Noninvasive Transdermal Vaccination Using Hyaluronan Nanocarriers and Laser Adjuvant

Vaccines are commonly administered by injection using needles. Although transdermal microneedles are less invasive promising alternatives, needle‐free topical vaccination without involving physical damage to the natural skin barrier is still sought after as it can further reduce needle‐induced anxiety and is simple to administer. However, this long‐standing goal has been elusive since the intact skin is impermeable to most macromolecules. Here, we show an efficient, noninvasive transdermal vaccination by employing two key innovations: the use of hyaluronan (HA) as vaccine carriers and non‐ablative laser adjuvants. Conjugates of a model vaccine ovalbumin (OVA) and HA—HA–OVA conjugates—induced more effective maturation of dendritic cells in vitro, compared to OVA. Following topical administration in the skin, HA–OVA conjugates penetrated into the epidermis and dermis in murine and porcine skins, as revealed by intravital microscopy and fluorescence assay. Topical administration of HA‐OVA conjugates significantly elevated both humoral and mucosal antibodies, with peak levels at four weeks. An OVA challenge at week eight elicited strong immune‐recall responses. With pretreatment of the skin using non‐ablative fractional laser beams as adjuvant, strong immunization was achieved with much reduced doses of HA–OVA (1 mg kg^–1 OVA). Our results demonstrate the potential of the noninvasive patch‐type transdermal vaccination platform.     

The effects of immunological castration against GnRH with recombinant OL protein (Ovalbumin-LHRH-7) on carcass and meat quality characteristics,histological appearance of testes and pituitary gland in Kıvırcık male lambs

The aims of the study were to investigate the effects of immunization against GnRH using OL protein (Ovalbumin-LHRH-7) on feedlot performance, carcass, meat quality and some reproductive traits in K?v?rc?k ram lambs. Ram lambs in the immunization (I, n = 7) group were immunized against GnRH using OL protein and boosted 2 weeks later. Control (C, n = 7) group was not treated. The animals were kept at pasture for 6 weeks after the first immunization, subjected to a 70 day fattening program, and then slaughtered. Growth performance, various carcass and meat quality characteristics were not affected from the immunization. GnRH immunization induced GnRH antibody production, suppressed testosterone production and testicular growth (P < 0.01). Testicular structure was negatively affected from the immunization, but not pituitary. These results suggest that immunization against GnRH with OL could be an alternative castration technique in ram lambs without negatively affecting carcass and meat quality characteristics.     

一种恶意软件传播的离散概率模型

 复杂网络理论为恶意软件传播的研究提供了新的思路和方法。本文针对恶意软件的实际传播机制,提出一种新的离散概率DP-SI模型, 该模型可适用于任意网络拓扑。同时提出了一种节点信息网络模型方法,为大规模复杂网络及复杂网络上的传播动力学的仿真,以及离散传播动力学模型的建立,提供了有效的研究平台。仿真结果表明本模型比传统模型更接近现实,对恶意软件的控制具有一定指导意义。     

Rh血型系统在安全输血中的意义

目的研究配血不合患者血样中不规则抗体的分布特征,确定Rh血型系统在安全输血中的意义及输血策略。方法采用盐水介质法、聚凝胺试验、抗人球蛋白试验和木瓜酶试验对2007年1月～2008年12月来河北省血液中心申请疑难配血的153例患者血样进行血型鉴定、抗体筛查和特异性鉴定及交叉配血试验。结果153例受血者血液中,有134例存在不规则抗体,其中Rh系统免疫抗体68例(占50.75%),12例由多次妊娠免疫产生,55例由反复输血引起,1例为自身特异性;ABO和Rh以外其他血型系统抗体10例(占7.46%),单纯自身抗体阳性者56例(占41.79%)。结论在引起配血不合或溶血性输血反应的原因中,Rh系统的免疫居第1位,为受血者提供Rh因子同型血液输注是减少长期输血治疗患者发生Rh免疫的重要策略。     

Polymeric Nanoparticles as a Self-Adjuvanting Peptide Vaccine Delivery System: The Role of Shape

Antigens incorporated in subunit vaccines are typically poorly immunogenic, so a strong immunostimulant (adjuvant) and/or delivery system is required to boost immunogenicity. In this work, the various functional polymer nanostructures, that is, rods, worms, spheres, and tadpoles are used to develop potent peptide antigen delivery systems. The antigen PADRE-J8 (PJ8), derived from Group A Streptococcus (GAS) M-protein, is either physically mixed or chemically conjugated to polymeric nanoparticles of different shapes. The physical mixture of polymeric nanoparticles and antigen is more effective in inducing antibody production than their chemical conjugates. Moreover, rod-shaped polymeric nanoparticles in physical mixture with PJ8 elicited higher and more opsonic antibody titers than powerful complete Freund's adjuvant (CFA)-adjuvanted antigen. Herein, for the first time it is demonstrated that a) the block copolymer, in nanoparticle form, can act as an immune adjuvant, b) nanoparticle shape plays a crucial role in their immunogenicity, and c) antigen conjugation is not required, nor is antigen encapsulation or absorption.     

基于自适应免疫因子的模糊检务文字提取

为了实现准确、高效地从模糊的检务图像中提取文字目标,本文针对多种不同类型的模糊检务图像,基于人工免疫原理,利用免疫因子的相关理念结合自适应滤波算法提出一种自适应免疫算法.该算法首先通过动态地改变滤波窗口实现自适应滤波,达到兼顾保留文字目标细节和滤除噪声的效果,再根据模糊类型的不同设计不同的免疫因子,从而实现最大程度地保...     

Antibody response to Engerix-B and Recombivax-HB hepatitis B vaccination in end-stage renal disease

Recombivax-HB (REC) and Engerix-B (ENG) are FDA-approved vaccines for hepatitis B virus (HBV) in end-stage renal disease (ESRD). This study compares antibody response rates between them in routine clinical practice. Patients completing the recommended 40 mug dose of REC (3 doses) or ENG (4 doses) between January 1, 2000 to April 30, 2003 were eligible. Patients with prior positive HBV surface antigen (HBsAg) or antibody (HBsAb) test results were excluded. The conversion rate and persistence of protective titer (HBsAb titer>or=10 IU/mL) were tracked for 1 year. A supplemental analysis of a one-to-one matched patient sample was also performed. REC patients (N=885) were older, had longer dialysis vintage, and had a larger proportion of whites than ENG patients (N=13,661). Cumulative conversion response was greater in ENG (58%) than REC (40%) at 1 year (p<0.0001). The odds ratio for response to ENG compared with REC was 1.96 (95% limits: 1.56, 2.45; p<0.0001) adjusted for age, gender, race, diabetes, vintage, BSA, hemoglobin, and eKt/V. Persistent protective HBsAb after 1 year was 77% (ENG) vs. 53% (REC). HBsAg was positive in 208 ENG patients (1.5%) with all but 1 because of transient, vaccine-related antigenemia. The difference in conversion response favoring ENG persisted in a one-to-one sample matched for age, gender, race, modality, and dialysis vintage. The study found higher seroconversion response to ENG compared with REC at several time points up to 1 year. Protective HBsAb disappeared in 23-47% of patients 1 year later, validating CDC recommendations to re-test HBsAb yearly. The observed difference in response rates may be related to the extra ENG dose given at the second month (0, 1, 2, 6 regimen). The study raises a hypothesis that requires confirmation in a prospective clinical trial.     

Interpretation of persuasive messages as a function of prior immunization.

2 experiments were conducted in which passive immunization was achieved by providing Ss with counterarguments against presuasive messages to which they were later exposed. In both studies, this procedure produced a significant tendency to displace the perceived content of the "change" message toward the stand advocated in the immunization message. These results were tentatively attributed to the Ss' attempts to minimize the discrepancy between the opposing statements, both of which appeared to emanate from prestigeful sources. Judgments were not affected by active immunization, a procedure in which Ss attempted to refute (in writing) weakened versions of the change message to which they were later exposed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Improving Routine Immunization Coverage Through Optimally Designed Predictive Models

Routine immunization (RI) of children is the most effective and timely public health intervention for decreasing child mortality rates around the globe. Pakistan being a low-and-middle-income-country (LMIC) has one of the highest child mortality rates in the world occurring mainly due to vaccine-preventable diseases (VPDs). For improving RI coverage, a critical need is to establish potential RI defaulters at an early stage, so that appropriate interventions can be targeted towards such population who are identified to be at risk of missing on their scheduled vaccine uptakes. In this paper, a machine learning (ML) based predictive model has been proposed to predict defaulting and non-defaulting children on upcoming immunization visits and examine the effect of its underlying contributing factors. The predictive model uses data obtained from Paigham-e-Sehat study having immunization records of 3,113 children. The design of predictive model is based on obtaining optimal results across accuracy, specificity, and sensitivity, to ensure model outcomes remain practically relevant to the problem addressed. Further optimization of predictive model is obtained through selection of significant features and removing data bias. Nine machine learning algorithms were applied for prediction of defaulting children for the next immunization visit. The results showed that the random forest model achieves the optimal accuracy of 81.9% with 83.6% sensitivity and 80.3% specificity. The main determinants of vaccination coverage were found to be vaccine coverage at birth, parental education, and socio-economic conditions of the defaulting group. This information can assist relevant policy makers to take proactive and effective measures for developing evidence based targeted and timely interventions for defaulting children.     

A Designer Scaffold with Immune Nanoconverters for Reverting Immunosuppression and Enhancing Immune Checkpoint Blockade Therapy

Current cancer immunotherapy based on immune checkpoint blockade (ICB) still suffers from low response rate and systemic toxicity. To overcome the limitation, a novel therapeutic platform that can revert nonimmunogenic tumors into immunogenic phenotype is highly required. Herein, a designer scaffold loaded with both immune nanoconverters encapsulated with resiquimod (iNCVs (R848)) and doxorubicin, which provides the polarization of immunosuppressive tumor‐associated macrophages (TAMs) and myeloid‐derived suppressor cells (MDSCs) into tumoricidal antigen‐presenting cells (APCs), rather than depleting them, as well as in situ vaccination that can be generated in vivo without the need to previously analyze and sequence tumor antigens to favor neoantigen‐specific T cell responses is suggested. Local and sustained release of iNCVs (R848) and doxorubicin from the designer scaffold not only reduces the frequency of immunosuppressive cells in tumors but also increases systemic antitumor immune response, while minimizing systemic toxicity. Reshaping the tumor microenivronment (TME) using the designer‐scaffold‐induced synergistic antitumor immunity with ICB effects and long‐term central and effector memory T cell responses, results in the prevention of postsurgical tumor recurrence and metastasis. The spatiotemporal modulation of TMEs through designer scaffolds is expected to be a strategy to overcome the limitations and improve the therapeutic efficacy of current immunotherapies with minimized systemic toxicity.