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1.
Adjuvant Therapies in Food Immunotherapy.
Loh, W, Tang, M
Immunology and allergy clinics of North America. 2018;(1):89-101
Abstract
Finding an effective curative treatment for food allergy is a research priority. Although oral immunotherapy (OIT) is effective at inducing desensitization, the temporary nature of this effect and high rates of adverse reactions have highlighted a need for novel strategies to improve tolerance induction and safety. One such strategy is the use of an adjuvant together with food immunotherapy to either suppress allergic reactions and/or modulate the underlying allergic immune response. In particular, the use of bacterial adjuvants seems to be a promising means of enhancing OIT-induced sustained unresponsiveness and warrants further investigation.
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2.
Computer-aided prediction of antigen presenting cell modulators for designing peptide-based vaccine adjuvants.
Nagpal, G, Chaudhary, K, Agrawal, P, Raghava, GPS
Journal of translational medicine. 2018;(1):181
Abstract
BACKGROUND Evidences in literature strongly advocate the potential of immunomodulatory peptides for use as vaccine adjuvants. All the mechanisms of vaccine adjuvants ensuing immunostimulatory effects directly or indirectly stimulate antigen presenting cells (APCs). While numerous methods have been developed in the past for predicting B cell and T-cell epitopes; no method is available for predicting the peptides that can modulate the APCs. METHODS We named the peptides that can activate APCs as A-cell epitopes and developed methods for their prediction in this study. A dataset of experimentally validated A-cell epitopes was collected and compiled from various resources. To predict A-cell epitopes, we developed support vector machine-based machine learning models using different sequence-based features. RESULTS A hybrid model developed on a combination of sequence-based features (dipeptide composition and motif occurrence), achieved the highest accuracy of 95.71% with Matthews correlation coefficient (MCC) value of 0.91 on the training dataset. We also evaluated the hybrid models on an independent dataset and achieved a comparable accuracy of 95.00% with MCC 0.90. CONCLUSION The models developed in this study were implemented in a web-based platform VaxinPAD to predict and design immunomodulatory peptides or A-cell epitopes. This web server available at http://webs.iiitd.edu.in/raghava/vaxinpad/ will facilitate researchers in designing peptide-based vaccine adjuvants.
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3.
Pediatric Wells syndrome (eosinophilic cellulitis) after vaccination: A case report and review of the literature.
Yu, AM, Ito, S, Leibson, T, Lavi, S, Fu, LW, Weinstein, M, Skotnicki, SM
Pediatric dermatology. 2018;(5):e262-e264
Abstract
A 4-year-old boy presented with erythematous vesicular plaques, ulceration, edema, and pruritus on the left foot and ankle 10 days after receiving the tetanus, diphtheria, pertussis, and polio; measles, mumps, rubella, and varicella; and hepatitis A/B vaccines. Biopsy showed eosinophilic infiltrates and flame figures, suggesting Wells syndrome. Patch testing showed a 1+ reaction to neomycin and aluminum hydroxide, with a recall reaction of Wells syndrome of the feet bilaterally. We report a rare case of pediatric Wells syndrome triggered by nonthimerosal vaccine components confirmed by patch testing.
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4.
Aluminum in vaccines: Does it create a safety problem?
Principi, N, Esposito, S
Vaccine. 2018;(39):5825-5831
Abstract
For almost a century, aluminum (Al) in the form of Al oxyhydroxide (a crystalline compound), Al hydroxyphosphate (an amorphous Al phosphate hydroxide), Al phosphate, and Al potassium sulfate has been used to improve the immunogenicity of vaccines. Al is currently included in vaccines against tetanus, hepatitis A, hepatitis B, human papillomavirus, Haemophilus influenzae type b, and infections due to Streptococcus pneumoniae and Neisseria meningitidis. Official health authorities consider the inclusion of Al in most of the presently recommended vaccines to be extremely effective and sufficiently safe. However, the inclusion of Al salts in vaccines has been debated for several years because of studies that seem to indicate that chronic Al exposure through vaccine administration can interfere with cellular and metabolic processes leading to severe neurologic diseases. Children, who in their first years of life receive several vaccine doses over a reduced period of time, would be most susceptible to any risk that might be associated with vaccines or vaccine components. The main aim of this paper was to discuss the data presently available regarding Al neurotoxicity and the risk for children receiving vaccines or other pharmaceutical preparations containing Al. Analysis of the literature showed that no apparent reason exists to support the elimination of Al from vaccines for fear of neurotoxicity. The only problem that deserves attention is the suggested relationship between Al oxyhydroxide-containing vaccines and macrophagic myofaciitis or myalgic encephalomyelitis/chronic fatigue syndrome. Currently, definitive conclusions cannot be drawn on these risks and further studies must be conducted. Until then, Al remains the best solution to improve vaccine efficacy.
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5.
Perioperative Immunonutrition Modulates Inflammatory Response after Radical Cystectomy: Results of a Pilot Randomized Controlled Clinical Trial.
Hamilton-Reeves, JM, Stanley, A, Bechtel, MD, Yankee, TM, Chalise, P, Hand, LK, Lee, EK, Smelser, W, Mirza, M, Wyre, H, et al
The Journal of urology. 2018;(2):292-301
Abstract
PURPOSE Poor preoperative nutritional status is associated with a higher complication rate after radical cystectomy in patients with bladder cancer. Given the short interval between diagnosis and radical cystectomy, we compared the effect of short-term specialized immunonutrition to that of a standard oral nutritional supplement on the acute inflammatory response and arginine status in patients treated with radical cystectomy. MATERIALS AND METHODS In this prospective, randomized study in 29 men 14 received specialized immunonutrition and 15 received oral nutritional supplement. Each group drank 3 cartons per day for 5 days before and 5 days after radical cystectomy. The Th1-Th2 balance, plasma interleukin-6 and plasma amino acids were measured at baseline, intraoperatively and on postoperative days 2, 14 and 30. Body composition was measured by dual energy x-ray absorptiometry at baseline and on postoperative days 14 and 30. Differences in outcomes were assessed using the generalized linear mixed model. RESULTS In the specialized immunonutrition group there was a 54.3% average increase in the Th1-Th2 balance according to the tumor necrosis factor-α-to-interleukin-13 ratio from baseline to intraoperative day, representing a shift toward a Th1 response. In the oral nutritional supplement group the Th1-Th2 balance decreased 4.8%. The change in the Th1-Th2 balance between the specialized immunonutrition and oral nutritional supplement groups significantly differed (p <0.027). Plasma interleukin-6 was 42.8% lower in the specialized immunonutrition group compared to the oral nutritional supplement group on postoperative day 2 (p = 0.020). In the specialized immunonutrition group plasma arginine was maintained from baseline to postoperative day 2 and yet the oral nutritional supplement group showed a 26.3% reduction from baseline to postoperative day 2 (p = 0.0003). The change in appendicular muscle loss between the groups was not statistically significant. CONCLUSIONS Th1-to-Th2 ratios, peak interleukin-6 levels and plasma arginine suggest that consuming specialized immunonutrition counteracts the disrupted T-helper balance, lowers the inflammatory response and prevents arginine depletion due to radical cystectomy.
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6.
Antioxidant action and protective and reparative effects of lentinan on oxidative damage in HaCaT cells.
Zi, Y, Zhang, B, Jiang, B, Yang, X, Liang, Z, Liu, W, He, C, Liu, L
Journal of cosmetic dermatology. 2018;(6):1108-1114
Abstract
BACKGROUND Lentinus edodes is one of the largest edible fungi. Lentinan, extracted from its fruiting body has clinically significant anticancer, antibacterial, antiviral, and anticoagulant effects; however, its preventive effects on skin oxidative damage are unclear. AIMS We aimed to evaluate the in vitro antioxidation capability of lentinan and its protective and reparative effects on a model of cell oxidative damage. METHODS We evaluated the in vitro antioxidant potential of lentinan by assessing its free-radical quenching ability using DPPH and ABTS and superoxide anions. Using the HaCaT cell line as the experimental system, we tested the protective and reparative effects of lentinan on a model of H2 O2 -induced cellular oxidative damage through assessment of cell survival rate, malondialdehyde (MDA) content, and superoxide dismutase (SOD) activity. RESULTS Lentinan displayed high antioxidant potential: DDPH and ABTS quenching rates were above 60%; superoxide anions, approximately 18%. Furthermore, lentinan could dose-dependently prevent the reduction of activity in HaCaT cells by H2 O2 , reduce MDA formation, and increase SOD activity. Moreover, lentinan showed not only a protective effect against oxidative damage but also reparative effects to a certain extent, in HaCaT cells. CONCLUSIONS Our findings demonstrated the ability of lentinan to enhance cellular tolerance to oxidative damage, stress resistance, and to have protective and reparative effects on damaged cells. Therefore, with L. edodes as a source for antiaging substances, cosmetics with homology to foods have great potential clinical applications.
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7.
Combination and inducible adjuvants targeting nucleic acid sensors.
Temizoz, B, Kuroda, E, Ishii, KJ
Current opinion in pharmacology. 2018;:104-113
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Abstract
Innate immune sensing of nucleic acids derived from invading pathogens or tumor cells via pattern recognition receptors is crucial for mounting protective immune responses against infectious disease and cancer. Recently, discovery of tremendous amounts of nucleic acid sensors as well as identification of natural and synthetic ligands for these receptors revealed the potential of adjuvants targeting nucleic acid sensing pathways for designing efficacious vaccines. Especially, current data indicated that unique adjuvants targeting TLR9 and stimulator of interferon genes (STING)-dependent cytosolic nucleic acid sensing pathways along with the combinations of already existing adjuvants are promising candidates for this purpose. Here, we review current vaccine adjuvants targeting nucleic acid sensors and their modes of action.
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Efficacy of Platelet-Rich Plasma in Pain and Self-Report Function in Knee Osteoarthritis: A Best-Evidence Synthesis.
Xu, Z, Luo, J, Huang, X, Wang, B, Zhang, J, Zhou, A
American journal of physical medicine & rehabilitation. 2017;(11):793-800
Abstract
OBJECTIVE The aim of this study was to assess the efficacy of platelet-rich plasma (PRP) in pain and self-report function of patients with knee osteoarthritis on the basis of comparisons with hyaluronic acid or placebo. DESIGN Best-evidence synthesis of randomized controlled trials (RCTs) was conducted. Literature retrieval was limited to RCTs assessing the efficacy of PRP in knee osteoarthritis. Methodology evaluation and data extraction were based on Cochrane Collaboration guidelines. Meta-analyses were performed using mean difference or standardized mean difference as effect size. RESULTS Ten RCTs were included and analyzed. Meta-analysis showed significant superiority of PRP in outcome scores when compared with hyaluronic acid (standardized mean difference = -0.85, P = 0.004, I = 93%), but no statistical difference was found in well-designed double-blind trials (standardized mean difference = -0.09, P = 0.38, I = 0%). Pooled standardized mean difference of trials comparing PRP with placebo directly was -2.13 (95% confidence interval = -3.29 to -0.98), and that of indirect comparison was -0.22 (95% confidence interval = -0.45 to -0.01). CONCLUSIONS In relieving pain and improving self-report function, PRP showed no superiority over hyaluronic acid in well-designed double-blind trials, and beneficial effects of PRP in most trials probably resulted from insufficient blinding methods. However, PRP is still considered more effective than placebo on the basis of present evidence.
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The effect of nebulised magnesium sulphate in the management of childhood moderate asthma exacerbations as adjuvant treatment.
Turker, S, Dogru, M, Yildiz, F, Yilmaz, SB
Allergologia et immunopathologia. 2017;(2):115-120
Abstract
BACKGROUND After the bronchodilator effect of magnesium was shown, the use of magnesium in treatment of asthma exacerbations became common. With the results of recent studies, the use of intravenous magnesium in severe asthma exacerbations took its place. We aimed to examine the effects of adding isotonic magnesium sulphate instead of isotonic saline into nebulised salbutamol on the Modified Pulmonary Index Score (MPIS) and the hospitalisation rate in moderate asthma exacerbations. METHODS Our study population included 100 children age between 3 and 15 years with asthma admitted to emergency department due to moderate asthma exacerbations. The patients were randomised to placebo or magnesium, with 50 patients in each arm. All patients received 1mg/kg of systemic methylprednisolone at the beginning of treatment and thereafter received either nebulised salbutamol (0.15mg/kg/dose) and 1ml magnesium sulphate (15%)+1.5ml isotonic saline on three occasions at roughly 20min intervals (Magnesium group) or nebulised salbutamol (0.15mg/kg/dose) and 2.5ml isotonic saline mixture on three occasions at roughly 20min intervals (Placebo group). The MPIS of patients on 0th min, 20th min, 40th and 120th min were calculated and compared. The primary outcome was to compare MPIS values at the end of 120th min. RESULTS Both groups have similar demographic, allergic characteristics and baseline MPIS scores. When the MPIS scores in the 120th min and admission rates in the 200th min, there was no significant difference between the two groups. CONCLUSIONS The use of nebulised magnesium sulphate in moderate asthma exacerbation as adjuvant treatment showed no benefit to standard treatment in our study.
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10.
Endoscopic and clinical benefits of hyaluronic acid in children with chronic adenoiditis and middle ear disease.
Torretta, S, Marchisio, P, Rinaldi, V, Carioli, D, Nazzari, E, Pignataro, L
European archives of oto-rhino-laryngology : official journal of the European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino-Laryngology - Head and Neck Surgery. 2017;(3):1423-1429
Abstract
Hyaluronic acid (HA) is involved in modulating inflammatory airway processes and mucociliary clearance. Some studies have tested the effectiveness of the topical administration of HA in patients with upper airway diseases with positive preliminary results. A prospective, single-blind, 1:1 randomised controlled study was performed to assess the efficacy and safety of the daily topical administration of 9 mg of sodium hyaluronate in 3 mL of a 0.9 % sodium saline solution on the basis of endoscopic and clinical parameters in children with chronic adenoiditis associated with recurrent acute otitis media and otitis media with effusion; age- and gender-matched children receiving normal 0.9 % sodium chloride saline solution were used as controls. Analysis was based on 103 (mean age 63.3 ± 18.2 months; 52 males, 50.5 %) children: 54 in the study group and 49 in the control group. A statistically significant reduction in the mean number of all acute otitis media episodes (AOME) (mean reduction 0.8 ± 0.4 per month; p value 0.05) and AOME without tympanic membrane perforation (mean reduction 0.6 ± 0.3 per month; p value 0.04) after recruitment was documented only in the study group. HA significantly improved all the endoscopic outcomes (p values ranging between 0.05 and <0.01) but one. Nasal washing with saline solution was effective on only three of them (p values ranging between 0.03 and <0.01). No untoward effects were documented. Our results confirm the safety and document the positive effect of topically administered HA solution on children with chronic adenoiditis associated with middle ear disease.