BACKGROUND & AIMS: :The aim of the study was to investigate changes in the incidences of Varicella and Herpes Zoster (HZ) following introduction of single dose Varicella vaccine (VV) in Turkey. Changes in the incidences of varicella and HZ per 100,000 population were compared with pre (2011-2012) and post-VV period (2018-2019) throughout years between years 2011 and 2019 both for children and adults. In children ≤5 years of age, the annual incidences of varicella significantly decreased from 290 per 100000 children in 2011 to 24 per 100000 children in 2019 [p = .0001]. Also, for children ≤5 years the mean annual incidence of varicella decreased significantly [326/100000 ±51/100000 vs 23/100000 ± 1/100000; p = .014] between pre- and post-VV period. Moreover, the annual incidences of varicella significantly decreased from 43 per 100000 children in 2011 to 26 per 100000 children in 2019 in children age between 6 and 17 years. On the other hand, incidence of varicella in adult population (age >17 years) did not change significantly. Besides, the annual incidences of Herpes Zoster did not change significantly in children age stratas but significant increment observed in adult population. This increment was significant in adult age strata of 18-44 years, but non-significant in age strata of 45-64 years and >64 years. Thus, our study showed a significant reduction in the incidences of Varicella in children age stratas whereas significant increment in the incidence of HZ in adult population after the implementation of VV into the NIP of Turkey.

背景与目标： ：该研究的目的是调查在土耳其引入单剂量水痘疫苗（VV）后水痘和带状疱疹（HZ）发病率的变化。将2011年至2019年儿童和成人的所有年份的水痘和HZ发病率变化与2011年之前（2011-2012年）和VV后时期（2018-2019年）进行了比较。在5岁以下的儿童中，水痘的年发病率从2011年的每100000名儿童290名下降到2019年的每100000名儿童24名[p = .0001]。此外，对于≤5岁的儿童，水痘的平均年发病率显着降低[326/100000±51/100000与23/100000±1/100000; p = .014]在VV前后之间。此外，在6至17岁的儿童中，水痘的年发病率从2011年的每10万名儿童中的43个下降到2019年的每10万名儿童中的26个。另一方面，成年人口（> 17岁）的水痘发病率没有显着变化。此外，带状疱疹的年发病率在儿童年龄层中没有显着变化，但在成年人口中却有显着增加。该增加在18-44岁的成年人年龄层中是显着的，但在45-64岁和> 64岁的年龄层中是不显着的。因此，我们的研究显示，在土耳其的NIP中实施VV后，成年儿童中水痘的发生率显着降低，而成年人中HZ的发生率显着增加。

BACKGROUND & AIMS: :Primary immunization with a single inoculum of either micelles or iscoms containing influenza A virus glycoproteins failed to induce either B or cytotoxic T (Tc) cell responses. In contrast, immunization with two inocula of iscoms, but not micelles, resulted in the appearance of influenza virus-specific antibody-secreting cells (ASC) but not Tc cells in the lung. There was a 10-fold increase in Tc cell precursor frequency and an increase in ASC generated by secondary in vitro stimulation of lung cell cultures obtained from mice primed with iscoms but not micelles. In mice primed with infectious virus, secondary immunization with either micelles or iscoms increased the number of ASC in the lung and elicited virus-specific Tc cell responses. In contrast homologous virus challenge failed to induce detectable secondary B or Tc cell responses.

背景与目标： ：一次接种含A型流感病毒糖蛋白的胶束或iscoms的初次免疫未能诱导B或细胞毒性T（Tc）细胞反应。相比之下，用两个接种的iscoms而不是胶束进行免疫接种，会导致肺中出现流感病毒特异性抗体分泌细胞（ASC），但未出现Tc细胞。 Tc细胞前体频率增加了10倍，而二次体外刺激从用iscoms而非胶束引发的小鼠获得的肺细胞培养物中产生的ASC则增加了10倍。在感染了传染性病毒的小鼠中，用胶束或胰酶进行二次免疫会增加肺中ASC的数量，并引起病毒特异性Tc细胞反应。相反，同源病毒攻击不能诱导可检测的继发性B或Tc细胞应答。

BACKGROUND & AIMS: :We compared the primary response in vitro with the secondary response in vivo of A/J inbred and CD-1 outbred mice to digoxin-HSA. The frequencies of hybrid formation and growth, and of the hybridomas that secreted antibody to digoxin were similar in both strains regardless of the immunization procedure. The patterns of cross-reactivity of the monoclonal antibodies to two compounds structurally related to digoxin (ouabain and digitoxin) were likewise similar for both strains and immunization procedures.

背景与目标： ：我们比较了A / J近交和CD-1近交小鼠对地高辛-HSA的体外主要反应与体内次要反应。不管免疫程序如何，两种菌株中杂种形成和生长的频率以及分泌地高辛抗体的杂交瘤的频率都相似。对于菌株和免疫程序，单克隆抗体对两种与地高辛结构相关的化合物（哇巴因和洋地黄毒苷）的交叉反应模式也相似。

BACKGROUND & AIMS: OBJECTIVE:To evaluate functional potential and phenotypic markers in HIV-1-infected patients immunized with HIV-1 rgp160. METHODS:We assessed changes in T-cell phenotype and immune function in 12 HIV-1-infected individuals that were part of a therapeutic vaccine study from 1992 to 1995 [Sandstrom E, Wahren B. Therapeutic immunisation with recombinant gp160 in HIV-1 infection: a randomised double-blind placebo-controlled trial. Nordic VAC-04 Study Group. Lancet 1999;353(9166):1735-42]. The patients received 160 microg HIV-1 rgp160 or placebo i.m. at baseline (day 0), and months 1, 2, 3, 4, 6, and thereafter every 3 months. Frozen peripheral blood mononuclear cells (PBMC) were retrieved from time points 0, 9, 12 and 24 months for phenotypic analysis utilizing flow cytometry. RESULTS:Up-regulation of immune activation markers HLA-DR and CD38 was observed at baseline and throughout the monitoring period on both CD4+ and CD8+ T cells in all patients, reflecting immune activation due to persistent high viral load. Further enhanced expression of activation markers was observed over time in the vaccine group, but not the placebo group. We also observed a consistent long-term increase of the CD4+ central memory population (CD3+CD4+CD45RA-CCR7+) in the vaccinated group. CONCLUSIONS:Administration of eight doses of rgp160 in a year appeared to partially reverse some of the defects exerted by HIV-1 on the immune system. A combination of vaccination with effective antiretroviral therapy (ART) may thus represent an immunotherapeutic intervention for treatment of chronic HIV-1 infection. The improvement of a HIV-1-specific central memory population and HIV-1 antigen-specific CD4+ lymphoproliferative responses may have contributed to the short-term improved survival reported in the vaccinated group.

背景与目标： 目的：评估用HIV-1 rgp160免疫的HIV-1感染患者的功能潜能和表型标记。
方法：我们评估了1992年至1995年治疗性疫苗研究的12名HIV-1感染者的T细胞表型和免疫功能的变化[Sandstrom E，Wahren B.重组gp160对HIV-1感染的治疗性免疫：一项随机双盲安慰剂对照试验。北欧VAC-04研究小组。 Lancet 1999； 353（9166）：1735-42]。患者接受160 microg HIV-1 rgp160或i.m安慰剂治疗。在基准（第0天），以及第1、2、3、4、6个月，此后每3个月。从0、9、12和24个月的时间点检索冷冻的外周血单核细胞（PBMC），以利用流式细胞仪进行表型分析。
结果：所有患者的CD4和CD8 T细胞在基线期和整个监测期间均观察到免疫激活标记HLA-DR和CD38的上调，反映了由于持续的高病毒载量引起的免疫激活。随着时间的推移，在疫苗组中观察到了激活标志物表达的进一步增强，但在安慰剂组中却没有。我们还观察到，接种组的CD4中央记忆种群（CD3 CD4 CD45RA-CCR7）长期持续增加。
结论：一年内服用八剂rgp160似乎可以部分逆转HIV-1对免疫系统造成的某些缺陷。因此，疫苗接种与有效的抗逆转录病毒疗法（ART）的结合可能代表了一种用于治疗慢性HIV-1感染的免疫治疗干预措施。 HIV-1特异性中央记忆群和HIV-1抗原特异性CD4淋巴组织增生反应的改善可能有助于接种组中短期生存率的提高。

BACKGROUND & AIMS: :Foot-and-mouth disease (FMD) causes morbidity to livestock and serious economic consequences to its associated industry and therefore it is necessary to develop a safe and efficient vaccine to prevent or control this disease. A recombinant live attenuated virus vaccine, designated PRV-P1, was generated by insertion of an expression cassette containing CMV promoter, FMDV P1 gene and SV 40 poly-A into the gG gene region of a live attenuated pseudorabies virus vaccine strain (TK-/gG-/LacZ+). To determine the induction of protective immunity, 16 FMDV and PRV seronegative white swine were randomly divided into four groups and immunized intramuscularly. The parental virus (TK-/gG-/LacZ+) was injected into three pigs, the recombinant virus PRV-P1 into five pigs and commercial FMD-inactivated vaccine into five pigs, with PBS (negative control) into three pigs. All animals were immunized again 4 weeks later to boost the immune response and challenged with virulent type O FMDV O/ES/2001 strain 4 weeks after the second immunization. Results showed PRV-P1 vaccinated pigs induced high-level neutralizing antibody response to both FMDV and PRV, and strong CTL response against FMD antigen activation. Three of five pigs were completely protected against challenge with FMDV, one pig minimally protected and the other one had increased protection but not complete. However, one pig vaccinated with commercial FMD vaccine developed constant pyrexia. Average levels of antibodies against non-structural 3ABC proteins were significantly lower and efficacy on inhibition of FMDV replication was much increased in swine vaccinated with PRV-P1 than those immunized with commercial FMD vaccine after FMDV challenge. Our results showed that the recombinant PRV-P1 can induce not only humoral and cell-mediated immune responses but also partial protection against FMDV challenge, making it a good candidate for future development of the FMD vaccine.

背景与目标： 口蹄疫（FMD）会导致牲畜发病并对其相关行业造成严重的经济后果，因此有必要开发一种安全有效的疫苗来预防或控制这种疾病。通过将含有CMV启动子，FMDV P1基因和SV 40 poly-A的表达盒插入减毒活伪狂犬病病毒减毒活疫苗株（TK- / gG- / LacZ）。为了确定保护性免疫的诱导，将16株FMDV和PRV血清阴性的白猪随机分为4组，并进行肌肉内免疫。将亲本病毒（TK- / gG- / LacZ）注入三只猪，重组病毒PRV-P1注入五只猪，商业FMD灭活疫苗注入五只猪，并用PBS（阴性对照）注入三只猪。第二次免疫4周后，所有动物再次免疫以增强免疫反应，并用强毒的O型FMDV O / ES / 2001毒株攻击。结果显示，接种PRV-P1的猪诱导了对FMDV和PRV的高水平中和抗体应答，以及针对FMD抗原激活的强CTL应答。五只猪中的三头受到FMDV的完全保护，免受攻击，一头猪受最低保护，另一头则增加了保护，但不完整。但是，一头接种了商业口蹄疫疫苗的猪出现了持续的发热。与非FMD疫苗接种的FMD疫苗相比，接种PRV-P1疫苗的猪的抗非结构性3ABC蛋白抗体的平均水平显着降低，抑制FMDV复制的功效大大提高。我们的结果表明，重组PRV-P1不仅可以诱导体液和细胞介导的免疫反应，而且还可以部分抵抗FMDV攻击，使其成为FMD疫苗未来开发的良好候选者。

BACKGROUND & AIMS: :The coccidian parasite Cryptosporidium parvum causes diarrhea in humans, calves, and other mammals. Neither immunization nor parasite-specific pharmaceuticals that are consistently effective against this organism are available. While polyclonal antibodies against whole C. parvum reduce infection, their efficacy and predictability are suboptimal. We hypothesized that passive immunization against cryptosporidiosis could be improved by using neutralizing monoclonal antibodies (MAbs) targeting functionally defined antigens on the infective stages. We previously reported that the apical complex and surface-exposed zoite antigens CSL, GP25-200, and P23 are critical in the infection process and are therefore rational targets. In the present study, a panel of 126 MAbs generated against affinity-purified CSL, GP25-200, and P23 was characterized to identify the most efficacious neutralizing MAb formulation targeting each antigen. To identify neutralizing MAbs, sporozoite infectivity following exposure to individual MAbs was assessed by enzyme-linked immunosorbent assay. Of 126 MAbs evaluated, 47 had neutralizing activity. These were then evaluated individually in oocyst-challenged neonatal mice, and 14 MAbs having highly significant efficacy were identified for further testing in formulations. Epitope specificity assays were performed to determine if candidate MAbs recognized the same or different epitopes. Formulations of two or three neutralizing MAbs, each recognizing distinct epitopes, were then evaluated. A formulation of MAbs 3E2 (anti-CSL [alphaCSL]), 3H2 (alphaGP25-200), and 1E10 (alphaP23) provided highly significant additive efficacy over that of either individual MAbs or combinations of two MAbs and reduced intestinal infection by 86 to 93%. These findings indicate that polyvalent neutralizing MAb formulations targeting epitopes on defined antigens may provide optimal passive immunization against cryptosporidiosis.

背景与目标： ：球虫寄生虫小隐孢子虫会导致人类，小牛和其他哺乳动物的腹泻。一直无法有效抵抗这种生物体的免疫或寄生虫特异性药物。虽然针对整个小球藻的多克隆抗体可减少感染，但它们的功效和可预测性欠佳。我们假设可以通过在感染阶段使用针对功能界定的抗原的中和单克隆抗体（MAb）来改善针对隐孢子虫病的被动免疫。我们之前曾报道过，根尖复合物和表面暴露的动物齿抗原CSL，GP25-200和P23在感染过程中至关重要，因此是合理的靶标。在本研究中，针对亲和纯化的CSL，GP25-200和P23生成的126个单克隆抗体的特征在于鉴定靶向每种抗原的最有效的中和单克隆抗体制剂。为了鉴定中和的单克隆抗体，通过酶联免疫吸附试验评估暴露于单个单克隆抗体后的子孢子感染性。在评估的126种单克隆抗体中，有47种具有中和活性。然后在卵囊感染的新生小鼠中对它们进行单独评估，并鉴定出具有高度显着功效的14种单克隆抗体，以便在制剂中进一步测试。进行表位特异性测定以确定候选单克隆抗体是否识别相同或不同的表位。然后评估各自识别不同表位的两个或三个中和单克隆抗体的制剂。单抗3E2（抗CSL [alphaCSL]），3H2（alphaGP25-200）和1E10（alphaP23）的配方提供了比单个MAb或两种MAb组合更高的显着加和功效，并将肠道感染减少了86-93 ％。这些发现表明，针对限定抗原上的表位的多价中和MAb制剂可提供针对隐孢子虫病的最佳被动免疫。

BACKGROUND & AIMS: OBJECTIVE:To review the varicella-zoster virus (VZV) and herpes zoster disease and to summarize published reports on the use of the live-attenuated varicella zoster vaccine to enhance cell-mediated immunity in elderly individuals. DATA SOURCE:A MEDLINE search (1966-August 1999) for English-language clinical studies and review articles pertaining to VZV and the live-attenuated varicella vaccine was conducted; references obtained from these publications were subsequently reviewed for additional relevant articles. STUDY SELECTION AND DATA EXTRACTION:Representative clinical trials were summarized and relevant information was selected to assist in the understanding of VZV, the subsequent immune response, and the live-attenuated varicella vaccine. DATA SYNTHESIS:The physiologic, age-related decline in VZV cell-mediated immunity has been shown to be restored on administration of live-attenuated varicella vaccine. Various studies report serum anti-VZV antibody concentrations, and production of interferon-gamma were increased following vaccination. Concentrations subsequently returned to baseline one year after vaccination. Increase in responder cell frequency, a measure of cell-mediated immunity, has been reported to last up to four years after vaccination, at concentrations similar or superior to those observed following herpes zoster. CONCLUSIONS:Enhancement of cell-mediated immune response in elderly individuals through vaccination with live-attenuated varicella vaccine is a possible measure to protect this population from herpes zoster and to attenuate its complications. A summary of immunogenicity studies to identify the immune response to live-attenuated varicella vaccine in the elderly is presented. The absolute clinical significance, as well as appropriate administration guidelines of this prophylactic intervention, will become evident following forthcoming large, masked, placebo-controlled trials.

背景与目标： 目的：回顾水痘带状疱疹病毒（VZV）和带状疱疹疾病，并总结有关使用减毒水痘带状疱疹活疫苗增强老年人细胞介导的免疫力的已发表报告。
资料来源：MEDLINE搜索（1966年8月至1999年8月）进行英语临床研究，并复习了有关VZV和减毒活水痘疫苗的文章；随后对从这些出版物中获得的参考文献进行了审查，以获取其他相关文章。
研究的选择和数据提取：总结了代表性的临床试验，并选择了相关的信息以帮助理解VZV，随后的免疫反应和减毒的水痘活疫苗。
数据合成：已证明，减毒水痘活疫苗的接种可以恢复生理性，与年龄相关的VZV细胞介导的免疫力下降。各种研究报告了血清抗VZV抗体的浓度，接种疫苗后γ干扰素的产生增加。疫苗接种一年后，浓度随后恢复到基线。据报道，接种细胞后反应细胞频率的增加（一种衡量细胞介导的免疫力的方法）可持续长达四年，其浓度与带状疱疹后观察到的浓度相似或更高。
结论：通过减毒活水痘疫苗接种来增强老年人的细胞介导的免疫反应是保护该人群免受带状疱疹和减轻其并发症的可能措施。概述了免疫原性研究，以鉴定老年人对减毒活水痘疫苗的免疫应答。在即将进行的大型的，有掩盖的，安慰剂对照的试验之后，这种预防性干预措施的绝对临床意义以及适当的给药指南将变得显而易见。

BACKGROUND & AIMS: PROBLEM:To determine whether an increase in the number of previous miscarriages in recurrent spontaneous abortion patients is a risk factor in subsequent pregnancies with paternal lymphocyte immunotherapy. METHOD OF STUDY:Live birth rates with reference to previous abortion numbers in recurrent spontaneous abortion patients were statistically compared between paternal lymphocyte immunotherapy and control groups, the latter retrospectively researched using historical data before 1981 in our clinic. RESULTS:The overall live birth rate was 73% (169/232) in the immunotherapy group, and 48% (47/97) in controls (P <0.05). According to previous abortion numbers, the rates were 77% (114/148) versus 55% (36/65) (P < 0.05) for three previous abortions, 70% (40/57) versus 38% (8/21) (P < 0.05) for four and 56% (15/27) versus 27% (3/11) (not significant) for five, in the study and control groups, respectively. CONCLUSIONS:The results confirm the efficacy of paternal lymphocyte immunotherapy, but demonstrate that the success rate deteriorates with the number of previous miscarriages.

背景与目标： 问题：要确定复发性自然流产患者先前流产次数的增加是否是随后通过父系淋巴细胞免疫疗法怀孕的危险因素。
研究方法：对父本淋巴细胞免疫疗法与对照组之间在复发性自然流产患者中参考先前流产数的活产率进行统计学比较，对后者进行回顾性研究，其依据是我们1981年以前的临床资料。
结果：免疫治疗组的总活产率为73％（169/232），对照组为48％（47/97）（P <0.05）。根据先前的堕胎次数，前三次堕胎的比率分别为77％（114/148）和55％（36/65）（P <0.05），分别为70％（40/57）和38％（8/21）（在研究组和对照组中，分别为4％和56％（15/27）的P <0.05），而5人分别为27％（3/11）（不显着）。
结论：该结果证实了父本淋巴细胞免疫疗法的有效性，但证明成功率随先前流产次数的增加而降低。

BACKGROUND & AIMS: :Clostridium difficile is the leading cause of infectious antibiotic-associated diarrhoea, particularly among the elderly. Its surface-layer protein (SLP) was tested as a vaccine component in a series of immunization and challenge experiments with Golden Syrian hamsters, combined with different systemic and mucosal adjuvants. Some regimens were also tested in a nonchallenge BALB/c mouse model, enabling closer monitoring of the immune response. None of the regimens conferred complete protection in the hamster model, and antibody stimulation was variable within regimens, and generally modest or poor. Mice displayed stronger antibody responses to SLP compared with hamsters. Two hamsters of five given SLP with Ribi (monophosphoryl lipid A and synthetic trehalose dicorynomycolate) survived the challenge, as did two of three given SLP with Ribi and cholera toxin. This modest trend to protection is interpreted with caution, because the survivors had low anti-SLP serum antibody titres. The hamsters were an outbred line, and subject to more genetic variability than inbred animals; however, BALB/c mice also showed strongly variable antibody responses. There is a clear need for better adjuvants for single-component vaccines, particularly for mucosal delivery. The hamster challenge model may need to be modified to be useful in active immunization experiments with SLP.

背景与目标： ：艰难梭菌是与抗生素相关的传染性腹泻的主要原因，尤其是在老年人中。它的表面层蛋白（SLP）在与金叙利亚仓鼠结合不同的全身和粘膜佐剂组合进行的一系列免疫和攻毒实验中作为疫苗成分进行了测试。还在非挑战性BALB / c小鼠模型中测试了某些方案，从而可以更紧密地监测免疫反应。没有一种方案可以在仓鼠模型中提供完全的保护，并且抗体刺激在方案中是可变的，并且通常适度或较差。与仓鼠相比，小鼠对SLP的抗体反应更强。含Ribi的SLP（单磷酰脂质A和合成的海藻糖dicorynomycolate）中的五个仓鼠中的两只仓鼠在挑战中幸存，三个具有Ribi和霍乱毒素的SLP的仓鼠中也有两个。谨慎解释这种适度的保护趋势，因为幸存者的抗SLP血清抗体滴度较低。仓鼠是近交系，比自交系动物的遗传变异性更大。然而，BALB / c小鼠也显示出强烈可变的抗体反应。显然需要用于单组分疫苗，特别是用于粘膜递送的更好的佐剂。仓鼠攻击模型可能需要修改才能在SLP主动免疫实验中使用。

BACKGROUND & AIMS: OBJECTIVE:Evaluate immunogenicity and clinical efficacy of two immunization strategies with the ALVAC-HIV-recombinant canarypox vaccine (vCP1452) in treated HIV-infected patients. DESIGN:Randomized, double-blind, placebo-controlled, phase II study of vCP1452 immunization in chronically HIV-infected patients on therapy with CD4 T-cell count more than 350 cells/microl, CD4 nadir less than 400 cells/microl and pHIV-RNA less than 400 copies/ml. Patients were equally randomized to four injections at weeks 0, 4, 8, 20; three injections at weeks 4, 8, 20; and placebo. The primary endpoint was vaccine immunogenicity at week 24 measured by enzyme-linked immunospot-interferon-gamma against the HIV-gag-reverse transcriptase-nef vaccine sequences. Secondary endpoints included time to treatment resumption and viral quantitation following treatment interruption at week 24. Criteria to resume therapy included CD4 T-cell count decline less than 250 cells/microl or 50% decrease from baseline or pHIV-RNA more than 50,000 copies/ml. RESULTS:Sixty-five patients enrolled. Changes from baseline in HIV-specific T cells in the four injection arms (+480 spot-forming cells/M-peripheral blood mononuclear cell) were significant compared to placebo (+8; P = 0.014), but not in the three injection arms (+322). The week 36 pHIV-RNA (log10 copies/ml) after treatment interruption was higher in the four (4.71; P = 0.023) and three (4.82; P = 0.009) injection arms compared to placebo (4.40). Percentages of patients reaching treatment resumption criteria by week 48 were 74, 55 and 23% in the three respective arms (P = 0.013). Two independent factors influenced time to therapy resumption: immunization (hazards ratio = 2.7, P = 0.048 for three injections; hazards ratio = 4.1, P = 0.003 for four injections) and CD4 nadir (hazards ratio = 0.4, P = 0.002). CONCLUSIONS:Significant immunogenicity was induced by vCP1452; however, this strategy was independently associated with a shorter time to resume therapy and higher viral rebound.

背景与目标： 目的：评估两种ALVAC-HIV重组金丝雀痘疫苗（vCP1452）的免疫策略的免疫原性和临床疗效。
设计：对慢性HIV感染患者进行vCP1452免疫的随机，双盲，安慰剂对照II期研究，接受CD4 T细胞计数大于350细胞/微升，CD4最低点小于400细胞/微升和pHIV- RNA小于400拷贝/ ml。在第0、4、8、20周，患者被随机分为四次注射。在第4、8、20周进行3次注射；和安慰剂。主要终点是在第24周时通过针对HIV-gag-逆转录酶-nef疫苗序列的酶联免疫斑点-干扰素-γ测得的疫苗免疫原性。次要终点包括在治疗的第24周后恢复治疗的时间和病毒定量。恢复治疗的标准包括CD4 T细胞计数下降小于250细胞/微升或比基线下降50％或pHIV-RNA超过50,000个拷贝/毫升。
结果：65例患者入组。与安慰剂相比，四个注射臂（480个点形成细胞/ M外周血单核细胞）中HIV特异性T细胞的基线变化较安慰剂（8； P = 0.014）显着，但三个注射臂中的HIV特异性T细胞的基线变化却不明显（322 ）。与安慰剂（4.40）相比，治疗中断后第36周的pHIV-RNA（log10拷贝/ ml）在四个（4.71; P = 0.023）和三个（4.82; P = 0.009）注射组中更高。到第48周时，在三个相应组中达到恢复治疗标准的患者百分比分别为74％，55％和23％（P = 0.013）。有两个独立的因素影响恢复治疗的时间：免疫（三次注射的危险比= 2.7，P = 0.048；四次注射的危险比= 4.1，P = 0.003）和CD4最低点（危险比= 0.4，P = 0.002）。
结论：vCP1452可诱导明显的免疫原性。但是，这种策略与恢复治疗时间较短和病毒反弹较高有关。

BACKGROUND & AIMS: Hepatitis A virus (HAV) infection is of public health significance among infants and diapered children. Although two licensed HAV vaccines are available, they have not been assessed widely in children under the age of 2 years and are not currently licensed for this age group. The purpose of this study was to evaluate the immunogenicity and reactogenicity of HAV vaccine in seronegative infants. Fifty-three healthy infants were immunized with 360 ELISA Units (EL.U.) of an inactivated HAV vaccine at 2, 4, and 6 (Group 1) or 2, 4, and 15 months of age (Group 2). These injections were not received on the same day that participants received their routine childhood immunizations. HAV serum antibodies were detected using a modified radioimmunoassay procedure and concentrations were calculated using a World Health Organization serum anti-HAV reference standard. No serious-systemic or local reactions were noted among the immunized infants. Three months following the third immunization, seroconversion rates were 100% and 93% in groups 1 and 2, respectively. No significant differences were observed in the geometric mean anti-HAV concentrations between the two groups at comparable time points, i.e. 2 months after the second dose, 3 months after the third dose, and 19 months after the first dose. Three infants, not included in the data presented above, had preexisting maternal antibodies; one never responded to the vaccine and the other two did not respond until maternal antibody levels had become reduced. The results indicate that the inactivated HAV vaccine is highly immunogenic in seronegative infants and could be included in the routine harmonized infant immunization schedule.

背景与目标： 甲型肝炎病毒（HAV）感染在婴儿和尿布儿童中具有公共卫生意义。尽管有两种许可的HAV疫苗可供使用，但尚未对2岁以下的儿童进行广泛的评估，并且目前尚未获得该年龄组的许可。这项研究的目的是评估血清阴性婴儿中HAV疫苗的免疫原性和反应原性。用灭活的HAV疫苗的360 ELISA单位（EL.U.）对53例健康婴儿进行免疫，分别于2、4和6岁（第1组）或2、4和15个月大（第2组）进行。在参加儿童常规免疫接种的同一天没有收到这些注射液。使用改良的放射免疫分析方法检测HAV血清抗体，并使用世界卫生组织血清抗HAV参考标准计算浓度。免疫婴儿中未发现严重的全身或局部反应。第三次免疫后三个月，第1组和第2组的血清转化率分别为100％和93％。在可比较的时间点，即第二次给药后2个月，第三次给药后3个月和第一次给药后19个月，两组之间抗HAV的几何平均浓度没有观察到显着差异。上述数据中未包括的三名婴儿已存在母体抗体。一个从未对疫苗产生反应，而另外两个直到母体抗体水平降低后才产生反应。结果表明，灭活的HAV疫苗在血清阴性婴儿中具有很高的免疫原性，可以纳入常规的统一婴儿免疫程序。

BACKGROUND & AIMS: BACKGROUND:Attention to evidence-informed policy has grown; however, efforts to strengthen the quality and use of evidence are not starting from a blank slate. Changes in health architectures and financing pose different considerations for investments in evidence-informed policy than in the past. We identify major trends that have shifted the environment in which health policies are made, and use the evolution and future aspirations of National Immunization Technical Advisory Groups (NITAGs) in low- and middle-income countries to identify questions the sector must confront when determining how best to structure and strengthen evidence-informed health policy. DISCUSSION:Trends over the last two decades have resulted in a dense arena with many issue-specific groups, discrete initiatives to strengthen evidence-informed policy and increasing responsibility for subnational institutions. Many countries face a shifting resource base, which for some reduces the amount of resources for health. There is global momentum around universal health coverage, reflecting a broader systems approach, but few examples of how the vast array of stakeholders relate within it are available. NITAG aspirations reflect four interconnected themes related to their scope, their integration in national policy processes, health financing and relationships with ministries of finance, and NITAG positioning relative to other domestic and international entities, raising questions such as, What are the bounds of issue-specific groups and their relationship to allocation decision-making processes across health areas? How do technical advisory groups interface with what are inherently political processes? When are finances considered, by whom and how? What is the future of existing groups whose creation was intended to enhance national ownership but who need continued external support to function? When should new entities be created, in what form and with what mandate? CONCLUSIONS:Countries must determine who makes decisions about resources, when, using what criteria, and how to do so in a robust yet efficient way given the existing and future landscape. While answers to these questions are necessarily country specific, they are collective matters that cannot be addressed by specialised groups alone and have implications for new investments in evidence-informed policy.

背景与目标： 背景：人们越来越重视以证据为依据的政策；但是，增强证据质量和使用证据的努力并非一帆风顺。与过去相比，卫生架构和资金的变化对以证据为依据的政策进行投资提出了不同的考虑因素。我们确定已经改变了制定卫生政策的环境的主要趋势，并利用中低收入国家的国家免疫技术咨询小组（NITAG）的演变和未来愿望，确定该部门在确定如何应对时必须面对的问题最好构造和加强有据可依的健康政策。
讨论：过去二十年来的趋势导致了一个密集的竞技场，其中有许多针对特定问题的团体，采取了一些离散的举措来加强以证据为依据的政策，并增加了对地方机构的责任。许多国家面临着不断变化的资源基础，这在某些方面减少了卫生资源。围绕全民健康覆盖的全球动力，反映了一种更广泛的系统方法，但是很少有有关广泛的利益相关者如何与之联系的例子。 NITAG的愿望反映了四个相互关联的主题，这些主题涉及其范围，它们在国家政策流程中的整合，卫生筹资以及与财政部的关系，以及NITAG在其他国内和国际实体中的相对位置，提出了以下问题：特定群体及其与跨卫生领域分配决策过程的关系？技术咨询小组如何与固有的政治流程互动？何时考虑财务，由谁以及如何考虑？现有团体的成立是为了增强国家所有权，但需要持续的外部支持才能发挥作用，它们的前景如何？什么时候应该以什么形式和什么任务创建新实体？
结论：在给定现有和未来形势的情况下，国家必须确定谁来决定资源，何时，使用什么标准以及如何以健壮而有效的方式做出决定。尽管对这些问题的回答必然是针对特定国家的，但它们是集体问题，不能由专门小组单独解决，并且对以证据为依据的政策进行新的投资具有影响。

BACKGROUND & AIMS: :In the vaccine strategy against HIV, bacillus Calmette-Guérin (BCG), a live attenuated strain of Mycobacterium bovis, is considered to be one of potential vectors for mucosal delivery of vaccine Ag. We analyzed the induction of the Ag-specific Ab response by nasal immunization with recombinant BCG vector-based vaccine (rBCG-V3J1) that can secrete the V3 principal neutralizing epitope of HIV. Mice were nasally immunized with rBCG-V3J1 (10 microg) three times at weekly intervals. Four weeks after the initial immunization, high titers of V3J1-specific IgG Abs were seen in serum. These high levels of HIV-specific serum IgG responses were maintained for >12 mo following nasal immunization without any booster immunization. V3J1-specific IgG-producing cells were detected in mononuclear cells isolated from spleen, nasal cavity, and salivary gland of the nasally vaccinated mice. Nasal rBCG-V3J1 also induced high levels of prolonged HIV-specific serum IgG responses in Th1 (IFN-gamma(-/-))- or Th2 (IL-4(-/-))-immunodeficient mice. Further, IgG3 was highest among V3 peptide-specific IgG subclass Ab responses in these immunodeficient mice as well as in wild-type mice. In addition, this Ag-specific serum IgG Abs induced by nasal immunization with rBCG-V3J1 possessed the ability to neutralize clinical isolate of HIV in vitro. These results suggested that the nasal rBCG-V3J1 system might be used as a therapeutic vaccine in addition to a prophylaxis vaccine for the control of AIDS.

背景与目标： ：在针对HIV的疫苗策略中，卡米特-圭兰杆菌（BCG）是牛分枝杆菌的减毒活株，被认为是粘膜递送疫苗Ag的潜在载体之一。我们通过重组BCG载体为基础的疫苗（rBCG-V3J1）经鼻免疫分析了Ag特异性Ab应答的诱导作用，该疫苗可分泌HIV的V3主要中和表位。每周用rBCG-V3J1（10微克）鼻腔免疫小鼠3次。初次免疫后四周，在血清中观察到高滴度的V3J1特异性IgG Abs。在不进行任何加强免疫的情况下，经鼻免疫后，这些高水平的HIV特异性血清IgG反应保持了> 12 mo。在从经鼻接种的小鼠的脾脏，鼻腔和唾液腺分离的单核细胞中检测到V3J1特异性IgG产生细胞。鼻rBCG-V3J1在Th1（IFN-γ（-/-））-或Th2（IL-4（-/-））免疫缺陷小鼠中也诱导了高水平的长时间HIV特异性血清IgG反应。此外，在这些免疫缺陷小鼠以及野生型小鼠中，V3肽特异性IgG亚类Ab亚型应答中IgG3最高。另外，通过用rBCG-V3J1鼻腔免疫诱导的这种Ag特异性血清IgG Ab具有在体外中和HIV临床分离株的能力。这些结果表明，除了用于预防艾滋病的预防性疫苗以外，鼻rBCG-V3J1系统还可以用作治疗性疫苗。

BACKGROUND & AIMS: :Reduced-antigen, combined diphtheria, tetanus, and three-component acellular pertussis vaccine (Tdap; Boostrix(®)) is indicated for booster vaccination against diphtheria, tetanus, and pertussis. In clinical trials, a single booster dose of Tdap induced high seroprotective levels of antibodies to its three component acellular pertussis antigens in virtually all children and adolescents, and in a high proportion of adults and elderly individuals, at ≈1 month post-vaccination, irrespective of their vaccination history. Seropositivity rates for antibodies against pertussis toxin had begun to decline by 5 years after a booster dose of Tdap in adolescents/adults, with a subsequent booster dose 10 years later generally as immunogenic and as well tolerated as the initial booster. Tdap was safe and well tolerated in all age groups.

背景与目标： ：降低抗原，联合白喉，破伤风和三组分脱细胞百日咳疫苗（Tdap;Boostrix®）可以用于白喉，破伤风和百日咳的加强疫苗接种。在临床试验中，单次加强剂量的Tdap几乎在所有儿童和青少年中以及在成年后约1个月的成人和老年人中都诱导了针对其三组分无细胞百日咳抗原的高血清保护水平的抗体他们的疫苗接种史。在青少年/成人中加强剂量的Tdap后，针对百日咳毒素的抗体的血清阳性率开始下降5年，随后的10年后一般随着最初的加强免疫原性和耐受性而增加。 Tdap在所有年龄段的人群中都是安全且耐受性良好的。

BACKGROUND & AIMS: Spontaneous recurrent abortion (SRA) has been treated by means of immunization with paternal or third-party white blood cells, yet the immunological basis for SRA and for the role of immunization protocols in pregnancy outcome remains controversial. To elucidate this question, nine women with SRA were immunized with paternal mononuclear cells and studied before and 2 weeks after immunization. Seven women who became pregnant gave birth to live newborns. Secretion of the T helper 1 cytokines IL-2 and interferon-gamma by patients, mononuclear cells decreased, while production of IL-10 increased. The levels of natural killer and lymphokine-activated killer cell-mediated cytotoxicity were markedly decreased. Monocyte functions such as secretion of IL-1 alpha, tumor necrosis factor alpha, IL-6, and cytotoxic activity decreased concurrently with elevations in IL-10 and transforming growth factor beta secretion. Production of IL-12, a pivotal regulatory cytokine, decreased. Furthermore, B7/1 expression on patients' mononuclear cells was downregulated. This resulted in a decrease in monocyte costimulatory activity of purified T cells with soluble anti-CD3, paralleled by a decline in allogeneic proliferative responses. These results suggest that the improved pregnancy success rate in women with SRA following immunization may be partly related to suppression of cell-mediated immunity and monocyte and natural killer cell activity.

背景与目标： 自发性反复流产（SRA）已通过父本或第三方白细胞免疫治疗，但SRA的免疫学基础以及免疫方案在妊娠结局中的作用仍存在争议。为了阐明这个问题，对9名SRA妇女进行了父系单核细胞免疫，并在免疫前和免疫后2周进行了研究。七名怀孕的妇女生了活的新生儿。患者分泌T辅助1细胞因子IL-2和干扰素-γ，单核细胞减少，而IL-10的产生增加。自然杀伤和淋巴因子激活的杀伤细胞介导的细胞毒性水平明显降低。单核细胞功能（例如IL-1α，肿瘤坏死因子α，IL-6的分泌和细胞毒性活性）与IL-10升高和转化生长因子β分泌同时降低。 IL-12（一种关键的调节细胞因子）的产量下降。此外，患者单核细胞上的B7 / 1表达下调。这导致具有可溶性抗CD3的纯化T细胞的单核细胞共刺激活性降低，同时同种异体增殖反应降低。这些结果表明，免疫接种后SRA妇女的妊娠成功率提高可能部分与抑制细胞介导的免疫力，单核细胞和自然杀伤细胞活性有关。