اخبار و اعلانات

 آمار

تعداد نشریات286
تعداد نشریات سازمان84
تعداد شماره‌ها2,975
تعداد مقالات33,408
تعداد مشاهده مقاله43,903,051
تعداد دریافت فایل اصل مقاله20,405,255
Taghizadeh, M, Dabaghian, M. (1401). Nasal Administration of M2e/CpG-ODN Encapsulated in N-Trimethyl Chitosan (TMC) Significantly Increases Specific Immune Responses in a Mouse Model. سامانه مدیریت نشریات علمی, 77(6), 2259-2268. doi: 10.22092/ari.2022.360447.2583
M Taghizadeh; M Dabaghian. "Nasal Administration of M2e/CpG-ODN Encapsulated in N-Trimethyl Chitosan (TMC) Significantly Increases Specific Immune Responses in a Mouse Model". سامانه مدیریت نشریات علمی, 77, 6, 1401, 2259-2268. doi: 10.22092/ari.2022.360447.2583
Taghizadeh, M, Dabaghian, M. (1401). 'Nasal Administration of M2e/CpG-ODN Encapsulated in N-Trimethyl Chitosan (TMC) Significantly Increases Specific Immune Responses in a Mouse Model', سامانه مدیریت نشریات علمی, 77(6), pp. 2259-2268. doi: 10.22092/ari.2022.360447.2583
Taghizadeh, M, Dabaghian, M. Nasal Administration of M2e/CpG-ODN Encapsulated in N-Trimethyl Chitosan (TMC) Significantly Increases Specific Immune Responses in a Mouse Model. سامانه مدیریت نشریات علمی, 1401; 77(6): 2259-2268. doi: 10.22092/ari.2022.360447.2583

Nasal Administration of M2e/CpG-ODN Encapsulated in N-Trimethyl Chitosan (TMC) Significantly Increases Specific Immune Responses in a Mouse Model

Archives of Razi Institute
مقاله 30، دوره 77، شماره 6، بهمن و اسفند 2022، صفحه 2259-2268    اصل مقاله (608.1 K)
نوع مقاله: Original Articles
شناسه دیجیتال (DOI): 10.22092/ari.2022.360447.2583
نویسندگان
M Taghizadeh1؛ M Dabaghian* 2
1Medical Vaccine Department, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran
2Department of Biotechnology, Razi Vaccine and Serum Research Institute, Agricultural Research, Education and Extension Organization (AREEO), Karaj, Iran
چکیده
The nasal passage is the primary entry point for many infectious agents. Therefore, nasal vaccines that can overcome the limitations associated with antigen uptake are likely to play an important role in protecting these infectious agents. Thus, adjuvants and antigen-carrying systems that can induce a suitable mucosal and systemic immune response against their accompanying antigens are highly important. In this study, synthetic oligodeoxynucleotides containing CpG motifs (CpG-ODN) accompanied by the recombinant ectodomain of influenza M2 protein were encapsulated in N-trimethyl chitosan (TMC) nanoparticles. After the preparation of TMC nanoparticles, the morphological characteristics and loading efficiency and in vitro antigen release, as well as their ability to induce efficient immune responses against M2e in intranasal inoculation in the mouse model, were studied. Based on the size and zeta potential of the nanoparticles prepared in this study, it was determined that they were all nanosized, and their positive zeta potential ranged from 25 to 28 mV, while their polydispersity index was between 0.1 to 0.2, indicating a narrow range of particle sizes. A significant increase in serum levels of the total M2e-specific IgG antibody and BALF anti-M2e IgA was observed in mice intranasally immunized with M2e/CpG-ODN/TMC as opposed to those that were intranasally immunized with M2e/TMC, M2e/CpG-ODN, free M2e, and CpG-ODN/TMC. There was also a significant change in the IgG2a/IgG1 ratio in favour of IgG2a seems that CpG-ODN is responsible for directing the immune system towards Th1. Our findings show that CpG-ODN can significantly enhance the mucosal and systemic humoral immune response against M2e when encapsulated in a suitable carrier such as TMC for intranasal administration. In conclusion, when combined with a suitable carrier, CpG-ODN can be considered an effective adjuvant for mucosal administration.
کلیدواژه‌ها
CpG-ODN 2006؛ M2e؛ TMC
عنوان مقاله [English]
تجویز داخل بینی M2e/CpG-ODN محصورشده درتری متیل کیتوزان (TMC) پاسخ های ایمنی اختصاصی را به طور قابل توجهی در مدل موشی افزایش می دهد
چکیده [English]
با توجه به این واقعیت که مجرای بینی نقطه ورود اولیه برای بسیاری از عوامل عفونی است، واکسن های بینی که قادر به غلبه بر محدودیت های مرتبط با جذب آنتی ژن هستند، احتمالا می توانند نقش مهمی در ارائه محافظت در برابر این عوامل عفونی ایفا کنند. از اینرو استفاده از ادجوانت ها و سیستم های حامل آنتی ژن که بتوانند پاسخ ایمنی مخاطی و سیستمیک مناسبی را بر علیه آنتی ژن همراهشان القا کنند حایز اهمیت بالایی میباشند.

در این مطالعه الیگودئوکسی نوکلئوتیدهای سنتتیک حاوی CpG (CpG-ODN) همراه با اکتودومین نوترکیب پروتئین M2 ویروس آنفلوانزا در نانوذرات N-تری متیل کیتوزان (TMC) کپسوله شدند. پس از تهیه نانوذرات ، ویژگیهای مورفولوژیک و کارآیی بارگزاری و میزان رهایش آنتی ژن و نیز توانایی آنها برای القای پاسخ های ایمنی کارآمد در برابر M2e در تلقیح داخل بینی درمدل موش مورد مطالعه قرار گرفت. بررسی سایز ذرات و پتانسیل زتا نانوذرات تهیه شده در این مطالعه نشان داد که همه آنها دارای اندازه نانو هستند و پتانسیل زتا مثبت آنها از 25 تا 28 میلی ولت متغیر است، در حالی که شاخص چند پراکندگی آنها بین 0.1 تا 0.2 بود که نشان میداد ذرات از نظر اندازه در محدوده باریکی قرار میگیرند.

در مقایسه با موش هایی که با M2e/TMC، M2e/CpG-ODN، M2e و CpG-ODN/TMC ایمن شدند ، افزایش قابل توجهی در سطح سرمی آنتی بادی IgG اختصاصی M2e وIgA موجود در BALF در موش هایی مشاهده شد که به صورت داخل بینی با M2e/CpG-ODN/TMC ایمن شده بودند . همچنین در گروه مذکور تغییر قابل توجهی در نسبت IgG2a/IgG1 به نفع IgG2a وجود داشت که به نظر می رسد CpG-ODN مسئول هدایت سیستم ایمنی به سمت Th1 است.

یافته های ما نشان می دهد که CpG-ODN در صورتیکه در تجویز داخل بینی در یک حامل مناسب مانند TMC کپسوله شود قادر است پاسخ ایمنی هومورال مخاطی و سیستمیک را در برابر M2e به طور قابل توجهی افزایش دهد.

در نتیجه، CpG-ODN در صورتیکه همراه با یک حامل مناسب مانند TMC مورد استفاده قرار گیرد میتواند در تجویز مخاطی به عنوان یک ادجوانت موثر جهت تحریک موثر سیستم ایمنی مورد توجه قرار گیرد.
کلیدواژه‌ها [English]
CpG-ODN 2006, M2e, TMC
سایر فایل های مرتبط با مقاله
مراجع
  1. Allen A, Leonard AJ, Sellers LA. The mucus barrier. Its role in gastroduodenal mucosal protection. J Clin Gastroenterol. 1988;10:93-8.
  2. Brett IC, Johansson BE. Immunization against influenza A virus: comparison of conventional inactivated, live-attenuated and recombinant baculovirus produced purified hemagglutinin and neuraminidase vaccines in a murine model system. Virology. 2005;339(2):273-80.
  3. Liu W, Zou P, Ding J, Lu Y, Chen Y-H. Sequence comparison between the extracellular domain of M2 protein human and avian influenza A virus provides new information for bivalent influenza vaccine design. Microbes Infect. 2005;7(2):171-7.
  4. Bessa J, Schmitz N, Hinton HJ, Schwarz K, Jegerlehner A, Bachmann MF. Efficient induction of mucosal and systemic immune responses by virus‐like particles administered intranasally: implications for vaccine design. Eur J Immunol. 2008;38(1):114-26.
  5. Fan J, Liang X, Horton MS, Perry HC, Citron MP, Heidecker GJ, et al. Preclinical study of influenza virus A M2 peptide conjugate vaccines in mice, ferrets, and rhesus monkeys. Vaccine. 2004;22(23-24):2993-3003.
  6. Huleatt JW, Nakaar V, Desai P, Huang Y, Hewitt D, Jacobs A, et al. Potent immunogenicity and efficacy of a universal influenza vaccine candidate comprising a recombinant fusion protein linking influenza M2e to the TLR5 ligand flagellin. Vaccine. 2008;26(2):201-14.
  7. Petrovsky N, Aguilar JC. Vaccine adjuvants: current state and future trends. Immunol Cell Biol. 2004;82(5):488-96.
  8. Slütter B, Jiskoot W. Dual role of CpG as immune modulator and physical crosslinker in ovalbumin loaded N-trimethyl chitosan (TMC) nanoparticles for nasal vaccination. J Control Release. 2010;148(1):117-21.
  9. Lamichhane A, Azegami T, Kiyono H. The mucosal immune system for vaccine development. Vaccine. 2014;32(49):6711-23.
  10. Gupta NK, Tomar P, Sharma V, Dixit VK. Development and characterization of chitosan coated poly-(ɛ-caprolactone) nanoparticulate system for effective immunization against influenza. Vaccine. 2011;29(48):9026-37.
  11. Cox R, Brokstad K, Ogra P. Influenza virus: immunity and vaccination strategies. Comparison of the immune response to inactivated and live, attenuated influenza vaccines. Scand J Immunol. 2004;59(1):1-15.
  12. Amidi M, Romeijn SG, Borchard G, Junginger HE, Hennink WE, Jiskoot W. Preparation and characterization of protein-loaded N-trimethyl chitosan nanoparticles as nasal delivery system. J Control Release. 2006;111(1-2):107-16.
  13. Köping-Höggård M, Sánchez A, Alonso MJ. Nanoparticles as carriers for nasal vaccine delivery. Expert Rev Vaccines. 2005;4(2):185-96.
  14. Smith A, Perelman M, Hinchcliffe M. Chitosan: a promising safe and immune-enhancing adjuvant for intranasal vaccines. Hum Vaccin Immunother. 2014;10(3):797-807.
  15. Islam MA, Firdous J, Choi Y-J, Yun C-H, Cho C-S. Design and application of chitosan microspheres as oral and nasal vaccine carriers: an updated review. Int J Nanomedicine. 2012;7:6077.
  16. Verheul RJ, Amidi M, van der Wal S, van Riet E, Jiskoot W, Hennink WE. Synthesis, characterization and in vitro biological properties of O-methyl free N, N, N-trimethylated chitosan. Biomaterials. 2008;29(27):3642-9.
  17. Hu L, Sun Y, Wu Y. Advances in chitosan-based drug delivery vehicles. Nanoscale. 2013;5(8):3103-11.
  18. Teng Z, Meng L-Y, Yang J-K, He Z, Chen X-G, Liu Y. Bridging nanoplatform and vaccine delivery, a landscape of strategy to enhance nasal immunity. J Control Release. 2022;351:456-75.
  19. Smith Pe, Krohn RI, Hermanson GT, Mallia AK, Gartner FH, Provenzano M, et al. Measurement of protein using bicinchoninic acid. Anal Biochem. 1985;150(1):76-85.
  20. Chen F, Zhang Z-R, Huang Y. Evaluation and modification of N-trimethyl chitosan chloride nanoparticles as protein carriers. Int J Pharm. 2007;336(1):166-73.
  21. Zhao G, Lin Y, Du L, Guan J, Sun S, Sui H, et al. An M2e-based multiple antigenic peptide vaccine protects mice from lethal challenge with divergent H5N1 influenza viruses. Virol J. 2010;7(1):1-8.
  22. Neutra MR, Kozlowski PA. Mucosal vaccines: the promise and the challenge. Nat Rev Immunol. 2006;6(2):148-58.
  23. Hervé P-L, Raliou M, Bourdieu C, Dubuquoy C, Petit-Camurdan A, Bertho N, et al. A novel subnucleocapsid nanoplatform for mucosal vaccination against influenza virus that targets the ectodomain of matrix protein 2. J Virol. 2014;88(1):325-38.
  24. Zeng W, Tan AC, Horrocks K, Jackson DC. A lipidated form of the extracellular domain of influenza M2 protein as a self-adjuvanting vaccine candidate. Vaccine. 2015;33(30):3526-32.
  25. Dhama K, Dhawan M, Tiwari R, Emran TB, Mitra S, Rabaan AA, et al. COVID-19 intranasal vaccines: current progress, advantages, prospects, and challenges. Hum Vaccin Immunother. 2022:1-11.
  26. Vila A, Sanchez A, Evora C, Soriano I, McCallion O, Alonso M. PLA-PEG particles as nasal protein carriers: the influence of the particle size. Int J Pharm. 2005;292(1-2):43-52.
  27. Gutierro I, Hernandez R, Igartua M, Gascon A, Pedraz J. Size dependent immune response after subcutaneous, oral and intranasal administration of BSA loaded nanospheres. Vaccine. 2002;21(1-2):67-77.
  28. Joseph A, Itskovitz-Cooper N, Samira S, Flasterstein O, Eliyahu H, Simberg D, et al. A new intranasal influenza vaccine based on a novel polycationic lipid—ceramide carbamoyl-spermine (CCS): I. Immunogenicity and efficacy studies in mice. Vaccine. 2006;24(18):3990-4006.
  29. Even-Or O, Joseph A, Itskovitz-Cooper N, Samira S, Rochlin E, Eliyahu H, et al. A new intranasal influenza vaccine based on a novel polycationic lipid-ceramide carbamoyl-spermine (CCS). II. Studies in mice and ferrets and mechanism of adjuvanticity. Vaccine. 2011;29(13):2474-86.
  30. Pardeshi CV, Belgamwar VS. Controlled synthesis of N, N, N-trimethyl chitosan for modulated bioadhesion and nasal membrane permeability. Int J Biol Macromol. 2016;82:933-44.
  31. Behrens I, Pena AIV, Alonso MJ, Kissel T. Comparative uptake studies of bioadhesive and non-bioadhesive nanoparticles in human intestinal cell lines and rats: the effect of mucus on particle adsorption and transport. Pharm Res. 2002;19(8):1185-93.
  32. Sandri G, Bonferoni MC, Rossi S, Ferrari F, Gibin S, Zambito Y, et al. Nanoparticles based on N-trimethylchitosan: evaluation of absorption properties using in vitro (Caco-2 cells) and ex vivo (excised rat jejunum) models. Eur J Pharm Biopharm. 2007;65(1):68-77.
  33. Slütter B, Plapied L, Fievez V, Sande MA, des Rieux A, Schneider Y-J, et al. Mechanistic study of the adjuvant effect of biodegradable nanoparticles in mucosal vaccination. J Control Release. 2009;138(2):113-21.
  34. McNeela EA, Jabbal-Gill I, Illum L, Pizza M, Rappuoli R, Podda A, et al. Intranasal immunization with genetically detoxified diphtheria toxin induces T cell responses in humans: enhancement of Th2 responses and toxin-neutralizing antibodies by formulation with chitosan. Vaccine. 2004;22(8):909-14.
  35. Lin H-T, Chen C-C, Chiao D-J, Chang T-Y, Chen X-A, Young J-J, et al. Nanoparticular CpG-adjuvanted SARS-CoV-2 S1 protein elicits broadly neutralizing and Th1-biased immunoreactivity in mice. Int J Biol Macromol. 2021;193:1885-97.
  36. Zhou J, Deng GM. The role of bacterial DNA containing CpG motifs in diseases. J Leukoc Biol. 2021;109(5):991-8.
  37. Huber VC, McKeon RM, Brackin MN, Miller LA, Keating R, Brown SA, et al. Distinct contributions of vaccine-induced immunoglobulin G1 (IgG1) and IgG2a antibodies to protective immunity against influenza. Clin Vaccine Immunol. 2006;13(9):981-90.
  38. Schmitz N, Beerli RR, Bauer M, Jegerlehner A, Dietmeier K, Maudrich M, et al. Universal vaccine against influenza virus: linking TLR signaling to anti‐viral protection. Eur J Immunol. 2012;42(4):863-9.
  39. Slütter B, Hagenaars N, Jiskoot W. Rational design of nasal vaccines. J Drug Target. 2008;16(1):1-17.
  40. Baker Jr JR, Farazuddin M, Wong PT, O’Konek J, Immunology C. The unfulfilled potential of mucosal immunization. J Allergy Clin Immunol. 2022;150(1):1-11.
  41. Vllasaliu D, Exposito-Harris R, Heras A, Casettari L, Garnett M, Illum L, et al. Tight junction modulation by chitosan nanoparticles: comparison with chitosan solution. Int J Pharm. 2010;400(1-2):183-93.
  42. Zhao X, Lu C, Yang S, Ni R, Peng T, Zhang J. Synthesis of N, N, N-trimethyl chitosan-based nanospheres for the prolonged release of curcumin. Food Hydrocoll Health. 2022;2:100092.
  43. Zare S, Kabiri M, Amini Y, Najafi A, Mohammadpour F, Ayati SH, et al. Immunological Assessment of Chitosan or Trimethyl Chitosan-Coated PLGA Nanospheres Containing Fusion Antigen as the Novel Vaccine Candidates Against Tuberculosis. AAPS PharmSciTech. 2022;23(1):1-14.
  44. Tan MP, Tan WS, Mohamed Alitheen NB, Yap WB. M2e-Based Influenza Vaccines with Nucleoprotein: A Review. Vaccines. 2021;9(7):739.
  45. Macpherson A, McCoy K, Johansen F, Brandtzaeg P. The immune geography of IgA induction and function. Mucosal Immunol. 2008;1(1):11-22.
  1. Burns JW, Siadat-Pajouh M, Krishnaney AA, Greenberg HB. Protective effect of rotavirus VP6-specific IgA monoclonal antibodies that lack neutralizing activity. Science. 1996;272(5258):104-7.
  2. Kaetzel CS, Robinson JK, Chintalacharuvu KR, Vaerman J-P, Lamm ME. The polymeric immunoglobulin receptor (secretory component) mediates transport of immune complexes across epithelial cells: a local defense function for IgA. Proc Natl Acad Sci U S A. 1991;88(19):8796-800.
آمار
تعداد مشاهده مقاله: 14,742
تعداد دریافت فایل اصل مقاله: 335


counter
سامانه مدیریت نشریات علمی. طراحی و پیاده سازی از سیناوب