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INTRODUCTION

Herpes Simplex Virus type 2 or HSV-2 is a major cause of genital herpes, contributing to increased susceptibility to HIV, encephalitis, and other severe complications. Despite the availability of antiviral therapies such as acyclovir, their effectiveness is limited due to resistance and side effects, emphasizing the urgent need for an effective vaccine.

METHODS

This study employed reverse vaccinology and immunoinformatics to design five multivalent, multiepitope mRNA vaccine constructs targeting HSV-2. Four key viral proteins-Glycoprotein B (gB), Ribonucleoside-diphosphate Reductase large subunit (RIR1), Infected Cell Protein 0 (ICP0), and VP23-were selected based on their roles in viral replication and immune evasion. Epitopes for Cytotoxic T Lymphocytes (CD8), Helper T Lymphocytes (CD4), and B cells were predicted and rigorously filtered for antigenicity, non-toxicity, and cytokine induction. Vaccine constructs were designed incorporating 50S ribosomal protein, Human β-defensin 3, and PADRE as adjuvants to enhance immune responses. Structural validation, molecular docking, codon optimization, and physiochemical analysis were performed to assess stability and immunogenic potential.

RESULTS

The vaccine constructs demonstrated favorable physiochemical properties, structural stability, and high antigenicity. Molecular docking revealed strong binding affinities between the predicted epitopes and their respective MHC class I and class II alleles. Proteasomal cleavage analysis confirmed efficient antigen processing, while codon optimization ensured compatibility with the human translational machinery. Computational immune simulations predicted a strong humoral and cellular immune response, including high IgG and IgM levels, robust CD4 and CD8 T-cell activation, and cytokine production.

CONCLUSION

The rationally designed multiepitope mRNA vaccine constructs exhibit strong antigenic potential, structural stability, and immune-stimulatory properties, positioning them as promising candidates for HSV-2 vaccine development. These findings offer a novel, safe, and effective approach to HSV-2 immunization, warranting further experimental validation and preclinical studies.

INTRODUCTION

METHODS

RESULTS

CONCLUSION

引言

2型单纯疱疹病毒（HSV - 2）是生殖器疱疹的主要病因，会增加感染HIV、患脑炎及其他严重并发症的易感性。尽管有阿昔洛韦等抗病毒疗法，但由于耐药性和副作用，其效果有限，这凸显了迫切需要一种有效的疫苗。

方法

本研究采用反向疫苗学和免疫信息学设计了五种针对HSV - 2的多价、多表位mRNA疫苗构建体。基于四种关键病毒蛋白——糖蛋白B（gB）、核糖核苷二磷酸还原酶大亚基（RIR1）、感染细胞蛋白0（ICP0）和VP23在病毒复制和免疫逃逸中的作用进行选择。预测了细胞毒性T淋巴细胞（CD8）、辅助性T淋巴细胞（CD4）和B细胞的表位，并针对抗原性、无毒性和细胞因子诱导进行了严格筛选。设计疫苗构建体时加入了50S核糖体蛋白、人β - 防御素3和PADRE作为佐剂以增强免疫反应。进行了结构验证、分子对接、密码子优化和理化分析以评估稳定性和免疫原性潜力。

结果

疫苗构建体表现出良好的理化性质、结构稳定性和高抗原性。分子对接显示预测的表位与其各自的MHC I类和II类等位基因之间具有强结合亲和力。蛋白酶体切割分析证实了有效的抗原加工，而密码子优化确保了与人类翻译机制的兼容性。计算免疫模拟预测了强烈的体液和细胞免疫反应，包括高IgG和IgM水平、强大的CD4和CD8 T细胞活化以及细胞因子产生。