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

Roanne Keeton; Simone I. Richardson; Thandeka Moyo-Gwete; Tandile Hermanus; Marius B. Tincho; Ntombi Benede; Nelia P. Manamela; Richard Baguma; Zanele Makhado; Amkele Ngomti; Thopisang Motlou; Mathilda Mennen; Lionel Chinhoyi; Sango Skelem; Hazel Maboreke; Deelan Doolabh; Arash Iranzadeh; Ashley D. Otter; Tim Brooks; Mahdad Noursadeghi; James C. Moon; Alba Grifoni; Daniela Weiskopf; Alessandro Sette; Jonathan Blackburn; Nei Yuan Hsiao; Carolyn Williamson; Catherine Riou; Ameena Goga; Nigel Garrett; Linda Gail Bekker; Glenda Gray; Ntobeko A.B. Ntusi; Penny L. Moore; Wendy A. Burgers

doi:10.1016/j.chom.2021.10.003

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

Roanne Keeton, Simone I. Richardson, Thandeka Moyo-Gwete, Tandile Hermanus, Marius B. Tincho, Ntombi Benede, Nelia P. Manamela, Richard Baguma, Zanele Makhado, Amkele Ngomti, Thopisang Motlou, Mathilda Mennen, Lionel Chinhoyi, Sango Skelem, Hazel Maboreke, Deelan Doolabh, Arash Iranzadeh, Ashley D. Otter, Tim Brooks, Mahdad NoursadeghiJames C. Moon, Alba Grifoni, Daniela Weiskopf, Alessandro Sette, Jonathan Blackburn, Nei Yuan Hsiao, Carolyn Williamson, Catherine Riou, Ameena Goga, Nigel Garrett, Linda Gail Bekker, Glenda Gray, Ntobeko A.B. Ntusi^*, Penny L. Moore, Wendy A. Burgers

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

59 Citations (Scopus)

Abstract

The Johnson and Johnson Ad26.COV2.S single-dose vaccine represents an attractive option for coronavirus disease 2019 (COVID-19) vaccination in countries with limited resources. We examined the effect of prior infection with different SARS-CoV-2 variants on Ad26.COV2.S immunogenicity. We compared participants who were SARS-CoV-2 naive with those either infected with the ancestral D614G virus or infected in the second wave when Beta predominated. Prior infection significantly boosts spike-binding antibodies, antibody-dependent cellular cytotoxicity, and neutralizing antibodies against D614G, Beta, and Delta; however, neutralization cross-reactivity varied by wave. Robust CD4 and CD8 T cell responses are induced after vaccination, regardless of prior infection. T cell recognition of variants is largely preserved, apart from some reduction in CD8 recognition of Delta. Thus, Ad26.COV2.S vaccination after infection could result in enhanced protection against COVID-19. The impact of the infecting variant on neutralization breadth after vaccination has implications for the design of second-generation vaccines based on variants of concern.

Original language	English
Pages (from-to)	1611-1619.e5
Number of pages	15
Journal	Cell Host and Microbe
Volume	29
Issue number	11
Early online date	13 Oct 2021
DOIs	https://doi.org/10.1016/j.chom.2021.10.003
Publication status	Published - 10 Nov 2021

Bibliographical note

Funding Information: We thank the study participants and the clinical staff and personnel at Groote Schuur Hospital, Cape Town for their dedication. We thank F. Ayres, D. Mhlanga, B. Oosthuysen, and B. Lambson for production of protein and pseudoviruses. The parental soluble spike was provided by J. McLellan. The parental pseudovirus plasmids were kindly provided by Drs E. Landais and D. Sok. We thank the Variant Consortium of South African scientists. The graphical abstract was created with BioRender.com. This research was supported by the South African Medical Research Council , with funds received from the South African Department of Science and Innovation (DSI), including grants 96825 , SHIPNCD 76756 , and DST / CON 0250/2012 . This work was supported by the Poliomyelitis Research Foundation ( 21/65 ) and the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), which is supported by core funding from the Wellcome Trust ( 203135/Z/16/Z and 222754 ). Funding support was received from NIH NIAID with the SARS-CoV-2 Assessment of Viral Evolution program and contract no. 75N9301900065 to A.S. and D.W. P.L.M. and S.I.R. are supported by the South African Research Chairs Initiative of DSI and the National Research Foundation (NRF; no. 98341 ). S.I.R. is a L’Oreal/UNESCO Women in Science South Africa Young Talents awardee. W.A.B. and C.R. are supported by the EDCTP2 program of the European Union’s Horizon 2020 program ( TMA2017SF-1951-TB-SPEC and TMA2016SF-1535-CaTCH-22 ). N.A.B.N. acknowledges funding from the SA-MRC , MRC UK, NRF, and the Lily and Ernst Hausmann Trust. M.N. is supported by the Wellcome Trust ( 207511/Z/17/Z ) and by NIHR Biomedical Research Funding to University College London Hospitals. For the purposes of open access, the authors have applied a CC BY public copyright license to any author-accepted version arising from this submission.

A.S. is a consultant for Gritstone, Flow Pharma, CellCarta, Arcturus, Oxford Immunotech, and Avalia. All of the other authors declare no competing interests. LJI has filed for patent protection for various aspects of vaccine design and identification of specific epitopes.

Publisher Copyright: © 2021 Elsevier Inc.

Citation: Roanne Keeton, Simone I. Richardson, Thandeka Moyo-Gwete, Tandile Hermanus, Marius B. Tincho, Ntombi Benede, Nelia P. Manamela, Richard Baguma, Zanele Makhado, Amkele Ngomti, Thopisang Motlou, Mathilda Mennen, Lionel Chinhoyi, Sango Skelem, Hazel Maboreke, Deelan Doolabh, Arash Iranzadeh, Ashley D. Otter, Tim Brooks, Mahdad Noursadeghi, James C. Moon, Alba Grifoni, Daniela Weiskopf, Alessandro Sette, Jonathan Blackburn, Nei-Yuan Hsiao, Carolyn Williamson, Catherine Riou, Ameena Goga, Nigel Garrett, Linda-Gail Bekker, Glenda Gray, Ntobeko A.B. Ntusi, Penny L. Moore, Wendy A. Burgers, Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant-dependent manner, Cell Host & Microbe, Volume 29, Issue 11, 2021,
Pages 1611-1619.e5, ISSN 1931-3128.

DOI: https://doi.org/10.1016/j.chom.2021.10.003.

Keywords

Ad26CoV2.S
Fc effector function
SARS-CoV-2
hybrid immunity
neutralization
vaccines
variants of concern

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

Access to Document

10.1016/j.chom.2021.10.003

Cite this

Keeton, R., Richardson, S. I., Moyo-Gwete, T., Hermanus, T., Tincho, M. B., Benede, N., Manamela, N. P., Baguma, R., Makhado, Z., Ngomti, A., Motlou, T., Mennen, M., Chinhoyi, L., Skelem, S., Maboreke, H., Doolabh, D., Iranzadeh, A., Otter, A. D., Brooks, T., ... Burgers, W. A. (2021). Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant-dependent manner. Cell Host and Microbe, 29(11), 1611-1619.e5. https://doi.org/10.1016/j.chom.2021.10.003

@article{ba3ce6e1cb9840a49a124f176c62140c,

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

abstract = "The Johnson and Johnson Ad26.COV2.S single-dose vaccine represents an attractive option for coronavirus disease 2019 (COVID-19) vaccination in countries with limited resources. We examined the effect of prior infection with different SARS-CoV-2 variants on Ad26.COV2.S immunogenicity. We compared participants who were SARS-CoV-2 naive with those either infected with the ancestral D614G virus or infected in the second wave when Beta predominated. Prior infection significantly boosts spike-binding antibodies, antibody-dependent cellular cytotoxicity, and neutralizing antibodies against D614G, Beta, and Delta; however, neutralization cross-reactivity varied by wave. Robust CD4 and CD8 T cell responses are induced after vaccination, regardless of prior infection. T cell recognition of variants is largely preserved, apart from some reduction in CD8 recognition of Delta. Thus, Ad26.COV2.S vaccination after infection could result in enhanced protection against COVID-19. The impact of the infecting variant on neutralization breadth after vaccination has implications for the design of second-generation vaccines based on variants of concern.",

keywords = "Ad26CoV2.S, Fc effector function, SARS-CoV-2, hybrid immunity, neutralization, vaccines, variants of concern",

author = "Roanne Keeton and Richardson, {Simone I.} and Thandeka Moyo-Gwete and Tandile Hermanus and Tincho, {Marius B.} and Ntombi Benede and Manamela, {Nelia P.} and Richard Baguma and Zanele Makhado and Amkele Ngomti and Thopisang Motlou and Mathilda Mennen and Lionel Chinhoyi and Sango Skelem and Hazel Maboreke and Deelan Doolabh and Arash Iranzadeh and Otter, {Ashley D.} and Tim Brooks and Mahdad Noursadeghi and Moon, {James C.} and Alba Grifoni and Daniela Weiskopf and Alessandro Sette and Jonathan Blackburn and Hsiao, {Nei Yuan} and Carolyn Williamson and Catherine Riou and Ameena Goga and Nigel Garrett and Bekker, {Linda Gail} and Glenda Gray and Ntusi, {Ntobeko A.B.} and Moore, {Penny L.} and Burgers, {Wendy A.}",

note = "Funding Information: We thank the study participants and the clinical staff and personnel at Groote Schuur Hospital, Cape Town for their dedication. We thank F. Ayres, D. Mhlanga, B. Oosthuysen, and B. Lambson for production of protein and pseudoviruses. The parental soluble spike was provided by J. McLellan. The parental pseudovirus plasmids were kindly provided by Drs E. Landais and D. Sok. We thank the Variant Consortium of South African scientists. The graphical abstract was created with BioRender.com. This research was supported by the South African Medical Research Council , with funds received from the South African Department of Science and Innovation (DSI), including grants 96825 , SHIPNCD 76756 , and DST / CON 0250/2012 . This work was supported by the Poliomyelitis Research Foundation ( 21/65 ) and the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), which is supported by core funding from the Wellcome Trust ( 203135/Z/16/Z and 222754 ). Funding support was received from NIH NIAID with the SARS-CoV-2 Assessment of Viral Evolution program and contract no. 75N9301900065 to A.S. and D.W. P.L.M. and S.I.R. are supported by the South African Research Chairs Initiative of DSI and the National Research Foundation (NRF; no. 98341 ). S.I.R. is a L{\textquoteright}Oreal/UNESCO Women in Science South Africa Young Talents awardee. W.A.B. and C.R. are supported by the EDCTP2 program of the European Union{\textquoteright}s Horizon 2020 program ( TMA2017SF-1951-TB-SPEC and TMA2016SF-1535-CaTCH-22 ). N.A.B.N. acknowledges funding from the SA-MRC , MRC UK, NRF, and the Lily and Ernst Hausmann Trust. M.N. is supported by the Wellcome Trust ( 207511/Z/17/Z ) and by NIHR Biomedical Research Funding to University College London Hospitals. For the purposes of open access, the authors have applied a CC BY public copyright license to any author-accepted version arising from this submission. A.S. is a consultant for Gritstone, Flow Pharma, CellCarta, Arcturus, Oxford Immunotech, and Avalia. All of the other authors declare no competing interests. LJI has filed for patent protection for various aspects of vaccine design and identification of specific epitopes. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc. Citation: Roanne Keeton, Simone I. Richardson, Thandeka Moyo-Gwete, Tandile Hermanus, Marius B. Tincho, Ntombi Benede, Nelia P. Manamela, Richard Baguma, Zanele Makhado, Amkele Ngomti, Thopisang Motlou, Mathilda Mennen, Lionel Chinhoyi, Sango Skelem, Hazel Maboreke, Deelan Doolabh, Arash Iranzadeh, Ashley D. Otter, Tim Brooks, Mahdad Noursadeghi, James C. Moon, Alba Grifoni, Daniela Weiskopf, Alessandro Sette, Jonathan Blackburn, Nei-Yuan Hsiao, Carolyn Williamson, Catherine Riou, Ameena Goga, Nigel Garrett, Linda-Gail Bekker, Glenda Gray, Ntobeko A.B. Ntusi, Penny L. Moore, Wendy A. Burgers, Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant-dependent manner, Cell Host & Microbe, Volume 29, Issue 11, 2021, Pages 1611-1619.e5, ISSN 1931-3128. DOI: https://doi.org/10.1016/j.chom.2021.10.003.",

year = "2021",

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language = "English",

volume = "29",

pages = "1611--1619.e5",

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Keeton, R, Richardson, SI, Moyo-Gwete, T, Hermanus, T, Tincho, MB, Benede, N, Manamela, NP, Baguma, R, Makhado, Z, Ngomti, A, Motlou, T, Mennen, M, Chinhoyi, L, Skelem, S, Maboreke, H, Doolabh, D, Iranzadeh, A, Otter, AD , Brooks, T, Noursadeghi, M, Moon, JC, Grifoni, A, Weiskopf, D, Sette, A, Blackburn, J, Hsiao, NY, Williamson, C, Riou, C, Goga, A, Garrett, N, Bekker, LG, Gray, G, Ntusi, NAB, Moore, PL & Burgers, WA 2021, 'Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant-dependent manner', Cell Host and Microbe, vol. 29, no. 11, pp. 1611-1619.e5. https://doi.org/10.1016/j.chom.2021.10.003

TY - JOUR

T1 - Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant-dependent manner

AU - Keeton, Roanne

AU - Richardson, Simone I.

AU - Moyo-Gwete, Thandeka

AU - Hermanus, Tandile

AU - Tincho, Marius B.

AU - Benede, Ntombi

AU - Manamela, Nelia P.

AU - Baguma, Richard

AU - Makhado, Zanele

AU - Ngomti, Amkele

AU - Motlou, Thopisang

AU - Mennen, Mathilda

AU - Chinhoyi, Lionel

AU - Skelem, Sango

AU - Maboreke, Hazel

AU - Doolabh, Deelan

AU - Iranzadeh, Arash

AU - Otter, Ashley D.

AU - Brooks, Tim

AU - Noursadeghi, Mahdad

AU - Moon, James C.

AU - Grifoni, Alba

AU - Weiskopf, Daniela

AU - Sette, Alessandro

AU - Blackburn, Jonathan

AU - Hsiao, Nei Yuan

AU - Williamson, Carolyn

AU - Riou, Catherine

AU - Goga, Ameena

AU - Garrett, Nigel

AU - Bekker, Linda Gail

AU - Gray, Glenda

AU - Ntusi, Ntobeko A.B.

AU - Moore, Penny L.

AU - Burgers, Wendy A.

N1 - Funding Information: We thank the study participants and the clinical staff and personnel at Groote Schuur Hospital, Cape Town for their dedication. We thank F. Ayres, D. Mhlanga, B. Oosthuysen, and B. Lambson for production of protein and pseudoviruses. The parental soluble spike was provided by J. McLellan. The parental pseudovirus plasmids were kindly provided by Drs E. Landais and D. Sok. We thank the Variant Consortium of South African scientists. The graphical abstract was created with BioRender.com. This research was supported by the South African Medical Research Council , with funds received from the South African Department of Science and Innovation (DSI), including grants 96825 , SHIPNCD 76756 , and DST / CON 0250/2012 . This work was supported by the Poliomyelitis Research Foundation ( 21/65 ) and the Wellcome Centre for Infectious Diseases Research in Africa (CIDRI-Africa), which is supported by core funding from the Wellcome Trust ( 203135/Z/16/Z and 222754 ). Funding support was received from NIH NIAID with the SARS-CoV-2 Assessment of Viral Evolution program and contract no. 75N9301900065 to A.S. and D.W. P.L.M. and S.I.R. are supported by the South African Research Chairs Initiative of DSI and the National Research Foundation (NRF; no. 98341 ). S.I.R. is a L’Oreal/UNESCO Women in Science South Africa Young Talents awardee. W.A.B. and C.R. are supported by the EDCTP2 program of the European Union’s Horizon 2020 program ( TMA2017SF-1951-TB-SPEC and TMA2016SF-1535-CaTCH-22 ). N.A.B.N. acknowledges funding from the SA-MRC , MRC UK, NRF, and the Lily and Ernst Hausmann Trust. M.N. is supported by the Wellcome Trust ( 207511/Z/17/Z ) and by NIHR Biomedical Research Funding to University College London Hospitals. For the purposes of open access, the authors have applied a CC BY public copyright license to any author-accepted version arising from this submission. A.S. is a consultant for Gritstone, Flow Pharma, CellCarta, Arcturus, Oxford Immunotech, and Avalia. All of the other authors declare no competing interests. LJI has filed for patent protection for various aspects of vaccine design and identification of specific epitopes. Publisher Copyright: © 2021 Elsevier Inc. Citation: Roanne Keeton, Simone I. Richardson, Thandeka Moyo-Gwete, Tandile Hermanus, Marius B. Tincho, Ntombi Benede, Nelia P. Manamela, Richard Baguma, Zanele Makhado, Amkele Ngomti, Thopisang Motlou, Mathilda Mennen, Lionel Chinhoyi, Sango Skelem, Hazel Maboreke, Deelan Doolabh, Arash Iranzadeh, Ashley D. Otter, Tim Brooks, Mahdad Noursadeghi, James C. Moon, Alba Grifoni, Daniela Weiskopf, Alessandro Sette, Jonathan Blackburn, Nei-Yuan Hsiao, Carolyn Williamson, Catherine Riou, Ameena Goga, Nigel Garrett, Linda-Gail Bekker, Glenda Gray, Ntobeko A.B. Ntusi, Penny L. Moore, Wendy A. Burgers, Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant-dependent manner, Cell Host & Microbe, Volume 29, Issue 11, 2021, Pages 1611-1619.e5, ISSN 1931-3128. DOI: https://doi.org/10.1016/j.chom.2021.10.003.

PY - 2021/11/10

Y1 - 2021/11/10

N2 - The Johnson and Johnson Ad26.COV2.S single-dose vaccine represents an attractive option for coronavirus disease 2019 (COVID-19) vaccination in countries with limited resources. We examined the effect of prior infection with different SARS-CoV-2 variants on Ad26.COV2.S immunogenicity. We compared participants who were SARS-CoV-2 naive with those either infected with the ancestral D614G virus or infected in the second wave when Beta predominated. Prior infection significantly boosts spike-binding antibodies, antibody-dependent cellular cytotoxicity, and neutralizing antibodies against D614G, Beta, and Delta; however, neutralization cross-reactivity varied by wave. Robust CD4 and CD8 T cell responses are induced after vaccination, regardless of prior infection. T cell recognition of variants is largely preserved, apart from some reduction in CD8 recognition of Delta. Thus, Ad26.COV2.S vaccination after infection could result in enhanced protection against COVID-19. The impact of the infecting variant on neutralization breadth after vaccination has implications for the design of second-generation vaccines based on variants of concern.

AB - The Johnson and Johnson Ad26.COV2.S single-dose vaccine represents an attractive option for coronavirus disease 2019 (COVID-19) vaccination in countries with limited resources. We examined the effect of prior infection with different SARS-CoV-2 variants on Ad26.COV2.S immunogenicity. We compared participants who were SARS-CoV-2 naive with those either infected with the ancestral D614G virus or infected in the second wave when Beta predominated. Prior infection significantly boosts spike-binding antibodies, antibody-dependent cellular cytotoxicity, and neutralizing antibodies against D614G, Beta, and Delta; however, neutralization cross-reactivity varied by wave. Robust CD4 and CD8 T cell responses are induced after vaccination, regardless of prior infection. T cell recognition of variants is largely preserved, apart from some reduction in CD8 recognition of Delta. Thus, Ad26.COV2.S vaccination after infection could result in enhanced protection against COVID-19. The impact of the infecting variant on neutralization breadth after vaccination has implications for the design of second-generation vaccines based on variants of concern.

KW - Ad26CoV2.S

KW - Fc effector function

KW - SARS-CoV-2

KW - hybrid immunity

KW - neutralization

KW - vaccines

KW - variants of concern

UR - http://www.scopus.com/inward/record.url?scp=85117842261&partnerID=8YFLogxK

U2 - 10.1016/j.chom.2021.10.003

DO - 10.1016/j.chom.2021.10.003

M3 - Article

AN - SCOPUS:85117842261

SN - 1931-3128

VL - 29

SP - 1611-1619.e5

JO - Cell Host and Microbe

JF - Cell Host and Microbe

IS - 11

ER -

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

Abstract

Bibliographical note

Keywords

UN SDGs

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