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Frank Wiedemann Ralf Link Konrad Pumpe Ulrich Jacobshagen Hans E. Schaefer Karl-Heinz Wiesmüller Rolf-Peter Hummel Günther Jung Wolfgang Bessler Traudel Bltz 《The Journal of pathology》1991,164(3):265-271
The inflammatory reactions following subcutaneous application of adjuvants revealed characteristic pathological patterns. The injection of complete Freund's adjuvant (CFA) resulted in the formation of large lipid deposits encircled by an inflammatory reaction and concentrically arranged collagen bundles. Bacterial lipopolysaccharide (LPS) caused granulomatous aggregations of mononuclear cells with thrombotic vessel occlusions. Inoculation of the lipopeptide adjuvants induced accumulation of mononuclear cells with only minimal fibrotic changes which were resolved after day 28. Lipopeptide conjugates based on the head group tripalmitoyl-S-glyceryl-cysteinyl-serin (P3CS) can thus be used as effective immunogens and adjuvants without long-term tissue damage. 相似文献
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Antigen presentation by naive macrophages, dendritic cells and B cells to primed T lymphocytes and their cytokine production following exposure to immunostimulating complexes.
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M Villacres-Eriksson 《Clinical and experimental immunology》1995,102(1):46-52
Influenza virus envelope proteins incorporated into immunostimulating complexes (iscoms) are taken up and processed by various kinds of antigen-presenting cells (APC), encompassing peritoneal cells (PEC), unfractionated splenocytes, splenic dendritic cells (DC) or B cells. The iscom-pulsed naive APC stimulated primed T cells to proliferate and produce cytokine in vitro. In contrast, only DC and B cells pulsed with the same antigen (Ag) in the micelle form functioned as accessory cells stimulating the primed T cells to proliferate and produce cytokine. In general, iscoms were better inducers of cell proliferation than micelles. Iscoms stimulated more secretion of IL-2 and interferon-gamma (IFN-gamma) than the micelles, but both antigenic forms stimulated secretion of IL-4. DC and B cells pulsed with iscoms stimulated most efficiently the secretion of IL-2 and IFN-gamma. DC were superior to the other APC in stimulating primed T cells to secrete IFN-gamma. On the other hand, micelles stimulated more efficiently than iscoms splenic T cells from micelle-primed as well as iscom-primed mice to secrete IL-10. These data indicate that influenza virus envelope proteins incorporated in iscoms stimulate a broad T cell response, possibly emphasizing a Th1 type of response. The same Ag in a micelle form induce a more prominent Th2 type of T cell response. The results indicate that the administration of an Ag in an adjuvant formulation can superimpose a different cytokine profile on the immune response than that induced by the protein Ag alone. 相似文献
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Effect of aluminum adjuvants on safety and immunogenicity of Haemophilus influenzae type b-CRM197 conjugate vaccine 总被引:1,自引:0,他引:1
güler Kanra Simonetta Viviani Kadriye Yurdakök Elif Özmert Alessandra Anemona SongüL Yalçn Okan Demiralp Nihan Bilgili Ates Kara Ali BüLent Cengiz Belgin Mutlu Alexandra Baldini Elisa Marchetti Audino Podda 《Pediatrics international》2003,45(3):314-318
OBJECTIVE: The present study was carried out to evaluate the safety and immunogenicity of the Haemophilus influenzae type b-CRM197 (Hib-CRM197) conjugate vaccine in relation to the change of adjuvant from aluminum hydroxide to aluminum phosphate (AlPO4). METHODS: The present study was a clinical phase II, observer-blind, randomized, multicenter, controlled study. Subjects were healthy infants aged 6-12 weeks, eligible for expanded program of immunization (EPI) routine vaccination and admitted to Hacettepe University Department of Social Pediatrics and Gülveren Health Center, Ankara. A total of 520 healthy infants were randomized in a 2:2:1 ratio to receive at either Chiron Hib/AlPO4 vaccine or VaxemHib (aluminum hydroxide adjuvant) vaccine or HibTiter (no adjuvant). Vaccines were administered simultaneously with routine diphtheria, tetanus and pertussis (DTaP) and oral polio vaccine (OPV) vaccines at 2, 4 and 6 months of age. Blood samples for anti-plain polysaccharide (PRP) antibody measurement were collected before the first vaccination and 1 month after the last vaccination. After each vaccination parents filled out a diary for 7 days. RESULTS: Out of 520 subjects enrolled, 514 received three doses and were included for safety analysis. Local and systemic reactions occurred with low and similar frequencies in all groups. Only erythema was more common in Chiron Hib/AlPO4 vaccine (19, 10, 11% in Chiron Hib/AlPO4, VaxemHib and HibTiter, respectively, P < 0.05). Nine serious adverse events were reported in seven cases of which none were related to vaccines. A total of 504 subjects were included in the immunogenicity analysis. The three vaccines were highly immunogenic and equivalent in terms of percentage of acquisition of long-term protective levels. The anti-PRP geometric mean titers were 9.9, 8.3 and 5.14 micro g/mL, respectively (P < 0.05). CONCLUSIONS: The use of aluminum compounds adjuvants in Hib-CRM197 conjugate vaccines does not impact the safety profile, while it does increase the magnitude of anti-PRP antibody titers. 相似文献
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Several global outbreaks of highly pathogenic avian influenza (HPAI) H5N1 virus have increased the urgency of developing effective and safe vaccines against H5N1. Compared with H5N1 inactivated vaccines used widely, H5N1 live-attenuated influenza vaccines (LAIVs) have advantages in vaccine efficacy, dose-saving formula, long-lasting effect, ease of administration and some cross-protective immunity. Furthermore, H5N1 LAIVs induce both humoral and cellular immune responses, especially including improved IgA production at the mucosa. The current trend of H5N1 LAIVs development is toward cold-adapted, temperature-sensitive or replication-defective vaccines, and moreover, H5N1 LAIVs plus mucosal adjuvants are promising candidates. This review provides an update on the advantages and development of H5N1 live-attenuated influenza vaccines. 相似文献
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《Vaccine》2015,33(13):1507-1514
Questions have been recently raised regarding the safety of vaccine adjuvants, particularly in relation to autoimmunity or autoimmune disease(s)/disorder(s) (AID). The International Life Sciences Institute (ILSI) Health and Environmental Sciences Institute (HESI) formed a scientific committee and convened a 2-day workshop, consisting of technical experts from around the world representing academia, government regulatory agencies, and industry, to investigate and openly discuss the issues around adjuvant safety in vaccines. The types of adjuvants considered included oil-in-water emulsions and toll-like receptor (TLR) agonists. The state of science around the use of animal models and biomarkers for the evaluation and prediction of AID were also discussed. Following extensive literature reviews by the HESI committee, and presentations by experts at the workshop, several key points were identified, including the value of animal models used to study autoimmunity and AID toward studying novel vaccine adjuvants; whether there is scientific evidence indicating an intrinsic risk of autoimmunity and AID with adjuvants, or a higher risk resulting from the mechanism of action; and if there is compelling clinical data linking adjuvants and AID. The tripartite group of experts concluded that there is no compelling evidence supporting the association of vaccine adjuvants with autoimmunity signals. Additionally, it is recommended that future research on the potential effects of vaccine adjuvants on AID should consider carefully the experimental design in animal models particularly if they are to be used in any risk assessment, as an improper design and model could result in misleading information. Finally, studies on the mechanistic aspects and potential biomarkers related to adjuvants and autoimmunity phenomena could be developed. 相似文献
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疾病管理可提高医疗的服务质量,减少不必要的医疗费用,执业药师在疾病管理尤其是慢病管理中可发挥重要作用。本文介绍了执业药师在疾病管理中的作用,并提出执业药师在慢病管理中的策略。 相似文献
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目的 从细胞因子的基因转录水平探讨两种新型佐剂霍乱毒素 B亚单位(CT B)和皂素(Saponin)在旋毛虫疫苗中的免疫调节作用。 方法 36只NIH小鼠随机分为CT B佐剂免疫组、Saponin佐剂免疫组和对照组。将CT B和Saponin分别与旋毛虫肌幼虫可溶性抗原混匀后,以口服或皮下注射途径免疫小鼠,隔周1次。第3次免疫后 1 周,经口感染旋毛虫感染期肌幼虫。感染后第8 d,采用RT PCR技术分析各组小鼠脾细胞在体外旋毛虫肌幼虫抗原刺激下,转录细胞因子 IFN γ、IL 2、IL 4及 IL 5 mRNA的水平。 结果 各组小鼠的脾细胞在体外抗原诱导下均未能转录 IL 2和 IFN γmRNA,但均有不同程度的 IL 4和 IL 5特异扩增,两免疫组的 IL 4 及 IL 5 mRNA转录水平明显高于对照组。结论 Th2细胞及其分泌的细胞因子在机体抗旋毛虫的保护性免疫中发挥着重要作用;从佐剂角度提高旋毛虫疫苗的保护性是可行的。 相似文献
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目的:社会药房的执业药师经过由三级医院构建的糖尿病管理团队的培训,对在本店配药的糖尿病患者进行管理,探讨社会药房执业药师的糖尿病管理模式。方法:经三级医院团队培训后的社会药房执业药师,对本店的糖尿病患者进行健康宣教及药学服务,患者随机分为对照组和试验组,试验组接受执业药师的药学服务,对照组未接受执业药师服务。结果:接受执业药师管理的患者前后体重指数(BMI)、收缩压(SBP)、空腹血糖(FPG)、餐后2小时血糖(2 h PPG)、糖化血红蛋白(HbA1c)、用药依从性都有明显改变,且腰臀比(WHR)、SBP、2hPPG、HbA1c、用药依从性等指标改善显著优于对照组,仅WHR、舒张压(DBP)无显著改善;未接受管理的患者,随访前后指标无显著差异。结论:经培训的社会药房执业药师在糖尿病管理工作中发挥着重要的作用,可明显改善糖尿病患者BMI、WHR、血压、血糖、用药依从性等指标;此模式为社会药房执业药师工作模式的探索提供了一种方案。 相似文献