Impact of rotavirus vaccination on diarrheal hospitalizations in children younger than 5 years of age in a rural southern Mozambique

BackgroundRotavirus vaccine (Rotarix®) was introduced in Mozambique through its Expanded Program of Immunization in September 2015. We assessed the impact of rotavirus vaccination on childhood gastroenteritis-associated hospitalizations post-vaccine introduction in a high HIV prevalence rural setting of southern Mozambique.MethodsWe reviewed and compared the trend of hospitalizations (prevalence) and incidence rates of acute gastroenteritis (AGE), and rotavirus associated-diarrhea (laboratory confirmed rotavirus) in pre- (January 2008–August 2015) and post-rotavirus vaccine introduction periods (September 2015–December 2020), among children <5 years of age admitted to Manhiça District Hospital.ResultsFrom January 2008 to December 2020, rotavirus vaccination was found to contribute to the decline of the prevalence of AGE from 19% (95% CI: 18.14–20.44) prior to the vaccine introduction to 10% (95% CI: 8.89–11.48) in the post-introduction period, preventing 40% (95 % IE: 38–42) and 84% (95 % IE: 80–87) of the expected AGE and laboratory confirmed rotavirus cases, respectively, among infants. Similarly, the overall incidence of rotavirus was 11.8-fold lower in the post-vaccine introduction period (0.4/1000 child-years-at-risk [CYAR]; 95% CI: 0.3–0.6) compared with the pre-vaccination period (4.7/1000 CYAR; 95% CI: 4.2–5.1) with the highest reduction being observed among infants (16.8-fold lower from the 15.1/1000 CYAR in the pre-vaccine to 0.9/1000 CYAR in the post-vaccine eras).ConclusionsWe documented a significant reduction in all-cause diarrhea hospitalizations and rotavirus positivity after vaccine introduction demonstrating the beneficial impact of rotavirus vaccination in a highly vulnerable population.     

Individual-level factors associated with COVID-19 vaccine acceptance among U.S. patients with cancer

IntroductionVaccine hesitancy in the wake of the COVID-19 pandemic is a major public health concern in the US. Cancer patients are especially vulnerable to adverse COVID-19 outcomes and require targeted prevention efforts against COVID-19.MethodsWe used longitudinal survey data from patients seen at Moffitt Cancer Center to identify attitudes, beliefs, and sociodemographic factors associated with COVID-19 vaccination acceptance among cancer patients. Patients with confirmed invasive cancer diagnosis through Cancer Registry data were asked about vaccine acceptance through the question “Now that a COVID-19 vaccine is available, are you likely to get it?” and dichotomized into high accepters (already received it, would get it when available) and low accepters (waiting for a doctor to recommend it, waiting until more people received it, not likely to get it).ResultsMost patients (86.8% of 5,814) were high accepters of the COVID-19 vaccine. High accepters had more confidence in the effectiveness and safety of the vaccine than low accepters. Multivariable logistic regression showed older individuals (70–89 vs.18–49: OR:2.57, 95% CI:1.33–4.86), those with greater perceived severity of COVID-19 infection (very serious vs. not at all serious: OR:2.55, 95% CI:1.76–3.70), practicing more risk mitigation behaviors (per one standard deviation OR:1.75, 95% CI:1.57–1.95), and history of receiving the flu shot versus not (OR:6.56, 95% CI:5.25–8.20) had higher odds of vaccine acceptance. Individuals living with more than one other person (vs. alone: OR: 0.53, 95% CI: 0.35, 0.79) and those who were more socioeconomically disadvantaged (per 10 percentile points: OR: 0.89, 95 %CI: 0.85, 0.93) had lower odds of reporting vaccine acceptance.ConclusionMost patients with cancer have or would receive the COVID-19 vaccine. Those who are less likely to accept the vaccine have more concerns regarding effectiveness and side effects, are younger, more socioeconomically disadvantaged, and have lower perceptions of COVID-19 severity.     

Use of a Clostridium perfringens vector to express high levels of SIV p27 protein for the development of an oral SIV vaccine

Clostridium perfringens is a normal bacterial flora of the small and large intestines of humans and other animals. The current study investigates the potential use of a noncytotoxic C. perfringens as an oral vaccine vehicle for expression and intestinal delivery of a large amount of SIV antigens. Here we report the construction of a recombinant C. perfringens vaccine vector expressing high levels of SIV p27 during sporulation. Following oral administration of this recombinant C. perfringens vaccine vector to mice, large amounts of intact p27 protein were detected in the terminal ileum where the majority of Peyer's Patches (PPs) are located. Furthermore, dendritic cells (DCs) beneath the mucosal surface in the PPs were able to capture SIV p27 antigen, when PPs were exposed to C. perfringens expressing SIV p27 antigen. In addition, uptake of C. perfringens was able to induce maturation of mouse DCs. These results support the potential use of C. perfringens as an oral SIV/HIV vaccine vector.     

Reactivity of human sera in a sensitive, high-throughput pseudovirus-based papillomavirus neutralization assay for HPV16 and HPV18

Sensitive high-throughput neutralization assays, based upon pseudoviruses carrying a secreted alkaline phosphatase (SEAP) reporter gene, were developed and validated for human papillomavirus (HPV)16, HPV18, and bovine papillomavirus 1 (BPV1). SEAP pseudoviruses were produced by transient transfection of codon-modified papillomavirus structural genes into an SV40 T antigen expressing line derived from 293 cells, yielding sufficient pseudovirus from one flask for thousands of titrations. In a 96-well plate format, in this initial characterization, the assay was reproducible and appears to be as sensitive as, but more specific than, a standard papillomavirus-like particle (VLP)-based enzyme-linked immunosorbent assay (ELISA). The neutralization assay detected type-specific HPV16 or HPV18 neutralizing antibodies (titers of 160-10240) in sera of the majority of a group of women infected with the corresponding HPV type, but not in virgin women. Sera from HPV16 VLP vaccinees had high anti-HPV16 neutralizing titers (mean: 45000; range: 5120-163840), but no anti-HPV18 neutralizing activity. The SEAP pseudovirus-based neutralization assay should be a practical method for quantifying potentially protective antibody responses in HPV natural history and prophylactic vaccine studies.     

幽门螺杆菌表位疫苗的设计、构建、表达及其免疫原性研究

目的 设计幽门螺杆菌（Hp）的表位疫苗并对其免疫原性进行研究。方法 将Hp的尿素酶B亚单位的三个Th表位及一个B细胞表位串联，表位之间用两个赖氨酸（KK）间隔，合成全基因，克隆到pET-22b载体上，在大肠杆菌B121（DE3）中表达；表达的重组蛋白经鉴定纯化后皮下免疫Balb／c小鼠，检测细胞免疫应答及体液免疫应答。结果 克隆表达的重组表位疫苗蛋白纯化后纯度达到95％，经N端测序证实为设计的表位疫苗蛋白，Th表位多肽（U546-561、U229-244、U237-251）、表位疫苗蛋白及rUreB均能够刺激表位疫苗致敏的小鼠淋巴细胞增殖（SI〉2），并且此疫苗能够刺激机体产生特异性抗体。结论 本研究中表位疫苗的设计方法能够使疫苗中包含的四个表位均发挥功能，并且具有较强的免疫原性，为研究Hp预防性和治疗性疫苗提供实验基础。     

重组结核抗原痘苗病毒Ankara株的构建及其免疫原性研究

目的 构建5种不同类型的表达结核杆菌特异抗原的重组痘苗病毒,并研究其特异免疫原性.方法 运用同源重组技术将含结核分泌抗原Ag85A和ESAT-6的基因片段插入痘苗病毒表达质粒p18中.重组质粒导入痘苗病毒Ankara(MVA)后构建重组痘苗病毒,经筛选和Western blot鉴定,得到5个种类的带有结核抗原基因的重组病毒.用构建的5种重组病毒免疫小鼠,MTT法检测免疫后小鼠脾淋巴细胞对特异结核抗原的增殖反应;ELISA检测小鼠脾淋巴细胞培养上清液中IFN-γ的含量;结核菌素纯蛋白衍化物(PPD)皮内试验以检测重组病毒引发的针对结核抗原的特异细胞免疫应答.结果 构建的5种蘑组病毒介导的细胞表达产物经Western blot鉴定确认相对分子质量与结核抗原一致.免疫小鼠两次后,5种重组病毒免疫组脾淋巴细胞体外与Ag85A-ESAT-6融合蛋白共培养后表现出明显的增殖活性(P<0.01),培养上清液中IFN-γ的浓度均较同组细胞经生理盐水刺激明显增高(P<0.05);与空痘苗病毒或生理盐水免疫后小鼠相比,5种重组MVA免疫组脾淋巴细胞与AgB5A.ESAT-6融合蛋白共培养后同样表现出明显的增殖活性(P<0.01),与Ag85A-ESAT-6融合蛋白共培养的细胞上清液中IFN-γ的浓度均升高(P<0.01).与空痘苗病毒或生理盐水免疫后小鼠相比,5种重组MVA免疫组小鼠对PPD都表现出显著的迟发型超敏反应应答(P<0.05).结论 成功构建了5种不同类型的表达结核杆菌抗原的重组痘苗病毒疫苗,其免疫小鼠后可激发针对结核杆菌抗原的特异性细胞免疫.     

CDCA8对肝细胞癌患者预后的影响

目的：肝细胞癌预后相关的分子标志物对提高患者生存质量和改善疗效至关重要,本研究旨在探究细胞分裂周期相关基因8(cell division cycle associated 8,CDCA8)对肝细胞癌预后的影响及潜在分子机制。方法：432例肝细胞癌样本的转录组数据及对应患者的临床信息下载自肿瘤基因表达图谱（The Cancer Genome Atlas,TCGA）数据库。分析肿瘤组织和正常组织中CDCA8 mRNA差异;根据CDCA8 mRNA中位数将肝细胞癌患者分为高表达组和低表达组,绘制生存曲线。采用Kruskal检验分析CDCA8与肿瘤分期、分级和T分期的相关性。采用单因素和多因素Cox回归分析探究CDCA8能否作为肝细胞癌患者的独立预后因子。采用基因集富集分析（gene set enrichment analysis,GSEA）探究CDCA8在肝细胞癌中的潜在作用机制。结果：CDCA8在肿瘤组织中的mRNA水平明显高于正常对照组织（P<0.001）,CDCA8高表达患者的生存率明显低于低表达组（P<0.001）。随着肿瘤分期（P<0.001）、分级（P<0...     

表达幽门螺杆菌过氧化氢酶的减毒沙门氏菌疫苗株的构建及其免疫保护作用的观察

目的 探讨表达幽门螺杆菌（Hp)过氧化氢酶（KatA)的减毒鼠伤寒沙门氏菌疫苗株在防御Hp感染中的作用。方法 构建表达KatA的重组质粒,用IPTG进行诱导表达,再将其转入减毒鼠伤寒沙门氏菌SL3261株中构建成口服活疫苗株,经口服免疫C57BL/6小鼠,并以Hp翻尼株进行攻击,用快速尿素酶试验和Hp定量培养对胃粘膜中的Hp进行检测。结果 SDS-PAGE凝胶电泳上显示一条相对分子质量约79000的新生蛋白带,占细菌总蛋白的19%,并能与抗谷胱甘肽-s-转移酶（GST）抗体发生特异性反应,动物实验结果显示;免疫小鼠能有效防御Hp的感染,结论 表达KatA的减毒沙门氏菌疫苗株能诱导抗Hp保护性免疫反应,有望在Hp感染及其相关性疾病的防治中发挥积极作用。     

91例免疫相关性皮肤病患者血清花粉IgG抗体检测结果分析

目的：检测免疫相关性皮肤病患者血清花粉IgG阳性情况。方法：采用Dot-ELISA法检测受检患者血清花粉IgG抗体。结果：56％受检患者血 清花粉IgG抗体阳性,其中荨麻疹、湿疹、接触性皮炎和过敏性紫癜等过敏性皮肤病患者血清花粉IgG抗体阳性率为83．0％,其它免疫相关性皮肤病为18．4％（P＜0．005）。血清花粉IgG抗体阳性的34例荨麻疹患者中,早春花粉抗体阳性高达91．2％,晚春花粉52．9％,夏秋花粉29．4％（P＜0．005）。结论：致敏性花粉与过敏性皮肤病有较大关系。春季花粉,特别是早春花粉,是本地区花粉相关性荨麻疹的主要致敏花粉。     

Correlative Expression of Glutathion S-Transferase-π and Multidrug Resistance Associated Protein in Bladder Transitional Cell Carcinoma

Chemotherapylswidelyappliedlnthetreatmentofsuperficial(instravesicaIinstiIlation)andinvasive(systemicadministration)bladdercancer.However,resistancetochemotherapenticagentsstillremainsacriticalprobIemintherapy,whichkeepsamuchhigherrecurrentrateofbIaddercancerandpreventsthecureofpat1ents.Previous1y,theresearchesonthemechanismsofdrugsres1stanceusuallyconcen-trateonthemembersoftheATP--bindingcassette(ABC)transportersuperfamlly(forinstance,P--gp,MRP,LRP,etc.)['2],butatpresentincreasingevi-d…