HBV患者血清YKL-40、CA19-9、GP73水平与其病情相关性

目的 分析HBV患者YKL-40、CA19-9、GP73水平差异及与患者病情轻重程度的相关性,探讨HBV患者病情的判定指标。方法 选取2015年5月—2018年5月收治的100例HBV患者,其中慢性HBV感染组40例、慢性乙型肝炎组36例、HBV相关肝硬化组24例,同期选择我院健康体检的健康者50例作为健康对照组;检测患者血中YKL-40、CA19-9、GP73水平;分析HBV感染患者血清YKL-40、CA19-9、GP73水平与病情轻重程度的相关性。结果 慢性HBV感染、慢性乙型肝炎及HBV相关肝硬化患者血中YKL-40水平分别为（36.38±4.19）ng/mL 、（49.02±4.32）ng/mL、（65.14±5.21）ng/mL ,CA19-9分别为（12.03±1.03）KU/L、（13.84±0.98）KU/L、（16.94±0.81）KU/L,GP73分别为（47.22±5.38）ng/mL 、（98.53±10.24）ng/mL 、（229.85±12.19）ng/mL,均明显高于对照组的（28.19±3.27）ng/mL 、（7.34±0.92）KU/L 、（30.93±3.89）ng/mL,均P=0.000 0。随着慢性HBV感染者、慢性乙型肝炎患者和不同HBV相关肝硬化患者肝脏炎症及纤维化程度加重,患者血中YKL-40、CA19-9和GP73也随之显著增加,均P=0.000 0;YKL-40、CA19-9和GP73均是影响HBV感染患者体内炎症坏死及肝脏纤维化的独立性影响因素,差异有统计学意义（P<0.05）。结论 HBV感染患者血清中YKL-40、CA19-9、GP73水平是HBV感染患者病情轻重程度的独立性影响因素。     

A prime-boost concept using a T-cell epitope-driven DNA vaccine followed by a whole virus vaccine effectively protected pigs in the pandemic H1N1 pig challenge model

Influenza A virus (IAV) vaccines in pigs generally provide homosubtypic protection but fail to prevent heterologous infections. In this pilot study, the efficacy of an intradermal pDNA vaccine composed of conserved SLA class I and class II T cell epitopes (EPITOPE) against a homosubtypic challenge was compared to an intramuscular commercial inactivated whole virus vaccine (INACT) and a heterologous prime boost approach using both vaccines. Thirty-nine IAV-free, 3-week-old pigs were randomly assigned to one of five groups including NEG-CONTROL (unvaccinated, sham-challenged), INACT-INACT-IAV (vaccinated with FluSure XP® at 4 and 7 weeks, pH1N1 challenged), EPITOPE-INACT-IAV (vaccinated with PigMatrix EDV at 4 and FluSure XP® at 7 weeks, pH1N1 challenged), EPITOPE-EPITOPE-IAV (vaccinated with PigMatrix EDV at 4 and 7 weeks, pH1N1 challenged), and a POS-CONTROL group (unvaccinated, pH1N1 challenged). The challenge was done at 9 weeks of age and pigs were necropsied at day post challenge (dpc) 5. At the time of challenge, all INACT-INACT-IAV pigs, and by dpc 5 all EPITOPE-INACT-IAV pigs were IAV seropositive. IFNγ secreting cells, recognizing vaccine epitope-specific peptides and pH1N1 challenge virus were highest in the EPITOPE-INACT-IAV pigs at challenge. Macroscopic lung lesion scores were reduced in all EPITOPE-INACT-IAV pigs while INACT-INACT-IAV pigs exhibited a bimodal distribution of low and high scores akin to naïve challenged animals. No IAV antigen in lung tissues was detected at necropsy in the EPITOPE-INACT-IAV group, which was similar to naïve unchallenged pigs and different from all other challenged groups. Results suggest that the heterologous prime boost approach using an epitope-driven DNA vaccine followed by an inactivated vaccine was effective against a homosubtypic challenge, and further exploration of this vaccine approach as a practical control measure against heterosubtypic IAV infections is warranted.     

Motivation for participating in phase 1 vaccine trials: Comparison of an influenza and an Ebola randomized controlled trial

Introduction/Hypothesis

Recruitment of participants into phase 1 vaccine clinical trials can be challenging since these vaccines have not been used in humans and there is no perceived benefit to the participant. Occasionally, as was the case with a phase 1 clinical trial of an Ebola vaccine in Halifax, Canada, during the 2014–2016 West African Ebola virus outbreak, recruitment is less difficult. In this study, we explored the motivations of participants in two phase 1 vaccine trials that were concurrently enrolling at the same centre and compared the motivations of participants in a high-profile phase 1 Ebola vaccine trial to those in a less high-profile phase 1 adjuvanted seasonal influenza vaccine study.

Changes in the Management of Patients having Radical Radiotherapy for Lung Cancer during the First Wave of the COVID-19 Pandemic in the UK

AimsIn response to the COVID-19 pandemic, guidelines on reduced fractionation for patients treated with curative-intent radiotherapy were published, aimed at reducing the number of hospital attendances and potential exposure of vulnerable patients to minimise the risk of COVID-19 infection. We describe the changes that took place in the management of patients with stage I–III lung cancer from April to October 2020.Materials and methodsLung Radiotherapy during the COVID-19 Pandemic (COVID-RT Lung) is a prospective multicentre UK cohort study. The inclusion criteria were: patients with stage I–III lung cancer referred for and/or treated with radical radiotherapy between 2nd April and 2nd October 2020. Patients who had had a change in their management and those who continued with standard management were included. Data on demographics, COVID-19 diagnosis, diagnostic work-up, radiotherapy and systemic treatment were collected and reported as counts and percentages. Patient characteristics associated with a change in treatment were analysed using multivariable binary logistic regression.ResultsIn total, 1553 patients were included (median age 72 years, 49% female); 93 (12%) had a change to their diagnostic investigation and 528 (34%) had a change to their treatment from their centre's standard of care as a result of the COVID-19 pandemic. Age ≥70 years, male gender and stage III disease were associated with a change in treatment on multivariable analysis. Patients who had their treatment changed had a median of 15 fractions of radiotherapy compared with a median of 20 fractions in those who did not have their treatment changed. Low rates of COVID-19 infection were seen during or after radiotherapy, with only 21 patients (1.4%) developing the disease.ConclusionsThe COVID-19 pandemic resulted in changes to patient treatment in line with national recommendations. The main change was an increase in hypofractionation. Further work is ongoing to analyse the impact of these changes on patient outcomes.     

The magnitude and timing of recalled immunity after breakthrough infection is shaped by SARS-CoV-2 variants

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Dengue vaccine: WHO position paper,September 2018 – Recommendations

This article presents the World Health Organization’s (WHO) recommendations on the use of dengue vaccine excerpted from the WHO position paper on dengue vaccine – September 2018, published in the Weekly Epidemiological Record [1]. This position paper replaces the July 2016 WHO position paper concerning the first licensed dengue vaccine, CYD-TDV [2]. The position paper presents new evidence that became available in November 2017. A retrospective analysis of data from clinical trials, using a new serological assay classified trial participants according to their dengue serostatus prior to receipt of the first vaccine dose. The analysis revealed an excess risk of severe dengue in seronegative vaccine recipients compared to seronegative non-vaccinated individuals, while confirming long-term protection in seropositive individuals [3]. The paper provides revised guidance on dengue vaccination strategies from a population health perspective.Footnotes to this paper provide a number of core references including references to grading tables that assess the quality of the scientific evidence, and to the evidence-to-recommendation table. In accordance with its mandate to provide guidance to Member States on health policy matters, WHO issues a series of regularly updated position papers on vaccines and combinations of vaccines against diseases that have an international public health impact. These papers are concerned primarily with the use of vaccines in large-scale immunization programmes; they summarize essential background information on diseases and vaccines, and conclude with WHO's current position on the use of vaccines in the global context. Recommendations on the use of dengue vaccine CYD-TDV were discussed by SAGE in April 2018; evidence presented at the meeting can be accessed at: http://www.who.int/immunization/sage/meetings/2018/april/presentations_background_docs/en/     

Cold-passaged isolates and bat-swine influenza a chimeric viruses as modified live-attenuated vaccines against influenza a viruses in pigs

Swine influenza A virus (swIAV) infections in pig populations cause considerable morbidity and economic losses. Frequent reverse zoonotic incursions of human IAV boost reassortment opportunities with authentic porcine and avian-like IAV in swine herds potentially enhancing zoonotic and even pre-pandemic potential. Vaccination using adjuvanted inactivated full virus vaccines is frequently used in attempting control of swIAV infections. Accelerated antigenic drift of swIAV in large swine holdings and interference of maternal antibodies with vaccine in piglets can compromise these efforts. Potentially more efficacious modified live-attenuated vaccines (MLVs) bear the risk of reversion of MLV to virulence. Here we evaluated new MLV candidates based on cold-passaged swIAV or on reassortment-incompetent bat-IAV-swIAV chimeric viruses. Serial cold-passaging of various swIAV subtypes did not yield unambiguously temperature-sensitive mutants although safety studies in mice and pigs suggested some degree of attenuation. Chimeric bat-swIAV expressing the hemagglutinin and neuraminidase of an avian-like H1N1, in contrast, proved to be safe in mice and pigs, and a single nasal inoculation induced protective immunity against homologous challenge in pigs. Reassortant-incompetent chimeric bat-swIAV vaccines could aid in reducing the amount of swIAV circulating in pig populations, thereby increasing animal welfare, limiting economic losses and lowering the risk of zoonotic swIAV transmission.     

A DNA vaccine expressing an optimized secreted FAPα induces enhanced anti-tumor activity by altering the tumor microenvironment in a murine model of breast cancer

Cancer-associated fibroblasts (CAFs), major components of the tumor microenvironment (TME), promote tumor growth and metastasis and inhibit the anti-tumor immune response. We previously constructed a DNA vaccine expressing human FAPα, which is highly expressed by CAFs, to target these cells in the TME, and observed limited anti-tumor effects in the 4T1 breast cancer model. When the treatment time was delayed until tumor nodes formed, the anti-tumor effect of the vaccine completely disappeared. In this study, to improve the safety and efficacy, we constructed a new FAPα-targeted vaccine containing only the extracellular domain of human FAPα with a tissue plasminogen activator signal sequence for enhanced antigen secretion and immunogenicity. The number of CAFs was more effectively reduced by CD8⁺ T cells induced by the new vaccine. This resulted in decreases in CCL2 and CXCL12 expression, leading to a significant decrease in the ratio of myeloid-derived suppressor cells in the TME. Moreover, when mice were treated after the establishment of tumors, the vaccine could still delay tumor growth. To facilitate the future application of the vaccine in clinical trials, we further optimized the gene codons and reduced the homology between the vaccine and the original sequence, which may be convenient for evaluating the vaccine distribution in the human body. These results indicated that the new FAPα-targeted vaccine expressing an optimized secreted human FAPα induced enhanced anti-tumor activity by reducing the number of FAPα⁺ CAFs and enhancing the recruitment of effector T cells in the 4T1 tumor model mice.     

Randomized study of immune responses to two Tdap vaccines among adolescents primed with DTaP and comparison with results among adolescents primed with DTwP

BackgroundIt has been reported that persons primed with acellular (DTaP) pertussis vaccines have reduced duration of pertussis protection compared with those primed with whole-cell (DTwP) vaccines. However, due to the rapid transition to acellular vaccines, studies attempting directly to compare protection among DTaP-primed vs DTwP-primed individuals are subject to confounding by age and other limitations of ecological studies. Using validated assay results and stored sera from multiple Tdap studies, we evaluated two licensed Tdap vaccines among DTaP-primed adolescents to allow comparison with results obtained in the same laboratory from earlier studies involving DTwP-primed adolescents.MethodsParticipants 11–12 years of age who had received exactly 5 doses of DTaP vaccine prior to 7 years of age were randomly assigned in 2012 to receive one of two licensed Tdap vaccines. Serum specimens obtained pre- and post-vaccination were assayed for responses to the vaccines. Current results were then compared to results obtained in the same laboratory from prior randomized Tdap studies conducted among adolescents primed with DTwP or DTaP.ResultsBoth Tdap vaccines produced strong antibody responses to diphtheria and tetanus; responses to contained pertussis antigens were consistent with the differing levels of those antigens in each Tdap vaccine. However, postvaccination pertussis antibody responses were as much as 71% lower in these DTaP-primed adolescents compared with responses among DTwP-primed adolescents in a prior study of the same two Tdap vaccines. In contrast, results from the present study were similar to those seen in another study of Tdap among DTaP-primed adolescents.DiscussionTaken together, these results from randomized clinical trials provide direct evidence of reduced antibody responses to both licensed Tdap vaccines among adolescents primed with DTaP vaccine, compared with adolescents primed with DTwP vaccine.Clinical trial registry number: ClinicalTrials.gov, NCT01629589.