Production of 5–15 µm Diameter Alginate-Polylysine Microcapsules by an Air-Atomization Technique

A novel method of preparing small-sized microcapsules using a Turbotak air-atomizer is reported. Alginate-polylysine microcapsules containing Bacillus Calmette Guérin vaccine have been prepared by an adaptation of the method of Lim (1) which allows the manufacture of small-sized microcapsules. A Turbotak is used to spray sodium alginate solution into calcium chloride solution to form temporary calcium alginate microgel capsules. These temporary microgel droplets are subsequently cross-linked with polylysine to form permanent membranes. Microcapules in the size range of 5–15 µm have been produced which can be compared to an average diameter of 300 µm obtained by the method reported by Lim. The microcapsule size is dependent on the conditions of operation of the Turbotak and the concentration of the sodium alginate solution. Particles within the size range 5–15 µm can be reproducibly manufactured using the conditions of operation reported here. Other size ranges below the minimum of 300 µm reported by Lim are also feasible using this technique.     

A residual cystic lesion in acute disseminated encephalomyelitis

We report a case of acute disseminated encephalomyelitis (ADEM) with a residual cystic lesion on MRI. This seemed to be induced by Japanese encephalitis vaccination. Despite complete clinical improvement with high-dose steroid therapy, the cystic lesion has persisted for 3 years on MRI. There have been no previous reports of residual cystic lesions in ADEM. Received: 20 August 1999/Accepted: 11 November 1999     

Hepatitis B vaccination in preterm infants

AIM—To investigate the immunogenicity and safety of existing recommendations for hepatitis B vaccination in preterm infants.METHODS—Recombinant hepatitis B vaccine (H-B-VAX II, 5 µg per dose) was given to 85 preterm infants divided into two groups, using two different schedules. Forty four group A infants with birthweights of < 2000 g received three doses at 1, 2, and 7 months of age. Forty one group B infants with birthweights of ?2000 g received three doses at 0, 1, and 6 months of age.RESULTS—After vaccination, 42 infants from group A (95%) and 37 infants from group B (90%) developed protective levels of antibody. The final seropositive rate and the geometric mean concentration of hepatitis B surface antibody between the two groups were not significantly different. The immune response of preterm infants to hepatitis B vaccines was similar to that of term infants in a previous study.CONCLUSIONS—Preterm infants can be given hepatitis B vaccines using one of the above two different schedules, at a cutoff birthweight of 2000 g.     

Economic evaluation of pertussis prevention by whole-cell and acellular vaccine in Germany

Acellular pertussis vaccines are less reactogenic than whole cell pertussis vaccines, but they are also more expensive. Based on simulation models, we compared the costs and effects of three alternative pertussis vaccination strategies in German children to ”no prevention”: (1) vaccination with whole-cell vaccine at 45% coverage (vaccine efficacy 90%), (2) vaccination with acellular vaccine at 45% coverage (vaccine efficacy 85%), and (3) vaccination with acellular vaccine at 90% coverage. In the two low coverage scenarios expected annual savings in direct medical costs through prevention of disease were larger for whole-cell than for acellular vaccination (252 vs 216 million DM, respectively). Direct costs for treating the more important adverse events induced by whole-cell vaccination (16.9 million DM annually) did not outweigh the higher direct costs of pertussis infections not prevented with the acellular vaccine and the higher price of the acellular vaccine. However, vaccination with acellular pertussis vaccine rapidly becomes as cost saving as vaccination with whole-cell vaccine as soon as vaccination coverage can be raised from 45% to 52.5% with acellular vaccine. Acellular vaccination is also the superior alternative when considering indirect cost savings resulting from reduction in work-loss due to adverse events. Conclusion In our simulations, the most cost-effective pertussis prevention strategy was the use of an effective whole-cell vaccine with a high coverage rate. Introduction of the more expensive acellular pertussis vaccines becomes cost saving if at least a 7.5% increase in coverage is achieved. If also non-medical indirect costs to parents resulting from vaccine associated side-effects are accounted for, acellular vaccines may be more cost-effective also in countries with already high whole-cell vaccine coverage. Received: 22 April 1997 / Accepted in revised form: 21 November 1997     

A novel cancer vaccine composed of human-recombinant epidermal growth factor linked to a carrier protein: Report of a pilot clinical trial

Background: There is evidence of a relationship between epidermal growth factor (EGF) and tumor cell proliferation, such as the overexpression of EGF receptor (EGF-R) in different human tumors, which makes this system an interesting target for cancer treatment. Up to now, passive immunotherapy with monoclonal antibodies against the EGF-R has been assayed in clinics. Our approach consists of active immunotherapy with human EGF (hu-EGF). We conducted a pilot clinical trial to define the safety, toxicity and immunogenicity of vaccination with hu-EGF coupled to a carrier protein.Patients and methods: Ten patients with histologically-proven malignant carcinomas (colon, lung, stomach and prostate) in advanced clinical stages were enrolled. Patients were immunized twice (on days 0 and 15) with hu-EGF linked to either tetanic toxoid (TT, five patients) or P64k Neisseria Meningitidis recombinant protein (P64k, five patients), intradermically, using aluminium hydroxyde as adjuvant.Results: In both groups 60% of patients developed anti-EGF antibody titers without evidence of toxicity. Secondary reactions were very mild, limited to erythema and itching at the site of injection, which disappeared without medication.Conclusions: We conclude that the proposed vaccination with hu-EGF was well tolerated and that antibody titers against self EGF were developed. The results of this trial may be useful in the design of new clinical trials with higher dose immunization protocols and using more effective adjuvants.     

hCGβ-C3d3融合蛋白免疫BALB/c小鼠及其抗血清对hCG诱导鼠子宫增重的抑制效应

目的:通过分子佐剂C3d3增强hCGb避孕疫苗的免疫原性。方法:采用分子生物学技术以phCMV1为载体分别构建分泌型、带有6个组氨酸纯化标签的真核表达质粒phCMV1-6His-hCGb-C3d3和phCMV1-6His-hCGb,在CHO细胞中获得稳定、高效表达的重组蛋白,并用镍柱和凝胶过滤层析对其进行分离、纯化。分别用hCGb-C3d3融合蛋白和单用hCGb间隔4周两次免疫生育期雌性BALB/c小鼠,ELISA测定血清中抗hCGb抗体滴度,并对各组小鼠产生的抗血清拮抗hCG诱导的小鼠子宫增重效应进行比较。结果:C3d3使hCGb蛋白疫苗的免疫原性增强1 995倍,hCGb-C3d3融合蛋白免疫小鼠产生的抗血清具有很强的抑制小鼠子宫增重作用。结论:通过分子佐剂C3d3可以大幅提高机体对hCGb的体液免疫应答能力,hCGb-C3d3融合蛋白免疫小鼠产生的抗血清对hCG的生物学作用具有更强的抑制效应。     

乙肝疫苗治疗乙型肝炎病毒携带者疗效观察

目的：探讨治疗性乙型肝炎（乙肝）疫苗对乙型肝炎病毒（HBV）携带者免疫调节作用。方法：将78例乙肝病毒携带者随机分成乙肝疫苗治疗组（A组）40例和对照组（B组）38例。A组用乙肝疫苗加猪苓多糖注射液，乙肝疫苗5ug／次，每周两次皮下注射，连续6周，猪苓多糖注射液40rag／日，一次肌注，连续20天后停一周再肌注，20天为一个疗程。B组单独应用猪苓多糖注射液，方法同上。结果：疗程结束后15天进行血清病原学测定，A组治疗其HBeAg和HBV-DNA阴转率明显高于B组。结论：乙肝疫苗治疗有病毒持续复制的乙肝病毒携带者是可行的。     

Immunogenicity and side‐effects of the inactivated hepatitis A vaccine in periodic fever,aphthous stomatitis,pharyngitis, and adenitis patients

The aim of this study was to compare the immunogenicity and side‐effects of hepatitis A virus (HAV) vaccination between periodic fever, aphthous stomatitis, pharyngitis, and adenitis (PFAPA) patients and healthy controls who have not been previously exposed to HAV. A prospective observational study was carried out of 28 PFAPA patients and 76 controls who received two doses of the vaccine. Immunogenicity was expressed as seroconversion and seroprotection rates; mean HAV‐immunoglobulin G concentration was measured at 0, 1, 7 and 18 months. Side‐effects were defined as incidence of adverse events and the effect of vaccination on PFAPA symptoms. All participants were seronegative and seroconverted at 1 month. One month after primary vaccination, 92.9% of PFAPA patients and 77.6% of the controls attained seroprotection, while the rates increased to 100% and 96.1%, respectively, 1 month after the second dose. Seroprotection rates remained adequate 1 year after completion of vaccination. In conclusion, two doses of the inactivated HAV vaccine are well‐tolerated and effective in children with PFAPA.     

结肠癌细胞膜仿生铜基金属有机框架对DC的激活和促血管新生作用

目的：探讨结肠癌细胞膜包裹的铜基金属有机框架（MOF@CCM）的DC激活和促进血管新生的潜力。方法：首先构建 1,3,5-苯三甲酸铜（Ⅱ）铜基金属有机框架（HKUST-1）,在其外层包覆结肠癌CT26细胞膜,获得MOF@CCM,对其进行物理表征。 用CCK-8法研究MOF@CCM的生物相容性,流式细胞术分析MOF@CCM对DC2.4成熟比例的影响,以验证MOF@CCM激活免疫 细胞的潜力。通过血管生成实验验证MOF@CCM促人脐静脉内皮细胞（HUVEC）形成血管的能力。结果：成功制备了MOF@CCM, 透射电镜观察显示其形状近似圆形,具有明显的核壳结构。MOF@CCM的平均粒径为（150.5±7.89） nm,平均Zeta 电位为–（5.12± 1.67） mV。体外实验结果显示,与对照组相比,MOF@CCM能够显著提高DC2.4成熟的比例（P<0.01）。此外,MOF和MOF@CCM 均能促进HUVEC形成管状结构（P<0.05或P<0.01）,且细胞膜修饰对MOF的促血管新生作用没有影响。结论：制备的MOF@CCM 在所使用的剂量下具有良好的细胞相容性,能够显著促进DC2.4的成熟和促进HUVEC血管生成,有望成为抗结肠癌和促进组织修 复的双功能治疗平台。