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Systemically administered DNA encoding a recombinant human immunodeficiency virus (HIV) derived immunogen effectively primes a cytotoxic T lymphocyte (CTL) response in macaques. In this further pilot study we have evaluated mucosal delivery of DNA as an alternative priming strategy. Plasmid DNA, pTH.HW, encoding a multi-CTL epitope gene, was incorporated into poly(D,L-lactic-co-glycolic acid) microparticles of less than 10 microm in diameter. Five intrarectal immunizations failed to stimulate a circulating vaccine-specific CTL response in 2 Mamu-A*01(+) rhesus macaques. However, 1 week after intradermal immunization with a cognate modified vaccinia virus Ankara vaccine MVA.HW, CTL responses were detected in both animals that persisted until analysis postmortem, 12 weeks after the final boost. In contrast, a weaker and less durable response was seen in an animal vaccinated with the MVA construct alone. Analysis of lymphoid tissues revealed a disseminated CTL response in peripheral and regional lymph nodes but not the spleen of both mucosally primed animals.  相似文献   
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《Vaccine》2021,39(39):5641-5649
Moraxella catarrhalis (Mcat) is a key pathogen associated with exacerbations of chronic obstructive pulmonary disease (COPD) in adults and playing a significant role in otitis media in children. A vaccine would help to reduce the morbidity and mortality associated with these diseases. UspA2 is an Mcat surface antigen considered earlier as vaccine candidate before the interest in this molecule vanished due to sequence variability. However, the observation that some conserved domains are the target of bactericidal antibodies prompted us to reconsider UspA2 as a potential vaccine antigen.We first determined its prevalence among the COPD patients from the AERIS study, as the prevalence of UspA2 in a COPD-restricted population had yet to be documented. The gene was found in all Mcat isolates either as UspA2 or UspA2H variant. The percentage of UspA2H variant was higher than in any report so far, reaching 51%. A potential link between the role of UspA2H in biofilm formation and this high prevalence is discussed.To study further UspA2 as a vaccine antigen, recombinant UspA2 molecules were designed and used in animal models and bactericidal assays. We showed that UspA2 is immunogenic and that UspA2 immunization clears Mcat pulmonary challenge in a mouse model. In a serum bactericidal assay, anti-UspA2 antibodies generated in mice, guinea pigs or rabbits were able to kill Mcat strains of various origins, including a subset of isolates from the AERIS study, cross-reacting with UspA2H and even UspA1, a closely related Mcat surface protein.In conclusion, UspA2 is a cross-reactive Mcat antigen presenting the characteristics of a vaccine candidate.  相似文献   
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《Vaccine》2022,40(41):5882-5891
BackgroundMethamphetamine (METH) addiction is a major public health concern globally with limited management options. The development of a METH vaccine through hapten design has received significant attention as a promising platform for the potential treatment of METH addiction and overdose, however there is yet to be a successful candidate in human trials.Research design and methods: In this study, we developed a novel conjugated METH vaccine using oxidized mannan (a polymannose) as an immunogenic carrier. A METH hapten was synthesized by using amphetamine and conjugated to mannan with a (Lysine-Glycine-Lysine-Glycine-lysine-Glycine-Lysine-Glycine-Lysine-Glycine) (KG)5 peptide linker.ResultsThe reaction between amphetamine and (KG)5, oxidation of mannan, and conjugation of amphetamine-(KG)5 with oxidized mannan were confirmed by color tests, Fourier-transform infrared spectroscopy, gas and liquid chromatography mass spectrometry, thin-layer chromatography, and ultraviolet spectrophotometer. Additionally, the ability of the vaccine to generate antibodies was confirmed in C57BL/6 mice.ConclusionsThe successful development and characterization of the METH-mannan conjugate vaccine, provides a potential therapeutic intervention to curb METH substance use disorders. Each step of vaccine development was characterized to aid in future research on these vaccines, and the immunogenicity shown in the animal models supports future evaluation of the approach. Future studies of the conjugated METH vaccine should evaluate the efficacy in animal models of acute and chronic METH to pave the way for human studies.  相似文献   
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IL-2活化瘤苗对胃癌术后复发和转移的抑制作用   总被引:3,自引:0,他引:3  
目的观察用细胞因子活化的特异性瘤苗辅助常规化疗,治疗外科手术后临床Ⅲ~Ⅳ期胃癌患者,抑制肿瘤术后复发、转移的临床疗效。方法于外科术后常规化疗结束后2周,用患者自体肿瘤细胞抗原致敏、IL-2活化的树突状细胞(DC)作为瘤苗给患者四肢皮下多点免疫注射1×106/(ml·次),每周1次,每疗程注射4次,0.5年后强化1次。定期胃镜、影象学和肿瘤标志物检查,随访至手术后第2年,观察生存期和生存率。结果经瘤苗治疗后,患者的免疫功能显著改善。术后24个月,瘤苗联合化疗组患者的生存率为50%,血清中CEA和CA724分别为(10±1.5)ng/ml和(5.5±1.5)U/ml,而单纯化疗组患者的生存率为10%,CEA和CA724的水平分别为(77.0±9.4)ng/ml和(55.0±7.6)U/ml;P<0.001。结论特异性瘤苗免疫治疗,能增强胃癌患者术后的特异性抗肿瘤免疫功能,提高手术后化疗疗效,抑制肿瘤复发和转移,能延长患者生存期,提高生存率。  相似文献   
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THEHUMORALANTITUMORRESPONSESINDUCEDBYIL4GENEMODIFIEDTUMORVACCINE1YuYizhi于益芝CaoXuetao2曹雪涛ZhangMinghui张明徽LeiHong雷虹TaoQun陶群Dep...  相似文献   
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HPV与宫颈癌   总被引:1,自引:0,他引:1  
人乳头瘤病毒(HPV)的感染已被证实与宫颈癌的发生有密切关系.超过2/3的宫颈癌与HPV16或HPV18感染有关.HPV预防性疫苗研制的成功则是子宫颈癌预防研究的里程碑.  相似文献   
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Despite that clinical trials have been examining the safety profile of coronavirus disease 2019 (COVID-19) vaccines, there are concerns about long-term side effects as the number of vaccinations increases. Herein, we report a case of new-onset renal-limited anti-myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis after booster vaccination with the mRNA 1273 (Moderna) vaccine. A 72-year-old woman with no specific past history, and who had a normal renal function, developed ANCA-associated vasculitis following heterologous booster with mRNA1273 (Moderna) vaccine. After a kidney biopsy, she was diagnosed with ANCA-associated pauci-immune crescentic glomerulonephritis. Her renal function and constitutional symptoms have been improved with treatment with plasmapheresis, intravenous cyclophosphamide and steroid pulse therapy (intravenous 500 mg of methylprednisolone sodium succinate for 3 days) followed by a reduced steroid regimen.  相似文献   
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肠道病毒71型感染的药物治疗和疫苗预防   总被引:1,自引:0,他引:1  
肠道病毒71型(EV71)是引起手足口病的重要病原,能引发严重的神经系统并发症甚至死亡,构成严重的危害,但目前对ET71尚无有效的抗病毒治疗策略.此文就抗EV71的药物、疫苗及RNA干扰技术的研究进展作了综述,为EV71的防治工作提供借鉴.  相似文献   
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