Negligible impact of SARS-CoV-2 variants on CD4<sup>+</sup>and CD8<sup>+</sup>T cell reactivity in COVID-19 exposed donors and vaccinees

Tarke, Alison; Sidney, John; Methot, Nils; Zhang, Yun; Dan, Jennifer M.; Goodwin, Benjamin; Rubiro, Paul; Sutherland, Aaron; Antunes, Ricardo da Silva; Fraizer, April; Rawlings, Stephen A.; Smith, Davey M; Peters, Bjoern; Scheuermann, Richard H.; Weiskopf, Daniela; Crotty, Shane; Grifoni, Alba; Sette, Alessandro

doi:10.1101/2021.02.27.433180

Cited by 168 publications

(184 citation statements)

References 73 publications

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“…current VOC (B.1.1.7 and B.1.351). This data is compatible with a recent preprint report that the epitope sequences of the vast majority of SARS-CoV-2 T cell epitopes are not affected by the mutations found in the B.1.1.7 or B.1.351 variants40 , with no signi cant differences observed in CD4 and CD8 responses to a pool of S peptides corresponding to the ancestral sequence and those corresponding to the different variants. T cell responses to SARS-CoV-2 are known to target a wide range of regions in spike41 .…”

supporting

confidence: 92%

Two doses of SARS-CoV-2 vaccination induce more robust immune responses to emerging SARS-CoV-2 variants of concern than does natural infection.

Skelly¹,

Harding²,

Gilbert‐Jaramillo³

et al. 2021

Preprint

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Both natural infection with SARS-CoV-2 and immunization with vaccines induce protective immunity. However, the extent to which such immune responses protect against emerging variants is of increasing importance. Such variants of concern (VOC) include isolates of lineage B.1.1.7, first identified in the UK, and B.1.351, first identified in South Africa. Our data confirm that VOC, particularly those with substitutions at residues 484 and 417, escape neutralization by antibodies directed to the ACE2-binding Class 1 and the adjacent Class 2 epitopes but are susceptible to neutralization by the generally less potent antibodies directed to Class 3 and 4 epitopes on the flanks of the receptor-binding domain. To address the potential threat posed by VOC, we sampled a SARS-CoV-2 uninfected UK cohort recently vaccinated with BNT162b2 (Pfizer-BioNTech, two doses delivered 18-28 days apart), alongside a cohort sampled in the early convalescent stages after natural infection in the first wave of the pandemic in Spring 2020. We tested antibody and T cell responses against a reference isolate of the original circulating lineage, B, and the impact of sequence variation in the B.1.1.7 and B.1.351 VOC. Neutralization of the VOC compared to B isolate was reduced, and this was most evident for the B.1.351 isolate. This reduction in antibody neutralization was less marked in post-boost vaccine-induced responses compared to naturally induced immune responses and could be largely explained by the potency of the homotypic antibody response. After a single vaccination, which induced only modestly neutralizing homotypic antibody titres, neutralization against the VOC was completely abrogated in the majority of vaccinees. Importantly, high magnitude T cell responses were generated after two vaccine doses, with the majority of the T cell response directed against epitopes that are conserved between the prototype isolate B and the VOC. These data indicate that VOC may evade protective neutralizing responses induced by prior infection, and to a lesser extent by immunization, particularly after a single vaccine dose, but the impact of the VOC on T cell responses appears less marked. The results emphasize the need to generate high potency immune responses through vaccination in order to provide protection against these and other emergent variants.

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supporting

confidence: 92%

Two doses of SARS-CoV-2 vaccination induce more robust immune responses to emerging SARS-CoV-2 variants of concern than does natural infection.

Skelly¹,

Harding²,

Gilbert‐Jaramillo³

et al. 2021

Preprint

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“…Limited data on the immunological determinants of protection are available, however recent data from rhesus macaques indicate that relatively low neutralizing antibody titers are sufficient for protection against SARS-CoV-2, and that cellular immune responses may contribute to protection if antibody responses are suboptimal 21 . Induction of binding and neutralizing antibodies as well as SARS-CoV-2 cellular spike protein-specific T cell responses after vaccination have been reported 22,23 and most SARS-CoV-2 specific T cell epitopes in both convalescent and vaccinated individuals are not affected by the AA substitutions found in the spike protein of the B.1.1.7 and B.1.351 variants 24 . Protection against severe COVID-19 disease might be mediated by T cells and would therefore not be different between the current variants.…”

Section: Mainmentioning

confidence: 94%

ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7

Fischer

Doremalen

Adney

et al. 2021

Preprint

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We investigated ChAdOx1 nCoV-19 (AZD1222) vaccine efficacy against SARS-CoV-2 variants of concern (VOCs) B.1.1.7 and B.1.351 in Syrian hamsters. We previously showed protection against SARS-CoV-2 disease and pneumonia in hamsters vaccinated with a single dose of ChAdOx1 nCoV-19. Here, we observed a 9.5-fold reduction of virus neutralizing antibody titer in vaccinated hamster sera against B.1.351 compared to B.1.1.7. Vaccinated hamsters challenged with B.1.1.7 or B.1.351 did not lose weight compared to control animals. In contrast to control animals, the lungs of vaccinated animals did not show any gross lesions. Minimal to no viral subgenomic RNA (sgRNA) and no infectious virus was detected in lungs of vaccinated animals. Histopathological evaluation showed extensive pulmonary pathology caused by B.1.1.7 or B.1.351 replication in the control animals, but none in the vaccinated animals. These data demonstrate the effectiveness of the ChAdOx1 nCoV-19 vaccine against clinical disease caused by B.1.1.7 or B.1.351 VOCs.

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“…In addition to neutralising and binding antibodies, SARS-CoV-2 infection also elicits a vast repertoire of T cell responses and dominant epitopes had the capacity to bind multiple HLA allelic variants [22]. A further study by the same authors found that "CD4+ and CD8+ T cell responses in convalescent COVID-19 subjects or COVID-19 mRNA vaccinees are not substantially affected by mutations found in the SARS-CoV-2 variants" [23]. A major limitation of that study is that all donors were recruited in California and had no known exposure to the escape variants first found in the UK, South Africa or Brazil.…”

Section: Cell Binding and Functional Immunitymentioning

confidence: 99%

Severe acute respiratory syndrome coronavirus 2 escape mutants and protective immunity from natural infections or immunizations

Cunha

Petrosillo

et al. 2021

Clinical Microbiology and Infection

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Although coronaviruses have lower mutation rates than other respiratory RNA viruses, the scale of the pandemic has brought the importance of viral evolution for coronaviruses to centre stage. Three recently detected SARS-CoV-2 lineages (B.1.1.7, B.1.351, and P.1), have been scrutinized because they are unusually divergent and each possesses a unique constellation of mutations of potential biological importance, several of which are in the gene coding for the Spike protein. We briefly summarize the current knowledge on these variants, and their possible implications.

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Negligible impact of SARS-CoV-2 variants on CD4⁺and CD8⁺T cell reactivity in COVID-19 exposed donors and vaccinees

Cited by 168 publications

References 73 publications

Two doses of SARS-CoV-2 vaccination induce more robust immune responses to emerging SARS-CoV-2 variants of concern than does natural infection.

Two doses of SARS-CoV-2 vaccination induce more robust immune responses to emerging SARS-CoV-2 variants of concern than does natural infection.

ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7

Severe acute respiratory syndrome coronavirus 2 escape mutants and protective immunity from natural infections or immunizations

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Negligible impact of SARS-CoV-2 variants on CD4+and CD8+T cell reactivity in COVID-19 exposed donors and vaccinees

Cited by 168 publications

References 73 publications

Two doses of SARS-CoV-2 vaccination induce more robust immune responses to emerging SARS-CoV-2 variants of concern than does natural infection.

Two doses of SARS-CoV-2 vaccination induce more robust immune responses to emerging SARS-CoV-2 variants of concern than does natural infection.

ChAdOx1 nCoV-19 (AZD1222) protects Syrian hamsters against SARS-CoV-2 B.1.351 and B.1.1.7

Severe acute respiratory syndrome coronavirus 2 escape mutants and protective immunity from natural infections or immunizations

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Product

Resources

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Negligible impact of SARS-CoV-2 variants on CD4⁺and CD8⁺T cell reactivity in COVID-19 exposed donors and vaccinees