A medically relevant capsular polysaccharide in Acinetobacter baumannii is a potential vaccine candidate

Concerns of Acinetobacter baumannii infection have increased due to the emergence of multi-drug resistance. In the present study, we determined the capsular polysaccharide (CPS) structure of A. baumannii SK44, a clinical isolate from Taiwan, to consist of pentasaccharide repeats. We found that CPS-induced antibody provided 55% protection against challenge in an animal model. The CPS-specific antibody reacted with the surface components of about 62% clinical isolates (342/554 strains) from cross-sectional and longitudinal studies by dot-immunoassay. Pulsed-field gel electrophoresis of positive strains showed the antibody covered different clonalites of A. baumannii clinical isolates. Meanwhile, using the CPS antibody as a probe, we found a number of outer membrane proteins bound to the antibody, including OmpA/motB, TonB-dependent receptor, and Omp38, indicating their association with CPS. These results might lead to the use of the capsular polysaccharide as a vaccine to prevent A. baumannii infection.     

Investigating adverse events following immunisation with pneumococcal polysaccharide vaccine using electronic General Practice data

BackgroundIn early 2011, following an increased number of reports of severe vaccine-related injection site reactions, Australian authorities recommended against administering repeat doses of the 23-valent pneumococcal polysaccharide vaccine (23vPPV) in otherwise healthy adults. The aim of this study was to assess a source of electronic medical record data from primary care providers (General Practitioners, GPs), for validity and ability to retrospectively detect this adverse event signal.MethodsThe General Practice Research Network (GPRN) holds data routinely collected from a representative sample of Australian GPs. Data were extracted on persons 18 years or older who had received at least one dose of 23vPPV or influenza vaccine (as comparator) between January 2002 and June 2012. Increases above background levels were assessed using 95% confidence intervals of reaction rates, calculated from the Poisson distribution of counts.ResultsThere was an average of 253 practices and 532 GPs contributing data per year. Over the study period there were 95,760 recorded 23vPPV administrations and 823 reactions, of which 233 were local. For influenza vaccine the numbers were 683,829 doses, 3001 and 387 respectively. Patterns of vaccinations and reactions were consistent with known safety profiles. There were 3 local reactions following 23vPPV in early 2011 (235/100,000 doses, 95% CI 49–717), which was not significantly different to the historical average (260, 225–298). We estimate that this system could have detected a 3-fold increase over background levels.ConclusionsUsing GP consultation data, we were unable to confirm an increase in local reactions detected by passive surveillance, suggesting that this apparent signal was artefactual. GP consultation data captures large numbers of vaccine recipients and medically attended adverse reactions at low cost. If available in a timely manner and expanded, this system has significant potential for use in validation of apparent signals from passive surveillance.     

Safety,tolerability, and immunogenicity of a 4-antigen Staphylococcus aureus vaccine (SA4Ag): Results from a first-in-human randomised,placebo-controlled phase 1/2 study

BackgroundA prophylactic Staphylococcus aureus four-antigen vaccine (SA4Ag) is under development for prevention of invasive S. aureus disease. A preliminary S. aureus three-antigen vaccine (SA3Ag) was reformulated to include a novel manganese transporter protein (MntC or rP305A). This study describes the first-in-human dose-finding, safety, and immunogenicity results for SA4Ag.MethodsIn this double-blind, sponsor-unblind, placebo-controlled, phase 1/2 study, 454 healthy adults aged 18–64 years were randomised to receive a single dose of one of three formulations of SA4Ag with escalating dose levels of rP305A or placebo. Functional immune responses were measured using opsonophagocytic activity (OPA) killing and fibrinogen-binding inhibition (FBI) assays; antigen-specific immunogenicity was assessed using a four-plex competitive Luminex® immunoassay (cLIA).ResultsA high proportion of SA4Ag recipients met the pre-defined antibody thresholds for each antigen at Day 29. A substantial and dose-level dependent immune response was observed for rP305A, with up to 18-fold rises in cLIA titres at Day 29. Robust functional responses were demonstrated, with >80-fold and >20-fold rises in OPA assay titres at Day 29 using S. aureus strains expressing capsular polysaccharide serotypes 5 and 8, respectively. Durable antibody responses were observed through month 12, gradually waning from peak levels achieved by days 11–15. SA4Ag was well tolerated, and no vaccine-related serious adverse events were reported.ConclusionsSingle-dose vaccination of SA4Ag in healthy adults aged 18–64 years safely induced rapid and robust functional immune responses that were durable through month 12, supporting further development of this vaccine. Trial registration number: NCT01364571     

箬叶多糖及其衍生物对小鼠艾滋病作用的研究

目的　研究箬叶多糖及其衍生物硫酸酯多糖和硒酸酯多糖对小鼠艾滋病的治疗作用。方法　采用 Ｌ Ｐ Ｂ Ｍ５ 鼠白血病病毒（ Ｍｕ Ｌ Ｖ） 感染 Ｃ５７ Ｂ Ｌ／６ Ｊ 小鼠的方法建立艾滋病模型。结果　硫酸酯多糖５０ ｍｇ·ｋｇ － １·ｄ － １（ｉｐ） 具有较好地抑制小鼠脾肿大、血清 Ｉｇ Ｇ 增高的作用,硒酸酯多糖在两种给药方式中有一定的保护作用。此外,还首次发现感染小鼠出现 Ｇ Ｓ Ｈ Ｐｘ 活力下降,脂质过氧化产物升高,这与 Ｈ Ｉ Ｖ感染的病人的症状是一致的,硒多糖对提高机体的抗氧化功能有较好的作用。多糖经硫酸酯化、硒酸酯化等化学修饰后,活性有不同程度的提高。结论　作为抗氧化剂和免疫增强剂的微量元素硒和多糖类可能对 Ｈ Ｉ Ｖ 感染的病人有一定的治疗作用     

大肠杆菌K5多糖对糖尿病视网膜病变小鼠视网膜新生血管形成作用的研究

目的 探究大肠杆菌K5多糖对糖尿病视网膜病变小鼠视网膜新生血管形成的影响.方法 发酵培养大肠杆菌K5菌株,对培养液进行分离纯化制备K5多糖,并分析K5多糖的纯度;雄性ICR小鼠被随机分为正常纽、模型组和干预组,其中正常组是健康小鼠,而模型组和干预组均使用链脲佐菌素建立糖尿病小鼠模型,干预组于造模后使用K5多糖干预4周,造模后8周各组取小鼠眼球组织,行HE染色及视网膜铺片ADPase染色;采用Real-time PCR和Western blotting检测各组小鼠眼球组织血管内皮生长因子(vascular endothelial gTowth factor,VEGF)及基质金属蛋白酶-2(matrix metalloproteinase,MMP-2)的表达情况.结果 HPLC结果显示制备的K5多糖纯度在95％以上:HE染色及ADPase染色结果显示正常组小鼠视网膜只见少量血管,模型组小鼠视网膜血管数目显著高于正常组,而干预组小鼠视网膜血管数目较模型组显著下降(P＜ 0.05);Real-time PCR和Western blot结果显示,模型组小鼠眼球组织VEGF和MMP-2的mRNA及蛋白表达水平显著高于正常组(均为P＜0.05),而干预组VEGF和MMP-2的mRNA及蛋白表达水平显著低于模型组(均为P＜0.05).结论 大肠杆菌K5多糖能够抑制糖尿病视网膜病变小鼠视网膜新生血管形成,其作用机制可能与抑制VEGF及MMP-2的表达有关.     

藻酸双酸钠的降血糖作用

家兔1次灌胃藻酸双酯钠(ISS)1.8mg·kg~(-1)、5.4mg·kg~(-1)及18mg·kg~(-1)可显著降低四氧嘧啶型糖尿病兔血糖.并可对抗由肾上腺素引起的高血糖.PSS1.8mg·kg~(-1).5.4mg·kg~(-1)对正常家兔血糖无影响.18mg·kg~(-1)可降低正常家兔血糖.糖耐量实验表明.大鼠5g·kg~(-1)葡萄糖灌胃.PSS5.4和18mg·kg~(-1)可对抗由粮负荷引起的血糖升高.PSS5.4和18mg·kg~(-1)连续灌胃5d可持续使四氧嘧啶型糖尿病大鼠血糖下降.     

地黄多糖b对正常及S180荷瘤小鼠T淋巴细胞功能的影响

地黄多糖ｂ，在体内与体外实验中能明显提高正常小鼠Ｔ淋巴细胞的增殖反应能力，促进白介素２的分泌，显示了明显的元疫调节活性．在对应于其产生明显抑瘤作用的时相里，能相对改善荷瘤小鼠由于肿瘤生长引起的白介素２分泌功能的下降，以及显著的提高此时细胞毒性Ｔ淋巴细胞（ＣＴＬ）的活力。因此认识到地黄多糖ｂ增强ＣＴＬ对肿瘤细胞的杀伤效应功能是其产生抑瘤作用的一个重要途径。     

蜜环菌多糖对小鼠免疫功能的影响

蜜环菌多糖(100mg/kg·d×5d,ig)能显著增加正常小鼠和注射环磷酰胺所致免疫功能抑制小鼠的溶血素生成。当剂量为50mg/kg·d×5d,ig时,它还能显著增加正常小鼠的空斑形成细胞数。体外试验,蜜环菌多糖(10、50μg/ml)显著增强刀豆素A诱导的小鼠淋巴细胞增殖反应,但对二硝基氯苯所致小鼠迟发型过敏反应无显著增强作用。此外,蜜环菌多糖还能增加小鼠静注碳粒廓清速率及腹腔巨噬细胞的吞噬百分数和吞噬指数。     

文蛤多糖对小鼠调节血糖和抗应激功能的影响

目的观察文蛤多糖的降血糖作用和抗应激能力,为资源开发利用提供基础研究资料。方法以四氧嘧啶糖尿病小鼠为模型,对文蛤多糖进行降血糖的实验研究。以小鼠游泳时间、常压耐缺氧、高温及低温环境下生存时间观察文蛤多糖对小鼠抗应激能力的影响。结果文蛤多糖高剂量组可显著降低四氧嘧啶糖尿病小鼠的血糖,延长小鼠游泳时间、常压耐缺氧时间、耐高温时间及耐低温时间。结论文蛤多糖具有降低血糖和增强抗应激能力的作用。     

1种新的天然α-葡萄糖苷酶抑制剂的分离纯化及其活性测定

目的从中草药中分离并得到α-葡萄糖苷酶抑制剂。方法中草药地榆通过水提、脱色、离心、离子交换色谱得到地榆多糖。用4-硝基酚-2-D吡喃葡萄糖苷(PNPG)法测定其对不同来源的α-葡萄糖苷酶活性的抑制率。结果地榆多糖显著抑制α-葡萄糖苷酶活性,并且可以降低大鼠餐后血糖浓度。结论地榆多糖是1种新的α-葡萄糖苷酶抑制剂。