Codon optimization of G protein enhances rabies virus-induced humoral immunity
| Autor: | Zhaochen Luo, Fei Huang, Ming Zhou, Zhen-fang Fu, Juncheng Ruan, Yachun Zhang, Qiong Wu, Ling Zhao, Jie Pei, Yingying Li |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Rabies 030106 microbiology Antibodies Viral medicine.disease_cause Mice Viral Proteins 03 medical and health sciences Virology medicine Animals Humans Codon Glycoproteins Mice Inbred ICR biology Immunogenicity Rabies virus Germinal center medicine.disease Antibodies Neutralizing Reverse genetics Immunity Humoral 030104 developmental biology Rabies Vaccines Immunization Humoral immunity biology.protein Female Antibody |
| Zdroj: | Journal of General Virology. 100:1222-1233 |
| ISSN: | 1465-2099 0022-1317 |
| DOI: | 10.1099/jgv.0.001299 |
| Popis: | Rabies, caused by rabies virus (RABV), is a fatal zoonosis, which still poses a threat to public health in most parts of the world. Glycoprotein of RABV is the only viral surface protein, which is critical for the induction of virus-neutralizing antibodies (VNA). In order to improve the production of VNA, recombinant RABVs containing two copies of G gene and codon-optimized G gene were constructed by using reverse genetics, named LBNSE-dG and LBNSE-dOG, respectively. After being inoculated into the mouse brains, LBNSE-dOG induced more apoptosis and recruited more inflammatory cells than LBNSE-dG and LBNSE, resulting in reduced virulence in vivo. After intramuscular (im) immunization in mice, LBNSE-dOG promoted the formation of germinal centres (GCs), the recruitment of GC B cells and the generation of antibody-secreting cells (ASCs) in the draining lymph nodes (LNs). Consistently, LBNSE-dOG boosted the production of VNA and provided better protection against lethal RABV challenge than LBNSE-dG and LBNSE when it was used as both live and inactivated vaccines. Our results demonstrate that the codon-optimized RABV LBNSE-dOG displays attenuated pathogenicity and enhanced immunogenicity, therefore it could be a potential candidate for the next generation of rabies vaccines. |
| Databáze: | OpenAIRE |
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