Pigs immunized with Chinese highly pathogenic PRRS virus modified live vaccine are protected from challenge with North American PRRSV strain NADC-20

Modified live virus (MLV) vaccines developed to protect against PRRSV circulating in North America (NA) offer limited protection to highly pathogenic (HP) PRRSV strains that are emerging in Asia. MLV vaccines specific to HP-PRRSV strains commercially available in China provide protection to HP-PRRSV; however, the efficacy of these HP-PRRSV vaccines to current circulating NA PRRS viruses has not been reported. The aim of this study is to investigate whether pigs vaccinated with attenuated Chinese HP-PRRSV vaccine (JXA1-R) are protected from infection by NA PRRSV strain NADC-20. We found that pigs vaccinated with JXA1-R were protected from challenges with HV-PRRSV or NADC-20 as shown by fewer days of clinical fever, reduced lung pathology scores, and lower PRRS virus load in the blood. PRRSV-specific antibodies, as measured by IDEXX ELISA, appeared one week after vaccination and virus neutralizing antibodies were detected four weeks post vaccination. Pigs vaccinated with JXA1-R developed broadly neutralizing antibodies with high titers to NADC-20, JXA1-R, and HV-PRRSV. In addition, we also found that IFN-α and IFN-β occurred at higher levels in the lungs of pigs vaccinated with JXA1-R. Taken together, our studies provide the first evidence that JXA1-R can confer protection in pigs against the heterologous NA PRRSV strain NADC-20.     

Systemic immune responses to an inactivated,whole H9N2 avian influenza virus vaccine using class B CpG oligonucleotides in chickens

Commercial vaccines against avian influenza viruses (AIV) in chickens consist mainly of inactivated AIV, requiring parenteral administration and co-delivery of an adjuvant. Limitations in T helper 1 or T helper 2 biased responses generated by these vaccines emphasize the need for alternative, more efficacious adjuvants. The Toll-like receptor (TLR) 21 ligand, CpG oligodeoxynucleotides (ODN), has been established as immunomodulatory in chickens. Therefore, the objective of this study was to investigate the adjuvant potential of high (20 μg) and low (2 μg) doses of CpG ODN 2007 (CpG 2007) and CpG ODN 1826 (CpG 1826) when administered to chickens with a formalin-inactivated H9N2 AIV. Antibody responses in sera were evaluated in 90 specific pathogen free (SPF) chickens after intramuscular administration of vaccine formulations at 7 and 21 days post-hatch. Antibody responses were assessed based on haemagglutination inhibition (HI) and virus neutralization (VN) assays; virus-specific IgM and IgY antibody responses were evaluated by ELISA. The results suggest that the vaccine formulation containing low dose CpG 2007 was significantly more effective at generating neutralizing (both HI and VN) responses than formulations with high or low doses of CpG 1826 or high dose CpG 2007. Neutralizing responses elicited by low dose CpG 2007 significantly exceeded those generated by a squalene-based adjuvanted vaccine formulation during peak responses. A significantly higher IgM response was elicited by the formulation containing low dose CpG 2007 compared to high and low doses of 1826. Although the low dose of CpG 2007 elicited a higher IgY response than CpG 1826, the difference was not statistically significant. In conclusion, 2 μg of CpG 2007 is potentially promising as a vaccine adjuvant when delivered intramuscularly with inactivated H9N2 virus to chickens. Future studies may be directed at determining the mucosal antibody responses to the same vaccine formulations.     

The Return of Actionable Variants Empirical (RAVE) Study,a Mayo Clinic Genomic Medicine Implementation Study: Design and Initial Results

Objectives

To identify clinically actionable genetic variants from targeted sequencing of 68 disease-related genes, estimate their penetrance, and assess the impact of disclosing results to participants and providers.

清热合剂对上呼吸道感染常见致病菌的体外抑菌试验

目的观察清热合剂对上呼吸道感染常见致病菌的体外抑菌活性。方法上呼吸道感染常见致病菌163株中不产超广谱β-内酰胺酶(ESBLs)革兰阴性菌74株(大肠埃希菌33株,肺炎克雷伯菌24株,铜绿假单胞菌17株);产ESBLs革兰阴性菌10株(大肠埃希菌6株,肺炎克雷伯菌4株);革兰阳性菌79株[耐甲氧西林金黄色葡萄球菌(MRSA)11株、甲氧西林敏感金黄色葡萄球菌(MSSA)46株,肺炎链球菌22株]。采用琼脂稀释法对清热合剂进行定量抑菌试验,配制含有不同药物浓度的琼脂平板,在平板上接种待测菌株菌悬液,孵育后观察含药平板,记录最低抑菌浓度(MIC)。结果清热合剂对大肠埃希菌、肺炎克雷伯菌、铜绿假单胞菌等革兰阴性菌的MIC90分别为88、176、22 g/L,其对产ESBLs与不产ESBLs革兰阴性菌的抑菌效果一致;不同浓度药物对铜绿假单胞菌的累积抑菌率均最高。清热合剂对MSSA、MRSA和肺炎链球菌等革兰阳性菌的MIC90分别为11、11、22 g/L,MRSA的MIC90与MSSA相同,但MIC50略高于MSSA;不同浓度药物对MSSA和MRSA的累积抑菌率均高于肺炎链球菌,对MSSA与MRSA的累积抑菌率相近。结论清热合剂对上呼吸道感染常见的致病菌除肺炎克雷伯菌之外均有一定的抑菌作用,对革兰阳性菌的抑菌效果明显优于革兰阴性菌。     

Influenza A(H5N8) Virus Similar to Strain in Korea Causing Highly Pathogenic Avian Influenza in Germany

Highly pathogenic avian influenza (H5N8) virus, like the recently described H5N8 strain from Korea, was detected in November 2014 in farmed turkeys and in a healthy common teal (Anas crecca) in northeastern Germany. Infected wild birds possibly introduced this virus.     

Novel Reassortant Influenza A(H5N8) Viruses among Inoculated Domestic and Wild Ducks,South Korea, 2014

An outbreak of highly pathogenic avian influenza, caused by a novel reassortant influenza A (H5N8) virus, occurred among poultry and wild birds in South Korea in 2014. The aim of this study was to evaluate the pathogenesis in and mode of transmission of this virus among domestic and wild ducks. Three of the viruses had similar pathogenicity among infected domestic ducks: the H5N8 viruses were moderately pathogenic (0%–20% mortality rate); in wild mallard ducks, the H5N8 and H5N1 viruses did not cause severe illness or death; viral replication and shedding were greater in H5N8-infected mallards than in H5N1-infected mallards. Identification of H5N8 viruses in birds exposed to infected domestic ducks and mallards indicated that the viruses could spread by contact. We propose active surveillance to support prevention of the spread of this virus among wild birds and poultry, especially domestic ducks.     

Pathologic Changes in Wild Birds Infected with Highly Pathogenic Avian Influenza A(H5N8) Viruses,South Korea, 2014

In January 2014, an outbreak of infection with highly pathogenic avian influenza (HPAI) A(H5N8) virus began on a duck farm in South Korea and spread to other poultry farms nearby. During this outbreak, many sick or dead wild birds were found around habitats frequented by migratory birds. To determine the causes of death, we examined 771 wild bird carcasses and identified HPAI A(H5N8) virus in 167. Gross and histologic lesions were observed in pancreas, lung, brain, and kidney of Baikal teals, bean geese, and whooper swans but not mallard ducks. Such lesions are consistent with lethal HPAI A(H5N8) virus infection. However, some HPAI-positive birds had died of gunshot wounds, peritonitis, or agrochemical poisoning rather than virus infection. These findings suggest that susceptibility to HPAI A(H5N8) virus varies among species of migratory birds and that asymptomatic migratory birds could be carriers of this virus.     

利用诱导性多能干细胞技术研究环境致病因素诱导帕金森病发病的进展

帕金森病是一种十分普遍的中枢神经系统退行性疾病,以中脑黑质纹状体多巴胺能神经元丢失为主要特征,诱发因素较多。本文简述帕金森病的环境及职业致病因素和诱导性多能干细胞(i PScs)技术的研究进展,并分析了i PScs技术在研究环境、职业致病因素诱导帕金森病发病机制中的应用前景,提出了将i PScs技术应用于研究帕金森病的发病机制具有重要意义。     

98例下肢静脉曲张患者术后院内感染病原菌的分布及其耐药性研究

目的:探究下肢静脉曲张患者术后院内感染病原菌的分布及其对抗菌药物的耐药性。方法:采用回顾性分析法,抽取2013年2月-2018年2月间在医院接受治疗的下肢静脉曲张术后院内感染患者98例临床资料,分析患者术后院内感染病原菌培养与分离情况,以及药敏试验结果对不同抗菌药物耐药程度的影响。结果:98例下肢静脉曲张术后院内感染患者标本中,检出84株病原菌,其中革兰阴性菌51株(占60.71%)、革兰阳性菌30株(占35.71%)和真菌3株(占3.58%),经组间数据比较其差异有统计学意义(P<0.05);革兰阴性菌以铜绿假单胞菌、大肠埃希菌、肺炎克雷伯菌为主,革兰阳性菌以表皮葡萄球菌、金黄色葡萄球菌为主;铜绿假单胞菌对氨苄西林、头孢唑林、头孢曲松的耐药性较高;大肠埃希菌对氨苄西林、头孢唑林、头孢曲松、氨曲南的耐药性较高;肺炎克雷伯菌对氨苄西林、头孢曲松、阿米卡星的耐药性较高;表皮葡萄球菌对头孢唑林、青霉素G、克林霉素的耐药性较高;金黄色葡萄球菌对环丙沙星、青霉素G、克林霉素的耐药性较高。结论:下肢静脉曲张患者手术后院内感染病原菌以革兰阴性菌为主,且革兰阴性菌和革兰阳性菌对氨苄西林、头孢唑林、头孢曲松、氨曲南、克林霉素、青霉素G等抗菌药物的耐药性较高;临床治疗应依据药敏试验结果选用抗菌药物治疗。