真菌感染（隐球菌病）每年导致超过 100,000 人死亡。没有获得许可的疫苗。我们探讨了用阳离子佐剂配方 01 (CAF01) 佐剂的亚单位隐球菌疫苗的功效和免疫反应。 CAF01 促进体液和辅助 T (Th) 1 和 Th17 免疫反应，并已安全用于人体疫苗试验。四种皮下疫苗，每种都含有单一重组新型隐球菌蛋白抗原，部分保护小鼠免受实验性隐球菌病的侵害。接受二价和四价疫苗制剂的小鼠的保护作用增加高达 100%。接受新型隐球菌肺部攻击的疫苗接种小鼠的白细胞大量涌入肺部，其中包括大量多功能 CD4 T 细胞，这些细胞产生干扰素 γ (IFNγ)、肿瘤坏死因子 α (TNFα) 和白细胞介素 (IL)-17在离体抗原刺激后。还发现了产生细胞因子的肺 CD8 T 细胞，尽管数量较少。在肺、脾和血液中观察到显着、持久的 IFNγ 反应。此外，离体刺激后的 IFNγ 分泌与肺部真菌控制直接相关。因此，我们开发了多价隐球​​菌疫苗，使用已在人体中安全测试的佐剂来保护小鼠免受实验性隐球菌病的侵害。这些临床前研究为人类隐球菌疫苗试验提供了一条途径。版权所有：© 2024 Wang 等人。这是一篇根据知识共享署名许可条款分发的开放获取文章，允许在任何媒体上不受限制地使用、分发和复制，前提是注明原始作者和来源。

The fungal infection, cryptococcosis, is responsible for >100,000 deaths annually. No licensed vaccines are available. We explored the efficacy and immune responses of subunit cryptococcal vaccines adjuvanted with Cationic Adjuvant Formulation 01 (CAF01). CAF01 promotes humoral and T helper (Th) 1 and Th17 immune responses and has been safely used in human vaccine trials. Four subcutaneous vaccines, each containing single recombinant Cryptococcus neoformans protein antigens, partially protected mice from experimental cryptococcosis. Protection increased, up to 100%, in mice that received bivalent and quadrivalent vaccine formulations. Vaccinated mice that received a pulmonary challenge with C. neoformans had an influx of leukocytes into the lung including robust numbers of polyfunctional CD4+ T cells which produced Interferon gamma (IFNγ), tumor necrosis factor alpha (TNFα), and interleukin (IL)-17 upon ex vivo antigenic stimulation. Cytokine-producing lung CD8+ T cells were also found, albeit in lesser numbers. A significant, durable IFNγ response was observed in the lungs, spleen, and blood. Moreover, IFNγ secretion following ex vivo stimulation directly correlated with fungal control in the lungs. Thus, we have developed multivalent cryptococcal vaccines which protect mice from experimental cryptococcosis using an adjuvant which has been safely tested in humans. These preclinical studies suggest a path towards human cryptococcal vaccine trials.Copyright: © 2024 Wang et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.