The evaluation of immune responses to hepatitis B vaccination in diabetic and non-diabetic haemodialysis patients and the use of tetanus toxoid

Aim: The aim of this study was to investigate whether haemodialysis (HD) patients suffering from diabetes mellitus could be considered at risk for the development of the protective antibodies to hepatitis B (HB) vaccination and, to evaluate the effectiveness of tetanus toxoid (TT) administrated 2 days before HB vaccination. Methods: Forty-nine HD patients were divided into two groups: group A (19 diabetic patients) and group B (30 non-diabetic patients). A dose of 40 μg recombinant HB vaccine was injected intramuscularly to the patients at 0, 1, 2 and 6 months. Results: After the completion of the course, the patients in group A were found to have a lower protective antibody rates than the patients in group B (57.8% vs 70%) (P > 0.05). After the administration of additional booster doses during 12 months, the protective antibody to hepatitis B surface antigen (HBsAb) levels were detected in 78.9% and 96.6% of the patients in group A and group B, respectively (P > 0.05). The patients not having protective HBsAb levels were administered TT and HB vaccines, and after course, all of them have produced protective HBsAb levels. Conclusion: The present study showed that diabetic patients on HD may carry a greater risk of not seroconverting than non-diabetic ones for antibody response to HB vaccination. The use of TT 2 days before HB vaccination may be a useful and effective method of enhancing the immune response to HB vaccination, especially in the patients with diabetes mellitus on HD.     

Hypersensitivity to the diphtheria component in the Di-Te-Pol vaccinene. A type I allergic reaction demonstrated by basophil histamine release

We describe a two year-old multiallergic boy who developed generalized urticaria after the third Di-Te-Pol vaccination. A Type I reaction to the vaccine was demonstrated by performing basophil histamine release to the complete vaccine. Further, we found that the reaction could be exclusively ascribed to Diphtheria Toxoid whereas no release was observed by the Polio and Tetanus component. The latter result was confirmed since no specific IgE to Tetanus Toxoid could be demonstrated.     

Response to vaccination against tetanus in chronic haemodialysed patients.

We studied the response to vaccination against tetanus and the changes in the antibody titers 6 months after this vaccination in 66 haemodialysed patients with chronic renal failure. We also investigated the factors that may affect the quality of this immune response. After the booster injection 96.5% of patients had antitetanus antibody titres considered to be protective (0.06 HU/ml). However, the titre of these antibodies rapidly declined and after 6 months, only 62% of the haemodialysed patients had a titre greater than 0.06 HU/ml. Among the different factors considered, only age significantly impaired or reduced the immune response. In addition, the acquisition of protection against tetanus was independent of the response to vaccination against hepatitis B in the same subjects. This study showed the efficacy and safety of vaccination against tetanus in hemodialysed patients, though the antibody titres should be assayed several months after vaccination to confirm the persistence of immunization.     

Structure and Protective Capacity of Tetanus and Diphtheria Antibodies Produced During Human Pregnancy and Transferred to New-Born

PROBLEM: The structure and protective activity of antibodies against tetanus (anti-T) and diphtheria (anti-D), produced during human pregnancy and transferred to new-born, was studied. METHOD: Antibody levels were measured by ELISA in non-pregnant women (control group), primiparae, and multiparae, and in their children. The proportion of symmetric and asymmetric IgG molecules was determined and their respective protective capacity evaluated. RESULTS: The quantity of asymmetric anti-T and anti-D antibodies in mothers at the time of delivery was roughly four- and three-fold that of the control group, respectively, dropping significantly 1 month later. A similar proportion of these antibodies was observed in the new-born. The lower neutralizing capacity of asymmetric molecules was demonstrated in vivo. CONCLUSION: Results show that during pregnancy there is a modulation of the immune response with an increase in the production of asymmetric molecules of lower protective capacity.     

α‐Galactosylceramide stimulates splenic lymphocyte proliferation in vitro and increases antibody production in vivo in late neonatal‐age mice

The neonatal stage is characterized by weak responses to various infections and vaccines, thus the development of efficient formulas to improve vaccine effectiveness is of high priority. The glycolipid alpha galactosylceramide (αGalCer) is known as a potent immune modulator due mainly to natural killer (NK) T cell activation. Using a mouse tetanus toxoid (TT) immunization model, we observed that neonatal mice given αGalCer at the time of primary immunization on postnatal day (pnd) 17 had a significantly higher TT‐specific immunoglobulin (Ig)M response as well as a memory IgG response, while αGalCer given on pnd 7 resulted in only marginal boosting. Consistently, immunostaining of the spleen sections from αGalCer‐treated pnd 17 immunized neonates showed a higher number of Ki67⁺ cells in the splenic germinal centre area, suggesting a stronger response after immunization. In‐vitro kinetic studies revealed that spleen cells from newborn to pnd 7 neonates did not respond to αGalCer stimulation, whereas cell proliferation was increased markedly by αGalCer after pnd 7, and became dramatic around neonatal pnd 17–18, which was accompanied by increased B, T and NK T cell populations in the spleen. In addition, in pnd 17 spleen cells, αGalCer significantly stimulated the production of NK T cytokines, interleukin (IL)‐4 and interferon (IFN)‐γ, and promoted the proliferation of CD23⁺ B cells, a subset of B cells enriched in germinal centres. These data suggest that αGalCer is an effective immune stimulus in the late neonatal stage, and thus may be useful in translational studies to test as a potential adjuvant to achieve a more efficient response to immunization.     

20％的硫酸镁在成人重症破伤风中的治疗作用

目的 探讨20％的硫酸镁治疗成人重症破伤风的安全性及有效性.方法 对2005年4月- 2010年10月收治的27例成人重症破伤风住院病例行回顾性分析.结果 血镁超过4 mmol/L者2例(2/27,7.4％);气管切开者25例(25/27,92.6％),机械通气22例(22/25,88.0％),机械通气时间为4～16d,平均(7.5±3.7)d;肺部感染25例(25/27,92.6％);死亡4例(4/27,14.8％);治愈23例(23/27,85.2％),住院时间25～48 d,平均(32.2±18.8)d.结论 20％的硫酸镁治疗成人重症破伤风安全,可有效控制肌肉强直、抽搐和自律性不稳定,以减少安定和氯丙嗪等镇静药的用量,操作简单,价格便宜,易于在临床推广.     

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.     

New trends in the management of tetanus

The prevalence of tetanus reflects a failure of immunization. Prompt diagnosis and prediction of severity are crucial for the prevention of early lifethreatening complications and the institution of appropriate management. The current symptomatic treatment of heavy sedation, paralysis and artificial ventilation for 3–5 weeks for moderate and severe tetanus, is, even in the best centers, still associated with unacceptably high mortality, due to the disease and complications of the therapy itself. It is especially inappropriate for the developing world where intensive care resources are minimal. New options reported to avoid artificial ventilation and sedation are dantrolene (Dantrium^®, Procter and Gamble Pharmaceuticals), baclofen (Lioresal^®, Novartis) and magnesium. Magnesium therapy has the advantages of controlling spasms and sympathetic over activity without sedation. This simplifies nursing care and minimizes the need for ventilatory support except in the very severe disease and the elderly. Magnesium is recommended as the first-line therapy in tetanus.