A prime-boost concept using a T-cell epitope-driven DNA vaccine followed by a whole virus vaccine effectively protected pigs in the pandemic H1N1 pig challenge model

Influenza A virus (IAV) vaccines in pigs generally provide homosubtypic protection but fail to prevent heterologous infections. In this pilot study, the efficacy of an intradermal pDNA vaccine composed of conserved SLA class I and class II T cell epitopes (EPITOPE) against a homosubtypic challenge was compared to an intramuscular commercial inactivated whole virus vaccine (INACT) and a heterologous prime boost approach using both vaccines. Thirty-nine IAV-free, 3-week-old pigs were randomly assigned to one of five groups including NEG-CONTROL (unvaccinated, sham-challenged), INACT-INACT-IAV (vaccinated with FluSure XP® at 4 and 7 weeks, pH1N1 challenged), EPITOPE-INACT-IAV (vaccinated with PigMatrix EDV at 4 and FluSure XP® at 7 weeks, pH1N1 challenged), EPITOPE-EPITOPE-IAV (vaccinated with PigMatrix EDV at 4 and 7 weeks, pH1N1 challenged), and a POS-CONTROL group (unvaccinated, pH1N1 challenged). The challenge was done at 9 weeks of age and pigs were necropsied at day post challenge (dpc) 5. At the time of challenge, all INACT-INACT-IAV pigs, and by dpc 5 all EPITOPE-INACT-IAV pigs were IAV seropositive. IFNγ secreting cells, recognizing vaccine epitope-specific peptides and pH1N1 challenge virus were highest in the EPITOPE-INACT-IAV pigs at challenge. Macroscopic lung lesion scores were reduced in all EPITOPE-INACT-IAV pigs while INACT-INACT-IAV pigs exhibited a bimodal distribution of low and high scores akin to naïve challenged animals. No IAV antigen in lung tissues was detected at necropsy in the EPITOPE-INACT-IAV group, which was similar to naïve unchallenged pigs and different from all other challenged groups. Results suggest that the heterologous prime boost approach using an epitope-driven DNA vaccine followed by an inactivated vaccine was effective against a homosubtypic challenge, and further exploration of this vaccine approach as a practical control measure against heterosubtypic IAV infections is warranted.     

Isolated Donor Specific Alloantibody-Mediated Rejection after ABO Compatible Liver Transplantation

Antibody-mediated rejection (AMR) after liver transplantation is recognized in ABO incompatible and xeno-transplantation, but its role after ABO compatible liver transplantation is controversial. We report a case of ABO compatible liver transplantation that demonstrated clinical, serological and histological signs of AMR without evidence of concurrent acute cellular rejection. AMR with persistently high titers of circulating donor specific antibodies resulted in graft injury with initial centrilobular hepatocyte necrosis, fibroedematous portal expansion mimicking biliary tract outflow obstruction, ultimately resulting in extensive bridging fibrosis. Immunofluorescence microscopy demonstrated persistent, diffuse linear C4d deposits along sinusoids and central veins. Despite intense therapeutic intervention including plasmapheresis, IVIG and rituximab, AMR led to graft failure. We present evidence that an antibody-mediated alloresponse to an ABO compatible liver graft can cause significant graft injury independent of acute cellular rejection. AMR shows distinct histologic changes including a characteristic staining profile for C4d.     

普拉固和鱼油对高胆固醇血症患者血脂与心脑血管事件影响的比较

目的:比较普拉固和鱼油对高胆固醇血症患者的血脂、血粘度、血管内皮功能和心脑血管事件的影响。方法:对266例原发性高胆固醇血症患者经2周洗脱期后,随机分为两组,普拉固组,初服10mg,每晚一次,8周后若TC仍>5.2mmol/L,LDL—ch>3.12mmol/L,则加量至20mg/d,每8周再查血脂,以达到TC<5.2mmol/L,LDL—ch<3.12mmol/L的量作治疗量继续服用。鱼油组,服美国深海鱼油一日三次,一次3g,均于服药8周复查血脂、血粘度及血管内皮功能等并作16月随访。结果:治疗8周,TC,普拉固组下降26％,鱼油组下降12％(P<0.01)。LDL—ch,普拉固组下降31％,鱼油组下降11％(P<0.01),肱动脉流量介导的舒张与硝酸甘油介导的舒张,普拉固组分别增加104％和19％,鱼油组无明显改变。全血低切粘度,普拉固组减少23％,鱼油组减少10％(P<0.01)。平均随访16月,普拉固组中脑出血1例(0.8％),鱼油组发生心脑血管事件7例(5.3％),死亡1例(P<0.05)。两组均无明显的不良反应。结论:普拉固是一个安全有效的降脂药,能改善血管内皮功能,降低血粘度,减少高胆固醇血症病人心脑血管事件发生。     

A case of nocturnal fainting: supine vasovagal syncope.

Supine loss of consciousness is a relatively rare occurrence prompting investigations for underlying causes as diverse as cardiac arrhythmia, hypoglycaemia and nocturnal epilepsy. Neurally mediated syncope is rarely implicated as the cause of symptoms in supine loss of consciousness because of the absence of orthostatic stress and gravitational relative preservation of cerebral perfusion, but we report here on a case of recurrent, atypical and troublesome vasovagal syncope occurring at night while supine. Diagnosis aided by head-up tilt table testing and conservative management brought about complete resolution of symptoms.     

Cell mediated immunity (CMI) and post transplant viral infections — Role of a functional immune assay to titrate immunosuppression

Cell mediated immunity (CMI) was assessed by the ImmuKnow assay in 12 patients after kidney transplantation, who presented with viral infection. Treatment included lowering of immunosuppression in all cases and antiviral treatment if indicated. The assay was repeated during the follow up. The ImmuKnow assay at time of presentation of viral infections was 56.8 ± 58.2 (range 3–178; median 22) ATP ng/ml. With the clearance of viral infection and lowering of immunosuppression, the assay showed an increase in the level of CMI at 194.5 ± 118.9 (range 53–409; median 150) ATP ng/ml. There was viral clearance or stabilization in all cases and there was no incidence of allograft rejection. The ImmuKnow assay of CMI can be used to titrate initial immunosuppression reduction and its subsequent increase, in patients with viral infection after transplantation.     

Hypersensitivity pneumonitis in rabbits. Modulation of pulmonary inflammation by long-term aerosol challenge with antigen

Immunized rabbits that were aerosol challenged for 2 to 3 wk with pigeon dropping extract, an etiologic agent of hypersensitivity pneumonitis, developed chronic pulmonary inflammation associated with cell-mediated immunity in bronchoalveolar cells. However, prolonged aerosol challenge for 12 wk resulted in the diminution of pulmonary inflammation (modulation) and the loss of demonstrable cell-mediated immunity. This was probably not due to loss of sensitized lymphocytes that mediated pulmonary inflammation. Furthermore, rabbits undergoing modulation when they were challenged with an unrelated antigen were refractory to the development of pulmonary inflammation for at least 9 wk. After this refractory period, animals reimmunized and aerosol challenged with pigeon dropping extract displayed an anamnestic response and produced pulmonary lesions that were strikingly similar to the histopathology of human hypersensitivity pneumonitis.     

介绍一种制备特异性TF和特异性iRNA的方法

以乙肝疫苗、人喉癌细胞膜抗原为抗原，猪脾细胞为效应细胞，经体外免疫后收集应答细胞，制备ＰＳＨＢＶ－ＴＦ ＰＳＡＣ－ｉＲＮＡ。通过抗原特异性细胞免疫功能试验证实，ＰＳＨＢＶ－ＴＦ和ＰＳＡＣ－ｉＲＮＡ都能转移特异性细胞免疫功能。采用体外免疫法制备ＰＳＨＢＶ－ＴＦ和ＰＳＡＣ－ｉＲＮＡ是可行的，并且具有诸多优点。