Q&A #19 : Some questions from a good friend

Q 1

‍What are the mechanism(s) that (largely) bypass the innate immune system upon vaccination with non-replicating vaccines (like mRNA)?  Is this simply because it is a localized injection that doesn't replicate/spread throughout other tissues and organs? Or is this due to additives in mRNA vaccines that prevent innate immune stimulation in order for the mRNA itself to not be degraded before being absorbed into target cells?

A 1

‍Only replicating virus will present virus-derived (self-mimicking)motifs/patterns (on the surface of infected cells) that can be recognized by innate effector cells (NK cells).

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‍Q 2

‍Why does C19 vaccination in young children prevent training of their innate immune systems for recognizing other viruses that they would later encounter? I understand how specific Abs can outcompete innate antibodies for a given virus, but why would specific Abs for SARS-CoV-2 Spike outcompete innate antibodies for something like influenza?

A 2

‍Because innate Abs bind to all glycosylated viruses. Although innate Abs can recognize a myriad of viruses, these very same viruses will require (self-mimicking) pattern recognition by NK cells to be recognized later on. It is through this pattern recognition mechanism that NK cells can be trained more specifically for the pattern presented by a particular virus (but which has reasonable homology with self-mimicking patterns presented by other glycosylated viruses).

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‍Q 3

‍Can you elaborate on this pattern recognition?

A 3

‍Innate Abs are typically polyspecific! They recognize self-like surface-expressed sugar patterns. In the case of enveloped glycosylated viruses, those are of course derived from the infected host cells (which provide the envelope of the virus!). This is why these sugar patterns are broadly shared amongst glycosylated viruses.