{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,23]],"date-time":"2026-10-23T21:16:08Z","timestamp":1792790168463,"version":"4.5.0"},"reference-count":28,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"FCT\u2014Funda\u00e7\u00e3o para a Ci\u00eancia e Tecnologia","award":["UID\/04378\/2025"],"award-info":[{"award-number":["UID\/04378\/2025"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"crossref"}]},{"award":["UID\/04378\/2025"],"award-info":[{"award-number":["UID\/04378\/2025"]}],"id":[{"id":"https:\/\/ror.org\/00snfqn58","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Research Unit on Applied Molecular Biosciences\u2014UCIBIO","award":["UID\/PRR\/04378\/2025"],"award-info":[{"award-number":["UID\/PRR\/04378\/2025"]}]},{"name":"Associate Laboratory Institute for Health and Bioeconomy\u2014i4HB","award":["LA\/P\/0140\/2020"],"award-info":[{"award-number":["LA\/P\/0140\/2020"]}]},{"name":"1H-TOXRUN\u2014CESPU","award":["PhytoCandd_GI2-CESPU-2023"],"award-info":[{"award-number":["PhytoCandd_GI2-CESPU-2023"]}]},{"name":"1H-TOXRUN\u2014CESPU","award":["ToxiBug4Ca-GI2-CESPU-2025"],"award-info":[{"award-number":["ToxiBug4Ca-GI2-CESPU-2025"]}]},{"name":"FCT\/MCTES (PIDDAC), Exploratory Project ToxiBug4Candida","award":["2024.13432.PEX"],"award-info":[{"award-number":["2024.13432.PEX"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Vaccines"],"abstract":"<jats:p>Over the past decade, antifungal vaccinology has produced genuine proof of concept: adhesin-based candidates such as NDV-3A have completed Phase II human trials, and reverse-vaccinology pipelines now routinely generate multi-epitope constructs with high predicted population coverage against Candida albicans and the multidrug-resistant Candida auris. However, no antifungal vaccine has reached the market, and the reasons for this gap are rarely examined together in a single, critical account. This review argues that the bottleneck is not primarily antigen discovery, but a layered set of translational barriers: biological constraints inherent to a commensal, morphologically plastic pathogen; manufacturing and purity requirements that complicate subunit vaccine production; a historical bias in preclinical animal models toward chemically immunosuppressed, rather than genetically susceptible, hosts; an underutilization of key insights from veterinary medicine; and a fragmented regulatory and commercial landscape that structurally disincentivizes investment in niche, high-risk patient populations. We further examine emerging immunotherapeutic strategies\u2014passive antibody engineering, cytokine-based adjuvant approaches, phytocompound-derived antifungals, and dual-action nanovaccines\u2014as partial, rather than complete, solutions to the immunocompromised-host paradox that limits active immunization in the patients who need protection most. Finally, we situate Candida vaccine development within a One Health and global-equity framework, arguing that diagnostic infrastructure, HLA population diversity, and cold-chain economics must be addressed as part of vaccine design rather than as an afterthought.<\/jats:p>","DOI":"10.3390\/vaccines14090825","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:35:28Z","timestamp":1790868928000},"page":"825","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Rethinking Candida Vaccine Translation: Barriers, Immunotherapies and a One Health Imperative"],"prefix":"10.3390","volume":"14","author":[{"given":"Julie","family":"Krier","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Sciences, CESPU University, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5960-3610","authenticated-orcid":false,"given":"Francisco A. M.","family":"Silva","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, CESPU University, 4585-116 Gandra, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8633-2230","authenticated-orcid":false,"given":"C\u00e9lia Fortuna","family":"Rodrigues","sequence":"additional","affiliation":[{"name":"Department of Pharmaceutical Sciences, CESPU University, 4585-116 Gandra, Portugal"},{"name":"Associate Laboratory i4HB\u2014Institute for Health and Bioeconomy, CESPU University, 4585-116 Gandra, Portugal"},{"name":"UCIBIO\u2014Research Unit on Applied Molecular Biosciences Unit, Translational Toxicology Research Laboratory, CESPU University, 4585-116 Gandra, Portugal"},{"name":"LEPABE\/ALiCE\u2014Laboratory for Process Engineering, Environment, Biotechnology and Energy and Associate Laboratory in Chemical Engineering, Faculty of Engineering, University of Porto, Rua Dr. Roberto Frias, 4200-465 Porto, Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"549","DOI":"10.2147\/CLEP.S459600","article-title":"Epidemiology of Invasive Candidiasis","volume":"16","author":"Bays","year":"2024","journal-title":"Clin. Epidemiol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1569","DOI":"10.1093\/jac\/dkad139","article-title":"Invasive Candidiasis: Current Clinical Challenges and Unmet Needs in Adult Populations","volume":"78","author":"Soriano","year":"2023","journal-title":"J. Antimicrob. Chemother."},{"key":"ref_3","first-page":"20499361231161387","article-title":"Flucytosine and Its Clinical Usage","volume":"10","author":"Sigera","year":"2023","journal-title":"Ther. Adv. Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"104879","DOI":"10.1016\/j.micpath.2021.104879","article-title":"In-Silico Design of a Multivalent Epitope-Based Vaccine against Candida auris","volume":"155","author":"Akhtar","year":"2021","journal-title":"Microb. Pathog."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e1007460","DOI":"10.1371\/journal.ppat.1007460","article-title":"The NDV-3A Vaccine Protects Mice from Multidrug Resistant Candida auris Infection","volume":"15","author":"Singh","year":"2019","journal-title":"PLoS Pathog."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1928","DOI":"10.1093\/cid\/ciy185","article-title":"A Fungal Immunotherapeutic Vaccine (NDV-3A) for Treatment of Recurrent Vulvovaginal Candidiasis\u2014A Phase 2 Randomized, Double-Blind, Placebo-Controlled Trial","volume":"66","author":"Edwards","year":"2018","journal-title":"Clin. Infect. Dis."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"105462","DOI":"10.1016\/j.compbiomed.2022.105462","article-title":"Subtractive Proteomics Assisted Therapeutic Targets Mining and Designing Ensemble Vaccine against Candida auris for Immune Response Induction","volume":"145","author":"Khan","year":"2022","journal-title":"Comput. Biol. Med."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"100474","DOI":"10.1016\/j.jgeb.2025.100474","article-title":"Designing of Multi-Valent Epitope Vaccine Displaying Interactions with Diverse HLA Alleles against Candida auris Using Immuno Informatics","volume":"23","author":"Ahlawat","year":"2025","journal-title":"J. Genet. Eng. Biotechnol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s43141-022-00415-3","article-title":"Design of a Multi-Epitope Vaccine against the Pathogenic Fungi Candida tropicalis Using an in Silico Approach","volume":"20","author":"Akhtar","year":"2022","journal-title":"J. Genet. Eng. Biotechnol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"89","DOI":"10.3897\/pharmacia.68.e49384","article-title":"The Study of the Therapeutic Effectiveness of the Associated Inactivated and Subunit Vaccines Based on Candida albicans and Candida tropicalis Fungi","volume":"68","author":"Rybalkin","year":"2021","journal-title":"Pharmacia"},{"key":"ref_11","first-page":"79","article-title":"Management of Invasive Candidiasis in the ICU: Challenges and Advances (Review)","volume":"5","author":"Elmasry","year":"2025","journal-title":"Med. Int."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1339501","DOI":"10.3389\/fcimb.2024.1339501","article-title":"Promising Immunotherapeutic Targets for Treating Candidiasis","volume":"14","author":"Feng","year":"2024","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e00339-19","DOI":"10.1128\/mSphere.00339-19","article-title":"Experimental Mouse Models of Disseminated Candida auris Infection","volume":"4","author":"Xin","year":"2019","journal-title":"mSphere"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"1641373","DOI":"10.3389\/fcimb.2025.1641373","article-title":"Innovative Antifungal Strategies to Combat Drug-Resistant Candida auris: Recent Advances and Clinical Implications","volume":"15","author":"Du","year":"2025","journal-title":"Front. Cell. Infect. Microbiol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"101752","DOI":"10.1016\/j.smim.2023.101752","article-title":"Exploiting Antifungal Immunity in the Clinical Context","volume":"67","author":"Lionakis","year":"2023","journal-title":"Semin. Immunol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"95","DOI":"10.1016\/j.mib.2017.10.018","article-title":"Modulating Host Immune Responses to Fight Invasive Fungal Infections","volume":"40","author":"Scriven","year":"2017","journal-title":"Curr. Opin. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1007\/s00203-024-04010-7","article-title":"Fungal Vaccines and Adjuvants: A Tool to Reveal the Interaction between Host and Fungi","volume":"206","author":"Wang","year":"2024","journal-title":"Arch. Microbiol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"925821","DOI":"10.3389\/fimmu.2022.925821","article-title":"Antibodies Targeting Candida albicans Als3 and Hyr1 Antigens Protect Neonatal Mice from Candidiasis","volume":"13","author":"Singh","year":"2022","journal-title":"Front. Immunol."},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Ivanov, M., \u0106iri\u0107, A., and Stojkovi\u0107, D. (2022). Emerging Antifungal Targets and Strategies. Int. J. Mol. Sci., 23.","DOI":"10.3390\/ijms23052756"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"102862","DOI":"10.1016\/j.jddst.2021.102862","article-title":"Synthesis and Evaluation of Metallic Nanoparticles-Based Vaccines against Candida albicans Infections","volume":"68","author":"Abdelnaby","year":"2022","journal-title":"J. Drug Deliv. Sci. Technol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/j.actbio.2016.05.001","article-title":"Protective Effect of Antigen Delivery Using Monoolein-Based Liposomes in Experimental Hematogenously Disseminated Candidiasis","volume":"39","author":"Carneiro","year":"2016","journal-title":"Acta Biomater."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"115362","DOI":"10.1016\/j.biopha.2023.115362","article-title":"Design of a Lipid Nano-Delivery System Containing Recombinant Candida albicans Chitinase 3 as a Potential Vaccine against Fungal Infections","volume":"166","author":"Pacheco","year":"2023","journal-title":"Biomed. Pharmacother."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"100489","DOI":"10.1016\/j.jgeb.2025.100489","article-title":"The Evaluation of a Novel Multi-Epitope Vaccine against Human Papillomavirus and Candida albicans","volume":"23","author":"Ahmadifar","year":"2025","journal-title":"J. Genet. Eng. Biotechnol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Branda, F., Petrosillo, N., Ceccarelli, G., Giovanetti, M., De Vito, A., Madeddu, G., Scarpa, F., and Ciccozzi, M. (2025). Antifungal Agents in the 21st Century: Advances, Challenges, and Future Perspectives. Infect. Dis. Rep., 17.","DOI":"10.3390\/idr17040091"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"7559","DOI":"10.1039\/D3SC01242E","article-title":"Synthesis of Oligosaccharides to Identify an Immunologically Active Epitope against Candida auris Infection","volume":"14","author":"Singh","year":"2023","journal-title":"Chem. Sci."},{"key":"ref_26","first-page":"309","article-title":"Vaccines in the Treatment of Invasive Candidiasis","volume":"6","author":"Wang","year":"2015","journal-title":"Virulence"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1111\/cmi.13238","article-title":"Protective Effect of Fungal Extracellular Vesicles against Murine Candidiasis","volume":"22","author":"Vargas","year":"2020","journal-title":"Cell. Microbiol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"326","DOI":"10.4274\/tjps.galenos.2020.81226","article-title":"Prophylaxis and Therapeutic Ability of Inactivated Dermatophytic Vaccine Against Dermatophytosis in the Rabbits as an Animal Model","volume":"18","year":"2021","journal-title":"Turk. J. Pharm. Sci."}],"container-title":["Vaccines"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/9\/825\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T15:36:18Z","timestamp":1790868978000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-393X\/14\/9\/825"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,19]]},"references-count":28,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["vaccines14090825"],"URL":"https:\/\/doi.org\/10.3390\/vaccines14090825","relation":{},"ISSN":["2076-393X"],"issn-type":[{"value":"2076-393X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,19]]}}}