Draft

[Kiang-Hua Goh]

Hi Shin

I have no problem with you quoting what I wrote.

I just want to emphasize that I analysed the topic from the angle of human physiology and biology. I am no expert in immunology so it might be worthwhile for you to consult an immunologist to check if what I wrote is correct from the immunological standpoint.

Moreover, the LNPs may have properties that may defy my assumptions and behave differently from what I wrote.

There is always a possibility of some novel mechanism that can traffic the LNPs to the brain.

Warmest regards

Dr. Goh

[Shin jie Yong]

Hello Dr. Goh (and others), 

Thank you for your kind email. I have heeded your suggestion and contacted an expert in mRNA vaccine, Dr. Steve Pascolo, about this matter. 

I have also emailed other mRNA vaccine immunologist but received no responses as of now. 

Based on Dr. Pascolo's email response, I have revised the draft, adding an important point that he mentioned (see a text excerpt below). 

"""

Steve Pascolo, Ph.D., co-founder of CureVac, is one of the earliest researchers to advocate for mRNA vaccines' potential in 2004. He also has an impressive publishing record on mRNA vaccines and was kind enough to respond to my email inquiring about this topic. Dr. Pascolo admits that some cells that take up the mRNA and express spike proteins on their surface might get destroyed by cytotoxic T-cells. But he added: 

…that is what happens to a much higher grade and in all organs when we get infected by SARS-CoV-2…or vaccinated with live viral vaccines…With the mRNA vaccine (30 micrograms in the muscle) the eventual destruction of cells by CD8 [cytotoxic T-cells] would always be very minor compared to what happens in infection when the viruses infect virtually all cells in all organs and the immune system is fully activated to get rid of it…”

Thus, the mere 30 micrograms of mRNA vaccine injected intramuscularly pale in comparison to the actual virus infection in the capacity to trigger cytotoxic T-cell attacks in the brain or elsewhere. And yes, SARS-CoV-2 is capable of invading the brain and many other organs.

"""

He looked over the current working draft and said it was good, giving me permission to quote him as well. 

Although Dr. Pascolo did not comment on whether the LNP might carry the mRNA vaccine into the brain or elsewhere, the broad-ranging tissue tropism of SARS-CoV-2 itself may be a much greater concern. 

Interestingly, he also told me that the mRNA-induced spike protein production may not be secreted, contrary to what other review papers have stated. Dr. Pascolo wrote in an email, "Depending on the protein encoded by the ivt mRNA, it will be in the cytosol, in the ER or on the surface or secreted. The full length spike from SARS-CoV-2 is a transmembrane protein that largely remains in the ER and a part reaches the cell surface but normally, as far as I know, this precise SARS-CoV-2 Spike protein is not secreted (it remains attached the membrane)." 

I hope this email finds you all well. Have a pleasant weekend. :)) 

Kind regards,

Shin 

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