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Adjuvant effect of dendritic cells activator Imiquimod in genetic immunization with HIV-1 p55 Gag. 树突状细胞激活剂咪喹莫特在 HIV-1 p55 Gag 基因免疫中的辅助作用
Pub Date : 2023-01-01 Epub Date: 2023-01-10
Janaina M Alves, Mikhail Inyushin, Vassiliy Tsytsarev, Joshua A Roldan-Kalil, Eric Miranda-Valentin, Gerónimo Maldonado-Martinez, Karla M Ramos-Feliciano, Robert Hunter-Mellado

Dendritic cells (DC) are important antigen-presenting cells that have abilities to induce and maintain T-cell immunity, or attenuate it during hyperimmunization. Additional activation of DCs may be useful for vaccination purposes. Imiquimod is known to be a specific agonist of the Toll-like receptors (TLR7), which are located mainly on DCs. To study the effect of DC stimulation on the effectiveness of an HIV-1 p55 gag DNA vaccine in a mice model, we employed 25, 50, and 100 nM of Imiquimod as an adjuvant. Subsequently, Western blot analysis was used to quantify p55 protein production after the immunization. To characterize T-cells immune response, both the frequency of IFN-γ -secreting cells and IFN-γ and IL-4 production were measured, via an ELIspot assay and ELISA, respectively. Low concentrations of Imiquimod were found to effectively stimulate Gag production and the magnitude of the T-cell immune response, whereas higher concentrations reduced vaccination effects. Our results show that the adjuvant effects of Imiquimod depend on concentration. The use of Imiquimod may be helpful to study DC to T cell communication, including possible induction of immunotolerance.

树突状细胞(DC)是重要的抗原递呈细胞,具有诱导和维持 T 细胞免疫或在过度免疫时减弱 T 细胞免疫的能力。进一步激活树突状细胞可能有助于疫苗接种。咪喹莫特是Toll样受体(TLR7)的特异性激动剂,而Toll样受体主要位于DC上。为了研究在小鼠模型中直流刺激对 HIV-1 p55 gag DNA 疫苗有效性的影响,我们使用了 25、50 和 100 nM 的咪喹莫特作为佐剂。随后,我们使用 Western 印迹分析法对免疫后 p55 蛋白的生成进行了定量分析。为了确定T细胞免疫反应的特征,分别通过ELIspot检测法和ELISA法测定了分泌IFN-γ细胞的频率以及IFN-γ和IL-4的产生。研究发现,低浓度的咪喹莫特能有效刺激 Gag 的产生和 T 细胞免疫反应的强度,而高浓度的咪喹莫特则会降低疫苗接种效果。我们的研究结果表明,咪喹莫特的佐剂效应取决于浓度。使用咪喹莫特可能有助于研究DC与T细胞的通讯,包括可能诱导免疫耐受。
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引用次数: 0
Investigation of a Rotavirus Gastroenteritis Outbreak among Immunosuppressed Patients in a Hospital Setting. 一起轮状病毒肠胃炎在医院免疫抑制患者中的爆发调查
Pub Date : 2017-01-14 DOI: 10.4172/2329-9541.1000153
Ken Sugata, Jennifer Hull, Houping Wang, Kimberly Foytich, Sung-Sil Moon, Yoshiyuki Takahashi, Seiji Kojima, Tetsushi Yoshikawa, Baoming Jiang

Objective: Rotavirus (RV) is the most common cause of severe dehydrating diarrhoea in healthy infants and young children. The aims of this study were to investigate a RV outbreak in the pediatric hematology and oncology ward and to examine possible associations between immune status and RV infection.

Patients and methods: Twenty-eight children (19 boys and 9 girls) who were hospitalized for treatment of hematological malignancy and solid organ tumor during the RV outbreak were enrolled in this study. Fourteen of the 28 patients developed RV gastroenteritis (GE) during the observation period. RV antigen and RV IgG and IgA were measured by enzyme-linked immunosorbent assays. RV G and P types were determined by reverse transcriptase-polymerase chain reaction.

Results: Mean duration of RVGE in 14 patients was 13.9 days and mean severity score was 7.4. Two RV strains (G3P [8] and G2P [4]) were mainly circulating in the ward, which might result in the formation of a reassortant G2P [8] strain and mixed infection with G2+3P [8] in the immunocompromised patients. RV antigenemia was detected in 22 of the 28 patients (78.6%). RV-specific IgG titers in acute-phase sera of RVGE group were significantly lower than those in non-RVGE group (P=0.001). Mean age of the patients was significantly lower in RVGE group (5.5 ± 4.6 years) than non RVGE group (10.6 ± 4.5 years) (P=0.015).

Conclusion: Our data demonstrate that host factors including age, underlying diseases, and immune status may be associated with the susceptibility of RV infection in immunocompromised patients at the time of the nosocomial infection.

目的:轮状病毒(RV)是健康婴幼儿严重脱水腹泻的最常见原因。本研究的目的是调查小儿血液学和肿瘤学病房的RV爆发,并检查免疫状态与RV感染之间可能的关联。患者和方法:在RV爆发期间住院治疗血液恶性肿瘤和实体器官肿瘤的28名儿童(19名男孩和9名女孩)纳入本研究。28例患者中有14例在观察期间发生RV胃肠炎(GE)。采用酶联免疫吸附法检测RV抗原和RV IgG、IgA。逆转录-聚合酶链反应检测RV G型和P型。结果:14例RVGE患者的平均持续时间为13.9天,平均严重程度评分为7.4。病房内主要流行两种RV菌株G3P[8]和G2P[4],这可能导致免疫功能低下患者形成重组G2P[8]菌株,并与G2+3P[8]混合感染。28例患者中有22例(78.6%)检测到RV抗原血症。RVGE组急性期血清中病毒特异性IgG滴度显著低于非RVGE组(P=0.001)。RVGE组患者平均年龄(5.5±4.6岁)明显低于非RVGE组(10.6±4.5岁)(P=0.015)。结论:我们的数据表明,包括年龄、基础疾病和免疫状态在内的宿主因素可能与免疫功能低下患者院内感染时RV感染的易感性有关。
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引用次数: 0
Neighborhood Influences on Seasonal Influenza Vaccination among Older African Americans in Atlanta, Georgia. 乔治亚州亚特兰大市老年非裔美国人对季节性流感疫苗接种的影响
Pub Date : 2016-06-01 Epub Date: 2016-03-23 DOI: 10.4172/2329-9541.1000139
N Niyibizi, J Schamel, P M Frew

Background: Influenza vaccination coverage in the US is lower than the recommended Healthy People 2020 threshold, especially among older African Americans. This analysis explores the complex relationship among neighborhood-level factors, socio behavioral influences, and influenza vaccination outcomes among older African Americans.

Methods: We analyzed data from 221 Black/African American participants' age ≥50 years living in Atlanta, Georgia. Generalized Estimating Equations for linear and logistic models assessed associations among socio demographic factors, census-tract neighborhood characteristics, and reported 2012-2013 seasonal influenza vaccination receipt, controlling for correlations among individuals within the same census tracts. Evaluated environmental factors included neighborhood deprivation indicators such as vacant housing percentage, vehicle availability, area violent crimes, and racial/ethnic composition.

Results: Reported greater influenza immunization uptake was significantly associated with older age ≥65 years [OR=1.05, p=0.04], positive vaccination attitudes [OR=5.30, p<0.01], having health insurance [OR=14.37, p=0.03], lower perceived neighborhood security [OR=0.51, p=0.02], and lower neighborhood vehicle ownership [OR=1.07, p=0.04], a proxy for neighborhood affluence and transportation ease. Having a post-secondary education was significantly associated with both positive perceived neighborhood security [β=0.28, p=0.02] and positive vaccination attitudes [β=0.27, p=0.02].

Conclusion: The findings provide evidence for distal neighborhood-level influences on influenza vaccination uptake among older African Americans. Lower vehicle ownership and lower perceived neighborhood security influenced seasonal influenza immunizations. Those who perceived personal risk, based on reported neighborhood security, displayed intent to obtain the seasonal influenza vaccine. Further investigation of multilevel, socio geographic factors is therefore warranted to more effectively address suboptimal influenza vaccine coverage among this population.

背景:美国流感疫苗接种覆盖率低于健康人2020年推荐的阈值,特别是在老年非洲裔美国人中。本分析探讨了社区水平因素、社会行为影响和老年非裔美国人流感疫苗接种结果之间的复杂关系。方法:我们分析了221名年龄≥50岁的居住在佐治亚州亚特兰大的黑人/非裔美国人参与者的数据。线性和逻辑模型的广义估计方程评估了社会人口因素、普查区社区特征之间的关联,并报告了2012-2013年季节性流感疫苗接种情况,控制了同一普查区内个体之间的相关性。评估的环境因素包括邻里剥夺指标,如空置住房百分比、车辆可用性、地区暴力犯罪和种族/民族构成。结果:报告的流感免疫接种率较高与年龄≥65岁[OR=1.05, p=0.04]和积极的疫苗接种态度[OR=5.30, p]显著相关。结论:研究结果为远端社区水平对老年非洲裔美国人流感疫苗接种率的影响提供了证据。较低的车辆拥有量和较低的社区安全意识影响季节性流感免疫接种。根据报告的社区安全情况,那些认为有个人风险的人表示有意接种季节性流感疫苗。因此,有必要进一步调查多层次的社会地理因素,以更有效地解决这一人群中流感疫苗覆盖率欠佳的问题。
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引用次数: 7
Infection and Activation of Human Neutrophils with Fluorescent Leishmania infantum. 荧光婴儿利什曼原虫对人中性粒细胞的感染和活化。
Pub Date : 2016-01-01 Epub Date: 2016-05-10 DOI: 10.4172/2329-9541.1000146
R E Davis, C J Thalhofer, M E Wilson

Neutrophils (PMNs) are recruited in high numbers to sites of host infection by the protozoan parasites of the genus Leishmania. Although PMNs are capable of phagocytizing Leishmania parasites and are potent producers of anti-microbial compounds including reactive oxygen species (ROS), they are unable to control the establishment of infection. Prior studies document production of ROS in isolated PMNs incubated with Leishmania under conditions allowing phagocytosis, but without a measure of single cells' responses it cannot be discerned whether PMN activation and ROS production is suppressed or ineffective in the cells that internalize the parasite. To address these interactions, we engineered a strain of fluorescent, mCherry-expressing Leishmania infantum (mCherry-Li). By infecting isolated human PMNs in vitro with mCherry-Li, we observed ready association of the parasites with PMNs in a time- and dose-dependent fashion. We also examined production of PMN ROS (using the fluorescent compound DHR123) and PMN activation (as evidence by loss of surface CD62L expression). Whereas many Li-associated (mCherry+) PMNs responded to parasite interactions and uptake with ROS production and/or activation, a proportion exhibited neither response. Furthermore, a large proportion of mCherry - "bystander" PMNs displayed both ROS production and activation. The heterogeneous response of PMNs to Leishmania exposure leads us to hypothesize, first, that some PMNs exhibit decreased activation upon phagocytosis of Leishmania, and could support their maintenance. Second, responses of bystander PMNs may contribute to a local inflammatory environment that is ineffective at parasite clearance.

嗜中性粒细胞(pmn)被利什曼属原生动物寄生虫大量招募到宿主感染部位。虽然pmn能够吞噬利什曼原虫寄生虫,并且是抗微生物化合物(包括活性氧)的有效生产者,但它们无法控制感染的建立。先前的研究记录了在允许吞噬的条件下,与利什曼原虫孵养的分离PMN中ROS的产生,但由于没有测量单个细胞的反应,因此无法辨别在内化寄生虫的细胞中PMN的激活和ROS的产生是否受到抑制或无效。为了解决这些相互作用,我们设计了一种荧光的,表达mccherry的利什曼原虫(mCherry-Li)。通过用mccherry - li体外感染分离的人pmn,我们观察到寄生虫与pmn有时间和剂量依赖性的直接关联。我们还检测了PMN ROS的产生(使用荧光化合物DHR123)和PMN的激活(作为表面CD62L表达缺失的证据)。尽管许多锂离子相关(mCherry+) pmn对寄生虫的相互作用和摄取有ROS产生和/或激活的反应,但有一部分pmn没有表现出任何反应。此外,很大一部分mCherry -“旁观者”pmn同时表现出ROS的产生和激活。pmn对利什曼原虫暴露的异质反应使我们假设,首先,一些pmn在吞噬利什曼原虫时表现出活性降低,并可能支持其维持。其次,旁观者pmn的反应可能导致局部炎症环境对寄生虫清除无效。
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引用次数: 5
A Viable and Simple Self-Sampling Method for Human Papillomavirus Detection among South African Adolescents. 在南非青少年中检测人乳头瘤病毒的一种可行和简单的自抽样方法。
Pub Date : 2013-09-18 DOI: 10.4172/2329-9541.1000113
David H Adler, Fatima Laher, Erica Lazarus, Katherine Grzesik, Glenda E Gray, Bruce Allan, Anna-Lise Williamson

Background: Self-sampling for Human Papillomavirus (HPV) testing may offer improved patient acceptability, decreased cost, and greater practicality than clinician collection of specimens. HPV testing among adolescents is necessary to conduct vaccine surveillance and may play a role in cervical cancer screening among some populations.

Methods: A cross-sectional prevalence study was conducted to compare the results of self-collected and clinician-collected specimens for Human papillomavirus (HPV) testing among South African adolescent females. All participants provided self-sampled vaginal swabs and underwent clinician-collection of cervical swabs for HPV DNA analysis. The level of agreement between HPV DNA results from the two specimen collection methods was measured.

Results: The level of agreement between HPV DNA results from self-collected and clinician-collected specimens was high (κ=86.7; p<0.001). A high prevalence of HPV overall was found by both specimen collection methods (57%; 95% CI 0.37-0.75). Low-risk HPV (LR-HPV) types were found slightly more frequently in self-collected specimens.

Conclusion: There is a high level of agreement between the HPV DNA results from self-collected and clinician-collected specimens. Self-collection of specimens for HPV testing is a viable alternative among adolescents.

背景:人乳头瘤病毒(HPV)检测的自采样可能比临床医生收集标本更能提高患者的接受度,降低成本和实用性。在青少年中进行HPV检测对于进行疫苗监测是必要的,并且可能在某些人群中发挥宫颈癌筛查的作用。方法:在南非青少年女性中进行了一项横断面流行病学研究,以比较自我收集和临床收集的人乳头瘤病毒(HPV)检测结果。所有的参与者都提供了自己的阴道拭子样本,并接受了临床收集宫颈拭子用于HPV DNA分析。测量了两种标本采集方法的HPV DNA结果之间的一致程度。结果:自我采集的HPV DNA结果与临床采集的HPV DNA结果一致性高(κ=86.7;结论:自我采集的HPV DNA结果与临床采集的HPV DNA结果高度一致。在青少年中,自行收集标本进行HPV检测是一种可行的选择。
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引用次数: 14
High Rate of Multiple Concurrent Human Papillomavirus Infections among HIV-Uninfected South African Adolescents. 未感染艾滋病毒的南非青少年多重并发人乳头瘤病毒感染率高。
David Adler, Fatima Laher, Melissa Wallace, Katherine Grzesik, Heather Jaspan, Linda-Gail Bekker, Glenda Gray, Ziyaad Valley-Omar, Bruce Allan, Anna-Lise Williamson

Background: The epidemiology and impact of multiple concurrent Human papillomavirus (HPV) infections on the natural history of cervical disease is uncertain, but could have significant implications for cervical cancer prevention and HPV vaccination strategies.

Methods: A cross-sectional prevalence study was conducted to determine the overall prevalence of HPV and the rate of multiple concurrent HPV infections, in a cohort of sexually active HIV-uninfected South African adolescents. HPV genotyping was performed using the polymerase chain reaction.

Results: Overall prevalence of HPV was 64.1%. Multiple concurrent HPV infections were found in 43.6% of participants and 68% of HPV-infected participants. Non-vaccine high-risk HPV (HR-HPV) genotypes were found much more often than vaccine types (HPV16 and HPV18).

Conclusions: Our cohort of young South African females was found to have a high overall prevalence of HPV and multiple concurrent HPV infections. Most HR-HPV infections found were genotypes other than HPV16 or HPV18.

背景:多种并发人乳头瘤病毒(HPV)感染的流行病学和对宫颈疾病自然史的影响尚不确定,但可能对宫颈癌预防和HPV疫苗接种策略具有重要意义。方法:在一组性活跃的未感染hiv的南非青少年中,进行了一项横断面流行病学研究,以确定HPV的总体流行率和多重并发HPV感染率。采用聚合酶链反应进行HPV基因分型。结果:HPV总患病率为64.1%。在43.6%的参与者和68%的HPV感染参与者中发现多重并发HPV感染。非疫苗高危型HPV (HR-HPV)基因型比疫苗型(HPV16和HPV18)更常见。结论:我们的年轻南非女性队列发现HPV和多重并发HPV感染的总体患病率很高。大多数HR-HPV感染是HPV16或HPV18以外的基因型。
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引用次数: 0
High Rate of Multiple Concurrent Human Papillomavirus Infections among HIV-Uninfected South African Adolescents. 未感染艾滋病毒的南非青少年多重并发人乳头瘤病毒感染率高。
Pub Date : 2013-01-01 DOI: 10.4172/2329-9541.1000106
D. Adler, F. Laher, M. Wallace, K. Grzesik, H. Jaspan, L. Bekker, G. Gray, Z. Valley-Omar, B. Allan, A. Williamson
BACKGROUND The epidemiology and impact of multiple concurrent Human papillomavirus (HPV) infections on the natural history of cervical disease is uncertain, but could have significant implications for cervical cancer prevention and HPV vaccination strategies. METHODS A cross-sectional prevalence study was conducted to determine the overall prevalence of HPV and the rate of multiple concurrent HPV infections, in a cohort of sexually active HIV-uninfected South African adolescents. HPV genotyping was performed using the polymerase chain reaction. RESULTS Overall prevalence of HPV was 64.1%. Multiple concurrent HPV infections were found in 43.6% of participants and 68% of HPV-infected participants. Non-vaccine high-risk HPV (HR-HPV) genotypes were found much more often than vaccine types (HPV16 and HPV18). CONCLUSIONS Our cohort of young South African females was found to have a high overall prevalence of HPV and multiple concurrent HPV infections. Most HR-HPV infections found were genotypes other than HPV16 or HPV18.
背景多重并发人乳头瘤病毒(HPV)感染的流行病学和对宫颈疾病自然史的影响尚不确定,但可能对宫颈癌预防和HPV疫苗接种策略具有重要意义。方法进行了一项横断面流行病学研究,以确定在性活跃的hiv未感染的南非青少年中HPV的总体流行率和多重并发HPV感染率。采用聚合酶链反应进行HPV基因分型。结果HPV总患病率为64.1%。在43.6%的参与者和68%的HPV感染参与者中发现多重并发HPV感染。非疫苗高危型HPV (HR-HPV)基因型比疫苗型(HPV16和HPV18)更常见。结论:一组年轻的南非女性被发现有很高的HPV总体患病率和多重并发HPV感染。大多数HR-HPV感染是HPV16或HPV18以外的基因型。
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引用次数: 13
期刊
Journal of immunological techniques in infectious diseases
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