Serum antibody response to Moraxella catarrhalis proteins OMP CD,OppA, Msp22, Hag,and PilA2 after nasopharyngeal colonization and acute otitis media in children

BackgroundThere is no licensed vaccine for Moraxella catarrhalis (Mcat), which is a prominent bacterium causing acute otitis media (AOM) in children and lower respiratory tract infections in adults. Nasopharyngeal (NP) colonization caused by respiratory bacteria results in natural immunization of the host. To identify Mcat antigens as vaccine candidates, we evaluated the development of naturally induced antibodies to 5 Mcat surface proteins in children 6–30 months of age during Mcat NP colonization and AOM.MethodsHuman serum IgG against the recombinant Mcat proteins, outer membrane protein (OMP) CD, oligopeptide permease (Opp)A, hemagglutinin (Hag), Moraxella surface protein (Msp)22, and PilA clade 2 (PilA2) was quantitated by using an ELISA assay.ResultsThere were 223 Mcat NP colonization episodes documented in 111 (60%) of 184 children in the study. Thirty five Mcat AOM episodes occurred in 30 (16%) of 184 children. All 5 Mcat candidate vaccine antigens evaluated stimulated a significant rise in serum IgG levles over time from 6 to 36 months of age (P < 0.001), with a rank order as follows: Msp22 = OppA > OMP CD = Hag = PilA2. Children with no detectable Mcat NP colonization showed a higher serum IgG level against OppA, Hag, and Msp22 compared to those with Mcat NP colonization (P < 0.05). Individual data showed that some children responded to AOM with an antibody increase to one or more of the studied Mcat proteins but some children failed to respond.ConclusionsSerum antibody to Mcat candidate vaccine proteins OMP CD, OppA, Msp22, Hag, and PilA2 increased with age in naturally immunized children age 6–30 months following Mcat NP colonization and AOM. High antibody levels against OppA, Msp22, and Hag correlated with reduced carriage. The results support further investigation of these vaccine candidates in protecting against Mcat colonization and infection.     

血吸虫病免疫诊断抗原的研究

基于循环抗体检测的诊断抗原一直是血吸虫病免疫诊断研究的热点.随着分子生物学技术和免疫学技术的发展,血吸虫病免疫诊断技术取得了飞跃的进步,发展了多种诊断效果较好的检测抗原.该文将就近几十年来发展的检测抗原及其检测技术的研究进展和应用前景进行综述.     

Acute Alcohol Intoxication Impairs the Hematopoietic Precursor Cell Response to Pneumococcal Pneumonia

Background: Alcohol abuse is associated with an increased incidence and severity of pneumonia. In both the general population and individuals consuming excess alcohol, Streptococcus pneumoniae is the most frequent lung infection pathogen. Alcoholic patients with pneumonia frequently present with granulocytopenia, which is predictive of increased mortality. The mechanisms underlying this impaired granulopoietic response to pneumococcal pneumonia have yet to be elucidated. Methods: Acute alcohol intoxication was induced in mice 30 minutes before intrapulmonary infection with S. pneumoniae. Bone marrow, lung, and blood samples were collected. Bone marrow cells were also isolated from naïve mice and treated in vitro with plasma from mice infected with S. pneumoniae. Results: Alcohol intoxication impaired the pneumococcal‐induced increase in granulocyte recruitment into the alveolar space, decreased bacterial clearance from the lung, and increased mortality. Pneumococcal pneumonia significantly increased bone marrow lineage^?c‐Kit⁺Sca‐1⁺ (LKS) cell number and colony‐forming unit—granulocytes and monocyte (CFU‐GM) activity of these cells. Both enhanced proliferation of LKS cells and re‐expression of Sca‐1 surface protein on downstream progenitor cells bearing lineage^?c‐Kit⁺Sca‐1^? surface markers accounted for the expansion of marrow LSK cells during pneumonia. Alcohol intoxication impaired these 2 mechanisms of LKS cell population expansion and was associated with a relative granulocytopenia during pneumococcal lung infection. Conclusions: Alcohol inhibits the hematopoietic precursor cell response to pneumonia, which may serve as a mechanism underlying the granulocytopenia and impaired host defense in alcohol abusers with bacterial pneumonia.     

Release characteristics of microspheres prepared by co-spray drying Actinobacillus pleuropneumoniae antigens and aqueous ethyl-cellulose dispersion

Using formalin inactivated Actinobacillus pleuropneumoniae antigens and aqueous ethylcellulose dispersions, microspheres of oral vaccines were developed by a co-spray drying process. The present study attempted to determine whether the dosage formulations of microspheres could form enteric matrices. To assess the enteric characteristics, an in vitro dissolution test was performed with the AQ6-AP microspheres; 95% of the A. pleuropneumoniae protein was released within 3 h at pH 7, but there was no release at pH 1.5. The scanning microscopy revealed that the surface structure of AQ6-AP microspheres became porous at neutral pH. The SDS-PAGE analysis showed that the release rate of proteins from the microspheres was pH dependent not only for the AQ6-AP formulation but also when antigens of A. pleuropneumoniae were replaced with porcine serum. The results suggest that the A. pleuropneumoniae antigens were entrapped in the AQ6 microspheres under the acidic conditions. In a mouse model, oral immunization with AQ6-AP microspheres containing A. pleuropneumoniae evoked systemic IgG and mucosal IgA responses against A. pleuropneumoniae antigens. Thus, the present method may further provide an opportunity to develop oral vaccines and mucosal immunity.     

Comparison of in vivo fate and immunogenicity of hepatitis B surface antigen incorporated in cationic and neutral liposomes

To compare cationic liposomes (CatL) and neutral liposomes (NeuL), as a vaccine carrier, the in vivo fate and immunogenicity of hepatitis B surface antigen (HBsAg), incorporated in CatL and NeuL, were investigated. CatL, composed of phosphatidyl choline (PC) and stearyl amine (SA) with a molar ratio of 9:1, showed a 2.5-fold higher incorporating efficiency of HBsAg than NeuL composed of PC alone. Most of HBsAg incorporated in both liposomes existed in an antibody-available form on the outer surface of liposomes. After intramuscular injection to rats, HBsAg in CatL resided at the injection site for a longer period than that in NeuL with terminal half lives of 52.5 and 42.9h, respectively. However, HBsAg in NeuL was more efficiently taken up by the lymphatic organs and spleen than that in CatL. Furthermore, the group treated with HBsAg in NeuL showed earlier sero-conversion with higher anti-HBsAg titre than the group treated with HBsAg in CatL. Sero-conversion rates (SCRs) in both CatL- and NeuL-treated animals were 100% after every injection carried out, except the primary injection of CatL. These results demonstrate that CatL can enhance the retention of incorporated antigen at the injection site, compared with NeuL. However, the production of antibody by HBsAg in NeuL is more effective than that by HBsAg in CatL, probably due tothe higher lymphatic targeting ability of NeuL. Thus, NeuL appears to be a better carrier for HBsAg than CatL.     

日本血吸虫未成熟虫卵67kDa分子抗原诊断血吸虫病的研究

本文通过SDS－PAGE和电渗方法，从日本血吸虫未成熟虫卵可溶性抗原（SIEA）中分离纯化出67kDa蛋白分子，以该分子包被微板进行ELISA，检测了急、慢性日本血吸虫病人血清，其阳性检出率达100％和94．6％，与60例正常人血清、30例肝吸虫和31例肺吸虫病人血清均未出现明显交叉反应，慢性血吸虫病人治疗后3个月、半年和1年的阴转率分别为58．1％，75．4％和84．6％。提示SIEA67kDa分子抗原具有较好的疗效考核价值和现场应用前景。     

Precore and core promoter mutants are associated with higher HBeAg seroconversion but low disease remission rates in HBV patients treated with nucleos(t)ide analogues

HBeAg seroconversion in HBV patients is considered an important event. We determined precore (PC) and base core promoter (BCP) mutations in 137 HBeAg‐positive nucleos(t)ide analogues (NA) treated patients by INNO‐LiPA HBV PreCore assay (Innogenetics). The majority of patients with nongenotype A had PC/BCP mutants present at baseline (P = 0.02). During 29 months of therapy, 45 patients achieved HBeAg seroconversion. Probability of HBeAg seroconversion was higher in patients with PC and/or BCP mutants (P = 0.01). After HBeAg seroconversion, patients with BCP mutants had more HBeAg relapse (P = 0.07), and PC mutants less often achieved HBV DNA < 2000 IU/mL (P = 0.07).     

Fas Antigen Expression on Hepatocytes Predicts the Short- and Long-term Response to Interferon Therapy in Patients with Chronic Hepatitis C

Background: Interaction between Fas antigen on hepatocytes and Fas ligand on cytotoxic T cells induces apoptosis, a major mechanism of hepatitis C virus (HCV)-induced hepatocyte injury. We investigated the usefulness of Fas expression on hepatocytes as a predictor of short- and long-term response to interferon (IFN) therapy in 72 patients with chronic hepatitis C. Methods:     

ERAP1结构与功能研究进展

内质网氨基肽酶1（endoplasmic reticulum aminopeptidase1,ERAPl）是氨基肽酶M1家族中的一个多功能的酶,在血压调节、血管发生、细胞因子受体的胞外区脱落,以及对递呈至I型主要组织相容性抗原复合物（major histocompatibility complexclassI,MHCI）的抗原肽的加工中发挥作用。ERAP1等位基因变异体与多种人类疾病相关,包括自身免疫性强直性脊柱炎（ankylosing spondylitis,As）、糖尿病、子宫颈癌以及高血压等。