How does Covid immunity work and what does it mean for vaccines? | Immunology



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What are the main components of the immune system? involved in the fight against Covid?

The immune system has several parts, including a first-line response that involves immune cells that alert the body to an attack and target infected cells. This response leads to the activation of what is known as the “adaptive” immune system, which is important for future immunity.

“[The adaptive immune system] it has this special feature of memory, which is what is exploited in vaccines, ”said Professor Danny Altmann, an expert in infectious disease immunology at Imperial College London.

It involves two main types of white blood cells, known as lymphocytes. B cells produce antibody proteins that can stick to the virus to prevent it from entering cells. T cells destroy virus-infected cells and produce proteins called cytokines. These cytokines help turn B cells into long-lived cells that make even better antibodies and “memory” B cells that can quickly produce specialized antibodies should the body be exposed to the virus again.

“Normally, T-cell immunity, B-cell immunity and their product, antibodies, go hand-in-hand in defeating a virus,” Altmann said.

But studies have found that while many people who have had Covid-19 have both T cells and antibodies to the virus, some only appear to have one or the other. “It’s very difficult to know what that means,” Altmann said.

And not all immune responses are helpful: Recent research has suggested that stubborn antibodies may play a role in conditions like prolonged Covid, where symptoms persist for many weeks to months after infection, as proteins wreak havoc ranging from the alteration of the defense mechanisms until the attack of organs.

What happens after an infection passes?

After an infection, antibody levels begin to decline, while memory B cells and T cells tend to stay longer.

A pre-print study published in July suggested that Covid antibody levels drop over a three-month period, and in some cases become undetectable. Research has also suggested that the speed and scale of this decline may differ between men and women. The level of antibodies produced, and how long they remain, appears to be related to the severity of the disease.

However, other research, which has yet to be peer-reviewed, has suggested that Covid antibodies show only small decreases over a six-month period after infection. The same study found that T cell levels halved over three to five months, but then leveled off after six months, and memory B cells became more abundant.

As Covid is a new disease, it will take more time before the longer-term trajectory of each of these components is known. But Deborah Dunn-Walters, a professor of immunology at the University of Surrey, was optimistic. “The fact that these cells are there, and they don’t look like they’re going to fall down very fast, means that we would expect to see them later,” he said.

What does all this mean for immunity?

A recent study found that when a Covid outbreak occurred on a fishing boat in August, none of the crew members who had antibodies to the virus became infected. “If you have [neutralising antibodies] on board, and you have them at a high enough level, I would bet my house that you are protected, ”said Altmann.

But what about memory B cells and T cells? Some studies have suggested that other coronaviruses, including those behind some common colds, subvert memory B cell production, meaning that even if these cells are present, they are less effective than you might expect.

“[There are] There are very good newspapers that say that this is the reason why these coronaviruses are so intelligent and that you can get, for example, the common cold winter after winter after winter and your memory does not help you, “said Altmann.

There are also questions about the T cell response and whether it is sufficient to offer protection on its own. While one study, which has yet to be peer-reviewed, found that people with higher levels of T cells towards Covid were less likely to become infected, more than half of these people also had antibodies to the virus.

“The fact that people are regularly reinfected throughout their lives with seasonal coronaviruses suggests that immunity, whether or not antibody-mediated and / or T-cell mediated, is probably not very durable,” said Professor Wendy. Barclay, chair of influenza virology at Imperial College London, has previously said.

This appears to be supported by increasing reports of reinfections. Sebastian Johnston, professor of respiratory and allergy medicine at Imperial College London, said that if a reinfection did occur, it was likely to be less severe than the first time, or even asymptomatic, although this is not always the case.

The potential for reinfection is the reason that Boris Johnson, who had Covid in the spring, recently had to isolate himself after coming into contact with another person with the virus, and one of the reasons the idea of ​​’immunity group ”natural is problematic.

“You may be immune to getting sick, but you are still transmitting the virus,” Dunn-Walters said. “Even if immunity lasts two to three years in one person, that doesn’t mean it lasts that long in another. One person may have a different level of memory cell response than another. “

Could there be some protection against T cells generated by exposure to other coronaviruses, such as those that cause some common colds?

It’s possible. In the T-cell study mentioned above, 45% of the participants with high levels of T-cells appeared to be protected against Covid but did not have antibodies to the virus.

That raises a number of possibilities. One is that this group had protective T cells generated by exposure to other distantly related coronaviruses, something known as protective “cross-reactivity.”

Altmann said that other studies had suggested that 30-40% of pre-pandemic blood samples showed a T-cell response by virtue of such cross-reactivity.

But he said that didn’t necessarily mean that these T cells offered a lot of protection against Covid. “[It isn’t clear] why your T cells from the common cold should protect you from this if they don’t even protect you from the common cold every winter. ”

Johnston said that the protection brought about by other coronaviruses could help explain why so many Covid infections are asymptomatic. “You can’t possibly have 70% of people who test positive say they have no symptoms unless they have a significant degree of immunity,” he said.

What can all this tell us about the protection we could get from a vaccine?

The good news is that Moderna, Pfizer / BioNTech and Oxford / AstraZeneca vaccines have been found to elicit an immune response and offer protection against the development of Covid. What’s more, although seasonal flu requires a different vaccine each year because it mutates rapidly, there is still little sign that this is the case for Covid.

Altmann said the new strain of Covid detected in England is unlikely to cause problems for vaccination, noting that the vaccine-induced neutralizing antibodies bind to many different parts of the so-called spike protein, part of the virus that helps it. to enter cells. “The mutation [in the virus] it is expected to make a fairly small change at a small peak, “he said.

But it is not yet clear how long the protection induced by vaccination will last, or whether vaccines prevent infection and transmission as well as disease. “Vaccines might work better than natural immunity, but we won’t know until we study both in the long term,” Johnston said.

Dunn-Walters said it was now important to find out how different aspects of the immune response correlate with protection, and how best to measure them, so that it is possible to better assess immunity levels in people and determine the frequency with which vaccination would be needed. . “This is an area of ​​ongoing research,” he said.

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