在12月號的英國《自然—醫(yī)學》雜志上刊登了一項研究成果稱,，美國布里格姆婦科醫(yī)院的研究人員發(fā)明了一種藥效比目前使用的傳統(tǒng)疫苗更為強大的新疫苗,。這種復合糖疫苗原型劑的藥效是傳統(tǒng)復合糖疫苗的100倍。
復合糖疫苗由共價碳水化合物和蛋白質(zhì)分子組成,。人們在生產(chǎn)預防如肺炎和腦膜炎這種常見疾病的疫苗時，會把復合糖疫苗當成是標準底本來使用,。
研究人員之所以能設計出新疫苗,，是因為發(fā)現(xiàn)被稱作T細胞的免疫細胞能夠識別出疫苗中的碳水化合物，并因此引發(fā)免疫反應,。這一發(fā)現(xiàn)對目前的流行看法提出了質(zhì)疑：后者認為免疫細胞只能識別復合糖疫苗中的蛋白質(zhì)成分,。
研究人員使用不同種類的B型鏈球菌復合糖疫苗對實驗鼠進行接種。一組接種的疫苗中含有不同種類的蛋白質(zhì),，另一組的疫苗則含有相同的蛋白質(zhì),。兩組疫苗里的碳水化合物鏈是一樣的。
研究人員發(fā)現(xiàn)兩組實驗鼠的免疫反應完全相同,，這就表示蛋白質(zhì)成分的變化對免疫反應沒有影響,。研究人員因此得知，T細胞識別出了碳水化合物,，并因此產(chǎn)生了持續(xù)的免疫反應,。
既然了解到T細胞的識別對象不止是蛋白質(zhì)，還包括碳水化合物,，研究人員于是研制出一種能夠在免疫系統(tǒng)處理過程中產(chǎn)生大量碳水化合物粒子的疫苗,，這也就能夠激發(fā)出更強的免疫反應。他們相信藥效更強的疫苗原型劑有朝一日可以幫助保護容易染病的高危人群,。
布里格姆婦科醫(yī)院的丹尼斯·卡斯珀解釋說：“我們希望通過研制這種新疫苗,，制造出對所有高危人群都有效的疫苗產(chǎn)品。”（生物谷Bioon.com）
doi:10.1038/nm.2535
PMC:
PMID:
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.
