Self-amplifying mRNA (saRNA) vaccines offer several advantages. Compared with HIV protein vaccines, they can be rapidly produced with reduced development time and costs by using a common manufacturing platform and purification methods. The antigen would be expressed in situ, allowing for transmembrane domains and multimeric complexes to be formed and more naturally presented to the immune system to illicit broadly neutralizing antibodies. Compared with DNA vaccine, mRNA vaccine only requires cytosolic delivery and do not have the potential risk of integration of exogenous DNA into host genome, which makes mRNA a more promising nucleic acid immunogen. In addition, saRNA has been shown to induce protein expression for up to 60 days and elicit immune responses with lower dosing than conventional mRNA. Despite these advantages of saRNA, due to its large size and negative charge, a potent, well-tolerated delivery system facilitating efficient cellular uptake and degradation protection is needed for the development of saRNA-based vaccine. Zymeron develops a nanoparticle-in-hydrogel immunogen-adjuvant co-delivery HIV saRNA vaccine for targeted delivery to antigen-presenting cells and enhancing endosomal escape and the subsequent translation of saRNA, therefore to illicit effective HIV-specific immune responses.
