VARIABLE REGION EXPRESSION IN THE ANTIBODY-RESPONSES OF INFANTS VACCINATED WITH HAEMOPHILUS-INFLUENZAE TYPE-B POLYSACCHARIDE-PROTEIN CONJUGATES - DESCRIPTION OF A NEW LAMBDA LIGHT CHAIN-ASSOCIATED IDIOTYPE AND THE RELATION BETWEEN IDIOTYPE EXPRESSION, AVIDITY, AND VACCINE FORMULATION
VARIABLE REGION EXPRESSION IN THE ANTIBODY-RESPONSES OF INFANTS VACCINATED WITH HAEMOPHILUS-INFLUENZAE TYPE-B POLYSACCHARIDE-PROTEIN CONJUGATES - DESCRIPTION OF A NEW LAMBDA LIGHT CHAIN-ASSOCIATED IDIOTYPE AND THE RELATION BETWEEN IDIOTYPE EXPRESSION, AVIDITY, AND VACCINE FORMULATION
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DOI：
10.1172/jci116298
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发表时间：
1993-03-01
影响因子：
15.9
通讯作者：
MESCHIEVITZ, CK
中科院分区：
文献类型：
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作者：
GRANOFF, DM;SHACKELFORD, PG;MESCHIEVITZ, CK
流感嗜血杆菌B多糖（Hi B PS）-蛋白结合疫苗在化学和免疫学上不同。为了确定抗Hib PS可变区表达是否可能根据疫苗配方而不同，在2、4和6月龄时用与脑膜炎球菌外膜蛋白复合物（Hib PS-OMPC）或破伤风类毒素（Hib PS-T）偶联的Hib PS或与突变白喉毒素偶联的Hib PS寡聚体（Oligo-CRM）接种婴儿。在第三次注射后获得的血清中测量了两种抗Hib PS独特型：HibId-1，由具有kappaII-A2可变区的抗Hib PS抗体表达，和HibId-2，一种新定义的交叉反应独特型，与具有kappaVII可变区的抗Hib PS抗体亚组相关。在接受Hib PS-OMPC、Oligo-CRM或Hib PS-T的婴儿中，HibId-1分别为33%、68%和64%（P < 0.001）。HibId-2的相应值分别为47、18和10%（P = 0.001）。接种Hib PS-OMPC或Hib PS-T疫苗并产生可检测HibId-1阳性抗体的受试者的平均抗体亲合力显著高于不产生HibId-1阳性抗体的受试者。与此相反，寡核苷酸CRM诱发高亲和力抗Hib PS抗体，无论独特型的档案。这些发现表明由不同Hib PS缀合物疫苗引起的可变区含量和抗体质量两者的根本差异。
Haemophilus influenzae b polysaccharide (Hib PS)-protein conjugate vaccines differ chemically and immunologically. To determine whether anti-Hib PS variable region expression might differ according to vaccine formulation, infants were vaccinated at 2, 4, and 6 mo of age with Hib PS coupled to either meningococcal outer membrane protein complex (Hib PS-OMPC) or tetanus toxoid (Hib PS-T), or Hib PS oligomers coupled to a mutant diphtheria toxin (Oligo-CRM). Two anti-Hib PS idiotypes were measured in sera obtained after the third injection: HibId-1, expressed by anti-Hib PS antibodies having the kappaII-A2 variable region, and HibId-2, a newly defined cross-reactive idiotype associated with a subset of anti-Hib PS antibodies having lambdaVII variable regions. HibId-1 was present in 33, 68, and 64% of infants given either Hib PS-OMPC, Oligo-CRM, or Hib PS-T, respectively (P < 0.001). The respective values for HibId-2 were 47, 18, and 10% (P = 0.001). Subjects who were vaccinated with Hib PS-OMPC or Hib PS-T and who produced detectable HibId-1-positive antibody, had significantly higher mean antibody avidity than subjects who did not produce HibId-1 positive antibodies. In contrast, Oligo-CRM evoked high avidity anti-Hib PS antibodies, irrespective of the idiotypic profile. These findings indicate fundamental differences in both variable region content and antibody quality elicited by different Hib PS conjugate vaccines.