| 95 | 0 | 288 |
| 下载次数 | 被引频次 | 阅读次数 |
埃可病毒11型（Echovirus 11,E11）是一种常被检出的肠道病毒，近年来在亚洲与欧洲地区多次报道由E11引发新生儿重症病例甚至导致死亡。自1994年E11在我国被首次检出后，其基因型历经多次更替。为探究基因型更替与型间交叉中和能力是否存在相关性，本研究选取了曾经在中国流行的A1、A2、C1、C3、D5以及E基因型的代表性毒株，依次进行噬斑试验、浓缩、纯化和灭活，随后与铝佐剂混合，于第0周、第2周、第4周，分三次对6周龄雌性BALB/c小鼠进行免疫。在末次免疫1周后，采集小鼠抗血清进行交叉中和效果评估。中和实验结果表明，不同基因型间的交叉中和能力存在显著差异。部分毒株能够突破前代毒株所形成的免疫保护屏障，这一现象与E11流行基因型转换的规律相契合。其中，D5基因型毒株展现出较高的免疫原性以及较为广谱的交叉保护特性，具备作为理想疫苗候选株的特征。同时，当前流行的D5基因型毒株抗血清对C1和C3基因型毒株提供的交叉保护作用有限，提示未来有可能出现新的基因型更替。此外，通过序列分析发现，VP1-BC loop和VP2-EF loop区域的差异可能对E11毒株的抗原性产生影响，进一步揭示了E11免疫逃逸的潜在机制。本研究系统地探讨了E11的交叉免疫效应及其对基因型更替的影响，为制订E11感染的防控策略和开展疫苗研发提供了重要的参考依据。
Abstract：Echovirus 11(E11) is a frequently detected enterovirus. In recent years, that has been increasingly reported to, sometimes leading to death, in Asia and Europe. Since E11 was first detected in China in 1994, its genotype has undergone multiple replacements. To investigate whether there is a correlation between genotype replacements and cross-neutralization ability, representative strains of six E11 genotypes(A1, A2, C1, C3, D5, and E) that have circulated in China were selected. These strains were subjected to plaque assay, concentration, purification, and inactivation, and then mixed with aluminum adjuvant. Six-week-old female BALB/c mice were immunized three times at week 0, week 2, and week 4. One week after the final immunization, mouse antisera were collected for evaluation of the cross-neutralization effect. The results of neutralization assays indicated significant differences in cross-immunity between different genotypes. Some strains were able to break through the immune protection barrier formed by previous strains, which aligns with the patterns of E11 genotype replacement observed in the epidemic. Among the strains, the D5 genotype strains exhibited high immunogenicity and relatively broad cross-spectrum cross protection, making it a promising candidate for vaccine development. However, the current D5 genotype antiserum provided limited cross-protection against the C1 and C3 genotype strains, suggesting the possibility of new genotype replacements in the future. In addition, sequence analysis revealed that the variations in the VP1-BC loop and VP2-EF loop regions could potentially influence the antigenicity of E11 strains, offering further insight into the mechanisms of immune evasion by E11. This study systematically explored the cross-immune effect of E11 and their impact on genotype replacement, providing important reference points for the development of prevention and control strategies for E11 infections, as well as for vaccine research and development.
[1] Dahllund L, Nissinen L, Pulli T, et al. The genome of echovirus 11[J]. Virus Res, 1995, 35(2):215-222.DOI:10. 1016/0168-1702(94)00104-K.
[2]陈前进，曹春远，张彦锋，等.病毒性脑炎病例中埃可病毒11型病毒的基因特征分析[J].病毒学报，2015,31(1):36-41. DOI:10. 13242/j. cnki.bingduxuebao. 002623.
[3] Morens DM. Enteroviral disease in early infancy[J]. J Pediatr, 1978, 92(3):374-377. DOI:10. 1016/s0022-3476(78)80422-3.
[4] Liu Y, Li J, Zhang Y. Update on enteroviral protease2A:structure, function, and host factor interaction[J].Biosaf Health, 2023, 5(6):331-338. DOI:10. 1016/j.bsheal. 2023. 09. 001.
[5] Li J, Yan D, Chen L, et al. Multiple genotypes of echovirus 11 circulated in China's mainland between 1994and 2017[J]. Sci Rep, 2019, 9(1):10583. DOI:10. 1038/s41598-019-46870-w.
[6]周晓芳，寸建萍，姜黎黎，等.云南省4株埃可病毒11型VP1基因特征分析[J].病毒学报，2021, 37(1):140-145.
[7] Fernandez-Garcia MD, Garcia-Iba?ez N, Camacho J, et al. Enhanced echovirus 11 genomic surveillance in neonatal infections in Spain following a European alert reveals new recombinant forms linked to severe cases,2019 to 2023[J]. Euro Surveill, 2024, 29(44):2400221.DOI:10. 2807/1560-7917.ES. 2024. 29. 44. 2400221.
[8] Grapin M, Mirand A, Pinquier D, et al. Severe and fatal neonatal infections linked to a new variant of echovirus 11, France, July 2022 to April 2023[J]. Euro Surveill, 2023, 28(22):2300253. DOI:10. 2807/1560-7917. ES. 2023. 28. 22. 2300253.
[9] Ikuse T, Matsui T, Shoji K, et al. Neonatal acute liver failure cases with echovirus 11 infections, Japan,August to November 2024[J]. Euro Surveill, 2025, 30(1):2400822. DOI:10. 2807/1560-7917.ES. 2025. 30. 1. 2400822.
[10]Piralla A, Borghesi A, Di Comite A, et al. Fulminant echovirus 11 hepatitis in male non-identical twins in northern Italy, April 2023[J]. Euro Surveill, 2023, 28(24):2300289. DOI:10. 2807/1560-7917.ES. 2023. 28. 24. 2300289.
[11]黄淑芬，张薇，陈美钟，等.广州市生活污水中埃可病毒11型循环动态变化及基因特征分析[J].病毒学报，2022, 38(5):1108-1116. DOI:10. 13242/j. cnki.bingduxuebao. 004198.
[12]Liu Y, Sun Q, Xiao J, et al. Genetic variation and evolutionary characteristics of echovirus 11:new variant within genotype D5 associated with neonatal death found in China[J]. Emerg Microbes Infect, 2024, 13(1):2361814. DOI:10. 1080/22221751. 2024. 2361814.
[13]Dai W, Li X, Liu Z, et al. Identification of four neutralizing antigenic sites on the enterovirus D68 capsid[J]. J Virol, 2023, 97(12):e0160023. DOI:10. 1128/jvi. 01600-23.
[14]Tan XH, Chong WL, Lee VS, et al. Substitution of coxsackievirus A16 VP1 BC and EF loop altered the protective immune responses in Chimera enterovirus A71[J]. Vaccines(Basel), 2023, 11(8):1363. DOI:10. 3390/vaccines11081363.
[15]Kumar S, Stecher G, Tamura K. MEGA7:molecular evolutionary genetics analysis version 7. 0 for bigger datasets[J]. Mol Biol Evol, 2016, 33(7):1870-1874.DOI:10. 1093/molbev/msw054.
[16]Han Z, Song Y, Xiao J, et al. Genomic epidemiology of coxsackievirus A16 in mainland of China, 2000-18[J]. Virus Evol, 2020, 6(2):veaa084. DOI:10. 1093/ve/veaa084.
[17]红梅，刘莹，顿珠多吉，等. 2020年西藏自治区0~5岁健康儿童携带埃可病毒11型的基因特征分析[J].国际病毒学杂志，2023, 30(3):187-191. DOI:10. 3760/cma. j. issn. 1673-4092. 2023. 03. 003.
[18]孙强，刘莹，唐海淑，等.肠道病毒C组96型（EVC96）新疆株的全基因组序列分析[J].病毒学报，2022, 38(2):332-340. DOI:10. 13242/j. cnki.bingduxuebao. 004084.
[19]Catching A, Yeh MT, Bianco S, et al. A tradeoff between enterovirus A71 particle stability and cell entry[J]. Nat Commun, 2023, 14(1):7450. DOI:10. 1038/s41467-023-43029-0.
[20]Lu H, Xiao J, Song J, et al. The immunogenicity of coxsackievirus A6(D3a sub-genotype)virus-like particle and mRNA vaccines[J]. J Med Virol, 2025, 97(2):e70201. DOI:10. 1002/jmv. 70201.
[21]毛群颖，高帆，胡亚林，等.上市后肠道病毒71型灭活疫苗的动物保护效果研究[J].中国病毒病杂志，2018, 8(6):463-468. DOI:10. 16505/j. 2095-0136. 2018. 0101.
[22]Smith DJ, Lapedes AS, de Jong JC, et al. Mapping the antigenic and genetic evolution of influenza virus[J].Science, 2004, 305(5682):371-376. DOI:10. 1126/science. 1097211.
[23]Wang P, Nair MS, Liu L, et al. Antibody resistance of SARS-CoV-2 variants B. 1. 351 and B. 1. 1. 7[J].bioRxiv, 2021:2021. 01. 25. 428137. DOI:10. 1101/2021. 01. 25. 428137.
[24]Morosky S, Wells AI, Lemon K, et al. The neonatal Fc receptor is a pan-echovirus receptor[J]. Proc Natl Acad Sci USA, 2019, 116(9):3758-3763. DOI:10. 1073/pnas. 1817341116.
[25]Chen X, Qu X, Liu C, et al. Human FcRn is a two-inone attachment-uncoating receptor for echovirus 18[J].mBio, 2022, 13(4):e0116622. DOI:10. 1128/mbio. 01166-22.
[26]Wang K, Zhu L, Sun Y, et al. Structures of Echovirus30 in complex with its receptors inform a rational prediction for enterovirus receptor usage[J]. Nat Commun, 2020, 11(1):4421. DOI:10. 1038/s41467-020-18251-9.
[27]Zhang C, Xu C, Dai W, et al. Functional and structural characterization of a two-MAb cocktail for delayed treatment of enterovirus D68 infections[J]. Nat Commun, 2021, 12(1):2904. DOI:10. 1038/s41467-021-23199-5.
[28]Zeng H, Yi L, Chen X, et al. Emergence of a non vaccine-cognate enterovirus A71 genotype C1 in China's mainland[J]. J Infect, 2021, 82(3):407-413.DOI:10. 1016/j. jinf. 2020. 12. 020.
[29]Gao F, Liu P, Huo Y, et al. A screening study on the detection strain of Coxsackievirus A6:the key to evaluating neutralizing antibodies in vaccines[J]. Emerg Microbes Infect, 2024, 13(1):2322671. DOI:10. 1080/22221751. 2024. 2322671.
[30]Warner NL, Archer J, Park S, et al. A self-amplifying RNA vaccine prevents enterovirus D68 infection and disease in preclinical models[J]. Sci Transl Med, 2024,16(759):eadi1625. DOI:10. 1126/scitranslmed.adi1625.
基本信息:
DOI：10.13242/j.cnki.bingduxuebao.250051
中图分类号:R373.2
引用信息:
[1]刘莹,李冀琛,王蕊等.埃可病毒11型不同基因型间交叉中和效应及抗原性变异的初步研究[J].病毒学报,2025,41(02):291-300.DOI:10.13242/j.cnki.bingduxuebao.250051.
基金信息:
国家重点研究计划（项目号：2024YFC2310403）,题目：新型肠道病毒疫苗的临床前研究; 北京市自然科学基金：（项目号：L234052）,题目：我国手足口病病原谱及重要肠道病毒变异变迁规律~~