9 Genes that Impact the Response to Vaccines

Way back in 1796, a scientist name Edward Jenner injected some cowpox into a boy in hopes it would inoculate the child against smallpox. It worked and was the first crude vaccine. Lots more to that story – and not all of it is nice – but the point is that vaccines have been around for a couple hundred years.

Fast forward to now, and we know a whole lot 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 the trivalent flu vaccines, there can be a 100-fold difference in response. [ref]

Vaccines:

When you look at the population as a whole, there is no doubt that vaccines have saved saved millions of lives over the past century. The average lifespan increased by 30 years from 1900 to the year 2000.  Researchers think that the majority of that increase (25 years) was due to public health interventions such as vaccinations.   (Note that this is average lifespan — so the decrease in childhood deaths due to polio, measles, smallpox, etc is big here. ) [ref]  Prior to the measles vaccine, about 95% of kids caught the measles, resulting in about 4 million deaths per year. [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 now know a lot 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 to mimic having previously come in contact with a viral or bacterial pathogen.  The key is that only an inactive part of the virus is included in the vaccine, thus triggering the production of immune system cells without the pathogen making you sick.

Your immune system has two parts:

  • the innate immune system jumps into action immediately, trying to fight off any pathogen in a non-specific 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 for pathogens that have previously been know, the specific response is much faster. This is why you don’t get sick the second time that you meet up with a virus. Your adaptive immune system just takes it out without you 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 cell 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 so that they will 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 (MHC’s).  The MHC’s are coded for by the HLA genes (below in the genetic section). This is where individual genetic differences come into play, big time.

T-cell then come and bind to these foreign antigens on the macrophages and are activated. Some of these activated T-cells eventually become memory T-cells that are always circulating 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 diary maid and injected the puss 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 of 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 – 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 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 that a DNA vaccine can be created is to use a viral vector, which means that researchers put the target DNA (genes) into an adenovirus, and injecting 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 agains 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 that are included with the vaccine that cause 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 there are effects from vaccines 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. Similar reduction in all-cause mortality were 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 a the 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 it 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]

There is a new area of vaccine research that takes 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, and this 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 who have compromised immune systems can have adverse reactions to vaccines also. For example, the shingles vaccine can cause chicken pox 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 an 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 an immunization.  Additionally, the combination and timing of vaccines is important. For example, when the oral polio vaccine is given along with the rotavirus vaccine, there is a greater risk of poor response to the rotavirus vaccine.[ref]

Here is a good example: When the chicken pox vaccine first came out in 1996, it was recommended to get 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]


Genetics and Vaccine Response:

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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.  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 is a huge topic that needs to covered in a future article).

Take the measles vaccine as an example: 
In the 80s, it was thought that measles was almost eradicated. But from 1989-1991, there were suddenly 55,000 documented cases of the measles. This wasn’t due just to kids that weren’t vaccinated. Up to 40% of the cases were in people who had been vaccinated already.  Researchers found that the immune response for 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]

HLA genes:

The celiac disease associated HLA-DQ2 genotype is associated with an increased association of not creating antibodies in response to the hepatitis B vaccine.[ref]

HLA-DQ2 is also referred to as HLA-DQB1*0201. This genetic variant is fairly common and found in about 25% of European Caucasians.

Check your genetic data for rs2187668 (23andMe v4, v5; AncestryDNA):

  • C/C: typical
  • C/T: one allele for HLA-DQ2.5 allele; decreased antibody response to hepatitis B vaccine [ref] lower antibody response to measles vaccine [ref]
  • T/T: two alleles for HLA-DQ2.5; decreased antibody response to hepatitis B vaccine; more likely to have chronic hepatitis B [ref]; lower antibody response to the measles vaccine[ref]

Members: Your genotype for rs2187668 is .

HLA-DPB1 gene:

Check your genetic data for rs3117230 (23andMe v4, v5; AncestryDNA):

  • A/A: normal
  • A/G: lower antibody response to rubella vaccine
  • G/G:  low antibody response to the rubella vaccine[ref]

Members: Your genotype for rs3117230 is .

Cell receptors and Immune system Genes:

SLAM gene: signaling lymphocyte activation molecule, which is the cell receptor through with the measles virus enters the body.

Check your genetic data for rs3796504 (23andMe v4, v5; AncestryDNA):

  • G/G: normal response to measles vaccine
  • G/T: 4-fold lower antibody response to measles vaccine
  • T/T: 8-fold lower antibody response to the measles vaccine[ref]

Members: Your genotype for rs3796504 is .

CD46 gene: complement system protein

Check your genetic data for rs2724384 (23andMe v4, v5; AncestryDNA):

  • A/A: normal response to measles vaccine
  • A/G: lower antibody response to measles vaccine
  • G/G: low antibody response to the measles vaccine, increased antibody response to mumps vaccine[ref]

Members: Your genotype for rs2724384 is .

TLR3 gene: Toll-like receptor 3, part of the innate immune system responsible for recognizing pathogens

Check your genetic data for rs7657186 (23andMe v4, v5; AncestryDNA):

  • G/G: typical
  • A/G:  lower antibody response to the meningitis (MenC) vaccine
  • A/A: lower antibody response to the meningitis (MenC) vaccine[ref]

Members: Your genotype for rs7657186 is .

IL12B gene: interleukin-12, subunit B – important in activating T-cells and natural killer cells.

Check your genetic data for rs3212227 (23andMe v4, v5; AncestryDNA):

  • TT: typical
  • GT:  lower response to some flu vaccines
  • GG: low response to some flu vaccines[ref]

Members: Your genotype for rs3212227 is .

IL-12RB2 gene: the receptor for IL-12B (above)

Check your genetic data for rs2201584 (23andMe v4,):

  • GG: typical
  • AG:  lower antibody response to mumps vaccine
  • AA: lower antibody response to mumps vaccine[ref]

Members: Your genotype for rs2201584 is .

IL6 gene: codes for interleukin-6, a pro-inflammatory cytokine

Check your genetic data for rs1800796 (23andMe v4, v5; AncestryDNA):

  • G/G: increased response to some flu vaccines [ref]
  • C/G: typical
  • C/C: typical

Members: Your genotype for rs1800796 is .

IL-28B gene: codes for a member of the interferon family

Check your genetic data for rs8099917 (23andMe v4, v5; AncestryDNA):

  • G/G: twice as likely to produce antibodies in response to flu vaccines [ref]
  • G/T: twice as likely to produce antibodies in response to flu vaccines
  • T/T: typical

Members: Your genotype for rs8099917 is .

 

Intergenic region: area between genes that influences nearby genes

Check your genetic data for rs10489759 (23andMe v4, v5; AncestryDNA):

  • C/C: typical
  • C/T: greatly decrease antibody response to smallpox vaccine (Caucasian population) [ref]
  • T/T: greatly decrease antibody response to smallpox vaccine (Caucasian population)

Members: Your genotype for rs10489759 is .


Lifehacks:

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]

mTOR inhibitors, such as rapamycin, given for several weeks before the vaccine have been shown to improve the response to the flu vaccine.[ref]

Vitamin D?
Vitamin D levels play a role in the immune response. T-lymphocytes and macrophages can convert the inactive form of vitamin D (25-OHD) into the active form (1,25-(OH)2D3). But studies on kids and the MMR and flu vaccines show that vitamin D levels or supplementation makes no difference in vaccine response. There is also little evidence linking vitamin D levels to response to the tuberculosis vaccine (BCG) or pneumonia vaccine. [ref]

There is also little effect from multivitamins in children when it comes to vaccine seroconversion rates. [ref]

Genital Warts Cream:
A study in aged mice (to represent older adults) showed that using a cream called imiquimod, on the injection site boosted the formation of T helper cells. Imiquimod is currently used in humans as a genital wart cream.[ref]



Author Information:   Debbie Moon
Debbie Moon is the founder of Genetic Lifehacks. She holds a Master of Science in Biological Sciences from Clemson University and an undergraduate degree in engineering. Debbie is a science communicator who is passionate about explaining evidence-based health information. Her goal with Genetic Lifehacks is to bridge the gap between the research hidden in scientific journals and everyone's ability to use that information. To contact Debbie, visit the contact page.