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      Characterization of SARS-CoV-specific memory T cells from recovered individuals 4 years after infection

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          Abstract

          SARS-CoV infection of human results in antigen-specific cellular and humoral immune responses. However, it is critical to determine whether SARS-CoV-specific memory T cells can persist for long periods of time. In this study, we analyzed the cellular immune response from 21 SARS-recovered individuals who had been diagnosed with SARS in 2003 by using ELISA, CBA, ELISpot and multiparameter flow cytometry assays. Our results demonstrated that low levels of specific memory T cell responses to SARS-CoV S, M, E and N peptides were detected in a proportion of SARS-recovered patients, and IFN-γ was the predominant cytokine produced by T cells after stimulation with peptides. Cytometry analysis indicated that the majority of memory CD8 + T cells produced IFN-γ, whereas memory CD4 + T cells produced IFN-γ, IL-2 or TNF-α. These results might provide valuable information on the cellular immune response in recovered SARS-CoV patients for the rational design of vaccines against SARS-CoV infection.

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          Most cited references21

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          The spike protein of SARS-CoV — a target for vaccine and therapeutic development

          Key Points This Review provides an overview on the spike (S) protein of severe acute respiratory syndrome-coronavirus (SARS-CoV) as a target for the development of vaccines and therapeutics for the prevention and treatment of SARS. SARS is a newly emerging infectious disease, caused by SARS-CoV, a novel coronavirus that caused a global outbreak of SARS. SARS-CoV S protein mediates binding of the virus with its receptor angiotensin-converting enzyme 2 and promotes the fusion between the viral and host cell membranes and virus entry into the host cell. SARS-CoV S protein induces humoral and cellular immune responses against SARS-CoV. SARS S protein is the target of new SARS vaccines. These vaccines are based on SARS-CoV full-length S protein and its receptor-binding domain, including DNA-, viral vector- and subunit-based vaccines Peptides, antibodies, organic compounds and short interfering RNAs are additional anti-SARS-CoV therapeutics that target the S protein. The work on SARS-CoV S protein-based vaccines and drugs will be useful as a model for the development of prophylactic strategies and therapies against other viruses with class I fusion proteins that can cause emerging infectious diseases.
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            Multifunctional TH1 cells define a correlate of vaccine-mediated protection against Leishmania major.

            CD4+ T cells have a crucial role in mediating protection against a variety of pathogens through production of specific cytokines. However, substantial heterogeneity in CD4+ T-cell cytokine responses has limited the ability to define an immune correlate of protection after vaccination. Here, using multiparameter flow cytometry to assess the immune responses after immunization, we show that the degree of protection against Leishmania major infection in mice is predicted by the frequency of CD4+ T cells simultaneously producing interferon-gamma, interleukin-2 and tumor necrosis factor. Notably, multifunctional effector cells generated by all vaccines tested are unique in their capacity to produce high amounts of interferon-gamma. These data show that the quality of a CD4+ T-cell cytokine response can be a crucial determinant in whether a vaccine is protective, and may provide a new and useful prospective immune correlate of protection for vaccines based on T-helper type 1 (TH1) cells.
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              Coronavirus as a possible cause of severe acute respiratory syndrome

              Summary Background An outbreak of severe acute respiratory syndrome (SARS) has been reported in Hong Kong. We investigated the viral cause and clinical presentation among 50 patients. Methods We analysed case notes and microbiological findings for 50 patients with SARS, representing more than five separate epidemiologically linked transmission clusters. We defined the clinical presentation and risk factors associated with severe disease and investigated the causal agents by chest radiography and laboratory testing of nasopharyngeal aspirates and sera samples. We compared the laboratory findings with those submitted for microbiological investigation of other diseases from patients whose identity was masked. Findings Patients' age ranged from 23 to 74 years. Fever, chills, myalgia, and cough were the most frequent complaints. When compared with chest radiographic changes, respiratory symptoms and auscultatory findings were disproportionally mild. Patients who were household contacts of other infected people and had older age, lymphopenia, and liver dysfunction were associated with severe disease. A virus belonging to the family Coronaviridae was isolated from two patients. By use of serological and reverse-transcriptase PCR specific for this virus, 45 of 50 patients with SARS, but no controls, had evidence of infection with this virus. Interpretation A coronavirus was isolated from patients with SARS that might be the primary agent associated with this disease. Serological and molecular tests specific for the virus permitted a definitive laboratory diagnosis to be made and allowed further investigation to define whether other cofactors play a part in disease progression.
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                Author and article information

                Contributors
                +86-20-87331552 , +86-20-87331552 , changyou_wu@yahoo.com
                Journal
                Arch Virol
                Arch. Virol
                Archives of Virology
                Springer Vienna (Vienna )
                0304-8608
                1432-8798
                13 June 2009
                2009
                : 154
                : 7
                : 1093-1099
                Affiliations
                [1 ]GRID grid.12981.33, ISNI 000000012360039X, Key Laboratory of Tropical Disease Control Research of Ministry of Education, Department of Immunology, Zhongshan School of Medicine, , Sun Yat-Sen University, ; 74 Zhongshan 2nd Road, 510080 Guangzhou, People’s Republic of China
                [2 ]GRID grid.412536.7, ISNI 0000000417917851, Second Affiliated Hospital of the Sun Yat-Sen University, ; 510120 Guangzhou, China
                [3 ]GRID grid.419681.3, ISNI 0000000121649667, Vaccine Research Center, , NIAID/NIH, ; Bethesda, MD 20892 USA
                Article
                409
                10.1007/s00705-009-0409-6
                2796960
                19526193
                5d3a4b61-b860-40c7-b515-38712d101530
                © Springer-Verlag 2009

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 7 March 2009
                : 22 May 2009
                Categories
                Original Article
                Custom metadata
                © Springer-Verlag 2009

                Microbiology & Virology
                cellular immune response,ionomycin,elispot assay,intracellular cytokine staining,cytometric bead array

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