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      DNA vaccine protection against SARS-CoV-2 in rhesus macaques

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      Science (New York, N.y.)
      American Association for the Advancement of Science

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          Abstract

          The global COVID-19 pandemic caused by the SARS-CoV-2 virus has made the development of a vaccine a top biomedical priority. In this study, we developed a series of DNA vaccine candidates expressing different forms of the SARS-CoV-2 Spike (S) protein and evaluated them in 35 rhesus macaques. Vaccinated animals developed humoral and cellular immune responses, including neutralizing antibody titers comparable to those found in convalescent humans and macaques infected with SARS-CoV-2. Following vaccination, all animals were challenged with SARS-CoV-2, and the vaccine encoding the full-length S protein resulted in >3.1 and >3.7 log 10 reductions in median viral loads in bronchoalveolar lavage and nasal mucosa, respectively, as compared with sham controls. Vaccine-elicited neutralizing antibody titers correlated with protective efficacy, suggesting an immune correlate of protection. These data demonstrate vaccine protection against SARS-CoV-2 in nonhuman primates.

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          Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China

          Summary Background A recent cluster of pneumonia cases in Wuhan, China, was caused by a novel betacoronavirus, the 2019 novel coronavirus (2019-nCoV). We report the epidemiological, clinical, laboratory, and radiological characteristics and treatment and clinical outcomes of these patients. Methods All patients with suspected 2019-nCoV were admitted to a designated hospital in Wuhan. We prospectively collected and analysed data on patients with laboratory-confirmed 2019-nCoV infection by real-time RT-PCR and next-generation sequencing. Data were obtained with standardised data collection forms shared by WHO and the International Severe Acute Respiratory and Emerging Infection Consortium from electronic medical records. Researchers also directly communicated with patients or their families to ascertain epidemiological and symptom data. Outcomes were also compared between patients who had been admitted to the intensive care unit (ICU) and those who had not. Findings By Jan 2, 2020, 41 admitted hospital patients had been identified as having laboratory-confirmed 2019-nCoV infection. Most of the infected patients were men (30 [73%] of 41); less than half had underlying diseases (13 [32%]), including diabetes (eight [20%]), hypertension (six [15%]), and cardiovascular disease (six [15%]). Median age was 49·0 years (IQR 41·0–58·0). 27 (66%) of 41 patients had been exposed to Huanan seafood market. One family cluster was found. Common symptoms at onset of illness were fever (40 [98%] of 41 patients), cough (31 [76%]), and myalgia or fatigue (18 [44%]); less common symptoms were sputum production (11 [28%] of 39), headache (three [8%] of 38), haemoptysis (two [5%] of 39), and diarrhoea (one [3%] of 38). Dyspnoea developed in 22 (55%) of 40 patients (median time from illness onset to dyspnoea 8·0 days [IQR 5·0–13·0]). 26 (63%) of 41 patients had lymphopenia. All 41 patients had pneumonia with abnormal findings on chest CT. Complications included acute respiratory distress syndrome (12 [29%]), RNAaemia (six [15%]), acute cardiac injury (five [12%]) and secondary infection (four [10%]). 13 (32%) patients were admitted to an ICU and six (15%) died. Compared with non-ICU patients, ICU patients had higher plasma levels of IL2, IL7, IL10, GSCF, IP10, MCP1, MIP1A, and TNFα. Interpretation The 2019-nCoV infection caused clusters of severe respiratory illness similar to severe acute respiratory syndrome coronavirus and was associated with ICU admission and high mortality. Major gaps in our knowledge of the origin, epidemiology, duration of human transmission, and clinical spectrum of disease need fulfilment by future studies. Funding Ministry of Science and Technology, Chinese Academy of Medical Sciences, National Natural Science Foundation of China, and Beijing Municipal Science and Technology Commission.
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            A Novel Coronavirus from Patients with Pneumonia in China, 2019

            Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
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              A pneumonia outbreak associated with a new coronavirus of probable bat origin

              Since the outbreak of severe acute respiratory syndrome (SARS) 18 years ago, a large number of SARS-related coronaviruses (SARSr-CoVs) have been discovered in their natural reservoir host, bats 1–4 . Previous studies have shown that some bat SARSr-CoVs have the potential to infect humans 5–7 . Here we report the identification and characterization of a new coronavirus (2019-nCoV), which caused an epidemic of acute respiratory syndrome in humans in Wuhan, China. The epidemic, which started on 12 December 2019, had caused 2,794 laboratory-confirmed infections including 80 deaths by 26 January 2020. Full-length genome sequences were obtained from five patients at an early stage of the outbreak. The sequences are almost identical and share 79.6% sequence identity to SARS-CoV. Furthermore, we show that 2019-nCoV is 96% identical at the whole-genome level to a bat coronavirus. Pairwise protein sequence analysis of seven conserved non-structural proteins domains show that this virus belongs to the species of SARSr-CoV. In addition, 2019-nCoV virus isolated from the bronchoalveolar lavage fluid of a critically ill patient could be neutralized by sera from several patients. Notably, we confirmed that 2019-nCoV uses the same cell entry receptor—angiotensin converting enzyme II (ACE2)—as SARS-CoV.
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                Author and article information

                Journal
                Science
                Science
                SCIENCE
                Science (New York, N.y.)
                American Association for the Advancement of Science
                0036-8075
                1095-9203
                20 May 2020
                : eabc6284
                Affiliations
                [1 ]Center for Virology and Vaccine Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA.
                [2 ]University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA.
                [3 ]Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA.
                [4 ]Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115, USA.
                [5 ]Bioqual, Rockville, MD 20852, USA.
                [6 ]Janssen Vaccines & Prevention BV, Leiden, Netherlands.
                [7 ]Children’s Hospital, Boston, MA 02115, USA.
                [8 ]Massachusetts Consortium on Pathogen Readiness, Boston, MA 02215, USA.
                Author notes
                [*]

                These authors contributed equally to this work.

                []Corresponding author. Email: dbarouch@ 123456bidmc.harvard.edu
                Author information
                https://orcid.org/0000-0002-0775-6623
                https://orcid.org/0000-0001-9255-5684
                https://orcid.org/0000-0002-2105-7503
                https://orcid.org/0000-0001-7769-7326
                https://orcid.org/0000-0002-3933-0539
                https://orcid.org/0000-0003-4094-8739
                https://orcid.org/0000-0002-0678-9765
                https://orcid.org/0000-0003-0504-2181
                https://orcid.org/0000-0001-7821-5552
                https://orcid.org/0000-0003-3680-0627
                https://orcid.org/0000-0002-7489-0232
                https://orcid.org/0000-0003-2307-3379
                https://orcid.org/0000-0003-1282-8211
                https://orcid.org/0000-0001-8288-787X
                https://orcid.org/0000-0002-2625-6595
                https://orcid.org/0000-0002-3708-3810
                https://orcid.org/0000-0002-5209-9220
                https://orcid.org/0000-0002-2126-3008
                https://orcid.org/0000-0002-1240-9044
                https://orcid.org/0000-0003-3387-6693
                https://orcid.org/0000-0002-1564-5798
                https://orcid.org/0000-0003-2733-2753
                https://orcid.org/0000-0003-2822-6231
                https://orcid.org/0000-0002-9821-1492
                https://orcid.org/0000-0001-9409-5052
                https://orcid.org/0000-0002-9872-6074
                https://orcid.org/0000-0001-8520-2178
                https://orcid.org/0000-0001-6641-0342
                https://orcid.org/0000-0003-4082-6029
                https://orcid.org/0000-0002-7595-6205
                https://orcid.org/0000-0002-3288-8505
                https://orcid.org/0000-0002-4373-3242
                https://orcid.org/0000-0001-6958-9464
                https://orcid.org/0000-0002-3628-3802
                https://orcid.org/0000-0002-8625-1657
                https://orcid.org/0000-0003-3627-2553
                https://orcid.org/0000-0002-6690-944X
                https://orcid.org/0000-0001-6827-8701
                https://orcid.org/0000-0002-7680-9215
                https://orcid.org/0000-0003-1103-9608
                https://orcid.org/0000-0001-7852-0135
                https://orcid.org/0000-0001-5127-4659
                Article
                abc6284
                10.1126/science.abc6284
                7243363
                32434945
                3ed45639-ff5d-454d-8a10-3811d3ab7649
                Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

                This is an open-access article distributed under the terms of the Creative Commons Attribution license, which permits use, distribution, and reproduction in any medium, so long as the resultant use is not for commercial advantage and provided the original work is properly cited.

                History
                : 05 May 2020
                : 16 May 2020
                Funding
                Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: OD024917, AI129797, AI124377, AI128751, AI126603
                Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: AI007151
                Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: AI146779
                Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: AI121394, AI139538
                Funded by: doi http://dx.doi.org/10.13039/100000002, National Institutes of Health;
                Award ID: 272201700036I-0-759301900131-1, AI100625, AI110700, AI132178, AI149644, AI108197
                Funded by: doi http://dx.doi.org/10.13039/100000861, Burroughs Wellcome Fund;
                Funded by: doi http://dx.doi.org/10.13039/100005615, Beth Israel Deaconess Medical Center;
                Funded by: Ragon Institute of MGH, MIT, and Harvard;
                Funded by: Mark and Lisa Schwartz Foundation;
                Funded by: Massachusetts Consortium on Pathogen Readiness;
                Funded by: Janssen Vaccines and Prevention BV;
                Categories
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                R-Articles
                Immunology
                Microbio
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