Dear Dr. Armen Sanosyan

It is observed that, Once the vaccine is given, It start producing the spike proteins. However, It remains unclear, which cells produce Spike proteins. We all know that, Ribosomes are the protein factories, known to synthesize the number of proteins. May be ribosome also synthesize the spike because it is also a proteins.

Hello Armen Sanosyan

After IM injection the vaccine particles get into the cells, and I feel the vaccine particles may be getting into whichever cells they come in contact and could be called as vaccinated cells. Once inside the vaccinated cell, the mRNA is released into the cell. The vaccinated cell protein machinery namely, the ribosomes will read the sequence of mRNA and make the spike proteins. The mRNA eventually gets destroyed. These spike proteins formed in the vaccinated cells then move to the cell surface and will be presented either as whole spike protein or fragments of spike proteins because some of the spike proteins may be broken down by the vaccinated cells. Eventually, the vaccinated cells die, and the debris containing spike proteins and its fragments are taken up the professional Antigen Presenting cells (APC). The APCs presents these spike proteins on its surface to the cytotoxic CD8+ T cells via the MHC II which then destroys the corona virus infected cells which display the spike protein fragments on their surfaces. The B cells are also activated by the helper T cells as a result of which the B cells will proliferate and its progeny will differentiate into antibody secreting cells.

I hope this is helpful.

Best Wishes.

Thank you for the answers,

You are right. The logic is that the vaccinated cells produce the protein. Although before this vaccine, we did not have the term "a vaccinated cell", now it completely fits into the picture.

However, based on what type of cells produce the antigen, we may have different results. The questions that raised are following:

1) See, when somatic cells produce self protein far in ovaries, kidney, liver and etc, those fragments are presented not by MHC II, but MHC I. If the environment does not contain inflammation or pro-inflammatory elements it may lead to T-cell peripheral anergy rather than activation. Thus, rendering to tolerance. in that, a person can be infected but not reacting to the infection. How do we avoid immune tolerance towards the vaccine?

2) The cells contain retrotransposons and telomerase that use the enzyme reverse transcriptase. While we say that COVID vaccine mRNA does not enter into the genome, we have to specify in what kind of cells? I do not possess data if these studies have been done on all human cell types, or only in immune cells?

The virus has a spherical shape with a diameter of approximately 125 nm. The most striking feature of the coronavirus is the club-shaped spike protein projecting from the virion surface. These spike proteins serve as attachment proteins for the virus to enter host cells.

Dr Baratha Jyothi,

That's true for the infection. My question concerns of the vaccine, which is mRNA enclosed in either a synthetic particle or an adenoviral vector. We inject the vaccine, and we say that the mRNA translates to spike protein and the latter is presented by MHC II by APC to naive T cells leading to immunity. So my primary question is: what defines the tropism of the vaccine towards the APC? or can the vaccine be presented to any other cells?

My secondary question is: if the vaccine mRNA can enter into the many cells, how do we know that it can not integrate into the human genome in a particular tissue?

Vaccines work by presenting a piece of or a weakened form of the disease-causing agent ‒ the virus in this case ‒ to our body’s immune system, which flags it as a foreign invader and produces antibodies against it. The immune system has a long memory; when the actual viruses show up, it remembers what they look like, and quickly produces antibodies to quell them.

RNA vaccines

Just two months after the genetic sequence of the novel coronavirus was published, a healthy volunteer received the first shot of an experimental vaccine(link is external) built using a tiny strip of artificial genetic material called mRNA.

This vaccine mimics the mRNA molecule found in our cells ‒ a key component of protein synthesis ‒ and carries the blueprint for making proteins that are part of the virus structure. Once the vaccine enters our cells, the protein-making machinery can ‘read’ it and start churning out viral proteins, which can then be displayed on the cell surface for immune cells to find and commit to memory.

mRNA vaccines(link is external) can be rapidly produced in the lab, and are less expensive to make than traditional vaccines, because they do not need complex manufacturing processes. They do not carry bits of the virus itself directly into our body, only the ‘instructions’ for our cells to make the viral proteins. Unlike DNA, there is no risk that they will be incorporated into the host genome, so they are likely to be safe. They can also be adapted for any type of protein.

While much research has been done on how to synthesize, stabilize and deliver mRNA into cells, no vaccine has made it to the market so far. There is also concern(link is external) that it is being tested too soon in humans, before extensive animal testing.

See Dr. Baratha Jyothi,

You are right about the idea of vaccines (your first paragraph).

About mRNA.

It is not a protein. It is a sequence of nucleic acids which codes for a peptide or protein, in this case - spike protein of COVID-19.

However, the "producer" of the spike protein after vaccination is still the human cells. The proteins that are produced inside the cells are degraded and presented on the surface using other machinery compared to the proteins that are endocytosed. Also, most of the human cells are not antigen-presenting cells.

So again, my primary question is what cells produce spike protein when we vaccinate the individual with mRNA vaccine? Because if it is produced by most of the human cells, it is possible to develop tolerance rather than immunity.

Secondary: we know that human cells possess reverse transcriptase, which may turn RNA into cDNA. Although the manufacturers say that mRNA vaccine is not turned into DNA, we have to ask a question, in what kind of cells it has been shown?

From mRNA injection, the Spike proteins are made by ribosomes in the muscle cells and APCs. In nanomedicine, I target the Spike proteins and glycoproteins, including (escape) epitopes derived from proteolytic transformation and cleavage from the Spike so that bioactive nanoscale species bind to them to inactivate them.

Armen, did you ever get an answer to your question? I was curious as well.

Thank you,

Debra Hottenrott

Dear Debra, I asked the question to Dr. Racaniello as well "does an mRNA vaccine have a specific affinity to antigen-presenting cells (APC) or it targets every human cell including APC"? And the answer was that the mRNA vaccine is not created specific for APCs and it can get into every cell.

And with this answer, tons of other questions come into play. Simply because mRNA translated in the pancreatic islet cells and mRNA translated in a dendritic cell have different fates.