Harris Shannon L, Finn Adam, Granoff Dan M
Children's Hospital, Oakland Research Institute, Oakland, California 94069, USA.
Infect Immun. 2003 Jun;71(6):3402-8. doi: 10.1128/IAI.71.6.3402-3408.2003.
Polysaccharide-protein conjugate vaccines elicit higher concentrations of serum anticapsular antibody in infants and children than do unconjugated polysaccharide vaccines. The conjugate-induced antibodies also have higher avidity and complement-mediated bactericidal activity. Similar vaccine-related differences in the magnitude or functional activity of antibody are observed infrequently in immunized adults. We compared the antibody responses of adults immunized with an investigational group A and C meningococcal conjugate vaccine to those elicited by an unconjugated meningococcal polysaccharide vaccine. Although there were no significant differences between the respective geometric mean bactericidal titers of the two vaccine groups, it took, on average, three- to fourfold higher concentrations of polysaccharide-induced serum anticapsular antibody to achieve 50% complement-mediated bacteriolysis than conjugate-induced antibody (P < 0.001 for groups A and C). At limiting doses, the polysaccharide-induced anticapsular antibodies also were less effective in conferring passive protection against meningococcal bacteremia in infant rats challenged with a group C strain (P < 0.04). The avidity index of the group C antibodies was higher in the conjugate vaccine group than in the polysaccharide vaccine group (P < 0.005). The disparities in the functional activity of the anticapsular antibodies elicited in adults by the two vaccines imply fundamental differences in the respective B-cell populations stimulated.
与未结合的多糖疫苗相比,多糖-蛋白质结合疫苗在婴幼儿中可诱导产生更高浓度的血清抗荚膜抗体。结合疫苗诱导产生的抗体也具有更高的亲和力和补体介导的杀菌活性。在免疫的成年人中,很少观察到抗体的量或功能活性方面类似的疫苗相关差异。我们比较了接种研究性A群和C群脑膜炎球菌结合疫苗的成年人与接种未结合的脑膜炎球菌多糖疫苗的成年人的抗体反应。虽然两个疫苗组各自的几何平均杀菌效价之间没有显著差异,但多糖诱导的血清抗荚膜抗体平均需要高出三到四倍的浓度才能达到50%的补体介导的细菌溶解,而结合疫苗诱导的抗体则不然(A群和C群的P均<0.001)。在极限剂量下,多糖诱导的抗荚膜抗体在为感染C群菌株的幼鼠提供被动保护以抵抗脑膜炎球菌血症方面也效果较差(P<0.04)。结合疫苗组中C群抗体的亲和力指数高于多糖疫苗组(P<0.005)。两种疫苗在成年人中诱导产生的抗荚膜抗体功能活性的差异意味着各自刺激的B细胞群体存在根本差异。