{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T00:42:34Z","timestamp":1791247354533,"version":"4.1.0"},"reference-count":223,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T00:00:00Z","timestamp":1747094400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Immunol."],"abstract":"<jats:p>HIV (human immunodeficiency virus) presents a global health crisis, causing significant AIDS-related deaths and over one million new infections annually. The curbing of HIV is an intricate and continuously evolving domain, marked by numerous challenges, including drug resistance and the absence of a significant cure or vaccine because of its mutating ability and diverse antigens in its envelope, prompting research for functional cures and long-term remission strategies. The endeavor to devise an HIV vaccine capable of eliciting robust and broadly cross-reactive humoral and cellular immune responses is a formidable undertaking, primarily due to the pronounced genetic heterogeneity of HIV-1, the variances observed in virus subtypes (clades) across distinct geographic regions, and the polymorphic nature of human leukocyte antigens (HLA). The viral envelope protein (gp120) selectively interacts with CD4 and chemokine receptors on the surface of target cells. It serves as the key initiator in the intricate viral entry into host cells, rendering it a compelling candidate for vaccine development. This study used bioinformatic tools to design a safe, hypoallergenic, and non-toxic mRNA HIV-1 vaccine by assembling immunogenic B- and T-cell epitopes from the gp120 protein. We identified antigenic, non-toxic, and non-allergic B-cell epitopes (IEPLGIAPTRAKRRVVER) and T-cell epitopes (QQKVHALFY, ITIGPGQVF, WQGVGQAMY, APTRAKRRV, KQQKVHALFYRLDIV, QQKVHALFYRLDIVQ, QKVHALFYRLDIVQI, SLAEEEIIIRSENLT, and IRSENLTNNVKTIIV). For designing the mRNA vaccine against HIV-1 gp120, we assembled the epitopes with 5\u2032 m7G cap, 5\u2032 UTR (untranslated region), Kozak sequence, signal peptide (tPA), RpfE (resuscitation-promoting factor E) adjuvant at N-terminal and MITD (MHC class I trafficking domain) adjuvant, stop codon, 3\u2032 UTR, and 120-nucleotide long poly(A) tail at the C-terminal with immunogenic robustness linkers. The mRNA vaccine is translated into a protein-based vaccine by the host body\u2019s ribosomes. Their comprehensive computational findings, including physicochemical, structural, and 3D refinement analyses, substantiated the stability and quality of the translated vaccine. Molecular docking and simulation revealed a strong and stable binding affinity of vaccine immunization with immune cells\u2019 pattern recognition receptors (TLR4). Immune simulations demonstrated a potent primary immune response characterized by a gradual increase in immunoglobulins and a corresponding decline in antigen concentration. This bioinformatics-driven study presents a promising HIV-1 mRNA vaccine candidate, underscoring the need for further experimental validation through preclinical and clinical trials. At the same time, its methodologies hold the potential for addressing other challenging infectious diseases, thereby impacting vaccinology broadly.<\/jats:p>","DOI":"10.3389\/fimmu.2025.1480025","type":"journal-article","created":{"date-parts":[[2025,5,13]],"date-time":"2025-05-13T05:29:54Z","timestamp":1747114194000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":17,"title":["Immunoinformatic-driven design and evaluation of multi-epitope mRNA vaccine targeting HIV-1 gp120"],"prefix":"10.3389","volume":"16","author":[{"given":"Muhammad Zeeshan","family":"Ahmed","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tazeen","family":"Rao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zeeshan","family":"Mutahir","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sarfraz","family":"Ahmed","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Najeeb","family":"Ullah","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suvash Chandra","family":"Ojha","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,5,13]]},"reference":[{"key":"B1","unstructured":"Washington, D.C., USA\n          HIV.gov\n          Epidemic global statistics\n          \n          2022"},{"key":"B2","unstructured":"HIV\n          \n          2023"},{"key":"B3","unstructured":"HIV\n          \n          2023"},{"key":"B4","unstructured":"Maryland, USA\n          NIH\n          HIV treatment: the basics\n          \n          2016"},{"key":"B5","unstructured":"HIV\/AIDS prevention and treatment\n          \n          \n            \n              Bertozzi\n              S\n            \n            \n              Padian\n              NS\n            \n            \n              Wegbreit\n              J\n            \n            \n              DeMaria\n              LM\n            \n            \n              Feldman\n              B\n            \n            \n              Gayle\n              H\n            \n          \n          Maryland, USA\n          The International Bank for Reconstruction and Development\/The World Bank\n          Disease control priorities in developing countries\n          \n          2006"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1038\/news.2008.595","article-title":"HIV can \u201cnever be cured","author":"Hopkin","year":"2008","journal-title":"Nature"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a007161","article-title":"HIV-1 antiretroviral drug therapy","volume":"2","author":"Arts","year":"2012","journal-title":"Cold Spring Harb. 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