Whole genome and structural protein sequence analysis of PM1503-02 strain applied to human diploid cell rabies vaccine research
10.13200/j.cnki.cjb.004591
- VernacularTitle:用于人二倍体细胞狂犬病疫苗研究的PM1503-02毒株全基因组及结构蛋白序列分析
- Author:
Jing ZUO
1
Author Information
1. R&D Center, Beijing Minhai Biotechnology Co., Ltd., Daxing 102600, Beijing, China
- Publication Type:Journal Article
- Keywords:
Rabies virus(RV);
Rabies vaccine;
Whole genome sequence;
Glycoprotein(G);
Homology;
Phylogenetic tree;
Genetic stability
- From:
Chinese Journal of Biologicals
2025;38(11):1281-1291+1298
- CountryChina
- Language:Chinese
-
Abstract:
Objective To analyze the application of PM1503-02 strain in human diploid cell rabies vaccine(HDCV)production research at the molecular level.Methods The whole genome sequences and amino acid sequences of PM1503-02 were studied in comparison with 18 domestic and foreign vaccine strains using homology comparison and phylogenetic trees, and the antigen-binding sites and glycosylation sites of the glycoproteins(Gs) of PM1503-02 and 18 domestic and foreign vaccine strains were also studied in comparison. In addition, a phylogenetic tree was also constructed with 56 domestic street strains simultaneously to analyze the affinities between PM1503-02 and domestic street strains. The genetic stability of the whole genome sequence of PM1503-02 was confirmed across different passage generations.Results The whole genome sequence of PM1503-02 strain showed the highest homology with PM1503 and CVS-11 strains, reaching more than 99%, and showed the next highest homology with HEP-Flury, Flury LEP and Flury-LEP-C strains, reaching more than95%. There were few mutations in the antigenic sites in the extra-membrane domain of the G protein of PM1503-02, and only the 40 th amino acid of the antigenic siteⅡwas mutated to glutamic acid(E). The glycosylation sites were at amino acid positions 37, 247 and 319, respectively. The results of phylogenetic tree construction with 56 domestic strains showed that PM1503-02 was closely related to domestic street strains. PM1503-02 strain was passaged to the 63 rd, 64 th, 65 th, 66 th and70 th generations in HDCs, and single-point mutations appeared in the 66 th and 70 th generations of the whole genome sequences, but all of them were synonymous mutations with no effect on the protein structure.Conclusion This study provides favorable support for developing a more effective HDCV using PM1503-02 at the molecular level, which has a better prospect for application in China.