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利用计算免疫学设计针对家禽传染性法氏囊病的靶向亚单位疫苗。

Harnessing computational immunology to design targeted subunit vaccines for infectious bursal disease in poultry.

作者信息

Oladipo Elijah Kolawole, Adeyemo Stephen Feranmi, Oshoneye Ayomiposi Isaiah, Akintola Hannah Blessing, Elegbede Bolatito Islam, Ayoomoba Tobiloba Uren, Atilade Dorcas Ayomide, Adegboye Omolara Omoboye, Ejikeme Abuoma Elizabeth, Balogun Chris Olamide, Aderibigbe Kehinde Abolade, Popoola Possible Okikiola, Alabi Victoria Ajike, Irewolede Boluwatife Ayobami, Ano-Edward Gbemi Henry, Ayeleso Ademola Olabode, Onyeaka Helen

机构信息

Division of Vaccine and Pharmacotherapies Design and Development, Helix Biogen Institute, Ogbomoso, Oyo, Nigeria.

Department of Microbiology, Laboratory of Molecular Biology, Immunology and Bioinformatics, Adeleke University, Ede, Osun, Nigeria.

出版信息

Front Bioinform. 2025 Apr 4;5:1562997. doi: 10.3389/fbinf.2025.1562997. eCollection 2025.

Abstract

INTRODUCTION

Infectious bursal disease (IBD), caused by the infectious bursal disease Q8 virus (IBDV), is a highly contagious disease in young chickens, leading to immunosuppression with great economic importance. IBDV, a non-enveloped virus with a bipartite dsRNA genome, infects the bursa of Fabricius, causing severe gastrointestinal disease. Effective vaccines are urgently needed due to the limitations of current oral vaccines, including gastrointestinal degradation and low immunogenicity. This study designs and evaluates a multiepitope subunit vaccine using immunoinformatics.

METHODS

Sequences of the IBDV structural proteins VP2 and VP3 were obtained from the National Centre for Biotechnology Information) NCBI. These are structural proteins VP2 and VP3 were subjected to the Vaxijen 2.0 webserver to predict the antigenicity, ToxiPred to predict the toxicity and further analyzed to identify immunogenic epitopes of Chicken Leukocyte Antigens (CLAs) using the NetMHCpan 4.1 webserver.

RESULTS

The final vaccine construct includes 2 HTL, 21 CTL, and 7 LBL epitopes, with gallinacin-3 precursor as an adjuvant. The construct is antigenic (0.5605), non-allergenic, and non-toxic, consisting of 494 amino acids with a molecular weight of 54.88 kDa and a positive charge (pI of 9.23). It is stable, hydrophilic, and soluble. Population coverage analysis revealed a global immune coverage of 89.83%, with the highest in Europe (99.86%) and the lowest in Central America (25.01%). Molecular docking revealed strong interactions with TLR-2_1, TLR-4, and TLR-7, with TLR-7 exhibiting the highest binding affinity (-366.15 kcal/mol). Immune simulations indicated a robust immune response, with high initial IgM levels, sustained IgG, memory cell formation, and activation of T helper (Th) cells 1 and 2, Natural Killer (NK) cells, and dendritic cells, suggesting potential long-lasting immunity against IBDV.

DISCUSSION

This study presents a promising multi-epitope subunit vaccine candidate capable of effective immunization against IBDV with broad population coverage. However, further experimental validation is required to confirm its efficacy and safety.

摘要

引言

传染性法氏囊病(IBD)由传染性法氏囊病病毒(IBDV)引起,是幼鸡的一种高度传染性疾病,会导致免疫抑制,具有重大经济影响。IBDV是一种具有双链RNA基因组的无包膜病毒,感染法氏囊,引发严重的胃肠道疾病。由于当前口服疫苗存在局限性,包括胃肠道降解和免疫原性低等问题,因此迫切需要有效的疫苗。本研究利用免疫信息学设计并评估了一种多表位亚单位疫苗。

方法

IBDV结构蛋白VP2和VP3的序列从美国国立生物技术信息中心(NCBI)获取。这些结构蛋白VP2和VP3通过Vaxijen 2.0网络服务器预测抗原性,通过ToxiPred预测毒性,并使用NetMHCpan 4.1网络服务器进一步分析以鉴定鸡白细胞抗原(CLA)的免疫原性表位。

结果

最终的疫苗构建体包含2个辅助性T淋巴细胞(HTL)表位、21个细胞毒性T淋巴细胞(CTL)表位和7个线性B淋巴细胞(LBL)表位,以gallinacin-3前体作为佐剂。该构建体具有抗原性(0.5605),无致敏性且无毒,由494个氨基酸组成,分子量为54.88 kDa,带正电荷(等电点为9.23)。它稳定、亲水性好且可溶。群体覆盖率分析显示全球免疫覆盖率为89.83%,其中欧洲最高(99.86%),中美洲最低(25.01%)。分子对接显示与Toll样受体2_1(TLR-2_1)、TLR-4和TLR-7有强烈相互作用,TLR-7表现出最高的结合亲和力(-366.15千卡/摩尔)。免疫模拟表明有强大的免疫反应,初始IgM水平高,IgG持续存在,有记忆细胞形成,辅助性T细胞1和2、自然杀伤(NK)细胞以及树突状细胞被激活,表明对IBDV可能具有持久免疫力。

讨论

本研究提出了一种有前景的多表位亚单位疫苗候选物,能够有效免疫预防IBDV,且群体覆盖率广。然而,需要进一步的实验验证来确认其有效性和安全性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb9e/12006097/94f71f0ca1da/fbinf-05-1562997-g001.jpg

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