mRNA vaccine immunity improves when liver cells are avoided and does not rely on immune cell production

In mouse mRNA-LNP vaccine models, detargeting hepatocyte expression boosted antigen-specific immunity while professional antigen-presenting cell expression was not required.

Preclinical mouse vaccine and lymphoma experiments used microRNA target sites to silence mRNA expression in professional antigen-presenting cells, hepatocytes, or myocytes and measured immune responses and tumor burden.

The evidence is limited to preclinical mouse and tumor models, so human vaccine efficacy, safety, and translation were not tested.