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  • Title: Codon optimization of G protein enhances rabies virus-induced humoral immunity.
    Author: Pei J, Huang F, Wu Q, Luo Z, Zhang Y, Ruan J, Li Y, Zhou M, Fu Z, Zhao L.
    Journal: J Gen Virol; 2019 Aug; 100(8):1222-1233. PubMed ID: 31259681.
    Abstract:
    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.
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