Immune responses against hepatitis C virus genotype 3a virus-like particles in mice: A novel VLP prime-adenovirus boost strategy

Chronic hepatitis C virus (HCV) infection represents a major health threat to global population. In India, approximately 15–20% of cases of chronic liver diseases are caused by HCV infection. Although, new drug treatments hold great promise for HCV eradication in infected individuals, the treatments are highly expensive. A vaccine for preventing or treating HCV infection would be of great value, particularly in developing countries. Several preclinical trials of virus-like particle (VLP) based vaccine strategies are in progress throughout the world. Previously, using baculovirus based system, we have reported the production of hepatitis C virus-like particles (HCV-LPs) encoding structural proteins for genotype 3a, which is prevalent in India. In the present study, we have generated HCV-LPs using adenovirus based system and tried different immunization strategies by using combinations of both kinds of HCV-LPs with other genotype 3a-based immunogens. HCV-LPs and peptides based ELISAs were used to evaluate antibody responses generated by these combinations. Cell-mediated immune responses were measured by using T-cell proliferation assay and intracellular cytokine staining. We observed that administration of recombinant adenoviruses expressing HCV structural proteins as final booster enhances both antibody as well as T-cell responses. Additionally, reduction of binding of VLP and JFH1 virus to human hepatocellular carcinoma cells demonstrated the presence of neutralizing antibodies in immunized sera. Taken together, our results suggest that the combined regimen of VLP followed by recombinant adenovirus could more effectively inhibit HCV infection, endorsing the novel vaccine strategy.     

Acceptance of multiple injectable vaccines in a single immunization visit in The Gambia pre and post introduction of inactivated polio vaccine

BackgroundAs the World Health Organization (WHO) currently recommends that children be protected against 11 different pathogens, it is becoming increasingly necessary to administer multiple injectable vaccines during a single immunization visit. In this study we assess Gambian healthcare providers’ and infant caregivers’ attitudes and practices related to the administration of multiple injectable vaccines to a child at a single immunization visit before and after the 2015 introduction of inactivated polio vaccine (IPV). IPV introduction increased the number of injectable vaccines recommended for the 4-month immunization visit from two to three in The Gambia.MethodsWe conducted a cross-sectional questionnaire-based survey before and after the introduction of IPV at 4 months of age in a representative sample of all health facilities providing immunizations in The Gambia. Healthcare providers who administer vaccines at the selected health facilities and caregivers who brought infants for their 4 month immunization visit were surveyed.FindingsPrior to IPV introduction, 9.9% of healthcare providers and 35.7% of infant caregivers expressed concern about a child receiving more than 2 injections in a single visit. Nevertheless, 98.8% and 90.9% of infants received all required vaccinations for the visit before and after IPV introduction, respectively. The only reason why vaccines were not received was vaccine stock-outs. Infant caregivers generally agreed that vaccinators could be trusted to provide accurate information regarding the number of vaccines that a child needed.ConclusionHealthcare providers and infant caregivers in this resource limited setting accepted an increase in the number of injectable vaccines administered at a single visit even though some expressed concerns about the increase.     

Inactivated influenza vaccine formulated with single-stranded RNA-based adjuvant confers mucosal immunity and cross-protection against influenza virus infection

Influenza vaccination is considered the most valuable means to prevent and control seasonal influenza infections, which causes various clinical symptoms, ranging from mild cough and fever to even death. Among various influenza vaccine types, the inactivated subunit type is known to provide improved safety with reduced reactogenicity. However, there are some drawbacks associated with inactivated subunit type vaccines, with the main ones being its low immunogenicity and the induction of Th2-biased immune responses. In this study, we investigated the role of a single-stranded RNA (ssRNA) derived from the intergenic region in the internal ribosome entry site of the Cricket paralysis virus as an adjuvant rather than the universal vaccine for a seasonal inactivated subunit influenza vaccine. The ssRNA adjuvant stimulated not only well-balanced cellular (indicated by IgG2a, IFN-γ, IL-2, and TNF-α) and humoral (indicated by IgG1 and IL-4) immune responses but also a mucosal immune response (indicated by IgA), a key protector against respiratory virus infections. It also increases the HI titer, the surrogate marker of influenza vaccine efficacy. Furthermore, ssRNA adjuvant confers cross-protective immune responses against heterologous influenza virus infection while promoting enhanced viral clearance. Moreover, ssRNA adjuvant increases the number of memory CD4⁺ and CD8⁺ T cells, which can be expected to induce long-term immune responses. Therefore, this ssRNA-adjuvanted seasonal inactivated subunit influenza vaccine might be the best influenza vaccine generating robust humoral and cellular immune responses and conferring cross-protective and long-term immunity.     

狂犬病病毒致病机制研究概况

狂犬病病毒（RV）是一种高度嗜神经性病毒，由RV引发的狂犬病通常是一种急性致死性神经系统损伤性疾病。RV通过周围神经末梢和中枢神经系统（CNS）的神经元进行病毒的复制和传播。绝大多数狂犬病例CNS病理学表现为急性脑脊髓炎，常常没有显著的显微镜下改变，脑部可以轻度肿胀，脑膜和脑实质血管轻度充血并伴有少量炎症细胞浸润，这也是其他急性病毒性脑炎常见的共同表现。     

云南东川非铀矿山矿工血清IL-2、IL-6、TNF-α检测及其基因多态性的初步研究

目的 通过对云南非铀矿山矿工血清IL-2、IL-6和TNF-α浓度及基因多态性位点的检测,对氡致非铀矿山矿工机体生物效应进行初步探讨。方法 血清中IL-2、IL-6和TNF-α的浓度测定采用双抗夹心ABC-ELISA法。TNF-α(-308,G→A)检测基因型采用基因体外扩增限制性片段长度多态性分析方法,IL-2(-330, T→G)基因型检测采用PCR体外扩增后测序的方法。结果 矿工组与对照组比较,年龄(F＝1.07,P>0.05),工龄(F＝0.40,P>0.05),血清IL-2浓度(F＝0.71,P>0.05),血清IL-6浓度(F＝1.09,P>0.05),血清TNF-α浓度(F＝0.95,P>0.05),IL-2基因型频度(χ²=0.02,P>0.05)和TNF-α基因型频度(χ²=2.21,P>0.05),差异均无统计学意义。结论 云南东川非铀矿山矿工血清IL-2、IL-6和TNF-α平均浓度有下降的趋势, TNF-α(-308,A A)基因型频度有增高的趋势。     

电离辐射调控脂质体介导的p16基因在HeLa细胞中的表达

目的探讨不同剂量γ射线照射后诱导脂质体介导的p16基因在HeLa细胞中的表达及抗癌作用。方法用脂质体Lipofectamin介导重组质粒Egr-p16转染人HeLa细胞，采用RT-PCR的方法检测了。Coγ射线照射转染后的人HeLa细胞剂量效应和时程变化，用细胞计数检测细胞增殖的变化，用流式细胞术检测细胞周期的变化。结果研究证实0．5～8Gv照射后p16的转录水平高于对照，在2～4Gy照射后达到峰值，2Gy照射后2—24h高于对照组，在照射后4h达到峰值，然后逐渐下降。细胞生长曲线显示体外稳定转染联合。Coγ射线照射对HeLa细胞的增殖具有明显的抑制作用。细胞周期变化显示转染后的HeLa细胞经过照射后G0／G1期比例呈现剂量依赖性的下降，而S期则出现剂量依赖性的增加，出现明显的S期阻滞，G2／M期在2Gy出现明显的阻滞，在5和10Gy时逐渐下降，但是仍然高于对照组。结论^60Coγ射线可诱导转染的HeLa细胞p16转录水平的增强，同时在细胞增殖上出现明显的变化。     

肺结核病人健康教育现状调查与影响因素分析

目的　调查活动性肺结核病人在诊断前接受结核病知识的教育现状 ,分析病人接受结核病知识与社会经济因素的影响。方法　对 2 0 0 0年全国结核病流行病学抽样调查中的 1 2 78名活动性肺结核病人进行社会经济个案调查 ,调查以问卷的形式进行。结果　 1 2 78例肺结核病人在诊断前有 5 1 4例接受过不同形式的健康教育 ,占 40 2 % ,男性接受健康教育比例为 41 8% ,女性为 3 6 9%。各年龄组接受健康教育比例 <1 5岁组最低为2 5 9% ,其次是 65～年龄组为 3 0 9%。随着病人文化程度的增高和家庭人均年收入的增高 ,接受健康教育比例增高。肺结核病人各种职业的分类中 ,无工作者接受健康教育比例最低为 3 5 5 % ,其次为农林牧渔劳动者。按照病人是否有症状、有症状后是否就诊及最后诊断为肺结核病人的 3个过程接受不同形式的健康教育的频率 ,均以广播电视、健康教育和亲友教育为主。结论　在开展健康教育活动中 ,应注意对儿童和老年人群 ,对于文化程度低、家庭经济收入低、无工作者和农林牧渔劳动者等重点人群的教育     

与铁稳态有关的生物分子

根据近几年来发表的与铁稳态有关的生物分子的研究文献 ,将这些生物分子根据其与铁的吸收、转运、储存以及对铁稳态的监控调节等方面的关系 ,对这些生物分子进行了分类。特别是对细胞膜载体、运铁蛋白受体、铁调蛋白及铁反应元件等作了较为详细地论述     

NaFeEDTA预防大鼠铅中毒的研究及其对锌、铜的影响

为探讨乙二胺四乙酸铁钠 (NaFeEDTA)在预防大鼠铅中毒及减低铅毒性中的作用 ,同时研究其对锌、铜二元素的影响 ,采用随机分组的动物实验设计方法 ,将 60只Wistar大鼠随机分为空白对照组、模型对照组、阳性药物组和高、中、低NaFeEDTA组 ,共 6组 ,除空白对照组外 ,对其余各组大鼠进行持续性染铅 ,而且除模型对照组外的 4个染铅组分别同时给予二巯基丁二酸 (DMSA)、高、中、低浓度的NaFeEDTA溶液。 5周后实验结束 ,对相关指标进行测定。结果显示 ,三个NaFeEDTA组的血红蛋白含量均显著高于其它各组 ,同时其血铅、脑铅、肝脏铅、肾脏铅及胫骨铅含量显著低于模型对照组 ,而且它们的肝脏铅、肾脏铅和胫骨铅含量与每日每只大鼠铁补充量之间存在显著负相关 ,相关系数分别为 - 0 4432、- 0 61 34和 - 0 3878;除中、高浓度NaFeEDTA组的脑锌水平低于模型对照组以及低浓度NaFeEDTA组的肾脏铜含量高于模型对照组外 ,其余各NaFeEDTA组的脏器锌、铜含量与模型对照组相比均无显著性差异。提示NaFeEDTA可有效提高大鼠的血红蛋白含量 ,能够预防大鼠铅中毒 ,减低铅对大鼠的毒性作用 ;同时对体内锌、铜含量无太大影响     

中国鼠疫菌种资源遗传特征分析

目的 建立《中国甲类传染病菌种资源库》，选择适当的指标，以反映中国鼠疫菌种的遗传背景。方法 使用传统的和分子生物学方法，测定中国鼠疫菌种代表菌株的遗传特征。并对遗传特征的分布及其意义进行分析。结果 利用6项指标，将中国的鼠疫菌划分成15种遗传型，每一型占据一片相对独立的而又自相延续的地理空间。分析遗传型之间的亲缘关系，并根据菌株间的差异，追溯鼠疫耶尔森菌作为一个生物种形成后的进化过程。结论 中国各鼠疫自然疫源地存在着不同特征的鼠疫菌株，但为达到对菌株认同的目标，还需要确定更多的遗传指征。