Virus-mimetic nanovesicles as a versatile antigen-delivery system

Significance The previously unidentified virus-mimetic nanovesicles (VMVs) described in this manuscript consist of phospholipid derived from mammalian cell plasma membrane, recombinant protein anchored to cell membrane via the route of signal peptide sorting, and surfactants capable of controlling the VMV size and strength, which allows the VMVs to display functional polypeptides or maintain the correct conformation of protein antigen. The protein integrated into VMV by its hydrophobic transmembrane peptide has more modifications, such as glycosylation, than proteins in conventional subunit vaccines. Moreover, many viral envelope glycoproteins can be genetically engineered onto VMV liposomal surface so as to mimic the properties and conformational epitopes of natural virus. VMV provides an effective, straightforward, and tunable approach against a wide range of emerging enveloped viruses. It is a critically important challenge to rapidly design effective vaccines to reduce the morbidity and mortality of unexpected pandemics. Inspired from the way that most enveloped viruses hijack a host cell membrane and subsequently release by a budding process that requires cell membrane scission, we genetically engineered viral antigen to harbor into cell membrane, then form uniform spherical virus-mimetic nanovesicles (VMVs) that resemble natural virus in size, shape, and specific immunogenicity with the help of surfactants. Incubation of major cell membrane vesicles with surfactants generates a large amount of nano-sized uniform VMVs displaying the native conformational epitopes. With the diverse display of epitopes and viral envelope glycoproteins that can be functionally anchored onto VMVs, we demonstrate VMVs to be straightforward, robust and tunable nanobiotechnology platforms for fabricating antigen delivery systems against a wide range of enveloped viruses.