BACKGROUND & AIMS: :Protection against intracellular pathogens or tumor antigens requires T-cell mediated responses. Recently, it has become apparent that protection against disease correlates with T cells of the central memory type in many instances. Here, we analyze current data to distill a set of rules for the induction and maintenance of central memory T-cell responses. Recent studies show that T-cell help and the lack of overt inflammation at the time of priming are prerequisite for the induction, maintenance and expansion of memory T cells. Central to our hypothesis is that, in addition to these factors, successful vaccination in the immunologically inexperienced individual should be based on low antigen dose, to decelerate replicative senescence in responding cells and favor lineage differentiation of central memory T cells. In the immunologically experienced individual, it will be necessary, in addition, to abate the antigen load in plasma before vaccination. These guiding principles might help to raise improved protective T-cell responses by vaccination in humans.

背景与目标： : 针对细胞内病原体或肿瘤抗原的保护需要T细胞介导的反应。最近，很明显，在许多情况下，对疾病的保护与中央记忆类型的T细胞有关。在这里，我们分析当前数据以提取用于诱导和维持中央记忆T细胞响应的一组规则。最近的研究表明，T细胞的帮助和在启动时缺乏明显的炎症是诱导，维持和扩增记忆T细胞的前提。我们的假设的核心是，除了这些因素外，免疫无经验个体的成功疫苗接种应基于低抗原剂量，以减缓应答细胞中的复制性衰老并有利于中央记忆T细胞的谱系分化。在具有免疫经验的个体中，有必要在接种疫苗之前减轻血浆中的抗原负荷。这些指导原则可能有助于通过人类疫苗接种提高保护性T细胞反应。

BACKGROUND & AIMS: :Immune therapy have shown new and exciting perspectives for cancer treatment. Aim of our study was to evaluate toxicity and possible adverse effects from vaccination of patients with advanced colorectal cancer with autologous dendritic cells (DC) pulsed with lysate from a newly developed melanoma cell line, DDM-1.13. Six patients were enrolled in the phase I trial. Autologous DCs were generated in vitro from peripheral blood monocytes in the presence of granulocyte-macrophage colony-stimulating factor (GM-CSF) and interleukin-4 (IL-4). DCs were pulsed with melanoma cell lysate from a cloned and selected melanoma cell line enriched in expression of MAGE-A antigens and deficient in expression of melanoma differentiation antigens: tyrosinase, MART-1 and gp100. Vaccinations were administered intradermally on the proximal thigh with a total of five given vaccines at 2 weeks intervals. Each vaccine contained 3-5 x 10(6) DCs. Five of the six patients received all five vaccines. The treatment was well tolerated in all patients without any observed vaccine-correlated adverse effects. Treatment with this DC-based cancer vaccine proved safe and non-toxic.

背景与目标： : 免疫疗法为癌症治疗展示了新的令人兴奋的观点。我们研究的目的是评估用新开发的黑色素瘤细胞系DDM-1.13的裂解液对自体树突状细胞 (DC) 进行疫苗接种的毒性和可能的不良反应。6名患者参加了I期试验。在存在粒细胞-巨噬细胞集落刺激因子 (gm-csf) 和interleukin-4 (IL-4) 的情况下，从外周血单核细胞体外产生自体dc。用来自克隆和选择的黑色素瘤细胞系的黑色素瘤细胞裂解液对dc进行脉冲，该细胞系富含MAGE-a抗原的表达，并且缺乏黑色素瘤分化抗原的表达: 酪氨酸酶，MART-1和gp100。在大腿近端皮内接种疫苗，每隔2周共接种5种疫苗。每种疫苗含有3-5x10(6) dc。六名患者中有五名接受了全部五种疫苗。所有患者的治疗耐受性良好，没有观察到任何与疫苗相关的不良反应。使用这种基于DC的癌症疫苗进行治疗被证明是安全且无毒的。

BACKGROUND & AIMS: :Guillain-Barré syndrome (GBS) has been rarely reported after liver transplantation and generally has good outcome. We report a liver transplant patient on FK506 (tacrolimus) who developed GBS 6 months after liver transplantation. There was no evidence of liver rejection or active infection. Despite treatment with intravenous immunoglobulin, the patient expired. GBS occurred despite downregulation of T cells by FK506, suggesting that humoral dysfunction might be the predominant mechanism of GBS in this report.

背景与目标： : 肝移植后很少报道格林-巴利综合征 (GBS)，并且通常具有良好的疗效。我们报告了一名FK506 (他克莫司) 肝移植患者，该患者在肝移植后6个月出现了GBS。没有肝脏排斥或活动性感染的证据。尽管使用静脉注射免疫球蛋白治疗，但患者仍过期。尽管FK506下调了T细胞，但仍发生了GBS，这表明体液功能障碍可能是本报告中GBS的主要机制。

BACKGROUND & AIMS: -2

背景与目标： -2

BACKGROUND & AIMS: :During chronic HIV-1 infection, continuing viral replication is associated with impaired proliferative capacity of virus-specific CD8+ T cells and with the expansion and persistence of oligoclonal T cell populations. TCR usage may significantly influence CD8+ T cell-mediated control of AIDS viruses; however, the potential to modulate the repertoire of functional virus-specific T cells by immunotherapy has not been explored. To investigate this, we analyzed the TCR Vbeta usage of CD8+ T cells populations which were expanded following vaccination with modified vaccinia virus Ankara expressing a HIV-1 gag/multiepitope immunogen (MVA.HIVA) in HIV-1-infected patients receiving highly active antiretroviral therapy. Vaccinations induced the re-expansion of HIV-1-specific CD8+ T cells and these showed broad TCR Vbeta usage which was maintained for at least 1 year in some individuals. By contrast, virus-specific CD8+ T cell populations in the same donors which failed to expand after vaccination and in unvaccinated controls were oligoclonal. Simultaneously, we observed that CD8+ T cells recognizing vaccine-derived HIV-1 epitopes displayed enhanced capacity to proliferate and to inhibit HIV-1 replication in vitro, following MVA.HIVA immunizations. Taken together, these data indicate that an attenuated viral-vectored vaccine can modulate adaptive CD8+ T cell responses to HIV-1 and improve their antiviral functional capacity. The potential therapeutic benefit of this vaccination approach warrants further investigation.

背景与目标： : 在慢性HIV-1感染期间，持续的病毒复制与病毒特异性CD8 + T细胞的增殖能力受损以及寡克隆T细胞群体的扩增和持续存在有关。TCR的使用可能会显着影响CD8 T细胞介导的AIDS病毒es的控制; 但是，尚未探索通过免疫疗法调节功能性病毒特异性T细胞库的潜力。为了研究这一点，我们分析了在接受高活性抗逆转录病毒治疗的HIV-1-infected患者中，用表达HIV-1 gag/多表位免疫原 (MVA.HIVA) 的改良痘苗病毒安卡拉疫苗接种后扩大的CD8 + T细胞群体的TCR Vbeta使用情况。疫苗接种诱导了HIV-1-specific CD8 + T细胞的再扩增，这些细胞显示了广泛的TCR Vbeta使用，在一些个体中维持了至少1年。相比之下，同一供体中的病毒特异性CD8 T细胞群体在疫苗接种后未能扩大，而未接种疫苗的对照则是寡克隆。同时，我们观察到识别疫苗衍生的HIV-1表位的CD8 + T细胞在MVA.HIVA免疫后表现出增强的体外增殖和抑制HIV-1复制的能力。综合起来，这些数据表明，减毒的病毒载体疫苗可以调节对HIV-1的适应性CD8 + T细胞反应并提高其抗病毒功能能力。这种疫苗接种方法的潜在治疗益处值得进一步研究。

BACKGROUND & AIMS: :The present study reports animal immuno-toxicological data of pulmonary vaccination against inactivated seasonal influenza. Its aims were (i) to monitor the temporal kinetics of lung inflammation in normal mice over a period of 2 weeks following pulmonary vaccination in order to assess the risk of chronic lung inflammation, (ii) to evaluate the impact of pulmonary vaccination on the asthmatic phenotype in an established allergen-sensitized murine model of asthma. Both sets of experiments were performed using high doses of split influenza virus vaccine. In the first part of this study, we showed that pulmonary influenza vaccination induced a slight local inflammatory response which was limited in duration since it was no longer observed at 2 weeks post-vaccination. At this time point, it has previously been shown that the immunogenic efficacy was maintained. In the second part, we demonstrated that pulmonary influenza vaccination did not significantly exacerbate the cardinal features of asthma, i.e., allergen-specific IgE formation, the development of airway hyperreactivity (AHR) and eosinophilic airway inflammation. Our data therefore suggest that the overall immuno-toxicological profile of pulmonary vaccination against seasonal influenza was acceptable, even in an animal model of pulmonary hypersensitivity.

背景与目标： : 本研究报告了针对灭活季节性流感的肺疫苗接种的动物免疫毒理学数据。其目的是 (i) 在肺部疫苗接种后的2周内监测正常小鼠肺部炎症的时间动力学，以评估慢性肺部炎症的风险，(ii) 在建立的过敏原致敏小鼠哮喘模型中评估肺部疫苗接种对哮喘表型的影响。两组实验均使用高剂量的流感病毒裂解疫苗进行。在这项研究的第一部分中，我们表明肺流感疫苗会引起轻微的局部炎症反应，由于在疫苗接种后2周不再观察到，因此持续时间有限。在此时间点，先前已显示维持了免疫原性功效。在第二部分中，我们证明了肺流感疫苗接种并未显着加剧哮喘的基本特征，即过敏原特异性IgE的形成，气道高反应性 (AHR) 的发展以及嗜酸性气道炎症。因此，我们的数据表明，即使在肺超敏反应的动物模型中，针对季节性流感的肺疫苗接种的总体免疫毒理学特征也是可以接受的。

BACKGROUND & AIMS: :It will likely be more than 20 years before there is unequivocal evidence available that HPV vaccination decreases the incidence of invasive cervical cancer. However, existing data strongly suggests that as many as 440,000 cervical cancer cases and 220,000 deaths due to this malignancy will be prevented with the establishment of an effective worldwide HPV immunization program.

背景与目标： : 可能需要20多年的时间才能有明确的证据表明HPV疫苗可以降低浸润性宫颈癌的发生率。然而，现有数据强烈表明，通过建立有效的全球HPV预防接种计划，将预防多达440,000例宫颈癌病例和由于这种恶性肿瘤导致的220,000死亡。

BACKGROUND & AIMS: BACKGROUND:Pandemic influenza ethics frameworks are based on respect of values and principles such as regard for autonomy, responsibility, transparency, solidarity and social justice. However, very few studies have addressed the way in which the general population views these moral norms. OBJECTIVES:(i) To analyse the receptiveness of the population of French-speaking Quebecers to certain ethical principles promoted by public health authorities during the AH1N1 vaccination campaign. (ii) To add to the limited number of empirical studies that examine the population's perception of ethical values. DESIGN:Eight months after the end of the AH1N1 vaccination campaign in the Province of Quebec (Canada), 100 French-speaking Quebecers were assembled in ten focus groups. Discussions focussed on the level of respect shown by public health authorities for individual autonomy, the limits of appeals for solidarity, the balance between vaccination efficiency and social justice towards non-prioritized subpopulations, vaccination as a demonstration of civic duty and social responsibility. RESULTS:The population acknowledged a high level of individual responsibility towards family members and agreed to vaccination to protect children and ageing parents. However, the concepts of civic duty and solidarity did not elucidate unanimous support, despite the fact that social justice stood out as a dominant value of public morals. CONCLUSION:The ethical principles promoted in influenza pandemic ethics frameworks are subject to reinterpretation by the population. An ethic of public health must consider their understanding of the fundamental values that legitimize mass vaccination.

背景与目标：

BACKGROUND & AIMS: :Pregnant women and their newborns are at elevated risk for influenza-associated hospitalization and death. The Advisory Committee on Immunization Practices (ACIP) and the American College of Obstetricians and Gynecologists (ACOG) have recommended influenza vaccination for all women who are or will be pregnant during the influenza season, regardless of trimester. To estimate influenza vaccination coverage among pregnant women for the 2011-12 influenza season, CDC analyzed data from an Internet panel survey conducted April 3-17, 2012, among women pregnant at any time during the 4-month period October 2011-January 2012. Among 1,660 survey respondents, 47.0% reported they had received influenza vaccination; 9.9% were vaccinated before pregnancy, 36.5% during pregnancy, and <1.0% after pregnancy. Overall, 43.7% of women reported receipt of both a health-care provider recommendation and offer of influenza vaccination; these women had higher vaccination coverage (73.6%) than women who received only a recommendation but no offer of vaccination (47.9%) and women who received neither a recommendation nor an offer (11.1%). Continued efforts are needed to encourage providers of medical care to routinely recommend and offer influenza vaccination to women who are pregnant or who might become pregnant.

背景与目标： : 孕妇及其新生儿患流感相关住院和死亡的风险较高。预防接种实践咨询委员会 (ACIP) 和美国妇产科学院 (ACOG) 建议所有在流感季节怀孕或将要怀孕的妇女接种流感疫苗，无论孕期如何。为了估计2011-12流感季节孕妇的流感疫苗接种覆盖率，疾病预防控制中心分析了2012年4月3至17日进行的互联网小组调查的数据，该调查在2011年10月2012年1月的4个月内的任何时间对孕妇进行了调查。在1,660调查受访者中，47.0% 报告他们接受了流感疫苗接种; 9.9% 在怀孕前接种了疫苗，36.5% 在怀孕期间接种了疫苗，并且在怀孕后 <1.0%。总体而言，43.7% 的妇女报告收到了卫生保健提供者的建议和流感疫苗接种的提议; 这些妇女的疫苗接种覆盖率 (73.6%) 高于只收到建议但没有提供疫苗接种的妇女 (47.9%) 和既没有收到建议也没有收到建议的妇女 (11.1%)。需要继续努力鼓励医疗服务提供者定期向怀孕或可能怀孕的妇女推荐和提供流感疫苗。

BACKGROUND & AIMS: :Vaccination against hepatitis B virus has rarely been associated with lichen planus. We report a case of this kind in a child from Nepal. A 12-year-old boy had developed generalized itchy violaceous papules and plaques six weeks after the second dose of hepatitis B virus vaccine. Serum HBsAg and HBeAb were negative, but HBsAb was positive. New crops of generalized, similar eruptions developed after the booster dose of vaccine. All the lesions resolved within three months of systemic steroid therapy. There was no recurrence after one year of follow up. Awareness of such an association is necessary, especially in children, because vaccination campaigns are increasing.

背景与目标： : 针对乙型肝炎病毒的疫苗接种很少与扁平苔藓有关。我们报告了一名来自尼泊尔的儿童的此类案件。一名12岁男孩在第二剂乙型肝炎病毒疫苗接种六周后出现了全身发痒的紫红色丘疹和斑块。血清HBsAg和HBeAb均为阴性，但HBsAb为阳性。在加强剂量的疫苗之后，出现了普遍的，类似的爆发的新作物。所有病变在全身类固醇治疗后三个月内消失。随访1年后无复发。对这种关联的认识是必要的，尤其是在儿童中，因为疫苗接种运动正在增加。

BACKGROUND & AIMS: :Concentrations of serum anti-Haemophilus influenzae type b (anti-Hib) capsular polysaccharide (CPS) >/=0.15 and >/=1.0 microgram/mL are widely used as surrogates for protection against invasive Hib disease. However, the relationship between serum anti-Hib CPS following immunization and protection against colonization is not known, making it difficult to evaluate new Hib vaccines or combination vaccines. In the Dominican Republic, nasopharyngeal swabs were collected from 546 9-month-old infants who had received Hib conjugate vaccine at ages 2, 4, and 6 months and from 600 unvaccinated infants of the same age. The prevalence of Hib colonization was lower among vaccinated infants than among unvaccinated infants (0.9% vs. 2.3%). Among vaccinated infants, protection against colonization was significantly correlated with anti-Hib CPS concentrations >/=5 microgram/mL 1 month following the third dose of vaccine. These results suggest that the concentration of serum anti-Hib CPS needed for protection against colonization is greater than that needed for protection for invasive disease.

背景与目标： : 血清抗流感嗜血杆菌b型 (抗Hib) 荚膜多糖 (CPS) 的浓度>/= 0.15和>/= 1.0微克/毫升被广泛用作预防侵袭性Hib疾病的替代物。然而预防接种后血清抗Hib CPS与抗定植保护之间的关系尚不清楚，因此难以评估新的Hib疫苗或组合疫苗。在多米尼加共和国，从546名在2、4和6个月龄接受Hib结合疫苗的9个月大婴儿和600名同龄未接种疫苗的婴儿中收集鼻咽拭子。接种疫苗的婴儿中Hib定植的患病率低于未接种疫苗的婴儿 (0.9% 对2.3%)。在接种疫苗的婴儿中，在第三剂疫苗接种后1个月，抗定植的保护作用与抗Hib CPS浓度>/= 5微克/毫升显着相关。这些结果表明，预防定植所需的血清抗Hib CPS浓度高于预防侵袭性疾病所需的血清抗Hib CPS浓度。

BACKGROUND & AIMS: OBJECTIVES:In June 2015, Alberta, Canada instituted a universal publicly funded rotavirus vaccination programme (Rotarix, RV1), with vaccine doses scheduled for 2 and 4 months of age. Vaccination was restricted so that infants were only allowed to receive first dose between 6 and 20 weeks of age, and second dose before eight calendar months of age. We assessed the coverage and schedule non-compliance of rotavirus vaccination for babies born between June 2015 and August 2016, that is, since the inception of the publicly funded rotavirus vaccination programme, and determined factors associated with rotavirus vaccine uptake. DESIGN:Retrospective cohort study using linked administrative health data. SETTING:Alberta, Canada. PARTICIPANTS:Cohort of 66 689 children. PRIMARY AND SECONDARY OUTCOME MEASURES: (1) First and second dose rotavirus vaccination coverage, (2) percent of children non-compliant with recommended vaccine schedule and (3) adjusted ORs for factors associated with vaccination status. RESULTS:For the 66 689 children included in the study, coverage levels for one-dose and two-dose rotavirus vaccination were 87% and 83%, respectively. In comparison, two-dose diphtheria-tetanus-pertussis-polio-Haemophilus influenzae type b vaccine coverage was 92%, despite having the same dosing schedule. Schedule non-compliance during the publicly funded programme was very low. We observed socioeconomic disparities in the uptake of the vaccine, with income, location of residence and number of children in the household all contributing to the odds of a child being vaccinated with rotavirus. CONCLUSIONS:Compliance to the recommended rotavirus schedule was very high, suggesting that even with the restrictive rotavirus vaccine schedule, the vaccine can be delivered on-time. However, rotavirus vaccine coverage remained lower than DTaP, a similarly scheduled childhood vaccination. We also observed socioeconomic disparities in vaccine uptake. These findings raise concerns about rotavirus protection in the groups at highest risk for gastrointestinal illness, including low-income and rural populations.

背景与目标：

BACKGROUND & AIMS: :The authors evaluated the association between receipt of measles-mumps-rubella (MMR) vaccine and asthma-like disease in early childhood in a Danish nationwide cohort study (N = 871,234). Two outcomes were included: hospitalizations with asthma diagnoses and use of anti-asthma medications (for a subset of the cohort only). Poisson regression was used to estimate rate ratios according to vaccination status. MMR-vaccinated children were less often hospitalized with an asthma diagnosis (rate ratio (RR) = 0.75, 95% confidence interval (CI): 0.73, 0.78) and used fewer courses of anti-asthma medication (RR = 0.92, 95% CI: 0.91, 0.92) than unvaccinated children. This "protective" effect of MMR vaccine was more pronounced for hospitalizations with severe asthma diagnoses (status asthmaticus: RR = 0.63, 95% CI: 0.49, 0.82) and use of medication that was highly specific for asthma (long-acting beta2-agonist inhalant: RR = 0.68, 95% CI: 0.63, 0.73). MMR vaccine was not negatively associated with anti-asthma medications often used for wheezing illnesses in early childhood (systemic beta2-agonist: RR = 1.02, 95% CI: 1.01, 1.02). These results are compatible not with an increased risk of asthma following MMR vaccination but rather with the hypothesis that MMR vaccination is associated with a reduced risk of asthma-like disease in young children.

背景与目标： : 作者在丹麦的一项全国队列研究 (N = 871,234) 中评估了麻疹-腮腺炎-风疹 (MMR) 疫苗接种与儿童早期哮喘样疾病之间的关系。包括两个结果: 诊断为哮喘的住院治疗和使用抗哮喘药物 (仅针对该队列的一个子集)。泊松回归用于根据疫苗接种状况估计比率。与未接种疫苗的儿童相比，接种MMR的儿童因哮喘诊断而住院的频率较低 (率比 (RR) = 0.75，95% 置信区间 (CI): 0.73，0.78)，使用抗哮喘药物的疗程较少 (RR = 0.92，95% CI: 0.91，0.92)。MMR疫苗的这种 “保护” 作用对于严重哮喘诊断 (哮喘状态: RR = 0.63，95% CI: 0.49，0.82) 和使用对哮喘具有高度特异性的药物 (长效beta2-agonist吸入剂: RR = 0.68，95% CI: 0.63，0.73)。MMR疫苗与儿童早期经常用于喘息疾病的抗哮喘药物没有负相关 (系统beta2-agonist: RR = 1.02，95% CI: 1.01，1.02)。这些结果与MMR疫苗接种后哮喘风险增加不一致，而是与MMR疫苗接种与幼儿哮喘样疾病风险降低相关的假设一致。

BACKGROUND & AIMS: BACKGROUND:Hepatitis B virus infection is a major health problem. Although non-response is known to increase with age, hepatitis B vaccinations are considered to have only minor non-response rates (anti-HBs<10IU/L) in healthy subjects. OBJECTIVES:The aim of this study was to quantify immunosenescence in a large retrospective cohort of 11,439 healthy adults who received HBV immunisation according to the standard vaccination regime. STUDY DESIGN:We evaluated the response to the standard three-dose vaccination regimen, consisting of 20-μg doses of the HbsAg recombinant DNA hepatitis B vaccine, among 11,439 healthy employees using a retrospective cohort design. Logistic regression was applied to predict the non-response rate, and multivariate regression analysis was applied to predict antibody response. Predictors of responsiveness included sex, age and time between the last vaccination and antibody titre measurement. RESULTS:From the age of 29 on in men and 43 on in women, more than 5% of subjects did not respond. Compared with women, men had a higher risk of non-response and exhibited a steeper decline in antibody titres produced with increasing age. CONCLUSIONS:This retrospective cohort study demonstrates that immunosenescence starts at young age, especially among men, underlining the importance of vaccination at a young age to achieve long-lasting immunity. Moreover, HBV vaccination should always include testing for antibodies to facilitate the performance of necessary interventions to prevent long-term fatal complications.

背景与目标：

BACKGROUND & AIMS: BACKGROUND:To evaluate the immunological responses of personalized peptide vaccination combined with low-dose glucocorticoids for advanced hormone refractory prostate cancer (HRPC) patients (pts). METHODS:Eleven pts with advanced HRPC were treated with the vaccination and low-dose glucocorticoids; 6 pts with 10 mg/day of prednisolone (PDL) followed by 1 mg/day of dexamethasone at the time of progression, 1 pt with PDL, and 4 pts with dexamethasone. Peptide-specific cellular and humoral responses were employed to monitor pre- and post- (6th) vaccination samples. RESULTS:The vaccination combined with glucocorticoids was well tolerated with no severe adverse effects. Increments of IgG responses were observed in 1 of 4 or 8 of 10 pts tested who received PDL or dexamethasone, respectively, increment of cytotoxic T lymphocyte activity was observed in 2 of 4 or 5 of 7 pts tested, respectively. Vaccination with PDL or dexamethasone resulted in a decline of PSA (at least 50%) in 1 of 7 or 6 of 10 pts with significantly longer median TTP in the dexamethasone group, respectively. CONCLUSION:Vaccination combined with dexamethasone could be recommended for further clinical trials from both immunological and clinical points of view.

背景与目标：