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VaximmutorDB: A Web-Based Vaccine Immune Factor Database and Its Application for Understanding Vaccine-Induced Immune Mechanisms.

ABSTRACT: Vaccines stimulate various immune factors critical to protective immune responses. However, a comprehensive picture of vaccine-induced immune factors and pathways have not been systematically collected and analyzed. To address this issue, we developed VaximmutorDB, a web-based database system of vaccine immune factors (abbreviated as "vaximmutors") manually curated from peer-reviewed articles. VaximmutorDB currently stores 1,740 vaccine immune factors from 13 host species (e.g., human, mouse, and pig). These vaximmutors were induced by 154 vaccines for 46 pathogens. Top 10 vaximmutors include three antibodies (IgG, IgG2a and IgG1), Th1 immune factors (IFN-γ and IL-2), Th2 immune factors (IL-4 and IL-6), TNF-α, CASP-1, and TLR8. Many enriched host processes (e.g., stimulatory C-type lectin receptor signaling pathway, SRP-dependent cotranslational protein targeting to membrane) and cellular components (e.g., extracellular exosome, nucleoplasm) by all the vaximmutors were identified. Using influenza as a model, live attenuated and killed inactivated influenza vaccines stimulate many shared pathways such as signaling of many interleukins (including IL-1, IL-4, IL-6, IL-13, IL-20, and IL-27), interferon signaling, MARK1 activation, and neutrophil degranulation. However, they also present their unique response patterns. While live attenuated influenza vaccine FluMist induced significant signal transduction responses, killed inactivated influenza vaccine Fluarix induced significant metabolism of protein responses. Two different Yellow Fever vaccine (YF-Vax) studies resulted in overlapping gene lists; however, they shared more portions of pathways than gene lists. Interestingly, live attenuated YF-Vax simulates significant metabolism of protein responses, which was similar to the pattern induced by killed inactivated Fluarix. A user-friendly web interface was generated to access, browse and search the VaximmutorDB database information. As the first web-based database of vaccine immune factors, VaximmutorDB provides systematical collection, standardization, storage, and analysis of experimentally verified vaccine immune factors, supporting better understanding of protective vaccine immunity.

SUBMITTER: Berke K

PROVIDER: S-EPMC7994782 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundThis is a review article on heparin-induced thrombocytopenia, an adverse effect of heparin therapy, and vaccine-induced immune thrombotic thrombocytopenia, occurring in some patients administered certain coronavirus vaccines.Main body/textImmune-mediated thrombocytopenia occurs when specific antibodies bind to platelet factor 4 /heparin complexes. Platelet factor 4 is a naturally occurring chemokine, and under certain conditions, may complex with negatively charged molecules and polyanions, including heparin. The antibody-platelet factor 4/heparin complex may lead to platelet activation, accompanied by other cascading reactions, resulting in cerebral sinus thrombosis, deep vein thrombosis, lower limb arterial thrombosis, myocardial infarction, pulmonary embolism, skin necrosis, and thrombotic stroke. If untreated, heparin-induced thrombocytopenia can be life threatening. In parallel, rare incidents of spontaneous vaccine-induced immune thrombotic thrombocytopenia can also occur in some patients administered certain coronavirus vaccines. The role of platelet factor 4 in vaccine-induced thrombosis with thrombocytopenia syndrome further reinforces the importance the platelet factor 4/polyanion immune complexes and the complications that this might pose to susceptible individuals. These findings demonstrate, how auxiliary factors can complicate heparin therapy and drug development. An increasing interest in biomanufacturing heparins from non-animal sources has driven a growing interest in understanding the biology of immune-mediated heparin-induced thrombocytopenia, and therefore, the development of safe and effective biosynthetic heparins.Short conclusionIn conclusion, these findings further reinforce the importance of the binding of platelet factor 4 with known and unknown polyanions, and the complications that these might pose to susceptible patients. In parallel, these findings also demonstrate how auxiliary factors can complicate the heparin drug development.

Project description:During the COVID-19 pandemic, vaccination is the most important countermeasure. Pharmacovigilance concerns however emerged with very rare, but potentially disastrous thrombotic complications following vaccination with ChAdOx1. Platelet factor-4 antibody mediated vaccine-induced immune thrombotic thrombocytopenia (VITT) was described as an underlying mechanism of these thrombotic events. Recent work moreover suggests that mechanisms of immunothrombosis including neutrophil extracellular trap (NET) formation might be critical for thrombogenesis during VITT. In this study, we investigated blood and thrombus specimens of a female patient who suffered severe stroke due to VITT after vaccination with ChAdOx1 in comparison to 13 control stroke patients with similar clinical characteristics. We analyzed cerebral thrombi using histological examination, staining of complement factors, NET-markers, DNase and LL-37. In blood samples at the hyper-acute phase of stroke and 7 days later, we determined cell-free DNA, myeloperoxidase-histone complexes, DNase activity, myeloperoxidase activity, LL-37 and inflammatory cytokines. NET markers were identified in thrombi of all patients. Interestingly, the thrombus of the VITT-patient exclusively revealed complement factors and high amounts of DNase and LL-37. High DNase activity was also measured in blood, implying a disturbed NET-regulation. Furthermore, serum of the VITT-patient inhibited reactive oxygen species-dependent NET-release by phorbol-myristate-acetate to a lesser degree compared to controls, indicating either less efficient NET-inhibition or enhanced NET-induction in the blood of the VITT-patient. Additionally, the changes in specific cytokines over time were emphasized in the VITT-patient as well. In conclusion, insufficient resolution of NETs, e.g. by endogenous DNases or protection of NETs against degradation by embedded factors like the antimicrobial peptide LL-37 might thus be an important factor in the pathology of VITT besides increased NET-formation. On the basis of these findings, we discuss the potential implications of the mechanisms of disturbed NETs-degradation for diagnostic and therapeutic approaches in VITT-related thrombogenesis, other auto-immune disorders and beyond.

Project description:BackgroundA critical issue in understanding the benefits of Web-based interventions is the lack of information on the sustainability of those benefits. Sustainability in studies is often determined using group-level analyses that might obscure our understanding of who actually sustains change. Person-centric methods might provide a deeper knowledge of whether benefits are sustained and who tends to sustain those benefits.ObjectiveThe aim of this study was to conduct a person-centric analysis of longitudinal outcomes, examining well-being in participants over the first 3 months following a Web-based happiness intervention. We predicted we would find distinct trajectories in people's pattern of response over time. We also sought to identify what aspects of the intervention and the individual predicted an individual's well-being trajectory.MethodsData were gathered from 2 large studies of Web-based happiness interventions: one in which participants were randomly assigned to 1 of 14 possible 1-week activities (N=912) and another wherein participants were randomly assigned to complete 0, 2, 4, or 6 weeks of activities (N=1318). We performed a variation of K-means cluster analysis on trajectories of life satisfaction (LS) and affect balance (AB). After clusters were identified, we used exploratory analyses of variance and logistic regression models to analyze groups and compare predictors of group membership.ResultsCluster analysis produced similar cluster solutions for each sample. In both cases, participant trajectories in LS and AB fell into 1 of 4 distinct groups. These groups were as follows: those with high and static levels of happiness (n=118, or 42.8%, in Sample 1; n=306, or 52.8%, in Sample 2), those who experienced a lasting improvement (n=74, or 26.8% in Sample 1; n=104, or 18.0%, in Sample 2), those who experienced a temporary improvement but returned to baseline (n=37, or 13.4%, in Sample 1; n=82, or 14.2%, in Sample 2), and those with other trajectories (n=47, or 17.0%, in Sample 1; n=87, or 15.0% in Sample 2). The prevalence of depression symptoms predicted membership in 1 of the latter 3 groups. Higher usage and greater adherence predicted sustained rather than temporary benefits.ConclusionsWe revealed a few common patterns of change among those completing Web-based happiness interventions. A noteworthy finding was that many individuals began quite happy and maintained those levels. We failed to identify evidence that the benefit of any particular activity or group of activities was more sustainable than any others. We did find, however, that the distressed portion of participants was more likely to achieve a lasting benefit if they continued to practice, and adhere to, their assigned Web-based happiness intervention.

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VaximmutorDB: A Web-Based Vaccine Immune Factor Database and Its Application for Understanding Vaccine-Induced Immune Mechanisms.

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