By William Park
14th October 2020
The strategy for rolling out a Covid-19 vaccine might be undermined by older people’s immune systems.
In a hypothetical alternative universe where we already have a vaccine against Covid-19, world leaders will have a choice about how to deliver it to the population. The most vulnerable people, along with the nurses, doctors and care workers who look after them, are likely to be protected first.
If only it were that straightforward. The most vulnerable age group, the elderly, are particularly tricky to vaccinate.
“We have very few vaccines designed for older populations,” says Shayan Sharif, a professor of vaccinology at the University of Guelph, Canada. “More often than not in the last century, most vaccines have targeted childhood diseases.”
Shingles is one exception, usually given to patients in their 70s, and there are one or two other vaccines for diseases like meningitis or human papillomavirus developed for young adults. But otherwise immunology is skewed in favour of children.
“We have a tremendous amount of knowledge about childhood diseases,” says Sharif. “When it comes to young adults, middle age and old age, we don’t have a lot of experience.”
Just like many other parts of the body, our immune system shows signs of our ageing. Some of the immune cells lose their function. The immune system is a very complex network of cell types that interact with each other. If something, somewhere within the system is not working, it interrupts the delicate balance of the immune response.
How does the aging immune system work? When you are infected by a pathogen, the first layer of the immune system, the innate immune response, starts attacking the pathogen at the site of infection. For respiratory diseases, that could be the lungs, trachea or nose. White blood cells, or macrophages, attack the pathogen, swallowing it up before destroying it.
As those macrophages break apart the pathogen inside themselves, they present bits and pieces of it to another type of immune cell known as T cells. These serve as the “memory” of the immune system. T cells cannot see the pathogen by themselves and need certain macrophages, called antigen presenting cells, to show them the pathogen. That activates the next layer, the adaptive immune system.
There are several types of T cells. Killer T cells, or cytotoxins, attack our own bodies’ cells in order to eliminate those already infected by the pathogen, reducing its proliferation. Helper T cells provide assistance to B cells, another part of the adaptive immune system.
B cells can see the pathogen on their own but for optimum function they need helper T cells. B cells produce antibodies. But to produce the most effective antibodies, they need this complex interaction with T cells.
The goal of a vaccination is to stimulate our immune systems to produce effective antibodies before we are exposed to the pathogen. Much has been made in the news of antibody tests as a way of proving who has had Covid-19. However, not all antibodies work, not everyone who has been infected with Sars-Cov-2 – the virus that causes Covid-19 – has antibodies and some antibodies have a limited lifespan. (Read more about whether we can be immune to Covid-19.)
The issue for vaccinologists is that the delicate balance between all of these cells in elderly people becomes disrupted. So, what happens in an older person’s immune system?
“Basically all of those cell types are impaired in their function,” says Birgit Weinberger, from the University of Innsbruck, who studies immunosenescence and vaccinations of the elderly. “They produce a different set of cytokines [proteins that aid communication between immune cells]. I think the important issue one has to keep in mind is that none of those cell types act on their own.”
If antigen presentation by the macrophages is impaired in old age this could lead to a decrease in T cell activation, less help for the B cells and a lower antibody response. But it might be because of issues with the very first innate response.
“You have to keep in mind how all those different parts of the immune system come together in concert,” says Weinberger.
We also have a finite number of B cells and T cells in our adaptive immune system, says Sharif, and we lose some of them over time. That can create problems in later life. “When we encounter a new pathogen our ability to respond becomes a lot more limited.”
Immunosenescence does not affect all people equally. As with other body parts, some people age better than others either by looking after themselves or being lucky enough to have the right genetic make-up. But it’s not all bad news. Some parts of our immune system improve with age, too.
“There are some cells in our immune system that become more vigorous as we age,” says Sharif. “If we have been exposed to a wide variety of pathogens, we have an immune memory to them so we don’t need to have an armoury of cells to respond to novel antigens.” But Sars-CoV-2 is one virus we have never been exposed to, so we do not have that memory.
This is the balance struck by our immune system: older people have a better immune memory for things they have already been exposed to, but have a more limited repertoire to respond to novel diseases. Ordinarily, this might be fine. But as humans come into contact with more pathogens that jump species (what’s called zoonotic disease) more frequently, our ability to handle novel disease might be more important.
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