ENHANCEMENT OF 19F ANTIBODY RESPONSE BY 19F PS-INACTIVATED PNEUMOLYSIN CONJUGATE

作为正在进行的关于改进肺炎球菌疫苗的研究的一部分， 两种确定的肺炎球菌溶血素类毒素（肺炎球菌溶血素）的基因，Pd-A（具有 氨基酸428处的Cys-Gly取代）和Pd-B（具有Try-Phe取代）。 433位取代），插入大肠杆菌中的pKK 233 -2载体中。 大肠杆菌中表达，并对表达产物进行纯化。 用肺炎链球菌或 用强毒肺炎球菌攻击天然毒素。 所有小鼠 免疫组的存活时间显著长于假免疫组 对照 两种肺炎球菌溶血素都比肺炎球菌溶血素更有效， 保护性免疫原 将Pd-B与19 F型PS共价缀合， 测定小鼠对蛋白质和PS的抗体应答 缀合物的部分。 显著的抗肺炎球菌溶血素滴度为 获得，并且19 F PS部分的免疫原性显著增强 与未结合的PS相比。 缀合还将19 F PS转化为能够诱导加强效应的抗原。 这些结果 支持肺炎球菌疫苗的有效性可以通过以下方式提高的观点： 以共价PS-气溶胶形式加入气溶胶 共轭

As part of an ongoing study concerned with improving pneumococcal vaccine, the genes for two defined pneumolysin toxoids (pneumolysoids), Pd-A (with a Cys--Gly substitution at amino acid 428) and Pd-B (with a Try--Phe substitution at position 433), were inserted into a pKK233-2 vector in E. coli and the expressed pneumolysoids were purified. Groups of mice which had been immunized with either pneumolysoid or the native toxin were challenged with virulent pneumococci. Mice in all immunized groups survived significantly longer than sham-immunized controls. Both pneumolysoids were more effective than pneumolysin as protective immunogens. Pneumolysoid Pd-B was conjugated covalently with type 19F PS and the antibody responses of mice were determined to both the protein and the PS moieties of the conjugate. Significant anti-pneumolysin titers were obtained, and the immunogenicity of the 19F PS moiety was markedly enhanced compared with that of unconjugated PS. Conjugation also converted the 19F PS into an antigen capable of inducing a booster effect. These results support the notion that efficacy of pneumococcal vaccine can be improved by addition of pneumolysoid in the form of a covalent PS-pneumolysoid conjugate.