Vaccination with chimeric protein induces protection in murine model against ascariasis

An estimated 400 million people are infected by parasites of the genus Ascaris and the existing control measures are inefficient. Vaccine development using B cell antigens is a promising strategy for increased protection against this parasite. The present study aimed at developing a chimeric protein capable of conferring protection against infection by Ascaris sp. For this purpose, we performed B-cell epitope predictions on previously described vaccine candidate proteins from Ascaris suum and the corresponding peptides were used to construct a chimeric protein. Female BALB / c mice were immunized subcutaneously in three doses at 10 day intervals with a vaccine formulation comprised of the chimeric protein together with monophosphoryl lipid A (MPLA). Control groups included protein alone, MPLA, or PBS. After challenge infection, animals vaccinated with chimeric protein plus MPLA showed a reduction of 73.54% of larval load in the lung compared to control group animals. Animals immunized with chimeric protein plus MPLA also display higher IgG response and a reduction in lung inflammation. Our study highlights how chimeric proteins containing more than one B cell epitope can enhance immune protection against helminthic infection and offer new approaches to the development of Ascaris vaccines.     

Long-term persistent immunogenicity after successful standard and triple-dosed hepatitis B vaccine in hemodialysis patients: A 3-year follow-up study in China

BackgroundAlthough the efficacy of hepatitis B vaccines among hemodialysis patients has been documented, the long-term persistence of immunogenicity in this population remains largely unknown. We explored the long-term persistence of immunogenicity induced by different hepatitis B vaccine regimens in hemodialysis patients.MethodsIn initial study, we conducted a randomized, multicenter, double-blind, parallel-controlled trial among hemodialysis patients in 13 hospitals in Shanxi Province, China. A total of 352 hemodialysis patients were allocated to receive 3-dose 20 μg (IM20 group) and 3-dose 60 μg (IM60 group) recombinant hepatitis B vaccine at months 0, 1, and 6. Vaccine-induced immune responses were measured at month 7. In this study, the responders (anti-HBs ≥ 10 mIU/mL) were followed up at months 18, 24, 30, 36 and 42, respectively. We used the generalized log-rank test and generalized estimating equations (GEE) to analyze the long-term durability of responses and the kinetics of anti-HBs levels, respectively.ResultsA total of 284 patients were involved in the extended follow-up period. The duration of vaccine-induced response with 75% of patients maintained protective antibody were 12 months and 18 months in the IM20 group and IM60 group, respectively (P = 0.291). The long-term persistent immunogenicity induced by 3-dose 60 μg was more satisfactory than that by 3-dose 20 μg hepatitis B vaccine in patients with hemodialysis duration ≥ five years (P = 0.023). The peak anti-HBs levels in 100–1000 mIU/mL or ≥ 1000 mIU/mL were more likely to maintain long-term protective antibody compared to anti-HBs levels in 10–100 mIU/mL (P ＜ 0.05). The kinetic profile was similar between the two groups (P = 0.334).ConclusionHigh-dose 60 μg hepatitis B vaccine could lead a satisfactory long-term durability of immunogenicity among patients with hemodialysis duration of five years or more. Peak anti-HBs level after vaccination was associated with the long-term persistence of immunogenicity.     

Serological response with Heplisav-B® in prior Hepatitis B vaccine non-responders living with HIV

BackgroundAs people living with HIV (PLWH) are at risk for contracting Hepatitis B Virus (HBV), they should be screened for HBV and vaccinated if not immune. Seroconversion rates in PLWH receiving traditional recombinant HBV vaccines (Engerix-B® and Recombivax-HB®) have historically been low with at most 70% achieving immunity. In 2017, a recombinant, adjuvanted HBV vaccine (Heplisav-B®) was approved for use in HIV-negative patients.Heplisav-B® has shown superior seroprotection in this population compared to Engerix-B® and Recombivax-HB®, as well as interim analysis showing higher seropositivity rates in patients undergoing dialysis. However, its efficacy in PLWH is currently unknown. This study evaluates the rate of seroconversion following Heplisav-B® administration in PLWH with previous HBV vaccination failure.MethodsRetrospective, cross-sectional study at The Brooklyn Hospital Center’s HIV primary care clinic in Brooklyn, NY. HIV-positive adults who received at least two doses of Heplisav-B® and had previously failed to seroconvert after vaccination with Engerix-B® or Recombivax-HB® were included. The primary outcome is the percentage of PLWH who became seropositive following Heplisav-B®.ResultsA total of 67 patients met the inclusion criteria. Twenty-five (37.3%) PLWH had failed at least 2 courses of recombinant vaccines. Fifty-eight (86.6%) PLWH became seropositive (Anti-HBs > 10 mIU/mL) at least two months after completing Heplisav-B®. For the 9 (13.4%) patients that did not develop immunity, 3 (33%) had a detectable HIV RNA and 3 (33%) had a CD4 count < 200 cells/uL³.ConclusionsHeplisav-B® was highly effective in achieving immunity to HBV in PLWH who failed non-adjuvanted recombinant vaccines.     

Prevention of hepatitis B mother-to-child transmission in Namibia: A cost-effectiveness analysis

Despite access to a safe and effective vaccine, mother-to-child transmission (MTCT) of hepatitis B virus (HBV) persists in Africa. This is of concern since perinatally-infected infants are at highest risk of developing hepatocellular carcinoma, a life-threatening consequence of chronic HBV infection. While tools to prevent HBV MTCT are available, the cost implications of these interventions need consideration prior to implementation. A Markov model was developed to determine the costs and health outcomes of (1) universal HBV birth dose (BD) vaccination, (2) universal BD vaccination and targeted hepatitis B immunoglobulin (HBIG), (3) maternal antiviral prophylaxis using sequential HBV viral load testing added to HBV BD vaccination and HBIG, and (4) maternal antiviral prophylaxis using sequential HBeAg testing combined with HBV BD vaccination and HBIG. Health outcomes were assessed as the number of paediatric infections averted and disability-adjusted life years (DALYs) averted. Primary cost data included consumables, human resources, and hospital facilities. HBV epidemiology, transitions probabilities, disability weights, and the risks of HBV MTCT were extracted from the literature. Incremental cost-effectiveness ratios (ICERs) were calculated to compare successive more expensive interventions to the previous less expensive one. One-way sensitivity analyses were conducted to test the robustness of the model’s outputs. At the Namibian cost/DALY averted threshold of US$3 142, the (1) BD vaccination + targeted HBIG, and (2) maternal antiviral prophylaxis with sequential HBeAg testing interventions were cost-effective. These interventions had ICERs equal to US$1909.03/DALY and US$2598.90/DALY averted, respectively. In terms of effectiveness, the maternal antiviral prophylaxis with sequential HBeAg testing intervention was the intervention of choice. The analysis showed that elimination of HBV MTCT is achievable using maternal antiviral prophylaxis with active and passive immunization. There is an urgent need for low cost diagnostic tests to identify those women who will most benefit from drug therapy to attain this laudable goal.     

Serogroup B meningococcal disease in persons previously vaccinated with a serogroup B meningococcal vaccine – United States, 2014–2019

Since serogroup B meningococcal (MenB) vaccines became available in the United States, six serogroup B meningococcal disease cases have been reported in MenB-4C (n = 4) or MenB-FHbp (n = 2) recipients. Cases were identified and characterized through surveillance and health record review. All five available isolates were characterized using whole genome sequencing; four isolates (from MenB-4C recipients) were further characterized using flow cytometry, MenB-4C-induced serum bactericidal activity (SBA), and genetic Meningococcal Antigen Typing System (gMATS). Three patients were at increased meningococcal disease risk because of an outbreak or underlying medical conditions, and only four of the six patients had completed a full 2-dose MenB series. Isolates were available from 5 patients, and all contained sub-family A FHbp. The four isolates from MenB-4C recipients expressed NhbA but were mismatched for the other MenB-4C vaccine antigens. These four isolates were relatively resistant to MenB-4C-induced SBA, but predicted by gMATS to be covered. Overall, patient risk factors, incomplete vaccine series completion, waning immunity, and strain resistance to SBA likely contributed to disease in these six patients.     

用体外器官培养方法研究EDCs对新生小鼠睾丸的影响

目的 通过已建立的小鼠睾丸体外培养系统,研究四种内分泌干扰物（Endocrine Disrupting Chemicals,EDCs）对男性内分泌系统的影响。 方法 将新生小鼠的睾丸组织在体外环境中培养24h,而后在培养基中分别加入浓度为0.1μM, 1μM, 10μM and 100μM的四种（DEHP、MEHP、NP、p, p’-DDE）内分泌干扰物并培养72h,同时设置对照组;培养结束后进行组织学观察,测定冻存培养基中睾酮和抑制素βB (INH-βB)的分泌水平,同时测定细胞色素P450侧链裂解酶(P450Scc)、3β-羟基类固醇脱氢酶(3β-HSD)、细胞色素P45017α-羟化酶(P450C17)和波形蛋白（vimentin）的基因表达情况。 结果 所有剂量组中睾酮的分泌水平均发生改变;P450Scc、3β-HSD、P450C17和INH-βB蛋白质的表达及mRNA水平均受到四种内分泌干扰物的影响（P<0.05）;DEHP和MEHP降低了波形蛋白的mRNA水平（P<0.05）,而NP和p, p’-DDE对波形蛋白没有显著影响（P>0.05）。 结论 本研究建立的体外培养新生小鼠睾丸模型中,所选的四种已知EDCs改变了两种睾丸激素水平,三种类固醇合成酶以及与支持细胞功能相关的波形蛋白的表达。     

云南省跨境婚姻家庭艾滋病、梅毒和乙肝检测现状分析

目的 了解云南省中-缅、中-老、中-越跨境婚姻家庭艾滋病、梅毒和乙肝检测情况,为完善跨境婚姻家庭预防母婴传播相关服务政策提供科学依据。 方法 对目前居住在云南省边境地区的中国籍和跨境婚姻家庭进行调查和访谈,收集一般人口学特征、最近一次怀孕期间三病检测情况等信息。经整理后,使用构成比和率对指标进行计算,使用卡方检验、秩和检验比较中国籍和跨境婚姻家庭各项检测服务状况。 结果 外籍媳妇主要以农民、文盲/小学、无经济收入的少数民族为主。配偶检测率,老挝籍低于当地中国籍媳妇（〖XC五号.EPS;P〗=7.87,P=0.005）,缅甸籍、越南籍与当地中国籍没有差异;缅甸籍高于老挝籍和越南籍（〖XC五号.EPS;P〗=41.84,P＜0.001）。三病检测点知晓率,缅甸籍媳妇低于当地中国籍媳妇（〖XC五号.EPS;P〗=6.11,P＜0.03）,越南籍、老挝籍与当地中国籍没有差异;老挝籍高于缅甸籍和越南籍（〖XC五号.EPS;P〗=44.03,P＜0.001）。获得预防母婴传播相关知识比例,三个外籍媳妇均低于当地中国籍（〖XC五号.EPS;P〗=19.84,P＜0.001;〖XC五号.EPS;P〗=7.52,P=0.006;〖XC五号.EPS;P〗=4.38,P=0.036）。 结论 边境地区针对跨境婚姻家庭开展艾滋病、梅毒和乙肝预防母婴传播相关工作取得实效,三病检测情况与当地中国籍基本一致,但在其他服务利用上仍存在一定差距,外籍媳妇孕早期三病检测率及其配偶检测率、相关预防母婴传播知识获取还有待提升,需要运用更加有效的服务管理模式来促进三病检测可及性的进一步提高。     

慢性乙型肝炎患者外周血细胞因子IL-17A、IL-2、IL-21、IL-4表达水平及意义

目的 探索初治慢性乙型肝炎（CHB）患者外周血中细胞因子表达水平及其与病毒载量和肝脏炎症程度的关系,以期为临床动态评估病情和预后方面提供新思路。方法 选择2018年10月至2019年11月就诊于海军军医大学第一附属医院感染科的初治慢性乙型肝炎病毒（HBV）感染者68例,健康对照者12名,通过ELISA检测外周血中细胞因子IL-17A、IL-2、IL-21和IL-4表达水平,同时检测HBV DNA及转氨酶水平。统计学处理采用Mann-Whitney U检验、Kruskal-Wallis H检验及Spearman相关性分析。结果 相较于健康对照者,初治CHB患者外周血IL-17A高 [17.50（11.99,25.36）vs14.14（9.01,23.68）pg/ml,Z=-2.001,P=0.045],IL-2低[57.19（31.10,79.92）vs73.06（62.41,105.84）pg/ml,Z=-2.509,P=0.012],IL-21高[37.12（23.85,77.66）vs（20.95±5.72）pg/ml,Z=-3.485,P<0.01],IL-4表达水平无差异。不同免疫状态的IL-17A表达有明显差异（H=8.870,P=0.031）。炎症活动状态CHB患者的IL-17A和IL-21更低、IL-2更高（P＜0.05）,IL-4无差异（P＞0.05）。HBeAg阳性CHB患者、HBeAg阴性CHB患者与健康对照者外周血细胞因子IL-17A、IL-2、IL-21比较,差异有统计学意义（IL-17A：H=10.061,P=0.007;IL-2：H=6.576,P=0.037;IL-21：H=12.444,P=0.002）。初治CHB患者外周血IL-17A、IL-21、IL-4与HBV DNA无相关性（r=0.02、0.23、0.07,均P>0.05）,IL-2与HBV DNA存在弱相关（r=0.32,P=0.01）。初治HBV患者外周血IL-17A、IL-21与ALT存在相关性（IL-17A：r=0.59,P<0.01;IL-21：r=0.49,P<0.01）,与AST存在相关性（IL-17A：r=0.47,P<0.01;IL-21：r=0.36,P<0.01）,而IL-2、IL-4与ALT和AST均无明显相关。ALT≥300U/L的初治CHB组、ALT＜300U/L的初治CHB组与健康对照者外周血细胞因子IL-17A、IL-2、IL-21比较,差异有统计学意义（IL-17A：H=27.557,P<0.01;IL-2：H=8.581,P=0.014;IL-21：H=21.438,P<0.01）。ROC曲线分析结果显示,IL-17A判断肝脏炎症程度的AUC值为0.8933（95%CI：0.7930-0.9936）,IL-21判断肝脏炎症程度的AUC值为0.7600（95%CI：0.6227-0.8973）。结论 IL-17A、IL-2和IL-21参与慢性HBV感染进程：初治CHB患者无论HBeAg阳性与否或炎症程度高低,外周血IL-17A和IL-21升高,IL-2下降;IL-2与HBV DNA有一定相关性;IL-17A和IL-21与ALT及AST均存在正相关;检测IL-17A和IL-2有助于病情评估与预后判断。     

The neu-protein and breast cancer

The neu-protein is overexpressed in about 20% of invasive duct cell carcinomas of the breast. The only reliable sign for neu-overexpression by immunohistochemistry is membrane staining. Its overexpression is correlated with decreased overall survival and disease free survival due to increased metastatic activity of neu-overexpressing tumour cells. This increased metastatic potential is a consequence of the motility enhancing activity of the neu-protein, which is exclusively expressed on pseudopodia, and to a lesser extent of its growth stimulating effect. From a clinical point of view, the assessment of neu-overexpression in breast cancer might become a useful tool in the future treatment of patients by chemotherapy, since patients whose tumour shows neu-overexpression benefit from higher doses of chemotherapy. The molecule plays a key role in the pathogenesis of Paget's disease of the breast. A chemotactic factor which is secreted by epidermal keratinocytes attracts the Paget cells to spread into the epidermis and acts via the neu-protein. In ductal carcinoma in situ, the combination of neu-overexpression and large cell type is highly correlated with extent of disease and therefore neu-overexpression might be a predictive marker for recurrence of disease after tumour resection.     

建立人微小病毒B19的PCR检测方法

人微小病毒Ｂ１９是微小病毒科中唯一能感染人的病毒。能够提供Ｂ１９抗原的病毒体外培养系统尚未建成，因此限制了血清学实验的开发和普及。为此作者建立起Ｂ１９病毒的ＰＣＲ检测方法。设计引物在表达外壳蛋白ＶＰ１基因区，扩增长度为４００ｂｐ。