Immunological aspects of exposure to emissions from burning coal of high beryllium content

An epidemiological study was conducted on groups of people exposed occupationally (45 persons) and nonoccupationally (36 persons) to the combustion products of coal containing a comparatively high concentration of beryllium. The concentration of beryllium in the working atmosphere ranged between 30 and 800 × 10^?5 mg × m^?3; in the town S, dwelling place of a nonoccupationally exposed cohort between 0.39 and 1.68 × 10^?5 mg × m^?3. A group of 100 subjects who had no occupational contact with beryllium and other industrial toxic agents, and lived outside of the polluted region served as control cohort. In all examined persons the main classes of immunoglobulins and autoantibodies (lung, heart, liver, spleen, thyroid gland, suprarenals, and native DNA) and antibodies against nuclear (ANA) and mitochondrial (AMA) antigens (obtained from the lungs of intact and of experimental berylliosis rats) were determined. In both exposed groups elevated levels of IgG and IgA and increased concentrations of autoantibodies were found in comparison with the control cohort of people. Specific AMA and ANA were also found in both the exposed groups, with higher values in women. The demonstrated immunological changes in humoral immunoreactivity might be considered as signs of beryllium exposure. In the discussion the authors emphasize the increasing importance of immunological aspects in the study of environmental pollution.     

A long-term follow-up of workers exposed to beryllium

ABSTRACT The relationship of features of beryllium disease to the estimated exposure to beryllium has been investigated over a 30-year period at a factory manufacturing beryllium products. The factory opened in 1952. Of the 146 men who had worked there for more than six months up to 1963, 89% were seen at that time and were followed up in 1973. The nine who continued to work in the factory and those who were engaged subsequently were examined in 1977. On each occasion a clinical interview, occupational history, chest radiograph, and assessment of lung function were carried out. The findings of the main survey were related to the beryllium content of the dust measured by mass spectrometry for 1952-60 when over 3000 determinations were made. In no part of the plant did the estimated average daily exposure exceed 2 μg m^-3, and only 9% of individual determinations exceeded this level. Twenty determinations exceeded 25 μg m^-3. During the period under review, four men developed the clinical, radiographic, and physiological features of beryllium disease. Two men acquired abnormal chest radiographs consistent with beryllium disease but without other features, and one developed probable beryllium disease despite the diagnosis not being confirmed at necropsy. The affected men were all exposed to beryllium oxide or hydroxide but in a wide range of estimated doses. In six the changes developed after exposure had ceased; trigger factors including patch testing may have contributed to their illness. Seventeen men recalled episodes of brief exposure to high concentrations of dust, two developed pneumonitis from which they recovered completely, and one developed chronic beryllium disease after a further 23 years' exposure. In subjects without clinical or radiographic evidence of disease no convincing evidence was obtained for any association between the lung function and the estimated exposure to beryllium.     

BHV-1 DNA vaccination: effect of the adjuvant RN-205 on the modulation of the immune response in mice

It is well documented that adjuvants improve the immune response generated by traditional viral vaccines, but less is known about the effects of adjuvants on the immune response elicited by DNA vaccines. In this study, we have investigated the use of RN-205 (immunomodulator containing a membrane rich in lipopolysaccharide from gram-negative bacteria) as an adjuvant and analyzed the humoral and cellular specific immune responses elicited by DNA vaccines based on the bovine herpesvirus-1 (BHV-1) glycoprotein D (gD). The comparison of the antibody response induced in mice by a mixture of the three different versions of DNA gD (membrane-anchored, secreted and cytosolic) formulated with or without RN-205 showed that the immunomodulator did not affect the total specific humoral response. The cellular immune response induced in mice immunized with vaccines plus RN-205 was higher than that obtained in mice vaccinated without RN-205, not only in the indexes of proliferation tests but in the number of IL-4 and gammaIFN secreting cells. When total spleen cells were marked with specific monoclonal antibodies against surface markers, a significant increase in the macrophage population of all the groups receiving RN-205 was observed. CD8 and CD4 positive cells were also increased but to a lesser extent. Our results indicate that the incorporation of RN-205 into DNA vaccines induces an increase of the cellular specific immune response in mice.     

Beryllium sensitization and disease among long-term and short-term workers in a beryllium ceramics plant

OBJECTIVE: Workers at a beryllium ceramics plant were tested for beryllium sensitization and disease in 1998 to determine whether the plant-wide prevalence of sensitization and disease had declined since the last screening in 1992; an elevated prevalence was associated with specific processes or with high exposures; exposure-response relationships differed for long-term workers hired before the last plant-wide screening and short-term workers hired since then. METHODS: Current workers were asked to complete a questionnaire and to provide blood for the beryllium lymphocyte proliferation test (BeLPT). Those with an abnormal BeLPT were classified as sensitized, and were offered clinical evaluation for beryllium disease. Task- and time-specific measurements of airborne beryllium were combined with individual work histories to compute mean, cumulative, and peak beryllium exposures for each worker. RESULTS: The 151 participants represented 90% of 167 eligible workers. Fifteen (9.9% of 151) had an abnormal BeLPT and were split between long-term workers (8/77 = 10.4%) and short-term workers (7/74 = 9.5%). Beryllium disease was detected in 9.1% (7/77) of long-term workers but in only 1.4% (1/74) of short-term workers (P = 0.06), for an overall prevalence of 5.3% (8/151). These prevalences were similar to those observed in the earlier survey. The prevalence of sensitization was elevated in 1992 among machinists, and was still elevated in 1998 among long-term workers (7/40 = 18%) but not among short-term workers (2/36 = 6%) with machining experience. The prevalence of sensitization was also elevated in both groups of workers for the processes of lapping, forming, firing, and packaging. The data suggested a positive relationship between peak beryllium exposure and sensitization for long-term workers and between mean, cumulative, and peak exposure and sensitization for short-term workers, although these findings were not statistically significant. Long-term workers with either a high peak exposure or work experience in forming were more likely to have an abnormal BeLPT (8/51 = 16%) than the other long-term workers (0/26, P = 0.05). All seven sensitized short-term workers either had high mean beryllium exposure or had worked longest in forming or machining (7/55 = 13% versus 0/19, P = 0.18). CONCLUSIONS: A plant-wide decline in beryllium exposures between the 1992 and 1998 surveys was not matched by a decline in the prevalence of sensitization and disease. Similar to findings from other studies, beryllium sensitization/disease was associated with specific processes and elevated exposures. The contrast in disease prevalence between long-term and short-term workers suggests that beryllium sensitization can occur after a short period of exposure, but beryllium disease usually requires a longer latency and/or period of exposure. The findings from this study motivated interventions to more aggressively protect and test workers, and new research into skin exposure as a route of sensitization and the contribution of individual susceptibility.     

TNF-alpha polymorphisms in chronic beryllium disease and beryllium sensitization

OBJECTIVE: Tumor necrosis factor-alpha (TNF-alpha) is a potent cytokine involved in normal immune functions. The aim of this study was to investigate if there is an association between chronic beryllium disease or beryllium sensitization and two variants of the TNF-alpha gene located at -308 and -238 called TNF-alpha-308*02 and TNF-alpha-238*02. METHODS: TNF-alpha-308 and TNF-alpha-238 genotyping was conducted in a large, population-based cohort consisting of 886 beryllium workers (92 individuals with chronic beryllium disease, 64 who were beryllium sensitized, and 730 individuals without sensitization or disease). RESULTS: The odds of chronic beryllium disease in the presence of at least one TNF-alpha-308*02 or TNF-alpha-238*02 allele was not significant (OR=1.0; 95% CI=0.7, 1.7 and OR=0.8; 95% CI=0.4, 1.6). This was true regardless of whether a worker was homozygous or heterozygous for TNF-alpha-308*02 or TNF-alpha-238*02. Similarly, neither allele was associated with sensitization (P>0.05). CONCLUSIONS: Unlike an earlier report, there was no association between these specific TNF-alpha alleles and either chronic beryllium disease or sensitization to beryllium.     

Assessment of personal airborne exposures and surface contamination from x-ray vaporization of beryllium targets at the National Ignition Facility

This article presents air and surface sampling data collected over the first two years since beryllium was introduced as a target material at the National Ignition Facility. Over this time, 101 experiments with beryllium-containing targets were executed. The data provides an assessment of current conditions in the facility and a baseline for future impacts as new, reduced regulatory limits for beryllium are being proposed by both the Occupational Safety and Health Administration and Department of Energy. This study also investigates how beryllium deposits onto exposed surfaces as a result of x-ray vaporization and the effectiveness of simple decontamination measures in reducing the amount of removable beryllium from a surface. Based on 1,961 surface wipe samples collected from entrant components (equipment directly exposed to target debris) and their surrounding work areas during routine reconfiguration activities, only one result was above the beryllium release limit of 0.2 µg/100 cm² and 27 results were above the analytical reporting limit of 0.01 µg/100 cm², for a beryllium detection rate of 1.4%. Surface wipe samples collected from the internal walls of the NIF target chamber, however, showed higher levels of beryllium, with beryllium detected on 73% and 87% of the samples during the first and second target chamber entries (performed annually), respectively, with 23% of the samples above the beryllium release limit during the second target chamber entry. The analysis of a target chamber wall panel exposed during the first 30 beryllium-containing experiments (cumulatively) indicated that 87% of the beryllium contamination remains fixed onto the surface after wet wiping the surface and 92% of the non-fixed contamination was removed by decontaminating the surface using a dry wipe followed by a wet wipe. Personal airborne exposures assessed during access to entrant components and during target chamber entry indicated that airborne beryllium was not present in workers' breathing zones. All the data thus far have shown that beryllium has been effectively managed to prevent exposures to workers during routine and non-routine work.     

Efficient augmentation of a long-lasting immune responses in HIV-1 gag DNA vaccination by IL-15 plasmid boosting

Cytokines are major regulators of the immune response, and have been used as adjuvants to improve vaccine potency. In this study, we investigated the adjuvant effects of interleukin (IL)-15 on improving the immunogenicity of human immunodeficiency virus (HIV)-1 gag DNA vaccine in Balb/c mice. During a 370-day follow-up, cellular and humoral immune responses in three separate cohorts of mice were monitored. These results were exemplified through: lymphocyte proliferation, induction of antigen-specific CD8(+) T lymphocytes, long-term production of specific antibodies, and proportion of differentiated memory CD8(+) T cells. These data revealed that just boost of IL-15 at day 8 after co-immunization induced more homeostatic cell proliferation, augmented proliferation frequency of IFN-gamma-secreting antigen-specific CD8(+) T lymphocytes, maintained the long-lasting humoral immune response and promoted the turnover of memory T cell precursors into central memory T cells. Taken together, our data demonstrated that a single IL-15 boosting can enhance both the humoral and cellular immune responses of the HIV-1 gag DNA vaccination. This novel boosting strategy may facilitate the application of IL-15 as an adjuvant for HIV vaccination.     

Surface modified liposomes for nasal delivery of DNA vaccine

The aim of the present work was to investigate the potential utility of glycol chitosan coated liposomes as nasal vaccine delivery vehicle for eliciting viral specific humoral mucosal and cellular immune responses. Plasmid pRc/CMV-HBs(S) encapsulated liposomes were prepared by dehydration-rehydration method and subsequently coated with glycol chitosan by simple incubation method. Liposomes were then characterized for their size, surface charge, entrapment efficiency, and ability to protect encapsulated DNA against nuclease digestion and for their mucoadhesiveness. The liposomes were then administered to mice in order to study their feasibility as nasal vaccine carriers. The developed liposomes possessed +9.8 mV zeta potential and an average vesicle size less than 1 microm and entrapment efficiency of approximately 53%. Following intranasal administration, glycol chitosan coated liposomes elicited humoral mucosal and cellular immune responses that were significant as compared to naked DNA justifying the potential advantage of mucosal vaccination in the production of local antibodies at the sites where pathogens enters the body.     

Nasal vaccination with r4M2e.HSP70c antigen encapsulated into N-trimethyl chitosan (TMC) nanoparticulate systems: Preparation and immunogenicity in a mouse model

In this study, the potential of N-trimethyl chitosan (TMC) nanoparticles as a carrier system for the nasal delivery of the r4M2e.HSP70c, as an M2e-based universal recombinant influenza virus vaccine candidate, was investigated in mice. The anti-M2e specific cellular and humoral immune responses were assessed and the protective efficacy against a 90% lethal dose (LD90) of influenza A/PR/8/34 (H1N1) in a mice model was evaluated.Our results showed that the intranasal immunization of mice with r4M2e.HSP70c+TMC rather than the control groups, r4M2e+TMC, r4M2e and PBS (Phosphate buffer saline), significantly elevated both longevity and serum level of the total M2e-specific IgG antibody with a significant shift in the IgG2a/IgG1 ratio toward IgG2a, induced a Th1 skewed humoral and cellular immune responses, increased IFN-γ, IgG, and IgA in the bronchoalveolar lavage fluid (BALF), and promoted the proliferation of peripheral blood lymphocytes with lower morbidity and mortality rate against viral challenge.In conclusion, based on evidence to our finding, nasal vaccination with r4M2e.HSP70c antigen encapsulated into N-Trimethyl Chitosan (TMC) nanoparticulate system showed to induce a long lasting M2e-specific humoral and cellular immune responses and also provided full protection against a 90% lethal dose (LD90) of the influenza virus A/PR/8/34 (H1N1). It seems, protective immunity following intranasal administration of r4M2e could be resulted by the cooperation of both adjuvants, TMC and HSP70c.     

A mortality study of workers at seven beryllium processing plants.

The International Agency for Research on Cancer (IARC) has found that the evidence for the carcinogenicity of beryllium is sufficient based on animal data but "limited" based on human data. This analysis reports on a retrospective cohort mortality study among 9,225 male workers employed at seven beryllium processing facilities for at least 2 days between January 1, 1940, and December 31, 1969. Vital status was ascertained through December 31, 1988. The standardized mortality ratio (SMR) for lung cancer in the total cohort was 1.26 (95% confidence interval [CI] = 1.12-1.42); significant SMRs for lung cancer were observed for two of the oldest plants located in Lorain, Ohio (SMR = 1.69; 95% CI = 1.28-2.19) and Reading, Pennsylvania (SMR = 1.24; 95% CI = 1.03-1.48). For the overall cohort, significantly elevated SMRs were found for "all deaths" (SMR = 1.05; 95% CI = 1.01-1.08), "ischemic heart disease" (SMR = 1.08; 95% CI = 1.01-1.14), "pneumoconiosis and other respiratory diseases" (SMR = 1.48; 95% CI = 1.21-1.80), and "chronic and unspecified nephritis, renal failure, and other renal sclerosis" (SMR = 1.49; 95% CI = 1.00-2.12). Lung cancer SMRs did not increase with longer duration of employment, but did increase with longer latency (time since first exposure). Lung cancer was particularly elevated (SMR = 3.33; 95% CI = 1.66-5.95) among workers at the Lorain plant with a history of (primarily) acute beryllium disease, which is associated with very high beryllium exposure. The lung cancer excess was not restricted to plants operating in the 1940s, when beryllium exposures were known to be extraordinarily high. Elevated lung cancer SMRs were also observed for four of the five plants operating in the 1950s for workers hired during that decade. Neither smoking nor geographic location fully explains the increased lung cancer risk. Occupational exposure to beryllium compounds is the most plausible explanation for the increased risk of lung cancer observed in this study. Continued mortality follow-up of this cohort will provide a more definitive assessment of lung cancer risk at the newer plants and among cohort members hired in the 1950s or later at the older plants. Further clarification of the potential for specific beryllium compounds to induce lung cancer in humans, and the possible contribution of other exposures in specific processes at these plants, would require a nested case-control study. We are currently assessing whether available industrial hygiene data would support such an analysis.     

The beryllium lymphocyte proliferation test: Relevant issues in beryllium health surveillance

BACKGROUND: The beryllium lymphocyte proliferation test (Be-LPT) measures beryllium-specific cellular immune response, and is useful in medical surveillance of beryllium sensitivity and chronic beryllium disease (CBD). METHODS: Current and former employees (n = 12,194) of 18 United States Department of Energy (DOE) sites were tested for beryllium sensitization at four laboratories with Be-LPT expertise. Beryllium sensitized individuals were offered evaluations for CBD. The sensitivity, specificity, and positive predictive value (PPV) of the Be-LPT were determined, as was inter- and intra-laboratory agreement. RESULTS: False positives were calculated to be 1.09%, with a laboratory range of 0.00-3.35% for the 10-year investigation. Be-LPTs performed on inter-laboratory split blood specimens from sensitized individuals showed a false negative rate of 31.7%. The intra-laboratory repeatability of abnormal Be-LPT results ranged from 80.4-91.9%. The sensitivity of the Be-LPT was determined to be 0.683, with a specificity of 0.969. The PPV of one abnormal Be-LPT was 0.253. CONCLUSIONS: The Be-LPT is efficacious in medical surveillance of beryllium-exposed individuals. The PPV of the Be-LPT is comparable to other widely accepted medical tests. Confirmation of an abnormal result is recommended to assure appropriate referral for CBD medical evaluation.     

Potent enhancement of cellular and humoral immune responses against recombinant hepatitis B antigens using AS02A adjuvant in healthy adults

Recombinant subunit protein vaccines generally elicit good humoral immune responses, weak helper T cell responses and no cytotoxic T cell responses. Certain adjuvants are known to enhance humoral and cellular immune responses. This study evaluated the humoral, CD4+ T helper and CTL responses induced by the recombinant SL* protein adjuvanted with AS02A in comparison with non-adjuvanted SL* in PBS in two groups of 15 healthy adult volunteers. The AS02A adjuvant contains monophosphoryl lipid A (MPL), QS21 and an oil in water emulsion. The adjuvanted vaccine induced fast and vigorous humoral and helper T cell responses of the Th1 type. Using a pool of overlapping 20mer peptides a cytotoxic response was detected in 6 out of 14 HLA-A2-positive (+) and HLA-A2-negative (-) recipients of the adjuvanted vaccine. All HLA-A2-positive subjects in the adjuvanted group and up to 30% of the subjects in the SL* PBS group displayed a CTL response against selected HLA-A2-restricted CD8+ T cell epitopes. The non-adjuvanted vaccine induced a very weak antibody response and no helper T cell responses. Local and general reactions were more frequently reported by AS02A recipients than in the non-adjuvanted group but the safety profile was considered acceptable. AS02A can be considered as a useful adjuvant that strongly enhances the cellular and humoral responses of subunit protein vaccines.     

Immunological tools for the assessment of both humoral and cellular immune responses in Foxes (Vulpes vulpes) using ovalbumin and cholera toxin B as an antigenic model

The immune response in the fox (Vulpes vulpes), despite the success of the oral rabies vaccine is not well characterized, and specific immunological tools are needed. To investigate both the humoral and cellular immune response, we used ovalbumin (OVA) and cholera toxin B (CTB) as an antigenic model to set-up ELISA and ELISPOT antibodies secreting cells (ASC) assays in the fox model. Identification of antibodies that cross-react with fox immunoglobulin was performed by Western blot, and their use was adapted for both the ELISA and ELISPOT ASC assay. The humoral and cellular specific immune responses were assessed after intra-muscular or intra-nasal immunization. Intra-muscular immunization resulted in the development of both cellular and humoral anti-OVA and anti-CTB responses in peripheral blood mononuclear cells (PBMCs). Immunization via the intra-nasal route resulted in the development of a cellular and humoral response against CTB in PBMCs. This immune response was confirmed using splenocytes from immunized animals by ELISPOT assay at euthanasia. Females immunized via the intra-nasal route developed specific anti-CTB IgM, IgA and IgG in vaginal fluids after the initial boost (day 26) showing that mucosal immunization produces a vaginal immune response in foxes. These immunological tools developed here are now available to be adapted to other antigenic models to facilitate further immune studies in foxes.     

人乳头瘤病毒16E7 DNA疫苗微针给药效果研究

目的 探讨DNA疫苗微针给药方法的有效性.方法 构建pcDNA3.1-HPV16E7重组质粒,在体外透皮条件下,观察pcDNA-HPV16E7皮肤透过量,再利用微针给药方式免疫BALB/c小鼠,分三组(实验组、空载体对照组、阴性对照组),每组10只,每2周免疫1次,共3次,每次免疫剂量为200 μg/只,对照组参照实验组进行,最后1次免疫后2周采血,分别分离血清和淋巴细胞,用间接免疫荧光试验检测小鼠的体液免疫功能,用淋巴细胞转化试验检测小鼠的细胞免疫功能.结果 体外透皮试验显示DNA疫苗微针给药可以透过皮肤,而且透过量随着时间的延长而逐步增加,在第30小时时可以达到0.738 19 mg/cm2;通过微针给药方法DNA疫苗可以诱导小鼠产生特异性抗体,淋巴细胞转化试验显示:实验组(平均淋巴细胞转化率为47.25%)和阴性对照组(平均淋巴细胞转化率为30.00%)之间比较,χ2=12.903,P＜0.001,差异有显著统计学意义;空载体组(平均淋巴细胞转化率为43.00%)和阴性对照组之间比较,χ2=7.292,P=0.007,差异有显著统计学意义;实验组和空载体组之间比较,χ2=0.817,P=0.366,差异无统计学意义.结论 HPV16E7 DNA疫苗经微针给药可以透过皮肤吸收并诱导小鼠产生体液免疫和细胞免疫反应.     

淋病奈瑟菌主要外膜蛋白DNA疫苗的构建及免疫效果观察

目的克隆淋病奈瑟菌孔蛋白IB型（PIB）基因并构建其真核表达载体pCI-PIB,了解pCI-PIB免疫接种后诱导小鼠特异性体液和细胞免疫反应的效果。方法采用聚合酶联反应（PCR）扩增淋病奈瑟菌主要外膜蛋白PIB全长基因片段（960bp）,构建表达PIB的真核表达载体pCI-PIB。pCI-PIB肌内注射免疫BALB／c小鼠65只,100μg/次／只,亲和素-生物素-过氧化酶复合物（ABC）法检测其中10只pCI-PIB免疫小鼠肌细胞中PIB的表达,酶联免疫吸附试验（ELISA）和特异性淋巴细胞增殖反应（MTT）法检测余下pCI-PIB免疫小鼠的特异性体液和细胞免疫应答效果。采用玻片凝集试验和补体溶菌试验检测pCI-PIB免疫小鼠血清的抗菌活性。结果PCR可扩增出预期大小的全长PIB基因片段（960bp）,与报道PIB基因序列（GenBank No：AF090801）比较,重组质粒pCI-PIB中目的插入片段的核苷酸序列同源性可达99．28％。免疫小鼠的肌细胞能摄取pCI-PIB并表达PIB。pCI-PIB免疫小鼠的血清中可产生较高效价的特异性IgG（1：4000）,并产生特异性T细胞增殖反应,增殖指数（4．031）明显高于对照组（1．127）（t=71．71,P〈0．05）。pCI-PIB免疫小鼠血清及阴道冲洗液均有凝集淋病奈瑟菌的作用,在补体参与下可杀灭细菌。结论本研究成功地构建了淋病奈瑟菌PIB基因重组真核表达载体pCI-PIB。pCI-PIB接种小鼠后可有效地引起特异性体液和细胞免疫反应,具有作为淋病奈瑟菌候选DNA疫苗的应用前景。     

Mycobacterium bovis BCG as a delivery system for the RAP-1 antigen from Babesia bovis

Babesia bovis is the causative agent of babesiosis, a tick-borne disease that is a major cause of loss to livestock production in Latin America. Vaccination against Babesia species represents a major challenge against cattle morbidity and mortality in enzootic areas. The aim of this study was to evaluate the capacity of Bacille Calmette-Guerin (BCG) to deliver the rhoptry associated protein (RAP-1) antigen of B. bovis and to stimulate specific cellular and humoral immune responses in mice. Two of five mycobacterial expression vectors efficiently expressed the antigen. These constructs were subsequently studied in vivo following three immunization protocols. The construct with the greatest in vivo stability proved to be the one that induced the strongest immune responses. Our data support the hypothesis that specific T lymphocyte priming by rBCG can be employed as a component of a combined vaccine strategy to induce long-lasting humoral and cellular immune responsiveness towards B. bovis and encourage further work on the application of rBCG to the development of Babesia vaccines.     

Surface area of respirable beryllium metal,oxide, and copper alloy aerosols and implications for assessment of exposure risk of chronic beryllium disease

The continued occurrence of chronic beryllium disease (CBD) suggests the current occupational exposure limit of 2 microg beryllium per cubic meter of air does not adequately protect workers. This study examined the morphology and measured the particle surface area of aerodynamically size-separated powders and process-sampled particles of beryllium metal, beryllium oxide, and copper-beryllium alloy. The beryllium metal powder consisted of compact particles, whereas the beryllium oxide powder and particles were clusters of smaller primary particles. Specific surface area (SSA) results for all samples (N=30) varied by a factor of 37, from 0.56 +/- 0.07 m(2)/g (for the 0.4-0.7 microm size fraction of the process-sampled reduction furnace particles) to 20.8 +/- 0.4 m(2)/g (for the 6 microm) to 20.8 +/- 0.44 m(2)/g (for the particle size fraction 相似文献   

Cell mediated and antibody immune response to inactivated hepatitis A vaccine

The humoral and cellular immune response to inactivated hepatitis A vaccine was investigated dynamically in a time elapse study over 1 year. Fourty-five healthy volunteers, seronegative for anti-HAV, were vaccinated with 1440 enzyme-linked immunosorbent assay units (EU) of formalin-inactivated hepatitis A virus following a 0--6-month schedule. Serum anti-HAV levels and HAV-specific proliferation of peripheral blood mononuclear cells were measured at several time points over a 26- and 28-week period after the first and second injection, respectively. Distinct B and T cell responses were determined within 14 days after primary vaccination. The booster vaccination-induced immediate peak levels for the humoral (anti-HAV GMC=5376mIU/ml) as well as the cellular (median Deltacpm=14173cpm) response.     

Immune tolerance against HBV can be overcome in HBV transgenic mice by immunization with dendritic cells pulsed by HBVsvp

In chronic Hepatitis B Virus (HBV) infection the function of dendritic cells (DC), T- and B-cells is impaired. DC vaccination is an option to overcome this. DC pulsed in vitro with HBV sub viral particles (HBVsvp) and used to immunize mice can activate HBV directed humoral and cellular immune responses. In the present study we vaccinated HBV transgenic mice as a model for chronic HBV infection and observed humoral and cellular immune responses. In these mice, the lacking immune response against HBV is mainly due to peripheral tolerance. HBVsvp, together with LPS as a co-activating molecule, were used for pulsing and in vitro activation of DC. HBV transgenic mice were injected with pulsed DC two times. Four weeks after DC vaccination humoral and cellular immune responses, viral antigen levels and liver histology were analyzed. DC vaccinated HBV-transgenic mice developed a strong HBV specific antibody and T-cell response after DC vaccination. Neither circulating HBV antigen levels nor viremia, however, were controlled. No liver damage was observed. These results demonstrate that in vitro activation of DC and loading with HBVsvp can overcome tolerance against HBV and reactivate B- and T-cell responses in HBV transgenic mice, but were not sufficient to lead to virus control in these mice. Vaccination using DC, the key players of cellular and humoral immunity, after in vitro reactivation promises to break tolerance against HBV and may help patients with chronic hepatitis B to clear the infection.