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用C群脑膜炎球菌结合疫苗免疫的幼儿经多糖攻击后杀菌抗体的早期出现:其在维持保护作用中扮演什么角色?

Early appearance of bactericidal antibodies after polysaccharide challenge of toddlers primed with a group C meningococcal conjugate vaccine: what is its role in the maintenance of protection?

作者信息

Tsai Theodore F, Borrow Ray, Gnehm Hanspeter E, Vaudaux Bernard, Heininger Ulrich, Desgrandchamps Daniel, Aebi Christoph, Balmer Paul, Pedersen Ronald D, Fritzell Bernard, Siegrist Claire-Anne

机构信息

Wyeth Research, 500 Arcola Rd., Collegeville, Pennsylvania 19426, USA.

出版信息

Clin Vaccine Immunol. 2006 Aug;13(8):854-61. doi: 10.1128/CVI.00059-06.

Abstract

The contribution of memory responses after meningococcal vaccination to protection may depend on the rapidity of the response. Toddlers were challenged with a licensed polysaccharide (PS) vaccine 1 year after vaccination with a single dose of meningococcal group C-CRM(197) conjugate (MCC) vaccine at the age of 12 to 15 months. Bactericidal antibodies and immunoglobulin G (IgG) antibodies detected by an enzyme-linked immunosorbent assay (ELISA) were measured before challenge and 4, 7, 14, or 21 Days later ("Days" refer to treatment groups, "days" to sampling days). Among 281 subjects in the intent-to-treat population, 173 per-protocol (PP) subjects were challenged with 10 microg PS antigen and 103 others with a 50-microg PS vaccinating dose. Capsular PS-specific ELISA IgG titers were negligible in baseline samples and increased only twofold within 4 days of PS administration. In contrast, the proportion of PP subjects with serum bactericidal antibody (SBA) titers of >or=1:8 or >or=1:128 increased, respectively, from 41% and 16% before challenge to 84% and 74% at Day 4 and to 100% and 97% at Day 7. Recipients of 50 microg PS responded with similar kinetics but showed a trend toward higher antibody levels. Unexpectedly, 69% of subjects bled on days 2 to 3 already had achieved SBA titers of >or=1:8. The majority of toddlers previously immunized with MCC and challenged 1 year later with PS antigen mounted protective levels of bactericidal antibody within 2 to 4 days.

摘要

脑膜炎球菌疫苗接种后的记忆反应对保护作用的贡献可能取决于反应的速度。在12至15个月龄时单剂量接种C群脑膜炎球菌结合疫苗(MCC)的幼儿,在接种1年后接受了一种已获许可的多糖(PS)疫苗的激发。在激发前以及激发后4、7、14或21天(“天”指治疗组,“天”指采样日)测量通过酶联免疫吸附测定(ELISA)检测的杀菌抗体和免疫球蛋白G(IgG)抗体。在意向性治疗人群的281名受试者中,173名符合方案(PP)受试者接受了10微克PS抗原的激发,另外103名接受了50微克PS接种剂量的激发。在基线样本中,荚膜PS特异性ELISA IgG滴度可忽略不计,在PS给药后4天内仅增加两倍。相比之下,血清杀菌抗体(SBA)滴度≥1:8或≥1:128的PP受试者比例分别从激发前的41%和16%增加到激发后第4天的84%和74%,以及第7天的100%和97%。接受50微克PS的受试者反应动力学相似,但抗体水平有升高趋势。出乎意料的是,69%在第2至3天采血的受试者已经达到了≥1:8的SBA滴度。大多数先前接种MCC且1年后接受PS抗原激发的幼儿在2至4天内产生了保护性水平的杀菌抗体。

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