IMMUNE RESPONSE TO S PNEUMONIAE CAPSULAR POLYSACCHARIDE

性状（改编自申请人摘要）：肺炎链球菌 荚膜多糖（PS），特别是6A和6B血清型 胶囊是重要的人类病原体，并且通常具有抗生素抗性。 抗S. pneumoniae是使用荚膜PS开发的， 可以引发针对6A的抗体的感染的保护性抗体（AB 人类的PS囊。 现有疫苗以及结合疫苗 仅含有血清型6B PS。 他们发现，10至 25%的疫苗可能产生对S.肺炎6A 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沙门氏菌的免疫反应。2016年06月08日06：00 PM（ 原始抗原sin）。他们还发现，抗6A抗体通常 来源于两个V λ 2家族基因，其产物表达8.12 独特型，致肾炎Ab对dsDNA的标记。 肺炎球菌感染 可引发B细胞产生抗dsDNA Ab。其具体目标 本研究的目的是：A）研究Ab不良调理S. pneumoniae 6A血清型，通过测定其体内保护活性， 婴儿中调理素（至6A）抗体较差的个体频率， 老年人疫苗 B）研究肺炎球菌疫苗接种的潜在诱导作用 免疫记忆对Ab调理作用差的S.肺炎6A血清型， 包括对SCID中免疫记忆发育（抗原sin）的影响 小鼠 C）研究肺炎球菌疫苗接种对B细胞的潜在引发 其随后产生抗dsDNAAb。在公式化S. pneumoniae疫苗的一个重要特征是交叉反应性Ab是功能性的。 目前为止 交叉反应性Ab的功能尚未得到严格的检验。 如果他们的 研究发现，6B PS常诱导产生抗体，但保护作用不大 对于S.肺炎6A，那么疫苗制剂可能需要 修改. PS蛋白缀合物疫苗是有前途的方法， 使儿童免疫许多来自细菌病原体的PS抗原。 然而 它们的免疫生物学仍然知之甚少。 调查员很长时间 长期研究目标是研究PS和PS蛋白缀合物的免疫生物学 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.