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 journalArticlepeer-review

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 languageEnglish
JournalCell Host and Microbe
DOIs
Publication statusAccepted/In press - 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.

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. W.A.B. P.L.M. and N.A.B.N. designed the study. W.A.B. and P.L.M. analyzed the data and wrote the manuscript. R.K. S.I.R. and T.M.G. generated and analyzed the data and wrote the manuscript. S.I.R. T.M.G. T.H. N.P.M. Z.M. and T.M. performed antibody assays. R.K. M.B.T. N.B. R.B. and A.N. performed T cell assays. M.M. S.S. and L.R.C. managed the HCW cohort and contributed clinical samples. A.O. and T.B. characterized the serological profiles. N.Y.H. contributed samples, and A.G. D.W. and A.S. provided variant peptide pools. D.D. A.I. and C.W. performed viral sequencing. H.M. and J.B. contributed to cohort characterization. C.R. contributed to data analysis. A.G. N.G. L.G.B. and G.G. established and led the Sisonke vaccine study. N.A.B.N. J.M. and M.N. established and led the HCW cohort. All authors reviewed and edited the manuscript. 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.

Keywords

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

Fingerprint

Dive into the research topics of 'Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant-dependent manner'. Together they form a unique fingerprint.

Cite this