Singh Shakti, Youssef Eman G, Barbarino Ashley, Hautau Haley, Nabeela Sunna, Gebremariam Teclegiorgis, Alkhazraji Sondus, Ostroff Gary, Christensen Dennis, Cochrane Terrence, Ibrahim Ashraf S
The Lundquist Institute at Harbor-UCLA Medical Center.
University of Massachusetts Chan Medical School.
Res Sq. 2025 Sep 5:rs.3.rs-7270678. doi: 10.21203/rs.3.rs-7270678/v1.
species, including and , represent a growing public health concern due to their increasing prevalence and resistance to antifungal agents. is known for causing both superficial and invasive infections, while is a newly emerged, multidrug-resistant pathogen responsible for severe hospital outbreaks with a high mortality rate of ~ 60% in bloodstream infections. Vaccine candidates targeting hyphal cell wall proteins Als3p and Hyr1p have shown protective efficacy in mice. NDV-3A, an alum-formulated Als3p-based vaccine, protects against recurrent vulvovaginal candidiasis in women. We earlier showed that both Als3p and Hyr1p have orthologs in , and that the NDV-3A vaccine, alongside an anti-Hyr1p monoclonal antibody, protect mice from lethal candidemia. Here, we optimized Als3p and Hyr1p dual antigen vaccine formulations with the clinical-stage adjuvant CAF01, demonstrating robust immunity and CD4 T celldependent protection against lethal and . The vaccine formulations also showed enhanced protective efficacy when combined with antifungal drugs. This study highlights the potential of the CAF01-formulated Als3p/Hyr1p dual antigen vaccine in providing durable protective immunity against systemic and mucosal and cross-protection against systemic multidrug-resistant infections.
包括[具体物种1]和[具体物种2]在内的一些物种，因其日益增加的流行率和对抗真菌药物的耐药性，成为日益严重的公共卫生问题。[具体物种1]已知会引起浅表和侵袭性感染，而[具体物种2]是一种新出现的多重耐药病原体，可导致严重的医院感染暴发，在血流感染中的死亡率高达约60%。针对[具体物种]菌丝细胞壁蛋白Als3p和Hyr1p的候选疫苗已在小鼠中显示出保护效果。NDV - 3A是一种基于明矾配方的Als3p疫苗，可预防女性复发性外阴阴道念珠菌病。我们之前表明，Als3p和Hyr1p在[具体物种]中都有直系同源物，并且NDV - 3A疫苗与抗Hyr1p单克隆抗体一起可保护小鼠免受致死性[具体物种]念珠菌血症的侵害。在此，我们用临床阶段佐剂CAF01优化了Als3p和Hyr1p双抗原疫苗配方，证明其具有强大的免疫力以及针对致死性[具体物种1]和[具体物种2]的CD4 T细胞依赖性保护作用。当与抗真菌药物联合使用时，这些疫苗配方还显示出增强的保护效果。这项研究突出了CAF01配方的Als3p/Hyr1p双抗原疫苗在提供针对系统性和黏膜性[具体物种1]的持久保护性免疫以及针对系统性多重耐药[具体物种2]感染的交叉保护方面的潜力。
