{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,10]],"date-time":"2026-02-10T17:51:41Z","timestamp":1770745901739,"version":"3.49.0"},"reference-count":44,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T00:00:00Z","timestamp":1749600000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Background\/objectives:\u00a0Candida albicans is a major fungal pathogen that poses a serious threat to immunocompromised individuals. The increasing prevalence of fluconazole-resistant strains presents a critical clinical challenge, emphasizing the urgent need for novel therapeutic strategies. This study aimed to evaluate the prophylactic potential of a new liposomal vaccine formulation, Tuft-lip-WCAgs, comprising Tuftsin and C. albicans whole cell antigens, in providing immune protection against systemic candidiasis. Methods: The vaccine formulation was tested in a murine model of systemic C. albicans infection. The efficacy of the Tuft-lip-WCAg vaccine was evaluated through a survival analysis, fungal burden assessments, and immunological profiling. Immune responses were assessed by measuring serum antibody titers and isotypes, T cell proliferation, and cytokine secretion (IFN-\u03b3 and IL-4) from splenocytes. Results: FLZ treatment showed weak antifungal activity, high MIC values, and limited biofilm disruption and failed to ensure long-term survival, resulting in 100% mortality by day 40. In contrast, Tuft-lip-WCAg vaccination was well tolerated and conferred complete protection, with no detectable fungal burden by day 40. Vaccinated mice exhibited significantly elevated total antibody titers (166,667 \u00b1 14,434), increased IgG2a levels, and enhanced T cell proliferation (stimulation index: 3.9 \u00b1 0.84). Splenocytes from immunized mice secreted markedly higher levels of IFN-\u03b3 (634 \u00b1 128 pg\/mL) and IL-4 (582 \u00b1 82 pg\/mL), indicating a balanced Th1\/Th2 immune response. Tuft-lip-WCAg vaccination also achieved 100% survival and the lowest kidney fungal burden (556 \u00b1 197 CFUs\/g). Conclusions: Tuft-lip-WCAg formulation is a safe, immunogenic, and highly effective vaccine candidate that offers complete protection against drug-resistant C. albicans in a murine model. These findings support its promise as a novel immunoprophylactic strategy, particularly for immunocompromised populations at high risk of invasive candidiasis.<\/jats:p>","DOI":"10.3390\/vaccines13060630","type":"journal-article","created":{"date-parts":[[2025,6,11]],"date-time":"2025-06-11T06:11:49Z","timestamp":1749622309000},"page":"630","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Targeting Azole-Resistant Candida albicans: Tetrapeptide Tuftsin-Modified Liposomal Vaccine Induces Superior Immune Protection"],"prefix":"10.3390","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-4031-4189","authenticated-orcid":false,"given":"Masood A.","family":"Khan","sequence":"first","affiliation":[{"name":"Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah 51412, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4528-2668","authenticated-orcid":false,"given":"Arif","family":"Khan","sequence":"additional","affiliation":[{"name":"Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah 51412, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9306-609X","authenticated-orcid":false,"given":"Abdullah M.","family":"Alnuqaydan","sequence":"additional","affiliation":[{"name":"Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah 51412, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8697-5340","authenticated-orcid":false,"given":"Aqel","family":"Albutti","sequence":"additional","affiliation":[{"name":"Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah 51412, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6863-469X","authenticated-orcid":false,"given":"Basmah F.","family":"Alharbi","sequence":"additional","affiliation":[{"name":"Department of Basic Health Sciences, College of Applied Medical Sciences, Qassim University, Buraydah 51412, Saudi Arabia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7377-7388","authenticated-orcid":false,"given":"Mohammad","family":"Owais","sequence":"additional","affiliation":[{"name":"Interdisciplinary Biotechnology Unit, Faculty of Life Sciences, Aligarh Muslim University, Aligarh 202002, India"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,6,11]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/j.mib.2020.05.006","article-title":"The gut, the bad and the harmless: Candida albicans as a commensal and opportunistic pathogen in the intestine","volume":"56","author":"Kumamoto","year":"2020","journal-title":"Curr. 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