Article SARS-CoV-2-specific T cell immunity in cases of COVID-19 and SARS, and uninfected controls
Nina Le Bert1,9, Anthony T. Tan1,9, Kamini Kunasegaran1 , Christine Y. L. Tham1 , Morteza Hafezi1 , Adeline Chia1 , Melissa Hui Yen Chng1 , Meiyin Lin1,2, Nicole Tan1 , Martin Linster1 , Wan Ni Chia1 , Mark I-Cheng Chen3 , Lin-Fa Wang1 , Eng Eong Ooi1 , Shirin Kalimuddin4 , Paul Anantharajah Tambyah5,6, Jenny Guek-Hong Low1,4, Yee-Joo Tan2,7 & Antonio Bertoletti
Memory T cells induced by previous pathogens can shape susceptibility to, and the clinical severity of, subsequent infections1 . Little is known about the presence in humans of pre-existing memory T cells that have the potential to recognize severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Here we studied T cell responses against the structural (nucleocapsid (N) protein) and non-structural (NSP7 and NSP13 of ORF1) regions of SARS-CoV-2 in individuals convalescing from coronavirus disease 2019 (COVID-19) (n = 36). In all of these individuals, we found CD4 and CD8 T cells that recognized multiple regions of the N protein. Next, we showed that patients (n = 23) who recovered from SARS (the disease associated with SARS-CoV infection) possess long-lasting memory T cells that are reactive to the N protein of SARS-CoV 17 years after the outbreak of SARS in 2003; these T cells displayed robust cross-reactivity to the N protein of SARS-CoV-2. We also detected SARS-CoV-2-specifc T cells in individuals with no history of SARS, COVID-19 or contact with individuals who had SARS and/or COVID-19 (n = 37). SARS-CoV-2-specifc T cells in uninfected donors exhibited a diferent pattern of immunodominance, and frequently targeted NSP7 and NSP13 as well as the N protein. Epitope characterization of NSP7-specifc T cells showed the recognition of protein fragments that are conserved among animal betacoronaviruses but have low homology to ‘common cold’ human-associated coronaviruses. Thus, infection with betacoronaviruses induces multi-specifc and long-lasting T cell immunity against the structural N protein. Understanding how pre-existing N- and ORF1-specifc T cells that are present in the general population afect the susceptibility to and pathogenesis of SARS-CoV-2 infection is important for the management of the current COVID-19 pandemic.
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