Artesunate enhances the immune response of rabies vaccine as an adjuvant

Rabies is an ancient zoonosis that continues to be an important health problem worldwide. Vaccination with rabies vaccine is the most important strategy to prevent rabies. Adjuvants contribute to the immune response of viral vaccine. The aim of this study was to investigate whether artemisinin derivatives artesunate and dihydroartemisinin could enhance the immunogenicity of inactivated rabies virus in mice. Administration of artesunate or dihydroartemisinin by intramuscular injection at a dose of 5 mg/kg did not cause body weight loss and unusual symptoms in mice. Mice were immunized with inactivated CVS-11 or inactivated rHEP-dG together with either artesunate or dihydroartemisinin through intramuscular injection. Blood samples were collected to investigate the virus-neutralizing antibody (VNA) titers, and challenge assays were then conducted. The results showed that the rabies VNA titers in mice co-treated with artesunate rather than dihydroartemisinin were significantly higher than in the control animals treated with the phosphate buffered saline (PBS). In addition, mice co-treated with artesunate survived from lethal rabies virus challenge compared with those treated with PBS. In contrast, co-treatment with dihydroartemisinin did not improve the survival rate of the challenged mice. The findings indicate that artesunate could be used as a new candidate adjuvant for rabies vaccination. (C) 2019 Elsevier Ltd. All rights reserved.