Spike protein

[Kiang-Hua Goh]

Hi Shin

Just a comment on Dr. Pascolo's opinion that the spike protein is not secreted.

My understanding is that the secreted spike proteins will be phagocytosed by the APCs, broken up and displayed on their surfaces for presentation to the lymphocytes in the lymph nodes - this is the basis for activation of the adaptive immunity.

If the spike proteins remain attached to the surface of the muscle cells, is there another pathway for activation of the adaptive immune response?

Regards

Dr. Goh

[Shin jie Yong]

Hello Dr. Goh,

I was wondering if the APCs themselves take up the mRNA vaccines, produce the spike protein, and express and present the antigen to T-cells and B-cells? 

I read this information from an article in Nature Reviews Drug Discovery, stating that:

"""

DCs are the most potent antigen-presenting cells of the immune system. They initiate the adaptive immune response by internalizing and proteolytically processing antigens and presenting them to CD8+ and CD4+ T cells on major histocompatibility complexes (MHCs), namely, MHC class I and MHC class II, respectively. Additionally, DCs may present intact antigen to B cells to provoke an antibody response60. DCs are also highly amenable to mRNA transfection. For these reasons, DCs represent an attractive target for transfection by mRNA vaccines, both in vivo and ex vivo.

Although DCs have been shown to internalize naked mRNA through a variety of endocytic pathways...

"""

Another review paper also mentioned that DCs or APCs could migrate to the injection site and take up the mRNA vaccine.

Interestingly, both reviews do not seem to indicate that the mRNA-induced spike protein production is secreted into the extracellular environment.

I hope that's clear. But if not, I think I will ask Dr. Pascolo about this. 

Kind regards,

Shin

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