The use of databases,data mining and immunoinformatics in vaccinology: where are we?

Introduction: Vaccinology has evolved from a sub-discipline focussed on simplistic vaccine development based on antibody-mediated protection to a separate discipline involving epidemiology, host and pathogen biology, immunology, genomics, proteomics, structure biology, protein engineering, chemical biology, and delivery systems. Data mining in combination with bioinformatics has provided a scaffold linking all these disciplines to the design of vaccines and vaccine adjuvants.

Areas covered: This review provides background knowledge on immunological aspects which have been exploited with informatics for the in silico analysis of immune responses and the design of vaccine antigens. Furthermore, the article presents various databases and bioinformatics tools, and discusses B and T cell epitope predictions, antigen design, adjuvant research and systems immunology, highlighting some important examples, and challenges for the future.

Expert opinion: Informatics and data mining have not only reduced the time required for experimental immunology, but also contributed to the identification and design of novel vaccine candidates and the determination of biomarkers and pathways of vaccine response. However, more experimental data is required for benchmarking immunoinformatic tools. Nevertheless, developments in immunoinformatics and reverse vaccinology, which are nascent fields, are likely to hasten vaccine discovery, although the path to regulatory approval is likely to remain a necessary impediment.     

Increased prevalence of familial autoimmunity in simplex and multiplex families with juvenile rheumatoid arthritis

OBJECTIVE: To determine if the prevalence of autoimmunity among relatives of patients with juvenile rheumatoid arthritis (JRA) is greater than that among relatives of healthy volunteer control subjects. METHODS: Interviews were used to obtain histories of the following disorders among living first- and second-degree relatives of 110 patients and 45 controls: alopecia areata, ankylosing spondylitis, dermatomyositis, Graves' disease, Hashimoto thyroiditis, insulin-dependent diabetes mellitus, inflammatory bowel disease, iritis, JRA, multiple sclerosis, psoriasis, RA, systemic lupus erythematosus, and vitiligo. Chi-squares, odds ratios (ORs), and 95% confidence intervals (95% CIs) were calculated. Families of 23 JRA affected sibpairs were interviewed subsequently. RESULTS: There were no significant differences between patients and controls with regard to age, sex, ethnicity, or family size. Patients had 1,228 relatives and controls had 496 relatives. Of all the relatives of the patients, 155 had at least 1 autoimmune disorder, compared with 20 relatives of the controls (12.6% versus 4.0%; OR 3.4 [95% CI 2.1-5.7], P < 0.000001). The prevalence of autoimmunity was increased in first-degree and in second-degree relatives of patients (16.1% and 10.6%, respectively). The prevalence of Hashimoto thyroiditis was significantly higher in the relatives of patients (OR 3.5 [95% CI 1.6-7.9], P = 0.0008). The prevalences of other disorders were not significantly different. JRA affected sibpair families had an increased prevalence of autoimmunity (15.0%). A history of arthritis was found significantly more frequently in the JRA affected sibpair families, but not in the simplex families. CONCLUSION: These data demonstrate that the prevalence of autoimmunity is significantly higher among first- and second-degree relatives of JRA patients. This suggests that clinically different autoimmune phenotypes may share common susceptibility genes, which may act as risk factors for autoimmunity.     

Autologous right atrial patch for closure of atrial septal defect

BACKGROUND: Prosthetic or pericardial patches used for the closure of atrial septal defects are associated with infrequent but definite problems. As an alternative, we used a right atrial free-wall patch in 12 patients, 7-54 years of age. METHODS AND RESULTS: The presence of a large secundum atrial septal defect (n=2). associated mitral valve regurgitation (n=7), primum atrial septal defect (n=2) and sinus venosus defect (n=1) necessitated the use of a patch. The mitral valve was repaired in 9 patients (including 2 with a primum defect). One patient with a primum defect who was in congestive heart failure preoperatively died after 3 weeks due to refractory ventricular fibrillation. The remaining patients were discharged 5 to 7 days post procedure. No flow was detected across the septal patch on predischarge echocardiography. One patient underwent reoperation for failed mitral valve repair one month postprocedure. At reoperation, the patch was found to be intact with normal texture and without any suture dehiscence. Histopathological examination of the explanted patch revealed viable endothellum and subendothelial muscle on both surfaces of the patch. Follow-up ranged from 6 to 36 months. Echocardiography performed after 6 to 32 months post procedure showed an intact patch with no residual defect. All the patients are in sinus rhythm. Holter monitoring performed in 6 patients was normal in all of them. Electrophysiological study was performed in 2 patients using a mapping catheter 4 and 6 months post-procedure, respectively, and recorded normal atrial potentials from the site of the patch. CONCLUSIONS: The use of an autologous free right atrial wall as a patch for atrial septal defect closure is a viable option.     

Cationic peptides neutralize Ox-LDL,prevent its uptake by macrophages,and attenuate inflammatory response

Objective

Apolipoprotein A1 (ApoA1) and apolipoprotein E (ApoE) mimetic peptides have attracted attention due to their ability to reduce atherosclerosis and exhibit antioxidant, anti-inflammatory, and hypolipidemic properties. In this study, we tested whether three distinct and unrelated cationic peptides would inhibit the oxidation of lipoproteins and whether they would counteract and neutralize the negatively charged modified lipoproteins, inhibit their uptake and inflammation by macrophages.

Methods and results

5F-mimetic peptide of ApoA1, LL27 derived from the anti-microbial peptide hCAP, and a human glycodelin derived peptide were commercially synthesized. We noted that these three distinct cationic lysine-rich peptides, two of which were unrelated to any known apolipoproteins, inhibited copper-mediated oxidation of lipoproteins and reduced lipid peroxides in a lysine dependent manner. The peptides also retarded the electrophoretic mobility of previously oxidized LDL and acetylated LDL by virtue of their net positive charge. Pre-incubation of peptides with modified lipoproteins reduced the uptake of the latter by macrophages, thus preventing the formation of foam cells. The cationic peptides inhibited oxidized LDL (Ox-LDL)-induced inflammatory response both in vitro and in vivo.

Conclusion

Based on these results, we suggest that in addition to the well known mimetic peptides, other suitable cationic peptides may be of use for controlling Ox-LDL mediated inflammation and atherosclerotic progression.     

Improved Sensitivity for Molecular Detection of Bacterial and Candida Infections in Blood

The rapid identification of bacteria and fungi directly from the blood of patients with suspected bloodstream infections aids in diagnosis and guides treatment decisions. The development of an automated, rapid, and sensitive molecular technology capable of detecting the diverse agents of such infections at low titers has been challenging, due in part to the high background of genomic DNA in blood. PCR followed by electrospray ionization mass spectrometry (PCR/ESI-MS) allows for the rapid and accurate identification of microorganisms but with a sensitivity of about 50% compared to that of culture when using 1-ml whole-blood specimens. Here, we describe a new integrated specimen preparation technology that substantially improves the sensitivity of PCR/ESI-MS analysis. An efficient lysis method and automated DNA purification system were designed for processing 5 ml of whole blood. In addition, PCR amplification formulations were optimized to tolerate high levels of human DNA. An analysis of 331 specimens collected from patients with suspected bloodstream infections resulted in 35 PCR/ESI-MS-positive specimens (10.6%) compared to 18 positive by culture (5.4%). PCR/ESI-MS was 83% sensitive and 94% specific compared to culture. Replicate PCR/ESI-MS testing from a second aliquot of the PCR/ESI-MS-positive/culture-negative specimens corroborated the initial findings in most cases, resulting in increased sensitivity (91%) and specificity (99%) when confirmed detections were considered true positives. The integrated solution described here has the potential to provide rapid detection and identification of organisms responsible for bloodstream infections.     

Drug eluting biliary stents to decrease stent failure rates: A review of the literature

Biliary stenting is clinically effective in relieving both malignant and non-malignant obstructions. However, there are high failure rates associated with tumor ingrowth and epithelial overgrowth as well as internally from biofilm development and subsequent clogging. Within the last decade, the use of prophylactic drug eluting stents as a means to reduce stent failure has been investigated. In this review we provide an overview of the current research on drug eluting biliary stents. While there is limited human trial data regarding the clinical benefit of drug eluting biliary stents in preventing stent obstruction, recent research suggests promise regarding their safety and potential efficacy.     

Effect of a spinal cord photolesion injury on catalase

Ischemic injury to the spinal cord results in cell and tissue damage. Oxygen free radicals have been implicated in post-ischemic cell injury and death while free radical scavengers like superoxide dismutase and catalase are associated with an amelioration of ischemic injury. Measurement of catalase enzyme activity or protein in ischemic tissue presents mechanical problems due to extensive tissue destruction. Therefore, we looked at the effects of a photochemical lesion (which reproduces ischemic injury) on the levels of catalase mRNA in the spinal cord tissues of rodents under various experimental conditions. A significant depletion in the levels of catalase mRNA was observed in the spinal cord tissues of rats that received a severe lesion and were sacrificed 6 days post-lesion, while levels of catalase mRNA in the spinal cord tissues of similarly lesioned rats sacrificed 14 days post-lesion showed a return to control values.