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口服脊髓灰质炎减毒活疫苗（Oral poliovirus vaccine,OPV）的大规模接种使全球脊髓灰质炎病例数急剧下降，但由于OPV的遗传不稳定性，复制过程中由于错误的累积且RNA聚合酶缺乏纠错功能，导致基因表达异常，基因组会发生点突变，一些突变可导致神经毒力回复，导致疫苗衍生脊髓灰质炎病毒（Vaccine-derived poliovirus,VDPV）的出现。其中免疫缺陷相关VDPV(Immunodeficiency-associated vaccine-derived poliovirus,iVDPV)是原发性免疫缺陷（Primary immunodeficiency disorders,PID）患者在接种OPV或与OPV接种者接触后，因宿主免疫功能异常而在体内长期复制导致的。突变与重组共同促成了病毒的进化，可导致抗原性改变与传播风险。iVDPV病例多来自于中等收入国家，男性及婴幼儿高发，58%伴瘫痪，且型别分布随疫苗策略调整呈2型减少、1型和3型上升趋势。防控策略包括强化急性弛缓性麻痹（Acute flaccid paralysis,AFP）监测与PID筛查、推广脊髓灰质炎灭活疫苗（Inactivated poliovirus vaccine,IPV）序贯接种及新型稳定疫苗应用、探索Pocapavir联合疗法等抗病毒干预。未来研究需聚焦病毒进化机制解析、全球监测网络协同及防控技术可及性提升，以助力全球脊髓灰质炎根除目标的最终实现。
Abstract：The large-scale vaccination with oral poliovirus vaccine(OPV) has led to a dramatic decline in the number of global polio cases. However, due to the genetic instability of OPV, the accumulation of errors in the replication process and the lack of proof-reading function of RNA polymerase, abnormal gene expression will occur in the genome. Some mutations can lead to neurovirulence reversion, resulting in the emergence of vaccine-derived polioviruses(VDPVs). Among them, immunodeficiency-associated VDPVs(iVDPVs) occur in patients with primary immunodeficiency(PID) who receive OPV or have close contact with vaccine recipients and experience long-term replication of the virus in their bodies due to abnormal host immune function. Mutations and recombination together promote viral evolution, which results in antigenic changes and transmission risks. Most iVDPV cases are reported in middle-income countries, with higher incidence in males and infants. 58% of these cases were accompanied by paralysis, and the viral type distribution showed a trend of decrease in type 2 and an increase in types 1 and 3 along with adjustments in vaccination strategies. Prevention and control strategies include strengthening surveillance for acute flaccid paralysis(AFP) and screening for PID, promoting sequential vaccination with inactivated poliovirus vaccine(IPV) and application of new stable vaccines, and exploring antiviral interventions such as Pocapavir combination therapy. Future research should focus on clarifying the mechanisms of viral evolution, coordinating global surveillance networks, and improving the accessibility of prevention and control technologies to help achieve the ultimate goal of global polio eradication.
[1]WHO. GPEI-wild poliovirus count[EB/OL].(2025-06-20)[2025-06-20]. https：//polioeradication. org/wildpoliovirus-count/.
[2]Macklin G, Diop OM, Humayun A, et al. Update on immunodeficiency-associated vaccine-derived polioviruses-worldwide, July 2018-December 2019[J]. MMWR Morb Mortal Wkly Rep, 2020, 69(28):913-917. DOI:10. 15585/mmwr. mm6928a4.
[3]Kishore N, Krow-Lucal E, Diop OM, et al.Surveillance to track progress toward polio eradicationworldwide, 2022-2023[J]. MMWR Morb Mortal Wkly Rep, 2024, 73(13):278-285. DOI:10. 15585/mmwr.mm7313a1.
[4]Xie H, Rhoden EE, Liu HM, et al. Antiviral development for the polio endgame:current progress and future directions[J]. Pathogens, 2024, 13(11):969. DOI:10. 3390/pathogens13110969.
[5]Burns CC, Diop OM, Sutter RW, et al. Vaccinederived polioviruses[J]. J Infect Dis, 2014, 210(suppl1):S283-S293. DOI:10. 1093/infdis/jiu295.
[6]Estivariz CF, Krow-Lucal ER, Mach O.Immunodeficiency-related vaccine-derived poliovirus(iVDPV)infections:a review of epidemiology and progress in detection and management[J]. Pathogens,2024, 13(12):1128. DOI:10. 3390/pathogens13121128.
[7]Minor PD. The molecular biology of poliovaccines[J].J Gen Virol, 1992, 73(Pt 12):3065-3077. DOI:10. 1099/0022-1317-73-12-3065.
[8]Troy SB, Musingwini G, Halpern MS, et al. Vaccine poliovirus shedding and immune response to oral polio vaccine in HIV-infected and-uninfected Zimbabwean infants[J]. J Infect Dis, 2013, 208(4):672-678. DOI:10. 1093/infdis/jit208.
[9]Kalkowska DA, Pallansch MA, Thompson KM.Updated modelling of the prevalence of immunodeficiency-associated long-term vaccine-derived poliovirus(iVDPV)excreters[J]. Epidemiol Infect,2019, 147:e295. DOI:10. 1017/S095026881900181X.
[10]Singanayagam A, Klapsa D, Burton-Fanning S, et al.Asymptomatic immunodeficiency-associated vaccinederived poliovirus infections in two UK children[J]. Nat Commun, 2023, 14(1):3413. DOI:10. 1038/s41467-023-39094-0.
[11]Guo J, Bolivar-Wagers S, Srinivas N, et al.Immunodeficiency-related vaccine-derived poliovirus(iVDPV)cases:a systematic review and implications for polio eradication[J]. Vaccine, 2015, 33(10):1235-1242. DOI:10. 1016/j. vaccine. 2015. 01. 018.
[12]Macklin G, Liao Y, Takane M, et al. Prolonged excretion of poliovirus among individuals with primary immunodeficiency disorder:an analysis of the World Health Organization registry[J]. Front Immunol, 2017,8:1103. DOI:10. 3389/fimmu. 2017. 01103.
[13]WHO. Standard operating procedures:responding to a poliovirus event or outbreak, version 4[M]. 1st ed.Geneva:WHO, 2022.
[14]McDonald SL, Weldon WC, Wei L, et al.Neutralization capacity of highly divergent type 2 vaccine-derived polioviruses from immunodeficient patients[J].Vaccine, 2020, 38(14):3042-3049. DOI:10. 1016/j.vaccine. 2020. 02. 035.
[15]Dunn G, Klapsa D, Wilton T, et al. Twenty-eight years of poliovirus replication in an immunodeficient individual:impact on the global polio eradication initiative[J]. PLoS Pathog, 2015, 11(8):e1005114.DOI:10. 1371/journal. ppat. 1005114.
[16]Avellón A, Cabrerizo M, de Miguel T, et al. Paralysis case and contact spread of recombinant vaccine-derived poliovirus, Spain[J]. Emerg Infect Dis, 2008, 14(11):1807-1809. DOI:10. 3201/eid1411. 080517.
[17]Mohanty MC, Govindaraj G, Ahmad M, et al.Immunodeficiency-related vaccine-derived poliovirus(iVDPV)excretion in an infant with severe combined immune deficiency with spillover to a parent[J].Vaccines, 2024, 12(7):759. DOI:10. 3390/vaccines12070759.
[18]Yao N, Liu Y, Zhang ZY, et al. Excretion and clearance of Sabin-like type 3 poliovirus in a child diagnosed with severe combined immunodeficiency[J].Hum Vaccines Immunother, 2025, 21(1):2484882.DOI:10. 1080/21645515. 2025. 2484882.
[19]Shaghaghi M, Irannejad M, Abolhassani H, et al.Clearing vaccine-derived poliovirus infection following hematopoietic stem cell transplantation:a case report and review of literature[J]. J Clin Immunol, 2018, 38(5):610-616. DOI:10. 1007/s10875-018-0521-z.
[20]Mohanty MC, Madkaikar MR, Desai M, et al. Natural clearance of prolonged VDPV infection in a child with primary immunodeficiency disorder[J]. Front Immunol,2019, 10:1567. DOI:10. 3389/fimmu. 2019. 01567.
[21]Jorba J, Campagnoli R, De L, et al. Calibration of multiple poliovirus molecular clocks covering an extended evolutionary range[J]. J Virol, 2008, 82(9):4429-4440. DOI:10. 1128/JVI. 02354-07.
[22]Kew O, Pallansch M. Breaking the last chains of poliovirus transmission:progress and challenges in global polio eradication[J]. Annu Rev Virol, 2018, 5(1):427-451. DOI:10. 1146/annurev-virology-101416-041749.
[23]蒋玉艳，黄林.疫苗衍生脊髓灰质炎病毒分子生物学研究进展[J].中国热带医学，2010, 10(8):1018-1020. DOI:10. 13604/j. cnki. 46-1064/r. 2010. 08. 017.
[24]Shaghaghi M, Soleyman-Jahi S, Abolhassani H, et al.New insights into physiopathology of immunodeficiencyassociated vaccine-derived poliovirus infection;systematic review of over 5 decades of data[J].Vaccine, 2018, 36(13):1711-1719. DOI:10. 1016/j.vaccine. 2018. 02. 059.
[25]张勇，严冬梅，王东艳，等.我国首例iVDPV病例Ⅱ型脊髓灰质炎病毒分离株的基因特征[J].病毒学报，2007, 23(3):188-194.DOI:10. 13242/j. cnki. bingduxuebao. 001809??.
[26]Guo Q, Zhu S, Wang D, et al. Genetic characterization and molecular evolution of type 3 vaccine-derived polioviruses from an immunodeficient patient in China[J]. Virus Res, 2023, 334:199177. DOI:10. 1016/j.virusres. 2023. 199177.
[27]Jegouic S, Joffret ML, Blanchard C, et al.Recombination between polioviruses and co-circulating Coxsackie A viruses:role in the emergence of pathogenic vaccine-derived polioviruses[J]. PLoS Pathog, 2009, 5(5):e1000412. DOI:10. 1371/journal. ppat. 1000412.
[28]Joffret ML, Jégouic S, Bessaud M, et al. Common and diverse features of cocirculating type 2 and 3 recombinant vaccine-derived polioviruses isolated from patients with poliomyelitis and healthy children[J]. J Infect Dis,2012, 205(9):1363-1373. DOI:10. 1093/infdis/jis204.
[29]Stern A, Yeh MT, Zinger T, et al. The evolutionary pathway to virulence of an RNA virus[J]. Cell, 2017,169(1):35-46. e19. DOI:10. 1016/j.cell. 2017. 03. 013.
[30]Shahmahmoodi S, Parvaneh N, Burns C, et al.Isolation of a type 3 vaccine-derived poliovirus(VDPV)from an Iranian child with X-linked agammaglobulinemia[J]. Virus Res, 2008, 137(1):168-172. DOI:10. 1016/j. virusres. 2008. 07. 006.
[31]Fan Q, Ma J, Li X, et al. Molecular evolution and antigenic drift of type 3 iVDPVs excreted from a patient with immunodeficiency in Ningxia, China[J]. J Med Virol, 2023, 95(1):e28215. DOI:10. 1002/jmv. 28215.
[32]Kitamura K, Shimizu H. The molecular evolution of type 2 vaccine-derived polioviruses in individuals with primary immunodeficiency diseases[J]. Viruses, 2021,13(7):1407. DOI:10. 3390/v13071407.
[33]Ren RB, Moss EG, Racaniello VR. Identification of two determinants that attenuate vaccine-related type 2poliovirus[J]. J Virol, 1991, 65(3):1377-1382. DOI:10. 1128/JVI. 65. 3. 1377-1382. 1991.
[34]Shulman LM, Manor Y, Handsher R, et al. Molecular and antigenic characterization of a highly evolved derivative of the type 2 oral poliovaccine strain isolated from sewage in Israel[J]. J Clin Microbiol, 2000, 38(10):3729-3734. DOI:10. 1128/JCM. 38. 10. 3729-3734. 2000.
[35]DeVries AS, Harper J, Murray A, et al. Vaccinederived poliomyelitis 12 years after infection in Minnesota[J]. N Engl J Med, 2011, 364(24):2316-2323. DOI:10. 1056/NEJMoa1008677.
[36]Martín J, Dunn G, Hull R, et al. Evolution of the Sabin strain of type 3 poliovirus in an immunodeficient patient during the entire 637-day period of virus excretion[J]. J Virol, 2000, 74(7):3001-3010. DOI:10. 1128/jvi. 74. 7. 3001-3010. 2000.
[37]Xiao T, Leng H, Zhang Q, et al. Isolation and characterization of a Sabin 3/Sabin 1 recombinant vaccine-derived poliovirus from a child with severe combined immunodeficiency[J]. Virus Res, 2022, 308:198633.DOI:10. 1016/j. virusres. 2021. 198633.
[38]汤晶晶，张杰，张筱碟，等. 2021年云南省环境污水中检出1株疫苗衍生脊髓灰质炎病毒[J].病毒学报，2022, 38(6):1289-1296. DOI:10. 13242/j. cnki.bingduxuebao. 004220.
[39]Zhang W, Yan D, Zeng H, et al. Genetic characterization of type 3 vaccine-derived poliovirus from a patient with hand, foot, and mouth disease in China[J]. Virol J, 2025, 22(1):208. DOI:10. 1186/s12985-025-02827-2.
[40]Yang CF, Chen HY, Jorba J, et al. Intratypic recombination among lineages of type 1 vaccine-derived poliovirus emerging during chronic infection of an immunodeficient patient[J]. J Virol, 2005, 79(20):12623-12634. DOI:10. 1128/JVI. 79. 20. 12623-12634. 2005.
[41]Shaw J, Jorba J, Zhao K, et al. Dynamics of evolution of poliovirus neutralizing antigenic sites and other capsid functional domains during a large and prolonged outbreak[J]. J Virol, 2018, 92(9):e01949-17. DOI:10. 1128/JVI. 01949-17.
[42]Yakovenko ML, Cherkasova EA, Rezapkin GV, et al.Antigenic evolution of vaccine-derived polioviruses:changes in individual epitopes and relative stability of the overall immunological properties[J]. J Virol, 2006, 80(6):2641-2653. DOI:10. 1128/JVI. 80. 6. 2641-2653. 2006.
[43]Mohanty MC, Desai M, Mohammad A, et al.Assessment of enterovirus excretion and identification of VDPVs in patients with primary immunodeficiency in India:outcome of ICMR-WHO collaborative study phase-I[J]. Vaccines, 2023, 11(7):1211. DOI:10. 3390/vaccines11071211.
[44]Kalkowska DA, Wassilak SGF, Pallansch MA, et al.Outbreak response strategies with type 2-containing oral poliovirus vaccines[J]. Vaccine, 2023, 41(Suppl 1):A142-A152. DOI:10. 1016/j. vaccine. 2022. 10. 060.
[45]郑凝旋，陈致飞，张苏晗，等.福建省脊髓灰质炎疫苗转换前后AFP病例病原学监测结果分析[J].病毒学报，2021, 37(4):872-878. DOI:10. 13242/j. cnki.bingduxuebao. 003941.
[46]Yao N, Liu Y, Xu JW, et al. Detection of a highly divergent type 3 vaccine-derived poliovirus in a child with a severe primary immunodeficiency disorderChongqing, China, 2022[J]. MMWR Morb Mortal Wkly Rep, 2022, 71(36):1148-1150. DOI:10. 15585/mmwr. mm7136a2.
[47]王萌萌，纪峰，刘尧，等. 2019—2024年山东省城市污水中脊髓灰质炎病毒基因特征分析[J].病毒学报，2025, 41(3):733-740. DOI:10. 13242/j. cnki.bingduxuebao. 250085.
[48]Fischer TK, Johannesen CK, Benschop KSM, et al.Poliovirus circulation in the WHO European region,2015-2022:a review of data from WHO’s three core poliovirus surveillance systems[J]. Lancet Reg Health Eur, 2024, 47:101104. DOI:10. 1016/j.lanepe. 2024. 101104.
[49]Shulman LM, Weil M, Somech R, et al.Underperformed and underreported testing for persistent oropharyngeal poliovirus infections in primary immune deficient patients-risk for reemergence of polioviruses[J]. J Pediatric Infect Dis Soc, 2021, 10(3):326-333.DOI:10. 1093/jpids/piaa053.
[50]Korotkova EA, Prostova MA, Gmyl AP, et al. Case of poliomyelitis caused by significantly diverged derivative of the poliovirus type 3 vaccine sabin strain circulating in the orphanage[J]. Viruses, 2020, 12(9):970. DOI:10. 3390/v12090970.
[51]Yeh MT, Bujaki E, Dolan PT, et al. Engineering the live-attenuated polio vaccine to prevent reversion to virulence[J]. Cell Host Microbe, 2020, 27(5):736-751. e8. DOI:10. 1016/j. chom. 2020. 04. 003.
[52]Bandyopadhyay AS, Zipursky S. A novel tool to eradicate an ancient scourge:the novel oral polio vaccine type 2 story[J]. Lancet Infect Dis, 2023, 23(2):e67-e71. DOI:10. 1016/S1473-3099(22)00582-5.
[53]Yeh MT, Smith M, Carlyle S, et al. Genetic stabilization of attenuated oral vaccines against poliovirus types 1 and 3[J]. Nature, 2023, 619(7968):135-142.DOI:10. 1038/s41586-023-06212-3.
[54]Global Commission for the Certification of Poliomyelitis Eradication. Summary report from the twenty-sixth meeting of the global commission for certification of poliomyelitis eradication. WHO/GPEI/POLIO/2024. 11[R]. Geneva:World Health Organization,2024.
[55]Ranchod H, Howard W, Roux A, et al. Stem cell transplant in immune-deficiency-associated vaccinederived poliovirus[J]. Open Forum Infect Dis, 2024, 11(2):ofad678. DOI:10. 1093/ofid/ofad678.
基本信息:
DOI：10.13242/j.cnki.bingduxuebao.250289
中图分类号:R373.22
引用信息:
[1]高尚,林婕,朱成林,等.免疫缺陷相关疫苗衍生脊髓灰质炎病毒（iVDPV）研究进展：从病毒进化到公共卫生应对[J].病毒学报,2026,42(02):611-619.DOI:10.13242/j.cnki.bingduxuebao.250289.
基金信息:
国家重点研发计划（项目号：2024YFC2310403）,题目：新型肠道病毒疫苗的临床前研究项目~~
2025-09-16
2025
2025-10-21
2026-03-26
2026
1
2025-12-19
2025-12-19
2025-12-19