Data_Sheet_1_Genome-wide scan for potential CD4+ T-cell vaccine candidates in Candida auris by exploiting reverse vaccinology and evolutionary information.PDF

Candida auris is a globally emerging fungal pathogen responsible for causing nosocomial outbreaks in healthcare associated settings. It is known to cause infection in all age groups and exhibits multi-drug resistance with high potential for horizontal transmission. Because of this reason combined with limited therapeutic choices available, C. auris infection has been acknowledged as a potential risk for causing a future pandemic, and thus seeking a promising strategy for its treatment is imperative. Here, we combined evolutionary information with reverse vaccinology approach to identify novel epitopes for vaccine design that could elicit CD4+ T-cell responses against C. auris. To this end, we extensively scanned the family of proteins encoded by C. auris genome. In addition, a pathogen may acquire substitutions in epitopes over a period of time which could cause its escape from the immune response thus rendering the vaccine ineffective. To lower this possibility in our design, we eliminated all rapidly evolving genes of C. auris with positive selection. We further employed highly conserved regions of multiple C. auris strains and identified two immunogenic and antigenic T-cell epitopes that could generate the most effective immune response against C. auris. The antigenicity scores of our predicted vaccine candidates were calculated as 0.85 and 1.88 where 0.5 is the threshold for prediction of fungal antigenic sequences. Based on our results, we conclude that our vaccine candidates have the potential to be successfully employed for the treatment of C. auris infection. However, in vivo experiments are imperative to further demonstrate the efficacy of our design.

耳念珠菌（Candida auris）是一种全球新兴的致病性真菌，可在医疗机构相关场景中引发院内暴发感染。该病原体可感染所有年龄段人群，且表现出多重耐药性，同时具备极强的水平传播潜力。鉴于上述特征，加之可用治疗手段有限，耳念珠菌感染已被认定为未来引发大流行的潜在风险，因此开发有效的治疗策略迫在眉睫。本研究将进化信息与反向疫苗学（reverse vaccinology）方法相结合，旨在筛选可诱导抗耳念珠菌CD4+ T细胞应答的新型疫苗表位，用于疫苗研发。为此，我们系统性地筛查了耳念珠菌基因组编码的蛋白质家族。此外，病原体在演化过程中可能在表位区域发生氨基酸替换，进而逃避免疫应答，最终导致疫苗失效。为降低该设计风险，我们剔除了耳念珠菌中所有受正选择驱动的快速进化基因。我们进一步利用多株耳念珠菌的高度保守区域，筛选出两个兼具免疫原性与抗原性的T细胞表位，其可引发针对耳念珠菌的高效免疫应答。经计算，本次预测的候选疫苗抗原性评分分别为0.85和1.88，而真菌抗原序列预测的阈值为0.5。基于上述结果，我们认为本次筛选的候选疫苗具备用于治疗耳念珠菌感染的潜力，但仍需开展体内（in vivo）实验以进一步验证其有效性。