تولید و ارزیابی های درون تنی واکسن بالقوه طراحی شده به صورت اینسیلیکو علیه HPV مبتنی بر پروتئین L2

نگهداری پور, مانیکا and نظافت, نوید and حیدری, رضا and عرفانی, نصراله and حاجی قهرمانی, نسیم and قشون, محمدباقر and شولیان, اسکندر and رهبر, محمد رضا and نجف پور, سهراب and دهشهری, علی and مروت, محمد حسین and قاسمی, یونس (1399) تولید و ارزیابی های درون تنی واکسن بالقوه طراحی شده به صورت اینسیلیکو علیه HPV مبتنی بر پروتئین L2. Current Pharmaceutical Biotechnology ــ 21 (4). pp. 316-324. شاپا 13892010

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Production and Preliminary In Vivo Evaluations of a Novel in silico-designed L2-based Potential HPV Vaccine

English Abstract

Background: L2-based human papillomavirus (HPV) prophylactic vaccines, containing epitopes from HPV minor capsid proteins, are under investigation as second-generation HPV vaccines. No such vaccine has passed clinical trials yet, mainly due to the low immunogenicity of peptide vaccines; so efforts are being continued. A candidate vaccine composed of two HPV16 L2 epitopes, flagellin and a toll-like receptor (TLR) 4 agonist (RS09) as adjuvants, and two universal T-helper epitopes was designed in silico in our previous researches. Methods: The designed vaccine construct was expressed in E. coli BL21 (DE3) and purified through metal affinity chromatography. Following mice vaccination, blood samples underwent ELISA and flow cytometry analyses for the detection of IgG and seven Th1 and Th2 cytokines. Results: Following immunization, Th1 (IFN-γ, IL-2) and Th2 (IL-4, IL-5, IL-10) type cytokines, as well as IgG, were induced significantly compared with the PBS group. Significant increases in IFN-γ, IL-2, and IL-5 levels were observed in the vaccinated group versus Freund’s adjuvant group. Conclusion: The obtained cytokine induction profile implied both cellular and humoral responses, with a more Th-1 favored trend. However, an analysis of specific antibodies against L2 is required to confirm humoral responses. No significant elevation in inflammatory cytokines, (IL-6 and TNF-α), suggested a lack of unwanted inflammatory side effects despite using a combination of two TLR agonists. The designed construct might be capable of inducing adaptive and innate immunity; nevertheless, comprehensive immune tests were not conducted at this stage and will be a matter of future work.

Item Type:Article
زبان سند : انگلیسی
نویسنده اول :مانیکا نگهداری پور
نویسنده :نوید نظافت
نویسنده :رضا حیدری
نویسنده :نصراله عرفانی
نویسنده :نسیم حاجی قهرمانی
نویسنده :محمدباقر قشون
نویسنده :اسکندر شولیان
نویسنده :محمد رضا رهبر
نویسنده :سهراب نجف پور
نویسنده :علی دهشهری
نویسنده :محمد حسین مروت
نویسنده مسئول :یونس قاسمی
Additional Information:IMPACT FACTOR:1.516 Indexed in: ISI, Scopus, PubMed/Medline, Embase
کلیدواژه ها (انگلیسی):Human papillomavirus (HPV), L2, cervical cancer, epitope vaccine, flagellin, TLR4 agonist, TLR5 agonist, adjuvant.
Subjects:QV pharmacology > QV 737 Pharmaceutical Biotechnology
Divisions:School of Pharmacy > Department of Pharmaceutical Biotechnology
ID Code:12914
Deposited By: Dr Nasim Hajighahramani
Deposited On:14 Feb 1399 07:14
Last Modified:14 Feb 1399 07:14

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