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1.
《Vaccine》2022,40(27):3721-3726
We initiated a randomized, placebo-controlled, phase 1/2 trial to evaluate the safety and immunogenicity of the S-268019-b recombinant protein vaccine, scheduled as 2 intramuscular injections given 21 days apart, in 60 randomized healthy Japanese adults. We evaluated 2 regimens of the S-910823 antigen (5 μg [n = 24] and 10 μg [n = 24]) with an oil-in-water emulsion formulation and compared against placebo (n = 12). Reactogenicity was mild in most participants. No serious adverse events were noted. For both regimens, vaccination resulted in robust IgG and neutralizing antibody production at days 36 and 50 and predominant T-helper 1-mediated immune reaction, as evident through antigen-specific polyfunctional CD4+ T-cell responses with IFN-γ, IL-2, and IL-4 production on spike protein peptides stimulation. Based on the interim analysis, the S-268019-b vaccine is safe, produces neutralizing antibodies titer comparable with that in convalescent serum from COVID-19-recovered patients. However, further evaluation of the vaccine in a large clinical trial is warranted. 相似文献
2.
《Vaccine》2016,34(39):4724-4731
Human papillomavirus (HPV) infection is the most common sexually transmitted disease worldwide. HPVs are oncogenic small double-stranded DNA viruses that are the primary causal agent of cervical cancer and other types of cancers, including in the anus, oropharynx, vagina, vulva, and penis. Prophylactic vaccination against HPV is an attractive strategy for preventing cervical cancer and some other types of cancers. However, there are few safe and effective vaccines against HPV infections. Current first-generation commercial HPV vaccines are expensive to produce and deliver.The goal of this study was to develop an alternate potent HPV recombinant L1-based vaccines by producing HPV virus-like particles into a vaccine that is currently used worldwide. Live attenuated measles virus (MV) vaccines have a well-established safety and efficacy record, and recombinant MV (rMV) produced by reverse genetics may be useful for generating candidate HPV vaccines to meet the needs of the developing world.We studied in non-human primate rMV-vectored HPV vaccine in parallel with a classical alum adjuvant recombinant HPV16L1 and 18L1 protein vaccine produced in Pichia pastoris. A combined prime-boost approach using both vaccines was evaluated, as well as immune interference due to pre-existing immunity against the MV.The humoral immune response induced by the MV, Pichia-expressed vaccine, and their combination as priming and boosting approaches was found to elicit HPV16L1 and 18L1 specific total IgG and neutralizing antibody titres. Pre-existing antibodies against measles did not prevent the immune response against HPV16L1 and 18L1. 相似文献
3.
目的研究快速成型(RP)技术辅助下制作的个体化假体复合珊瑚羟基磷灰石(CHA)、重组人骨形成蛋白2(rhBMP-2)修复兔下颌骨缺损的成骨效果。
方法以27只新西兰大白兔为实验对象,随机数字表法平均分成3组(每组9只),全部建立下颌骨连续性缺损模型,并在兔下颌骨缺损区分别植入个体化假体+自体骨(A组)、个体化假体+CHA(B组)、个体化假体+CHA+rhBMP-2(C组)。分别于术后4、12、24周3个时间点处死动物取材,进行大体标本观察,以及骨钙素(OC)、Ⅰ型胶原(COL-1)的免疫组化观察,分别比较各组修复骨缺损的能力,并对实验数据进行重复测量设计资料的单因素方差分析。
结果术后24周各组实验兔外形均对称,通过OC及COL-1的吸光度检测,骨缺损区均有大量新骨形成,A组(0.537 ± 0.010)、C组(0.530 ± 0.010)可见大量骨小梁及编织骨结构,缺损区的新骨OC、COL-1的免疫组化观察基本一致,差异无统计学意义(t = 0.007,P>0.05);但A组强于B组(0.415 ± 0.009,t = 0.122,P<0.001);C组也强于B组(t = 0.121,P<0.001),差异均有统计学意义。
结论在兔下颌骨缺损修复中,通过RP技术和组织工程技术相结合,CHA复合rhBMP-2后成骨能力明显增强,成骨效能肯定,为后期的临床应用提供可靠的实验基础。 相似文献
4.
携载rhBMP-2微球的新型可注射自凝固复合人工骨的制备及特性研究 总被引:7,自引:1,他引:6
[目的]制备一种具有良好降解性和成骨活性、可注射的自凝固新型骨修复材料。[方法]制备携载rhBMP-2的聚乳酸与聚乙醇酸共聚物(PLGA)微球,并将其与rhBMP-2/磷酸钙骨水泥(CPC)复合,制备出rhBMP-2/PLGA微球/CPC复合人工骨。探讨了材料的特性,包括形貌、固化时间、抗压强度及反映材料体外降解速度的指标一体外降解液Ca、P浓度变化,测定复合材料rhBMP乏的释药速度及体外诱导MSCs细胞成骨分化的能力。[结果]与单纯CPC-rhBMP-2相比,复合材料的固化时间少量增加,抗压强度下降明显。体外降解速度及体外释药明显提高,释放的rhBMP-2具有骨诱导活性。[结论]rhBMP-2/PLGA微球/磷酸钙骨水泥新型复合人工骨是具有良好应用前景的骨修复材料。 相似文献
5.
Hidetaro Mori Keisuke Hiraoka Ryoichi Yorifuji Tohru Iwasaki Syuzo Gomikawa Ohshi Inagaki Seishi Inoue Yoshihiro Takamitsu Yoshikazu Fujita 《Artificial organs》1994,18(10):725-728
Abstract: The adsorptive characteristics of 5 dialysis membranes for recombinant human erythropoietin (EPO) were studied in vitro in a closed circuit system. For 120 min, EPO added with bovine serum was significantly adsorbed by polymethylmetacrylate (PMMA) and polyacry–lonitrile (PAN) membranes but not by Cuprophan, ethylene vinyl alcohol (EVAL), or polysulfone (PS) membranes. In addition the EPO adsorptive rate, as well as that of β2 –microglobulin (β2 –MG), was greater with a PMMA membrane than with a PAN membrane. EPO was not detected in the ultrafiltrate at 15 min with 5 membranes. These results indicate that EPO was eliminated by membrane adsorption only with some dialysis membranes. 相似文献
6.
目的 通过测定生长激素缺乏症 (GHD)患儿用国产重组人生长激素 (recom bined hum angrowth horm one,rh GH)治疗时血清生长激素抗体 (GH- Ab)水平及其结合特性 ,探讨 rh GH的免疫原性及其对疗效的影响。方法 对 6 1例 (男 49例 ,女 12例 ) GHD患儿用国产 rh GH治疗 ,每晚睡前皮下注射 rh GH 0 .1IU /kg共6个月 ;用放射免疫法测定治疗期间患儿血清 GH- Ab水平和滴度 ,并计算抗体结合容量、亲和常数 (Ka)。结果 48%患儿 (2 9/6 1)用药后 3个月血清 GH - Ab呈阳性至试验结束时仍未消失 ,其中 2 0例抗体为弱阳性 (结合率 <10 % ) ,9例呈强阳性 (结合率 >15 % ) ;5 2 %患儿 (32 /6 1)治疗期间抗体为阴性 ;血清 GH- Ab的结合容量、Ka及滴度均为低水平 ,分别为 (0 .1~ 4.8) pmol/L、(1.7× 10 7~ 6 .5× 10 8) L /mol和 1∶ 4~ 1∶ 8。GH- Ab阳性患儿治疗后的身高、身高增长速率及身高落后于正常 SD值的变化与同期阴性者比较无统计学差异 (P>0 .0 5 )。结论 本试验所用国产 rh GH对 GHD患儿身高增长具有确切的促进作用 ,其免疫原性所导致产生的 GH - Ab未对患儿体格线性增长产生负性影响 相似文献
7.
白细胞介素-18基因修饰的胎肝细胞经脾移植对小鼠免疫功能的影响 总被引:2,自引:1,他引:1
目的:观察表达mIL-18的重组腺病毒基因修饰的胎肝细胞(AdmIL-18/BNL.CL2)经脾移植对正常小鼠免疫功能的影响。方法:实验组小鼠经脾移植AdmIL-18/BNL.CL2,同时设LacZ病毒对照组(Ad-LacZ/BNL.CL2),BNL.CL2细胞对照组及空白对照组。2周后处死,留取血清,制备腹腔巨噬细胞、脾淋巴细胞、肝组织匀浆液,提取肝组织总RNA。采用ELISA法检测各组小鼠血清、腹腔Mφ和脾细胞培养上清、肝匀浆中细胞因子的含量;采用半定量RT-PCR法,检测肝组织细胞因子mRNA相对表达量;以LDH释放法测定腹腔Mφ杀伤活性和脾NK细胞活性,用MTT还原比色法测定脾淋巴细胞的增殖活性。结果:实验组小鼠血清、细胞培养上清及肝匀浆中,IL-18、IL-2、IFN-γ、TNF-α稔均高于其它对照组,而IL-4、IL-10水平则低于对照组;半定量RT-PCR结果与ELISA检测结果一致;同时,实验组腹腔Mφ的杀伤活性和脾NK细胞活性,及脾淋巴细胞增殖活性也明显高于对照组。结论:AdmIL-18能有效转染至胎肝细胞并稳定表达mIL-18;AdmIL-18基因修饰的胎肝细胞经脾移植后,可显著提高肝脏、脾脏免疫细胞活性,活化腹腔Mφ,促进Th1类细胞因子表达,抑制Th2类细胞因子的分泌。 相似文献
8.
The aim was to determine whether the immunogenicity of an investigational hepatitis B vaccine (spHB) is at least as high as that of a licensed control vaccine, Engerix B®, and to evaluate its safety before inclusion in new pediatric combination vaccines. Two randomized, controlled, blind-observer, Phase 3 trials were performed: one in Argentina (344 participants aged 10–15 years, 10 μg HBsAg/dose) and one in Uruguay (344 participants aged 16–45 years, 20 μg HBsAg/dose). Both vaccines were given in a 0, 1, 6 month schedule to all participants with a baseline anti-Hep B antibody titer <0.6 mIU/mL. Antibody titers were measured pre-dose 1, 1 month after dose 2, pre-dose 3, and 1 month after dose 3. Statistical non-inferiority analyses were performed on seroprotection rates (SP) post-dose 3 (% with anti-Hep B titers ≥10 mIU/mL; delta non-inferiority limit of −10%). In both studies, SP for the spHB vaccine was 100% and the spHB vaccine was non-inferior in terms of SP to the licensed control vaccine. GMTs post-dose 3 were approximately 1.8- and 4.1-fold higher for spHB in the 10–15 year and 16–45 year age groups, respectively. Reactogenicity was low for each vaccine, after each dose. This highly immunogenic hepatitis B candidate vaccine was selected for further investigation as a component of new pediatric combination vaccines. 相似文献
9.
10.
Chandipura virus (CHPV) has emerged as an important pediatric encephalitis-causing pathogen with very high mortality in India. No specific vaccine or treatment is available till date. We attempted to prepare a candidate vaccine employing recombinant CHPV Glycoprotein (rGp). The Glycoprotein gene (G-gene) of CHPV was expressed using Baculovirus expression system. The rGp was purified by HPLC and used for mice immunization, 3 doses, and 4 weeks apart. One microgram rGp was found to be optimum. Sero-conversion was observed as early as 2nd week by detecting anti-CHPV IgG antibodies. Antibody titres were immunogen-concentration dependent. Intracerebral challenge of the immunized mice with 100 LD50 of the homologous strain demonstrated 90% protection. In in vitro neutralization, antibodies from the immunized mice were able to neutralize heterologous viruses. There was 60% T cell proliferation observed against rGp in immunized mice. The study shows that rGp induces both arms of immune response and represents an ideal vaccine candidate for further evaluations. 相似文献