[folli]

Derek Lowe, as usual, explains this quite nicely: https://blogs.sciencemag.org/pipeline/archives/2021/01/12/mo...

To quote:

One goal has been to try to selectively affect autoreactive T cells, but that’s a lot easier said than done. The regulatory T cells and regulatory B cells are key players in immune tolerance, the “friend or foe” recognition system that keeps our own immune systems from attacking everything in sight. If you could present some of the antigens involved to those cells in a way that they accepted them as normal human proteins rather than as an external threat, you could presumably turn down their response.

BioNTech and others have been trying to target the population of lymphoid antigen-presenting cells, known to be very important in immune tolerance mechanisms, but without setting off any of the general inflammation pathways. They have a liposomal formulation that when injected into the muscle tissue seems to end up almost entirely in the lymphatic system, and they’ve been doing all sorts of modifications to the RNA payload (such as replacement of uridine with methylpseudouridine) to make it as non-immunogenic by itself as possible. The liposome lipids themselves are also chosen to be as non-immunogenic as possible, too – the coronavirus mRNA vaccines actually get an adjuvant boost from such properties, but you don’t want that in this case.