Vanny Pornsinsiriruk, University of British Columbia

Vanny Pornsinsiriruk, Maria Tokuyama, both=Department of Microbiology and Immunology, University of British Columbia

Fighting & Responding

Herpes simplex virus type 2 (HSV-2) is a sexually transmitted infection causing genital lesions in adults, elevated fatality rates in infants, and increased susceptibility to HIV. Antiviral resistance is rising and there are no approved vaccines. Adenoviral vectors encoding virus-like particles (VLPs) expressing vaccine antigens have demonstrated efficacy as a cancer therapeutic. This combined approach leverages long-lasting T and B cell responses induced by viral vectors and strong antibody responses induced by high antigen density on VLPs. Endogenizing VLP creation via viral vector delivery increases vaccine stability and lowers production cost, two factors important for communities most affected by HSV-2. Taking challenges of past vaccine candidates and global health needs into account, we have designed a novel vaccine against HSV-2. Our VLP construct (VLPHSV-2) incorporates retroviral gag protein PEG10 for VLP self-assembly and HSV-2 glycoproteins gC2, gD2, and gE2 for induction of a broad and robust immune response against HSV-2. To optimize the generation efficiency and surface coverage of VLPs with HSV-2 glycoproteins, we have generated and compared constructs with various gene arrangements and quantified VLP and glycoprotein production in vitro using Western blot and nanoparticle analysis. Following assessment of immunogenicity and anti-HSV-2 disease protection in an established mouse model of infection, VLPHSV-2 will be cloned into an Ad5 vector (Ad5- VLPHSV-2) and the efficacy of this delivery system, as well as various vaccination routes, will be tested. Overall, we intend to further the understanding of immune mechanisms and design elements required for an effective anti-HSV-2 vaccine strategy.