在12月号的英国《自然—医学》杂志上刊登了一项研究成果称,美国布里格姆妇科医院的研究人员发明了一种药效比目前使用的传统疫苗更为强大的新疫苗。这种复合糖疫苗原型剂的药效是传统复合糖疫苗的100倍。
复合糖疫苗由共价碳水化合物和蛋白质分子组成。人们在生产预防如肺炎和脑膜炎这种常见疾病的疫苗时,会把复合糖疫苗当成是标准底本来使用。
研究人员之所以能设计出新疫苗,是因为发现被称作T细胞的免疫细胞能够识别出疫苗中的碳水化合物,并因此引发免疫反应。这一发现对目前的流行看法提出了质疑:后者认为免疫细胞只能识别复合糖疫苗中的蛋白质成分。
研究人员使用不同种类的B型链球菌复合糖疫苗对实验鼠进行接种。一组接种的疫苗中含有不同种类的蛋白质,另一组的疫苗则含有相同的蛋白质。两组疫苗里的碳水化合物链是一样的。
研究人员发现两组实验鼠的免疫反应完全相同,这就表示蛋白质成分的变化对免疫反应没有影响。研究人员因此得知,T细胞识别出了碳水化合物,并因此产生了持续的免疫反应。
既然了解到T细胞的识别对象不止是蛋白质,还包括碳水化合物,研究人员于是研制出一种能够在免疫系统处理过程中产生大量碳水化合物粒子的疫苗,这也就能够激发出更强的免疫反应。他们相信药效更强的疫苗原型剂有朝一日可以帮助保护容易染病的高危人群。
布里格姆妇科医院的丹尼斯·卡斯珀解释说:“我们希望通过研制这种新疫苗,制造出对所有高危人群都有效的疫苗产品。”(生物谷Bioon.com)
doi:10.1038/nm.2535
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A mechanism for glycoconjugate vaccine activation of the adaptive immune system and its implications for vaccine design
Fikri Y Avci, Xiangming Li, Moriya Tsuji & Dennis L Kasper
Glycoconjugate vaccines have provided enormous health benefits globally, but they have been less successful in some populations at high risk for developing disease. To identify new approaches to enhancing glycoconjugate effectiveness, we investigated molecular and cellular mechanisms governing the immune response to a prototypical glycoconjugate vaccine. We found that in antigen-presenting cells a carbohydrate epitope is generated upon endolysosomal processing of group B streptococcal type III polysaccharide coupled to a carrier protein. In conjunction with a carrier protein–derived peptide, this carbohydrate epitope binds major histocompatibility class II (MHCII) and stimulates carbohydrate-specific CD4+ T cell clones to produce interleukins 2 and 4—cytokines essential for providing T cell help to antibody-producing B cells. An archetypical glycoconjugate vaccine that we constructed to maximize the presentation of carbohydrate-specific T cell epitopes is 50–100 times more potent and substantially more protective in a neonatal mouse model of group B Streptococcus infection than a vaccine constructed by methods currently used by the vaccine industry. Our discovery of how glycoconjugates are processed resulting in presentation of carbohydrate epitopes that stimulate CD4+ T cells has key implications for glycoconjugate vaccine design that could result in greatly enhanced vaccine efficacy.