HYPERIMMUNE HUMAN IGG FOR TYPE III GROUP B STREPTOCOCCUS

针对 III 型 B 组链球菌的超免疫人 IGG

• 批准号: 3454223
• 负责人: LAURENCE B GIVNER
• 金额: $ 8.92万
• 依托单位: WAKE FOREST UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 1987
• 资助国家: 美国
• 起止时间: 1987-08-01 至 1992-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3454223
• 关键词: Streptococcus agalactiae; Streptococcus infection; Streptococcus vaccine; antibacterial antibody; antibody titering; antiserum; bacterial meningitis; bactericidal immunity; complement; complement fixation tests; congenital infection; disease /disorder model; disease /disorder prevention /control; dosage; genetic strain; human subject; human therapy evaluation; human tissue; hyperimmunization; immunodiffusion; immunoglobulin G; immunological substance; infant mortality; neutrophil; newborn animals; newborn human (0-6 weeks); passive immunization; serology /serodiagnosis; ultrafiltration; umbilical cord

Type III group B Streptococcus (III-GBS) is a common cause of serious infection in neonates; resulting morbidity and mortality remain high despite the use of antimicrobials. Therefore, methods of adjuvant therapy and/or prevention must be investigated. The proposed research will evaluate 1) the possible use of human IgG for such purposes, and 2) factors involved in susceptibility of this disease. A human, polyclonal IgG preparation hyperimmune for III-GBS (HHIG), prepared following immunization of a single adult volunteer with native III-GBS polysaccharide, has been shown to be functionally active when assessed using III-GBS strain M732 in 1) a bactericidal assay utilizing complement-containing cord sera obtained following delivery of healthy, full-term infants and neutrophils isolated from healthy adults, and 2) a mucin mouse model of III-GBS disease. Pooled human IgG from multiple donors will be required for ultimate use of such immunoglobulin preparations in humans on a large scale. Such a pooled human hyperimmune globulin for III- GBS (PHHIG) will be prepared following immunization of healthy adult volunteers. The HHIG, and then the PHHIG when prepared, will be evaluated in vitro in the bactericidal assay, utilizing: 1) neutrophils isolated from cord blood following term and pre-term deliveries with and without labor, and 2) cord, or newborn sera from term and pre- term infants. The effect of these variables in the assay also will be evaluated without added IgG, thus yielding basic knowledge concerning the pathogenesis of III-GBS disease in newborns. Evaluation of the efficacy of such IgG preparations in experimental models of III-GBS disease which closely simulate conditions in the human neonate also is important. Hence, these preparations will be evaluated in a neonatal rat model of III-GBS disease. The lethal dose (LD90) of III-GBS will be determined following intraperitoneal (ip) injection. Thereafter, the protective dose (PD50) of the IgG preparations will be determined when injected ip immediately following the LD90. Both the in vitro and in vivo studies will be performed with multiple strains of III-GBS. The above experiments are important with respect to the pathogenesis of III-GBS disease as well as the use of human hyperimmune IgG preparations for the prevention and/or therapy of III-GBS disease in human neonates.

III 型 B 族链球菌 (III-GBS) 是导致以下疾病的常见原因： 新生儿严重感染；由此产生的发病率和死亡率 尽管使用了抗菌药物，但仍然很高。 所以， 辅助治疗和/或预防的方法必须 调查了。 拟议的研究将评估 1) 可能的 将人 IgG 用于此类目的，以及 2) 涉及的因素 对这种疾病的易感性。 针对 III-GBS 的超免疫人类多克隆 IgG 制剂 (HHIG)，在单个成人免疫接种后准备 志愿者与天然 III-GBS 多糖，已被证明 使用 III-GBS 菌株 M732 进行评估时具有功能活性 1) 利用含补体的脐带血清进行杀菌测定 健康足月婴儿出生后获得 从健康成人中分离出的中性粒细胞，以及 2) 一只粘蛋白小鼠 III-GBS疾病模型。 需要来自多个捐赠者的汇集人类 IgG 此类免疫球蛋白制剂在人体中的最终用途 规模大。 这种混合的人超免疫球蛋白用于 III- GBS (PHHIG) 将在健康人免疫接种后准备 成人志愿者。 将评估 HHIG，然后评估准备好的 PHIG 体外杀菌测定中，利用：1) 分离的中性粒细胞 来自足月和早产后的脐带血 没有分娩，以及 2) 脐带血，或足月和产前的新生儿血清 足月婴儿。 这些变量对测定的影响也将 无需添加 IgG 即可进行评估，从而获得基础知识 关于新生儿 III-GBS 疾病的发病机制。 评估此类 IgG 制剂的功效 紧密模拟 III-GBS 疾病的实验模型 人类新生儿的状况也很重要。 因此，这些 将在 III-GBS 新生大鼠模型中对制剂进行评估 疾病。 III-GBS的致死剂量（LD90）将被测定 腹膜内 (ip) 注射后。 此后， 将确定 IgG 制剂的保护剂量 (PD50) 当注入 ip 时紧接着 LD90。 体外和体内研究都将进行 III-GBS 的多种菌株。 以上实验很重要 关于 III-GBS 疾病的发病机制以及 使用人超免疫IgG制剂进行预防 和/或人类新生儿III-GBS疾病的治疗。