Wu Ying, Li Haoqi, Wang Zongmei, Pei Tao, Shang Qinghua, Zhao Jianqing, Zhou Ming, Fu Zhen F, Zhang Chengguang, Zhao Ling
National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Preventive Veterinary Medicine of Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China.
National Key Laboratory of Agricultural Microbiology, Huazhong Agricultural University, Wuhan 430070, China; Key Laboratory of Preventive Veterinary Medicine of Hubei Province, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China; Frontiers Science Center for Animal Breeding and Sustainable Production, Wuhan 430070, China.
Vet Microbiol. 2025 May;304:110481. doi: 10.1016/j.vetmic.2025.110481. Epub 2025 Mar 16.
Rabies is a fatal zoonotic disease affecting various warm-blooded animals. The number of dogs and cats in China has surpassed 120 million, yet no domestic universal rabies vaccine for them. The glycoprotein (G) of the rabies virus (RABV) serves as the principal antigen for inducing virus-neutralizing antibodies (VNA). In this study, we constructed a recombinant RABV strain (designated SAD-tOG) carrying three copies of the codon-optimized G gene using reverse genetics. The SAD-tOG strain exhibited comparable growth kinetics to the parent strain in cell culture while demonstrating enhanced G protein expression. Mouse challenge experiments revealed significantly reduced pathogenicity and elevated immunogenicity in the recombinant strain. Subsequently, a safe and efficient water-based adjuvant was selected to prepare an inactivated rabies vaccine. In another experiment, the VNA titers of dogs and cats after vaccination were both greater than the WHO-recommended protective antibody titer of 0.5 IU/ml for 360 days. Comparative analysis showed these titers were higher than those induced by commercial vaccines currently used in China. These findings collectively indicate that the SAD-tOG strain represents a safer and more effective vaccine candidate for dog and cat rabies prevention.
狂犬病是一种影响多种温血动物的致命人畜共患病。中国的犬猫数量已超过1.2亿，但尚无针对它们的国产通用狂犬病疫苗。狂犬病病毒（RABV）的糖蛋白（G）是诱导病毒中和抗体（VNA）的主要抗原。在本研究中，我们利用反向遗传学构建了一种携带三个密码子优化的G基因拷贝的重组RABV毒株（命名为SAD-tOG）。SAD-tOG毒株在细胞培养中表现出与亲本毒株相当的生长动力学，同时显示出增强的G蛋白表达。小鼠攻毒实验表明，重组毒株的致病性显著降低，免疫原性增强。随后，选择了一种安全高效的水性佐剂来制备灭活狂犬病疫苗。在另一项实验中，犬猫接种疫苗后的VNA滴度在360天内均高于世界卫生组织推荐的0.5 IU/ml的保护性抗体滴度。比较分析表明，这些滴度高于中国目前使用的商业疫苗所诱导的滴度。这些发现共同表明，SAD-tOG毒株是预防犬猫狂犬病的一种更安全、更有效的候选疫苗。
