OPV疫苗液体剂型稳定性影响因素分析

 分析了温度、反复冻融、冷链运输过程对口服脊髓灰质炎减毒活疫苗(OPV)滴度的影响,检测结果显示OPV分别在37℃条件下放置3d,25℃放置14d,-20℃放置36个月、反复冻化35次,感染性滴度均无明显变化.在冷链条件下运输,其感染性滴度无明显变化.液体剂型的稳定性优于糖丸剂型(t=3.2043,P<0.01).     

Prospects for a vaccine against the hepatitis C virus

The recent discovery of natural immunity to the hepatitis C virus and vaccine efficacy in the chimpanzee challenge model has allowed optimism about the development of at least a partly effective vaccine against this heterogeneous pathogen that is responsible for much of the chronic liver disease around the world. The immune systems of some infected individuals can spontaneously clear the virus, whereas other people need treatment with antivirals that work partly by stimulating humoral and cellular immune responses. Therefore, therapeutic vaccine strategies are also being pursued to improve treatment outcome.     

猪瘟弱毒苗注射奶犊牛的E玫瑰花环试验

本实验用E玫瑰花环试验检测奶犊牛的细胞免疫状况,实验组8头奶犊牛注射疫苗前的E玫瑰花环率平均为20%,注射疫苗后第45天E玫瑰花环率平均为26%,而对照组5头犊牛E玫瑰花环率平均为22%,数据显示注射疫苗后比注射疫苗前上升了6%,比对照组上升了4%.实验结果表明犊奶牛注射猪瘟弱毒苗后能够引起细胞免疫的提高.     

A group specific anamnestic immune reaction against HIV-1 induced by a candidate vaccine against AIDS

The first experimental immunization of humans against the AIDS retrovirus, HIV-1, was started in a series of HIV seronegative, healthy volunteers in November 1986. For the primary vaccination recombinant vaccinia virus (V25) expressing the complete gp160 env protein of the HTLV-IIIB strain of HIV-1 was introduced by scarification. This elicited a weak primary response which we subsequently attempted to enhance by additional immunizations (boosting), using four different immunization protocols. We report here that intravenous injection of paraformaldehyde-fixed autologous cells infected in vitro with V25 (individual D.Z.) gave the best results. This individual received second and third boosts of intramuscular gp160 derived from an HTLV-IIIB clone using the hybrid vaccinia virus/bacteriophage T7 expression system. An anamnestic humoral and cellular immune reaction was achieved for over one year after the original vaccination, with high levels of antibodies to the viral envelope, and neutralizing antibodies against divergent HIV-1 strains such as HTLV-IIIB and HTLV-IIIRF (also called HTLV-III HAT) after the first boost. In addition, group-specific cell-mediated immunity and cell-mediated cytotoxicity against infected T4 cells were obtained after the primary vaccine and enhanced by the boosts. Finally, skin tests showed both immediate and delayed hypersensitivity to gp160 in vivo. Although this protocol is not practical for a large scale vaccine trial, our results show for the first time that an immune state against HIV can be obtained in man.     

Safety and immunogenicity in man of a synthetic peptide malaria vaccine against Plasmodium falciparum sporozoites

A 12 amino-acid synthetic peptide (NANP)3 comprising the immunodominant epitope of Plasmodium falciparum circumsporozoite protein was conjugated to tetanus toxoid (TT), adjuvanted with aluminium hydroxide, and administered intramuscularly in three doses at monthly intervals to 35 healthy males as a malaria vaccine. No significant adverse reactions were noted, with mild soreness at the injection site the only common symptom. Seroconversions against NANP occurred in 53% and 71% of recipients of 100 or 160 micrograms, respectively, measured by enzyme-linked immunosorbent assay (ELISA). Most ELISA-positive sera reacted with sporozoites by indirect immunofluorescence (IFA). Three vaccinees with the highest ELISA and IFA titres and four unimmunized controls were challenged with P. falciparum sporozoites introduced via the bites of infective Anopheles mosquitoes. Blood stage parasites were detected in all controls by 10 days (mean 8.5 days, range 7-10). In contrast, the two vaccinees who became infected did not manifest parasitaemia until day 11 and the third vacinee showed neither parasites nor symptoms during the 29 day observation period. This first synthetic peptide parenteral vaccine against a communicable disease tested in man is safe and stimulates biologically active antibodies. These observations encourage the development of improved vaccine formulations which, by enhancing immunogenicity, may lead to practical vaccines to assist in the control of falciparum malaria.     

Comparison of white pock (h) mutants of monkeypox virus with parental monkeypox and with variola-like viruses isolated from animals

Monkeypox mutants arising spontaneously or after serial, high multiplicity passage were characterized phenotypically and by restriction endonuclease mapping. Some resemble "whitepox" and variola viruses in several of the markers tested but all are distinguishable phenotypically from these. None resembles "whitepox" viruses in genome structure although near-terminal deletions or symmetrical, terminal rearrangements, relative to parental monkeypox, occurred. "Whitepox" viruses isolated from animals closely resemble variola in both phenotype and genome structure.     

EVA、MVA与项目投资评价

EVA是由Stern Stewar&Co.在1989年设计出来的,作为一种有用的管理工具,不仅可利用它来分析企业的管理绩效,作为企业经理人员报酬计划分配的一种手段,而且可用于企业并购、资本预算以及证券投资评价等.而本文则主要分析了EVA与MVA间的关系,并证明在项目投资评价中,MVA与NPV之间的等价性.     

Protein degradation and protection against misfolded or damaged proteins

The ultimate mechanism that cells use to ensure the quality of intracellular proteins is the selective destruction of misfolded or damaged polypeptides. In eukaryotic cells, the large ATP-dependent proteolytic machine, the 26S proteasome, prevents the accumulation of non-functional, potentially toxic proteins. This process is of particular importance in protecting cells against harsh conditions (for example, heat shock or oxidative stress) and in a variety of diseases (for example, cystic fibrosis and the major neurodegenerative diseases). A full understanding of the pathogenesis of the protein-folding diseases will require greater knowledge of how misfolded proteins are recognized and selectively degraded.     

Protection of cottontop tamarins against Epstein-Barr virus-induced malignant lymphoma by a prototype subunit vaccine

Epstein-Barr (EB) virus is one of the five herpesviruses of man. Strong links between this agent and the chain of events causing two human cancers, endemic Burkitt's lymphoma and undifferentiated nasopharyngeal carcinoma, have long been evident (reviewed in ref. 1). Because of this, and because of the very high incidence of nasopharyngeal carcinoma in certain large populations, it was suggested in 1976 that a vaccine should be developed against EB virus to prevent infection and thereby reduce tumour incidence amongst those at risk. The virus-determined membrane antigen (MA) was proposed as immunogen because it was known to elicit naturally occurring virus-neutralizing antibodies in man and because analogous antigens had been shown to act as effective experimental vaccines for preventing the herpesvirus-induced lymphomas of Marek's disease in chickens. Progress has been achieved in defining, quantifying and preparing MA molecules, and in enhancing their immunogenicity; a sensitive assay for antibodies to MA has been elaborated. Here we report that isolated cell membranes expressing MA, or purified MA glycoprotein of relative molecular mass (Mr) 340,000 (gp340), have been used to vaccinate cottontop tamarins (Saguinus oedipus oedipus), and that animals receiving either preparation were protected against the effects of a 100% tumour-inducing challenge dose of EB virus.     

Profound early control of highly pathogenic SIV by an effector memory T-cell vaccine

The acquired immunodeficiency syndrome (AIDS)-causing lentiviruses human immunodeficiency virus (HIV) and simian immunodeficiency virus (SIV) effectively evade host immunity and, once established, infections with these viruses are only rarely controlled by immunological mechanisms. However, the initial establishment of infection in the first few days after mucosal exposure, before viral dissemination and massive replication, may be more vulnerable to immune control. Here we report that SIV vaccines that include rhesus cytomegalovirus (RhCMV) vectors establish indefinitely persistent, high-frequency, SIV-specific effector memory T-cell (T(EM)) responses at potential sites of SIV replication in rhesus macaques and stringently control highly pathogenic SIV(MAC239) infection early after mucosal challenge. Thirteen of twenty-four rhesus macaques receiving either RhCMV vectors alone or RhCMV vectors followed by adenovirus 5 (Ad5) vectors (versus 0 of 9 DNA/Ad5-vaccinated rhesus macaques) manifested early complete control of SIV (undetectable plasma virus), and in twelve of these thirteen animals we observed long-term (≥1 year) protection. This was characterized by: occasional blips of plasma viraemia that ultimately waned; predominantly undetectable cell-associated viral load in blood and lymph node mononuclear cells; no depletion of effector-site CD4(+) memory T cells; no induction or boosting of SIV Env-specific antibodies; and induction and then loss of T-cell responses to an SIV protein (Vif) not included in the RhCMV vectors. Protection correlated with the magnitude of the peak SIV-specific CD8(+) T-cell responses in the vaccine phase, and occurred without anamnestic T-cell responses. Remarkably, long-term RhCMV vector-associated SIV control was insensitive to either CD8(+) or CD4(+) lymphocyte depletion and, at necropsy, cell-associated SIV was only occasionally measurable at the limit of detection with ultrasensitive assays, observations that indicate the possibility of eventual viral clearance. Thus, persistent vectors such as CMV and their associated T(EM) responses might significantly contribute to an efficacious HIV/AIDS vaccine.     

桥梁墩台的护坦防护局部冲刷深度计算

运用水力分析和试验观测的方法,研究了桥梁墩台的护坦防护机理及防护效果。提出护坦宽度(BH)和顶面埋置深度是影响护坦防护效果的主要因素,并根据试验资料提出护坦防护墩台局部冲刷深度的计算方法。试验结果表明,通过在桥梁墩台周围设置护坦可以有效地减小墩台局部冲刷深度。     

Monoclonal antibodies demonstrate protection of polymorphonuclear leukocytes against complement attack

Studies on erythrocytes have shown that the formation of the membrane attack complex on a cell surface inevitably results in lysis. However, it is known that nucleated cells are much more difficult to kill with complement, although the molecular basis of this resistance has never been established. We have shown that a very early intracellular event, occurring within seconds of formation of the attack complex in the membrane, is a rise in cytoplasmic Ca2+, which can activate cell responses without cell death 5,6. Here we report the use of a monoclonal antibody to the terminal complement component C9, quantified by 125I and visualized by fluorescein, to demonstrate a protection mechanism in polymorphonuclear leukocytes (PMNs) attacked by complement, involving removal of the attack complex by vesiculation. Concomitantly, there is a Ca2+-dependent activation of reactive oxygen metabolite production without cell lysis. These findings have important implications in the evolutionary and pathological significance of the terminal components of the complement pathway.     

鸭疫里默氏杆菌三价灭活疫苗的免疫保护期研究

选择免疫原性好的血清1,2,4型鸭疫里默氏杆菌（RA）分离株制备三价灭活油乳剂苗,疫苗抗原含量为5×109CFU/ml,分别用0.5,1.0和1.5ml/只剂量接种7日龄樱桃谷肉鸭以检验器其安全性;用0.25ml/只的剂量接种樱桃谷肉雏鸭,分别于免疫后第1、2、3,4、5和9周攻毒,以检验其免疫效果.安全性检验结果显示,肉雏鸭接种后未见局部和全身异常反应;攻毒保护试验结果显示,免疫后2～9周雏鸭对3个血清型的RA的攻毒保护率达70％ ～ 100％.证明该三价灭活疫苗具有良好的安全性免疫保护力,免疫保护期不少于9周.     

丁坝基础冲刷机理和防护措施

通过水力模型试验资料分析,建立了丁坝局部最大冲深的计算关系式;探讨了平台加齿坎基础冲刷防护措施的削弱作用;建立了平台或平台加齿坎基础防护形式的局部冲刷深度的计算模式.在水流稳定流条件下,通过不同条件下的长历时试验,分析了丁坝局部冲刷过程的特点及有关影响要素;实验结果提出的计算公式的计算值完全吻合.     

磨料射流割缝技术防突机理及应用

为改善李子垭南二井3102北机巷掘进碛头瓦斯预抽时间长、掘进速度慢的现状,通过对磨料射流使煤(岩)体损伤模型及防突机理的分析,研究了磨料射流切割破碎煤(岩)体的过程;利用磨料水射流切割煤矸石的实验研究,确定了磨料射流切割煤矸石的各种参数,并研制了一套新型的适合于现场应用的磨料水射流割缝装置。现场试验表明:磨料射流能够切穿单轴抗压强度为62MPa、60～80mm厚度的煤层夹矸,在煤层中形成缝槽,增大了瓦斯涌出自由面,促使煤体大范围快速卸压,增强煤层透气性,首月内瓦斯单孔平均抽采量提高了2.83倍。     

Specific anti-tumor effect induced by attenuated Salmonella typhimurium vaccine expressing extracellular region of vascular endothelial growth factor receptor 2

The purposes of this research were to study the stable expression of exogenous gene encoding therapeutic protein in attenuated Salmonella typhimurium, observe the metabolism of oral gene vaccine carried by attenuated Salmonella typhimurium in BALB/c mouse, and investigate the feasibility of prevention and treatment of tumors by the recombinant bacteria. Recombinant plasmid pcDNA3.1 VEGFR2(n1-7) was transformed into competent attenuated Salmonella typhimurium SL3261 to develop oral DNA vaccine SL3261-pcDNA3.1 VEGFR2(n1-7). To observe whether the exogenous gene can be expressed in the recombinant bacteria, PCR was performed to amplify the CMV promoter of the eukaryotic expression vector as the proof of stable expression of exogenous protein; transmission elec- tron microscopy (TEM) was applied to observe the morphology of the recombinant bacteria to confirm that the exogenous gene has no impact on the growth of the bacteria, and then BALB/c mice were immunized with the gene vaccine. After inoculation of the gene vaccine, the recombinant bacteria SL3261 could be detected in the tissues such as small intestine, colon, liver and spleen. And then, mice in each group were challenged with tumor cells. The results of animal experiment showed that tumor growth of the mice in experimental group was inhibited and survival time of immunized mice was prolonged compared with control groups. A higher lymphocyte infiltration in tumors from animals treated with DNA vaccine was observed. Immunohistochemical analysis of tumor samples revealed an en- hanced accumulation of CD8 cytotoxic T lymphocytes, as well as an increase in CD4 cells in the tumors of animals treated with the oral gene vaccine compared to tumors from control group mice. Ultrastructure of the tumor tissue showed that tumor cells in the samples of the immunized mice were well-differentiated. Our research confirmed that the exogenous gene can be stably expressed in the attenuated Salmonella typhimurium and has no impact on the growth of the recombinant bacteria; the exogenous gene can de delivered to the host by attenuated Salmonella typhimurium to produce anti-tumor effect with no obvious cytotoxity to the host. In this study, it is established that attenuated Salmonella typhimurium could be used as a vector for oral gene vaccine, and our study provided a theoretical basis for the body distribution and the metabolism of the recombinant bacteria. This strategy may provide a simple, safe and effective way for the prevention and treatment of tumors.     

基于Matlab的AIFF MVA液晶显示模拟及分析

用Matlab软件模拟了AIFF MVA模式液晶显示器光学透过率的电极尺寸效应.首先模拟了盒内电场分布,然后由盒内电场分布计算模拟液晶盒透过率,并在此基础上分析了像素电极尺寸大小和间隔尺寸大小对液晶盒透过率的影响.将软件模拟和实际实验相对照,验证计算机软件模拟的可靠性.结合软件模拟的结果提出了AIFF MVA模式下像素...     

Vaccine protection against acquisition of neutralization-resistant SIV challenges in rhesus monkeys

Preclinical studies of human immunodeficiency virus type 1 (HIV-1) vaccine candidates have typically shown post-infection virological control, but protection against acquisition of infection has previously only been reported against neutralization-sensitive virus challenges. Here we demonstrate vaccine protection against acquisition of fully heterologous, neutralization-resistant simian immunodeficiency virus (SIV) challenges in rhesus monkeys. Adenovirus/poxvirus and adenovirus/adenovirus-vector-based vaccines expressing SIV(SME543) Gag, Pol and Env antigens resulted in an 80% or greater reduction in the per-exposure probability of infection against repetitive, intrarectal SIV(MAC251) challenges in rhesus monkeys. Protection against acquisition of infection showed distinct immunological correlates compared with post-infection virological control and required the inclusion of Env in the vaccine regimen. These data demonstrate the proof-of-concept that optimized HIV-1 vaccine candidates can block acquisition of stringent, heterologous, neutralization-resistant virus challenges in rhesus monkeys.