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

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What are the major components of the immune system involved in fighting Covid?

The immune system has several parts, including a first-line response involving immune cells that alert the body to an attack and home in on 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] has this special feature of memory, which is what you exploit in vaccines,” said Prof Danny Altmann, an expert in immunology of infectious disease 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 kill virus-infected cells and make proteins called cytokines. These cytokines help to convert B cells into long-lived cells that produce even better antibodies, and “memory” B cells that can rapidly churn out specialised antibodies should the body be exposed to the virus again.

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

But studies have found that while many people who have had Covid-19 have both T cells and antibodies for the virus, some only seem to have one or the other. “It is so hard to know what that means,” Altmann said.

And not all immune responses are helpful: recent research has suggested wayward antibodies may play a role in conditions such as long Covid, where symptoms persist for many weeks or months after infectionas proteins cause havoc ranging from disrupting defence mechanisms to attacking organs.

What happens after an infection passes?

After an infection, antibody levels start to wane, while memory B cells and T cells tend to hang around for longer.

A pre-print study released in July, suggested Covid antibody levels fall over a period of three months, in some cases becoming 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 the length of time they hang around for, seems to be linked to the severity of the disease.

However, other research, also not yet peer-reviewed, has suggested that Covid antibodies show only small declines over a period of six months after infection. The same study found that T-cell levels dropped by half over three to five months but then plateaued after six months, and memory B-cells became more abundant.

As Covid is a new disease, more time will need to pass before the longer-term trajectory for 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 to be dropping off really quickly, means that we would expect to see them later on,” she said.

What does all this mean for immunity?

A recent study found that when a Covid outbreak occurred on a fishing vessel in August, none of the crew members who had antibodies to the virus became infected. “If you have got [neutralising antibodies] onboard, and you’ve got them at a high enough level, I’d bet my house on you being 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 the production of memory B cells, meaning that even if these cells are present, they are less effective than might be expected.

“[There are] quite good papers out there saying that’s the reason that these coronaviruses are so clever and that you can get, for example, the common cold winter after winter after winter and your memory doesn’t help you,” Altmann said.

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

“The fact that people get reinfected regularly throughout their lives with seasonal coronaviruses suggests that immunity, whether or not it is antibody-mediated and/or T cell-mediated, probably isn’t very long-lasting,” Prof Wendy Barclay, the chair of influenza virology at Imperial College London, has previously said.

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

The potential for reinfection is why Boris Johnson – who had Covid in the spring – recently had to self-isolate after coming into contact with someone else with the virus, and one reason why the idea of natural “herd immunity” is problematic.

“You could be immune to being sick but you are still passing the virus round,” said Dunn-Walters. “Even if the immunity lasts two to three years in one person, that does not mean it would last that long in another. One person may make a different level of memory cell response than another.”

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

It is possible. In the T cell study mentioned earlier, 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 other studies had suggested 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 these T cells offered much protection against Covid. “[It isn’t clear] why your common cold T cells should protect you from this thing if they don’t even protect you from the common cold every winter.”

Johnston said protection generated by other coronaviruses might help to explain why so many Covid infections are asymptomatic. “You could not possibly have 70% of people who test positive saying that they have no symptoms unless they have a signifiant degree of immunity,” he said.

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

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

Altmann said the new strain of Covid detected in England was unlikely to cause problems for vaccination, noting that the neutralising antibodies induced by the vaccine bind to many different parts of the so-called spike protein – part of the virus that helps it enter cells. “The mutation [in the virus] is predicted to make quite a small change to one little bit of spike,” he said.

But it is not yet clear how long protection induced by vaccination will last, or whether the vaccines prevent infection and transmission as well as disease. “The vaccines could do better than natural immunity, but we will not know until we study both longer-term,” said Johnston.

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

Hafta Ichi
Source: The Guardian
Keyword: How does Covid immunity work and what does it mean for vaccines? | Immunology

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