Article Alert: Extracellular Vesicles as Pathogenic Enveloped Virus Vaccines

Viral proteins expressed on the membranes of pathogenic enveloped viruses are pivotal determinants of immune system recognition. To develop effective vaccines, the proper membrane protein conformation must be presented in the context of lipid membranes to elicit a maximal protective response. Optimizing this process remains a primary goal in vaccine research.

In their new study, Choi et al. describe an exciting approach using extracellular vesicle (EV)-based technology to faithfully express viral membrane antigens on a specific type of EV (1). To preserve antigenic immunogenicity, the authors discovered that fusing the transmembrane and extracellular viral protein domains to a WW domain, which previous work had shown to be essential for EV cargo recruitment, was able to selectively target viral membrane antigens to what the researchers termed “WW domain-activated extracellular vesicles” (WAEVs). A variety of strategies was used to characterize these WAEVs, revealing that they are enriched in the integral membrane protein SCAMP3. SCAMP3 contains two separate domains that bind to WW domains and TSG101, thereby allowing WAEV budding. WAEVs displaying either influenza or HIV viral membrane proteins successfully triggered production of virus-specific neutralizing antibodies, with the influenza protein WAEV offering protection against lethal infection in mice. These intriguing findings suggest that WAEVs may represent a highly adaptable platform for vaccine development.

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