Precisely how does Pfizer's Covid-19 mRNA vaccine work?

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Discussion Overview

The discussion centers on the mechanisms of action of the Pfizer-BioNTech Covid-19 mRNA vaccine (BNT162b2), exploring its delivery, stability, and the immune response it elicits. Participants raise questions about the vaccine's formulation, cellular uptake, translation of mRNA, and the implications of spike protein synthesis.

Discussion Character

  • Exploratory
  • Technical explanation
  • Debate/contested

Main Points Raised

  • One participant questions how the mRNA in the vaccine is stabilized for delivery, suggesting it may require additional machinery such as proteins or sugars.
  • Another participant proposes that lipid nanoparticles (LNPs) encapsulate the mRNA, protecting it from degradation and facilitating its entry into cells.
  • Concerns are raised about how the mRNA is delivered into cells, with speculation on whether it requires specific protein machinery or mimics natural processes used by the body.
  • There is a discussion on whether the LNPs interfere with the translation of mRNA once inside the cytoplasm, with some participants asserting that they do not.
  • Questions are posed about how synthesized spike proteins are transported to the cell membrane and whether they include sequences that signal their trafficking.
  • Participants express uncertainty about the long-term effects of spike proteins becoming integral to cells and whether this could affect immune recognition.
  • Some participants mention that the vaccine codes for modified versions of spike proteins and discuss the biochemical mechanisms involved in their design and function.

Areas of Agreement / Disagreement

Participants express a range of views and uncertainties regarding the mechanisms of the vaccine, with no consensus reached on several technical aspects. Multiple competing hypotheses are presented, particularly concerning the stability and delivery of the mRNA, as well as the implications of spike protein synthesis.

Contextual Notes

Limitations include the lack of detailed information on the specific components of the vaccine formulation and the mechanisms of action, as well as the dependence on various assumptions about cellular processes and immune responses.

Who May Find This Useful

This discussion may be of interest to individuals studying vaccine technology, immunology, or molecular biology, as well as those seeking to understand the underlying mechanisms of mRNA vaccines.

  • #31
markar said:
Is the sequence of the mRNA (including modified nucleotides) in the public domain? Does it code any enzymes in addition to the spike protein?

Here's a good piece describing the components of the vaccine (though, again, the exact sequence of the mRNA appears to be proprietary): https://www.technologyreview.com/20...-the-ingredients-of-pfizers-covid-19-vaccine/

aheight said:
I assume the " trimerised SARS-CoV-2 S glycoprotein RBD antigen " is the spike protein consisting of three protein chains?
Yes. The S glycoprotein is another name for the spike protein (S stands for spike). A glycoprotein is a protein that has sugars attached to it. Most proteins on the surfaces of cells have sugars attached to them, and the spike protein in no exception. The RBD stands for the receptor binding domain, and refers to a specific part of the spike protein that binds to the ACE2 protein on the surface of cells. You want antibodies to target the RBD of the spike protein because these antibodies could interfere with attachment of the virus to cells. On the surface of the viruses, three spike proteins come together to form an active trimer, so timerization of the antigen in the vaccine helps to mimic how the spike protein looks on the outside of viruses.
 
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  • #32
markar said:
Is the sequence of the mRNA (including modified nucleotides) in the public domain? Does it code any enzymes in addition to the spike protein?

Here's a source that apparently has the sequence of the Pfizer mRNA vaccine:
 

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