Khairunisa Siti Qamariyah, Rachman Brian Eka, Fahmi Muhamad, Dinana Ichda Arini, Ito Masahiro
Institute of Tropical Disease, Universitas Airlangga, Surabaya, 60115, East Java, Indonesia.
Institute of Tropical Disease, Universitas Airlangga, Surabaya, 60115, East Java, Indonesia; Airlangga Hospital, Universitas Airlangga, Surabaya, 60115, East Java, Indonesia; Faculty of Medicine, Universitas Airlangga, Surabaya, 60132, East Java, Indonesia.
Comput Biol Med. 2025 Mar;187:109758. doi: 10.1016/j.compbiomed.2025.109758. Epub 2025 Jan 30.
HIV has markedly affected millions of people globally, with antiretroviral therapy (ART) transforming acquired immunodeficiency syndrome from a fatal disease to a manageable chronic condition. However, global disparities in ART access persist, particularly in low- and middle-income countries, highlighting the urgent need for affordable HIV vaccines. In this study, we investigated the potential development of a multi-epitope vaccine (MEV) targeting the HIV subtype CRF01_AE, which is prevalent in Indonesia. Using likelihood-based evolutionary inference based on site rates to analyze mutation rates, we identified the Pol and Env proteins as optimal targets. Nine T cell epitopes (five cytotoxic and four helper) were selected based on HLA binding affinity, conservation, antigenicity, and predicted immunogenicity, achieving broad population coverage (∼95 % globally and 99.58 % in Indonesia). The MEV construct incorporated epitopes conjugated to a Vibrio cholerae toxin B subunit adjuvant and a B cell epitope known to induce broadly neutralizing antibodies. In silico characterization, including physicochemical analysis, structural modeling (validated using ProSA-web and Ramachandran plot analysis), and protein-protein docking simulations (using HADDOCK and PRODIGY), demonstrated favorable properties, stable conformation, and high-affinity interaction with antibody fragments (ΔGbind = -10.8 kcal/mol). Molecular dynamics simulations confirmed the formation of a stable complex. Immunogenicity tests revealed a strong antibody and cytokine response. These findings suggest that this MEV construct is a promising and affordable HIV-1 vaccine candidate that warrants further validation.
人类免疫缺陷病毒（HIV）已在全球显著影响了数百万人，抗逆转录病毒疗法（ART）将获得性免疫缺陷综合征从一种致命疾病转变为一种可控制的慢性病。然而，在获得ART治疗方面的全球差异依然存在，尤其是在低收入和中等收入国家，这凸显了对价格可承受的HIV疫苗的迫切需求。在本研究中，我们调查了针对在印度尼西亚流行的HIV CRF01_AE亚型的多表位疫苗（MEV）的潜在开发情况。我们使用基于位点速率的似然进化推断来分析突变率，确定了Pol和Env蛋白为最佳靶点。基于HLA结合亲和力、保守性、抗原性和预测的免疫原性，选择了九个T细胞表位（五个细胞毒性表位和四个辅助性表位），实现了广泛的人群覆盖（全球约95%，印度尼西亚99.58%）。MEV构建体包含与霍乱弧菌毒素B亚基佐剂偶联的表位以及一个已知可诱导广泛中和抗体的B细胞表位。计算机模拟表征，包括物理化学分析、结构建模（使用ProSA-web和拉氏图分析进行验证）以及蛋白质-蛋白质对接模拟（使用HADDOCK和PRODIGY），证明了其良好的特性、稳定的构象以及与抗体片段的高亲和力相互作用（结合自由能ΔGbind = -10.8 kcal/mol）。分子动力学模拟证实了稳定复合物的形成。免疫原性测试显示出强烈的抗体和细胞因子反应。这些发现表明，这种MEV构建体是一种有前景且价格可承受的HIV-1疫苗候选物，值得进一步验证。
