Cao Longlong, Liu Jian, Li Yongfan, Xie Denglong, Yan Quanhui, Li Qiuyan, Cao Yiran, Du Wenxin, Li Jiakang, Ye Zijun, Zhou Dengyuan, Kang Chao, Cao Shengbo
Wuhan Keqian Biology Co., Ltd., Wuhan 430070, China.
National Key Laboratory of Agricultural Microbiology, College of Veterinary Medicine, Huazhong Agricultural University, Wuhan 430070, China.
Vaccines (Basel). 2023 Dec 15;11(12):1858. doi: 10.3390/vaccines11121858.
Feline calicivirus (FCV) is one of the most important pathogens causing upper respiratory tract diseases in cats, posing a serious health threat to these animals. At present, FCV is mainly prevented through vaccination, but the protective efficacy of vaccines in China is limited. In this study, based on the differences in capsid proteins of isolates from different regions in China, as reported in our previous studies, seven representative FCV epidemic strains were selected and tested for their viral titers, virulence, immunogenicity, and extensive cross-protection. Subsequently, vaccine strains were selected to prepare inactivated vaccines. The whole-genome sequencing and analysis results showed that these seven representative FCV strains and 144 reference strains fell into five groups (A, B, C, D, and E). The strains isolated in China mainly fall into groups C and D, exhibiting regional characteristics. These Chinese isolates had a distant evolutionary relationship and low homology with the current FCV-255 vaccine strain. The screened FCV-HB7 and FCV-HB10 strains displayed desirable in vitro culture characteristics, with the highest virus proliferation titers (10 TCID/mL) at 36 h post inoculation at a dose of 0.01 MOI. All five cats infected intranasally with FCV-HB7 or FCV-HB10 strains showed obvious clinical symptoms of FCV. The symptoms of cats infected with the FCV-HB7 strain were more severe than those infected with the FCV-HB10 strain. Both the single-strain inactivated immunization and combined bivalent inactivated vaccine immunization of FCV-HB7 and FCV-HB10 induced high neutralizing antibody titers in five cats immunized. Moreover, bivalent inactivated vaccine immunization protected cats from FCV-HB7 and FCV-HB10 strains. The cross-neutralizing antibody titer against seven representative FCV epidemic strains achieved by combined bivalent inactivated vaccine immunization was higher than that achieved by single-strain immunization, which was much higher than that achieved by commercial vaccine FCV-255 strain immunization. The above results suggest that the FCV-HB7 and FCV-HB10 strains screened in this study have great potential to become vaccine strains with broad-spectrum protective efficacy. However, their immune protective efficacy needs to be further verified by multiple methods before clinical application.
猫杯状病毒(FCV)是引起猫上呼吸道疾病的最重要病原体之一,对这些动物的健康构成严重威胁。目前,FCV主要通过接种疫苗来预防,但中国疫苗的保护效果有限。在本研究中,基于我们之前研究报道的中国不同地区分离株衣壳蛋白的差异,选择了7株具有代表性的FCV流行株,对其病毒滴度、毒力、免疫原性和广泛的交叉保护作用进行检测。随后,选择疫苗株制备灭活疫苗。全基因组测序和分析结果表明,这7株具有代表性的FCV毒株与144株参考毒株分为5组(A、B、C、D和E)。在中国分离的毒株主要属于C组和D组,呈现出区域特征。这些中国分离株与目前的FCV - 255疫苗株进化关系较远,同源性较低。筛选出的FCV - HB7和FCV - HB10毒株在体外培养特性良好,在接种剂量为0.01 MOI时,接种后36 h病毒增殖滴度最高(10⁷TCID₅₀/mL)。经鼻内感染FCV - HB7或FCV - HB10毒株的5只猫均表现出明显的FCV临床症状。感染FCV - HB7毒株的猫的症状比感染FCV - HB10毒株的猫更严重。FCV - HB7和FCV - HB10的单株灭活免疫以及联合二价灭活疫苗免疫均在5只免疫猫中诱导产生了高滴度的中和抗体。此外,二价灭活疫苗免疫保护猫免受FCV - HB7和FCV - HB10毒株的感染。联合二价灭活疫苗免疫对7株具有代表性的FCV流行株产生的交叉中和抗体滴度高于单株免疫,远高于商业疫苗FCV - 255株免疫产生的交叉中和抗体滴度。上述结果表明,本研究筛选出的FCV - HB7和FCV - HB10毒株具有成为具有广谱保护效果疫苗株的巨大潜力。然而,在临床应用前,它们的免疫保护效果还需要通过多种方法进一步验证。