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Could adjuvants in vaccines cause allergies or autoimmune diseases?

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Darko Savic
Darko Savic Dec 13, 2020
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Via which mechanisms could (or couldn't) adjuvants in vaccines cause allergies or autoimmune diseases?

With the world gearing up for regular mass vaccinations, these are some of the things we should understand well.

Adjuvants

Adjuvants are immunostimulatory molecules that are added to the vaccine to help boost immune responses by activating additional molecular receptors that predominantly recognize pathogens or danger signals.

Allergies

The immune system's state of heightened reactivity to antigens is called hypersensitivity. Hypersensitivity reactions are classified by mechanism:
  • type I hypersensitivity reactions involve IgE antibody triggering of mast cells
  • type II hypersensitivity reactions involve IgG antibodies against cell surface or matrix antigens
  • type III hypersensitivity reactions involve antigen-antibody complexes
  • type IV hypersensitivity reactions are T cell-mediated
Allergic reactions occur when an individual who has produced IgE antibodies in response to an antigen (could be an allergen), in the future encounters it again. The allergen triggers the activation of IgE-binding mast cells in the exposed tissue, leading to allergic reactions.

Autoimmunity

A misdirected immune response occurs when the immune system goes awry and attacks its own cells.

It is currently thought that viral-induced autoimmunity can be activated through multiple mechanisms including molecular mimicry, epitope spreading, bystander activation, and immortalization of infected B cells.

A few things I'm trying to figure out
  1. If autoimmunity could be induced by pathogens, why couldn't it be induced by make-believe pathogens (vaccines)?
  2. Could vaccine adjuvant-sensitized (biased?) immune system in the heat of the moment overreact to otherwise benign antigens (pollen, peanuts, self-antigens, etc) that happen to find themselves in the wrong place at the wrong time?
  3. There are people that are genetically (or environmentally) prone to hypersensitivity or autoimmunity but might not know it yet. Can vaccination kick their immune system in the nuts?
I realize that mRNA vaccines have little to do with adjuvants. Except maybe polyethylene glycol. This session is mainly about the rest.

[1]Chung, Young Hun et al. “COVID-19 Vaccine Frontrunners and Their Nanotechnology Design.” ACS nano vol. 14,10 (2020): 12522-12537. doi:10.1021/acsnano.0c07197

[2]Janeway CA Jr, Travers P, Walport M, et al. Immunobiology: The Immune System in Health and Disease. 5th edition. New York: Garland Science; 2001. Chapter 12, Allergy and Hypersensitivity. Available from: https://www.ncbi.nlm.nih.gov/books/NBK10756/

[3]https://en.wikipedia.org/wiki/Autoimmunity

[4]Smatti, Maria K et al. “Viruses and Autoimmunity: A Review on the Potential Interaction and Molecular Mechanisms.” Viruses vol. 11,8 762. 19 Aug. 2019, doi:10.3390/v11080762

[5]Wucherpfennig, K W. “Mechanisms for the induction of autoimmunity by infectious agents.” The Journal of clinical investigation vol. 108,8 (2001): 1097-104. doi:10.1172/JCI14235

[6]Wang, De-Yun. “Risk factors of allergic rhinitis: genetic or environmental?.” Therapeutics and clinical risk management vol. 1,2 (2005): 115-23. doi:10.2147/tcrm.1.2.115.62907

[7]Ramos, Paula S et al. “Genetics of autoimmune diseases: insights from population genetics.” Journal of human genetics vol. 60,11 (2015): 657-64. doi:10.1038/jhg.2015.94

[8]https://www.sciencemag.org/news/2020/12/suspicions-grow-nanoparticles-pfizer-s-covid-19-vaccine-trigger-rare-allergic-reactions

allergiesvaccinesimmunology
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Creative contributions

People with a history of allergic reactions may encounter some problems.

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Jamila
Jamila Dec 16, 2020
I think roughly two people in the UK have had allergic reactions to the Pfizer vaccine. The UK's regulatory body has sent a message to the general public, saying that people with a history of allergic reactions shouldn't have the Pfizer vaccine.

Both individuals had a history of severe allergic reactions and kept EpiPens with them. They reacted to having the vaccination but are fine now. Apparently, the researchers think they had an anaphylactoid reaction, not anaphylaxis.

Anaphylaxis
Anaphylaxis is a quick reaction that occurs due to the fast release of immune factors mediated by IgE.

Anaphylactoid reactions
Anaphylactoid reactions are also quick reactions that happen due to the release of factors, but IgE doesn't mediate these.

The Pfizer vaccine
The Pfizer vaccine is an mRNA-based vaccine. Meaning that it doesn’t contain live or attenuated SARS-CoV-2; it contains mRNA belonging to SARS-CoV-2. Once Pfizer’s mRNA vaccine is injected into the body, the cells use the mRNA to make the spike protein (found on the surface of SARS-CoV-2). This causes an immune response, whereby antibodies and T-cells are produced to eliminate the infected cells. If someone is infected with SAR-CoV-2, they will have the antibodies ready to fight COVID-19.

Although allergic reactions have been rare so far, it would be essential to determine what exactly caused the allergic reaction in these people. The UK’s regulatory body has released a list of ingredients in the Pfizer vaccine, which can be found here. However, I'm not sure what else is in the vaccine because Pfizer hasn’t specified its ingredients in great detail. So, it might be harder to pinpoint what caused the allergic reactions.

Further information
Allergic reactions can be seen in vaccination programs, but apparently, they aren't very common. According to Dr. Offit, one person out of a million people will have an allergic reaction to a vaccine.

People with a history of allergic reactions may have an allergic reaction to the Pfizer vaccine. Healthcare providers in the US will still be giving the Pfizer vaccine to individuals with a history of allergic reactions. These individuals will be having consultations about the possible risks associated with the Pfizer vaccine before their vaccination.


[1]Lagopoulos, V., and E. Gigi. "Anaphylactic and anaphylactoid reactions during the perioperative period." Hippokratia 15.2 (2011): 138.

[2]Sahin, Ugur, et al. "COVID-19 vaccine BNT162b1 elicits human antibody and TH 1 T cell responses." Nature 586.7830 (2020): 594-599.

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Research on irritable bowel syndrome as being caused by an unrelated infection

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Darko Savic
Darko Savic Jan 14, 2021
Here is an excerpt from this article:

They infected mice with a stomach bug, and at the same time fed them ovalbumin, a protein found in egg white that is commonly used in experiments as a model food antigen. An antigen is any molecule that provokes an immune response. Once the infection cleared, the mice were given ovalbumin again, to see if their immune systems had become sensitized to it. The results were affirmative: the ovalbumin on its own provoked mast cell activation, histamine release, and digestive intolerance with increased abdominal pain. This was not the case in mice that had not been infected with the bug and received ovalbumin.


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Research proposal: Check the prevalence of pollen allergies in people who have been vaccinated during the pollen season

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Darko Savic
Darko Savic Aug 02, 2021
It would be interesting to see the prevalence of pollen allergy (hay fever) in people who have been vaccinated as children during springtime in areas where there is an abundance of pollen in the air versus those who have been vaccinated at the same age with the same vaccines but in periods/areas with no pollen in the air.

This should be fairly easy to test. People have medical records of when/where they were vaccinated and which vaccines were used.

For example, if a child is scheduled to get a specific vaccine at 3 months old, and they were born in Europe in February, they would get the vaccine in the middle of the pollen season. In contrast, a child born in the same area in September would get that same vaccine in the winter.

Do we even need to check medical records? We can assume that in a country with mandatory vaccines X% of the population is vaccinated. We just have to know the country's vaccination schedule. Then compare the pollen allergy prevalence in people born in 2 different periods.

Facebook ads used to let advertisers target people by age, location, birthday. I'm not sure if birthday is still an option - it might have been disabled so as to prevent spammy/scammy ads. But I'm sure we can come up with a way to find people based on their age and birth-month.

A questionaire with a few thousand participants in each group might show good preliminary results. The next step could be to test the hypothesis by looking at the medical records.
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jnikola
jnikola3 years ago
Darko, the idea is great and could be easily stretched to cover more interesting facts that would help the understanding of the allergies.
First, the research proposal is well planned. I would do the same - see the prevalence of pollen allergies and the vaccination dates of different vaccines. If the adjuvants can trigger allergies, I would expect a correlation to exist between the vaccination month (of certain adjuvant-containing vaccines) and the pollen that is the most present at that time of the year.
Complementing experiment
On the other hand, it would be great to see the same but not with vaccines, but serious colds and flues. In other words, check the correlation between the time of having a cold, flu (or any other disease that strongly activates the immune response), and pollen allergies. As you mentioned, we are not sure why pathogens could trigger autoimmune diseases and pathogen parts (vaccines) not. Maybe the same works for allergies. If the correlations from your experiment and this one are similar, I would say that adjuvants in vaccines are not more dangerous than pathogens. It would be great if we find out the correlation is much weaker in the case of vaccines.
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Darko Savic
Darko Savic3 years ago
Juran agreed. That's a great addition to the experiment.
One downside could be that people don't go to the doctor for colds or even flu so those cases would be poorly documented. On the other hand, they go to the doctor for some more serious known diseases. Data on some of these could be used instead of colds and flu.
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Timing the vaccination in children based on a novel aluminum monitoring standard

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jnikola
jnikola Oct 15, 2021
In my opinion, accusing adjuvants (especially aluminum salts) of causing autoimmune diseases is counterproductive and does not bring benefit to humanity. Many diseases are shown to be induced by the accumulation of metals (Alzheimer's, autism, etc).
New aluminum monitoring standards
Therefore, my idea is to develop a detailed and precise system of monitoring the concentrations of aluminum and other metals in disease-related tissues (especially the brain). In addition, I would create a literature-supported panel of biomarkers that show the overall capability of a body or a tissue to accumulate and remove metals from the body. Based on all of this, the interventions like changes in dietary plans, cosmetics, or vaccinations could be planned. This should be obligatory when receiving aluminum-adjuvanted vaccines.
Obviously we have a problem with high aluminum concentrations accumulating in our bodies. Vaccination has a lot of benefits. Let's then just the time it perfectly to avoid/reduce the bad effects.
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jnikola
jnikola3 years ago
The fact that supports the idea of adjuvants just contributing to overall aluminum levels
The paper discussed that "despite its well-known toxicity, aluminum has been included in many vaccine preparations for many years because it has been calculated that the total amount of aluminum that children receive when they are given all the vaccine doses included in the national immunization schedules is significantly lower than that associated with neurotoxicity".

[1]https://www.frontiersin.org/articles/10.3389/fpubh.2020.00361/full

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Aluminum-absorbed non-target antigens could trigger allergies and autoimmune diseases (but not necessarily related to vaccines)

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jnikola
jnikola Oct 15, 2021
I recently found a comment to this paper that I found very specific to your topic.
In short, the paper describes the protocol for future assessment of the effects of aluminum adjuvants from vaccines on patients' health and outcomes. The bald comment beneath the paper deals with the vaccination and its possible connection with autoimmune diseases.
The author of the comment referred to the very high aluminum concentrations found in histological brain samples of children with autism. Vaccines are not 100% pure and contain many antigens, including non-target food proteins , that absorb on the surface on aluminum particles. Since aluminum adjuvants stimulate Th2 response related to allergies, the Th2 response applies to all these targets and non-target antigens. A possible connection with autoimmune diseases could be the bovine folate receptor alpha (FRA) protein found in bovine milk. A Th2 response against FRA results in anti-FRA IgE antibodies. When we consume milk, IgG4 antibodies against FRA are being synthesized and they react and bind to human FRA in the choroid plexus and block the folate uptake to the brain. Since cerebral folate deficiency decreases elimination of aluminium from the brain, it accumulates due to high-aluminium-low-elimination effect and possibly causes autism.
My questions here would be:
  • How can we be sure that the "impure" vaccines containing FRA protein are the primary and the most responsible source of the FRA absorbed on the aluminium particles during the vaccination? If we consume diary milk on a daily basis, our blood and tissues could be rich with all kind of proteins, including FRA. This FRA could theoretically be absorbed on aluminium particles during vaccination and cause the same thing. That way, "impurity" of vaccines could not solely be accounted for the autism.
  • Since we uptake aluminium through food, drinks, cosmetics and by breathing it in, should we control aluminium concentrations, especially in the young age when children get vaccinated, to avoid high aluminium-related disorders like autism?
  • If we show that vaccines are the main source of non-target antigens that are absorbed on aluminum particles, should we increase the standards for vaccine purity? Would it solve the problem?

[1]National Academies of Sciences and Medicine E. Finding a Path to Safety in Food Allergy: Assessment of the Global Burden, Causes, Prevention, Management, and Public Policy. Stallings VA, Oria MP, editors. Washington, DC: The National Academies Press; 2017.

[2]Arumugham V. Role of NMDA receptor autoimmunity induced by food protein containing vaccines, in the etiology of autism, type 1 diabetes, neuropsychiatric and neurodegenerative disorders [Internet]. 2018. Available from: https://doi.org/10.5281/zenodo.1463600

[3]Vaccine Excipient & Media Summary [Internet]. 2015 [cited 2016 Jan 16]. Available from: http://www.cdc.gov/vaccines/pubs/pinkbook/downloads/appendices/B/excipient‐table‐2.pdf

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The adjuvants could just be making up for the loss of immunogenicity, without changing the possibility of unwanted inflammation-driven autoimmune response

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jnikola
jnikola Oct 15, 2021
Vaccine antigens are becoming purer (safer and cheaper, too) at the cost of immunogenicity (Figure 1). Live attenuated or inactivated vaccines were known to provoke the strongest immune response in patients, which is now seen in the antibodies count between COVID-19 survivors and vaccinated people. To obtain a similar immune response, pure antigens in vaccines need adjuvants. The key thing to extract from here is the need for strong inflammation and immune response in order to develop antibodies.
Since adjuvants have a similar effect on a patient's immune response as live pathogens, would it be correct to say that adjuvants cause autoimmune diseases? Or would it be more logical to think of inflammation as the main "kickstarter" of allergies and autoimmune diseases?
In the beginning, I would suggest checking the prevalence of strong inflammation events in patients in tissues known to be tightly related to autoimmune diseases and find a correlation. Then I would compare that correlation to the correlation between the prevalence of autoimmune diseases and vaccinations. Then I would compare the groups of patients vaccinated with different vaccines.
Figure 1. Vaccine immunogenicity vs Antigen purity
Do you have any other ideas on how to find out if the effect of adjuvants is just making up for the loss of immunogenicity and thus, should not be accounted for the consequent development of autoimmune diseases?
**To understand better my point of view, please read the other contribution on this session.

[1]https://www.deseret.com/coronavirus/2021/8/24/22639546/antibodies-infection-vaccine-better-protection

[2]https://hesiglobal.org/wp-content/uploads/sites/11/2016/06/SOS_GOULD_vaccine_adjuvant.pdf

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Darko Savic
Darko Savic4 years ago
I'm still trying to figure out if the upcoming mRNA vaccines are adjuvanted, self-adjuvanting, self-amplifying and if self-amplification is all it takes to establish immunity.

And how long the immunity lasts.

Also there is this https://www.sciencemag.org/news/2020/12/suspicions-grow-nanoparticles-pfizer-s-covid-19-vaccine-trigger-rare-allergic-reactions
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