@article{Keeton2021,
abstract = {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 {\textgreater}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. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement Research reported in this publication was supported by the South African Medical Research Council (SA-MRC) with funds received from the South African Department of Science and Innovation, including grants 96825, SHIPNCD 76756 and DST/CON 0250/2012. This work was also 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). P.L.M. and S.I.R. are supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the National Research Foundation (NRF; Grant No 9834). S.I.R. is a LOreal/UNESCO Women in Science South Africa Young Talents awardee. W.A.B. and C.R. are supported by the EDCTP2 programme of the European Unions Horizon 2020 programme (TMA2017SF-1951-TB-SPEC to C.R. and TMA2016SF-1535-CaTCH-22 to W.A.B.). 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. {\#}{\#}{\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Human Research Ethics Committee (HREC 190/2020 and 209/2020) and the University of the Witwatersrand Human Research Ethics Committee (Medical) (no M210429). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data referred to in the manuscript is available in the manuscript or Supplementary files.},
author = {Keeton, Roanne and Richardson, Simone I and Moyo-Gwete, Thandeka and Hermanus, Tandile and Tincho, Marius B and Benede, Ntombi and Manamela, Nelia P and Baguma, Richard and Makhado, Zanele and Ngomti, Amkele and Motlou, Thopisang and Mennen, Mathilda and Chinoyi, Lionel and Skelem, Sango and Maboreke, Hazel and Doolabh, Deelan and Iranzadeh, Arash and Otter, Ashley and Brooks, Tim and Noursadeghi, Mahdad and Moon, James and Blackburn, Jonathan and Hsiao, Nei-Yuan and Williamson, Carolyn and Riou, Catherine and Goga, Ameena and Garrett, Nigel and Bekker, Linda-Gail and Gray, Glenda and Ntusi, Ntobeko A.B and Moore, Penny L and Burgers, Wendy A},
doi = {10.1101/2021.07.24.21261037},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Keeton et al. - 2021 - Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner.pdf:pdf},
journal = {medRxiv},
keywords = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {jul},
pages = {2021.07.24.21261037},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner}},
url = {https://www.medrxiv.org/content/10.1101/2021.07.24.21261037v1 https://www.medrxiv.org/content/10.1101/2021.07.24.21261037v1.abstract},
year = {2021}
}

{"_id":"DKGuB43aJ4E2XZhaB","bibbaseid":"keeton-richardson-moyogwete-hermanus-tincho-benede-manamela-baguma-etal-priorinfectionwithsarscov2boostsandbroadensad26cov2simmunogenicityinavariantdependentmanner-2021","author_short":["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.","Chinoyi, L.","Skelem, S.","Maboreke, H.","Doolabh, D.","Iranzadeh, A.","Otter, A.","Brooks, T.","Noursadeghi, M.","Moon, J.","Blackburn, J.","Hsiao, N.","Williamson, C.","Riou, C.","Goga, A.","Garrett, N.","Bekker, L.","Gray, G.","Ntusi, N. A.","Moore, P. L","Burgers, W. A"],"bibdata":{"bibtype":"article","type":"article","abstract":"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 \\textgreater6 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. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement Research reported in this publication was supported by the South African Medical Research Council (SA-MRC) with funds received from the South African Department of Science and Innovation, including grants 96825, SHIPNCD 76756 and DST/CON 0250/2012. This work was also 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). P.L.M. and S.I.R. are supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the National Research Foundation (NRF; Grant No 9834). S.I.R. is a LOreal/UNESCO Women in Science South Africa Young Talents awardee. W.A.B. and C.R. are supported by the EDCTP2 programme of the European Unions Horizon 2020 programme (TMA2017SF-1951-TB-SPEC to C.R. and TMA2016SF-1535-CaTCH-22 to W.A.B.). 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. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Human Research Ethics Committee (HREC 190/2020 and 209/2020) and the University of the Witwatersrand Human Research Ethics Committee (Medical) (no M210429). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data referred to in the manuscript is available in the manuscript or Supplementary files.","author":[{"propositions":[],"lastnames":["Keeton"],"firstnames":["Roanne"],"suffixes":[]},{"propositions":[],"lastnames":["Richardson"],"firstnames":["Simone","I"],"suffixes":[]},{"propositions":[],"lastnames":["Moyo-Gwete"],"firstnames":["Thandeka"],"suffixes":[]},{"propositions":[],"lastnames":["Hermanus"],"firstnames":["Tandile"],"suffixes":[]},{"propositions":[],"lastnames":["Tincho"],"firstnames":["Marius","B"],"suffixes":[]},{"propositions":[],"lastnames":["Benede"],"firstnames":["Ntombi"],"suffixes":[]},{"propositions":[],"lastnames":["Manamela"],"firstnames":["Nelia","P"],"suffixes":[]},{"propositions":[],"lastnames":["Baguma"],"firstnames":["Richard"],"suffixes":[]},{"propositions":[],"lastnames":["Makhado"],"firstnames":["Zanele"],"suffixes":[]},{"propositions":[],"lastnames":["Ngomti"],"firstnames":["Amkele"],"suffixes":[]},{"propositions":[],"lastnames":["Motlou"],"firstnames":["Thopisang"],"suffixes":[]},{"propositions":[],"lastnames":["Mennen"],"firstnames":["Mathilda"],"suffixes":[]},{"propositions":[],"lastnames":["Chinoyi"],"firstnames":["Lionel"],"suffixes":[]},{"propositions":[],"lastnames":["Skelem"],"firstnames":["Sango"],"suffixes":[]},{"propositions":[],"lastnames":["Maboreke"],"firstnames":["Hazel"],"suffixes":[]},{"propositions":[],"lastnames":["Doolabh"],"firstnames":["Deelan"],"suffixes":[]},{"propositions":[],"lastnames":["Iranzadeh"],"firstnames":["Arash"],"suffixes":[]},{"propositions":[],"lastnames":["Otter"],"firstnames":["Ashley"],"suffixes":[]},{"propositions":[],"lastnames":["Brooks"],"firstnames":["Tim"],"suffixes":[]},{"propositions":[],"lastnames":["Noursadeghi"],"firstnames":["Mahdad"],"suffixes":[]},{"propositions":[],"lastnames":["Moon"],"firstnames":["James"],"suffixes":[]},{"propositions":[],"lastnames":["Blackburn"],"firstnames":["Jonathan"],"suffixes":[]},{"propositions":[],"lastnames":["Hsiao"],"firstnames":["Nei-Yuan"],"suffixes":[]},{"propositions":[],"lastnames":["Williamson"],"firstnames":["Carolyn"],"suffixes":[]},{"propositions":[],"lastnames":["Riou"],"firstnames":["Catherine"],"suffixes":[]},{"propositions":[],"lastnames":["Goga"],"firstnames":["Ameena"],"suffixes":[]},{"propositions":[],"lastnames":["Garrett"],"firstnames":["Nigel"],"suffixes":[]},{"propositions":[],"lastnames":["Bekker"],"firstnames":["Linda-Gail"],"suffixes":[]},{"propositions":[],"lastnames":["Gray"],"firstnames":["Glenda"],"suffixes":[]},{"propositions":[],"lastnames":["Ntusi"],"firstnames":["Ntobeko","A.B"],"suffixes":[]},{"propositions":[],"lastnames":["Moore"],"firstnames":["Penny","L"],"suffixes":[]},{"propositions":[],"lastnames":["Burgers"],"firstnames":["Wendy","A"],"suffixes":[]}],"doi":"10.1101/2021.07.24.21261037","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Keeton et al. - 2021 - Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner.pdf:pdf","journal":"medRxiv","keywords":"OA,OA_PMC,fund_ack,genomics_fund_ack,original","mendeley-tags":"OA,OA_PMC,fund_ack,genomics_fund_ack,original","month":"jul","pages":"2021.07.24.21261037","publisher":"Cold Spring Harbor Laboratory Press","title":"Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner","url":"https://www.medrxiv.org/content/10.1101/2021.07.24.21261037v1 https://www.medrxiv.org/content/10.1101/2021.07.24.21261037v1.abstract","year":"2021","bibtex":"@article{Keeton2021,\r\nabstract = {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 {\\textgreater}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. {\\#}{\\#}{\\#} Competing Interest Statement The authors have declared no competing interest. {\\#}{\\#}{\\#} Funding Statement Research reported in this publication was supported by the South African Medical Research Council (SA-MRC) with funds received from the South African Department of Science and Innovation, including grants 96825, SHIPNCD 76756 and DST/CON 0250/2012. This work was also 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). P.L.M. and S.I.R. are supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the National Research Foundation (NRF; Grant No 9834). S.I.R. is a LOreal/UNESCO Women in Science South Africa Young Talents awardee. W.A.B. and C.R. are supported by the EDCTP2 programme of the European Unions Horizon 2020 programme (TMA2017SF-1951-TB-SPEC to C.R. and TMA2016SF-1535-CaTCH-22 to W.A.B.). 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. {\\#}{\\#}{\\#} Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The study was approved by the University of Cape Town Human Research Ethics Committee (HREC 190/2020 and 209/2020) and the University of the Witwatersrand Human Research Ethics Committee (Medical) (no M210429). All necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes All data referred to in the manuscript is available in the manuscript or Supplementary files.},\r\nauthor = {Keeton, Roanne and Richardson, Simone I and Moyo-Gwete, Thandeka and Hermanus, Tandile and Tincho, Marius B and Benede, Ntombi and Manamela, Nelia P and Baguma, Richard and Makhado, Zanele and Ngomti, Amkele and Motlou, Thopisang and Mennen, Mathilda and Chinoyi, Lionel and Skelem, Sango and Maboreke, Hazel and Doolabh, Deelan and Iranzadeh, Arash and Otter, Ashley and Brooks, Tim and Noursadeghi, Mahdad and Moon, James and Blackburn, Jonathan and Hsiao, Nei-Yuan and Williamson, Carolyn and Riou, Catherine and Goga, Ameena and Garrett, Nigel and Bekker, Linda-Gail and Gray, Glenda and Ntusi, Ntobeko A.B and Moore, Penny L and Burgers, Wendy A},\r\ndoi = {10.1101/2021.07.24.21261037},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Keeton et al. - 2021 - Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner.pdf:pdf},\r\njournal = {medRxiv},\r\nkeywords = {OA,OA{\\_}PMC,fund{\\_}ack,genomics{\\_}fund{\\_}ack,original},\r\nmendeley-tags = {OA,OA{\\_}PMC,fund{\\_}ack,genomics{\\_}fund{\\_}ack,original},\r\nmonth = {jul},\r\npages = {2021.07.24.21261037},\r\npublisher = {Cold Spring Harbor Laboratory Press},\r\ntitle = {{Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner}},\r\nurl = {https://www.medrxiv.org/content/10.1101/2021.07.24.21261037v1 https://www.medrxiv.org/content/10.1101/2021.07.24.21261037v1.abstract},\r\nyear = {2021}\r\n}\r\n","author_short":["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.","Chinoyi, L.","Skelem, S.","Maboreke, H.","Doolabh, D.","Iranzadeh, A.","Otter, A.","Brooks, T.","Noursadeghi, M.","Moon, J.","Blackburn, J.","Hsiao, N.","Williamson, C.","Riou, C.","Goga, A.","Garrett, N.","Bekker, L.","Gray, G.","Ntusi, N. A.","Moore, P. L","Burgers, W. A"],"key":"Keeton2021","id":"Keeton2021","bibbaseid":"keeton-richardson-moyogwete-hermanus-tincho-benede-manamela-baguma-etal-priorinfectionwithsarscov2boostsandbroadensad26cov2simmunogenicityinavariantdependentmanner-2021","role":"author","urls":{"Paper":"https://www.medrxiv.org/content/10.1101/2021.07.24.21261037v1 https://www.medrxiv.org/content/10.1101/2021.07.24.21261037v1.abstract"},"keyword":["OA","OA_PMC","fund_ack","genomics_fund_ack","original"],"metadata":{"authorlinks":{}}},"bibtype":"article","biburl":"https://drive.google.com/uc?export=download&id=1-JLqZ7RwZ3VC2d6ErLGHAtOeMRS_7GCz","dataSources":["Krmt6gt9ktB2s6ARh","y6ojaHcuarkmc4yRQ","wrEvssexmuYudwQw9","9bX4N36CTXtCXNFMd","6GMFi5DCojy3jHY44"],"keywords":["oa","oa_pmc","fund_ack","genomics_fund_ack","original"],"search_terms":["prior","infection","sars","cov","boosts","broadens","ad26","cov2","immunogenicity","variant","dependent","manner","keeton","richardson","moyo-gwete","hermanus","tincho","benede","manamela","baguma","makhado","ngomti","motlou","mennen","chinoyi","skelem","maboreke","doolabh","iranzadeh","otter","brooks","noursadeghi","moon","blackburn","hsiao","williamson","riou","goga","garrett","bekker","gray","ntusi","moore","burgers"],"title":"Prior infection with SARS-CoV-2 boosts and broadens Ad26.COV2.S immunogenicity in a variant dependent manner","year":2021}