Prevalence of neutralizing antibodies against liver-tropic adeno-associated virus serotype vectors in 100 healthy Chinese and its potential relation to body constitutions

doi:10.1016/S2095-4964(15)60200-X

Abstract

Recombinant adeno-associated virus (rAAV) serotype 2, 3 and 8 vectors are the most promising liver-tropic AAV serotype vectors. Liver diseases are significant problems in China. However, to date, few studies on AAV neutralizing antibodies (Nabs) were working with the Chinese population or with the rAAV3 vectors. The present study aimed to determine the prevalence of Nabs in Chinese population against wild-type AAV2, AAV3 and AAV8 capsids as well as additional two AAV3 variants. In addition, we performed a preliminary analysis to investigate the potential influence of traditional Chinese medicine body constitutions on AAV Nabs. Our work demonstrated that the majority of healthy Chinese subjects were positive for AAV Nabs, with the order of AAV2 > AAV3 = AAVLK03 > AAV8. There was no difference between: 1) AAV3 and its variants; 2) male and female subjects; and 3) different age cohorts (≤ 35, 36-50, and ≥ 51 years old). People in the Qi-deficiency constitution had significantly increased AAV8 Nabs than people in the Gentleness constitution. Our studies may have impact on the future clinical design of AAV-based gene therapy in the Chinese population.

Key words: Medicine, Chinese traditional, Recombinant adeno-associated virus vector, Neutralizing antibodies, Body constitutions

Chen Ling, Yuan Wang, Ying-lu Feng, Ya-ni Zhang, Jun Li, Xin-rui Hu, Li-na Wang, Mao-feng Zhong, Xiao-feng Zhai, Irene Zolotukhin, Arun SrivastavaChang-quan Ling. Prevalence of neutralizing antibodies against liver-tropic adeno-associated virus serotype vectors in 100 healthy Chinese and its potential relation to body constitutions. Journal of Integrative Medicine, 2015, 13(5): 341-346.

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URL: http://www.jcimjournal.com/EN/10.1016/S2095-4964(15)60200-X

http://www.jcimjournal.com/EN/Y2015/V13/I5/341

[1]	Mingozzi F, High KA . Therapeutic in vivo gene transfer for genetic disease using AAV: progress and challenges. Nat Rev Genet, 2011,12(5):341-355 doi: 10.1038/nrg2988 pmid: 21499295
[2]	Liu Y, Kim YJ, Ji M, Fang J, Siriwon N, Zhang LI, Wang P . Enhancing gene delivery of adeno-associated viruses by cell-permeable peptides. Mol Ther Methods Clin Dev, 2014, 1: 12 doi: 10.1038/mtm.2013.12 pmid: 26015948
[3]	Ponnazhagan S, Mukherjee P, Yoder MC, Wang XS, Zhou SZ, Kaplan J, Wadsworth S, Srivastava A . Adeno-associated virus 2-mediated gene transfer in vivo: organ-tropism and expression of transduced sequences in mice. Gene, 1997,190(1):203-210 doi: 10.1016/S0378-1119(96)00576-8
[4]	Snyder RO, Miao CH, Patijn GA, Spratt SK, Danos O, Nagy D, Gown AM, Winther B, Meuse L, Cohen LK, Thompson AR, Kay MA . Persistent and therapeutic concentrations of human factor IX in mice after hepatic gene transfer of recombinant AAV vectors. Nat Genet, 1997,16(3):270-276 doi: 10.1038/ng0797-270
[5]	Asokan A, Schaffer DV, Samulski RJ . The AAV vector toolkit: poised at the clinical crossroads. Mol Ther, 2012,20(4):699-708 doi: 10.1038/mt.2011.287 pmid: 22273577
[6]	Manno CS, Pierce GF, Arruda VR, Glader B, Ragni M, Rasko JJ, Ozelo MC, Hoots K, Blatt P, Konkle B, Dake M, Kaye R, Razavi M, Zajko A, Zehnder J, Rustagi PK, Nakai H, Chew A, Leonard D, Wright JF, Lessard RR, Sommer JM, Tigges M, Sabatino D, Luk A, Jiang H, Mingozzi F, Couto L, Ertl HC, High KA, Kay MA . Successful transduction of liver in hemophilia by AAV-factor IX and limitations imposed by the host immune response. Nat Med, 2006,12(3):342-347 doi: 10.1038/nm1358
[7]	Mingozzi F, Maus MV, Hui DJ, Sabatino DE, Murphy SL, Rasko JE, Ragni MV, Manno CS, Sommer J, Jiang H, Pierce GF, Ertl HC, High KA . CD8+ T-cell responses to adeno-associated virus capsid in humans. Nat Med, 2007,13(4):419-422 doi: 10.1038/nm1549 pmid: 17369837
[8]	Gao GP, Alvira MR, Wang L, Calcedo R, Johnston J, Wilson JM . Novel adeno-associated viruses from rhesus monkeys as vectors for human gene therapy. Proc Natl Acad Sci U S A, 2002,99(18):11854-11859 doi: 10.1073/pnas.182412299
[9]	Nakai H, Fuess S, Storm TA, Muramatsu S, Nara Y, Kay MA . Unrestricted hepatocyte transduction with adeno-associated virus serotype 8 vectors in mice. J Virol, 2005,79(1):214-224 doi: 10.1128/JVI.79.1.214-224.2005
[10]	Nathwani AC, Tuddenham EG, Rangarajan S, Rosales C, McIntosh J, Linch DC, Chowdary P, Riddell A, Pie AJ, Harrington C, O’Beirne J, Smith K, Pasi J, Glader B, Rustagi P, Ng CY, Kay MA, Zhou J, Spence Y, Morton CL, Allay J, Coleman J, Sleep S, Cunningham JM, Srivastava D, Basner-Tschakarjan E, Mingozzi F, High KA, Gray JT, Reiss UM, Nienhuis AW, Davidoff AM . Adenovirus-associated virus vector-mediated gene transfer in hemophilia B. N Engl J Med, 2011,365(25):2357-2365 doi: 10.1056/NEJMoa1108046 pmid: 3265081
[11]	Nathwani AC, Reiss UM, Tuddenham EG, Rosales C, Chowdary P, McIntosh J, Della Peruta M, Lheriteau E, Patel N, Raj D, Riddell A, Pie J, Rangarajan S, Bevan D, Recht M, Shen YM, Halka KG, Basner-Tschakarjan E, Mingozzi F, High KA, Allay J, Kay MA, Ng CY, Zhou J, Cancio M, Morton CL, Gray JT, Srivastava D, Nienhuis AW, Davidoff AM . Long-term safety and efficacy of factor IX gene therapy in hemophilia B. N Engl J Med, 2014,371(21):1994-2004 doi: 10.1056/NEJMoa1407309 pmid: 4278802
[12]	Blacklow NR, Hoggan MD, Rowe WP . Isolation of adenovirus-associated viruses from man. Proc Natl Acad Sci U S A, 1967,58(4):1410-1415 doi: 10.1073/pnas.58.4.1410 pmid: 4295829
[13]	Zincarelli C, Soltys S, Rengo G, Rabinowitz JE . Analysis of AAV serotypes 1-9 mediated gene expression and tropism in mice after systemic injection. Mol Ther, 2008,16(6):1073-1080 doi: 10.1038/mt.2008.76
[14]	Ling C, Lu Y, Kalsi JK, Jayandharan GR, Li B, Ma W, Cheng B, Gee SW, McGoogan KE, Govindasamy L, Zhong L, Agbandje-McKenna M, Srivastava A . Human hepatocyte growth factor receptor is a cellular coreceptor for adeno-associated virus serotype 3. Hum Gene Ther, 2010,21(12):1741-1747 doi: 10.1089/hum.2010.075
[15]	Cheng B, Ling C, Dai Y, Lu Y, Glushakova LG, Gee SW, McGoogan KE, Aslanidi GV, Park M, Stacpoole PW, Siemann D, Liu C, Srivastava A . Development of optimized AAV3 serotype vectors: mechanism of high-efficiency transduction of human liver cancer cells. Gene Ther, 2012,19(4):375-384 doi: 10.1038/gt.2011.105
[16]	Ling C, Wang Y, Zhang Y, Ejjigani A, Yin Z, Lu Y, Wang L, Wang M, Li J, Hu Z, Aslanidi GV, Zhong L, Gao G, Srivastava A . Selective in vivo targeting of human liver tumors by optimized AAV3 vectors in a murine xenograft model. Hum Gene Ther, 2014,25(12):1023-1034 doi: 10.1089/hum.2014.099
[17]	Lisowski L, Dane AP, Chu K, Zhang Y, Cunningham SC, Wilson EM, Nygaard S, Grompe M, Alexander IE, Kay MA . Selection and evaluation of clinically relevant AAV variants in a xenograft liver model. Nature, 2014,506(7488):382-386 doi: 10.1038/nature12875 pmid: 24390344
[18]	Masat E, Pavani G, Mingozzi F . Humoral immunity to AAV vectors in gene therapy: challenges and potential solutions. Discov Med, 2013,15(85):379-389 doi: 10.1590/1414-431X20131662 pmid: 23819952
[19]	Calcedo R, Wilson JM . Humoral immune response to AAV. Front Immunol, 2013,4: 341
[20]	Liu Q, Huang W, Zhao C, Zhang L, Meng S, Gao D, Wang Y . The prevalence of neutralizing antibodies against AAV serotype 1 in healthy subjects in China: implications for gene therapy and vaccines using AAV1 vector. J Med Virol, 2013,85(9):1550-1556 doi: 10.1002/jmv.v85.9
[21]	Liu Q, Huang W, Zhang H, Wang Y, Zhao J, Song A, Xie H, Zhao C, Gao D . Neutralizing antibodies against AAV2, AAV5 and AAV8 in healthy and HIV-1-infected subjects in China: implications for gene therapy using AAV vectors. Gene Ther, 2014,21(8):732-738 doi: 10.1038/gt.2014.47
[22]	van der Marel S, Comijn EM, Verspaget HW, van Deventer S, van den Brink GR, Petry H, Hommes DW, Ferreira V . Neutralizing antibodies against adeno-associated viruses in inflammatory bowel disease patients: implications for gene therapy. Inflamm Bowel Dis, 2011,17(12):2436-2442 doi: 10.1002/ibd.21673
[23]	Parks WP, Boucher DW, Melnick JL, Taber LH, Yow MD . Seroepidemiological and ecological studies of the adenovirus-associated satellite viruses. Infect Immun, 1970,2(6):716-722 pmid: 16557905
[24]	Mayor HD, Drake S, Stahmann J, Mumford DM . Antibodies to adeno-associated satellite virus and herpes simplex in sera from cancer patients and normal adults. Am J Obstet Gynecol, 1976,126(1):100-104 doi: 10.1016/0002-9378(76)90472-5
[25]	Calcedo R, Vandenberghe LH, Gao G, Lin J, Wilson JM . Worldwide epidemiology of neutralizing antibodies to adeno-associated viruses. J Infect Dis, 2009,199(3):381-390 doi: 10.1086/595830 pmid: 19133809
[26]	Qu Y, Nie X, Yang Z, Yin H, Pang Y, Dong P, Zhan S . The prevalence of hemophilia in mainland China: a systematic review and meta-analysis. Southeast Asian J Trop Med Public Health, 2014,45(2):455-466 doi: 10.1016/j.socscimed.2013.11.018 pmid: 24968688
[27]	Zhao CQ, Zhou Y, Ping J, Xu LM . Traditional Chinese medicine for treatment of liver diseases: progress, challenges and opportunities. J Integr Med, 2014,12(5):401-408 doi: 10.1016/S2095-4964(14)60039-X
[28]	Wang LN, Wang Y, Lu Y, Yin ZF, Zhang YH, Aslanidi GV, Srivastava A, Ling CQ, Ling C . Pristimerin enhances recombinant adeno-associated virus vector-mediated transgene expression in human cell lines in vitro and murine hepatocytes in vivo. J Integr Med, 2014,12(1):20-34 doi: 10.1016/S2095-4964(14)60003-0
[29]	Wang Q, Zhu YB . Epidemiological investigation of constitutional types of Chinese medicine in general population: Base on 21,948 epidemiological investigation data of nine provinces in China. Zhonghua Zhong Yi Yao Za Zhi, 2009,24(1):7-12
[30]	Meliani A, Leborgne C, Triffault S, Jeanson-Leh L, Veron P, Mingozzi F . Determination of anti-adeno-associated virus vector neutralizing antibody titer with an in vitro reporter system. Hum Gene Ther Methods, 2015,26(2):45-53 doi: 10.1089/hgtb.2015.037
[31]	Wang M, Crosby A, Hastie E, Samulski JJ, McPhee S, Joshua G, Samulski RJ, Li C . Prediction of adeno-associated virus neutralizing antibody activity for clinical application. Gene Ther. 2015 Jun 30. doi: 10.1038/gt.2015.69.[Epub ahead of print]. doi: 10.1038/gt.2015.69 pmid: 26125606
[32]	Mimuro J, Mizukami H, Shima M, Matsushita T, Taki M, Muto S, Higasa S, Sakai M, Ohmori T, Madoiwa S, Ozawa K, Sakata Y . The prevalence of neutralizing antibodies against adeno-associated virus capsids is reduced in young Japanese individuals. J Med Virol, 2014,86(11):1990-1997 doi: 10.1002/jmv.v86.11
[33]	Yao SL, Zhang ZZ, Yang XS, Xu X, Cao J, Xie GY, Zhang Q . Analysis of composite traditional Chinese medicine constitution: an investigation of 974 volunteers. J Chin Integr Med, 2012,10(5):508-515 doi: 10.3736/jcim20120505
[34]	Zhu YB, Wang Q, Wu CY, Pang GM, Zhao JX, Shen SL, Xia ZY, Yan X . Logistic regression analysis on relationships between traditional Chinese medicine constitutional types and overweight or obesity. J Chin Integr Med, 2010,8(11):1023-1028 doi: 10.3736/jcim201011
[35]	Zhu YB, Wang Q, Chen KF, Wu YE, Hong WL, Liu L . Stratified analysis of the relationship between traditional Chinese medicine constitutional types and health status in the general population based on data of 8 448 cases. J Chin Integr Med, 2011,9(4):382-389 doi: 10.3736/jcim201104

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