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In CNN's video Scientist says Coronavirus vaccine could be ready by 2021 after about 00:25 'Robin Shattock, the Head of Mucosal Infection and Immunity at Imperial College London' says:

We were able to access the sequence that was published by Chinese scientists and made globally available, which was a tremendous thing to do. And we went from that sequence to identifying part of the sequence that encodes for the surface proteins of the virus. And we’re using that sequence to manufacture our vaccine.

We’re using a particular approach where we make a synthetic vaccine based on RNA, so essentially it’s essentially genetic code, we package that in essentially a lipid droplet, and use that to inject in a muscle; it expresses that protein, and the body recognizes that as foreign and it makes protective antibodies.

I'm assuming that this is mRNA and so once it reaches the cytoplasm of the vaccine recipients muscle cells it will be expressed and somehow returned to the cells' membrane where it will be recognized as foreign by passing lymphocytes.

Questions:

  1. Is this basically correct as far as it goes?
  2. If so, what causes the lipid droplet to fuse with muscle (or other) cells in the first place?
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    $\begingroup$ From what I read transfection of DNA vaccines are based either on electroporation or viral vector $\endgroup$ – reuns Feb 8 at 6:43
  • $\begingroup$ @reuns There is a whole world of nonviral transfection reagents that do not depend on electroporation. They typically include cationic polymers, lipids, and peptides. $\endgroup$ – user137 Mar 4 at 19:51
  • $\begingroup$ @user137 It says you'd want a few of the mRNA lipid-PEG coated particles to become endosome in dendritic cells where (after release and translation by ribosome) the protein is taken by the MHC pathway for presentation on cell's surface. Then (because particles provoked an inflammation?) the surface MHC-antigen is processed by the immune system for acquisition of new antibodies. Is it the real-life scenario you are thinking to ? The possibility of replacing the mRNA by a replication competent RNA virus encoding it is briefly mentioned. $\endgroup$ – reuns Mar 4 at 20:35
  • $\begingroup$ @reuns I've just asked Do both DNA and mRNA-based vaccines sometimes require electrical pulses to work? $\endgroup$ – uhoh May 1 at 0:28
  • $\begingroup$ @user137 ditto. $\endgroup$ – uhoh May 1 at 0:28
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I can't give an authoritative answer on this because my PhD work was based on mRNA delivery using peptides instead of lipids, but many of the concepts are the same. I also don't have time to provide proper citations, but this is probably too much for a comment.

Anyway, mRNA is a very fragile molecule, it can be broken down extremely quickly in the blood by serum nucleases. Therefore we must protect the mRNA by mixing it with some other chemical, in this case a mixture of positively charged lipids. The positively charged lipids are attracted to the negatively charged phosphate backbone of the mRNA, and form a nanoparticle trapping the mRNA inside and hiding it from the nucleases. The lipids are often, but not always, PEGylated, which means that a molecule of polyethylene glycol (PEG) is attached to the lipid. The PEG groups form a layer on the outer surface of the nanoparticle that helps prevent protein binding.

These mRNA lipid nanoparticles are then injected into a patient. This will probably be an intramuscular injection so that the particles are most likely to be taken up by muscle cells. The exact mechanism explaining why lipid nanoparticles are attracted to cells isn't entirely clear, but it's likely a combination of electrostatic attraction between the positively charged nanoparticle and the negatively charged cell membrane and proteins that bind to the nanoparticle and are then recognized by receptors on the cell surface.

After the particle is taken up by a cell it is usually trapped inside a membrane-bound structure called an endosome. As the endosome matures it is acidified, and as the pH drops from about 7 to about 5.5 the nanoparticle is disrupted. The lipids that made up the nanoparticle can merge with the lipids that make up the endosomal membrane, disrupting that membrane and breaking open the endosome, allowing the mRNA to escape into the cytoplasm.

Once in the cytoplasm the mRNA will find a ribosome and produce protein. Just like you said, the protein in this case will be membrane bound and expressed on the outer surface of the cells for eventual immune recognition.

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  • $\begingroup$ well if you're going to write an answer as a comment, then might as well post your comment as an answer ;-) Thanks this is exactly the kind of explanation I needed with plenty to spare! $\endgroup$ – uhoh Mar 4 at 22:55

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