Novel rabies vaccine candidates development based on pseudotyped lentiviral vectors with rabies virus glycoprotein

Rabies, caused by the rabies virus (RABV), remains a global public health issue. Traditional inactivated rabies vaccines are costly, risky, and require multiple doses for post-exposure prophylaxis. The rabies virus glycoprotein (RABV-G), essential for inducing protective antibodies, is crucial for new vaccine development. Lentiviral vectors offer promise due to their efficient gene delivery and strong immune responses. We designed three recombinant pseudotyped lentiviral vector vaccines with enhanced green fluorescent protein (eGFP) as marker, among VSV-G/LV-RABV-G the RABV-G only lies in the core of pseudotyped lentiviral particle, among RABV-G/LV-RABV-G the RABV-G lies in both of the core and the envelop and among RABV-G/LV-eGFP the RABV-G only lies in the envelop. These were tested for antigenicity, infectivity, and neutralizing antibody response. All vaccines showed strong antigen specificity and high titers for virus particles production. Immunization tests in mice showed that VSV-G/LV-RABV-G and RABV-G/LV-RABV-G vaccines induced high neutralizing antibody levels within 3 days, sustained up to 10 weeks. The RABV-G/LV-eGFP vaccine, especially with CPG-ODN adjuvant, also generated significant antibody responses. In summary, the recombinant pseudotyped lentiviral vector vaccines based on the RABV-G show promise for effective, single-dose rabies vaccination.