Fate of spike protein

[Kiang-Hua Goh]

Hi Shin,

Another thought crossed my mind.

The mRNA will also be endocytosed by the muscle cells. After translation by the ribosomes, the resulting spike proteins will be displayed on the surface of the muscle cells. (According to Dr. Pascolo, they are not secreted)

After activation of the adaptive immune response, these muscle cells will be targeted by CD8+ T cells, resulting in their destruction. Hence, there should be inflammatory changes at the site of injection, resulting in pain and swelling. This should occur after ten days to 2 weeks - the patient should then complain of recurrence of pain and swelling at the injection site.

A similar phenomenon should happen after the 2nd dose but may be eariler.

However, this has not been seen with the mRNA vaccines. 

Does this imply that the spike proteins are rapidly degraded and no longer present on the surface of the muscle cells soon after synthesis? Have you come across any paper that studies the duration the spike proteins remain at the injection site? This will be importance with regards to the potential for localisation of LNPs in the central nervous system.

There are reports of delayed large local reactions after vaccination with a mean onset of 8 days with the moderna vaccine only (not the Pfizer vaccine). Not all of these patients had a similar reaction to the second dose and biopsy of one patient suggested this to be delayed type hypersensitivity. So these may just be an allergic reaction.

https://www.nejm.org/doi/full/10.1056/NEJMc2102131

Thanks for any info.

Warmest regards

Dr. Goh

[Shin jie Yong]

Dear Dr. Goh,

Thank you for contacting me again. 

After reading, I've seen articles acknowledging that common side effects from the first dose may be more intense (within a shorter period too) when receiving the second dose: 

• https://www.cdc.gov/coronavirus/2019-ncov/vaccines/expect/after.html
• https://www.theatlantic.com/health/archive/2021/02/second-vaccine-side-effects/617892/

But I think I see your point that the pain at the injection site should happen again (i.e. recurrence) when the adaptive immune system activates. 

However, I am also wondering if the adaptive immune system will get activated around the time of receiving the second vaccine shot since it has been primed from the first shot? 

I think this article from Forbes may explain it:
"That’s what your adaptive immune system can say when you get the second dose of the Covid-19 vaccine, the booster dose. This is supposed to remind your immune system about the spike protein by re-exposing your body to it. But if your adaptive immunity is already poised to act, more of a reaction may result. That’s why you may be more likely to get side effects following your second dose."

About the duration of the spike protein remaining at the injection site, I think the luciferase protein expression may be a proxy for that? I described a few studies about the luciferase expression in the draft. 

If this is true, maybe the spike protein's amount or expression peak within 24 hours and then decline, and gone in about a week. 

But I am also not sure if the luciferase expression correlates with how the spike proteins (produced via the mRNA vaccine) linger. 

Hope to hear your thoughts if any. 

Oh, since it has been about 8 days since I emailed two other researchers with a background in mRNA vaccines and received no responses, I will go ahead and publish this draft sometime today. 

Kind regards,

Shin 

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