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Could adjuvants in vaccines cause allergies or autoimmune diseases?

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Darko Savic
Darko Savic Dec 13, 2020
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?

[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

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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.

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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General comments

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Darko Savic
Darko Savic5 months 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