inactivated recombinant rabies CVS-11 virus expressing two copies of the glycoprotein elicits a higher level of neutralizing antibodies and provides better protection in mice

• Published in: Virus genes Vol. 48; no. 3; pp. 411 - 420
• Main Authors: Xue, Xiang-Hong, Zheng, Xue-Xing, Wang, Hua-Lei, Ma, Jin-Zhu, Li, Ling, Gai, Wei-Wei, Wang, Tie-Cheng, Yang, Song-Tao, Xia, Xian-Zhu
• Format: Journal Article
• Language: English
• Published: Boston Springer-Verlag 01.06.2014; Springer US; Springer Nature B.V
• Subjects: Animals; Antibodies, Neutralizing - immunology; Antibodies, Viral - immunology; Biomedical and Life Sciences; Biomedicine; Female; G-proteins; gene overexpression; genes; glycoproteins; Glycoproteins - administration & dosage; Glycoproteins - immunology; Humans; immune response; lethal dose 50; Medical Microbiology; Mice; Mice, Inbred BALB C; mortality; neutralization tests; neutralizing antibodies; pathogenicity; Plant Sciences; quantitative polymerase chain reaction; Rabies - immunology; Rabies - prevention & control; Rabies - virology; Rabies Vaccines - administration & dosage; Rabies Vaccines - genetics; Rabies Vaccines - immunology; Rabies virus; Rabies virus - genetics; Rabies virus - immunology; Vaccines, Inactivated - administration & dosage; Vaccines, Inactivated - genetics; Vaccines, Inactivated - immunology; Viral Envelope Proteins - administration & dosage; Viral Envelope Proteins - genetics; Viral Envelope Proteins - immunology; virion; Virology; viruses; Pathogenicity; Inactivated vaccines; Rabies virus; G protein
• ISSN: 0920-8569; 1572-994X
• DOI: 10.1007/s11262-014-1049-9

The rabies virus (RABV) G protein is the primary contributor to the pathogenicity and protective immunity of RABV. In this study, we generated a recombinant rCVS-11-G strain containing two copies of the G protein derived from the pathogenic wild-type (wt) CVS-11 strain and based on its infectious clone. Compared with the wtCVS-11 strain, the rCVS-11-G strain possessed a larger virion and 1.4-fold more G protein, but it exhibited a similar growth property to the rCVS-11 strain, including passaging stability in vitro. qPCR results showed that the two G genes were over-expressed in BHK-21 cells infected with the rCVS-11-G strain. However, the rCVS-11-G strain presented an 80 % lower LD₅₀ than the wtCVS-11 strain when intracranially (i.c.) inoculated in adult mice. Adult mice that were either intracranially (i.c.) or intramuscularly (i.m.) inoculated with rCVS-11-G strain developed more acute neurological symptoms and greater mortality than those inoculated with the wtCVS-11 strain. Furthermore, the rCVS-11-G strain was more easily and rapidly taken up by neuroblastoma cells. These data indicated that the rCVS-11-G strain might have increased neurotropism because of the over-expression of the pathogenic G protein. The inactivated rCVS-11-G strain induced significantly higher levels of virus neutralization antibodies and provided better protection from street rabies virus challenge in mice. Therefore, the rCVS-11-G strain may be a promising inactivated vaccine strain due to its better immunogenicity.