Conventional, self-amplifying, trans-amplifying, and circular RNA vaccine designs. 5′ 7-methylguanosine triphosphate (m7G), 5′ Untranslated region (5′UTR), 3′ untranslated region (3′UTR), and poly A tail are common in all RNA designs. (A) Conventional unmodified, and nucleoside modified mRNA encoding vaccine immunogen. (B) Self-amplifying RNA encoding replicase gene, a subgenomic promoter, and the vaccine immunogen. Replicase genes (e.g., Alphavirus nsP1-4) code for RNA dependent RNA polymerase complex (RdRP) that recognizes the subgenomic promoter sequences and amplifies vaccine immunogen. (C) Trans-amplifying mRNA relies on the same concept of the self-amplifying mRNA but uses two different RNA transcripts: a conventional RNA encoding replicase genes and, an RNA encoding subgenomic promoter along with the vaccine immunogen. (D) Circular RNA engineered to enable protein expression through the addition of internal ribosomal entry sites (IRES) (e.g., encephalomyocarditis virus IRES) and/or the incorporation of specific nucleoside modifications in the 5′ UTR.