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In this study, artificial intelligence (AI) and immunoinformatics were employed to design a novel multi-epitope DNA vaccine targeting conserved regions of the FIV gag, pol, and env genes. Predicted B-cell and T-cell epitopes were evaluated for their capacity to induce strong immune responses while minimizing allergenic or toxic effects and were linked to the immune adjuvant PADRE. Structural analysis indicated that the vaccine construct is stable, soluble, and biocompatible, with a well-folded tertiary structure that binds Toll-like receptor 9 (TLR9) and elicits robust humoral and cellular immune responses. These findings identify a promising FIV vaccine candidate and provide insights for the development of next-generation HIV vaccines.<\/jats:p>","DOI":"10.3390\/pathogens15030341","type":"journal-article","created":{"date-parts":[[2026,3,23]],"date-time":"2026-03-23T11:59:36Z","timestamp":1774267176000},"page":"341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Multi-Epitope DNA-Based Feline Immunodeficiency Virus Vaccine Construct Designed by Immunoinformatic and Machine Learning Tools as a Surrogate Model for HIV Vaccine Development"],"prefix":"10.3390","volume":"15","author":[{"given":"Tyler","family":"Michalka","sequence":"first","affiliation":[{"name":"Department of Veterinary Biomedical Sciences, Lewyt College of Veterinary Medicine, Long Island University, Brookville, NY 11548, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abid Ullah","family":"Shah","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biomedical Sciences, Lewyt College of Veterinary Medicine, Long Island University, Brookville, NY 11548, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tiffany","family":"Liang","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biomedical Sciences, Lewyt College of Veterinary Medicine, Long Island University, Brookville, NY 11548, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1663-5820","authenticated-orcid":false,"given":"Maged Gomaa","family":"Hemida","sequence":"additional","affiliation":[{"name":"Department of Veterinary Biomedical Sciences, Lewyt College of Veterinary Medicine, Long Island University, Brookville, NY 11548, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e5","DOI":"10.4081\/idr.2013.s1.e5","article-title":"HIV drug resistance: Problems and perspectives","volume":"5","author":"Pennings","year":"2013","journal-title":"Infect. 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