Can genetics influence how you respond to the COVID vaccine?

Right now, white blood cells known as T-cells are cruising through your body looking for any signs of an infection.  

New research has shown your genetics influence how well these immune system cells respond to SARS-CoV-2 (the virus that causes COVID-19).

But can your genetic make-up also influence how your T-cells react to the COVID-19 vaccine?

That’s the question Australian scientists like Corey Smith are keen to answer.

While studies have shown vaccines prompt a T-cell response, these responses have varied from person to person and it hasn’t been clear why, said Dr Smith of the QIMR Berghofer Medical Research Institute.

His team is investigating whether the same factors (such as genetics and age) that influence how well a person’s T-cells react to SARS-CoV-2 (the virus which causes COVID-19 disease) also influence their reaction to the vaccine.

“We think that kind of work is really important,” he said.

 “It may help to guide improvements in the vaccines as we move forward.”

Wait … what are T-cells?
Our bodies use B-cells and T-cells to build immunity.

B-cells fight infection by making antibodies, which bind to the surface of the virus and mark it so the body’s other immune cells know to destroy it.

T-cells, which Dr Smith described as the “workhorse of our immune system”, work very differently.

There are two main types of T-cells: helpers and killers.

Helper T-cells tell the body’s B-cells to make antibodies and they also help the killer cells develop.

Killer T-cells (as the name suggests) kill cells that have been infected by the virus.

But here’s where it gets complicated.

T-cells only look at part of the virus, not the entire thing. And the part of the virus your body shows its T-cells depends on which proteins are available.

We all have different protein molecules on the surface of our cells that are slightly different, depending on factors such as our genetic background.

There are potentially six different types of these proteins on the surface of the cell, explained Emily Edwards of Monash University’s B Cell Differentiation Laboratory.

“Each one has a different capacity to bind different fragments of the virus, so some will be more efficient than others and bind more strongly,” Dr Edwards said.

SARS-CoV-2 and T-cells
Dr Smith and his colleague recently published a paper that examined how T-cells become activated to fight SARS-CoV-2

Dr Smith’s team discovered that although antibodies need to recognise the spike protein of SARS-CoV-2 to mount an immune response, the spike protein did not prompt the optimal response in our T-cells.

This was generated by a different type of protein, called a nucleocapsid.  

Only a few people have T-cells specific to this nucleocapsid protein, but Dr Smith theorised that those who had these immune cells could be able to fight off SARS-CoV-2 more effectively if they were exposed to the virus.

“A lot of people won’t and that’s obviously important for people getting vaccinations moving forward.”

Implications for vaccination
The first generation of COVID-19 vaccines target the spike protein on SARS-CoV-2.

Dr Edwards said this was because the body’s B-cells (which makes antibodies) predominantly responded to the spike protein.

“That does not mean we will not generate a T-cell response,” she said.

“But this paper shows that there are other targets that maybe we should be looking at in addition [to the spike protein].”

It’s still not clear if, or more likely when, people will need booster shots for the COVID-19 vaccines (although Pfizer has flagged people will “likely” need a third dose between six and 12 months after the first two).

Dr Edwards said, theoretically, some people may need a booster more than others due to varied immune responses, which is what we see with other vaccines.

“That’s also the case with the hepatitis B vaccine – some people have the full course and then never need a booster,” she said.

“Then there are others that don’t generate a response and have to continually have boosters.”

Dr Edwards said longer-term vaccine development may also benefit from specifically targeting the nucleocapsid protein to maximise the body’s immune response.

Joanna Groom, laboratory head in the immunology division at the Walter and Eliza Hall Institute of Medical Research, said the research might help us understand the genetic reasons why some people can clear a coronavirus infection  faster than others.

“That really helps us to understand why we see that variability in the symptoms in people when they are infected,” Dr Groom said.

But, she pointed out, the findings could have limited implications for vaccines because the specific T-cells that target the nucleocapsid protein weren’t common.

“It accounts for too few of the population to really target [with a vaccine],” she said.

Dr Groom said the strategy of optimising the body’s T-cell response using a vaccine was a good one, but researchers would need to identify a protein that prompted a strong immune response in the wider population. 

T-cells respond to a wide number of proteins; some proteins spark a stronger killer response, others a stronger helper response.

“What you want to do is generate a range of different T-cells so you have a higher likelihood of being about to recognise the proteins of the virus,” Dr Groom said.

‘Get vaccinated’, experts urge
Moving forward, Dr Smith said his team wanted to learn more about the body’s T-cell response to vaccination, to understand if and why some people were more vulnerable to infection.

“If we do open up [the borders] and the virus starts to spread, there may be still parts of the population that are at risk, even if we’ve been vaccinated,” he said.

Both vaccines approved for use in Australia offer strong protection against severe disease and death from COVID-19 disease, and offer strong protection against SARS-CoV-2.

And all three experts urged those who are eligible to get vaccinated when they can.

“It’s really important that people go out and get vaccinated,” Dr Edwards said.

“We need to generate these B- and T-cell responses within the community so that we can help protect those individuals that either can’t receive the vaccine or will not generate as much of a protective response.”

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