Huai Yanyan, Dong Shuai, Zhu Ye, Li Xin, Cao Binrui, Gao Xiang, Yang Mingying, Wang Li, Mao Chuanbin
Institute of Cytology and Genetics, School of Life Sciences, Northeast Normal University, 5268 Renmin Street, Changchun City, Jilin Province, 130024, China.
Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma, 101 Stephenson Parkway, Norman, OK, 73019-5300, USA.
Adv Healthc Mater. 2016 Apr 6;5(7):786-94. doi: 10.1002/adhm.201500930. Epub 2016 Feb 18.
Candida albicans (CA) is a kind of fungus that can cause high morbidity and mortality in immunocompromised patients. However, preventing CA infection in these patients is still a daunting challenge. Herein, inspired from the fact that immunization with secreted aspartyl proteinases 2 (Sap2) can prevent the infection, it is proposed to use filamentous phage, a human-safe virus nanofiber specifically infecting bacteria (≈900 nm long and 7 nm wide), to display an epitope peptide of Sap2 (EPS, with a sequence of Val-Lys-Tyr-Thr-Ser) on its side wall and thus serve as a vaccine for preventing CA infection. The engineered virus nanofibers and recombinant Sap2 (rSap2) are then separately used to immunize mice. The humoral and cellular immune responses in the immunized mice are evaluated. Surprisingly, the virus nanofibers significantly induce mice to produce strong immune response as rSap2 and generate antibodies that can bind Sap2 and CA to inhibit the CA infection. Consequently, immunization with the virus nanofibers in mice dramatically increases the survival rate of CA-infected mice. All these results, along with the fact that the virus nanofibers can be mass-produced by infecting bacteria cost-effectively, suggest that virus nanofibers displaying EPS can be a vaccine candidate against fungal infection.
白色念珠菌（CA）是一种可在免疫功能低下患者中导致高发病率和死亡率的真菌。然而，预防这些患者的CA感染仍然是一项艰巨的挑战。在此，受分泌天冬氨酸蛋白酶2（Sap2）免疫可预防感染这一事实的启发，有人提出使用丝状噬菌体（一种专门感染细菌的对人类安全的病毒纳米纤维，长约900纳米，宽7纳米），在其侧壁展示Sap2的一个表位肽（EPS，序列为Val-Lys-Tyr-Thr-Ser），从而作为预防CA感染的疫苗。然后分别用工程化病毒纳米纤维和重组Sap2（rSap2）免疫小鼠。评估免疫小鼠的体液免疫和细胞免疫反应。令人惊讶的是，病毒纳米纤维能像rSap2一样显著诱导小鼠产生强烈的免疫反应，并产生能结合Sap2和CA以抑制CA感染的抗体。因此，用病毒纳米纤维免疫小鼠可显著提高CA感染小鼠的存活率。所有这些结果，以及病毒纳米纤维可通过经济高效地感染细菌进行大规模生产这一事实，表明展示EPS的病毒纳米纤维可作为抗真菌感染的候选疫苗。
