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      Rational Design of a Pan-Coronavirus Vaccine Based on Conserved CTL Epitopes

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          Abstract

          With the rapid global spread of the Coronavirus Disease 2019 (COVID-19) pandemic, a safe and effective vaccine against human coronaviruses (HCoVs) is believed to be a top priority in the field of public health. Due to the frequent outbreaks of different HCoVs, the development of a pan-HCoVs vaccine is of great value to biomedical science. The antigen design is a key prerequisite for vaccine efficacy, and we therefore developed a novel antigen with broad coverage based on the genetic algorithm of mosaic strategy. The designed antigen has a potentially broad coverage of conserved cytotoxic T lymphocyte (CTL) epitopes to the greatest extent, including the existing epitopes from all reported HCoV sequences (HCoV-NL63, HCoV-229E, HCoV-OC43, HCoV-HKU1, SARS-CoV, MERS-CoV, and SARS-CoV-2). This novel antigen is expected to induce strong CTL responses with broad coverage by targeting conserved epitopes against multiple coronaviruses.

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          Most cited references26

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          CD-HIT: accelerated for clustering the next-generation sequencing data

          Summary: CD-HIT is a widely used program for clustering biological sequences to reduce sequence redundancy and improve the performance of other sequence analyses. In response to the rapid increase in the amount of sequencing data produced by the next-generation sequencing technologies, we have developed a new CD-HIT program accelerated with a novel parallelization strategy and some other techniques to allow efficient clustering of such datasets. Our tests demonstrated very good speedup derived from the parallelization for up to ∼24 cores and a quasi-linear speedup for up to ∼8 cores. The enhanced CD-HIT is capable of handling very large datasets in much shorter time than previous versions. Availability: http://cd-hit.org. Contact: liwz@sdsc.edu Supplementary information: Supplementary data are available at Bioinformatics online.
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            Targets of T cell responses to SARS-CoV-2 coronavirus in humans with COVID-19 disease and unexposed individuals

            Summary Understanding adaptive immunity to SARS-CoV-2 is important for vaccine development, interpreting coronavirus disease 2019 (COVID-19) pathogenesis, and calibration of pandemic control measures. Using HLA class I and II predicted peptide ‘megapools’, circulating SARS-CoV-2−specific CD8+ and CD4+ T cells were identified in ∼70% and 100% of COVID-19 convalescent patients, respectively. CD4+ T cell responses to spike, the main target of most vaccine efforts, were robust and correlated with the magnitude of the anti-SARS-CoV-2 IgG and IgA titers. The M, spike and N proteins each accounted for 11-27% of the total CD4+ response, with additional responses commonly targeting nsp3, nsp4, ORF3a and ORF8, among others. For CD8+ T cells, spike and M were recognized, with at least eight SARS-CoV-2 ORFs targeted. Importantly, we detected SARS-CoV-2−reactive CD4+ T cells in ∼40-60% of unexposed individuals, suggesting cross-reactive T cell recognition between circulating ‘common cold’ coronaviruses and SARS-CoV-2.
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              Emerging coronaviruses: Genome structure, replication, and pathogenesis

              Abstract The recent emergence of a novel coronavirus (2019‐nCoV), which is causing an outbreak of unusual viral pneumonia in patients in Wuhan, a central city in China, is another warning of the risk of CoVs posed to public health. In this minireview, we provide a brief introduction of the general features of CoVs and describe diseases caused by different CoVs in humans and animals. This review will help understand the biology and potential risk of CoVs that exist in richness in wildlife such as bats.
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                Author and article information

                Contributors
                Role: Academic Editor
                Journal
                Viruses
                Viruses
                viruses
                Viruses
                MDPI
                1999-4915
                21 February 2021
                February 2021
                : 13
                : 2
                : 333
                Affiliations
                [1 ]School of Public Health (Shenzhen), Sun Yat-sen University, Shenzhen 518107, China; limch7@ 123456mail2.sysu.edu.cn (M.L.); zengjf7@ 123456mail2.sysu.edu.cn (J.Z.); lirt9@ 123456mail2.sysu.edu.cn (R.L.); wenzy3@ 123456mail2.sysu.edu.cn (Z.W.); shuylong@ 123456mail.sysu.edu.cn (Y.S.)
                [2 ]Key Laboratory of Tropical Disease Control (Sun Yat-sen University), Ministry of Education, Guangzhou 514400, China
                [3 ]Gilead Sciences, Inc. 333 Lakeside Dr, Foster City, CA 94404, USA; Jenny.cai1@ 123456gilead.com (Y.C.); Jeffrey.Wallin@ 123456gilead.com (J.W.)
                Author notes
                [†]

                These authors contribute equally to this work.

                Author information
                https://orcid.org/0000-0001-8184-8430
                https://orcid.org/0000-0002-2000-7053
                Article
                viruses-13-00333
                10.3390/v13020333
                7926959
                33670023
                739c112e-3997-4f69-81b1-2c625f5ddc3a
                © 2021 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 12 January 2021
                : 19 February 2021
                Categories
                Article

                Microbiology & Virology
                coronavirus,pan-vaccine,antigen design,conserved epitopes
                Microbiology & Virology
                coronavirus, pan-vaccine, antigen design, conserved epitopes

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