IMMUNE RESPONSE TO S PNEUMONIAE CAPSULAR POLYSACCHARIDE

简介(摘自申请者摘要)：肺炎链球菌 囊膜多糖(PS)，尤其是6A和6B血清型的 胶囊是重要的人类病原体，通常对抗生素产生抗药性。 针对肺炎链球菌的疫苗正在开发中，使用的是胶囊PS，它 诱导抗6A抗体可诱导保护性抗体(AB)抵抗感染 人类的囊性PS。当前的疫苗以及结合疫苗 正在开发中的病毒只含有6B型PS。他们发现，10%到10% 25%的疫苗可能产生对肺炎链球菌6A调理能力差的抗体 血清型。此外，通过诱导无效抗体的免疫记忆 疫苗可能会改变一个人随后对肺炎链球菌6A的免疫反应( 原始抗原性原罪)。他们还发现，抗6A抗体通常是 来源于两个V lambda 2家族基因，其产物表达8.12 独特型，抗dsDNA肾炎抗体的标志。肺炎球菌感染 可激发B细胞产生抗dsDNA抗体。他们的具体目标 研究的目的是：a)研究抗体调理能力差的S。 肺炎6A血清型，通过测定其体内保护活性和 婴儿和婴儿中配音能力差(对6A)抗体的个体频率 老年疫苗。B)研究肺炎球菌疫苗接种的潜在诱因 抗调理能力差的肺炎链球菌6A血清型的免疫记忆， 包括对免疫记忆发育(抗原性SIN)的影响 老鼠。C)研究肺炎球菌疫苗接种B细胞的可能性 随后产生抗dsDNA抗体。提出S。 肺炎疫苗的特点是交叉反应抗体具有功能性。到目前为止， 交叉反应抗体的功能还没有得到严格的研究。如果他们的 研究发现，6B PS经常诱导抗体，但保护作用很小 针对肺炎链球菌6A，那么疫苗配方可能需要 修改过的。PS蛋白结合疫苗是一种很有前途的疫苗 为儿童接种来自细菌病原体的多种PS抗原的免疫。还没有 他们的免疫生物学仍然知之甚少。调查员的长 学期研究目标是研究PS和PS蛋白结合物的免疫生物学 疫苗。

DESCRIPTION (Adapted from applicant's abstract): Streptococcus pneumoniae with capsular polysaccharide (PS) especially those with 6A and 6B serotype capsule, are significant human pathogens and often antibiotic resistant. Vaccines against S. pneumoniae are being developed using capsular PS, which can elicit protective antibodies (AB) against infection with elicit Ab to 6A capsular PS in humans. Current vaccines as well as the conjugate vaccines under development contain only serotype 6B PS. They have found that 10 to 25 percent of vaccines may produce Ab which poorly opsonize S. pneumoniae 6A serotype. Furthermore, by inducing immune memory for ineffective Ab these vaccines may alter one's subsequent immune response to S. pneumoniae 6A ( original antigenic sin ). They have also found that anti-6A Ab are often derived from two V lambda 2 family genes, products of which express 8.12 idiotype, a marker for nephritogenic Ab to dsDNA. Pneumococcal infections may prime B cells for production of anti dsDNA Ab. Specific aims of their study are to: A) Study clinical relevance of Ab poorly opsonizing S. pneumoniae 6A serotype, by determining their in vivo protective activity and frequency of individuals with poorly opsonic (to 6A) Ab among infant and elderly vaccines. B) Study pneumococcal vaccination for potential induction of immune memory for Ab poorly opsonizing S. pneumoniae 6A serotype, including the impact on immune memory development (antigenic sin) in SCID mice. C) Study pneumococcal vaccination for potential priming of B cells which later produce anti dsDNA Ab. A key assumption in formulating S. pneumoniae vaccines is that cross reactive Ab are functional. So far, the function of cross reactive Ab has not been critically examined. If their study finds that 6B PS often induces Ab with little protective function against S. pneumoniae 6A, then the vaccine formulation may need to be modified. PS protein conjugate vaccines are promising approaches for immunizing children against many PS antigens from bacterial pathogens. Yet their immunobiology is still poorly understood. The investigator's long term research goal is to study immunobiology of PS and PS protein conjugate vaccines.