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      Fighting flu: novel CD8 + T‐cell targets are required for future influenza vaccines

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          Abstract

          Seasonal influenza viruses continue to cause severe medical and financial complications annually. Although there are many licenced influenza vaccines, there are billions of cases of influenza infection every year, resulting in the death of over half a million individuals. Furthermore, these figures can rise in the event of a pandemic, as seen throughout history, like the 1918 Spanish influenza pandemic (50 million deaths) and the 1968 Hong Kong influenza pandemic (~4 million deaths). In this review, we have summarised many of the currently licenced influenza vaccines available across the world and current vaccines in clinical trials. We then briefly discuss the important role of CD8 + T cells during influenza infection and why future influenza vaccines should consider targeting CD8 + T cells. Finally, we assess the current landscape of known immunogenic CD8 + T‐cell epitopes and highlight the knowledge gaps required to be filled for the design of rational future influenza vaccines that incorporate CD8 + T cells.

          Abstract

          Seasonal influenza viruses continue to cause severe medical and financial complications annually despite vaccines being available. As such, there is a need for updated vaccines that provide long‐lasting protection to global populations. In this review, we summarise licenced influenza vaccines and those currently in clinical trials, highlighting their key advantages and limitations. Furthermore, we discuss activating CD8 + T cells for future influenza vaccinations, highlighting the current gaps in knowledge for rational vaccine design.

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          Most cited references104

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          UniProt: the Universal Protein Knowledgebase in 2023

          (2022)
          The aim of the UniProt Knowledgebase is to provide users with a comprehensive, high-quality and freely accessible set of protein sequences annotated with functional information. In this publication we describe enhancements made to our data processing pipeline and to our website to adapt to an ever-increasing information content. The number of sequences in UniProtKB has risen to over 227 million and we are working towards including a reference proteome for each taxonomic group. We continue to extract detailed annotations from the literature to update or create reviewed entries, while unreviewed entries are supplemented with annotations provided by automated systems using a variety of machine-learning techniques. In addition, the scientific community continues their contributions of publications and annotations to UniProt entries of their interest. Finally, we describe our new website ( https://www.uniprot.org/ ), designed to enhance our users’ experience and make our data easily accessible to the research community. This interface includes access to AlphaFold structures for more than 85% of all entries as well as improved visualisations for subcellular localisation of proteins.
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            The Immune Epitope Database (IEDB): 2018 update

            Abstract The Immune Epitope Database (IEDB, iedb.org) captures experimental data confined in figures, text and tables of the scientific literature, making it freely available and easily searchable to the public. The scope of the IEDB extends across immune epitope data related to all species studied and includes antibody, T cell, and MHC binding contexts associated with infectious, allergic, autoimmune, and transplant related diseases. Having been publicly accessible for >10 years, the recent focus of the IEDB has been improved query and reporting functionality to meet the needs of our users to access and summarize data that continues to grow in quantity and complexity. Here we present an update on our current efforts and future goals.
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              SARS-CoV-2 mRNA Vaccine Design Enabled by Prototype Pathogen Preparedness

              Summary A severe acute respiratory syndrome coronavirus (SARS-CoV-2) vaccine is needed to control the global coronavirus infectious disease (COVID-19) public health crisis. Atomic-level structures directed the application of prefusion-stabilizing mutations that improved expression and immunogenicity of betacoronavirus spike proteins 1 . Using this established immunogen design, the release of SARS-CoV-2 sequences triggered immediate rapid manufacturing of an mRNA vaccine expressing the prefusion-stabilized SARS-CoV-2 spike trimer (mRNA-1273). Here, we show that mRNA-1273 induces both potent neutralizing antibody responses to wild-type (D614) and D614G mutant 2 SARS-CoV-2 and CD8 T cell responses and protects against SARS-CoV-2 infection in lungs and noses of mice without evidence of immunopathology. mRNA-1273 is currently in Phase 3 efficacy evaluation.
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                Author and article information

                Contributors
                e.grant@latrobe.edu.au
                Journal
                Clin Transl Immunology
                Clin Transl Immunology
                10.1002/(ISSN)2050-0068
                CTI2
                Clinical & Translational Immunology
                John Wiley and Sons Inc. (Hoboken )
                2050-0068
                14 February 2024
                2024
                : 13
                : 2 ( doiID: 10.1002/cti2.v13.2 )
                : e1491
                Affiliations
                [ 1 ] Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science La Trobe University Bundoora VIC Australia
                [ 2 ] Department of Biochemistry and Molecular Biology, Biomedicine Discovery Institute Monash University Clayton VIC Australia
                Author notes
                [*] [* ] Correspondence

                EJ Grant, Department of Biochemistry and Chemistry, La Trobe Institute for Molecular Science, La Trobe University, Bundoora, VIC, Australia.

                E‐mail: e.grant@ 123456latrobe.edu.au

                Author information
                https://orcid.org/0000-0001-7416-038X
                Article
                CTI21491 CTI-23-REV-0248.R1
                10.1002/cti2.1491
                10867544
                38362528
                02710ae0-4887-4ec3-bd28-e53e56d53484
                © 2024 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology, Inc.

                This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

                History
                : 29 January 2024
                : 11 December 2023
                : 30 January 2024
                Page count
                Figures: 4, Tables: 4, Pages: 15, Words: 11521
                Funding
                Funded by: La Trobe University , doi 10.13039/501100001215;
                Funded by: National Health and Medical Research Council , doi 10.13039/501100000925;
                Award ID: #1159272
                Funded by: Australian Institute of Nuclear Science and Engineering , doi 10.13039/501100001023;
                Funded by: Australian Research Council , doi 10.13039/501100000923;
                Award ID: DE210101479
                Categories
                Review
                Review
                Custom metadata
                2.0
                2024
                Converter:WILEY_ML3GV2_TO_JATSPMC version:6.3.8 mode:remove_FC converted:15.02.2024

                cd8+ t cells,epitopes,hla‐i,influenza,vaccines
                cd8+ t cells, epitopes, hla‐i, influenza, vaccines

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