Genetic variants within the MHC region are associated with immune responsiveness to childhood vaccinations

The influence of genetic variability within the major histocompatibility complex (MHC) region on variations in immune responses to childhood vaccination was investigated. The study group consisted of 135 healthy infants who had been immunized with hepatitis B (HBV), 7-valent pneumococcal conjugate (PCV7), and diphtheria, tetanus, acellular pertussis (DTaP) vaccines according to standard childhood immunization schedules. Genotype analysis was performed on genomic DNA using Illumina Goldengate MHC panels (Mapping and Exon Centric). At the 1 year post vaccination check-up total, isotypic, and antigen-specific serum antibody levels were measured using multiplex immunoassays. A number of single nucleotide polymorphisms (SNPs) within MHC Class I and II genes were found to be associated with variations in the vaccine specific antibody responses and serum levels of immunoglobulins (IgG, IgM) and IgG isotypes (IgG1, IgG4) (all at p < 0.001). Linkage disequilibrium patterns and functional annotations showed that significant SNPs were strongly correlated with other functional regulatory SNPs. These SNPs were found to regulate the expression of a group of genes involved in antigen processing and presentation including HLA-A, HLA-C, HLA-G, HLA-H, HLA-DRA, HLA-DRB1, HLA-DRB5, HLA-DQA1, HLA-DQB1, HLA-DOB, and TAP-2. The results suggest that genetic variations within particular MHC genes can influence immune response to common childhood vaccinations, which in turn may influence vaccine efficacy.     

Preclinical safety evaluation of DNA vaccines encoding modified HPV16 E6 and E7

Persistent infection with high-risk human papillomaviruses (hrHPV) can result in the formation of anogenital cancers. As hrHPV proteins E6 and E7 are required for cancer initiation and maintenance, they are ideal targets for immunotherapeutic interventions. Previously, we have described the development of DNA vaccines for the induction of HPV16 E6 and E7 specific T cell immunity. These vaccines consist of 'gene-shuffled' (SH) versions of HPV16 E6 and E7 that were fused to Tetanus Toxin Fragment C domain 1 (TTFC) and were named TTFC-E6SH and TTFC-E7SH. Gene-shuffling was performed to avoid the risk of inducing malignant transformation at the vaccination site. Here, we describe the preclinical safety evaluation of these candidate vaccines by analysis of their transforming capacity in vitro using established murine fibroblasts (NIH 3T3 cells) and primary human foreskin keratinocytes (HFKs). We demonstrate that neither ectopic expression of TTFC-E6SH and TTFC-E7SH alone or in combination enabled NIH 3T3 cells to form colonies in soft agar. In contrast, expression of HPV16 E6WT and E7WT alone or in combination resulted in effective transformation. Similarly, retroviral transduction of HFKs from three independent donors with both TTFC-E6SH and TTFC-E7SH alone or in combination did not show any signs of immortalization. In contrast, the combined expression of E6WT and E7WT induced immortalization in HFKs from all donors. Based on these results we consider it justified to proceed to clinical evaluation of DNA vaccines encoding TTFC-E6SH and TTFC-E7SH in patients with HPV16 associated (pre)malignancies.     

东莞市流动人口新生儿破伤风发病状况及控制措施

目的了解流动人口新生儿破伤风发病情况,探讨综合干预措施对降低新生儿破伤风发病率的作用。方法开展常规监测和主动监测,采取旨在提高住院分娩率的综合干预措施,并比较加强干预前后新生儿破伤风发病率。结果1988—2003年,东莞市户籍人口无新生儿破伤风病例,流动人口新生儿破伤风年发病分别为101例、95例、116例、112例、69例、61例。加强综合干预后,流动人口新生儿破伤风发病率从0.68‰下降至0.33‰(P<0.01)。结论流动人口是控制新生儿破伤风的重点人群,加强综合干预对降低新生儿破伤风发病率有重要意义。     

我国6个省30个县新生儿破伤风流行病学调查分析

对６个省３０个县新生儿破伤风死亡率及相关影响因素进行了流行病学调查分析,结果显示：新生儿破伤风死亡率＞１‰的县有２４个,占被调查县的８０％．在新生儿死亡原因中,新生儿破伤风列第３位,占１６．３％．其中一个重要原因是在无科学条件保护下的产妇家分娩,由家属接生占８９．４％．同时,在接生过程中存在着诸多薄弱环节．应加强消毒接生和脐带护理知识的培训,制定农村接生及助产人员管理条例;在新生儿破伤风高危县,对育龄期妇女要进行破伤风类毒素免疫．     

Antibody persistence and safety and immunogenicity of a second booster dose nine years after a first booster vaccination with a reduced antigen diphtheria-tetanus-acellular pertussis vaccine (Tdap) in adults

BackgroundOver the last decades, pertussis showed periodic increases in its incidence among adults, despite being a vaccine-preventable disease.MethodsThis phase III, multicenter, extension study (NCT00489970) was conducted in adults from the United States, followed at Year (Y) 5 and Y9 post-vaccination with a dose of reduced-antigen-content tetanus-diphtheria-acellular pertussis vaccine containing either 3 (Tdap-B group) or 5 pertussis components (Tdap-A group). Willing participants in Tdap groups and newly-recruited participants (Control group) received one Tdap-B dose at Y9. Antibody persistence (at Y5 and Y9) and safety of Tdap-B at Y9 were assessed. Non-inferiority of immune response elicited by 2 Tdap doses was evaluated at Y9: (i) versus one Tdap-B dose for diphtheria and tetanus in terms of seroprotection rates; (ii) for all antigens in terms of booster response rates (Tdap-B and Tdap-A groups versus Control group); and (iii) for pertussis antigens in terms of geometric mean concentrations (GMCs) versus a 3-dose series of a combined diphtheria-tetanus-acellular pertussis vaccine (DTPa) administered during infancy.Results1257 participants were enrolled at Y5 and 809 participants were vaccinated at Y9. Seroprotection rates in both Tdap groups were ≥98.4% and ≥98.0% (Y5) and ≥98.3% and ≥98.1% (Y9) for diphtheria and tetanus, respectively. For pertussis antigens, antibody concentrations above assay cut-offs were observed for ≥76.6% (Y5) and ≥84.9% (Y9) of participants in Tdap groups. At Y9, one month post-Tdap vaccination, comparable seroprotection/seropositivity rates and antibody GMCs were observed among groups. Non-inferiority of immune responses in both Tdap groups was demonstrated when compared to the Control group for diphtheria and tetanus and to a 3-dose DTPa series for pertussis antigens. Non-inferiority criteria in terms of booster response were not met for all antigens. No safety concerns were raised.ConclusionA second dose of Tdap-B administered in adults, 9 years after initial Tdap vaccination, is immunogenic and well-tolerated.     

育龄期妇女接种破伤风类毒素血清学效果初步研究

为了评价育龄期妇女破伤风类毒素 (TT)突击接种的效果 ,并采用血清学回顾性研究探讨TT免疫应答 ,从而为开展育龄期妇女TT常规接种及制定育龄期妇女TT免疫策略提供科学依据。采用间接血凝方法 ,按容量比例概率抽样 ,随机抽取 36 7名 15～ 35岁育龄期妇女测定血清破伤风抗毒素 (TAT)水平。结果显示 ,5 6 %的育龄期妇女具有保护水平TAT(>0 0 1IU/ml) ,TAT几何平均滴度 (GMT)为 0 0 73IU/ml。接种 1针TT后育龄期妇女TAT >0 0 1IU/ml的占 5 0 % ,GMT为 0 0 39IU/ml;接种 2针TT后育龄期妇女TAT >0 0 1IU/ml的占 6 8% ,GMT为 0 14 5IU/ml,37个月后可检测到TAT ;接种 3针TT后育龄期妇女TAT>0 0 1IU/ml的占 90 % ,GMT为 0 5 76IU/ml,37个月后仍可检测到TAT ;育龄期妇女接种TT各剂次的TAT水平差异有显著的统计学意义。不同接种剂次免疫接种间隔、免疫年龄的TAT水平差异无显著统计学意义。建议 :提高重点地区和育龄期妇女中重点人群TT接种率 ;尽快开展TT常规接种 ;确定重点免疫人群策略     

中国消除新生儿破伤风现场认证调查

目的 现场调查认证中国是否消除新生儿破伤风（NT）。方法 采用批质量保证-群抽样（LQA-CS）方法,现场人户调查中国NT发病风险最高的广东省江门市和广西壮族自治区河池市各随机抽取的96个调查点、每个点调查12名符合条件（调查前一年内出生）活产儿的NT发病情况。结果 江门市共调查23465户家庭、1153名合格活产儿,河池市共调查21623户家庭、1152名合格活产儿。现场认证调查所设立的各项质控指标均符合要求。调查中两市均未发现因NT引起的死亡或者住院病例,已达到消除NT的标准,结合现场调查各项可靠质控指标,也证实调查点已消除NT。结论 在中国2个NT发生最高危的地区已调查证实消除了NT,据此可以推断其他地区也应消除了NT。按照WHO认证程序,中国已实现消除NT,建议此后工作重点应转为维持消除NT状态。     

Effect of nanomaterials on the compound action potential of the shore crab,Carcinus maenas

Abstract

Little is known about the effects of manufactured nanomaterials on the function of nerves. The experiment aimed to test the effects of three different nanomaterials (1 mg l^-1 of TiO₂ NPs, Ag NPs or SWCNT) on the compound action potential of the shore crab (Carcinus maenas) compared with an appropriate bulk powder or metal salt control (bulk TiO₂ powder, AgNO₃ and carbon black respectively). In single action potential recordings, there were no effects of any of the nanomaterials on the peak amplitude, duration, rate of rise (depolarisation), or rate of decrease (repolarisation) of the compound action potential in crab saline, despite settling of each nanomaterial directly onto the nerve preparation. The ability of the crab nerve to be stimulated to tetanus was also unaffected by exposure to the nanomaterials compared with the appropriate bulk powder or metal salt control. Solvent controls with sodium dodecyl sulfate (SDS) also had no effect on action potentials. Overall, the study concludes that there were no effects of the materials at the concentrations tested on the compound action potential of the shore crab in physiological saline.     

新生儿破伤风流行动态分析

目的:为了解龙岗区新生儿破伤风流行病学特征,掌握其流行动态,为政府相关部门制定干预措施提供依据,降低新生儿破伤风的发病率。方法:利用深圳市法定传染病报告系统和新生儿破伤风监测系统获得新生儿破伤风资料并进行统计分析。结果:龙岗区新生儿破伤风发病率和病死率呈逐年下降趋势;病例全部为流动人口;分娩方式均为院外分娩;94.74%的病例发病年龄在生后2周内;只有13.16%的母亲在孕期到医院进行过产前检查(次数≥1),85.09%的母亲未接种过破伤风类毒素疫苗。结论:结合新生儿破伤风的发病机制及流行病学特点,加强流动人口孕产妇管理,普及住院分娩、新法接生、开展育龄妇女破伤风类毒素接种是预防新生儿破伤风的有效措施。     

内蒙古自治区消除新生儿破伤风项目工作评价

目的落实卫生部和澳大利亚政府国际发展局援助内蒙古自治区开展消除新生儿破伤风(NT)项目,评价乌拉特中旗、乌拉特后旗、乌审旗、鄂托克前旗NT高危旗所有18~35岁的育龄期妇女开展破伤风疫苗(TV)接种效果。方法按照0、1、7个月程序开展突击接种3剂TV,每剂次0.5ml。结果4个旗应种35 138人,报告接种率TV192.79%,TV291.43%,TV390.30%,12个项目旗2003~2005年无NT病例报告。结论应在保证清洁接生的基础上,对NT高危旗育龄期妇女开展TV常规免疫接种,加强NT监测。