Utilizing Immunoinformatics for mRNA Vaccine Design against Influenza D Virus

E. K. Oladipo, Stephen Feranmi Adeyemo, M. Akinboade, Temitope Michael Akinleye, Kehinde Favour Siyanbola, Precious Ayomide Adeogun, Victor Michael Ogunfidodo, Christiana Adewumi Adekunle, Olubunmi Ayobami Elutade, Esther Eghogho Omoathebu, Blessing Oluwatunmise Taiwo, Elizabeth Olawumi Akindiya, Lucy Ochola, H. Onyeaka
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Abstract

Background: Influenza D Virus (IDV) presents a possible threat to animal and human health, necessitating the development of effective vaccines. Although no human illness linked to IDV has been reported, the possibility of human susceptibility to infection remains uncertain. Hence, there is a need for an animal vaccine to be designed. Such a vaccine will contribute to preventing and controlling IDV outbreaks and developing effective countermeasures against this emerging pathogen. This study, therefore, aimed to design an mRNA vaccine construct against IDV using immunoinformatic methods and evaluate its potential efficacy. Methods: A comprehensive methodology involving epitope prediction, vaccine construction, and structural analysis was employed. Viral sequences from six continents were collected and analyzed. A total of 88 Hemagglutinin Esterase Fusion (HEF) sequences from IDV isolates were obtained, of which 76 were identified as antigenic. Different bioinformatics tools were used to identify preferred CTL, HTL, and B-cell epitopes. The epitopes underwent thorough analysis, and those that can induce a lasting immunological response were selected for the construction. Results: The vaccine prototype comprised nine epitopes, an adjuvant, MHC I-targeting domain (MITD), Kozaq, 3′ UTR, 5′ UTR, and specific linkers. The mRNA vaccine construct exhibited antigenicity, non-toxicity, and non-allergenicity, with favourable physicochemical properties. The secondary and tertiary structure analyses revealed a stable and accurate vaccine construct. Molecular docking simulations also demonstrated strong binding affinity with toll-like receptors. Conclusions: The study provides a promising framework for developing an effective mRNA vaccine against IDV, highlighting its potential for mitigating the global impact of this viral infection. Further experimental studies are needed to confirm the vaccine’s efficacy and safety.
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利用免疫信息学设计抗 D 型流感病毒的 mRNA 疫苗
背景:D 型流感病毒(IDV)可能对动物和人类健康构成威胁,因此有必要开发有效的疫苗。虽然尚未有人类疾病与 IDV 有关的报道,但人类对感染 IDV 的易感性仍不确定。因此,有必要设计一种动物疫苗。这种疫苗将有助于预防和控制 IDV 的爆发,并针对这种新出现的病原体制定有效的应对措施。因此,本研究旨在利用免疫形式学方法设计一种针对 IDV 的 mRNA 疫苗构建体,并评估其潜在的功效。方法:本研究采用了包括表位预测、疫苗构建和结构分析在内的综合方法。收集并分析了来自六大洲的病毒序列。共从 IDV 分离物中获得 88 个血凝素酯酶融合(HEF)序列,其中 76 个被确定为抗原性序列。利用不同的生物信息学工具确定了首选的 CTL、HTL 和 B 细胞表位。对这些表位进行了全面分析,并选择了那些能诱导持久免疫反应的表位进行构建。结果:疫苗原型由九个表位、佐剂、MHC I靶向结构域(MITD)、Kozaq、3′UTR、5′UTR和特异性连接体组成。该 mRNA 疫苗构建体具有抗原性、无毒性和无过敏性,并具有良好的理化特性。二级和三级结构分析表明,该疫苗结构稳定、准确。分子对接模拟也显示了与收费样受体的强结合亲和力。结论这项研究为开发针对 IDV 的有效 mRNA 疫苗提供了一个前景广阔的框架,凸显了其减轻这种病毒感染对全球影响的潜力。疫苗的有效性和安全性还需要进一步的实验研究来证实。
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