9 Genes that Impact the Response to Vaccines

Key takeaways:
~ Genetic variants in your immune system genes influence your response to vaccines.
~ A small portion of the population won’t create antibodies to specific vaccines based on their genetic variants.
~ For some vaccines, such as hepatitis B and trivalent flu vaccines, there can be a 100-fold difference in response.[ref]

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Vaccines:

In 1796, a scientist named Edward Jenner inoculated a boy with cowpox in hopes it would protect the child against smallpox. It worked and was the first crude vaccine. There’s a lot more to that story – and not all of it is nice – but the point is that vaccines have been around for a couple of hundred years.

Fast forward to now, and we know much more about the immune system and how vaccines work. Genetics plays a huge role in how an individual responds to a vaccine. For some vaccines, such as hepatitis B and trivalent flu vaccines, there can be a 100-fold difference in response.[ref]

For the most part, vaccinations help to prevent childhood illnesses that could lead to death.[ref] But that is the population as a whole…there are always case studies and anecdotal stories about individuals who are harmed by vaccines.

With all the new research over the past 10 to 20 years, scientists know much more about how genetics interacts with vaccines. Not everyone creates antibodies in response to a vaccine. And some people are already genetically unable to get certain diseases.[ref]

At some point (hopefully soon!), doctors will be able to personalize vaccinations based on an individual’s genetics.

How do vaccines work?

Vaccines trigger an immune response mimicking a previous contact with a viral or bacterial pathogen. The key to triggering the production of immune system cells without the pathogen making you sick is to include only the inactive part of the virus in the vaccine.

Your immune system has two parts:

The innate immune system jumps into action immediately, trying to fight off any pathogen in a nonspecific way.
Your adaptive immune system learns about the pathogen and then creates specific cells to eliminate that one species of pathogen.

The adaptive immune system takes several days to attack a new pathogen, but the specific response is much faster for previously known pathogens. This is why you don’t get sick the second time that you meet up with a virus. Your adaptive immune system destroys it without realizing you have been exposed.

Vaccines give you a little bit of a virus or bacteria and cause the body to mount an adaptive immune response against a pathogen. This happens via a couple of specific immune system cell types.

T-cells and B-cells are types of white blood cells the body creates to get rid of invaders. T-cells come from the thymus and B-cells from the bone marrow. These cells actively fight new pathogens, but they also create memory cells to be ready to roll if they ever see that pathogen again.

For T-cells, this process starts with another type of immune cell called a macrophage.

Macrophages are big immune cells that can gobble up the inactivated pathogen from the vaccine. This process is called phagocytosis — kind of like PacMan coming along and engulfing the pathogen.

The macrophages then break up the pathogen and display parts of it on the surface of their cell using receptors known as the major histocompatibility complexes (MHCs). The MHCs are coded for by the HLA genes (below in the genetic section). This is where individual genetic differences come into play, big time.

T-cells locate and bind to the foreign antigens on the macrophages and activate. Some of these activated T-cells eventually become memory T-cells that always circulate at low levels, on the prowl for that foreign antigen.

B-cells can also differentiate and create long-lasting memory for the pathogen as well as antibodies that circulate in the plasma. So if you get exposed to the pathogen that you are vaccinated against, the body is ready, and the quick response overwhelms the pathogen.

Different types of vaccines:

We’ve come a long way since Edward Jenner cut open a cowpox on a dairymaid and injected the pus into a stable boy. (He then exposed the kid to smallpox a couple of weeks later to see if the procedure had worked!)

There are several different types of vaccines:

Live attenuated vaccines are made from a tamer version of the pathogen. This type of vaccine works well, but sometimes has the drawback of causing mild cases of the disease.[ref]
Inactive vaccines use dead pathogens or parts of dead pathogens. Subunit vaccines are made just with antigens – or parts of antigens – that can prompt specific responses. Researchers grow the pathogens and then inactivate them with chemicals (e.g., ascorbic acid, hydrogen peroxide, formaldehyde) or through heat treatment.[ref]
DNA vaccines are the latest in this field. They contain genetic material that contains the code for the antigen. Your own body then translates the DNA to make an antigen protein — and then creates an immune response against it. This causes a longer-lasting and more robust response. DNA vaccines are theoretically cheaper and easier to make.[ref] Currently, there aren’t any DNA vaccines on the market, though, because there are still some major technical problems in producing them. There are also potential problems with triggering autoimmune diseases. A human Ebola DNA vaccine, though, has gone through clinical trials.
One additional way a DNA vaccine can be created is to use a viral vector, meaning researchers put the target DNA (genes) into an adenovirus and inject that into the subject. Adenoviruses are common human viruses that give people cold-like symptoms. The problem with this is that a lot of people already have an immune response against the adenovirus (already had that cold), and thus the vaccine won’t work.[ref] Researchers are getting around this with monkey adenoviruses.

Adjuvants are substances included with the vaccine, causing the body to create a bigger immune response.

“Non-specific” immunity from live attenuated vaccines:

Vaccines are supposed to give you immunity from a specific disease — and this is the mechanism that is well understood. But researchers have also found that vaccines have effects on non-targeted pathogen infections.

For example, the live-attenuated measles vaccines cause a significant reduction in all-cause mortality — affecting the susceptibility to sepsis and pneumonia. A similar reduction in all-cause mortality was found for children receiving the oral polio vaccine. This is especially true in poorer countries that normally have higher childhood mortality rates.[ref]

So what is going on here – why would an oral (live attenuated) polio vaccine keep a child from dying of other infectious diseases? When the body responds to the live attenuated vaccine, it not only creates antibodies but also ramps up the innate immune system at the same time, creating interferon, natural killer cells, etc. Plus, the vaccine can cause the creation of cross-reactive antibodies.[ref]

A new area of vaccine research is taking this concept of non-specific immunity to the next level. Called ‘Trained Immunity-based Vaccines’, the idea is to create vaccines that stimulate a wider variety of pattern recognition receptors.[ref]

Vaccine response in the elderly:

Older individuals have a decreased immune response against pathogens, which also affects their response to immunizations. One reason for this is that the thymus gland begins to calcify with age and stops producing T-cells.

Flu vaccines are estimated to be less than 50% effective in older individuals. This is in years when the vaccine matches the circulating flu strain (best-case scenario).[ref][ref]

Older individuals with compromised immune systems can also have adverse reactions to vaccines. For example, the shingles vaccine can cause chickenpox in immunocompromised people.[ref]

In general, the data show that the shingles vaccine is about 50% effective in older adults.[ref]

Vaccine response in children:

Not everyone will develop immunity to a pathogen based on immunization. We are all different, and a percentage of the population won’t develop antibodies (more in the genetics section).

Age matters in kids, also, and the vaccination schedule takes into account the ages at which kids are likely to be able to mount an immune response and develop antibodies due to immunization. Additionally, the combination and timing of vaccines are important. For example, when the oral polio vaccine is given along with the rotavirus vaccine, a greater risk of poor response to the rotavirus vaccine exists.[ref]

Here is a good example: When the chickenpox vaccine first came out in 1996, the recommendation was for only one dose of the vaccine. It turned out that about 20% of kids did not seroconvert (have enough antibodies) after one dose, so the CDC in 2006 recommended doing two doses. This upped the protection to about 98% of kids.[ref]

Vaccine Response Genotype Report

Humans as a species have survived and thrived due to diversity and variability in our innate immune response to pathogens. Along comes a new virus – and part of the population is able to fight it off, surviving. A different virus comes along next year, and a different part of the population has a survival advantage. Diversity is key to species survival.

Vaccines cause our immune system to produce a response. With great variability in our immune system, we also have great variability in our response to vaccines. Some people, when given a vaccine, will produce a small immune response to it that may wear off quickly. Some may create no immune response; others may have a large and lasting immune response. (And yes, there are people who will have a bad response to vaccines — but that huge topic will be covered in a future article).

Take the measles vaccine as an example:
In the 80s, it was thought that measles had been almost eradicated. But from 1989-1991, there were suddenly 55,000 documented measles cases. This wasn’t due just to kids who weren’t vaccinated. Up to 40% of the cases were in people who had been vaccinated already. Researchers found that the immune response to measles was about 90% heritable or due to genetics. There is a huge range in how people mount an immune response to the measles vaccine.[ref]

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If you are going to get a vaccine, you want it to be effective and produce the needed antibody response, right?

The following have been shown in studies to affect the production of antibodies in response to vaccines:

Time of day may matter:
A study in the UK looked at the timing of vaccines for the annual flu vaccine in adults over age 65. People getting the H1N1 vaccine had a significantly greater antibody response if they were vaccinated in the morning vs. the afternoon. But that same study showed that the H3N2 vaccine didn’t have a response difference between morning and afternoon vaccines.[ref]

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Vaccines:

How do vaccines work?

Different types of vaccines:

“Non-specific” immunity from live attenuated vaccines:

Vaccine response in the elderly:

Vaccine response in children:

Vaccine Response Genotype Report

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