齐多夫定和单克隆抗体联合应用去除疫苗毒种中REV的污染
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摘要
禽网状内皮组织增生症病毒(REV)在禽弱毒疫苗中的污染被认为是REV感染的途径之一,去除疫苗毒种中REV的污染是生产合格疫苗的前提,此前我们研究证实了某IBDV疫苗毒种存在REV的污染,本研究试图通过核苷类逆转录酶抑制剂类药物齐多夫定(Azidothymidine,AZT)和针对REV的单克隆抗体(McAb)单独或联合应用来去除疫苗毒种中REV的污染。将污染REV的IBDV疫苗毒种接种DF-1细胞后,分别经5μg/mL的AZT,5%的McAb或两者联合应用干预后,毒种中污染的REV复制受到了明显的干扰,特别是经过AZT与McAb联合应用两次干预后,检测REV为完全阴性,毒种经检验合格。本研究通过AZT与McAb联合应用成功净化了IBDV疫苗毒种中REV的污染,为解决类似问题提供了新的思路。
The reticuloendotheliosis virus(REV)was contaminated in an attenuated vaccine by causing REV infection.Elimination of REV contamination from attenuated live vaccine strains is an important prerequisite for the qualified vaccines.quality.Studies had shown that REV contamination in vaccines against the infectious bursal disease virus(IBDV).We attempted to eliminate REV contamination in a live vaccine strain using the nucleoside reverse transcriptase inhibitor azidothymidine(AZT)and a monoclonal antibody against REV alone or in combination.The contaminated IBDV vaccine seed was inoculated into DF-1cells.Then,the replication of contaminated REV from the vaccine seed was investigated after intervention using AZT(5μg/mL)alone,a monoclonal antibody of the volume ratio of 5%alone,or their combination.After two interventions of combined application of AZT and monoclonal antibody,the S/P ratio for REV was negative and the IBDV vaccine showed good quality.This study indicated that elimination of REV contamination in an IBDV vaccine is possible through a combination of AZT and monoclonal antibody.
The reticuloendotheliosis virus(REV)was contaminated in an attenuated vaccine by causing REV infection.Elimination of REV contamination from attenuated live vaccine strains is an important prerequisite for the qualified vaccines.quality.Studies had shown that REV contamination in vaccines against the infectious bursal disease virus(IBDV).We attempted to eliminate REV contamination in a live vaccine strain using the nucleoside reverse transcriptase inhibitor azidothymidine(AZT)and a monoclonal antibody against REV alone or in combination.The contaminated IBDV vaccine seed was inoculated into DF-1cells.Then,the replication of contaminated REV from the vaccine seed was investigated after intervention using AZT(5μg/mL)alone,a monoclonal antibody of the volume ratio of 5%alone,or their combination.After two interventions of combined application of AZT and monoclonal antibody,the S/P ratio for REV was negative and the IBDV vaccine showed good quality.This study indicated that elimination of REV contamination in an IBDV vaccine is possible through a combination of AZT and monoclonal antibody.
引文
[1]Fadly A M,Witter R L,Smith E J,Silva R F,Reed W M,Hoerr F J,Putnam M R.An outbreak of lymphomas in commercial broiler breeder chickens vaccinated with a fowlpox vaccine contaminated with reticuloendotheliosis virus[J].Avian Pathol,1996,25(1):35-47.
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[3]Awad A M,El-Hamid H S A,Rawash A A A,Lbrahim H H.Detection of reticuloendotheliosis virus as a contaminant of fowl pox vaccines[J].Poultry Sci,2010,89(11):2389-2395.
[4]Wei K,Sun Z,Zhu S,Guo W,Sheng P,Wang Z,Zhao C,Zhao Q,Zhu R.Probable congenital transmission of reticuloendotheliosis virus caused by vaccination with contaminated vaccines[J/OL].PLoS One,2012,7(8):e43422.
[5]Liu Q,Zhao J,Su J,Pu J,Zhang G,Liu J.Full genome sequences of two reticuloendotheliosis viruses contaminating commercial vaccines[J].Avian Dis,53(3),341-346.
[6]Li J,Dong X,Yang C,Li Q,Cui Z,Chang S,Zhao P,Yu K,Yang H.Isolation,identification,and whole genome sequencing of reticuloendotheliosis virus from a vaccine against Marek’s disease[J].Poult Sci,2015,94(4):643-649.
[7]Akilimali P Z,Kashala-Abotnes E,Musumari P M,Kayembe P K,Tylleskar T,Mapatano M A.Predictors of Persistent Anaemia in the First Year of Antiretroviral Therapy:A Retrospective Cohort Study from Goma,the Democratic Republic of Congo[J/OL].PLoS One,2015,10(10):e0140240.
[8]Nsagha D S,Pokam B T,Assob J C,Njunda A L,Kibu O D,Tanue E A,Ayima C W,Weiedji P E.DOTS and renal disease of patients co-infected with HIV/AIDS and TB in the South West Region of Cameroon[J].BMC Public Health,2015,15:1040.doi:10.1186/s12889-015-2331-z.
[9]Okawa S,Chirwa M,Ishikawa N,Kapyata H,MsiskaC Y,Syakantu G,Miyano S,Komada K,Jimba M,Yasuoka J.Longitudinal adherence to antiretroviral drugs for preventing mother-to-child transmission of HIV in Zambia[J].BMC Pregnancy Childbirth,2015,15:258.doi:10.1186/s12884-015-0697-7.
[10]Sripan P,Le C S,Ingsrisawang L,Cressey T R,Bouazza N,Foissac F,Ngo-Giang-Huong N,Traisathit P,Srirompotong U,Ayudhaya O P,Puangsombat A,Jungpipun J,Jittayanun K,Tréluyer JM,Jourdain G,Lallemant M,Urien S.Contribution of different antiretroviral regimens containing zidovudine,lamivudine and ritonavir-boosted lopinavir on HIV viral load reduction during pregnancy[J].Antivir Ther,2016,21(5):435-440.
[11]Li Y,Cui S,Cui Z,Chang S,Zhao P.Genome analysis and pathogenicity of reticuloendotheliosis virus isolated from a contaminated vaccine seed against infectious bursal disease virus,first report in China[J].J Gen Virol,2016,97(11):2809-2815.
[12]李思菲,苏红芹,王一新,吕艳艳,赵颖洁,崔治中,常爽,赵鹏.拉米夫定对禽白血病病毒的体内外抑制效应及其应用[J].中国预防兽医学报,2016,38(9):700-704.LI Sifei,SU Hongqin,WANG Yixin,LV Yanyan,ZHAO Yingjie,CUI Zhizhong,CHANG Shuang,ZHAO Peng.Inhibition of avian leukosis virus by lamivudine in vitro and in vivo[J].Chinese J Pre Vet Med,2016,38(9):700-704.(in chinese).
[13]Cui Z Z,Lee L F,Smith E J,Witter R L,Chang T S.Monoclonal-antibody-mediated enzyme-linked immunosorbent assay for detection of reticuloendotheliosis viruses[J].Avian Dis,1988,32(1):32-40.
[14]Luan H,Wang Y,Li Y,Cui Z,Chang S,Zhao P.Development of a real-time quantitative RT-PCR to detect REV contamination in live vaccine[J].Poultry Sci,201695(9):2023-2029.
[2]Fadly A,Garcia M C.Detection of reticuloendotheliosis virus in live virus vaccines of poultry[J].Dev Biol,2006,126:301-305.
[3]Awad A M,El-Hamid H S A,Rawash A A A,Lbrahim H H.Detection of reticuloendotheliosis virus as a contaminant of fowl pox vaccines[J].Poultry Sci,2010,89(11):2389-2395.
[4]Wei K,Sun Z,Zhu S,Guo W,Sheng P,Wang Z,Zhao C,Zhao Q,Zhu R.Probable congenital transmission of reticuloendotheliosis virus caused by vaccination with contaminated vaccines[J/OL].PLoS One,2012,7(8):e43422.
[5]Liu Q,Zhao J,Su J,Pu J,Zhang G,Liu J.Full genome sequences of two reticuloendotheliosis viruses contaminating commercial vaccines[J].Avian Dis,53(3),341-346.
[6]Li J,Dong X,Yang C,Li Q,Cui Z,Chang S,Zhao P,Yu K,Yang H.Isolation,identification,and whole genome sequencing of reticuloendotheliosis virus from a vaccine against Marek’s disease[J].Poult Sci,2015,94(4):643-649.
[7]Akilimali P Z,Kashala-Abotnes E,Musumari P M,Kayembe P K,Tylleskar T,Mapatano M A.Predictors of Persistent Anaemia in the First Year of Antiretroviral Therapy:A Retrospective Cohort Study from Goma,the Democratic Republic of Congo[J/OL].PLoS One,2015,10(10):e0140240.
[8]Nsagha D S,Pokam B T,Assob J C,Njunda A L,Kibu O D,Tanue E A,Ayima C W,Weiedji P E.DOTS and renal disease of patients co-infected with HIV/AIDS and TB in the South West Region of Cameroon[J].BMC Public Health,2015,15:1040.doi:10.1186/s12889-015-2331-z.
[9]Okawa S,Chirwa M,Ishikawa N,Kapyata H,MsiskaC Y,Syakantu G,Miyano S,Komada K,Jimba M,Yasuoka J.Longitudinal adherence to antiretroviral drugs for preventing mother-to-child transmission of HIV in Zambia[J].BMC Pregnancy Childbirth,2015,15:258.doi:10.1186/s12884-015-0697-7.
[10]Sripan P,Le C S,Ingsrisawang L,Cressey T R,Bouazza N,Foissac F,Ngo-Giang-Huong N,Traisathit P,Srirompotong U,Ayudhaya O P,Puangsombat A,Jungpipun J,Jittayanun K,Tréluyer JM,Jourdain G,Lallemant M,Urien S.Contribution of different antiretroviral regimens containing zidovudine,lamivudine and ritonavir-boosted lopinavir on HIV viral load reduction during pregnancy[J].Antivir Ther,2016,21(5):435-440.
[11]Li Y,Cui S,Cui Z,Chang S,Zhao P.Genome analysis and pathogenicity of reticuloendotheliosis virus isolated from a contaminated vaccine seed against infectious bursal disease virus,first report in China[J].J Gen Virol,2016,97(11):2809-2815.
[12]李思菲,苏红芹,王一新,吕艳艳,赵颖洁,崔治中,常爽,赵鹏.拉米夫定对禽白血病病毒的体内外抑制效应及其应用[J].中国预防兽医学报,2016,38(9):700-704.LI Sifei,SU Hongqin,WANG Yixin,LV Yanyan,ZHAO Yingjie,CUI Zhizhong,CHANG Shuang,ZHAO Peng.Inhibition of avian leukosis virus by lamivudine in vitro and in vivo[J].Chinese J Pre Vet Med,2016,38(9):700-704.(in chinese).
[13]Cui Z Z,Lee L F,Smith E J,Witter R L,Chang T S.Monoclonal-antibody-mediated enzyme-linked immunosorbent assay for detection of reticuloendotheliosis viruses[J].Avian Dis,1988,32(1):32-40.
[14]Luan H,Wang Y,Li Y,Cui Z,Chang S,Zhao P.Development of a real-time quantitative RT-PCR to detect REV contamination in live vaccine[J].Poultry Sci,201695(9):2023-2029.