Genotype analysis of rotaviruses isolated from children during a phase III clinical trial with the hexavalent rotavirus vaccine in China

Wenqi Zou; Qingchuan Yu; Yan Liu; Qingliang Li; Hong Chen; Jiamei Gao; Chen Shi; Ying Wang; Wei Chen; Xuan Bai; Biao Yang; Jiuwei Zhang; Ben Dong; Bo Ruan; Liuyifan Zhou; Gelin Xu; Zhongyu Hu; Xiaoming Yang

doi:10.1016/j.virs.2023.11.002

December 2023

Citation: Wenqi Zou, Qingchuan Yu, Yan Liu, Qingliang Li, Hong Chen, Jiamei Gao, Chen Shi, Ying Wang, Wei Chen, Xuan Bai, Biao Yang, Jiuwei Zhang, Ben Dong, Bo Ruan, Liuyifan Zhou, Gelin Xu, Zhongyu Hu, Xiaoming Yang. Genotype analysis of rotaviruses isolated from children during a phase III clinical trial with the hexavalent rotavirus vaccine in China .VIROLOGICA SINICA, 2023, 38(6) : 889-899. http://dx.doi.org/10.1016/j.virs.2023.11.002

Genotype analysis of rotaviruses isolated from children during a phase III clinical trial with the hexavalent rotavirus vaccine in China

Wenqi Zou ^a ,
Qingchuan Yu ^b ,
Yan Liu ^b ,
Qingliang Li ^a ,
Hong Chen ^a ,
Jiamei Gao ^b ,
Chen Shi ^a ,
Ying Wang ^a ,
Wei Chen ^a ,
Xuan Bai ^a ,
Biao Yang ^a ,
Jiuwei Zhang ^a ,
Ben Dong ^a ,
Bo Ruan ^a ,
Liuyifan Zhou ^a ,
Gelin Xu ^a ,
Zhongyu Hu ^{b
,,} ,
Xiaoming Yang ^{a,c
,,}

a. National Engineering Technology Research Center for Combined Vaccines, Wuhan Institute of Biological Products Co., Ltd, Wuhan, 430207, China;
b. National Institutes for Food and Drug Control, Beijing, 100050, China;
c. China National Biotec Group, Beijing, 100024, China

Corresponding author: Zhongyu Hu, huzhy@nifdc.org.cn
Xiaoming Yang, yangxiaoming@sinopharm.com
Received Date: 02 February 2023
Accepted Date: 09 November 2023
Available online: 14 November 2023

Abstract

The oral hexavalent live human-bovine reassortant rotavirus vaccine (RV6) developed by Wuhan Institute of Biological Products Co., Ltd (WIBP) has finished a randomized, placebo-controlled phase III clinical trial in four provinces of China in 2021. The trail demonstrated that RV6 has a high vaccine efficacy against the prevalent strains and is safe for use in infants. During the phase III clinical trial (2019–2021), 200 rotavirus-positive fecal samples from children with RV gastroenteritis (RVGE) were further studied. Using reverse transcription-polymerase chain reaction and high-throughput sequencing, VP7 and VP4 sequences were obtained and their genetic characteristics, as well as the differences in antigenic epitopes of VP7, were analyzed in detail. Seven rotavirus genotypes were identified. The predominant rotavirus genotype was G9P [8] (77.0%), followed by prevalent strains G8P [8] (8.0%), G3P [8] (3.5%), G3P [9] (1.5%), G1P [8] (1.0%), G2P [4] (1.0%), and G4P [6] (1.0%). The amino acid sequence identities of G1, G2, G3, G4, G8, and G9 genotypes of isolates compared to the vaccine strains were 98.8%, 98.2%–99.7%, 88.4%–99.4%, 98.2%, 94.2%–100%, and 93.9%–100%, respectively. Notably, the vaccine strains exhibited high similarity in amino acid sequence, with only minor differences in antigenic epitopes compared to the Chinese endemic strains. This supports the potential application of the vaccine in preventing diseases caused by rotaviruses.
- Rotavirus (RV)
- , Hexavalent rotavirus vaccine
- , Epidemiology
- , Sequence analysis

Electronic Supplementary Material

10.1016j.virs.2023.11.002-ESM1.zip
10.1016j.virs.2023.11.002-ESM2.docx
10.1016j.virs.2023.11.002-ESM3.xlsx

References
1. Aoki, S. T., Settembre, E. C., Trask, S. D., Greenberg, H. B., Harrison, S. C., Dormitzer, P. R. 2009. Structure of rotavirus outer-layer protein VP7 bound with a neutralizing Fab. Science 324:1444-7.
2. Bergman, H., Henschke, N., Hungerford, D., Pitan, F., Ndwandwe, D., Cunliffe, N., Soares-Weiser, K. 2021. Vaccines for preventing rotavirus diarrhoea: vaccines in use. Cochrane Database Syst Rev. 11:CD008521.
3. CHen, H., Li, Q., Duan, K., Shi, C., Zhang, D., Dong, B., Bai, X., Qiao, J., Xu, G., Yang, X., Gao, Z., Li, F., Lv, H., Zhou, H., Yan, T., Shi, H. 2021. Molecular epidemiological characteristics of rotavirus VP7 gene in Zhengding County of Hebei Province, Xiangtan County of Hunan Province and Yuhuan City of Zhejiang Province, China from 2016 to 2017. Chinese Journal of Biologicals. 34: 415-427, 431.
4. Chen, S., Zhou, Y., Chen, Y., Gu, J. 2018. Fastp: an ultra-fast all-in-one FASTQ preprocessor. Bioinformatics. 34: i884-i890
5. Danecek, P., Bonfield, J. K., Liddle, J., Marshall, J., Ohan, V., Pollard, M. O., Whitwham, A., Keane, T., Mccarthy, S. A., Davies, R. M., Li, H. 2021. Twelve years of SAMtools and BCFtools. Gigascience 10:giab008.
6. Desselberger, U. 2017. Differences of Rotavirus Vaccine Effectiveness by Country: Likely Causes and Contributing Factors. Pathogens. 6:65.
7. Doan, Y. H., Nakagomi, T., Cunliffe, N. A., Pandey, B. D., Sherchand, J. B., Nakagomi, O. 2011. The occurrence of amino acid substitutions D96N and S242N in VP7 of emergent G2P[4] rotaviruses in Nepal in 2004-2005: a global and evolutionary perspective. Arch Virol. 156:1969-78
8. Folorunso, O. S., Sebolai, O. M. 2020. Overview of the Development, Impacts, and Challenges of Live-Attenuated Oral Rotavirus Vaccines. Vaccines (Basel). 8:341
9. Geng, Q., Lai, S., Yu, J., Zhang, Z., Yang, W., Li, Z., Wu, J., Yang, W. 2016. Epidemiological characteristics of rotavirus caused diarrhea in children aged〈5 years in 26 provinces in China, 2011-2014. Disease Surveillance 31: 463-470
10. Gouvea, V., Brantly, M. 1995. Is Rotavirus a population of reassortants? Trends Microbiol. 3:159-62
11. Grant, L., Esona, M., Gentsch, J., Watt, J., Reid, R., Weatherholtz, R., Santosham, M., Parashar, U., O'brien, K. 2011. Detection of G3P[3] and G3P[9] rotavirus strains in American Indian children with evidence of gene reassortment between human and animal rotaviruses. J Med Virol 83:1288-99.
12. Hoshino, Y., Jones, R. W., Ross, J., Honma, S., Santos, N., Gentsch, J. R., Kapikian, A. Z. 2004. Rotavirus serotype G9 strains belonging to VP7 gene phylogenetic sequence lineage 1 may be more suitable for serotype G9 vaccine candidates than those belonging to lineage 2 or 3. J Virol. 78:7795-802
13. Jiao, Y., Han, T., Qi, X., Gao, Y., Zhao, J., Zhang, Y., Li, B., Zhang, Z., Du, J., Sun, L. 2023. Human rotavirus strains circulating among children in the capital of China (2018-2022)_ predominance of G9P[8] and emergence ofG8P[8]. Heliyon. 9:e18236
14. Kopylova, E., Noé, L., Touzet, H. 2012. SortMeRNA: fast and accurate filtering of ribosomal RNAs in metatranscriptomic data. Bioinformatics. 28:3211-7
15. Li, R. C., Huang, T., Li, Y., Luo, D., Tao, J., Fu, B., Si, G., Nong, Y., Mo, Z., Liao, X., Luan, I., Tang, H., Rathi, N., Karkada, N., Han, H. H. 2014. Human rotavirus vaccine (RIX4414) efficacy in the first two years of life: a randomized, placebo-controlled trial in China. Hum Vaccin Immunother. 10:11-8
16. Lu, Y., Xie, H., Wang, D., Lu, J. 2021. Nosocomial infection caused by a rare G8P[8] rotavirus subtype in a pediatric unit in Guangzhou, Southern China. Hum Vaccin Immunother. 17:3619-3622
17. Maes, P., Matthijnssens, J., Rahman, M., Van Ranst, M. 2009. RotaC: a web-based tool for the complete genome classification of group A rotaviruses. BMC Microbiol. 9:238
18. Mao, T., Wang, M., Wang, J., Ma, Y., Liu, X., Wang, M., Sun, X., Li, L., Li, H., Zhang, Q., Li, D., Duan, Z. 2022. Phylogenetic analysis of the viral proteins VP4/VP7 of circulating human rotavirus strains in China from 2016 to 2019 and comparison of their antigenic epitopes with those of vaccine strains. Front Cell Infect Microbio 12: 927490.
19. MIshra, N., Reslan, L., El-Husseini, M., Raoof, H., Finianos, M., Guo, C., Thakkar, R., Inati, A., Dbaibo, G., Lipkin, W. I., Zaraket, H. 2020. Full genome characterization of human G3P[6] and G3P[9] rotavirus strains in Lebanon. Infect Genet Evol. 78:104133
20. Mo, Z., Mo, Y., Li, M., Tao, J., Yang, X., Kong, J., Wei, D., Fu, B., Liao, X., Chu, J., Qiu, Y., Hille, D. A., Nelson, M., Kaplan, S. S. 2017. Efficacy and safety of a pentavalent live human-bovine reassortant rotavirus vaccine (RV5) in healthy Chinese infants: A randomized, double-blind, placebo-controlled trial. Vaccine. 5:5897-5904
21. Mwangi, P. N., Potgieter, R. L., Simwaka, J., Mpabalwani, E. M., Mwenda, J. M., Mogotsi, M. T., Magagula, N., Esona, M. D., Steele, A. D., Seheri, M. L., Nyaga, M. M. 2023. Genomic Analysis of G2P[4] Group A Rotaviruses in Zambia Reveals Positive Selection in Amino Acid Site 7 of Viral Protein 3. Viruses 15: 501
22. PArker, E. P., Ramani, S., Lopman, B. A., Church, J. A., Iturriza-Gómara, M., Prendergast, A. J., Grassly, N. C. 2018. Causes of impaired oral vaccine efficacy in developing countries. Future Microbiol. 3: 97-118
23. Prjibelski, A., Antipov, D., Meleshko, D., Lapidus, A., Korobeynikov, A. 2020. Using SPAdes De Novo Assembler. Curr Protoc Bioinformatics. 70: e102
24. Rasebotsa, S., Uwimana, J., Mogotsi, M. T., Rakau, K., Magagula, N. B., Seheri, M. L., Mwenda, J. M., Mphahlele, M. J., Sabiu, S., Mihigo, R., Mutesa, L., Nyaga, M. M. 2021. Whole-Genome Analyses Identifies Multiple Reassortant Rotavirus Strains in Rwanda Post-Vaccine Introduction. Viruses 13: 95
25. Ruiz-Palacios, G. M., Pérez-Schael, I., Velázquez, F. R., Abate, H., Breuer, T., Clemens, S. C., Cheuvart, B., Espinoza, F., Gillard, P., Innis, B. L., Cervantes, Y., Linhares, A. C., López, P., Macías-Parra, M., Ortega-Barría, E., Richardson, V., Rivera-Medina, D. M., Rivera, L., Salinas, B., Pavía-Ruz, N., Salmerón, J., Rüttimann, R., Tinoco, J. C., Rubio, P., Nuñez, E., Guerrero, M. L., Yarzábal, J. P., Damaso, S., Tornieporth, N., Sáez-Llorens, X., Vergara, R. F., Vesikari, T., Bouckenooghe, A., Clemens, R., De Vos, B., O'ryan, M. 2006. Safety and efficacy of an attenuated vaccine against severe rotavirus gastroenteritis. N Engl J Med. 354:11-22
26. Sanger, F., Nicklen, S., Coulson, A. R. 1977. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 74:5463-7
27. Soares-Weiser, K., Bergman, H., Henschke, N., Pitan, F., Cunliffe, N. 2019. Vaccines for preventing rotavirus diarrhoea: vaccines in use. Cochrane Database Syst Rev. 2019: CD008521
28. Tacharoenmuang, R., Komoto, S., Guntapong, R., Ide, T., Sinchai, P., Upachai, S., Yoshikawa, T., Tharmaphornpilas, P., Sangkitporn, S., Taniguchi, K. 2016. Full Genome Characterization of Novel DS-1-Like G8P[8] Rotavirus Strains that Have Emerged in Thailand: Reassortment of Bovine and Human Rotavirus Gene Segments in Emerging DS-1-Like Intergenogroup Reassortant Strains. PLoS One 11: e0165826
29. Theamboonlers, A., Maiklang, O., Thongmee, T., Chieochansin, T., Vuthitanachot, V., Poovorawan, Y. 2013. Complete genome analysis of a rare human G3P[9] rotavirus posing as an AU-1 like strain. Springerplus 2: 569
30. Vesikari, T., Clark, H. F., Offit, P. A., Dallas, M. J., Distefano, D. J., Goveia, M. G., Ward, R. L., Schödel, F., Karvonen, A., Drummond, J. E., Dinubile, M. J., Heaton, P. M. 2006. Effects of the potency and composition of the multivalent human-bovine (WC3) reassortant rotavirus vaccine on efficacy, safety and immunogenicity in healthy infants. Vaccine 24: 4821-9
31. Wang, S. J., Chen, L. N., Wang, S. M., Zhou, H. L., Qiu, C., Jiang, B., Qiu, T. Y., Chen, S. L., Von Seidlein, L., Wang, X. Y. 2022. Genetic characterization of two G8P[8] rotavirus strains isolated in Guangzhou, China, in 2020/21: evidence of genome reassortment. BMC Infect Dis. 22: 579
32. Wei, Y., Li, J., Peng, R., Wang, M., Sun, X., Zhang, Q., Wang, H., Fan, J., Li, D., Duan, Z. 2022. Epidemiological and clinical characteristics of hospitalized children with G9P[8] group A rotavirus diarrhea in China from 2011 to 2019. Disease Surveillance. 2022:1-7
33. WHO, 2013. Rotavirus vaccines WHO position paper: January 2013 - Recommendations. Vaccine. 31:6170-1
34. Wu, Z., Li, Q., Liu, Y., Lv, H., Mo, Z., Li, F., Yu, Q., Jin, F., Chen, W., Zhang, Y., Huang, T., Hu, X., Xia, W., Gao, J., Zhou, H., Bai, X., Liu, Y., Liang, Z., Jiang, Z., Chen, Y., Zhang, J., Du, J., Yang, B., Xing, B., Xing, Y., Dong, B., Yang, Q., Shi, C., Yan, T., Ruan, B., Shi, H., Fan, X., Feng, D., Lv, W., Zhang, D., Kong, X., Zhou, L., Que, D., Chen, H., Chen, Z., Guo, X., Zhou, W., Wu, C., Zhou, Q., Liu, Y., Qiao, J., Wang, Y., Li, X., Duan, K., Zhao, Y., Yang, X., Xu, G. 2022. Efficacy, safety and immunogenicity of hexavalent rotavirus vaccine in Chinese infants. Virol Sin. 37: 724-730
35. Wu, Z. W., Li, Q. L., Zhou, H. S., Duan, K., Gao, Z., Zhang, X. J., Jiang, Z. J., Hao, Z. Y., Jin, F., Bai, X., Li, Q., Xu, G. L., Zhao, Y. L., Yang, X. M. 2021. Safety and immunogenicity of a novel oral hexavalent rotavirus vaccine：a phase I clinical trial. Hum Vaccin Immunother. 17: 2311-2318
36. Xia, S., Du, J., Su, J., Liu, Y., Huang, L., Yu, Q., Xie, Z., Gao, J., Xu, B., Gao, X., Guo, T., Liu, Y., Zhou, X., Yang, H. 2020. Efficacy, immunogenicity and safety of a trivalent live human-lamb reassortant rotavirus vaccine (LLR3) in healthy Chinese infants: A randomized, double-blind, placebo-controlled trial. Vaccine 38: 7393-7400.
37. Zeller, M., Patton, J. T., Heylen, E., De Coster, S., Ciarlet, M., Van Ranst, M., Matthijnssens, J. 2012. Genetic analyses reveal differences in the VP7 and VP4 antigenic epitopes between human rotaviruses circulating in Belgium and rotaviruses in Rotarix and RotaTeq. J Clin Microbiol. 50:966-976
38. Zhang, T., Li, J., Jiang, Y. Z., Xu, J. Q., Guan, X. H., Wang, L. Q., Chen, J., Liang, Y. 2022. Genotype distribution and evolutionary analysis of rotavirus associated with acute diarrhea outpatients in Hubei, China, 2013-2016. Virol Sin. 37: 503-512.
39. Zhao, L., Shi, X., Meng, D., Guo, J., Li, Y., Liang, L., Guo, X., Tao, R., Zhang, X., Gao, R., Gao, L., Wang, J. 2021. Prevalence and genotype distribution of group A rotavirus circulating in Shanxi Province, China during 2015-2019. BMC Infect Dis. 21: 94
40. Zhou, X., Wang, Y., Chen, N., Pang, B., Liu, M., Cai, K., Kobayashi, N. 2023. Surveillance of Human Rotaviruses in Wuhan, China (2019-2022): Whole-Genome Analysis of Emerging DS-1-like G8P[8] Rotavirus. Int J Mol Sci. 24: 12189
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Genotype analysis of rotaviruses isolated from children during a phase III clinical trial with the hexavalent rotavirus vaccine in China

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Genotype analysis of rotaviruses isolated from children during a phase III clinical trial with the hexavalent rotavirus vaccine in China

Corresponding author: Zhongyu Hu, huzhy@nifdc.org.cn

Corresponding author: Xiaoming Yang, yangxiaoming@sinopharm.com

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