Li Wei-Ji, Long Kai, Dong Hong-Liang, Gao Xiao-Ming
Department of Immunology, Peking University Health Science Center, Beijing, China.
Clin Vaccine Immunol. 2013 Apr;20(4):582-9. doi: 10.1128/CVI.00689-12. Epub 2013 Feb 13.
Polysaccharide-encapsulated fungi are the chief source of diseases in immunocompromised hosts such as those infected with human immunodeficiency virus or neutropenia patients. Currently available polysaccharide-protein conjugate vaccines are mainly T cell dependent and are usually ineffective in weakened immune systems. In this study, laminarin, a well-characterized β-1,3-glucan, was conjugated with a prokaryotically expressed recombinant fragment (amino acids [aa] 39 to 272) of calreticulin (rCRT/39-272), which exhibits extraordinarily potent immunogenicity and adjuvanticity in experimental animals. The resultant conjugate reserves the immunostimulatory effect of rCRT/39-272 on naïve murine B cells and is capable of eliciting anti-β-glucan IgG (mostly IgG1) responses in not only BALB/c mice but also athymic nude mice. Laminarin-CRT-induced mouse antibodies (Abs) are able to bind with Candida albicans and inhibit its growth in vitro. In addition, vaccination with laminarin-CRT partially protects mice from lethal C. albicans challenge. These results imply that rCRT/39-272 could be used as an ideal carrier or adjuvant for carbohydrate vaccines aimed at inducing or boosting IgG responses to fungal infections in immunodeficient hosts.
多糖包裹的真菌是免疫功能低下宿主(如感染人类免疫缺陷病毒的患者或中性粒细胞减少症患者)疾病的主要来源。目前可用的多糖-蛋白质结合疫苗主要依赖T细胞,在免疫系统较弱的情况下通常无效。在本研究中,将一种特性明确的β-1,3-葡聚糖海带多糖与钙网蛋白的原核表达重组片段(氨基酸[aa]39至272)(rCRT/39-272)偶联,该片段在实验动物中表现出极强的免疫原性和佐剂性。所得的偶联物保留了rCRT/39-272对未致敏小鼠B细胞的免疫刺激作用,不仅能够在BALB/c小鼠中,而且能够在无胸腺裸鼠中引发抗β-葡聚糖IgG(主要是IgG1)反应。海带多糖-CRT诱导的小鼠抗体(Abs)能够与白色念珠菌结合并在体外抑制其生长。此外,用海带多糖-CRT进行疫苗接种可部分保护小鼠免受致死性白色念珠菌攻击。这些结果表明,rCRT/39-272可作为一种理想的载体或佐剂,用于旨在诱导或增强免疫缺陷宿主对真菌感染的IgG反应的碳水化合物疫苗。