An adenovirus type 5 (AdV5) vector encoding an envelope domain III-based tetravalent antigen elicits immune responses against all four dengue viruses in the presence of prior AdV5 immunity

Dengue is a mosquito-borne viral disease caused by four antigenically distinct serotypes of dengue viruses (DENVs). This disease, which is prevalent in over a hundred tropical and sub-tropical countries of the world, represents a significant global public health problem. A tetravalent dengue vaccine capable of protecting against all four DENV serotypes has been elusive so far. Current efforts are focused on producing a tetravalent vaccine by mixing four monovalent vaccine components. In this work, we have utilized a discrete carboxy-terminal region of the major DENV envelope (E) protein, known as domain III (EDIII), which mediates virus entry into target cells and contains multiple serotype-specific neutralizing epitopes, to create a chimeric tetravalent antigen. This antigen derived by in-frame fusion of the EDIII-encoding sequences of the four DENV serotypes was expressed using a replication-defective recombinant human adenovirus type 5 (rAdV5) vaccine vector. This rAdV5 vector induced cell-mediated immune responses and virus-neutralizing antibodies specific to each of the four DENVs in mice. Interestingly, anti-AdV5 antibodies did not suppress the induction of DENV-specific neutralizing antibodies. We observed that anti-AdV5 antibodies in the sera of immunized mice could promote uptake of a rAdV5-derived reporter vector into U937 cells, suggesting that pre-existing immunity to AdV5 may in fact facilitate the uptake of rAdV5 vectored vaccines into antigen presenting cells. This work presents an alternative approach to developing a single component tetravalent vaccine that bypasses the complexities inherent in the currently adopted four-in-one physical mixture approach.     

Antibody Response Against the Glomerular Basement Membrane Protein Agrin in Patients with Transplant Glomerulopathy

Chronic allograft nephropathy (CAN) of renal allografts is still the most important cause of graft loss. A subset of these patients have transplant glomerulopathy (TGP), characterized by glomerular basement membrane (GBM) duplications, but of unknown etiology. Recently, a role for the immune system in the pathogenesis of TGP has been suggested. In 11 of 16 patients with TGP and in 3 of 16 controls with CAN in the absence of TGP we demonstrate circulating antibodies reactive with GBM isolates. The presence of anti-GBM antibodies was associated with the number of rejection episodes prior to diagnosis of TGP. Sera from the TGP patients also reacted with highly purified GBM heparan sulphate proteoglycans (HSPG). Indirect immunofluorescence with patient IgG showed a GBM-like staining pattern and colocalization with the HSPGs perlecan and especially agrin. Using patient IgG, we affinity purified the antigen and identified it as agrin. Reactivity with agrin was found in 7 of 16 (44%) of patients with TGP and in 7 of 11 (64%) patients with anti-GBM reactivity. In conclusion, we have identified a humoral response against the GBM-HSPG agrin in patients with TGP, which may play a role in the pathogenesis of TGP.     

分娩方式对新生儿补体系统,体液免疫水平的影响

为研究分娩方式是否影响新生儿免疫状态，检测和比较了６８例妊娠足月阴道产和６４例妊娠足月部宫产分娩的新生儿脐血Ｃ３、Ｃ４及ＩｇＧ、ＩｇＡ、ＩｇＭ的含量，其结果：ＩｇＧ的的含量阴产组明显高于剖宫产组，且男婴阴道产组ＩｇＧ的信明显高于剖宫产。说明剖宫产可参降低新生儿免疫应签及抗感染能力。     

粉被虫草提取物对巨噬细胞吞噬功能及CTL活性的影响

研究粉被虫草菌丝体提取物在体外对小鼠腹腔巨噬细胞吞噬功能和脾细胞免疫功能的影响，结果表明：粉被虫草提取物在正常情况下不仅能够促进小鼠腹腔巨噬细胞的吞噬功能，而在免疫抑制的情况下，一定浓度的粉被虫草菌丝体提取物还能恢复提高吞噬功能；它不仅能促进正常脾活化Ｔ细胞的增殖，而且能恢复环磷酰胺和氢化可的松抑制免疫小鼠脾活化Ｔ细胞的增殖；在较高浓度下能增高小鼠脾细胞毒Ｔ淋巴细胞（ＣＴＬ）活性，同时在一定浓度下能恢复免疫抑制小鼠脾ＣＴＬ活性。     

Passively transferable protection against Schistosoma japonicum induced in the mouse by multiple vaccination with attenuated larvae: the development of immunity, antibody isotype responses and antigen recognition

Vaccination of mice with attenuated S. japonicum cercariae induces protection against secondary infection which can be transferred to naive mice with serum (VMS). The presence of antibody does not per se impart protection as serum from mice carrying non-attenuated infections (CIS), contains high levels of specific antibody, but confers no protection. Here we describe the increased protection transferred (20 to 68%) with increased number of vaccinations (one to five) given to the donors, and its decline with time after the final vaccination. We also describe the development of IgM, IgA, IgE, total IgG and IgG subclass responses in VMS, giving different levels of protection and CIS, directed against sodium periodate-sensitive and -resistant epitopes in ‘skin-stage’, ‘lung-stage’and ‘liver-stage’schistosomula, adult worms and eggs. In addition, antibody affinity maturation, development of S. japonicum species-specific responses, and vaccination-specific responses were examined. No response developed in parallel with serum-mediated immunity, suggesting immunity may be due to responses against individual antigens. Preliminary examination of antigens recognized in Western blot showed that two schistosomal membrane antigens, of 13 and 40 kDa, were recognized by VMS from mice vaccinated five times (68% protection), but not by twice vaccinated VMS (27% protection). Neither antigen was recognized by non-protective CIS.     

中老年人膳食和体液免疫水平的调查

作者调查了１６１例（男：９８，女：６３）中老年人的营养素摄入量、血浆蛋白及体液免疫水平。结果：该人群的大部分人热能的摄入量达ＲＤＡ值；膳食蛋白质、维生素Ａ、Ｂ２、Ｃ、锌和铁的摄入量较低；脂肪摄入量按热能比高于３０％者约占３０％；血浆总蛋白、球蛋白水平较低，尤其是女性；免疫球蛋白ＩｇＡ偏低，ＩｇＧ和ＩｇＭ偏高。     

维生素E对烧伤小鼠免疫功能改善及其机制

本实验研究了维生素Ｅ（ＶＥ）改善烧伤后免疫功能的作用，并对其作用机制进行了探讨。结果显示，小鼠１１％～１２％总体表面积（ＴＢＳＡ）全层皮肤烧伤后血、肝、脾中过氧化脂质（ＬＰＯ）水平升高、谷胱甘肽（ＧＳＨ）含量下降，淋巴细胞增殖反应、白介素一２（ＩＬ一２）生成、空斑形成细胞（ＩＪＦＣ）形成及迟发型超敏反应（ＤＴＨ）均处于抑制状态。投予ＶＥ后可防止烧伤动物体内ＬＰＯ水平、ＧＳＨ含量明显变化，免疫功能受抑制的程度也明显小于未投予组。以超氧化物歧化酶（ＳＯＤ）处理的作用与ＶＥ相同。体外实验显示，过氧化亚油酸可抑制淋巴细胞增殖反应以及ＩＬ一２产生、诱发淋巴细胞脂质过氧化、降低淋巴细胞内ＧＳＨ含量。淋巴细胞上述功能的抑制与ＬＰＯ水平密切相关；加入ＶＥ可抑制过氧化亚油酸对淋巴细胞的上述作用。提示ＶＥ可改善烧伤后免疫功能，其机制可能是通过抗氧化作用而发挥的。     

Research highlights from the literature

Genes influencing the autonomic nervous system continue as a focus of research. Recent publications applied different methods to identify genes influencing autonomic cardiovascular regulation in humans. Two reports relied on a candidate gene approach. Common genetic polymorphisms in the promoter region of the tyrosine hydroxylase gene were shown to influence catecholamine synthesis and blood pressure. The same group tested the hypothesis that the GTP cyclohydrolase 1 (GCH1) gene influences catecholamine excretion and cardiovascular regulation. GCH1 affects tyrosine hydroxylase function indirectly. The authors concluded that the GCH1 gene may influence cardiovascular autonomic regulation through changes in nitric oxide production rather than a change in tyrosine hydroxylase activity. The third genetic study used a single nucleotide polymorphism chip to analyze 100,000 genetic polymorphisms scattered throughout the genome in participants of the Framingham study. The authors identified several polymorphisms that may influence QT interval duration, heart rate, and heart rate variability. The respective genes have not been identified with certainty. Another study suggested that catecholamines may be released from phagocytes and regulate pulmonary inflammation through alpha-2 adrenoreceptor activation in an autocrine or paracrine fashion.     

天然免疫模式识别途径:胞外识别与胞内识别

天然免疫系统通常籍模式识别受体识别病原体相关分子模式。取决于感染的性质,模式识别受体通过细胞外 或细胞内途径识别病原体,并传导相应的信号,激活宿主防御应答,消灭入侵病原体。     

Rational approaches to immune regulation

Our studies are mainly focused on developing strategies of immune regulation. In the case of infectious and neoplastic disease, our approach is to upregulate cell-mediated immunity to viral of tumor antigens using an intracellular bacterium as a vector for targeting these antigens to the major histocompatibility complex (MHC) class I and class II pathways of antigen processing, in addition to exploiting the adjuvant properties of the vector to stimulate innate immunity. In the area of autoimmunity, we are attempting to downregulate the immune response by specific immune intervention directed against autoreactive T cells. In these studies we use murine models for multiple sclerosis. Our approach is to use both rationally designed T cell receptor (TCR) peptide analogs and recombinant viral vectors that express TCR components to regulate the disease.