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• Source: [ @bansal2021 Cutting Edge: Circulating Exosomes with COVID Spike Protein Are Induced by BNT162b2 (Pfizer–BioNTech) Vaccination prior to Development of Antibodies: A Novel Mechanism for Immune Activation by mRNA Vaccines ]
• Tags: #Extracellular-Vesicle #COVID #Vaccine #Spike-Protein

It has been established that the mRNA vaccines generate immunity against SARS-CoV-2 , but the exact mechanisms can still be better explained. Interestingly, extracellular vesicles have been found to carry the spike protein after patients have been inoculated with the BioNTech vaccine. It seems that the exosomes are instrumental at generating Humoral immunity as well as Cell-mediated immunity

The plots above show the abundances of exosomes with the protein after 7 and 14 days of vaccination. The increase is clear, in the same way the decrease at the 4-month mark brings the numbers back to the baseline. The EV s were extracted from blood plasma (see: how to extract ev's from blood plasma , and Blood-derived EVs are more challenging to study ).

In essence, the paper shows that exosomes with a given protein are fundamental to generating antibodies beyond the place were the vaccine was applied. The methods used included Transmission electron microscopy in which the spike protein was labeled with immunogold, and NTA to count the number of exosomes. However, the entire method for extraction and purification is quite convoluted.

An important step was to inoculate mice with the extracted extracellular vesicles. The mice showed the generation of antibodies against SARS-CoV-2 , which shows two interesting paths forward: EVs can be used as a drug delivery platform , and that in the specific case of this vaccine, EV's are instrumental for generating immunity.

The question I have is why have the authors targeted the spike protein on the surface of the EV's instead of in the interior. In the virus, the Spike protein is a surface protein, but to me it is not clear why would EV's express the same protein on the outward-facing side.