Table 3.

Advantages and disadvantages of non-amplifying mRNA Vaccines and SAM Vaccines.

mRNA Vaccines	Structure	Advantages	Disadvantages	References
Non-amplifying mRNA Vaccines	Basic structure of the mRNA, with a coding region for the desired antigens.	- Relatively small mRNA size (~2–3 kb). - Absence of additional proteins, minimizing unwanted immune interactions. - Relatively easy to produce and amplify. - Simplified sequence engineering. - Direct antigen expression.	- Potential toxicity from modified nucleotides. - Short duration of expression. - Need for high RNA doses. - Low antigen quantity.	[8,86]
SAM Vaccines	Encode a manipulated RNA virus genome (replicon). It generally contains two different protein coding regions, one encoding nonstructural proteins involved in mRNA capping and replication, and the other in antigen expression.	- High yield of target antigen. - Enhanced and prolonged antigen expression. - Lower effective RNA doses (more safe). - Intrinsic adjuvant effect. - Potential apoptosis of vaccine-carrying cells due to vaccine self-amplification (enhanced cross-presentation). - Option for single-vector delivery of multiple or complex antigens.	- RNA replicons are not able to tolerate many of the synthetic nucleotide modifications and sequence alterations. - Inclusion of unrelated proteins, which may increase unwanted immunogenicity. - Large replicon size (~10 kb), decreasing cell internalization efficiency. - Interaction between nsPs and host factors yet to be addressed. - Longer RNA length (more difficult production). - Potential elevated inflammation.	[8,13,29,86,93]