S protein–ACE2–Ang II triad in using therapeutic sACE2 and vaccination

https://onlinelibrary.wiley.com/doi/10.1002/rmv.2213

The impact of mACE2 and sACE2 down regulation in vaccinated individuals can also be explained in the light of the above discussion. All the vaccines under clinical and preclinical trials have RNA-devoid virus S protein as final derivative to elicit immune response inside our body.90 SARS-CoV and SARS-CoV-2 S protein alone or expressed in pseudovirus vehicle showed to bind and internalize mACE2 but cannot replicate due to the absence of its RNA.5, 12, 49, 69 Accordingly, all vaccine ingredients can potentially internalize mACE2 upon binding and trigger mACE2 shedding by ADAM17 to release sACE2. Inactivated or weakened vaccines or vaccines with S protein expressed on pseudovirus or virus-like particles can bind the available sACE2. Partially saturated vaccine–sACE2 complex can bind to mACE2, and this internalization may reduce the overall ACE2 availability. This will raise Ang II level in the same way as original virus can do and pose additional risk to comorbid and older individuals. Healthy individuals may overcome this vaccine-induced transient Ang II rise as they do in viral infection. However, with already-elevated sACE2 level, older and comorbid individual taking vaccine may face sudden Ang II spike mediated harmful effects which need to be carefully observed…