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  • نقشDNA باکتریایی هم تیپ به عنوان اجوانت در ایجاد پاسخ های ایمنی هومورال و سلولی علیه آلودگی با پاستورلا مالتوسیدا در گوسفندان

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آدرس مقاله


کد مقاله : JMW-2203-2013 (R1) بازدید : 184 صفحه: 192 - 206

10.30495/jmw.2022.1954395.2013

20.1001.1.20083068.1401.15.0.3.5

نوع مقاله: پژوهشی

نقشDNA باکتریایی هم تیپ به عنوان اجوانت در ایجاد پاسخ های ایمنی هومورال و سلولی علیه آلودگی با پاستورلا مالتوسیدا در گوسفندان

محورهای موضوعی : ایمنی شناسی

کیواندخت عباسی 1 (دانش آموخته گروه میکروبیولوژی، دانشکده علوم، کشاورزی و فناوری های نوین، واحد شیراز، دانشگاه آزاد اسلامی، شیراز، ایران.)
یحیی تهمتن 2 (بخش میکروب شناسی، مؤسسه تحقیقات واکسن و سرم سازی رازی شعبه شیراز، سازمان تحقیق، آموزش و ترویج کشاورزی، شیراز، ایران.)
الهام معظمیان 3 (گروه میکروبیولوژی، دانشکده علوم، کشاورزی و فناوری های نوین، واحد شیراز، دانشگاه آزاد اسلامی، شیراز، ایران)
محمد حسین حسینی 4 (بخش ایمنی شناسی، مؤسسه تحقیقات واکسن و سرم سازی رازی شعبه شیراز، سازمان تحقیق، آموزش و ترویج کشاورزی، شیراز، ایران.)

تاریخ دریافت : 1401/03/28 تاریخ پذیرش : 1401/08/04 تاریخ انتشار : 1401/09/15

کلید واژه: واکسن, پاستورلا مالتوسیدا, DNA باکتریایی, اجوانت, TNF-α, آلوم,

چکیده مقاله :

سابقه و هدف: پاستورلا مالتوسیدا عامل بیماری پاستورلوز می باشد. حیوانات و گاهی انسان با این باکتری درگیر می شوند. هدف این مطالعه ارزیابی پاسخ های ایمنی در گوسفندان واکسینه شده با آنتی ژن غیرفعال همراه با اجوانت آلوم و AbDNA از طریق ردیابی میزان IgG و سایتوکین در سرم بود.مواد و روش ها: گوسفندان با دو دوز واکسن غیرفعال شده با فرمالین به فاصله 2 هفته ایمن شدند.در این واکسن ها از آلوم و DNA پاستورلا مالتوسیدا سروتیپ A بهعنوان اجوانت استفاده گردید. درهر مرحله، یک سیسی ایمونوژن بهصورت زیرجلدی به حیوانات تلقیح شد. پس از طراحی الایزا، پاسخ ایمنی اکتسابی با اندازه گیری تیتر آنتی بادی اختصاصی IgG و اندازه گیری TNF-α بر روی نمونه های سرم و کشت سلول لنفوسیت بررسی شد.یافته ها: نتایج نشان داد تیتر آنتی بادی در گروه دریافت کننده DNA نسبت به گروه دریافت کننده آلوم و گروه های کنترل بالاتر بود. بالاترین سطح آنتی بادی (1/463) مربوط به گروه FIV-AbDNA در هفته چهارم بود. در گروه FIV-Alum بالاترین تیتر 1/054 بود که نشان از پاسخ ایمنی ضعیف تر نسبت به گروه DNA می باشد. پس از ایمن سازی، AbDNA باعث افزایش تولید TNF-α نیز گردید. بطور کلی تیتر TNF-α در حیوانات ایمن شده نسبت به گروه های کنترل افزایش معناداری داشت. بالاترین تیتر TNF-α (1/44) مربوط به گروه FIV-AbDNA در نمونه سرم بود.نتیجه گیری: آنتی ژن پاستورلا مالتوسیدا همراه با DNA باکتریایی به عنوان اجوانت، گزینه ای برای ساخت واکسن های جدید علیه پاستورلا مالتوسیدا می باشد. با توجه به توانایی AbDNA در ایجاد پاسخ های ایمنی به واسطه آزاد سازی سایتوکاین های مختلف، ارزیابی انواع سایتوکاین ها پیشنهاد می گردد.

چکیده انگلیسی:

Backgronnd & Objectives: Pasteurella (P.) maltocida is the cause of pasteurellosis. Animals and sometimes humans are involved with this bacterium. The aim of this study was to evaluate immune responses in sheep vaccinated with inactive antigen along with alum and AbDNA adjuvant by tracking IgG and cytokine levels on serum samples.Material & Methods: Sheep were immunized with two doses of inactivated vaccine with formalin at an interval of 2 weeks. Alum and DNA of P.maltocida serotype A strain were used as an adjuvant. One milliliter of immunogen was inoculated subcutaneously to the animals. After  ELISA design, immune response was evaluated by measuring specific IgG antibody titer and TNF-α measurement on serum samples and lymphocyte cell culture.Results: The antibody titer in the group receiving DNA was higher than the group receiving Alum and the control groups. The highest antibody level (1.463) was related to the FIV-AbDNA group in the fourth week. In the FIV-Alum group, the highest titer was 1.054, which indicates a weaker immune response compared to the DNA group. AbDNA also increased the production of TNF-α. TNF-α in immunized animals increased significantly compared to the control groups. The highest titer of TNF-α (1.44) was related to the FIV-AbDNA group on the serum sample.Conclusion: P.maltocida antigen together with bacterial DNA as an adjuvant is an alternative candidate for making new vaccines against P.maltocida. Considering the ability of AbDNA to   create immune responses through the release of different cytokines, it is suggested to evaluate different types of cytokines. 

منابع و مأخذ:

References



  1. Kallili I, Ghadimipour R, Ghaderi R, Shokri GH, Jabbari AR, Razmaraii N, Ebrahimi M. Isolation, identification, and monitoring of antibiotic resistance in Pasteurella multocida and Mannheimia haemolytica isolated from sheep in East. Razi Vaccine and Serum Research Institute. 2016; 71(3): 153-160.
    2.
  2. Kubutzky KF. Pasteurella multocida and immune cells. Microbiology and Immunology. 2012; 361: 53-72.
    3.
  3. Orth JH, Aktories K. Molecular biology of Pasteurella multocida toxin. Curr Top Microbiol Immunol. 2012; 361: 73-92.
    4.
  4. Guan L, Zhang L, Xue Y, Yang J, Zhao Z. Molecular pathogenesis of the hyaluronic acid capsule of Pasteurella multocida. Microb Pathog. 2020; 149: 104380.
    5.
  5. Banu A, Lax AJ, Grigoriadis AE. In Vivo Targets of Pasteurella Multocida Toxin. Int J Mol Sci. 2020; 21(8): 2739.
    6.
  6. Wilson BA, Ho M. Pasteurella multocida: from Zoonosis to Cellular Microbiology. Clinical Microbiology Reviews. 2013; 26(3): 631-55.
    7.
  7. Zhu W, Fan Z, Qiu R, Chen L, Wei H, Hu B, Chen M, Wang F. Characterization of Pasteurella multocida isolates from rabbits in China. Vet Microbiol. 2020; 244: 108649.
    8.
  8. Tahamtan Y, Homayoon M, Kargar M. The effect of homologous and heterologous Bacterial DNA on the development of immune responses against Pasteurella multocida in BALB / c mice. Journal of Microbial World. 2019; 12(2): 101-113 [In persian].
    9.
  9. Mostaan S, Ghasemzadeh A, Sardari S, Shokrgozar MA, Nikbakht Brujeni G, Abolhassani M, Ehsani P, Asadi Karam MR. Pasteurella multocida Vaccine Candidates: A Systematic Review. Avicenna J Med Biotechnol. 2020; 12(3): 140-147.
    10.
  10. Pak S, Valencia D, Decker J, Valencia V, Askaroglu Y. Pasteurella multocida pneumonia in an immunocompetent patient: Case report and systematic review of literature. Lung India. 2018; 35(3): 237-240.
    11.
  11. Guo W, Lu , Liu L, Gong Z, liu l, weiNa G. Isolation, identification and virulence genes detection of Pasteurella multocida from chicken. Chines Veterinary Silence. 2017; 47(7): 890-896.
    12.
  12. Su A, Tong J, Fu Y, Müller S, Weldearegay YB, Becher P, Valentin-Weigand P, Meens J, Herrler G. Infection of bovine well-differentiated airway epithelial cells by Pasteurella multocida: actions and counteractions in the bacteria-host interactions. Vet Res. 2020; 51(1): 140.
    13.
  13. Ahmad AM. Efforts Towards the Development of Recombinant Vaccines Against Pasteurella multocida. Science World Journal. 2014; 9(2): 1-7.
    14.
  14. Boumart Z, Bamouh Z, Semmate N, Tadlaoui KO, Harrak M. Biological Characterisation and Pathogenicity of a Pasteurella multocida Isolate from Sheep in Morocco. Journal of Agricultural Science and Technology. 2021; 11: 53-64.
    15.
  15. Homayoon M, Tahamtan Y, Kargar M, Hosseini SMH, Akhavan SA. Adjuvant activity of Pasteurella maltocida A strain, Pasteurella maltocida B strain and salmonella typhimurium bacterial and on cellular responses against Pasteurella maltocida specific strain infectionsin Balb/C mice. Trop Med Asian Pac J. 2018; 11(5): 336-341.
    16.
  16. Dagleish MP, Christopher Hodgson J, Ataei S, Finucane A, Finlayson J, Sales J, et al. Safety and Protective Efficacy of Intramuscular Vaccination with a Live aroA Derivative of Pasteurella multocida B:2 against Experimental Hemorrhagic Septicemia in Calves. Infection and Immunity. 2007; 75(12): 5837-44.
    17.
  17. Gupta A, Chaphalkar SR. Vaccine Adjuvants: The Current Necessity of Life. Shiraz E-Med J. 2015; 16(7): e28061.
    18.
  18. Xie Z, Li H, Chen J, Zhang H-b, Wang Y-Y, Chen Q, Zhao ZZ, Cheng C, Zhang H, Yang Y,  Wang HN,  Gao R. Shuffling of pig interleukin-2 gene and its enhancing of immunity in mice to Pasteurella multocida vaccine. vaccine. 2007; 25(48): 8163-71.
    19.
  19. Petrovsky N, Aguilar JC. Vaccine adjuvants: current state and future trends. Immunol Cell Biol. 2004; 82(5): 488-96.
    20.
  20. Kukkonen K, Kuitunen M, Haahtela T, Korpela R, Poussa T, Savilahti E. High intestinal IgA associates with reduced risk of IgE-associated allergic diseases. Pediatric allergy and immunology: official publication of the European Society of Pediatric Allergy and Immunology. 2010; 21(1): 67-73.
    21.
  21. Tang ML, Lahtinen SJ, Boyle RJ. Probiotics and prebiotics: clinical effects in allergic disease. Current opinion in pediatrics. 2010; 22(5): 626-34.
    22.
  22. Mapletoft JW, Oumouna M, Kovacs-Nolan J, Latimer L, Mutwiri G, Babiuk LA, van Drunen Littel-van den Hurk S. Intranasal immunization of mice with a formalin-inactivated bovine respiratory syncytial virus vaccine co-formulated with CpG oligodeoxynucleotides and polyphosphazenes results in enhanced protection. J Gen Virol. 2008; 89 (Pt 1): 250-260.
    23.
  23. Kumar D, Singh A. Salmonella typhimurium grown in iron-rich media, inactivated with ferric chloride and adjuvanted with homologous bacterial DNA is potent and efficacious vaccine in mice. Vaccine. 2005; 23(48-49): 5590-5598.
    24.
  24. Homayoon M, Tahamtan Y, Kargar M, Hosseini SMH, Akhavan S.A. Pasteurella multocida inactivated with ferric chloride and adjuvanted with bacterial DNA is a potent and efficacious vaccine in Balb/c mice. Journal of Medical Microbiology. 2018; 67(9): 1383-1390.
    25.
  25. Cheng HR, Jiang N. Extremely rapid extraction of DNA from bacteria and yeasts. Biotechnology Letters. 2006; 28(1): 55-59
    26.
  26. Homayoon M, Tahamtan Y, Kargar M. The Comparison Detection of Cytokines (IL-6 and IL-12) from Spleen Cells and Serums in Balb/c Mice after Immunization with Killed P. multocida Vaccines Co-formulated with Bacterial DNAs as Adjuvant. Arch Clin Microbiol. 2020; 11(1): 103.
    27.
  27. Borowski SM, Silva SC, Schrank I, Cardoso M. Toxin detection in Pasteurella multocida strains isolated from swine lungs in the state of Rio Grande do Sul, Brazil. Arq Fac Vet. 2001; 29(2): 79-85.
    28.
  28. Fischer G, Cleff MB, Dummer LA, Paulino N, Paulino AS, Vilela CO, Campos FS, Storch T, Vargas GD, Hu¨bner SO, Vidor T. Adjuvant effect of green propolis on humoral immune response of bovines immunized with bovine herpesvirus type 5. Vet Immunol Immunopathol. 2007; 116(1-2): 79-84. 
    29.
  29. Arous JB, Deville S, Pal JK, Baksi S, Bertrand F, Dupuis L. Reduction of Newcastle disease vaccine dose using a novel adjuvant for cellular immune response in poultry. Procedia in Vaccinology. 2013; 7: 28 -33.
    30.
  30. Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology, eighth edition. Elsevier Saunders. 2015; 51-265.
    31.
  31. Silveira M, Vargas S, Mendonça M, Cunha CE, Hartwig D, Seixas A, et al. Xanthan gum enhances humoral immune response elicited by a DNA vaccine against leptospirosis in mice. BMC Proceedings. 2014; 8: 153.
    32.
  32. Wu C, Qin X, Li P, Pan T, Ren W, Li N, Peng Y. Transcriptomic Analysis on Responses of Murine Lungs to Pasteurella multocida Infection. Front Cell Infect Microbiol. 2017; 7: 251.
    33.
  33. Sayed HE, Ashry E, Ahmad TA. The use of propolis as vaccine’s adjuvant. Vaccine. 2012; 31(1): 31-39.
    34.
  34. Qureshi S, Saxena HM. Estimation of titers of antibody against Pasteurella multocida in cattle vaccinated with haemorrhagic septicemia alum precipitated vaccine. Veterinary World. 2014; 7(4): 224-8.
    35.
  35. Herath C, Kumar P, Singh M, Kumar D, Ramakrishnan S, Goswami TK, Singh A, Ram GC. Experimental iron-inactivated Pasteurella multocida A: 1 vaccine adjuvanted with bacterial DNA is safe and protects chickens from fowl cholera. Vaccine. 2010; 28(11): 2284-2289.
    36.
  36. Trevani AS, Chorny A, Salamone G, Vermeulen M, Gamberale R, Schettini J, Raiden S, Geffner J. Bacterial DNA activates human neutrophils by a CpG-independent pathway. Eur J Immunol. 2003; 33(11): 3164-3174.
    37.
  37. Bode C, Zhao G, Steinhagen F, Kinjo T, Klinman DM. CpG DNA as a vaccine adjuvant. Expert Rev Vaccines. 2011; 10(4): 499-511.
    38.
  38. Hanagata N. CpG oligodeoxynucleotide nanomedicines for the prophylaxis or treatment of cancers, infectious diseases, and allergies. Int J Nanomedicine. 2017; 12: 515-531.
    39.

 

_||_

References



  1. Kallili I, Ghadimipour R, Ghaderi R, Shokri GH, Jabbari AR, Razmaraii N, Ebrahimi M. Isolation, identification, and monitoring of antibiotic resistance in Pasteurella multocida and Mannheimia haemolytica isolated from sheep in East. Razi Vaccine and Serum Research Institute. 2016; 71(3): 153-160.
    2.
  2. Kubutzky KF. Pasteurella multocida and immune cells. Microbiology and Immunology. 2012; 361: 53-72.
    3.
  3. Orth JH, Aktories K. Molecular biology of Pasteurella multocida toxin. Curr Top Microbiol Immunol. 2012; 361: 73-92.
    4.
  4. Guan L, Zhang L, Xue Y, Yang J, Zhao Z. Molecular pathogenesis of the hyaluronic acid capsule of Pasteurella multocida. Microb Pathog. 2020; 149: 104380.
    5.
  5. Banu A, Lax AJ, Grigoriadis AE. In Vivo Targets of Pasteurella Multocida Toxin. Int J Mol Sci. 2020; 21(8): 2739.
    6.
  6. Wilson BA, Ho M. Pasteurella multocida: from Zoonosis to Cellular Microbiology. Clinical Microbiology Reviews. 2013; 26(3): 631-55.
    7.
  7. Zhu W, Fan Z, Qiu R, Chen L, Wei H, Hu B, Chen M, Wang F. Characterization of Pasteurella multocida isolates from rabbits in China. Vet Microbiol. 2020; 244: 108649.
    8.
  8. Tahamtan Y, Homayoon M, Kargar M. The effect of homologous and heterologous Bacterial DNA on the development of immune responses against Pasteurella multocida in BALB / c mice. Journal of Microbial World. 2019; 12(2): 101-113 [In persian].
    9.
  9. Mostaan S, Ghasemzadeh A, Sardari S, Shokrgozar MA, Nikbakht Brujeni G, Abolhassani M, Ehsani P, Asadi Karam MR. Pasteurella multocida Vaccine Candidates: A Systematic Review. Avicenna J Med Biotechnol. 2020; 12(3): 140-147.
    10.
  10. Pak S, Valencia D, Decker J, Valencia V, Askaroglu Y. Pasteurella multocida pneumonia in an immunocompetent patient: Case report and systematic review of literature. Lung India. 2018; 35(3): 237-240.
    11.
  11. Guo W, Lu , Liu L, Gong Z, liu l, weiNa G. Isolation, identification and virulence genes detection of Pasteurella multocida from chicken. Chines Veterinary Silence. 2017; 47(7): 890-896.
    12.
  12. Su A, Tong J, Fu Y, Müller S, Weldearegay YB, Becher P, Valentin-Weigand P, Meens J, Herrler G. Infection of bovine well-differentiated airway epithelial cells by Pasteurella multocida: actions and counteractions in the bacteria-host interactions. Vet Res. 2020; 51(1): 140.
    13.
  13. Ahmad AM. Efforts Towards the Development of Recombinant Vaccines Against Pasteurella multocida. Science World Journal. 2014; 9(2): 1-7.
    14.
  14. Boumart Z, Bamouh Z, Semmate N, Tadlaoui KO, Harrak M. Biological Characterisation and Pathogenicity of a Pasteurella multocida Isolate from Sheep in Morocco. Journal of Agricultural Science and Technology. 2021; 11: 53-64.
    15.
  15. Homayoon M, Tahamtan Y, Kargar M, Hosseini SMH, Akhavan SA. Adjuvant activity of Pasteurella maltocida A strain, Pasteurella maltocida B strain and salmonella typhimurium bacterial and on cellular responses against Pasteurella maltocida specific strain infectionsin Balb/C mice. Trop Med Asian Pac J. 2018; 11(5): 336-341.
    16.
  16. Dagleish MP, Christopher Hodgson J, Ataei S, Finucane A, Finlayson J, Sales J, et al. Safety and Protective Efficacy of Intramuscular Vaccination with a Live aroA Derivative of Pasteurella multocida B:2 against Experimental Hemorrhagic Septicemia in Calves. Infection and Immunity. 2007; 75(12): 5837-44.
    17.
  17. Gupta A, Chaphalkar SR. Vaccine Adjuvants: The Current Necessity of Life. Shiraz E-Med J. 2015; 16(7): e28061.
    18.
  18. Xie Z, Li H, Chen J, Zhang H-b, Wang Y-Y, Chen Q, Zhao ZZ, Cheng C, Zhang H, Yang Y,  Wang HN,  Gao R. Shuffling of pig interleukin-2 gene and its enhancing of immunity in mice to Pasteurella multocida vaccine. vaccine. 2007; 25(48): 8163-71.
    19.
  19. Petrovsky N, Aguilar JC. Vaccine adjuvants: current state and future trends. Immunol Cell Biol. 2004; 82(5): 488-96.
    20.
  20. Kukkonen K, Kuitunen M, Haahtela T, Korpela R, Poussa T, Savilahti E. High intestinal IgA associates with reduced risk of IgE-associated allergic diseases. Pediatric allergy and immunology: official publication of the European Society of Pediatric Allergy and Immunology. 2010; 21(1): 67-73.
    21.
  21. Tang ML, Lahtinen SJ, Boyle RJ. Probiotics and prebiotics: clinical effects in allergic disease. Current opinion in pediatrics. 2010; 22(5): 626-34.
    22.
  22. Mapletoft JW, Oumouna M, Kovacs-Nolan J, Latimer L, Mutwiri G, Babiuk LA, van Drunen Littel-van den Hurk S. Intranasal immunization of mice with a formalin-inactivated bovine respiratory syncytial virus vaccine co-formulated with CpG oligodeoxynucleotides and polyphosphazenes results in enhanced protection. J Gen Virol. 2008; 89 (Pt 1): 250-260.
    23.
  23. Kumar D, Singh A. Salmonella typhimurium grown in iron-rich media, inactivated with ferric chloride and adjuvanted with homologous bacterial DNA is potent and efficacious vaccine in mice. Vaccine. 2005; 23(48-49): 5590-5598.
    24.
  24. Homayoon M, Tahamtan Y, Kargar M, Hosseini SMH, Akhavan S.A. Pasteurella multocida inactivated with ferric chloride and adjuvanted with bacterial DNA is a potent and efficacious vaccine in Balb/c mice. Journal of Medical Microbiology. 2018; 67(9): 1383-1390.
    25.
  25. Cheng HR, Jiang N. Extremely rapid extraction of DNA from bacteria and yeasts. Biotechnology Letters. 2006; 28(1): 55-59
    26.
  26. Homayoon M, Tahamtan Y, Kargar M. The Comparison Detection of Cytokines (IL-6 and IL-12) from Spleen Cells and Serums in Balb/c Mice after Immunization with Killed P. multocida Vaccines Co-formulated with Bacterial DNAs as Adjuvant. Arch Clin Microbiol. 2020; 11(1): 103.
    27.
  27. Borowski SM, Silva SC, Schrank I, Cardoso M. Toxin detection in Pasteurella multocida strains isolated from swine lungs in the state of Rio Grande do Sul, Brazil. Arq Fac Vet. 2001; 29(2): 79-85.
    28.
  28. Fischer G, Cleff MB, Dummer LA, Paulino N, Paulino AS, Vilela CO, Campos FS, Storch T, Vargas GD, Hu¨bner SO, Vidor T. Adjuvant effect of green propolis on humoral immune response of bovines immunized with bovine herpesvirus type 5. Vet Immunol Immunopathol. 2007; 116(1-2): 79-84. 
    29.
  29. Arous JB, Deville S, Pal JK, Baksi S, Bertrand F, Dupuis L. Reduction of Newcastle disease vaccine dose using a novel adjuvant for cellular immune response in poultry. Procedia in Vaccinology. 2013; 7: 28 -33.
    30.
  30. Abbas AK, Lichtman AH, Pillai S. Cellular and molecular immunology, eighth edition. Elsevier Saunders. 2015; 51-265.
    31.
  31. Silveira M, Vargas S, Mendonça M, Cunha CE, Hartwig D, Seixas A, et al. Xanthan gum enhances humoral immune response elicited by a DNA vaccine against leptospirosis in mice. BMC Proceedings. 2014; 8: 153.
    32.
  32. Wu C, Qin X, Li P, Pan T, Ren W, Li N, Peng Y. Transcriptomic Analysis on Responses of Murine Lungs to Pasteurella multocida Infection. Front Cell Infect Microbiol. 2017; 7: 251.
    33.
  33. Sayed HE, Ashry E, Ahmad TA. The use of propolis as vaccine’s adjuvant. Vaccine. 2012; 31(1): 31-39.
    34.
  34. Qureshi S, Saxena HM. Estimation of titers of antibody against Pasteurella multocida in cattle vaccinated with haemorrhagic septicemia alum precipitated vaccine. Veterinary World. 2014; 7(4): 224-8.
    35.
  35. Herath C, Kumar P, Singh M, Kumar D, Ramakrishnan S, Goswami TK, Singh A, Ram GC. Experimental iron-inactivated Pasteurella multocida A: 1 vaccine adjuvanted with bacterial DNA is safe and protects chickens from fowl cholera. Vaccine. 2010; 28(11): 2284-2289.
    36.
  36. Trevani AS, Chorny A, Salamone G, Vermeulen M, Gamberale R, Schettini J, Raiden S, Geffner J. Bacterial DNA activates human neutrophils by a CpG-independent pathway. Eur J Immunol. 2003; 33(11): 3164-3174.
    37.
  37. Bode C, Zhao G, Steinhagen F, Kinjo T, Klinman DM. CpG DNA as a vaccine adjuvant. Expert Rev Vaccines. 2011; 10(4): 499-511.
    38.
  38. Hanagata N. CpG oligodeoxynucleotide nanomedicines for the prophylaxis or treatment of cancers, infectious diseases, and allergies. Int J Nanomedicine. 2017; 12: 515-531.
    39.

 

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