Goetsch Liliane, Haeuw Jean Francois, Champion Thierry, Lacheny Christine, N'Guyen Thien, Beck Alain, Corvaia Nathalie
Centre d'Immunologie Pierre Fabre, 74164 Saint-Julien en Genevois, France.
Clin Diagn Lab Immunol. 2003 Jan;10(1):125-32. doi: 10.1128/cdli.10.1.125-132.2003.
Most conventional vaccines consist of killed organisms or purified antigenic proteins. Such molecules are generally poorly immunogenic and need to be coupled to carrier proteins. We have identified a new carrier molecule, BB, derived from the G protein of Streptococcus strain G148. We show that BB is able to induce strong antibody responses when conjugated to peptides or polysaccharides. In order to localize T and B cell epitopes in BB and match them with the albumin-binding region of the molecule, we immunized mice with BB, performed B and T pepscan analyses, and compared the results with pepscan done with sera and cells from humans. Our results indicate that BB has two distinct T helper epitopes, seven linear B-cell epitopes, and one conformational B-cell epitope in BALB/c mice. Four linear B-cell epitopes were identified from human sera, three of which overlapped mouse B-cell epitopes. Finally, three human T-cell epitopes were detected on the BB protein. One of these T-cell epitopes is common to BALB/c mice and humans and was localized in the region that contains the albumin-binding site. These data are of interest for the optimization of new carrier molecules derived from BB.
大多数传统疫苗由灭活的生物体或纯化的抗原蛋白组成。这类分子通常免疫原性较差,需要与载体蛋白偶联。我们鉴定出一种新的载体分子BB,它源自链球菌G148菌株的G蛋白。我们发现,BB与肽或多糖偶联时能够诱导强烈的抗体反应。为了定位BB中的T细胞和B细胞表位,并将它们与该分子的白蛋白结合区域匹配,我们用BB免疫小鼠,进行B细胞和T细胞肽扫描分析,并将结果与用人血清和细胞进行的肽扫描结果进行比较。我们的结果表明,在BALB/c小鼠中,BB有两个不同的T辅助表位、七个线性B细胞表位和一个构象性B细胞表位。从人血清中鉴定出四个线性B细胞表位,其中三个与小鼠B细胞表位重叠。最后,在BB蛋白上检测到三个人类T细胞表位。这些T细胞表位中的一个在BALB/c小鼠和人类中是共同的,并且定位在包含白蛋白结合位点的区域。这些数据对于优化源自BB的新型载体分子具有重要意义。