Maternal immunization modulates the primary immune response to 2-phenyl-oxazolone in BALB/c mice

The development of the antibody repertoire in newborn mice is greatly influenced by idiotypic network interactions. It has been demonstrated that anti-idiotypic antibodies either directly injected or transferred from the mother may alter the repertoire for life. For an elucidation of the underlying mechanisms we have analyzed the primary immune response to 2-phenyl-5-oxazolone (phOx) coupled to chicken serum albumin (CSA) in BALB/c mice after complete disappearance of maternal antibodies which originated from different stages of affinity maturation. Depending on the serum titers of the mothers after primary (1° mo), secondary (2° mo) or tertiary (3° mo) immunization, maternal anti-phOx IgG persisted in F1 mice for up to 9 months. In addition, F1 mice born to 2° mo developed – even without immunization – an anti-phOx IgM titer which reached levels similar to an antigen-induced primary response. An enhancement of the early primary anti-phOx as well as anti-CSA response was seen in F1 mice born from 1° mo, whereas the response was delayed when born to 2° mo and 3° mo. The antibody titers in the latter group of mice remained at a lower level for 3 months. In contrast, mice of the F2 generation which received a smaller amount of the same collection of maternal antibodies as F1 mice from 3° mo exhibited a quite different primary response: (i) They showed an earlier onset in their anti-CSA response. (ii) Whereas normally a plateau in antibody titer was reached by the 4th weak after immunization, in 55 % of the F2 mice a prolonged increase of the anti-phOx and anti-CSA antibody titers was observed. At 12 weeks after antigenic challenge, titers reached plateau levels of 6 × 10⁵ which were never before seen in a primary phOx or CSA response. Thus, depending on its own immunological experience, the maternal immune system induces a state of memory in the offspring which results in a faster and/or enhanced immune response in the F1 and F3 generations.     

双价痢疾菌苗滴鼻免疫小鼠后不同部位淋巴细胞表型的变化

目的:观测双价痢疾工程菌苗滴鼻免疫小鼠后,不同时间、不同部位淋巴组织细胞表型的变化,探讨痢疾菌苗滴鼻免疫对黏膜和系统免疫应答的影响。方法:BALB/c小鼠随机分为3组,每组30只,分别以FSM-2117和FS-5416痢疾菌苗经滴鼻途径免疫小鼠4次,菌量依次为5×106、1×107、4×107和4×107CFU/只,对照组给予PBS,间隔2 wk。4次免疫后7、30和90 d活杀,分离NALT、鼻通道、脾、小肠PP结淋巴细胞,采用流式细胞术检测其淋巴细胞表型的变化。结果:4次免疫后7 d,小鼠鼻相关淋巴组织(NALT)、鼻通道(NP)和Peyer’s结(PP)淋巴细胞中,CD3 T细胞数均显著增加,其中以CD4 T细胞增加为主。FSM-2117免疫组的脾细胞中B220 细胞显著增加;而FS 5416免疫组的脾细胞中CD3 T细胞显著增加。4次免疫后30 d,NALT、NP和脾淋巴细胞仍出现上述变化;而90 d,仅NALT和NP淋巴细胞出现上述同样变化。结论:两株双价痢疾菌苗滴鼻免疫小鼠后,能有效地诱导黏膜和系统免疫应答,且持续时间较长,但该免疫应答的减弱是从距免疫部位较远的部位而开始的。     

30例麻疹暴发疫情的调查分析

目的调查本地某乡镇一次麻疹疫情的流行强度,描述其三间分布,分析暴发原因及影响因素。方法现场流行病学调查,酶联免疫捕获法检测麻疹IgM抗体,作免疫空白与麻疹发病关联的病例对照研究。结果2006年5月～7月,该乡镇发生30例麻疹局部暴发,其中29例儿童麻疹,1例成人麻疹,5例麻疹IgM抗体阳性。发病地点主要为小学和和幼儿园,罹患率分别为7.94%、7.87%。免疫空白与发病关系研究表明,初种免疫空白OR=7.2,X2=6.84,复种免疫空白OR=11.0,X2=9.48;影响免疫空白形成的社会因素调查,未接受麻疹疫苗初种或复种儿童的父母双亲常年在外务工占82.4%(28/34),有麻疹疫苗接种史儿童的父母常年在外务工占35.3%(12/34),二者有统计学差异(X2=15.54)。结论免疫空白是麻疹暴发形成的重要因素,农村儿童的父母常年在外务工形成隔代抚养教育对计免工作有负面影响。     

Repeated immunization with plasmid DNA formulated in poly(lactide-co-glycolide) microparticles is well tolerated and stimulates durable T cell responses to the tumor-associated antigen cytochrome P450 1B1

Injection of microparticle-encapsulated DNA elicits immune responses to plasmid-encoded antigens in mice and humans. Cytochrome P450 CYP1B1 (CYP1B1) is a member of the CYP1 P450 enzyme family that is overexpressed in a variety of solid tumors. The work described herein was performed to study the kinetics of stimulating T cell responsiveness with an encapsulated DNA encoding CYP1B1 and provides support for the clinical development of this formulation. Immunization of HLA-A2/Kb transgenic mice with human CYP1B1 encoding plasmid DNA formulated in poly(lactide-co-glycolide) (PLG) microparticles elicits CD8+ T cells that respond to human CYP1B1-positive target cells. The duration of the immune response, the effect on the immune response of multiple injections, and the safety of repeated injections were studied. These results show that the PLG-encapsulated DNA therapeutic elicits durable immune responses to CYP1B1, the responses are dependent on repeat immunization, and that the formulation is well tolerated.     

HPA polymorphism in sub-Saharan African populations: Beninese, Cameroonians, Congolese, and Pygmies

The frequency of human platelet antigen-1 (HPA-1) to HPA-11w (excluding HPA-8w) and HPA-15 systems was studied in four sub-Saharan populations: Beninese, Congolese (Democratic Republic of Congo Kinshasa), Cameroonians, and Aka pygmies (Central African Republic). No report of HPA prevalence has previously been published concerning these populations which are characterized by the highest HPA-2b gene frequencies of any reported to date (Aka 0.393, Benin 0.292, Cameroon 0.237, and Congo 0.224) and at lesser degree HPA-5b (Aka 0.405, Congo 0.268, Cameroon 0.254, and Benin 0.182). This study is of great importance (i) particularly in the context of the diversity caused by the population migrations, we may observe today in our hospitals (ii) to confirm that the Pygmy population with distinctive frequencies (absence of the HPA-1b, HPA-2b, and HPA-5b highest frequencies) is an isolated population.     

C3d-P28增强乙型肝炎病毒特异性基因免疫效果的研究

目的　观察补体C3d P2 8对基因免疫的调节作用及其不同拷贝数对调节作用的影响 ,为增强基因免疫效果寻求新方法。方法　PCR法获得补体C3d P2 8编码基因并以头尾串连方式将1～ 4拷贝C3d P2 8编码基因克隆至pVAON33,构建pVAON33 P2 8.[1～ 4 ]重组质粒 ,然后将HBV preS2 S编码基因分别插入pVAON33和pVAON33 P2 8.[1～ 4 ]质粒获得pVAON33 S2 S和pVAON33 S2 S P2 8.[1～ 4 ]重组质粒。肌肉注射各重组质粒DNA(每只 10 0 μg 10 0 μl)初次免疫小鼠 ,并以pVAON33为对照 ;12周后皮下注射HBsAg蛋白加强免疫各组小鼠 ,ELISA法检测免疫小鼠血清特异性抗 HBs IgG。结果　pVAON33 S2 S重组质粒免疫小鼠可诱导产生特异性抗 HBs IgG ,含不同拷贝C3d P2 8编码基因的重组质粒可诱导更高的特异性抗体 ,其中pVAON33 S2 S P2 8.4重组质粒诱导的抗体水平最高 (P <0 .0 1)。蛋白加强免疫后 ,含C3d P2 8编码基因重组质粒免疫组抗 HBs IgG迅速上升 ,并明显高于pVAON33 S2 S重组质粒免疫组 (P <0 .0 5 ) ,pVAON33 S2 S P2 8.4重组质粒诱导的抗体仍维持最高水平。结论　不同拷贝的C3d P2 8能不同程度地增强HBV preS2 S基因免疫诱导的特异性体液免疫及其蛋白加强后的回忆反应 ,其中 4拷贝C3d P2 8的增强作用较为显著。     

Long-term follow-up of children born to women immunized with tetanus toxoid during pregnancy

Ten years after transplacental immunization with tetanus toxoid, the antibody responses of the immunized children to a booster immunization with 5 Lf tetanus toxoid did not differ from those of the control children. The tetanus toxoid-stimulated lymphocyte proliferative responses showed that there was no tolerance to tetanus toxoid induced by transplacental immunization, and the stimulation indices suggested that there may be some long-term memory for tetanus toxoid among the T lymphocytes in children who had been transplacentally immunized by maternal immunization with a standard dose of tetanus toxoid.     

体外免疫制备抗大肠癌循环抗原的单克隆抗体

用带结肠癌HRT-18细胞株的BALB/c(nu/nu)小鼠的血清,体处免疫BALB/c小鼠的脾细胞.再与Sp2/0细胞融合,经免疫荧光法在人结肠癌石蜡切片上筛选出一组抗结肠癌的单克隆抗体;A15-6,C13-11,H16-8。间接免疫酶法显示这组单抗对结肠癌的阳性率为69％-72％。免疫组化的特点为:癌巢分泌物及其接触的细胞膜顶端多为阳性反应,其他部位呈阴性反应。3抗体对其他类型的组织无反应。可见,这是一组针对血液循环中肿瘤相关抗原的单克隆抗体,有较好的器官特异性,可能有益于大肠癌的临床血清学检测。     

流行性脑脊髓膜炎的流行趋势变化与其疫苗接种

在过去几十年,随着疫苗的广泛使用,不同国家和区域引起流行性脑脊髓膜炎(简称流脑)病原体的血清群也发生了变迁。本文将脑膜炎球菌疫苗免疫接种、感染人群、不同区域和国家流脑的流行趋势及其内在机制研究进展进行综述,为进一步了解流脑流行趋势变化与其疫苗接种和后续制定免疫策略提供参考。     

健康成年人接种两剂新型冠状病毒灭活疫苗后序贯加强免疫重组新型冠状病毒疫苗(CHO细胞)的免疫原性和安全性研究

目的 评价在接种两剂已上市新冠病毒灭活疫苗的人群中序贯加强免疫重组新型冠状病毒疫苗(CHO细胞)后的免疫原性和安全性,为制定新型冠状病毒疫苗的加强免疫策略提供科学依据。 方法 采用开放性试验设计,筛选入组360例已接种两剂新冠病毒灭活疫苗3～4个月、6～8个月、11～13个月的18周岁及以上研究对象并接种1剂重组新型冠状病毒疫苗(CHO细胞)。采集所有研究对象研究用疫苗接种前、接种后14 d血样,用于体液免疫检测,收集研究用疫苗接种后1个月内的所有不良事件。 结果 本研究入组360例研究对象,按研究对象加强免疫与基础免疫间隔时间分3组(A组91～120 d,B组181～240 d,C组331～390 d),各组120例,无研究对象脱落。三组年龄均值分别为38.13、40.22和45.73岁,各组间年龄差异有统计学意义(F=13.516,P＜0.001),A、B组差异无统计学意义(P=0.168),C组和A、B组间差异均有统计学意义(P＜0.001)。三组 IgG GMC(几何平均浓度)免疫前分别为4.81、4.23、2.12 AU/ml,差异有统计学意义(F=10.054,P＜0.001),C组和A、B组间差异均有统计学意义(P＜0.001),A、B组间差异无统计学意义(P=0.520);三组免疫后 IgG GMC 分别为106.69、124.05、80.04 AU/ml,差异无统计学意义(F=2.028,P=0.133)。三组 IgG 抗体阳转率分别为84.17%、87.50%、79.17%,差异无统计学意义(χ²=3.081,P=0.214)。免疫前血清针对Delta变异株和原型株不同组别的中和抗体滴度比较,三组原型株中和抗体GMT(几何平均滴度)为1∶2.18、1∶2.18、1∶2.19,差异无统计学意义(F=0.011,P=0.990);三组Delta变异株中和抗体GMT为1∶2.09、1∶2.17、1∶2.16,差异无统计学意义(F=0.378,P=0.686)。免疫后血清三组原型株中和抗体 GMT为1∶31.09、1∶34.90、1∶21.98,差异无统计学意义(F=2.262,P=0.106);三组Delta变异株中和抗体GMT为1∶61.46、1∶77.44、1∶43.71,差异无统计学意义(F=2.105,P=0.123)。序贯加强免疫后血清对新型冠状病毒Delta变异株和原型株的中和抗体阳转率分别达到82.78%、83.33%。三组 SARS-CoV-2原型株中和抗体阳转率分别为86.67%、87.50%、75.83%,差异有统计学意义(χ²=7.320,P=0.026),其中C组低于A组和B组;三组 SARS-CoV-2 Delta变异株中和抗体阳转率分别为87.50%、84.17%、76.67%,差异无统计学意义(χ²=5.183,P=0.075)。发生不良事件人数为124人,不良事件总体发生率为34.44%。各组发生率分别为35.83%、40.83%和26.67%,差异无统计学意义(χ²=5.487,P=0.064),所有研究对象出现的不良事件以接种部位不良事件为主,主要表现为疫苗接种部位疼痛(23.89%);全身不良事件主要表现为疲劳/乏力(6.94%),未发生与疫苗接种有关的SAEs。结论 接种两剂新型冠状病毒灭活疫苗后序贯加强免疫重组新型冠状病毒疫苗(CHO细胞)具有良好的免疫原性和安全性。较长间隔期的免疫前IgG和免疫后原型株中和抗体阳转率较低,不同间隔期的免疫后IgG 、Delta变异株和原型株中和抗体水平比较差异均无统计学意义,建议基础免疫后6~8个月为最佳的接种间隔。