Efficacy of recombinant Marek’s disease virus vectored vaccines with computationally optimized broadly reactive antigen (COBRA) hemagglutinin insert against genetically diverse H5 high pathogenicity avian influenza viruses

The genetic and antigenic drift associated with the high pathogenicity avian influenza (HPAI) viruses of Goose/Guangdong (Gs/GD) lineage and the emergence of vaccine-resistant field viruses underscores the need for a broadly protective H5 influenza A vaccine. Here, we tested experimental vector herpesvirus of turkey (vHVT)-H5 vaccines containing either wild-type clade 2.3.4.4A-derived H5 inserts or computationally optimized broadly reactive antigen (COBRA) inserts with challenge by homologous and genetically divergent H5 HPAI Gs/GD lineage viruses in chickens. Direct assessment of protection was confirmed for all the tested constructs, which provided clinical protection against the homologous and heterologous H5 HPAI Gs/GD challenge viruses and significantly decreased oropharyngeal shedding titers compared to the sham vaccine. The cross reactivity was assessed by hemagglutinin inhibition (HI) and focus reduction assay against a panel of phylogenetically and antigenically diverse H5 strains. The COBRA-derived H5 inserts elicited antibody responses against antigenically diverse strains, while the wild-type-derived H5 vaccines elicited protection mostly against close antigenically related clades 2.3.4.4A and 2.3.4.4D viruses. In conclusion, the HVT vector, a widely used replicating vaccine platform in poultry, with H5 insert provides clinical protection and significant reduction of viral shedding against homologous and heterologous challenge. In addition, the COBRA-derived inserts have the potential to be used against antigenically distinct co-circulating viruses and future drift variants.     

Virulence factors impair epithelial junctions during bacterial infection

Epithelial cells are typically connected through different types of cell junctions that are localized from the apical membrane to the basal surface. In this way, epithelium cells form the first barrier against pathogenic microorganisms and prevent their entry into internal organs and the circulatory system. Recent studies demonstrate that bacterial pathogens disrupt epithelial cell junctions through targeting junctional proteins by secreted virulence factors. In this review, we discuss the diverse strategies used by common bacterial pathogens, including Pseudomonas aeruginosa, Helicobacter pylori, and enteropathogenic Escherichia coli, to disrupt epithelial cell junctions during infection. We also discuss the potential of targeting the pathogenic mechanisms in the treatment of pathogen‐associated diseases.     

A guide to oral vaccination: Highlighting electrospraying as a promising manufacturing technique toward a successful oral vaccine development

Most vaccines approved by regulatory bodies are administered via intramuscular or subcutaneous injections and have shortcomings, such as the risk of needle-associated blood infections, pain and swelling at the injection site. Orally administered vaccines are of interest, as they elicit both systemic and mucosal immunities, in which mucosal immunity would neutralize the mucosa invading pathogen before the onset of an infection. Hence, oral vaccination can eliminate the injection associated adverse effects and enhance the person's compliance. Conventional approaches to manufacturing oral vaccines, such as coacervation, spray drying, and membrane emulsification, tend to alter the structural proteins in vaccines that result from high temperature, organic and toxic solvents during production. Electrohydrodynamic processes, specifically electrospraying, could solve these challenges, as it also modulates antigen release and has a high loading efficiency. This review will highlight the mucosal immunity and biological basis of the gastrointestinal immune system, different oral vaccine delivery approaches, and the application of electrospraying in vaccines development.     

164例艾滋病患者血液培养病原体分布及耐药性分析

目的 探讨艾滋病(AIDS)患者机会性感染的病原体种类及其药敏结果。方法 采用BeeT/Alert3D血培养仪进行血液标本的细菌和真菌培养;绝大部分菌株采用VITEK2 COMPACT微生物分析仪进行鉴定和药敏,部分菌株用手工方法鉴定,真菌药敏采用ATB药敏条。结果 164例艾滋病患者血液标本培养阳性34例,共分离34株病原菌,总阳性率为20.73％。其中真菌16株(47.06%),主要为新生隐球酵母菌12株(75.00％), 马尼菲青霉菌2株(12.50％), 2株因患者死亡未进一步鉴定(12.50％);革兰阳性球菌10株(29.41%),均为凝固酶阴性葡萄球菌,8株为耐甲氧西林菌株;革兰阳性杆菌6株(17.65%),均为星形诺卡菌;革兰阴性杆菌2株(5.88%),为甲型副伤寒沙门菌。12株新生隐球酵母菌对5-氟胞嘧啶、两性霉素B、氟康唑、伊曲康唑和伏立康唑敏感率均为100%;10株葡萄球菌对万古霉素、奎诺普叮-达福普叮、利奈唑胺、庆大霉素敏感率均为100%,对红霉素、青霉素G、克林霉素耐药率100%。6株星形诺卡菌对复方新诺明和庆大霉素敏感。结论 艾滋病患者发生机会性感染的病原体以真菌占优势,尤其以新生隐球酵母菌为主。     

呼吸机相关下呼吸道感染的病原菌调查

目的分析机械通气引发下呼吸道感染病原菌的构成及其耐药情况,指导早期经验性抗生素治疗. 方法对2001年1月～2004年9月间我院ICU收住的113例机械通气引发下呼吸道感染患者的病原菌及耐药情况进行回顾性调查分析. 结果检出病原菌138株,其中革兰阴性(G-)细菌87株(63.0%),革兰阳性细菌(G 菌)33株(23.9%),真菌18株(13.1%).大多数菌株多重耐药.结论机械通气引发下呼吸道感染院内感染病原菌以G-菌为主,其药敏实验呈多重耐药,临床早期经验性抗生素治疗应选择敏感广谱抗生素.     

吴寿善治疗燥证学术思想与临证经验总结

吴寿善教授对"燥气大纲"有独到见解,不仅提出了有凉燥、温燥伤人、燥化寒湿、湿热伤人,并且提出燥气有"胜复"不同:化热伤津之证属燥之复气伤人,寒湿之证是燥之胜气伤人。因此,可见《温病条辨》中所列杏苏散等方,正是为治燥之胜气、治燥之正化、治燥之本病而设。所列的桑杏汤等方则是为治燥之复病、治燥之对化、治燥之标病而设,从而使燥气之本标胜复病机霍然。吴教授还强调见化气为病有寒热之别,见寒湿者自当用温化,见湿热者自当用清泄。临证时还须注意表里寒热之不一,只有这样才能达到技药愈病之目的。燥伤本脏除识别复气现症外,还要选药精当。笔者在临床上发现,凡见杏苏散证而有痰黏、频咳、唾出不爽者,视其轻重而选加冬瓜仁、贝母、鱼腥草、半枝莲等品,以清复热,效果较好,若见小青龙汤证而兼复气为患者,追加药物亦可仿此。     

Two epithelial cell invasion-related loci of the oral pathogen Actinobacillus actinomycetemcomitans

Two invasion-related loci, apiA and the two-gene operon apiBC, were isolated from the oral pathogen Actinobacillus actinomycetemcomitans UT32. apiA encodes a 32.5 kDa protein that migrates on SDS-PAGE as a 101 kDa protein as detected by Western blot analysis or silver staining of an outer membrane-enriched fraction of Escherichia coli transformants. E. coli expressing ApiA have a different phenotype than the host vector, in broth and on solid media, and a colony morphology that resembles that of fresh A. actinomycetemcomitans isolates. These E. coli transformants bound to chicken collagen type II, human collagen type II, III, V and fibronectin. apiB and apiC encode proteins of 130.1 and 70.6 kDa, respectively. ApiBC conferred on E. coli a slightly enhanced ability to bind to collagen type III. ApiA- and ApiB-deficient mutants were constructed in A. actinomycetemcomitans. The ApiB-mutant had 4-fold diminished invasion of KB cells; the ApiA-mutant had increased invasion. Both loci were found in all A. actinomycetemcomitans strains, although polymorphism was detected only for apiBC. The deduced sequences of these invasion-related proteins are homologous to members of the YadA adhesin/invasin family.     

先天性心脏病合并社区获得性肺炎患儿呼吸道病毒及特殊病原体相关分析

【摘要】目的 探讨先天性心脏病（CHD）合并社区获得性肺炎患儿与单纯社区获得性肺炎患儿呼吸道病毒和特殊病原体抗体分布特点。方法 选取2014年1月～2019年8月于我院儿科住院的721例社区获得性肺炎患儿进行回顾性分析, 根据患儿有无合并先天性心脏病分为先天性心脏病组（CHD组）208例和单纯社区获得性肺炎组（LRI组）513例。采用间接免疫荧光法检测血清嗜肺军团菌IgM抗体（LP1A）、肺炎支原体IgM抗体(MPA)、Q热立克次体IgM抗体（QR-FA）、肺炎衣原体IgM抗体（CPnA）、腺病毒IgM抗体（ADVA）、呼吸道合胞病毒IgM抗体(RSVA)、甲型流感病毒IgM抗体（IAVA）、乙型流感病毒IgM抗体（IBVA）、副流感病毒IgM抗体(PIVsA)等9种呼吸道病原体抗体及特殊病原体IgM抗体。比较两组9种呼吸道病原体及特殊病原体检出阳性率、不同年龄阶段、不同季节分布情况。结果 CHD组纳入研究的呼吸道病原体抗体九项检测,阳性共136例,LRI组纳入研究的呼吸道病毒及特殊病原体九项,阳性共305例,CHD组病原体IgM总阳性率(65.4%)高于LRI组阳性率(59.4%),但两组比较差异无统计学意义（P＞0.05）。CHD组与LRI组均以肺炎支原体（MP）最常见,其次为乙型流感病毒（IBV）,其余病毒及呼吸道特殊病原体检出阳性率较低。CHD组和LRI组相比较,在婴幼儿时期,CHD组较易感染MP,但在1～3岁时,则是易感染IBV（均P＜0.05）;冬春季,CHD组较易感染MP及IBV,而LRI组较易感染LP1及ADV,但两组LP1阳性率均低,无临床指导意义。结论 合并社区获得性肺炎患儿特殊病原体抗体谱与单纯社区获得性肺炎患儿相似,以MP最常见;在婴幼儿期及冬春季,CHD合并社区获得性肺炎患儿较单纯社区获得性肺炎患儿易于感染MP;在1～3岁年龄段及冬春季,易于感染IBV。     

从“伏邪”理论论治反复呼吸道感染

"伏邪"是导致呼吸道感染反复发作、缠绵难愈的内因之一。根据"伏邪"理论,反复呼吸道感染病位在肺,病机为肺卫不固、肺失宣肃、肺气不足、邪伏于肾。该病的病机核心为"邪伏正虚",治疗应以"扶正透邪"为基本原则。根据该病标本虚实不同,处以不同方剂,旨在为反复呼吸道感染的临床辨治提供新的思路。