title: Live attenuated rabies virus co-infected with street rabies virus protects animals against rabies.
abstract: While current rabies post-exposure prophylaxis (PEP) is highly effective, it is costly and the vaccination regimen is complicated, requiring both inactivated vaccines and immunoglobulins. A one-dose rabies vaccine for human PEP remains a long-term goal. Here, we describe development of a highly attenuated rabies virus ERAg3m, with a mutation in the glycoprotein (G) gene and a switch of the G gene with the matrix protein gene in the viral genome. After a one-dose intramuscular vaccination, the ERAg3m virus protected 100% of mice and hamsters from lethal challenge. In co-infections, using a lethal dose of street rabies virus mixed with ERAg3m, 100% of hamsters and 90% of mice survived and were protected against subsequent infection. A mock co-infection, using inactivated commercial human rabies vaccine and a lethal dose of street rabies virus, protected 100% and 40% of hamsters and mice, respectively. In co-infections, when vaccine was administrated in the left leg and challenge virus in the right leg, the ERAg3m virus protected 40% of mice, while the inactivated vaccine showed no protection. Therefore, live attenuated rabies virus when given pre-exposure or co-infected with street rabies virus, is capable of preventing rabies in two different animal models. Overall, this highly attenuated live rabies virus offered better protection than the inactivated vaccine.
authors.affiliation: Centers for Disease Control and Prevention, 1600 Clifton Road, MS-G33, Atlanta, GA 30333, USA. XAW6@cdc.gov
authors.forename: Xianfu
authors.initials: X
authors.lastname: Wu
authors.forename: Richard
authors.initials: R
authors.lastname: Franka
authors.forename: Heather
authors.initials: H
authors.lastname: Henderson
authors.forename: Charles E
authors.initials: CE
authors.lastname: Rupprecht
mesh_terms: D000818:Animals; D006224:Cricetinae; D005260:Female; D007273:Injections, Intramuscular; D008647:Mesocricetus; D051379:Mice; D008813:Mice, Inbred ICR; D011818:Rabies / Q000276:immunology / Q000517:prevention & control*; D011819:Rabies Vaccines / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology*; D011820:Rabies virus / Q000276:immunology*; D016019:Survival Analysis; D014611:Vaccination / Q000379:methods*; D014613:Vaccines, Attenuated / Q000008:administration & dosage / Q000235:genetics / Q000276:immunology
chemical_list: D011819:Rabies Vaccines; D014613:Vaccines, Attenuated