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.
Highlights
As one of the most influential inventions in modern medicine, vaccines stimulate various immune responses in the host’s body to protect it from the antigen
We aim to look at the influence of experimental conditions and vaccine related factors through an in-depth look at the immune response elicited from vaccines
In terms of immune responses, only PubMed results were annotated in our database since VaximmutorDB focuses on the annotation and collection of experimentally verified vaccine immune factors reported in original peer-reviewed journal articles
Summary
As one of the most influential inventions in modern medicine, vaccines stimulate various immune responses in the host’s body to protect it from the antigen. The common vaccineinduced immune pathways include innate responses, antigen processing and presentation, adaptive T and B cell responses, and their specific regulations [1]. The innate immune system senses microbes through pattern-recognition receptors (PRRs) in various cells such as dendritic cells and macrophages [2]. Two types of adaptive immune responses can be induced: humoral response and cell-mediated immunity. The humoral response is primarily mediated by antibodies that are generated by B-cells and target specific areas of antigens. Cell-mediated immunity primarily involves the activation and production of T helper cells, cytotoxic T lymphocytes, macrophages, natural killer cells, and cytokines in response to antigens [6]. It has been hypothesized that vaccineinduced immune responses may have their specific immune patterns different from those of natural virulent pathogen infections [7]
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