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1.
Recent Advances in the Development of Protein- and Peptide-Based Subunit Vaccines against Tuberculosis.
Bellini, C, Horváti, K
Cells. 2020;(12)
Abstract
The World Health Organization (WHO) herald of the "End TB Strategy" has defined goals and targets for tuberculosis prevention, care, and control to end the global tuberculosis endemic. The emergence of drug resistance and the relative dreadful consequences in treatment outcome has led to increased awareness on immunization against Mycobacterium tuberculosis (Mtb). However, the proven limited efficacy of Bacillus Calmette-Guérin (BCG), the only licensed vaccine against Mtb, has highlighted the need for alternative vaccines. In this review, we seek to give an overview of Mtb infection and failure of BCG to control it. Afterward, we focus on the protein- and peptide-based subunit vaccine subtype, examining the advantages and drawbacks of using this design approach. Finally, we explore the features of subunit vaccine candidates currently in pre-clinical and clinical evaluation, including the antigen repertoire, the exploited adjuvanted delivery systems, as well as the spawned immune response.
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Role of Glutathionylation in Infection and Inflammation.
Checconi, P, Limongi, D, Baldelli, S, Ciriolo, MR, Nencioni, L, Palamara, AT
Nutrients. 2019;(8)
Abstract
Glutathionylation, that is, the formation of mixed disulfides between protein cysteines and glutathione (GSH) cysteines, is a reversible post-translational modification catalyzed by different cellular oxidoreductases, by which the redox state of the cell modulates protein function. So far, most studies on the identification of glutathionylated proteins have focused on cellular proteins, including proteins involved in host response to infection, but there is a growing number of reports showing that microbial proteins also undergo glutathionylation, with modification of their characteristics and functions. In the present review, we highlight the signaling role of GSH through glutathionylation, particularly focusing on microbial (viral and bacterial) glutathionylated proteins (GSSPs) and host GSSPs involved in the immune/inflammatory response to infection; moreover, we discuss the biological role of the process in microbial infections and related host responses.
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3.
Safety Assessment of Immune-Mediated Adverse Reactions to Novel Food Proteins.
Fernandez, A, Mills, ENC, Koning, F, Moreno, FJ
Trends in biotechnology. 2019;(8):796-800
Abstract
Current international guidelines for the risk assessment of biotechnology-derived foods date back to 2003. We present new strategies and directions for assessing immune adverse reactions to novel food proteins. Understanding genetic factors involved in food allergy and the role of the gastrointestinal tract will streamline risk assessment strategies.
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4.
ImmunomeBrowser: a tool to aggregate and visualize complex and heterogeneous epitopes in reference proteins.
Dhanda, SK, Vita, R, Ha, B, Grifoni, A, Peters, B, Sette, A
Bioinformatics (Oxford, England). 2018;(22):3931-3933
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Abstract
MOTIVATION Datasets that are derived from different studies (e.g. MHC ligand elution, MHC binding, B/T cell epitope screening etc.) often vary in terms of experimental approaches, sizes of peptides tested, including partial and or nested overlapping peptides and in the number of donors tested. RESULTS We present a customized application of the Immune Epitope Database's ImmunomeBrowser tool, which can be used to effectively aggregate and visualize heterogeneous immunological data. User provided peptide sets and associated response data is mapped to a user-provided protein reference sequence. The output consists of tables and figures representing the aggregated data represented by a Response Frequency score and associated estimated confidence interval. This allows the user to visualizing regions associated with dominant responses and their boundaries. The results are presented both as a user interactive javascript based web interface and a tabular format in a selected reference sequence. AVAILABILITY AND IMPLEMENTATION The 'ImmunomeBrowser' has been a longstanding feature of the IEDB (http://www.iedb.org). The present application extends the use of this tool to work with user-provided datasets, rather than the output of IEDB queries. This new server version of the ImmunomeBrowser is freely accessible at http://tools.iedb.org/immunomebrowser/.
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Effects of protein-carbohydrate supplementation on immunity and resistance training outcomes: a double-blind, randomized, controlled clinical trial.
Naclerio, F, Larumbe-Zabala, E, Ashrafi, N, Seijo, M, Nielsen, B, Allgrove, J, Earnest, CP
European journal of applied physiology. 2017;(2):267-277
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Abstract
PURPOSE To examine the impact of ingesting hydrolyzed beef protein, whey protein, and carbohydrate on resistance training outcomes, body composition, muscle thickness, blood indices of health and salivary human neutrophil peptides (HNP1-3), as reference of humoral immunity followed an 8-week resistance training program in college athletes. METHODS Twenty-seven recreationally physically active males and females (n = 9 per treatment) were randomly assigned to one of the three groups: hydrolyzed beef protein, whey protein, or non-protein isoenergetic carbohydrate. Treatment consisted of ingesting 20 g of supplement, mixed with orange juice, once a day immediately post-workout or before breakfast on non-training days. Measurements were performed pre- and post-intervention on total load (kg) lifted at the first and last workout, body composition (via plethysmography) vastus medialis thickness (mm) (via ultrasonography), and blood indices of health. Salivary HNP1-3 were determined before and after performing the first and last workout. RESULTS Salivary concentration and secretion rates of the HNP1-3 decreased in the beef condition only from pre-first-workout (1.90 ± 0.83 μg/mL; 2.95 ± 2.83 μg/min, respectively) to pre-last-workout (0.92 ± 0.63 μg/mL, p = 0.025, d = 1.03; 0.76 ± 0.74 μg/min, p = 0.049, d = 0.95), and post-last-workout (0.95 ± 0.60 μg/mL, p = 0.032, d = 1.00; 0.59 ± 0.52 μg/min, p = 0.027, d = 1.02). No other significant differences between groups were observed. CONCLUSIONS Supplementation with a carbohydrate-protein beverage may support resistance training outcomes in a comparable way as the ingestion of only carbohydrate. Furthermore, the ingestion of 20 g of hydrolyzed beef protein resulted in a decreased level and secretion rates of the HNP1-3 from baseline with no negative effect on blood indices of health.
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Classification epitopes in groups based on their protein family.
Kozlova, E, Viart, B, de Avila, R, Felicori, L, Chavez-Olortegui, C
BMC bioinformatics. 2015;(Suppl 19):S7
Abstract
BACKGROUND The humoral immune system response is based on the interaction between antibodies and antigens for the clearance of pathogens and foreign molecules. The interaction between these proteins occurs at specific positions known as antigenic determinants or B-cell epitopes. The experimental identification of epitopes is costly and time consuming. Therefore the use of in silico methods, to help discover new epitopes, is an appealing alternative due the importance of biomedical applications such as vaccine design, disease diagnostic, anti-venoms and immune-therapeutics. However, the performance of predictions is not optimal been around 70% of accuracy. Further research could increase our understanding of the biochemical and structural properties that characterize a B-cell epitope. RESULTS We investigated the possibility of linear epitopes from the same protein family to share common properties. This hypothesis led us to analyze physico-chemical (PCP) and predicted secondary structure (PSS) features of a curated dataset of epitope sequences available in the literature belonging to two different groups of antigens (metalloproteinases and neurotoxins). We discovered statistically significant parameters with data mining techniques which allow us to distinguish neurotoxin from metalloproteinase and these two from random sequences. After a five cross fold validation we found that PCP based models obtained area under the curve values (AUC) and accuracy above 0.9 for regression, decision tree and support vector machine. CONCLUSIONS We demonstrated that antigen's family can be inferred from properties within a single group of linear epitopes (metalloproteinases or neurotoxins). Also we discovered the characteristics that represent these two epitope groups including their similarities and differences with random peptides and their respective amino acid sequence. These findings open new perspectives to improve epitope prediction by considering the specific antigen's protein family. We expect that these findings will help to improve current computational mapping methods based on physico-chemical due it's potential application during epitope discovery.
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Unconditioned commercial embryo culture media contain a large variety of non-declared proteins: a comprehensive proteomics analysis.
Dyrlund, TF, Kirkegaard, K, Poulsen, ET, Sanggaard, KW, Hindkjær, JJ, Kjems, J, Enghild, JJ, Ingerslev, HJ
Human reproduction (Oxford, England). 2014;(11):2421-30
Abstract
STUDY QUESTION Which non-declared proteins (proteins not listed on the composition list of the product data sheet) are present in unconditioned commercial embryo culture media? SUMMARY ANSWER A total of 110 non-declared proteins were identified in unconditioned media and between 6 and 8 of these were quantifiable and therefore represent the majority of the total protein in the media samples. WHAT IS KNOWN ALREADY There are no data in the literature on what non-declared proteins are present in unconditioned (fresh media in which no embryos have been cultured) commercial embryo media. STUDY DESIGN, SIZE, DURATION The following eight commercial embryo culture media were included in this study: G-1 PLUS and G-2 PLUS G5 Series from Vitrolife, Sydney IVF Cleavage Medium and Sydney IVF Blastocyst Medium from Cook Medical and EmbryoAssist, BlastAssist, Sequential Cleav and Sequential Blast from ORIGIO. Two batches were analyzed from each of the Sydney IVF media and one batch from each of the other media. All embryo culture media are supplemented by the manufacturers with purified human serum albumin (HSA 5 mg/ml). The purified HSA (HSA-solution from Vitrolife) and the recombinant human albumin supplement (G-MM from Vitrolife) were also analyzed. PARTICIPANTS/MATERIALS, SETTING, METHODS For protein quantification, media samples were in-solution digested with trypsin and analyzed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). For in-depth protein identification, media were albumin depleted, dialyzed and concentrated before sodium dodecyl sulfate polyacrylamide gel electrophoresis. The gel was cut into 14 slices followed by in-gel trypsin digestion, and analysis by LC-MS/MS. Proteins were further investigated using gene ontology (GO) terms analysis. MAIN RESULTS AND THE ROLE OF CHANCE Using advanced mass spectrometry and high confidence criteria for accepting proteins (P < 0.01), a total of 110 proteins other than HSA were identified. The average HSA content was found to be 94% (92-97%) of total protein. Other individual proteins accounted for up to 4.7% of the total protein. Analysis of purified HSA strongly suggests that these non-declared proteins are introduced to the media when the albumin is added. GO analysis showed that many of these proteins have roles in defence pathways, for example 18 were associated with the innate immune response and 17 with inflammatory responses. Eight proteins have been reported previously as secreted embryo proteins. LIMITATIONS, REASONS FOR CAUTION For six of the commercial embryo culture media only one batch was analyzed. However, this does not affect the overall conclusions. WIDER IMPLICATIONS OF THE FINDINGS The results showed that the HSA added to IVF media contained many other proteins and that the amount varies from batch to batch. These variations in protein profiles are problematic when attempting to identify proteins derived from the embryos. Therefore, when studying the embryo secretome and analyzing conditioned media with the aim of finding potential biomarkers that can distinguish normal and abnormal embryo development, it is important that the medium used in the experimental and control groups is from the same batch. Furthermore, the proteins present in unconditioned media could potentially influence embryonic development, gestation age, birthweight and perhaps have subsequent effects on health of the offspring. STUDY FUNDING/COMPETING INTERESTS The study was supported by the Danish Agency for Science, Technology and Innovation. Research at the Fertility Clinic, Aarhus University Hospital is supported by an unrestricted grant from Merck Sharp & Dohme Corp and Ferring. The authors declare no conflicts of interest.
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Differential seminal plasma proteome according to semen retrieval in men with spinal cord injury.
da Silva, BF, Souza, GH, lo Turco, EG, Del Giudice, PT, Soler, TB, Spaine, DM, Borrelli Junior, M, Gozzo, FC, Pilau, EJ, Garcia, JS, et al
Fertility and sterility. 2013;(4):959-69
Abstract
OBJECTIVE To evaluate protein expression profile and to quantify proteins present in seminal plasma from men with spinal cord injury (SCI) and healthy men without SCI. DESIGN Experimental study. SETTING University hospital. PATIENT(S): Twelve SCI patients divided into two groups, six who underwent electroejaculation (EEJ) and six who underwent penile vibratory stimulation (PVS); and ten control subjects presenting normal sperm motility and concentration. INTERVENTION(S): EEJ and PVS. MAIN OUTCOME MEASURE(S): The seminal plasma protein profile was analyzed by two proteomic strategies: data-independent label-free quantitative proteomics (MS(E)) and two-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis (2D SDS-PAGE). RESULT(S): A total of 638 different proteins were identified by MS(E) and 18 by 2D SDS-PAGE followed by tandem mass spectrometry. Interactome analysis showed key reproductive biologic processes-insemination, sperm and oocyte fusion, and acrosome reaction-related to all groups, as were triglyceride stimuli. Processes related to actin and muscle function and to iron oxidation, transportation, and homeostasis were found only in the EEJ and PVS groups; response to hydrogen peroxide and increased immune response was found only in the PVS group. CONCLUSION(S): This study was able to demonstrate differential protein expression among control, PVS, and EEJ groups; SCI is responsible for alterations in seminal plasma protein profile leading to a deviation from homeostasis; proteins reported in both PVS and EEJ groups correlate with the pathophysiology of SCI-related infertility.
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War and peace between WAP and HIV: role of SLPI, trappin-2, elafin and ps20 in susceptibility to HIV infection.
Drannik, AG, Henrick, BM, Rosenthal, KL
Biochemical Society transactions. 2011;(5):1427-32
Abstract
Despite tremendous advances in our understanding of HIV/AIDS since the first cases were reported 30 years ago, we are still a long way from understanding critical steps of HIV acquisition, pathogenesis and correlates of protection. Our new understanding of the importance of the mucosa as a target for HIV infection, as well as our recent observations showing that altered expression and responses of innate pattern recognition receptors are significantly associated with pathogenesis and resistance to HIV infection, indicate that correlates of immunity to HIV are more likely to be associated with mucosal and innate responses. Most of the heterosexual encounters do not result in productive HIV infection, suggesting that the female genital tract is protected against HIV by innate defence molecules, such as antiproteases, secreted mucosally. The present review highlights the role and significance of the serine protease inhibitors SLPI (secretory leucocyte protease inhibitor), trappin-2, elafin and ps20 (prostate stromal protein 20 kDa) in HIV susceptibility and infection. Interestingly, in contrast with SLPI, trappin-2 and elafin, ps20 has been shown to enhance HIV infectivity. Thus understanding the balance and interaction of these factors in mucosal fluids may significantly influence HIV infection.
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Appropriate protein and specific amino acid delivery can improve patient outcome: fact or fantasy?
Lawson, CM, Miller, KR, Smith, VL, McClave, SA
Current gastroenterology reports. 2011;(4):380-7
Abstract
Protein utilization and requirements in critical illness are much researched and debated topics. The enhanced turnover and catabolism of protein in the setting of critical illness is well described and multifactorial in nature. The need to preserve lean body mass and enhance nitrogen retention in this state to improve immunologic function and reduce morbidity is well described. Debates as to the optimum amount of protein to provide in such states still exist, and a significant amount of research has contributed to our understanding of not only how much protein to supply to these patients, but how best to do so. Small peptide formulations, intact protein formulations, branched chain amino acids, and specialty formulas all exist, and their benefits, drawbacks, and potential uses have been investigated. Specific amino acid therapy has become part of the concept of immunonutrition, or the modification and enhancement of the immune response with specific nutrients. In this article, we describe the changes in outcomes demonstrated through the provision of protein, both as a macronutrient and as specific amino acids.