Ad26.COV2.S breakthrough infections induce high titers of antibodies capable of neutralizing variants of concern. Kitchin, D., Richardson, S. I, van der Mescht, M. A, Motlou, T., Mzindle, N., Moyo-Gwete, T., Makhado, Z., Ayres, F., Manamela, N. P, Spencer, H., Lambson, B., Oosthuysen, B., Mennen, M., Skelem, S., Williams, N., Ntusi, N. A B, Burgers, W. A, Gray, G. G, Bekker, L., Boswell, M. T, Rossouw, T. M, Ueckermann, V., & Moore, P. L medRxiv, Cold Spring Harbor Laboratory Press, nov, 2021.
Ad26.COV2.S breakthrough infections induce high titers of antibodies capable of neutralizing variants of concern [link]Paper  doi  abstract   bibtex   
The Janssen (Johnson & Johnson) Ad26.COV2.S non-replicating viral vector vaccine, which requires only a single dose and conventional cold chain storage, is a valuable tool for COVID-19 vaccination programs in resource-limited settings. Here we show that neutralizing and binding responses to Ad26.COV2.S vaccination are stable for 6-months post-vaccination, with responses highest against the ancestral vaccine-similar D614G variant. Secondly, using longitudinal samples from individuals who experienced clinically mild breakthrough infections 3-4 months after vaccination, we show dramatically boosted binding antibodies, Fc effector function and neutralization. These responses, which are cross-reactive against diverse SARS-CoV-2 variants and SARS-CoV-1, are of similar magnitude to humoral immune responses measured in severely ill, hospitalized donors. These data highlight the significant priming capacity of Ad26.COV2.S, and have implications for population immunity in areas where the single dose Ad26.COV2.S vaccine has been deployed. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement This study was funded by the South African Medical Research Council (grants 96825 and 96838). P.L.M. is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the National Research Foundation of South Africa (grant no. 98341). W.A.B. is supported by the EDCTP2 programme of the European Unions Horizon 2020 programme (TMA2016SF-1535-CaTCH-22), 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 the Poliomyelitis Research Foundation (PRF 21/65). N.A.B.N acknowledges funding from the SAMRC, MRC UK, NRF and the Lily and Ernst Hausmann Trust. S.I.R. is a LOreal/UNESCO Women in Science South Africa Young Talents awardee. Related research by the authors is conducted as part of the DST-NRF Centre of Excellence in HIV Prevention, which is supported by the South African Department of Science and Technology and the National Research Foundation. ### 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: Human Research Ethics Committees of the University of the Witwatersrand (ethics reference number: M210465), University of Pretoria (ethics reference number: 247/2020) and University of Cape Town (ethics reference numbers: 190/2020 and 209/2020) gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. 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 produced in the present study are available upon reasonable request to the authors.
@article{Kitchin2021,
abstract = {The Janssen (Johnson {\&} Johnson) Ad26.COV2.S non-replicating viral vector vaccine, which requires only a single dose and conventional cold chain storage, is a valuable tool for COVID-19 vaccination programs in resource-limited settings. Here we show that neutralizing and binding responses to Ad26.COV2.S vaccination are stable for 6-months post-vaccination, with responses highest against the ancestral vaccine-similar D614G variant. Secondly, using longitudinal samples from individuals who experienced clinically mild breakthrough infections 3-4 months after vaccination, we show dramatically boosted binding antibodies, Fc effector function and neutralization. These responses, which are cross-reactive against diverse SARS-CoV-2 variants and SARS-CoV-1, are of similar magnitude to humoral immune responses measured in severely ill, hospitalized donors. These data highlight the significant priming capacity of Ad26.COV2.S, and have implications for population immunity in areas where the single dose Ad26.COV2.S vaccine has been deployed. {\#}{\#}{\#} Competing Interest Statement The authors have declared no competing interest. {\#}{\#}{\#} Funding Statement This study was funded by the South African Medical Research Council (grants 96825 and 96838). P.L.M. is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and the National Research Foundation of South Africa (grant no. 98341). W.A.B. is supported by the EDCTP2 programme of the European Unions Horizon 2020 programme (TMA2016SF-1535-CaTCH-22), 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 the Poliomyelitis Research Foundation (PRF 21/65). N.A.B.N acknowledges funding from the SAMRC, MRC UK, NRF and the Lily and Ernst Hausmann Trust. S.I.R. is a LOreal/UNESCO Women in Science South Africa Young Talents awardee. Related research by the authors is conducted as part of the DST-NRF Centre of Excellence in HIV Prevention, which is supported by the South African Department of Science and Technology and the National Research Foundation. {\#}{\#}{\#} 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: Human Research Ethics Committees of the University of the Witwatersrand (ethics reference number: M210465), University of Pretoria (ethics reference number: 247/2020) and University of Cape Town (ethics reference numbers: 190/2020 and 209/2020) gave ethical approval for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. 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 produced in the present study are available upon reasonable request to the authors.},
author = {Kitchin, Dale and Richardson, Simone I and van der Mescht, Mieke A and Motlou, Thopisang and Mzindle, Nonkululeko and Moyo-Gwete, Thandeka and Makhado, Zanele and Ayres, Frances and Manamela, Nelia P and Spencer, Holly and Lambson, Bronwen and Oosthuysen, Brent and Mennen, Mathilda and Skelem, Sango and Williams, Noleen and Ntusi, Ntobeko A B and Burgers, Wendy A and Gray, Glenda G and Bekker, Linda-Gail and Boswell, Michael T and Rossouw, Theresa M and Ueckermann, Veronica and Moore, Penny L},
doi = {10.1101/2021.11.08.21266049},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Kitchin et al. - 2021 - Ad26.COV2.S breakthrough infections induce high titers of antibodies capable of neutralizing variants of concern.pdf:pdf},
journal = {medRxiv},
keywords = {OA,fund{\_}ack,original},
mendeley-tags = {OA,fund{\_}ack,original},
month = {nov},
pages = {2021.11.08.21266049},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Ad26.COV2.S breakthrough infections induce high titers of antibodies capable of neutralizing variants of concern}},
url = {https://www.medrxiv.org/content/10.1101/2021.11.08.21266049v1 https://www.medrxiv.org/content/10.1101/2021.11.08.21266049v1.abstract},
year = {2021}
}

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