Research Progress on DNA Immunization Technology in the Development of Monoclonal Antibodies

doi:10.13560/j.cnki.biotech.bull.1985.2018-0643

Abstract

Abstract: DNA immunization refers to a series of immune response processes in which the recombinant expression vector encoding a specific antigen is transferred into animal bodies,and the specific gene sequence is expressed in the animal cells and then induces to produce its specific antibody. At present,DNA immunization has become the main technical means for the research and development of various protective and diagnostic monoclonal antibodies,especially for those antigen that are difficult to express and purify in vitro. DNA immunization is superior to traditional protein immunization. DNA immunization expresses antigen in host cells and its presented manner is similar to viral infection,which can produce both humoral and cellular immunity,thereby overcoming the shortcomings of traditional protein immunization and providing an ideal technology platform for preparing high quality monoclonal antibodies. However,many challenges have been encountered in practical applications of this technique;especially the traditional intramuscular injection method is used to immunize a single plasmid DNA,which results in low delivery efficiency and antibody expression level,then leading to the low immunogenicity of DNA immunization. This article reviews the application of DNA immunoassay in the development of monoclonal antibodies,and to further discusses the DNA immunization technology in terms of its concepts,induction mechanism,vector construction,delivery methods,effects of different immunological adjuvants and its advantages and development prospects. Our aim is to provide an effective theoretical knowledge in the application of DNA immunization technology in preparing high quality monoclonal antibodies and improving its immune efficiency.

Key words: monoclonal antibody, DNA immunization, protein immunization

NUERTURE Yeernazhaer, QIU Li-fen, ZHANG Fu-chun, ZHANG Mao-xiang. Research Progress on DNA Immunization Technology in the Development of Monoclonal Antibodies[J]. Biotechnology Bulletin, 2019, 35(2): 204-211.

References

[1] Köhler G, Milstein C.Continuous cultures of fused cells secreting antibody of predefined specificity[J]. Journal of Immunology, 2005, 174(5):2453-2455.
[2] Ulmer JB, Donnelly JJ, Parker SE, et al.Heterologous protection against influenza by injection of DNA encoding a viral protein[J]. Science, 1993, 259(5102):1745-1749.
[3] Fynan EF, Webster RG, et al.DNA vaccines:protective immuniza-tions by parenteral, mucosal, and gene-gun inoculations[J]. Proc Natl Acad Sci USA, 1993, 90(24):11478-11482.
[4] Wang B, Ugen KE, Srikantan V, et al.Gene inoculation generates immune responses against human immunodeficiency virus type 1[J]. Proc Natl Acad Sci USA, 1993, 90(9):4156-4160.
[5] Wolff JA, Malone RW, et al.Direct gene transfer into mouse muscle in vivo[J]. Science, 1990, 247(4949):1465-1468.
[6] 刘淑颖, 陈雨欣, 等. DNA免疫技术在高质量单克隆抗体诱导开发中的应用进展[J]. 药学进展, 2017(9):662-669.
[7] 张钰, 李轶杰, 张富春. DNA疫苗免疫机制及构建优化载体的研究[J]. 生物技术通报, 2007(4):5-9.
[8] 翟永贞. 乙型脑炎DNA疫苗与ICAM-1编码基因重组子联合免疫BALB/c鼠所致细胞免疫功能的研究[D]. 沈阳:中国医科大学, 2010.
[9] 高义. DNA免疫法制备抗小鼠TIGIT多克隆抗体及其功能鉴定[D]. 武汉:华中科技大学, 2013.
[10] Costagliola S, Rodien P, Many MC, et al.Genetic immunization against the human thyrotropin receptor causes thyroiditis and allows production of monoclonal antibodies recognizing the native receptor[J]. J Immunol, 1998, 160(3):1458-1465.
[11] Costagliola S, Franssen JD, Bonomi M, et al.Generation of a mouse monoclonal TSH receptor antibody with stimulating activity[J]. Biochem Biophys Res Commun, 2002, 299(5):891-896.
[12] Nagata S, Salvatore G, Pastan I.DNA immunization followed by a single boost with cells:a protein-free immunization protocol for production of monoclonal antibodies against the native form of membrane proteins[J]. J Immunol Methods, 2003, 280(1/2):59-72.
[13] Carson SD, Switzer BL, Tracy SM, et al.Monoclonal antibody against mouse CAR following genetic immunization[J]. Hybrid Hybridomics, 2004, 23(1):19-22.
[14] Costagliola S, Bonomi M, Morgenthaler NG, et al.Delineation of the discontinuous-conformational epitope of a monoclonal antibody displaying full in vitro and in vivo thyrotropin activity[J]. MolEndocrinol, 2004, 18(12):3020-3034.
[15] Pupa SM, Forti S, Invernizzi AM, et al.Monoclonal antibody to fibulin-1 generated by genetic immunization[J]. J Cell Biochem, 2003, 89:647-652.
[16] Leinonen J, Niemela P, et al.Characterization of monoclonal antibodies against prostate specific antigen produced by genetic immunization[J]. J Immunol Methods, 2004;289:157-167.
[17] Bian C, Zhang F, Wang F, et al.Development of retinol-binding protein 4 immuno-colloidal gold fast test strip using high-sensitivity monoclonal antibodies generated by DNA immunization[J]. Acta Biochim Biophys Sin(Shanghai), 2010, 42:847-853.
[18] Garcia JF, Maestre L, Lucas E, et al.Genetic immunization:a new monoclonal antibody for the detection of BCL-6 protein in paraffin sections[J]. J Histochem Cytochem, 2006, 54:31-38.
[19] Maestre L, Fontan L, Martinez-Climent JA, et al.Generation of a new monoclonal antibody against MALT1 by genetic immunization[J]. Hybridoma(Larchmt), 2007, 26:86-91.
[20] Bates MK, Zhang G, Sebestyen MG, et al.Genetic immunization for antibody generation in research animals by intravenous delivery of plasmid DNA[J]. Biotechniques, 2006, 40(2):199-208.
[21] Daftarian P, Chowdhury R, Ames P, et al.In vivo electroporation and non-protein based screening assays to identify antibodies against native protein conformations[J]. Hybridoma(Larchmt), 2011, 30(5):409-418.
[22] Chen Y, Zhang T, Li T, et al.Preparation and characterization of a monoclonal antibody against CKLF1 using DNA immunization with in vivo electroporation[J]. Hybridoma(Larchmt), 2005, 24(6):305-308.
[23] Kilpatrick KE, Cutler T, Whitehorn E, et al.Gene gun delivered DNA -based immunizations mediate rapid production of murine monoclonal antibodies to the Flt-3 receptor[J]. Hybridoma, 1998, 17(6):569-576.
[24] Wongsena W, Sconocchia G, Cho HS, et al.Production and characterization of monoclonal antibodies against major histocompatibility complex class I chain-related gene A[J]. Tissue Antigens, 2008, 72(5):431-440.
[25] Brady JL, Mannering SI, Kireta S, et al.Monoclonal antibodies generated by DNA immunization recognize CD2 from a broad range of primates[J]. Immunol Cell Biol, 2009, 87(5):413-418.
[26] Xue T, Xue XP, et al.Monoclonal antibodies against human aspar-tyl(asparaginyl)beta-hydroxylase developed by DNA immuniza-tion[J]. Hybridoma(Larchmt), 2009, 28(4):251-257.
[27] Chen Y, Vaine M, Wallace A, et al.A novel rabbit monoclonal antibody platform to dissect the diverse repertoire of antibody epitopes for HIV-1Env immunogen design[J]. J Virol, 2013, 87(18):10232-10243.
[28] Ulivieri C, Burroni D, et al.Generation of a monoclonal antibody to a defined portion of the Helicobacter pylori vacuolating cytotoxin by DNA immunization[J]. J Biotechnol, 1996, 51(2):191-194.
[29] Zhang C, Jin K, Xiao Y, et al.Potent monoclonal antibodies against Clostridium difficile toxin A elicited by DNA immunization[J]. Hum Vaccin Immunother, 2013, 9(10):2157-2164.
[30] Puttikhunt C, Kasinrerk W, Srisa-ad S, et al. Production of anti-dengue NS1 monoclonal antibodies by DNA immunization[J]. J Virol Methods, 2003, 109(1):55-61.
[31] Kilpatrick KE, Danger DP, Hull-Ryde EA, et al.High-affinity monoclonal antibodies to PED/PEA-15 generated using 5 microg of DNA[J]. Hybridoma 2000, 19:297-302.
[32] Kilpatrick KE, Kerner S, Dixon EP, et al.In vivo expression of a GST-fusion protein mediates the rapid generation of affinity matured monoclonal antibodies using DNA -based immunizations[J]. Hybrid Hybridomics, 2002, 21:237-243.
[33] Hazen M, Bhakta S, et al.An improved and robust DNA immuniza-tion method to develop antibodies against extracellular loops of multi-transmembrane proteins[J]. MAbs, 2014, 1:95-107.
[34] Wang S, Farfan-Arribas DJ, Shen S, et al.Relative contributions of codon usage, promoter efficiency and leader sequence to the antigen expression and immunogenicity of HIV-1 Env DNA vaccine[J]. Vaccine, 2006, 24(21):4531-4540.
[35] 张钰. 卵透明带3(ZP_3)DNA疫苗免疫不育效果的研究[D]. 乌鲁木齐:新疆大学, 2007.
[36] Gomis S, Babiuk L, Godson DL, et al.Protection of chickens against Escherichia coli infections by DNA containing CpG motifs[J]. Infect Immun. 2003, 71(2):857-63.
[37] Qiu Y, Guo L, Zhang S, et al.DNA -based vaccination against hepatitis B virus using dissolving microneedle arrays adjuvanted by cationic liposomes and CpG ODN[J]. Drug Deliv. 2016, 23(7):2391-2398.
[38] Fujimoto A, Kosaka N, Hasegawa H, et al.Enhancement of antibody responses to native G protein-coupled receptors using E. coli GroEL asa molecular adjuvant in DNA immunization[J]. J Immunol Methods, 2012, 375(1/2):243-251.
[39] Takatsuka S, Sekiguchi A, Tokunaga M, et al.Generation of a panel of monoclonal antibodies against atypical chemokine receptor CCX-CKR by DNA immunization[J]. J Pharmacol Toxicol Methods, 2011, 63(3):250-257.
[40] 黄亮. 靶向急性髓系白血病干细胞的抗CD123单克隆抗体的制备及功能试验[D]. 武汉:华中科技大学, 2011.
[41] Chow YH, Chiang Bor-Luen, Lee YL, et al.Development of TH1 and TH2 populations and the nature of immune responses to hepatitis B virus DNA vaccines can be modulated by codelivery or various cytokine genes[J]. J Immunol, 1998, 160:1320.
[42] Cui FD, Asada H, Jin ML, et al.Cytokine genetic adjuvant facilitates prophylactic intravascular DNA vaccine against acute and latent herpes simplex virus infection in mice[J]. Gene Therapy, 2005, 12:160.
[43] Ledgerwood JE, Wei CJ, Hu Z, et al.DNA priming and influenza vaccine immunogenicity:two phase 1 open label randomised clinical trials[J]. Lancet Infect Dis, 2011, 11(12):916-924.
[44] Vaine M, et al.Profiles of human serum antibody responses elicited by three leading HIV vaccines focusing on the induction of Env-specific antibodies[J]. PLoS One, 2010, 5(11):e13916.
[45] Wang S, Kennedy JS, West K, et al.Cross-subtype antibody and cellular immune responses induced by a polyvalent DNA prime-protein boost HIV-1 vaccine in healthy human volunteers[J]. Vaccine, 2008, 26(31):3947-3957.
[46] Wang S, Parker C, Taaffe J, et al.Heterologous HA DNA vaccine prime-inactivated influenza vaccine boost is more effective than using DNA or inactivated vaccine alone in eliciting antibody responses against H1 or H3 serotype influenza viruses[J]. Vaccine, 2008, 26(29/30):3626-3633.
[47] Suguitan AL, Cheng X, Wang W, et al.Influenza H5 hemagglutinin DNA primes the antibody response elicited by the live attenuated influenza A/Vietnam/1203/2004 vaccine in ferrets[J]. PLoS One, 2011, 6(7):e21942.
[48] Pal R, Wang S, Kalyanaraman VS, et al.Polyvalent DNA prime and envelope protein boost HIV-1 vaccine elicits humoral and cellular responses and controls plasma viremia in rhesus macaques following rectal challenge with an R5 SHIV isolate[J]. J Med Primatol, 2005, 34(5/6):226-236.
[49] Wang S, Arthos J, et al.Enhanced immunogenicity of gp120 protein when combined with recombinant DNA priming to generate antibo-dies that neutralize the JR-FL primary isolate of human immunode-ficiency virus type 1[J]. J Virol, 2005, 79(12):7933-7937.
[50] Li W, Wang S, Lu S.Pilot study on the use of DNA priming immunization to enhance Y. pestis LcrV-specific B cell responses elicited by a recombinant LcrV protein vaccine[J]. Vaccines(Basel), 2013, 2(1):36-48.
[51] Vaine M, Wang S, Hackett A, et al.Antibody responses elicited through homologous or heterologous prime-boost DNA and protein vaccinations differ in functional activity and avidity[J]. Vaccine, 2010, 28(17):2999-3007.
[52] Alexander G, Claire S, Dmitry R. Pneumatic capillary gun for ballistic delivery of microscopic particles into tissue:US, 7892836[P].2011-02-22.
[53] Wang S, Joshi S, Lu S.Delivery of DNA to skin by particle bombardment[J]. Methods Mol Biol, 2004, 245:185-196.
[54] Robinson HL, Torres CA.DNA vaccines[J]. Semin Immunol, 1997, 9(5):271-283.
[55] 张亮, 李潇潇, 韩刚, 等. 不同方式递送质粒DNA诱导体内表达效果的实验研究[J]. 解放军医学院学报, 2010, 31(1):48-49.
[56] Alexandrenne C, Wijkhuisen A, Dkhissi F, et al.Generating antibodies against the native form of the human prion protein(hPrP)in wild-type animals:a comparison between DNA and protein immunizations[J]. J Immunol Methods, 2009(1/2):41-49.
[57] Wang S, Zhang C, Zhang L, et al.The relative immunogenicity of DNA vaccines delivered by the intramuscular needle injection, el-ectroporation and gene gun methods[J]. Vaccine, 2008, 26(17):2100-2110.
[58] Lu S.Two is better than one[J]. Lancet Infect Dis, 2011, 11(12):889-891.
[59] 张永久, 崔钰. 禽流感疫苗的种类与优缺点[J]. 畜牧兽医科技信息, 2006(3):12-15.
[60] 郎守民, 宋英今, 金海玉. 禽流感疫苗研究进展[J]. 吉林畜牧兽医, 2005(11):14-16.
[61] 陈吉祥, 李广林, 薛飞群, 等. 核酸免疫与核酸疫苗研究进展[J]. 中兽医医药杂志, 2000, 19(1):42-44.
[62] 牟玉莲, 孙少华, 董宝军. 核酸疫苗的研究进展[J]. 中国畜牧兽医, 2000, 27(4):47-49.
[63] 周璨林, 张富春. 增强DNA疫苗免疫应答的新进展[J]. 生物技术通报, 2006(1):22-25.