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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
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