Immune response to type III group B streptococcal polysaccharide-tetanus toxoid conjugate vaccine
Immune response to type III group B streptococcal polysaccharide-tetanus toxoid conjugate vaccine
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DOI：
10.1172/jci119042
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发表时间：
1996-11-15
影响因子：
15.9
通讯作者：
Baker, CJ
中科院分区：
文献类型：
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作者：
Kaspar, DL;Paoletti, LC;Baker, CJ
B组链球菌(GBS)是一种重要的围产期病原体，由于经胎盘获得的母体抗GBS衣壳多糖(CPS)抗体具有保护作用，因此对妇女免疫后婴儿疾病的预防是可能的。不幸的是，纯化的GBS蛋白仅对成人具有可变的免疫原性；因此，为了提高免疫原性，我们设计并开发了一种CPS-蛋白结合疫苗。在疫苗设计中，需要考虑包含关键唾液酸残基的III型CPS上构象依赖表位的不稳定性，100名妇女随机接受三种剂量之一的GBS III型CPS-破伤风环状结合(III-TT)疫苗；未结合的GBS III型CPS；或生理盐水，在免疫前和免疫后2、4、8和26wk采集血清样本，并检测III型CPS的特异性抗体。疫苗耐受性良好。在高剂量III-TT受者的血清中，CPS特异性免疫球蛋白水平从免疫前的0.09mU/ml上升到8周后的4.53mU/ml，而非结合型III型CPS的水平从0.21mU/ml上升到1.41mU/ml。低剂量导致较低的抗体水平，90%的III-TT受者的抗体浓度比接受III型CPS的50%的人高出4倍以上(P=0.0015)。由结合疫苗所激发的抗体识别III-CPS的构象依赖表位，促进对GBS的吞噬和杀伤，并在母体免疫后保护新生小鼠免受III型GBS的致死攻击。我们得出结论，将III型GBS多糖与载体蛋白定向偶联可产生结合疫苗，与未偶联的CPS相比，保留了含有唾液酸的高度不稳定构象表位的表达，并增强了免疫原性。
Group B Streptococcus (GBS) is an important perinatal pathogen, Because transplacentally acquired maternal antibodies to the GBS capsular polysaccharides (CPS) confer protection, prevention of infant disease may be possible after immunization of women. Unfortunately, the purified CPS of GBS are only variably immunogenic in adults; therefore to enhance immunogenicity we have designed and developed a CPS-protein conjugate vaccine. The lability of a conformationally dependent epitope on the III CPS containing a critical sialic acid residue was important to consider in vaccine design, 100 women were randomized to receive GBS type III CPS-tetanus toroid conjugate (III-TT) vaccine at one of three doses; unconjugated GBS type III CPS; or saline, Serum samples were obtained before immunization and 2, 4, 8, and 26 wk thereafter, and specific antibody to type III CPS was measured. Vaccines were well tolerated. In sera from recipients of the highest dose of III-TT, CPS-specific IgG levels rose from a geometric mean of 0.09 mu g/ml before immunization to 4.53 mu g/ml 8 wk later, whereas levels in recipients of unconjugated type III CPS rose from 0.21 mu g/ml to 1.41 mu g/ml. Lower doses resulted in lower antibody levels, A greater than or equal to 4-fold rise in antibody concentration was achieved in 90% of recipients of III-TT compared with 50% of those that received III CPS (P = 0.0015), Antibodies evoked by the conjugate vaccine recognized a conformationally dependent epitope of the III-CPS, promoted opsonophagocytosis and killing of GBS, and, after maternal immunization, protected neonatal mice from lethal challenge with type III GBS, We conclude that directed coupling of type III GBS polysaccharide to a carrier protein yielded a conjugate vaccine with preserved expression of a highly labile conformational epitope involving sialic acid and enhanced immunogenicity compared with uncoupled CPS.