SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees

Daryl Geers; Marc C. Shamier; Susanne Bogers; Gerco den Hartog; Lennert Gommers; Nella N. Nieuwkoop; Katharina S. Schmitz; Laurine C. Rijsbergen; Jolieke A.T. van Osch; Emma Dijkhuizen; Gaby Smits; Anouskha Comvalius; Djenolan van Mourik; Tom G. Caniels; Marit J. van Gils; Rogier W. Sanders; Bas B. Oude Munnink; Richard Molenkamp; Herbert J. de Jager; Bart L. Haagmans; Rik L. de Swart; Marion P.G. Koopmans; Robert S. van Binnendijk; Rory D. de Vries; Corine H. GeurtsvanKessel

doi:10.1126/sciimmunol.abj1750

SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees

Daryl Geers, Marc C. Shamier, Susanne Bogers, Gerco den Hartog, Lennert Gommers, Nella N. Nieuwkoop, Katharina S. Schmitz, Laurine C. Rijsbergen, Jolieke A.T. van Osch, Emma Dijkhuizen, Gaby Smits, Anouskha Comvalius, Djenolan van Mourik, Tom G. Caniels, Marit J. van Gils, Rogier W. Sanders, Bas B. Oude Munnink, Richard Molenkamp, Herbert J. de Jager, Bart L. HaagmansRik L. de Swart, Marion P.G. Koopmans, Robert S. van Binnendijk, Rory D. de Vries^*, Corine H. GeurtsvanKessel^*

^*Corresponding author for this work

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Abstract

The emergence of SARS-CoV-2 variants harboring mutations in the spike (S) protein has raised concern about potential immune escape. Here, we studied humoral and cellular immune responses to wild type SARS-CoV-2 and the B.1.1.7 and B.1.351 variants of concern in a cohort of 121 BNT162b2 mRNA-vaccinated health care workers (HCW). Twenty-three HCW recovered from mild COVID-19 disease and exhibited a recall response with high levels of SARS-CoV-2-specific functional antibodies and virus-specific T cells after a single vaccination. Specific immune responses were also detected in seronegative HCW after one vaccination, but a second dose was required to reach high levels of functional antibodies and cellular immune responses in all individuals. Vaccination-induced antibodies cross-neutralized the variants B.1.1.7 and B.1.351, but the neutralizing capacity and Fc-mediated functionality against B.1.351 was consistently 2-to 4-fold lower than to the homologous virus. In addition, peripheral blood mononuclear cells were stimulated with peptide pools spanning the mutated S regions of B.1.1.7 and B.1.351 to detect cross-reactivity of SARS-CoV-2-specific T cells with variants. Importantly, we observed no differences in CD4⁺ T-cell activation in response to variant antigens, indicating that the B.1.1.7 and B.1.351 S proteins do not escape T-cell-mediated immunity elicited by the wild type S protein. In conclusion, this study shows that some variants can partially escape humoral immunity induced by SARS-CoV-2 infection or BNT162b2 vaccination, but S-specific CD4⁺ T-cell activation is not affected by the mutations in the B.1.1.7 and B.1.351 variants.

Original language	English
Article number	eabj1750
Journal	Science immunology
Volume	6
Issue number	59
Early online date	25 May 2021
DOIs	https://doi.org/10.1126/sciimmunol.abj1750
Publication status	Published - 28 Jul 2021

Bibliographical note

Funding Information:
This work was financially supported by the Top Sector Life Sciences & Health; Health~Holland (grant EMCLHS20017: DG, LG. RDdV), the European Union?s Horizon 2020 research and innovation program under grant No. 101003589 (RECoVER: BBOM, MPGK), ZonMW (grant agreement No. 10150062010005: BBOM, MPGK; and No. 10150062010008: BLH), the Netherlands Organization for Scientific Research (NWO) Vici grant (RWS), the Bill & Melinda Gates Foundation grant INV-002022 (RWS), and an Amsterdam UMC AMC Fellowship (MJvG). Author contributions: Conceptualization RDdV, CHGvK Formal Analysis DG, MCS, RDdV, CHGvK Funding acquisition MJvG, RWS, BLH, RLdS, MPGK, RSvB, RDdV, CHGvK Investigation DG, MCS, SB, GdH, LG, NNN, KSS, LCR, GS, AC, DvM, BBOM, RM, RSvB, RDdV Project administration SB, JATvO, ED, RDdV, CHGvK Resources TGC, MJvG, RWS, HJdJ, BLH, RDdV, CHGvK Supervision RWS, BLH, RLdS,

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© 2021 American Association for the Advancement of Science. All rights reserved.

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Geers, D., Shamier, M. C., Bogers, S., den Hartog, G., Gommers, L., Nieuwkoop, N. N., Schmitz, K. S., Rijsbergen, L. C., van Osch, J. A. T., Dijkhuizen, E., Smits, G., Comvalius, A., van Mourik, D., Caniels, T. G., van Gils, M. J., Sanders, R. W., Oude Munnink, B. B., Molenkamp, R., de Jager, H. J., ... GeurtsvanKessel, C. H. (2021). SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees. Science immunology, 6(59), Article eabj1750. Advance online publication. https://doi.org/10.1126/sciimmunol.abj1750

@article{169f84e944d34f8b826a7ace59057497,

title = "SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees",

abstract = "The emergence of SARS-CoV-2 variants harboring mutations in the spike (S) protein has raised concern about potential immune escape. Here, we studied humoral and cellular immune responses to wild type SARS-CoV-2 and the B.1.1.7 and B.1.351 variants of concern in a cohort of 121 BNT162b2 mRNA-vaccinated health care workers (HCW). Twenty-three HCW recovered from mild COVID-19 disease and exhibited a recall response with high levels of SARS-CoV-2-specific functional antibodies and virus-specific T cells after a single vaccination. Specific immune responses were also detected in seronegative HCW after one vaccination, but a second dose was required to reach high levels of functional antibodies and cellular immune responses in all individuals. Vaccination-induced antibodies cross-neutralized the variants B.1.1.7 and B.1.351, but the neutralizing capacity and Fc-mediated functionality against B.1.351 was consistently 2-to 4-fold lower than to the homologous virus. In addition, peripheral blood mononuclear cells were stimulated with peptide pools spanning the mutated S regions of B.1.1.7 and B.1.351 to detect cross-reactivity of SARS-CoV-2-specific T cells with variants. Importantly, we observed no differences in CD4+ T-cell activation in response to variant antigens, indicating that the B.1.1.7 and B.1.351 S proteins do not escape T-cell-mediated immunity elicited by the wild type S protein. In conclusion, this study shows that some variants can partially escape humoral immunity induced by SARS-CoV-2 infection or BNT162b2 vaccination, but S-specific CD4+ T-cell activation is not affected by the mutations in the B.1.1.7 and B.1.351 variants.",

author = "Daryl Geers and Shamier, {Marc C.} and Susanne Bogers and {den Hartog}, Gerco and Lennert Gommers and Nieuwkoop, {Nella N.} and Schmitz, {Katharina S.} and Rijsbergen, {Laurine C.} and {van Osch}, {Jolieke A.T.} and Emma Dijkhuizen and Gaby Smits and Anouskha Comvalius and {van Mourik}, Djenolan and Caniels, {Tom G.} and {van Gils}, {Marit J.} and Sanders, {Rogier W.} and {Oude Munnink}, {Bas B.} and Richard Molenkamp and {de Jager}, {Herbert J.} and Haagmans, {Bart L.} and {de Swart}, {Rik L.} and Koopmans, {Marion P.G.} and {van Binnendijk}, {Robert S.} and {de Vries}, {Rory D.} and GeurtsvanKessel, {Corine H.}",

note = "Funding Information: This work was financially supported by the Top Sector Life Sciences & Health; Health~Holland (grant EMCLHS20017: DG, LG. RDdV), the European Union?s Horizon 2020 research and innovation program under grant No. 101003589 (RECoVER: BBOM, MPGK), ZonMW (grant agreement No. 10150062010005: BBOM, MPGK; and No. 10150062010008: BLH), the Netherlands Organization for Scientific Research (NWO) Vici grant (RWS), the Bill & Melinda Gates Foundation grant INV-002022 (RWS), and an Amsterdam UMC AMC Fellowship (MJvG). Author contributions: Conceptualization RDdV, CHGvK Formal Analysis DG, MCS, RDdV, CHGvK Funding acquisition MJvG, RWS, BLH, RLdS, MPGK, RSvB, RDdV, CHGvK Investigation DG, MCS, SB, GdH, LG, NNN, KSS, LCR, GS, AC, DvM, BBOM, RM, RSvB, RDdV Project administration SB, JATvO, ED, RDdV, CHGvK Resources TGC, MJvG, RWS, HJdJ, BLH, RDdV, CHGvK Supervision RWS, BLH, RLdS, Publisher Copyright: {\textcopyright} 2021 American Association for the Advancement of Science. All rights reserved.",

year = "2021",

month = jul,

day = "28",

doi = "10.1126/sciimmunol.abj1750",

language = "English",

volume = "6",

journal = "Science immunology",

issn = "2470-9468",

publisher = "American Association for the Advancement of Science",

number = "59",

}

Geers, D , Shamier, MC, Bogers, S, den Hartog, G, Gommers, L, Nieuwkoop, NN , Schmitz, KS , Rijsbergen, LC, van Osch, JAT, Dijkhuizen, E, Smits, G, Comvalius, A, van Mourik, D, Caniels, TG, van Gils, MJ, Sanders, RW, Oude Munnink, BB , Molenkamp, R, de Jager, HJ, Haagmans, BL , de Swart, RL , Koopmans, MPG, van Binnendijk, RS, de Vries, RD & GeurtsvanKessel, CH 2021, 'SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees', Science immunology, vol. 6, no. 59, eabj1750. https://doi.org/10.1126/sciimmunol.abj1750

TY - JOUR

T1 - SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees

AU - Geers, Daryl

AU - Shamier, Marc C.

AU - Bogers, Susanne

AU - den Hartog, Gerco

AU - Gommers, Lennert

AU - Nieuwkoop, Nella N.

AU - Schmitz, Katharina S.

AU - Rijsbergen, Laurine C.

AU - van Osch, Jolieke A.T.

AU - Dijkhuizen, Emma

AU - Smits, Gaby

AU - Comvalius, Anouskha

AU - van Mourik, Djenolan

AU - Caniels, Tom G.

AU - van Gils, Marit J.

AU - Sanders, Rogier W.

AU - Oude Munnink, Bas B.

AU - Molenkamp, Richard

AU - de Jager, Herbert J.

AU - Haagmans, Bart L.

AU - de Swart, Rik L.

AU - Koopmans, Marion P.G.

AU - van Binnendijk, Robert S.

AU - de Vries, Rory D.

AU - GeurtsvanKessel, Corine H.

N1 - Funding Information: This work was financially supported by the Top Sector Life Sciences & Health; Health~Holland (grant EMCLHS20017: DG, LG. RDdV), the European Union?s Horizon 2020 research and innovation program under grant No. 101003589 (RECoVER: BBOM, MPGK), ZonMW (grant agreement No. 10150062010005: BBOM, MPGK; and No. 10150062010008: BLH), the Netherlands Organization for Scientific Research (NWO) Vici grant (RWS), the Bill & Melinda Gates Foundation grant INV-002022 (RWS), and an Amsterdam UMC AMC Fellowship (MJvG). Author contributions: Conceptualization RDdV, CHGvK Formal Analysis DG, MCS, RDdV, CHGvK Funding acquisition MJvG, RWS, BLH, RLdS, MPGK, RSvB, RDdV, CHGvK Investigation DG, MCS, SB, GdH, LG, NNN, KSS, LCR, GS, AC, DvM, BBOM, RM, RSvB, RDdV Project administration SB, JATvO, ED, RDdV, CHGvK Resources TGC, MJvG, RWS, HJdJ, BLH, RDdV, CHGvK Supervision RWS, BLH, RLdS, Publisher Copyright: © 2021 American Association for the Advancement of Science. All rights reserved.

PY - 2021/7/28

Y1 - 2021/7/28

N2 - The emergence of SARS-CoV-2 variants harboring mutations in the spike (S) protein has raised concern about potential immune escape. Here, we studied humoral and cellular immune responses to wild type SARS-CoV-2 and the B.1.1.7 and B.1.351 variants of concern in a cohort of 121 BNT162b2 mRNA-vaccinated health care workers (HCW). Twenty-three HCW recovered from mild COVID-19 disease and exhibited a recall response with high levels of SARS-CoV-2-specific functional antibodies and virus-specific T cells after a single vaccination. Specific immune responses were also detected in seronegative HCW after one vaccination, but a second dose was required to reach high levels of functional antibodies and cellular immune responses in all individuals. Vaccination-induced antibodies cross-neutralized the variants B.1.1.7 and B.1.351, but the neutralizing capacity and Fc-mediated functionality against B.1.351 was consistently 2-to 4-fold lower than to the homologous virus. In addition, peripheral blood mononuclear cells were stimulated with peptide pools spanning the mutated S regions of B.1.1.7 and B.1.351 to detect cross-reactivity of SARS-CoV-2-specific T cells with variants. Importantly, we observed no differences in CD4+ T-cell activation in response to variant antigens, indicating that the B.1.1.7 and B.1.351 S proteins do not escape T-cell-mediated immunity elicited by the wild type S protein. In conclusion, this study shows that some variants can partially escape humoral immunity induced by SARS-CoV-2 infection or BNT162b2 vaccination, but S-specific CD4+ T-cell activation is not affected by the mutations in the B.1.1.7 and B.1.351 variants.

AB - The emergence of SARS-CoV-2 variants harboring mutations in the spike (S) protein has raised concern about potential immune escape. Here, we studied humoral and cellular immune responses to wild type SARS-CoV-2 and the B.1.1.7 and B.1.351 variants of concern in a cohort of 121 BNT162b2 mRNA-vaccinated health care workers (HCW). Twenty-three HCW recovered from mild COVID-19 disease and exhibited a recall response with high levels of SARS-CoV-2-specific functional antibodies and virus-specific T cells after a single vaccination. Specific immune responses were also detected in seronegative HCW after one vaccination, but a second dose was required to reach high levels of functional antibodies and cellular immune responses in all individuals. Vaccination-induced antibodies cross-neutralized the variants B.1.1.7 and B.1.351, but the neutralizing capacity and Fc-mediated functionality against B.1.351 was consistently 2-to 4-fold lower than to the homologous virus. In addition, peripheral blood mononuclear cells were stimulated with peptide pools spanning the mutated S regions of B.1.1.7 and B.1.351 to detect cross-reactivity of SARS-CoV-2-specific T cells with variants. Importantly, we observed no differences in CD4+ T-cell activation in response to variant antigens, indicating that the B.1.1.7 and B.1.351 S proteins do not escape T-cell-mediated immunity elicited by the wild type S protein. In conclusion, this study shows that some variants can partially escape humoral immunity induced by SARS-CoV-2 infection or BNT162b2 vaccination, but S-specific CD4+ T-cell activation is not affected by the mutations in the B.1.1.7 and B.1.351 variants.

UR - http://www.scopus.com/inward/record.url?scp=85106959623&partnerID=8YFLogxK

U2 - 10.1126/sciimmunol.abj1750

DO - 10.1126/sciimmunol.abj1750

M3 - Article

C2 - 34035118

AN - SCOPUS:85106959623

SN - 2470-9468

VL - 6

JO - Science immunology

JF - Science immunology

IS - 59

M1 - eabj1750

ER -

SARS-CoV-2 variants of concern partially escape humoral but not T-cell responses in COVID-19 convalescent donors and vaccinees

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