BACKGROUND & AIMS: :The current method for in vitro immunization (IVI) uses several antigens including toxins, food allergens, pathogenic bacteria, and self-antigen-derived peptides that induce an antigen-specific immune response in peripheral blood mononuclear cells (PBMCs). This protocol, however, requires donor blood collection and preparation of PBMCs before every IVI. In the present study, we aimed to design a more efficient system utilizing B cells immortalized with Epstein-Barr virus (EBV-B) as host cells for IVI to make antigen-specific antibodies. Results showed that previously antigen-sensitized, EBV-B cells exposed to the antigen along with IL-6, CpG oligonucleotides, and CD40 ligand signal produced antigen-specific antibodies. These results provide evidence for a novel and easy method to expand memory-type B cells and produce antigen-specific antibodies.

背景与目标： ：目前的体外免疫方法（IVI）使用多种抗原，包括毒素，食物过敏原，致病菌和自身抗原衍生肽，这些抗原在外周血单核细胞（PBMC）中诱导抗原特异性免疫反应。但是，该协议要求在每次IVI之前采集供体血液并准备PBMC。在本研究中，我们旨在设计一个更有效的系统，该系统利用以爱泼斯坦-巴尔病毒（EBV-B）永生的B细胞作为IVI的宿主细胞来制备抗原特异性抗体。结果表明，先前暴露于抗原的抗原致敏EBV-B细胞以及IL-6，CpG寡核苷酸和CD40配体信号产生了抗原特异性抗体。这些结果为扩大记忆型B细胞并产生抗原特异性抗体的新颖，简便方法提供了证据。

BACKGROUND & AIMS: OBJECTIVES:To inform strategic decisions on respiratory syncytial virus (RSV) vaccine development and identify critical endpoints likely to drive the vaccine's medical and economic impact. DESIGN:A decision-analysis model populated using healthcare utilization data and costs from the literature; vaccine efficacy and duration based on assumptions. SETTING:Vaccination in the physician office setting in the USA. PARTICIPANTS:A hypothetical cohort of newborn infants. INTERVENTION:Vaccination of children at low and high risk of respiratory sequelae with a theoretical RSV vaccine vs palivizumab prophylaxis for children at high risk. OUTCOME MEASURES:Medical and economic value of RSV vaccination, including cost per quality adjusted life-year (QALY) gained. RESULTS:Using base-case assumptions (efficacy 50% at birth; half-life 12 months), RSV vaccination would prevent 23,069 hospitalizations and 66 deaths per vaccinated birth cohort in the USA. Excluding vaccination costs, direct medical costs for RSV would reduce by $236 million, and income and productivity losses by $134 million. Assuming a vaccine cost per course similar to Rotarix® in the USA ($232 including administration fees), the cost per QALY gained would be $93,401 (95% CI: $65,815-$126,060) from the healthcare system perspective and $65,115 (95% CI: $41,003-$93,679) from the societal perspective. The net cost (healthcare system perspective) per life-year saved would be $216,120 (95% CI: $161,184-$263,981); the cost per hospitalization averted would be $19,172 (95% CI: $14,679-$22,093). Aside from efficacy, the vaccine's impact is sensitive to the start of protective immunity and the duration of protection. CONCLUSIONS:Development of an RSV vaccine would substantially reduce inpatient hospitalizations and outpatient visits. It would also have an impact on infant mortality. To demonstrate the full medical and economic value of the vaccine, appropriate endpoints or endpoint surrogates for hospitalization, mortality, and total case reductions should be collected during vaccine development.

背景与目标： 目的：为呼吸道合胞病毒（RSV）疫苗的开发提供战略决策，并确定可能推动该疫苗的医疗和经济影响的关键终点。
设计：使用医疗保健利用率数据和文献中的成本填充的决策分析模型；基于假设的疫苗效力和持续时间。
地点：在美国的医师办公室进行疫苗接种。
参与者：新生婴儿的假想队列。
干预：理论上RSV疫苗对低和高危呼吸系统后遗症的儿童进行疫苗接种，对高危儿童进行帕利珠单抗预防。
观察指标：RSV疫苗的医学和经济价值，包括获得的每质量调整生命年（QALY）的成本。
结果：使用基本病例假设（出生时效率为50％；半衰期为12个月），在美国，RSV疫苗接种可预防23,069例住院和每例接种出生队列66例死亡。不包括疫苗接种费用，RSV的直接医疗费用将减少2.36亿美元，收入和生产力损失将减少1.34亿美元。假设每个疗程的疫苗费用与美国的Rotarix®相似（232美元，包括管理费），那么从医疗保健系统的角度来看，每个QALY的费用将为93,401美元（95％CI：65,815-126,060美元），以及65,115美元（95％CI：41,003美元） -$ 93,679）。每个生命年节省的净成本（从医疗保健系统的角度来看）将为$ 216,120（95％CI：$ 161,184- $ 263,981）；避免的每次住院费用为$ 19,172（95％CI：$ 14,679- $ 22,093）。除了功效外，疫苗的影响还对保护性免疫的开始以及保护的持续时间敏感。
结论：RSV疫苗的开发将大大减少住院病人的住院和门诊病人的次数。这也将对婴儿死亡率产生影响。为证明疫苗的全部医学和经济价值，应在疫苗开发过程中收集住院，死亡率和总病例数减少的适当终点或终点替代指标。

BACKGROUND & AIMS: :The introduction of new vaccines with much higher prices than traditional vaccines results in increasing budgetary pressure on immunization programs in GAVI-eligible countries, increasing the need to ensure their financial sustainability. In this context, the third EPIVAC (Epidemiology and Vaccinology) technical conference was held from February 16 to 18, 2012 at the Regional Institute of Public Health in Ouidah, Benin. Managers of ministries of health and finance from 11 West African countries (GAVI eligible countries), as well as former EPIVAC students and European experts, shared their knowledge and best practices on immunization financing at district and country level. The conference concluded by stressing five major priorities for the financial sustainability of national immunization programs (NIPs) in GAVI-eligible countries. - Strengthen public financing by increasing resources and fiscal space, improving budget processes, increasing contribution of local governments and strengthen efficiency of budget spending. - Promote equitable community financing which was recognized as a significant and essential contribution to the continuity of EPI operations. - Widen private funding by exploring prospects offered by sponsorship through foundations dedicated to immunization and by corporate social responsibility programs. - Contain the potential crowding-out effect of GAVI co-financing and ensure that decisions on new vaccine introductions are evidence-based. - Seek out innovative financing mechanisms such as taxes on food products or a national solidarity fund.

背景与目标： ：引入价格比传统疫苗高得多的新疫苗导致符合GAVI资格的国家/地区对免疫计划的预算压力增大，从而增加了确保其财务可持续性的需求。在这种情况下，2012年2月16日至18日在贝宁Ouidah的公共卫生区域学院举行了第三次EPIVAC（流行病学和疫苗学）技术会议。来自11个西非国家（符合GAVI资格的国家）的卫生与财政部的经理以及EPIVAC的前学生和欧洲专家分享了他们在地区和国家/地区级的免疫融资知识和最佳实践。会议结束时强调了在符合GAVI资格的国家中国家免疫计划（NIP）的财务可持续性的五个主要优先事项。 -通过增加资源和财政空间，改善预算程序，增加地方政府的贡献并提高预算支出的效率来加强公共筹资。 -促进公平的社区融资，这被认为是对EPI运营连续性的重大和必不可少的贡献。 -通过致力于免疫的基金会和企业社会责任计划，探索赞助商提供的前景，从而扩大私人资金。 -遏制GAVI共同出资的潜在挤出效应，并确保有关新疫苗引入的决定是基于证据的。 -寻求创新的融资机制，例如食品税或国家团结基金。

BACKGROUND & AIMS: BACKGROUND:The study aimed to investigate the molecular epidemiology of severe viral gastroenteritis (AGE) in children in Taiwan after the implementation of the rotavirus vaccine in the private sector. METHODS:Fecal samples from hospitalized children with severe AGE from April 2004 to March 2011 were examined by reverse transcription-polymerase chain reaction or polymerase chain reaction to identify enteric viral pathogens. The study period was divided to prevaccine (before September 2006) and postvaccine (after October 2006) periods. The prevalence of enteric viruses between the 2 periods was analyzed. The disease burdens of rotavirus- and norovirus-associated diseases were assessed according to vaccine implementation status and were adjusted for age. RESULTS:A total of 755 stool samples were collected from hospitalized patients with AGE; enteric viruses were identified in 586 patients (77.6%), including 44 with concomitant bacterial infection. Viral enteric infection by rotavirus, norovirus, astrovirus, sapovirus, enteric adenovirus, multiple viruses and bacterial coinfections were found in 216 (28.6%), 128 (17.0%), 24 (3.2%), 6 (0.8%), 69 (9.1 %), 99 (13.1%) and 44 (5.8%) patients, respectively. A significant increase of norovirus infection was found in the postvaccine period (P < 0.001); on the other hand, rotavirus infection in infants has been reduced substainally (P = 0.056) and the annual peak of rotavirus infection has gradually become less prominent, with a significant decline of coinfection of rotavirus with other pathogens. CONCLUSIONS:Suboptimal use of rotavirus vaccines in the private sector caused a slow but modest impact on severe rotavirus AGE, whereas norovirus infection became more common.

背景与目标： 背景：这项研究旨在调查在私营部门实施轮状病毒疫苗后台湾儿童中的严重病毒性肠胃炎（AGE）的分子流行病学。
方法：采用逆转录-聚合酶链反应或聚合酶链反应方法检测2004年4月至2011年3月住院的重度AGE患儿的粪便样本，以鉴定肠道病毒病原体。研究期分为疫苗接种前（2006年9月之前）和疫苗接种后（2006年10月之后）两个时期。分析了这两个时期之间的肠道病毒患病率。根据疫苗实施状况评估轮状病毒和诺如病毒相关疾病的疾病负担，并根据年龄进行调整。
结果：从住院的AGE患者中共采集了755份粪便样本。 586例患者中检出了肠道病毒（77.6％），其中包括44例伴随细菌感染。轮状病毒，诺如病毒，星状病毒，沙波病毒，肠腺病毒，多种病毒和细菌合并感染引起的病毒性肠感染被发现为216（28.6％），128（17.0％），24（3.2％），6（0.8％），69（9.1） ％），99（13.1％）和44（5.8％）的患者。疫苗接种后发现诺如病毒感染显着增加（P <0.001）；另一方面，婴幼儿轮状病毒感染已得到实质性减少（P = 0.056），轮状病毒感染的年度高峰逐渐变得不那么突出，轮状病毒与其他病原体的共感染显着下降。
结论：在私营部门中轮状病毒疫苗的不理想使用对严重的轮状病毒AGE产生了缓慢但适度的影响，而诺如病毒感染变得更加普遍。

BACKGROUND & AIMS: :A vaccine remains a priority in the global fight against malaria. Here, we report on a single-center, randomized, double-blind, placebo and adjuvant-controlled, dose escalation phase 1a safety and immunogenicity clinical trial of full-length Plasmodium falciparum merozoite surface protein 1 (MSP1) in combination with GLA-SE adjuvant. Thirty-two healthy volunteers were vaccinated at least three times with MSP1 plus adjuvant, adjuvant alone, or placebo (24:4:4) to evaluate the safety and immunogenicity. MSP1 was safe, well tolerated and immunogenic, with all vaccinees sero-converting independent of the dose. The MSP1-specific IgG and IgM titers persisted above levels found in malaria semi-immune humans for at least 6 months after the last immunization. The antibodies were variant- and strain-transcending and stimulated respiratory activity in granulocytes. Furthermore, full-length MSP1 induced memory T-cells. Our findings encourage challenge studies as the next step to evaluate the efficacy of full-length MSP1 as a vaccine candidate against falciparum malaria (EudraCT 2016-002463-33).

背景与目标： ：在全球抗击疟疾的斗争中，疫苗仍然是优先事项。在这里，我们报告了全长恶性疟原虫裂殖子表面蛋白1（MSP1）与GLA-SE结合使用的单中心，随机，双盲，安慰剂和佐剂控制的剂量递增阶段1a安全性和免疫原性临床试验佐剂。对32名健康志愿者进行了至少3次MSP1加佐剂，单独佐剂或安慰剂的疫苗接种（24：4：4），以评估其安全性和免疫原性。 MSP1是安全的，耐受性良好且具有免疫原性，所有疫苗的血清转化都与剂量无关。上次免疫后至少六个月，MSP1特异性IgG和IgM滴度持续高于疟疾半免疫人群中发现的水平。该抗体具有超越变体和应变的特性，并能刺激粒细胞的呼吸活性。此外，全长MSP1诱导了记忆T细胞。我们的发现鼓励进行挑战性研究，作为评估全长MSP1作为抗恶性疟疾疫苗候选者的功效的下一步（EudraCT 2016-002463-33）。

BACKGROUND & AIMS: :Vaccinia virus immunization provides lifelong protection against smallpox, but the mechanisms of this exquisite protection are unknown. We used polychromatic flow cytometry to characterize the functional and phenotypic profile of CD8(+) T cells induced by vaccinia virus immunization in a comparative vaccine trial of modified vaccinia virus Ankara (MVA) versus Dryvax immunization in which protection was assessed against subsequent Dryvax challenge. Vaccinia virus-specific CD8(+) T cells induced by both MVA and Dryvax were highly polyfunctional; they degranulated and produced interferon gamma, interleukin 2, macrophage inflammatory protein 1beta, and tumor necrosis factor alpha after antigenic stimulation. Responding CD8(+) T cells exhibited an unusual phenotype (CD45RO(-)CD27(intermediate)). The unique phenotype and high degree of polyfunctionality induced by vaccinia virus also extended to inserted HIV gene products of recombinant NYVAC. This quality of the CD8(+) T cell response may be at least partially responsible for the profound efficacy of these vaccines in protection against smallpox and serves as a benchmark against which other vaccines can be evaluated.

背景与目标： ：痘苗病毒免疫可终生预防天花，但这种精致的保护机制尚不清楚。在改良牛痘病毒安卡拉（MVA）与Dryvax免疫的对比疫苗试验中，我们使用多色流式细胞仪表征了牛痘病毒免疫诱导的CD8（）T细胞的功能和表型特征，在该疫苗中，Dryvax免疫评估了针对随后的Dryvax攻击的保护作用。由MVA和Dryvax诱导的牛痘病毒特异性CD8（）T细胞具有高度的多功能性。抗原刺激后，它们脱粒并产生干扰素γ，白介素2，巨噬细胞炎性蛋白1beta和肿瘤坏死因子α。响应的CD8（）T细胞表现出不同寻常的表型（CD45RO（-）CD27（intermediate））。痘苗病毒诱导的独特表型和高度的多功能性也扩展到重组NYVAC的插入的HIV基因产物。 CD8（）T细胞反应的这种质量可能至少部分负责这些疫苗在预防天花方面的深远功效，并可以作为评估其他疫苗的基准。

BACKGROUND & AIMS: BACKGROUND:Pneumococcal conjugate vaccine (PCV) immunization of children decreases their risk of nasopharyngeal acquisition of vaccine serotypes. We studied the impact of routine infant PCV immunization alone on the epidemiology of nasopharyngeal pneumococcal colonization among a rural African community with high prevalence of HIV positivity. METHODS:Two cross-sectional surveys were undertaken in a rural South African community from May to October 2009 (period 1) and 2011 (period 2). Seven-valent PCV was introduced into the public immunization program for infants in April 2009, without catch-up campaign for older children. Randomly selected households with at least 1 child<2 years of age were recruited. Nasopharyngeal swabs from all consenting household members were obtained for Streptococcus pneumoniae culture and serotyping by Quellung method. RESULTS:The median ages (SD) of children enrolled were 4.32 (SD, 3.4) and 3.80 (SD, 3.4) years in periods 1 and 2, respectively. Overall, the prevalence of vaccine serotype colonization declined from 18.3% (368/2010) in period 1 to 11.4% (418/3659) by period 2 (P<0.0001). This included reductions (adjusted risk ratio) of 50% [95% confidence interval (95% CI): 0.42-0.59], 34% (95% CI: 0.48-0.92) and 64% (95% CI: 0.18-0.74) in age groups<2 years, 6-12 years and adults. The prevalence of vaccine serotype colonization among primary caregivers decreased from 10.2% to 5.4% (P≤0.001) by period 2. The prevalence of nonvaccine serotype colonization increased by 35% (95% CI: 1.17-1.56) among <2-year-old children by period 2, while it declined by 45-54% among adolescents and adults. CONCLUSIONS:An indirect effect of PCV7 was realized in a high HIV prevalence setting within 2 years of PCV introduction. The unexpected decline in nonvaccine serotypes colonization among adolescents/adults may indicate lag in replacement colonization by nonvaccine serotypes in this group.

背景与目标： 背景：对儿童进行肺炎球菌结合疫苗（PCV）免疫可降低其鼻咽获得疫苗血清型的风险。我们研究了单独的常规婴儿PCV免疫对一个HIV阳性高发的非洲农村社区中鼻咽肺炎球菌定植流行病学的影响。
方法：分别于2009年5月至10月（期间1）和2011年（期间2）在南非农村社区进行了两次横断面调查。 2009年4月，七价PCV被引入婴儿的公共免疫计划，而没有针对大龄儿童的追赶运动。招募了至少有1个孩子<2岁的随机选择的家庭。获得所有同意的家庭成员的鼻咽拭子用于肺炎链球菌培养并通过Quellung方法进行血清分型。
结果：在第1和第2阶段，入组儿童的中位年龄（SD）分别为4.32（SD，3.4）和3.80（SD，3.4）岁。总体而言，疫苗血清型定植的发生率从第1阶段的18.3％（368/2010）下降到第2阶段的11.4％（418/3659）（P <0.0001）。其中包括降低50％（调整后的风险比）[95％置信区间（95％CI）：0.42-0.59]，34％（95％CI：0.48-0.92）和64％（95％CI：0.18-0.74） <2岁，6-12岁和成人的年龄段。到第二阶段，初级护理人员中疫苗血清型定植的患病率从10.2％降低到5.4％（P≤0.001）。非疫苗血清型定植的患病率在2年以下的人群中增加了35％（95％CI：1.17-1.56）。到第2阶段的大孩子，而青少年和成人的年龄则下降了45-54％。
结论：PCV 7的间接影响是在PCV引入后2年内在艾滋病高流行的情况下实现的。青少年/成人中非疫苗血清型定殖的出乎意料的下降可能表明该组中非疫苗血清型的替代定植滞后。

BACKGROUND & AIMS: OBJECTIVE:To assess the immunization status of children in 90 districts of the country giving due representation to all States and UTs. METHODS:WHO 30 cluster survey methodology with certain modifications incorporating information on sex, literacy and distance of the village. RESULTS:Information was collected for about nineteen thousand children. Immunization program could touch about 90% of target children. About 63% of children received all the vaccines (BCG, DPT, OPV, Measles). In the states of Bihar, Rajasthan, UP, MP, and NE States (combined) coverage levels were relatively lower. The coverage levels were also lower for children of illiterate mothers and in small, inaccessible and tribal village. CONCLUSION:Immunization coverage of children has improved in recent years. Further improvement may be achieved by targeting illiterate mothers, inaccessible and tribal areas and low performing states.

背景与目标： 目的：评估该国90个地区的儿童的免疫状况，并应适当代表所有州和UT。
方法：WHO 30聚类调查方法，并进行了某些修改，并纳入了有关性别，识字率和村庄距离的信息。
结果：收集了大约1.9万名儿童的信息。免疫计划可以接触约90％的目标儿童。大约63％的儿童接种了所有疫苗（BCG，DPT，OPV，麻疹）。在比哈尔邦，拉贾斯坦邦，UP，MP和NE州（合并），覆盖率相对较低。文盲母亲的孩子以及在一个无法进入的部落小村庄的儿童的覆盖率也较低。
结论：近年来儿童的免疫接种覆盖率有所提高。通过针对文盲母亲，人迹罕至的地区和表现欠佳的州，可以实现进一步的改善。

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。