SARS-CoV-2 elicits robust adaptive immune responses regardless of disease severity

Abstract

The SARS-CoV-2 pandemic currently prevails worldwide. To understand the immunological signature of SARS-CoV-2 infections and aid the search for treatments and vaccines, comprehensive characterization of adaptive immune responses towards SARS-CoV-2 is needed. We investigated the breadth and potency of antibody-, and T-cell immune responses, in 203 recovered SARS-CoV-2 infected patients who presented with asymptomatic to severe infections. We report very broad serological profiles with cross-reactivity to other human coronaviruses. Further, >99% had SARS-CoV-2 epitope specific antibodies, with SARS-CoV-2 neutralization and spike-ACE2 receptor interaction blocking observed in 95% of individuals. A significant positive correlation between spike-ACE2 blocking antibody titers and neutralization potency was observed. SARS-CoV-2 specific CD8+ T-cell responses were clear and quantifiable in 90% of HLA-A2+ individuals. The viral surface spike protein was identified as the dominant target for both neutralizing antibodies and CD8+ T cell responses. Overall, the majority of patients had robust adaptive immune responses, regardless of disease severity. These data support the possibility of achieving protective immunity through natural infection and bode well for the prospects of inducing immunological memory through vaccination.

SARS-CoV-2 human T cell epitopes: Adaptive immune response against COVID-19

“…Some specific epitopes are highlighted as being immunodominant in multiple studies. For example, in the context of the HLA-A*02:01 class I molecule, which is the most studied for CD8 SARS-CoV-2 responses, the S 269-277 epitope (sequence YLQPRTFLL) is detected in 81% of HLA-A2+ individuals in the Nielsen study (Nielsen et al, 2020). The same A2 dominant epitope is also reported by Shomuradova et al, who tested 13 A2 peptides in total, and also identified a less strongly recognized epitope (Shomuradova et al, 2020).…”

“…This breadth of response is apparently at variance with other reports describing only a limited number of epitopes for SARS-COV-2 (Chen et al, 2021;Le Bert et al, 2020;Lee et al, 2020;Nielsen et al, 2020;Rha et al, 2021;Sekine et al, 2020;Kared et al, 2021;Sahin et al, 2020). In some cases, in vitro expansion with artificial antigens has been utilized, and/or a limited number of subjects, cells, and/or epitope candidates were screened.…”

“…The same study also found that the response is broad and multi-specific, with 8-9 different antigens required to cover about 80% of the total CD4 and CD8 response (Tarke et al, 2021a). Nielsen et al also concluded that the response is broad, since the top three immunogenic epitopes derived from separate SARS CoV-2 proteins (Nielsen et al, 2020). Keller et al reported immunodominant epitopes defined as epitopes being recognized in multiple donors from M, N, and S (Keller et al, 2020).…”

“…Here, we focus on a specific topic: our current knowledge concerning the definition and recognition of SARS-CoV-2-derived T cell epitopes in humans. While the data related to this topic was initially sparse, 25 different studies have now been published as of March 15, 2021 (Chen et al, 2021;Ferretti et al, 2020;Gangaev et al, 2020;Habel et al, 2020;Joag et al, 2021;Kared et al, 2021;Keller et al, 2020;Le Bert et al, 2021Lee et al, 2020;Mahajan et al, 2020;Mateus et al, 2020;Nelde et al, 2021;Nielsen et al, 2020;Peng et al, 2020;Poran et al, 2020bPoran et al, , 2020aPrakash et al, 2020;Rha et al, 2021;Sahin et al, 2020;Saini et al, 2020, 2021, Schulien et al, 2021Sekine et al, 2020;Shomuradova et al, 2020;Snyder et al, 2020;Tarke et al, 2021a), which collectively report data from 1,197 human subjects (870 COVID-19 and 327 unexposed controls), leading to the identification of over 1,400 different CD4 (n = 382) and CD8 (n = 1052) T cell epitopes. These studies are listed in Table 1, which also captures whether these studies defined class I/CD8 epitopes and/or class II/CD4 epitopes.…”

Landscape of epitopes targeted by T cells in 852 individuals recovered from COVID-19: Meta-analysis, immunoprevalence, and web platform

“…Habel et al 25 Figure 2B T cell epitopes from convalescent COVID-19 patients Hu et al 31 Table 1 T cell epitopes from convalescent COVID-19 patients Nielsen et al 21 Figure 5B T cell epitopes from convalescent COVID-19 patients Tarke et al 36 Tables S3 and S5 T cell epitopes from convalescent COVID-19 patients Sekine et al 23 Table S2 T cell epitopes from convalescent COVID-19 patients Saini et al 14 Table S5 T cell epitopes from convalescent COVID-19 patients Lee et al 34 Figure 13 T cell epitopes from convalescent COVID-19 patients Rha et al 28 Figure 1C T cell epitopes from convalescent COVID-19 patients Lineburg et al 33 Table S3 T cell epitopes from convalescent COVID-19 patients Nguyen et al 24 Figure 3C Response…”