An 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 |
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Authors: | Xiang-Hong Xue Xue-Xing Zheng Hua-Lei Wang Jin-Zhu Ma Ling Li Wei-Wei Gai Tie-Cheng Wang Song-Tao Yang Xian-Zhu Xia |
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Affiliation: | 1. College of Veterinary Medicine, Jilin University, Changchun, 130062, China 2. Institute of Military Veterinary Medicine, Academy of Military Medical Science, Changchun, 130122, China 3. Biotechnology Research Institute, Chinese Academy of Agricultural Sciences, Beijing, 100081, China 4. College of Life Science and Biotechnology, Heilongjiang Bayi Agricultural University, Daqing, 163319, China
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Abstract: | 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. |
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