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HGNC Genes

SARS-CoV-2 proteins

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    Induction of Th1 HGNC/Th2-Balanced Protection Against SARS-CoV-2 Through Mucosal Delivery of An Adenovirus Vaccine Expressing an Engineered Spike Protein PROTEIN

    Authors: Nai-Hsiang Chung; Ying-Chin Chen; Shiu-Ju Yang; Yu-Ching Lin; Horng-Yunn Dou; Ching-Len Liao; Yen-Hung Chow

    doi:10.21203/rs.3.rs-134494/v1 Date: 2020-12-23 Source: ResearchSquare

    We developed a series of recombinant human type 5 adenoviruses that express the full-length or membrane-truncated spike protein (S PROTEIN) of SARS-CoV-2 (AdCoV2-S or AdCoV2-SdTM, respectively). We tested the immunoprotective efficacy against SARS-CoV-2 via intranasal (i.n.) or subcutaneous (s.c.) immunization in a rodent model following two-dose immunizations. Mucosal delivery of adenovirus (Ad) vaccines could induce anti-SARS-CoV-2 IgG and IgA in the serum and in the mucosal, respectively as indicated by vaginal wash (vw). Serum anti-SARS-CoV-2 IgG but not IgA was induced in the vw by s.c. injection of AdCoV2-S. Intranasal administration of AdCoV2-S was able to induce higher anti-SARS-CoV-2 antibody levels than s.c. injection. Immunization with AdCoV2-SdTM induced a lower antibody response than AdCoV2-S. In addition, the degree of neutralization of clinically isolated SARS-CoV-2 in the serum correlated with the above anti-SARS-CoV-2 responses; the most potent neutralizing activity was observed in the AdCoV2-S i.n. group, and less viral neutralizing activity was observed in response to AdCoV2-S s.c. and AdCoV2dTM i.n. Novelty, S-specific IgG1 which represented Th2-mediated humoral response was dominantly induced in Ad i.n.-immunized serum in contrast to more IgG2a which represented Th1 HGNC-mediated cellular response found in Ad s.c.-immunized serum. The activation of S-specific IFN-ɣ and IL-4 HGNC in Th1 HGNC and Th2 cells, respectively, was observed in the AdCoV2s i.n. and s.c. groups, indicating the Th1 HGNC/Th2-balenced immunity was activated. During the protection study, two doses of i.n. AdCoV2-S or i.n. AdCoV2-SdTM significantly prevented body weight loss MESHD and reduced pulmonary viral loads in hamsters. A significant reduction in inflammation MESHD in the lungs was observed in AdCoV-S-immunized hamsters following a SARS-CoV-2 challenge. It correlated to Th1 HGNC cytokine but no inflammatory cytokines secretions found in i.n. AdCoV-immunized respiratory tract. These results indicate that intranasal delivery of AdCoV2-S vaccines is safe and potent at preventing SARS-CoV-2 infections MESHD SARS-CoV-2 infections MESHD.

    Highly functional virus-specific cellular immune response in asymptomatic SARS-CoV-2 infection MESHD

    Authors: Nina Le Bert; Hannah E Clapham; Anthony T Tan; Wan Ni Chia; Christine YL Tham; Jane M Lim; Kamini Kunasegaran; Linda Tan; Charles-Antoine Dutertre; Nivedita Shankar; Joey ME Lim; Louisa Jin Sun; Marina Zahari; Zaw M Tun; Vishakha Kumar; Beng Lee Lim; Siew Hoon Lim; Adeline Chia; Yee-Joo Tan; Paul Anantharajah Tambyah; Shirin Kalimuddin; David CB Lye; Jenny GH Low; Lin-Fa Wang; Wei Yee Wan; Li Yang Hsu; Antonio Bertoletti; Clarence C Tam; Martina Recalde; Paula Casajust; Jitendra Jonnagaddala; Vignesh Subbian; David Vizcaya; Lana YH Lai; Fredrik Nyberg; Daniel R. Morales; Jose D. Posada; Nigam H. Shah; Mengchun Gong; Arani Vivekanantham; Aaron Abend; Evan P Minty; Marc A. Suchard; Peter Rijnbeek; Patrick B Ryan; Daniel Prieto-Alhambra

    doi:10.1101/2020.11.25.399139 Date: 2020-11-27 Source: bioRxiv

    The efficacy of virus-specific T cells in clearing pathogens involves a fine balance between their antiviral and inflammatory features. SARS-CoV-2-specific T cells in individuals who clear SARS-CoV-2 infection MESHD without symptoms or disease could reveal non-pathological yet protective characteristics. We therefore compared the quantity and function of SARS-CoV-2-specific T cells in a cohort of asymptomatic individuals (n=85) with that of symptomatic COVID-19 MESHD patients (n=76), at different time points after antibody seroconversion. We quantified T cells reactive to structural proteins (M PROTEIN, NP and Spike) using ELISpot assays, and measured the magnitude of cytokine secretion ( IL-2 HGNC, IFN-{gamma HGNC}, IL-4 HGNC, IL-6 HGNC, IL-1{beta}, TNF- and IL-10) in whole blood following T cell activation with SARS-CoV-2 peptide pools as a functional readout. Frequencies of T cells specific for the different SARS-CoV-2 proteins in the early phases of recovery were similar between asymptomatic and symptomatic individuals. However, we detected an increased IFN-{gamma HGNC} and IL-2 HGNC production in asymptomatic compared to symptomatic individuals after activation of SARS-CoV-2-specific T cells in blood. This was associated with a proportional secretion of IL-10 HGNC and pro-inflammatory cytokines ( IL-6 HGNC, TNF HGNC- and IL-1{beta} HGNC) only in asymptomatic infection, while a disproportionate secretion of inflammatory cytokines was triggered by SARS-CoV-2-specific T cell activation in symptomatic individuals. Thus, asymptomatic SARS-CoV-2 infected MESHD individuals are not characterized by a weak antiviral immunity; on the contrary, they mount a robust and highly functional virus-specific cellular immune response. Their ability to induce a proportionate production of IL-10 HGNC might help to reduce inflammatory events during viral clearance.

    A Rational Design of a Multi-Epitope Vaccine Against SARS-CoV-2 Which Accounts for the Glycan Shield of the Spike Glycoprotein PROTEIN

    Authors: William R. Martin; Feixiong Cheng

    doi:10.26434/chemrxiv.12770225.v1 Date: 2020-08-07 Source: ChemRxiv

    The ongoing global health crisis caused by Severe Acute Respiratory Syndrome Coronavirus 2 MESHD (SARS-CoV-2), the virus which leads to Coronavirus Disease 2019 MESHD ( COVID-19 MESHD) has impacted not only the health of people everywhere, but the economy in nations across the world. While vaccine candidates and therapeutics are currently undergoing clinical trials, there is yet to be a proven effective treatment or cure for COVID-19 MESHD. In this study, we have presented a synergistic computational platform, including molecular dynamics simulations and immunoinformatics techniques, to rationally design a multi-epitope vaccine candidate for COVID-19 MESHD. This platform combines epitopes across Linear B Lymphocytes (LBL), Cytotoxic T MESHD Lymphocytes (CTL) and Helper T Lymphocytes (HTL) derived from both mutant and wild-type spike glycoproteins PROTEIN from SARS-CoV-2 with diverse protein conformations. In addition, this vaccine construct also takes the considerable glycan shield of the spike glycoprotein PROTEIN into account, which protects it from immune response. We have identified a vaccine candidate (a 35.9 kDa protein), named COVCCF, which is composed of 5 LBL, 6 HTL, and 6 CTL epitopes from the spike glycoprotein PROTEIN of SARS-CoV-2. Using multi-dose immune simulations, COVCCF induces elevated levels of immunoglobulin activity (IgM, IgG1, IgG2), and induces strong responses from B lymphocytes, CD4 HGNC T-helper lymphocytes, and CD8 HGNC T-cytotoxic lymphocytes. COVCCF induces cytokines important to innate immunity, including IFN-γ HGNC, IL4 HGNC, and IL10 HGNC. Additionally, COVCCF has ideal pharmacokinetic properties and low immune-related toxicities MESHD. In summary, this study provides a powerful, computational vaccine design platform for rapid development of vaccine candidates (including COVCCF) for effective prevention of COVID-19 MESHD.

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