Working models of lipid nanoparticle-based SARS-CoV-2 mRNA vaccines. Non-replicating and self-amplifying mRNAs are encapsulated with lipid nanoparticles (LNPs) and delivered into cells. Non-replicating mRNAs only encode target proteins whereas self-amplifying mRNAs encode both target proteins and viral non-structural proteins that are required for mRNA amplification. Target proteins translated from these mRNAs are recognized by antigen-presenting cells (APCs), including dendritic cell and macrophage, followed by activation of T (CD4+ and CD8+) and B cells that kill virus-infected cells or generate specific neutralizing antibodies (nAbs) that combat SARS-CoV-2 infection. GC B cell, germinal center B cell. 5’- and 3’-UTR, 5’- and 3’-untranslated regions. MHC I and II, major histocompatibility complex class I and class II molecules. nAbs, neutralizing antibodies.