流行性出血灭活疫苗二针与三针接种效果的比较

本文研究人体接种流行性出血热灭活疫苗总量为三毫升时,比较观察分三次接种和分二次接种的反应及免疫效果。试验分三组进行,第一组根据常规方法０、７、２８天免疫三针,每针１毫升;第二组０、２８天免疫二针,每针１．５毫升;第三组０、２８天免疫二针,和一针２毫升,第二针１毫升。结果三组均未发生全身或局部的不良反应,未针１５－３０天,采血测定ＥＨＦ中和抗体,阳转率分别为８７．１％、７９．４％和７６．６％经统计处     

国产重组酵母乙型肝炎疫苗接种小学生的3年免疫效果观察

本文报告对２５８ 名小学生应用０、１、６ 月程序,接种２ 批国产酵母疫苗（５ μｇ／０．５ ｍ ｌ）,１ 批Ａｍ ｇｅｎ 酵母疫苗（１０ μｇ／ｍ ｌ）,１ 批Ｍ ＳＤ 酵母疫苗（５ μｇ／０．５ ｍ ｌ）的小学生免后３ 年（（Ｔ３６）效果观察。结果表明,Ｔ３６ 时抗体 ＧＭＴ（几何平均滴度）,Ａｍ ｇｅｎ 疫苗组（１４５．７５）显著高于 ２ 批国产疫苗（９２．１１、８３．５２）和Ｍ．Ｓ．Ｄ 苗组（７４．６２）,抗体ＧＭＴ 峰值显著低于Ａｍ ｇｅｎ 和Ｍ ．Ｓ．Ｄ 苗的２ 批国产酵母疫苗,与Ｍ．Ｓ．Ｄ 苗抗体ＧＭＴ 水平无显著差异（Ｐ＞ ０．０５）。抗体阳转率间各疫苗组均无显著差异（９３．１０％ ～７４．１４％ ）。本次随访结果表明,采用０,１,６ 免疫程序,国产酵母疫苗免后３ 年的抗体阳转率和抗体ＧＭＴ水平不低于进口同类酵母疫苗的水平。     

厌氧—1号活菌制剂对高脂血症小鼠模型的影响

本实验应用血脂检测及肠道菌群检查法,探讨了对人工高血脂症小鼠模型灌喂厌氧－１号活菌制剂后,小鼠血脂的变化。结果表明：每天给予模型小鼠厌氧－１号菌液（１亿活菌／毫升）０．５毫升,第７天血指即明显下降,与空白对照（自然恢复）组比有显著性差别,血清胆固醇（Ｐ＜０．０１）,降低率为４５．１％;高密度脂蛋白胆固醇（Ｐ＜０．０５）,降低率为４９．１％;甘清三酯（Ｐ＜０．０５）,降低率为１９．２％。到第１４天时血脂均已恢复至正常水平,而自然恢复组小鼠血清胆固醇水平仍比正常对照组略高。     

进口、国产人用狂犬病疫苗免疫后中和抗体水平测定

应用间接免疫荧光法（ＩＦＡ）检测１６６例不同产地（国产、进口）人用狂犬病疫苗免后血清抗体水平,结果：国产苗抗体阳转率为９５．４２％,ＧＭＴ为９．４８,进口苗抗体阳转率为６２．８５％,ＧＭＴ为４．３５。经统计学处理,二者差异有非常显著性意义（Ｘ２＝２８．６１Ｐ＜０．００５）,初步提示了国产的（浓缩）原代地鼠肾组织培养狂犬病疫苗比某进口ＶＥＲＯ细胞狂犬病疫苗免疫效果要好,是一种高效、安全、价格便宜的预防狂犬病免疫制品     

戊型肝炎病毒(HEV)合成肽及基因重组抗原免疫反应性研究

用ＯＲＦ２、ＯＲＦ３合成肽抗原（１～１０号）及基因工程重组的ＯＲＦ２抗原（１和２号）分别建立了酶联免疫方法（ＥＩＡ）,检测６０份戊型肝炎病人血清中ＨＥＶＩｇＧ及ＩｇＭ１０个合成肽抗原（Ｓｐ１－Ｓｐ１０）及２个重组抗原（Ｒｅ１、Ｒｅ２）,均和ＨＥＶ阳性血清发生特异反应,但阳性率和反应强度差别很大。以Ｒｅ１（ＯＲＦ２,４０２～６６０）检测的抗体阳性率最高,为９６．７％（５８／６０）;Ｓｐ６（ＯＲＦ３,８８～１２３）次之,为９３．３％（５６／６０）;以上两种抗原混合使用阳性率为１００％（６０／６０）。Ｓｐ６、Ｒｅ１及这两种抗原混合使用检测抗ＨＥＶＩｇＭ,阳性率分别为１８．３％（１１／６０）、６６．７％（４０／６０）和６６．７％（４０／６０）。研究结果表明：合成肽６号（Ｓｐ６）及重组抗原１号（Ｒｅ１）是制备戊肝抗体诊断试剂的理想抗原。     

不同预处理方法对大麦花药－花粉培养的影响

研究了甘露醇预处理的适应性以及ｐＨ值对甘露醇预处理效果的影响;并首次将山梨醇预处理应用到大麦花药培养中,获得理想的实验结果。第一,采用甘露醇预处理,１７种材料平均愈伤组织诱导率为２０．６７块／花药,绿苗产量为２．４６株／花药。第二,甘露醇预处理溶液的ｐＨ值不同,其预处理的效果也不同。其中,愈伤组织诱导率和绿苗产量均以ｐＨ５．６最高。第三,不同浓度（０．１—０．５ｍｏｌ／Ｌ）的山梨醇预处理３天绿苗产量差异不显著;但同一浓度（０．３ｍｏｌ／Ｌ）山梨醇预处理不同天数（１—７天）绿苗产量差异极显著,以３天处理效果最好,绿苗产量是对照的５１．２倍。     

香蕉试管苗黄瓜花叶病毒检疫检验技术研究

建立了香蕉试管苗黄瓜花叶病毒ＤＡＣ－ＥＬＩＳＡ检测技术。应用０．１ｍｏｌ／Ｌ磷酸盐缓冲液（ｐＨ７．２,内含１％ＮａＤＩＥＣＡ）作为样品制备缓冲液,检测灵敏度可达到１／５１２０（稀释度）。两年来检测了１２８７个样品,香蕉试管苗生产繁殖材料的带毒率为２．８％。     

液化沙雷氏菌胞外脂肪酶产生条件的研究

新分离的一株液化沙雷氏菌（Ｓｅｒｒａｔｉａｌｉｑｕｅｆａｃｉｅｎｓ）能产生大量胞外碱性脂肪酶,本文在摇瓶发酵水平上考察了培养基组成、培养条件等因素对其生成脂肪酶的影响。在优选条件下,即培养基组成为（％）玉米油１．２５,豆饼粉２．０,蛋白胨１．０,酵母膏０．２,Ｋ_２ＨＰＯ_４０．２,ＭｇＳＯ_４·７Ｈ_２Ｏ０．１,初始ｐＨ为７．２５时,２８℃,１５０ｒ／ｍｉｎ旋转摇床振荡培养４０ｈ,该菌株的发酵液酶活达到４３ｕ／     

兔2—细胞胚胎电融合及其融合胚体外发育的研究

本文对兔２－细胞胚胎卵裂球电融合制作四倍体胚胎的适宜条件进行了研究。电场强度为２．０千伏／厘米,脉冲时程为４０微秒时,可获得最好的融合率（６８．９－１００％,平均为７７．３％）及融合胚发育率（７４．５％）,该发育率与受精卵体外囊胚发育率（７９．３％）相似。对于电融合及融合胚发育,非电解质溶液（０．３ｍｏｌ／Ｌ甘露醇＋０．１ｍｍｏｌ／Ｌ氯化钙＋０．１ｍｍｏｌ／Ｌ硫酸镁）优于电解质溶液。融合后,７２．     

α肾上腺素能受体介导去甲肾上腺素促大鼠培养心肌细胞蛋白…

在无血清和含１．０％、５．０％血清培养的新生大鼠心肌细胞标本上,去甲肾上腺素（ＮＥ,２．０μｍｏ１／Ｌ）使细胞蛋白质含量（Ｌｏｗｒｙ法）分别比相应对照组增加４０％、２６％、１９％（Ｐ均＜０．０１）;细胞＾３Ｈ－亮氨酸参入量与ＮＥ浓度呈正性剂量依赖性,最大效应浓度为２０．０μｍｏ１／Ｌ;无血清培养体系中,０．２．２．０、２０μｍｏ１／Ｌ的ＮＥＷ使参入量分别比对照增加１７．８％、３５．３％、３７．７％     

Vaccination of small Asian mongoose (Herpestes javanicus) against rabies

Oral vaccination of free-ranging wildlife is a promising technique in rabies control. The small Asian mongoose (Herpestes javanicus) is an important reservoir of rabies on several Caribbean islands, but no vaccines have been evaluated for this species. Captive mongooses were used to test the safety and efficacy of the commercially licensed vaccinia-rabies glycoprotein (V-RG) recombinant vaccine and a newly developed genetically engineered oral rabies virus vaccine (SPBNGA-S). In one study using V-RG, no vaccinated animals developed detectable rabies virus-neutralizing antibodies, and all but one died after experimental challenge with rabies virus. In contrast, all animals given SPBNGA-S demonstrated seroconversion within 7 to 14 days after vaccination and survived rabies virus challenge. On the basis of these preliminary results indicating the greater efficacy of SPBNGA-S vs. V-RG vaccine, additional investigations will be necessary to determine the optimal dose and duration of vaccination, as well as incorporation of the SPBNGA-S vaccine into edible bait.     

Essential Role of T Cells in the Postexposure Prophylaxis of Rabies in Mice

Athymic nude mice injected intramuscularly with a street strain of rabies virus were not protected against rabies by postexposure administration of beta-propiolactone-inactivated rabies vaccine. In contrast, their normal littermates were completely protected from death by the same vaccination regimens. Nude mice did not produce IgG antibody as a result of the vaccine during the test period of 15 days, whereas normal littermates produced IgG antibody from day 5 after vaccination. However, passive immunization with antirabies hyperimmune mouse ascites showed that antibody was completely ineffective in protecting either nude mice or their normal littermates against rabies when given later than 2 days after infection. No significant difference in the induction of circulating interferon by the vaccination was noted in these mice. Passive transfer of immune spleen cells to nude mice immediately after infection resulted in 30 to 37.5% protection of the mice. Passively transferred spleen cells did not produce detectable amounts of neutralizing antibody in the recipient mice except on day 2 after the transfer, when a low level of antibody was detected. These observations demonstrate the essential role of T cells in the postexposure prophylaxis of rabies in mice. The mechanisms of the failure of postexposure vaccination in nude mice are discussed.     

Exhaustive Exercise Does Not Affect Humoral Immunity and Protection after Rabies Vaccination in a Mouse Model

Rabies is one of the most dangerous and widespread zoonosis and is characterized by severe neurological signs and a high case-mortality rate of nearly 100%. Vaccination is the most effective way to prevent rabies in humans and animals. In this study, the relationship between exhaustive exercise and the humoral immune response after immunization with inactivated rabies vaccine was investigated in a mouse model with one-time exhaustive exercise. It was found that compared with the mice with no exercise after vaccination, no significant differences were found in those with exhaustive exercise after vaccination on body-weight changes, virus-neutralizing antibody (VNA) titers, antibody subtypes and survivor ratio after lethal rabies virus (RABV) challenge. This study indicated that exhaustive exercise does not reduce the effects of the rabies inactivated vaccine.     

Evaluation of live trivalent vaccine of measles AIK-C strain, mumps Hoshino strain and rubella Takahashi strain, by virus-specific interferon-gamma production and antibody response

A trivalent measles-mumps-rubella live virus vaccine, containing measles AIK-C strain, mumps Hoshino strain, and rubella Takahashi strain, was evaluated in 229 children, aged 1 to 5 years. The vaccine induced a high seroconversion rate: 221 (98.7%) out of 224 subjects initially seronegative for measles virus, 167 (93.3%) out of 179 initially seronegative for mumps virus, and 212 (99.1%) out of 214 initially seronegative for rubella virus. It also induced a sufficient cellular immunity against each of the three viruses in over 90% of the subjects, as judged by virus-specific interferon-gamma (IFN-gamma) production. Virus-specific IFN-gamma production was observed 10 days after vaccination by stimulation with measles virus and rubella virus and 14 days after vaccination by stimulation with mumps virus. Mumps-virus-specific IFN-gamma production was observed in 7 out of 12 recipients without seroconversion for mumps virus. And measles-virus-specific IFN-gamma production was demonstrated in one out of three recipients without seroconversion for measles virus. A significant correlation was observed between the serum antibody and IFN-gamma production six weeks after vaccination for measles virus (r = 0.201, P less than 0.01) and for mumps virus (r = 0.174, P less than 0.05) but not for rubella virus (r = -0.045, P less than 0.05). The incidence of febrile reactions of greater than or equal to 37.5 C was quite low, 14.4%, and that of greater than or equal to 39 C occurred in only 1.3% of the recipients. These results suggested that the trivalent vaccine induced sufficient humoral and cellular immunity and yet resulted in no more untoward reaction than observed from the measles vaccine alone.     

Safety of lyophilized SAG2 oral rabies vaccine in collared lemmings

Fifteen collared lemmings (Dicrostonyx groenlandicus) were exposed to a lyophilized oral rabies vaccine designed to immunize wild carnivore populations. No animals contracted rabies from the vaccine as determined by the absence of clinical signs after 37 days and lack of rabies virus in brain tissue determined by the fluorescent antibody (FA) test. These results suggest that collared lemmings would not contract rabies if they ingested this lyophilized vaccine in the wild during bait vaccination programs for arctic foxes (Alopex lagopus).     

Antibody Response to a Human Diploid Cell Rabies Vaccine

An experimentally killed rabies virus vaccine prepared in a human diploid cell strain (WI-38)—Wyeth rabies vaccine (WRV)—was used by various injection schedules in two separate studies to define more closely in human volunteer subjects an effective vaccination schedule for pre- or postexposure immunization, particularly for donors of rabies-hyperimmune plasma. To permit valid comparisons between our results and those of other workers, antibody levels achieved were expressed in terms of international units (IU) per milliliter of serum. Antibody response of previously nonvaccinated persons were only modest after a single dose of WRV, never reaching a level higher than 0.80 IU/ml over a 56-day testing period. Moreover, antibody was not detected at 0.16 IU/ml before the 14th day, either after a single dose or after two doses given 3 days apart. The best response followed four doses of WRV given within 4 weeks. This schedule resulted in the highest rate of seroconversion to the ≥6 IU/ml antibody level required of potential rabies-immune plasma donors. Giving the first vaccine dose in aluminum hydroxide diluent did not enhance the antibody response. There was a definite suggestion in the various injection schedules that higher and more sustained antibody levels were reached when the interval between the first and second vaccine doses was longest. The greater immunogenicity of WRV as compared with duck embryo vaccine was best demonstrated by the fact that a single booster dose of duck embryo vaccine to previously vaccinated individuals resulted in only a sevenfold antibody rise during the following 56 days, whereas a booster dose of WRV elicited a 69-fold rise. Al(OH)₃ in the first dose of WRV had no effect, but the enhancing effect of a longer interval between vaccine doses was noted once again; 20 of 20 subjects who received three doses of WRV with 4 weeks between doses developed good levels of rabies antibody, and 19 exceeded 6 IU/ml.     

42例狂犬疫苗免疫后抗体水平监测

本文报告了42例狂犬疫苗免疫后抗体水平的监测,并将其抗体效价与性别、年令免疫的天数进行了比较,从几何平均滴度上看,抗体效价与性别、年令均无明显区别,而免疫后的天数,则直接影响着抗体水平的高低,提示:狂犬疫苗免疫后抗体水平的监测具有重要意义.     

Immunization of arctic foxes (Alopex lagopus) with oral rabies vaccine

Arctic foxes (Alopex lagopus) were successfully immunized against rabies using an orally-administered, liquid SAD-BHK21 live virus vaccine in a sausage bait. Immunization was determined by serologic response and by resistance to challenge with an arctic rabies virus strain. Virus was not shed in saliva following oral vaccination, indicating that arctic foxes would not infect other foxes after ingesting this vaccine. High antibody levels were present in all experimental foxes 2 wk following initial vaccination. A booster vaccination at 56 wk induced a significant serologic response within 1 wk, suggesting an anamnestic response but titers began to decline within 8 wk in most foxes. Foxes were observed for 16 mo following the challenge and exhibited no symptoms of rabies. The SAD-BHK21 rabies vaccine in a sausage bait system has a strong potential for vaccinating wild populations of arctic fox.     

Safety of the malaria vaccine candidate, RTS,S/AS01E in 5 to 17 month old Kenyan and Tanzanian Children

The malaria vaccine candidate, RTS,S/AS01(E), showed promising protective efficacy in a trial of Kenyan and Tanzanian children aged 5 to 17 months. Here we report on the vaccine's safety and tolerability. The experimental design was a Phase 2b, two-centre, double-blind (observer- and participant-blind), randomised (1∶1 ratio) controlled trial. Three doses of study or control (rabies) vaccines were administered intramuscularly at 1 month intervals. Solicited adverse events (AEs) were collected for 7 days after each vaccination. There was surveillance and reporting for unsolicited adverse events for 30 days after each vaccination. Serious adverse events (SAEs) were recorded throughout the study period which lasted for 14 months after dose 1 in Korogwe, Tanzania and an average of 18 months post-dose 1 in Kilifi, Kenya. Blood samples for safety monitoring of haematological, renal and hepatic functions were taken at baseline, 3, 10 and 14 months after dose 1. A total of 894 children received RTS,S/AS01(E) or rabies vaccine between March and August 2007. Overall, children vaccinated with RTS,S/AS01(E) had fewer SAEs (51/447) than children in the control group (88/447). One SAE episode in a RTS,S/AS01(E) recipient and nine episodes among eight rabies vaccine recipients met the criteria for severe malaria. Unsolicited AEs were reported in 78% of subjects in the RTS,S/AS01(E) group and 74% of subjects in the rabies vaccine group. In both vaccine groups, gastroenteritis and pneumonia were the most frequently reported unsolicited AE. Fever was the most frequently observed solicited AE and was recorded after 11% of RTS,S/AS01(E) doses compared to 31% of doses of rabies vaccine. The candidate vaccine RTS,S/AS01(E) showed an acceptable safety profile in children living in a malaria-endemic area in East Africa. More data on the safety of RTS,S/AS01(E) will become available from the Phase 3 programme.     

A mouse model of the pathogenesis and postexposure prophylaxis of rabies

A mouse model for the study of postexposure prophylaxis of rabies was established. Mice injected intramuscularly with a street strain of rabies virus were significantly protected from death by five daily 0.2-ml doses of inactivated rabies vaccine of chick embryo cell culture origin initiated immediately or 3 hr after infection. In these mice, a large amount of circulating interferon was induced as early as 1 hr after the first dose of vaccine and lasted until at least 12 hr but no such amount of interferon was induced by additional doses of vaccine. Serum antibody was first detected in the mice on day 6. It was noted that some of the surviving mice manifested an ataxia or paralysis of the legs. Increasing mortality rates were shown in mice treated with decreasing doses of the vaccine. Passive protection tests using concentrated IgG and IgM antibodies with equivalent neutralization titers showed that IgG antibody gave total protection when given 24 hr before the infection, while it was almost totally ineffective in reducing the mortality when given 2 days or more after infection. IgM antibody did not protect the mice even when given 24 hr before infection. These results suggest that interferon production is more important than antibody production in the initial stages of protection by postexposure vaccination. However, the mechanisms of postexposure prophylaxis in this model could not be explained only by the interferon produced by the vaccine and the possible contributions of additional mechanisms were suggested.