.

This is reassuring, because the virus’ spike protein has changed a lot during the pandemic, suggesting that it might always be mutating out of reach of antibodies.

However, T cells should be less susceptible to viral mutation. T cells designed to fight covid also appear to last much longer in the human body than antibodies.

But do T cells have a major effect?

We already know a lot about the critical role of T cells in other viral infections.

This knowledge suggests that, against Covid, a good T cell response is not only necessary to help B cells produce antibodies, but should also create killer T cells that can broadly recognize the coronavirus, protecting against multiple variants.

Evidence about Covid and T cells is still being gathered. However, it is gradually becoming clearer that T cells appear to play a significant role in this disease.

A woman is vaccinated against covid
Antibodies against Covid don’t persist as well, hence the need for booster shots. (Photo: GETTY IMAGES)

The generation of broadly reactive T cells, which recognize a variety of viral characteristics, has been shown to be associated with a strong response against the disease.

In particular, generating good numbers of broadly reactive killer T cells seems to make covid less severe.

Conversely, poor T-cell response associated with poorer patient outcomes. In fact, some people who have had severe covid have been found to have persistent defects in their T-cell response.

Many studies that demonstrate the efficacy of T cells in the case of Covid have a common characteristic: the need for a wide range of responses, with T cells (and B cells) recognizing multiple characteristics of the virus. It is believed that this could be the key to experiencing a milder disease.

This breadth could even extend beyond this coronavirus specifically. The virus that causes covid is a betacoronavirus, and there are several betacoronaviruses that already infect us, including those that cause the common cold.

The shared characteristics between these cold-causing viruses and Covid may mean that the T cells we already had against the cold are now protecting us against Covid. Evidence of this is being discovered in both adults and children.

What does this mean for vaccines?

Many of the vaccines designed to date, including those from Moderna, Pfizer and AstraZeneca, have focused on a single main target of the coronavirus: its spike protein.

These vaccines have been tremendously effective in generating antibodies. They also stimulate a T cell response to the spike protein.

But now that we understand more about the role of T cells, the importance of having a broad T cell response, and the issue of antibody decline, perhaps we should consider refocusing our vaccine strategies and direct them to generate T cells and target more than one protein.

woman sneezing
If we want to develop long-lasting immunity to Covid, it may be time to take a fresh look at our broader immune response. (Photo: GETTY IMAGES)

There is research in this direction. The first clinical trials of vaccines that can elicit much more reactive helper and killer T-cell responses have been completed, and several other T-cell vaccines are also entering clinical trials.

These T-cell vaccines could be the key to strengthening existing immunity and generating long-lasting protection against severe symptoms generated by variants of the virus that causes Covid.

If this is so, these vaccines would be a fundamental contribution to help the world live with covid more safely.

*This article was originally published on The Conversation. You can read the original version here.

Sheena Cruickshank is a professor of biomedical sciences at the University of Manchester in the UK.

It may interest you:

* COVID: How long can you continue to spread the virus if you got sick
* Covid: The reason an antigen test comes back positive with orange juice
* Covid: these are the differences between a PCR and the antigen test and which one is better

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