Natural development of antibodies to pneumococcal surface protein A, pneumococcal surface adhesin A, and pneumolysin in relation to pneumococcal carriage and acute otitis media

Pneumococcal surface protein A (PspA), pneumococcal surface adhesin A (PsaA), and pneumolysin (Ply) are common to virtually all Streptococcus pneumoniae isolates. They are immunogenic and protective against pneumococcal challenge in animals and are the major candidates for a protein-based pneumococcal vaccine for humans. However, little is known of the natural development of antibodies to these proteins in humans. The objective of this study was to evaluate the natural development of antibodies to PspA, PsaA, and Ply in relation to pneumococcal infection and carriage in young children. Serum antibodies to these proteins were measured by EIA in children at ages 6, 12, 18, and 24 months and in their mothers. All age groups were capable of producing antibodies to the 3 proteins. The antibody concentrations increased with age and were strongly associated with pneumococcal exposure, whether by carriage or infection (acute otitis media).     

造血干细胞移植与临床感染的防治

学术背景:造血干细胞移植技术在临床上已得到广泛应用,移植后感染是关系到移植成败的重要因素。目的:探讨造血干细胞移植后各阶段的感染的特点、预防及治疗,以进一步减低造血干细胞移植后感染的发生率及死亡率。检索策略:由作者应用计算机检Medline 1994-01/2007-05关于造血干细胞移植及移植后感染的文章,检索词为"hematopoietic stem cell transplantation,infection",限定语言种类为"English";同时检索中国期刊全文数据库1994-01/2007-05相关文章,检索词"造血干细胞移植,感染,防治",限定语言种类为中文。纳入标准:随机对照研究;实验或临床研究包含平行对照组。排除标准:重复性研究文献评价:初检得到212篇文献,初审后选取与造血干细胞移植后感染有关的文章126篇,删除明显无关及相关性不强的文章,进一步查找全文,29个实验符合标准,予以纳入。29个研究包括324例患者和140个实验动物,分别阐述了造血干细胞移植后感染的原因、途径、特点、种类及各种感染的预防及治疗措施。资料综合:造血干细胞移植后感染发病隐匿,由于患者免疫力低下,感染不易控制,在不同阶段致病菌的种类有所不同,细菌感染普遍,在移植后各个时期均可出现,真菌感染和病毒感染致死性强,故预防和治疗感染至关重要,其治疗分为预防治疗、抢先治疗、经验性治疗和针对治疗。结论:造血干细胞移植后感染的治疗已成为影响移植疗效的一个重要原因,及早的诊断及正确的治疗将成为移植后感染治疗成功的关键。     

Multivalent Pneumococcal Protein Vaccines Comprising Pneumolysoid with Epitopes/Fragments of CbpA and/or PspA Elicit Strong and Broad Protection

Immunization with the pneumococcal proteins pneumolysin (Ply), choline binding protein A (CbpA), or pneumococcal surface protein A (PspA) elicits protective responses against invasive pneumococcal disease in animal models. In this study, we used different mouse models to test the efficacy of a variety of multivalent protein-based vaccines that comprised various combinations of full-length or peptide regions of the immunogens Ply, CbpA, or PspA: Ply toxoid with the L460D substitution (referred to herein as L460D); L460D fused with protective peptide epitopes from CbpA (YPT-L460D-NEEK [YLN]); L460D fused with the CD2 peptide containing the proline-rich region (PRR) of PspA (CD2-L460D); a combination of L460D and H70 (L460D+H70), a slightly larger PspA-derived peptide containing the PRR and the SM1 region; H70+YLN; and other combinations. Each mouse was immunized either intraperitoneally (i.p.) or subcutaneously (s.c.) with three doses (at 2-week intervals) of the various antigen combinations in alum adjuvant and then challenged in mouse models featuring different infection routes with multiple Streptococcus pneumoniae strains. In the i.p. infection sepsis model, H70+YLN consistently provided significant protection against three different challenge strains (serotypes 1, 2, and 6A); the CD2+YLN and H70+L460D combinations also elicited significant protection. Protection against intravenous (i.v.) sepsis (type 3 and 6A challenge strains) was largely dependent on PspA-derived antigen components, and the most protection was elicited by H70 with or without L460D or YLN. In a type 4 intratracheal (i.t.) challenge model that results in progression to meningitis, antigen combinations that contained YLN elicited the strongest protection. Thus, the trivalent antigen combination of H70+YLN elicited the strongest and broadest protection in diverse pneumococcal challenge models.