Unlike DNA vaccines, which deliver genetic material into the nucleus, mRNA is delivered into the cytoplasm (Pardi et al., 2018). As for DNA vaccines, ribosomes translate the RNA to generate viral antigens, proteolysis takes place in the proteasome, and epitopes loaded onto Class I MHC proteins are displayed on the cell surface for recognition by CD8 cells. Antibody responses are generated against intact antigen that is secreted from the cell, or expressed on the cell surface if a transmembrane domain is included .Secreted protein can be take np by APCs ,degraded ,and presented by MHCII to CD4 cells (Pardietal.,2018). In 1993 it was established that liposome-encapsulated RNA induced in vivo Tcell stimulation (Kallen& Theß,2014;Verbekeetal.,2019).

Extensive research efforts have seen the development of many RNA vaccines that use cationic polymers, nanoparticles, and viral vectors as delivery systems, and are in different phases of clinical development. These include vaccines against Influenza virus (Petsch et al., 2012), rabies virus (Schnee et al., 2016), HIV-1 (Pollard et al., 2013), RSV (Geall et al., 2012), Zika virus (Richner et al., 2017), melanoma (Weide et al., 2009), nonsmall-cell lung cancer (Sebastian et al., 2014), and prostate cancer (Ku¨bler et al., 2015). At the time of writing, two human mRNA vaccines have been approved for use, the Moderna and Pfizer/BioNTech COVID-19 vaccines.

RNA vaccines share the advantages of DNA vaccines over conventional vaccines in that they are noninfectious, and manufacture follows the same pathway for vaccines against multiple indications. However, adverse reactions to RNA vaccines might be seen in individuals susceptible to autoimmunity (Pardi et al., 2018). Reactogenicity has also been reported in clinical trials of COVID-19 RNA vaccines (Wadman, 2020). Manufacture of RNA vaccines is described in the chapter addressing approaches to cancer vaccination.

References
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