SARS -CoV-2 T-cell immunity to variants of concern following vaccination

Gallagher, Kathleen M.E.; Leick, Mark B.; Larson, Rebecca C.; Berger, Trisha R.; Katsis, Katelin; Yam, Jennifer; Brini, Gabrielle; Grauwet, Korneel; Maus, Marcela V.

doi:10.1101/2021.05.03.442455

Cited by 33 publications

(31 citation statements)

References 52 publications

(85 reference statements)

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“…Vaccination induced T cell responses that crossrecognized pooled peptides based on Beta spike, suggesting that most vaccinees target conserved epitopes in spike. These data are in accordance with several recent studies (Reynolds et al, 2021;Gallagher et al, 2021;Geers et al, 2021;Tarke et al, 2021), including our own (Riou et al, 2021b), describing a minimal impact of mutations in SARS-CoV-2 variants on T cell responses in the context of infection and vaccination.…”

Section: Discussionsupporting

confidence: 93%

Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner

Keeton

Richardson

Moyo-Gwete

et al. 2021

Preprint

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The Johnson and Johnson Ad26.COV2.S single dose vaccine, designed as an emergency response to the pandemic, represents an attractive option for the scale-up of COVID-19 vaccination in resource-limited countries. We examined the effect of prior infection with ancestral (D614G) or Beta variants on Ad26.COV2.S immunogenicity approximately 28 days post-vaccination. We compared healthcare workers who were SARS-CoV-2 naive (n=20), to those infected during the first wave prior to the emergence of Beta (n=20), and those infected in the second wave (n=20), when Beta was the dominant variant. We demonstrate that a priming exposure from infection significantly increased the magnitude of spike binding antibodies, neutralizing antibodies and antibody-dependent cellular cytotoxicity activity (ADCC) against D614G, Beta and Delta variants. The magnitude of antibody boosting was similar in both waves, despite the longer time interval between wave 1 infection and vaccination (7 months), compared to wave 2 (2 months). ADCC and binding cross-reactivity was similar in both waves. However, neutralization cross-reactivity varied by wave, showing that the antibody repertoire was shaped by the spike sequence of the infecting variant. Robust CD4 and CD8 T cell responses to spike of similar or higher magnitude as those elicited by infection were induced after vaccination. In contrast to antibody responses, prior infection was not required for the generation of high magnitude T cell responses, and T cell recognition of the Beta variant was fully preserved. Therefore, Ad26.COV2.S vaccination following prior infection, even >6 months previously, may result in substantially enhanced protection against COVID-19, of particular relevance in settings of high SARS-CoV-2 seroprevalence. Furthermore, the dominant impact of the infecting variant on neutralization breadth after vaccination has important implications for the design of second-generation vaccines based on variants of concern.

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Section: Discussionsupporting

confidence: 93%

Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner

Keeton

Richardson

Moyo-Gwete

et al. 2021

Preprint

View full text Add to dashboard Cite

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“…More importantly, while nearly all patients generated an antibody response, the threshold antibody concentration for disease protection is unknown. We also have no data on T cell response 31 as it appears that robust T cell responses are not necessarily linked to the development of a high titer of neutralizing antibodies. 32 Nevertheless, our data are supportive that the mRNA 2-dose vaccines result in the development of anti-spike antibodies in nearly all patients with PCD.…”

Section: Discussionmentioning

confidence: 98%

COVID-19 Vaccine Responses in Patients With Plasma Cell Dyscrasias After Complete Vaccination

Shah

Gabel

Beers

et al. 2022

Clinical Lymphoma Myeloma and Leukemia

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“…We performed ELISpot assays with peripheral blood mononuclear cells (PBMCs) from six convalescent individuals expressing HLA-A*02:01 and monitored IFNg secretion in response to a pool of 15 HLA-I peptides from canonical ORFs and 7 peptides from the out-of-frame ORFs. As a positive control, we compared the T cell responses with a pool of 102 peptides tiling the N protein measured in the same individuals as part of another study (Gallagher et al, 2021). We observed positive responses to the non-canonical pool in two of the six samples (Figures 6C and 6D).…”

Section: Out-of-frame Hla-i Peptides Elicit T Cell Responses In Humanized Hla-a2 Mice and Individuals With Covid-19mentioning

confidence: 93%

Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs

Weingarten-Gabbay

Klaeger

Sarkizova

et al. 2021

Cell

Self Cite

103

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T cell-mediated immunity plays an important role in controlling SARS-CoV-2 infection, but the repertoire of naturally processed and presented viral epitopes on class I human leukocyte antigen (HLA-I) remains uncharacterized. Here, we report the first HLA-I immunopeptidome of SARS-CoV-2 in two cell lines at different times post infection using mass spectrometry. We found HLA-I peptides derived not only from canonical open reading frames (ORFs) but also from internal out-of-frame ORFs in spike and nucleocapsid not captured by current vaccines. Some peptides from out-of-frame ORFs elicited T cell responses in a humanized mouse model and individuals with COVID-19 that exceeded responses to canonical peptides, including some of the strongest epitopes reported to date. Whole-proteome analysis of infected cells revealed that early expressed viral proteins contribute more to HLA-I presentation and immunogenicity. These biological insights, as well as the discovery of out-of-frame ORF epitopes, will facilitate selection of peptides for immune monitoring and vaccine development.

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SARS -CoV-2 T-cell immunity to variants of concern following vaccination

Cited by 33 publications

References 52 publications

Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner

Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner

COVID-19 Vaccine Responses in Patients With Plasma Cell Dyscrasias After Complete Vaccination

Profiling SARS-CoV-2 HLA-I peptidome reveals T cell epitopes from out-of-frame ORFs

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