What is immune imprinting, and should the public be worried about it?

Biology/Immunity Infectious Diseases Vaccines

Q: What is immune imprinting, and should the public be worried about it?

A: Don’t let statements about imprinting stop you from getting your annual vaccines for COVID and flu. Immune imprinting refers to the fact that our immune response to a vaccine (or infection) is affected by previous exposures to similar vaccines (or infections). Imprinting has both pros and cons – it allows our immune system to respond quickly to pathogens (any organisms that make you sick) that are familiar, but it can interfere with an optimal vaccine response. The public does not need to worry about imprinting, because we have good evidence that annual vaccines are effective.

Over the last few years you may have heard of imprinting as a bad thing because it may impact the response our immune system has to new variants of COVID-19. Imprinting occurs when the immune system relies on previously made antibodies to respond to new variants or strains of a pathogen (disease-causing-organisms). Imprinting is not new. Scientists have known about and studied imprinting in the context of influenza for a while now. We know that the first influenza virus or vaccine someone receives can impact their response to future infections and vaccines.

How does imprinting work?

When your immune system is first exposed to a pathogen, it starts from scratch. It takes time for your immune system to identify the pathogen and make cells and molecules that help fight it. Once the pathogen is removed, your immune system makes memory cells that will help if exposed to the same pathogen again.

Some pathogens do not mutate (change) much so these memory cells can help prevent you from getting infected again or greatly limit severity if you do. For example, the measles virus doesn’t change much over time. So a measles vaccine can protect you from measles many years later. Other pathogens, like influenza or SARS-CoV-2, mutate quickly. What happens then?

This is when scientists start to look for signs of imprinting, also sometimes called “original antigenic sin.” Researchers have found that when exposed to a pathogen that is *slightly* different from one you saw before, the immune system still recruits the older memory cells from that first exposure. This is helpful from an evolutionary perspective because it is much faster to use these memory cells than to make brand-new ones. In an infection, time can sometimes be the difference between living or dying. Alternatively, the *more* different a new variant or strain is from the original infection or vaccine, the less imprinting occurs. In other words, your immune system doesn’t rely on memory cells as much, and instead responds from scratch.

Why does imprinting come up now?

Using previously made memory cells to respond to new variants can be at the expense of making new immune cells. Scientists care about this when developing vaccines for things like influenza and SARS-CoV-2. They want to make sure that the new vaccines provide the maximum protection possible to new variants. However, the immune response can be impacted by previous infections and/or vaccination for that pathogen. This knowledge allows scientists to study ways of generating new memory cells when vaccinating for variants or strains that take into account the benefits and challenges of imprinting.

What does this mean for updated COVID vaccines?

Since the COVID-19 pandemic first started, people have discussed imprinting a lot and have concerns about its impact on immunity from annual vaccines or repeat COVID infections. A recent paper looked specifically at this in the context of variant boosters and found that while there is evidence of imprinting, those who received updated COVID vaccines this past fall did produce antibodies that could cross-react with many different variants. This supports the continued benefit of updated COVID vaccines for decreasing infection severity.