@article{Moyo-Gwete2023,
abstract = {The impact of previous SARS-CoV-2 infection on the durability of Ad26.COV2.S vaccine-elicited responses, and the effect of homologous boosting has not been well explored. We followed a cohort of healthcare workers for 6 months after receiving the Ad26.COV2.S vaccine and a further one month after they received an Ad26.COV2.S booster dose. We assessed longitudinal spike-specific antibody and T cell responses in individuals who had never had SARS-CoV-2 infection, compared to those who were infected with either the D614G or Beta variants prior to vaccination. Antibody and T cell responses elicited by the primary dose were durable against several variants of concern over the 6 month follow-up period, regardless of infection history. However, at 6 months after first vaccination, antibody binding, neutralization and ADCC were as much as 33-fold higher in individuals with hybrid immunity compared to those with no prior infection. Antibody cross-reactivity profiles of the previously infected groups were similar at 6 months, unlike at earlier time points suggesting that the effect of immune imprinting diminishes by 6 months. Importantly, an Ad26.COV2.S booster dose increased the magnitude of the antibody response in individuals with no prior infection to similar levels as those with previous infection. The magnitude of spike T cell responses and proportion of T cell responders remained stable after homologous boosting, concomitant with a significant increase in long-lived early differentiated CD4 memory T cells. Thus, these data highlight that multiple antigen exposures, whether through infection and vaccination or vaccination alone, result in similar boosts after Ad26.COV2.S vaccination. {\#}{\#}{\#} 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 (DSI), 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 Wellcome Trust (203135/Z/16/Z and 222574). We acknowledge funding from the Bill and Melinda Gates Foundation, through the Global Immunology and Immune Sequencing for Epidemic Response (GIISER) program. PLM is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and National Research Foundation of South Africa (NRF 9834), the SA Medical Research Council SHIP program, the Centre for the AIDS Programme of Research in South Africa (CAPRISA). TMG is funded by a South African Medical Research Council Self-Initiated Research Grant. SIR is funded by the Poliomyelitis Research Foundation. WAB and CR are supported by the EDCTP2 programme of the European Union Horizon 2020 programme (TMA2017SF-1951-TB-SPEC to C.R. and TMA2016SF-1535-CaTCH-22 to WAB) and the Wellcome Trust (226137/Z/22/ Z). CR is supported by the National Institutes of Health (NIH) (R21AI148027). NABN acknowledges funding from the SA MRC, MRC UK, NRF and the Lily and Ernst Hausmann Trust. {\#}{\#}{\#} 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 (Ethics number: HREC 190/2020 and 209/2020) and the University of the Witwatersrand Human Research Medical Ethics Committee (Ethics number: M210429). Written informed consent was obtained from all participants. 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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data are readily available upon request to the corresponding authors.},
author = {Moyo-Gwete, Thandeka and Richardson, Simone I and Keeton, Roanne and Hermanus, Tandile and Spencer, Holly and Manamela, Nelia P and Ayres, Frances and Makhado, Zanele and Motlou, Thopisang and Tincho, Marius B and Benede, Ntombi and Ngomti, Amkele and Baguma, Richard and Chauke, Masego V and Mennen, Mathilda and Adriaanse, Marguerite and Skelem, Sango and Goga, Ameena and Garrett, Nigel and Bekker, Linda-Gail and Gray, Glenda and Ntusi, Ntobeko A B and Riou, Catherine and Burgers, Wendy A and Moore, Penny L},
doi = {10.1101/2023.03.15.23287288},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Moyo-Gwete et al. - 2023 - Homologous Ad26.COV2.S vaccination results in reduced boosting of humoral responses in hybrid immunity, but e.pdf:pdf},
journal = {medRxiv},
keywords = {ADCC,Ad26COV2S vaccine,OA,SARS-CoV-2,T cells,antibodies,fund{\_}ack,genomics{\_}fund{\_}ack,hybrid immunity,memory differentiation,neutralization,original},
mendeley-tags = {OA,fund{\_}ack,genomics{\_}fund{\_}ack,original},
month = {mar},
pages = {2023.03.15.23287288},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Homologous Ad26.COV2.S vaccination results in reduced boosting of humoral responses in hybrid immunity, but elicits antibodies of similar magnitude regardless of prior infection}},
url = {https://www.medrxiv.org/content/10.1101/2023.03.15.23287288v1 https://www.medrxiv.org/content/10.1101/2023.03.15.23287288v1.abstract},
volume = {10},
year = {2023}
}

{"_id":"RLiAnyH3E9tuhzPBe","bibbaseid":"moyogwete-richardson-keeton-hermanus-spencer-manamela-ayres-makhado-etal-homologousad26cov2svaccinationresultsinreducedboostingofhumoralresponsesinhybridimmunitybutelicitsantibodiesofsimilarmagnituderegardlessofpriorinfection-2023","author_short":["Moyo-Gwete, T.","Richardson, S. I","Keeton, R.","Hermanus, T.","Spencer, H.","Manamela, N. P","Ayres, F.","Makhado, Z.","Motlou, T.","Tincho, M. B","Benede, N.","Ngomti, A.","Baguma, R.","Chauke, M. V","Mennen, M.","Adriaanse, M.","Skelem, S.","Goga, A.","Garrett, N.","Bekker, L.","Gray, G.","Ntusi, N. A B","Riou, C.","Burgers, W. A","Moore, P. L"],"bibdata":{"bibtype":"article","type":"article","abstract":"The impact of previous SARS-CoV-2 infection on the durability of Ad26.COV2.S vaccine-elicited responses, and the effect of homologous boosting has not been well explored. We followed a cohort of healthcare workers for 6 months after receiving the Ad26.COV2.S vaccine and a further one month after they received an Ad26.COV2.S booster dose. We assessed longitudinal spike-specific antibody and T cell responses in individuals who had never had SARS-CoV-2 infection, compared to those who were infected with either the D614G or Beta variants prior to vaccination. Antibody and T cell responses elicited by the primary dose were durable against several variants of concern over the 6 month follow-up period, regardless of infection history. However, at 6 months after first vaccination, antibody binding, neutralization and ADCC were as much as 33-fold higher in individuals with hybrid immunity compared to those with no prior infection. Antibody cross-reactivity profiles of the previously infected groups were similar at 6 months, unlike at earlier time points suggesting that the effect of immune imprinting diminishes by 6 months. Importantly, an Ad26.COV2.S booster dose increased the magnitude of the antibody response in individuals with no prior infection to similar levels as those with previous infection. The magnitude of spike T cell responses and proportion of T cell responders remained stable after homologous boosting, concomitant with a significant increase in long-lived early differentiated CD4 memory T cells. Thus, these data highlight that multiple antigen exposures, whether through infection and vaccination or vaccination alone, result in similar boosts after Ad26.COV2.S vaccination. ### 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 (DSI), 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 Wellcome Trust (203135/Z/16/Z and 222574). We acknowledge funding from the Bill and Melinda Gates Foundation, through the Global Immunology and Immune Sequencing for Epidemic Response (GIISER) program. PLM is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and National Research Foundation of South Africa (NRF 9834), the SA Medical Research Council SHIP program, the Centre for the AIDS Programme of Research in South Africa (CAPRISA). TMG is funded by a South African Medical Research Council Self-Initiated Research Grant. SIR is funded by the Poliomyelitis Research Foundation. WAB and CR are supported by the EDCTP2 programme of the European Union Horizon 2020 programme (TMA2017SF-1951-TB-SPEC to C.R. and TMA2016SF-1535-CaTCH-22 to WAB) and the Wellcome Trust (226137/Z/22/ Z). CR is supported by the National Institutes of Health (NIH) (R21AI148027). NABN acknowledges funding from the SA MRC, MRC UK, NRF and the Lily and Ernst Hausmann Trust. ### 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 (Ethics number: HREC 190/2020 and 209/2020) and the University of the Witwatersrand Human Research Medical Ethics Committee (Ethics number: M210429). Written informed consent was obtained from all participants. 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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data are readily available upon request to the corresponding authors.","author":[{"propositions":[],"lastnames":["Moyo-Gwete"],"firstnames":["Thandeka"],"suffixes":[]},{"propositions":[],"lastnames":["Richardson"],"firstnames":["Simone","I"],"suffixes":[]},{"propositions":[],"lastnames":["Keeton"],"firstnames":["Roanne"],"suffixes":[]},{"propositions":[],"lastnames":["Hermanus"],"firstnames":["Tandile"],"suffixes":[]},{"propositions":[],"lastnames":["Spencer"],"firstnames":["Holly"],"suffixes":[]},{"propositions":[],"lastnames":["Manamela"],"firstnames":["Nelia","P"],"suffixes":[]},{"propositions":[],"lastnames":["Ayres"],"firstnames":["Frances"],"suffixes":[]},{"propositions":[],"lastnames":["Makhado"],"firstnames":["Zanele"],"suffixes":[]},{"propositions":[],"lastnames":["Motlou"],"firstnames":["Thopisang"],"suffixes":[]},{"propositions":[],"lastnames":["Tincho"],"firstnames":["Marius","B"],"suffixes":[]},{"propositions":[],"lastnames":["Benede"],"firstnames":["Ntombi"],"suffixes":[]},{"propositions":[],"lastnames":["Ngomti"],"firstnames":["Amkele"],"suffixes":[]},{"propositions":[],"lastnames":["Baguma"],"firstnames":["Richard"],"suffixes":[]},{"propositions":[],"lastnames":["Chauke"],"firstnames":["Masego","V"],"suffixes":[]},{"propositions":[],"lastnames":["Mennen"],"firstnames":["Mathilda"],"suffixes":[]},{"propositions":[],"lastnames":["Adriaanse"],"firstnames":["Marguerite"],"suffixes":[]},{"propositions":[],"lastnames":["Skelem"],"firstnames":["Sango"],"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":["Riou"],"firstnames":["Catherine"],"suffixes":[]},{"propositions":[],"lastnames":["Burgers"],"firstnames":["Wendy","A"],"suffixes":[]},{"propositions":[],"lastnames":["Moore"],"firstnames":["Penny","L"],"suffixes":[]}],"doi":"10.1101/2023.03.15.23287288","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Moyo-Gwete et al. - 2023 - Homologous Ad26.COV2.S vaccination results in reduced boosting of humoral responses in hybrid immunity, but e.pdf:pdf","journal":"medRxiv","keywords":"ADCC,Ad26COV2S vaccine,OA,SARS-CoV-2,T cells,antibodies,fund_ack,genomics_fund_ack,hybrid immunity,memory differentiation,neutralization,original","mendeley-tags":"OA,fund_ack,genomics_fund_ack,original","month":"mar","pages":"2023.03.15.23287288","publisher":"Cold Spring Harbor Laboratory Press","title":"Homologous Ad26.COV2.S vaccination results in reduced boosting of humoral responses in hybrid immunity, but elicits antibodies of similar magnitude regardless of prior infection","url":"https://www.medrxiv.org/content/10.1101/2023.03.15.23287288v1 https://www.medrxiv.org/content/10.1101/2023.03.15.23287288v1.abstract","volume":"10","year":"2023","bibtex":"@article{Moyo-Gwete2023,\r\nabstract = {The impact of previous SARS-CoV-2 infection on the durability of Ad26.COV2.S vaccine-elicited responses, and the effect of homologous boosting has not been well explored. We followed a cohort of healthcare workers for 6 months after receiving the Ad26.COV2.S vaccine and a further one month after they received an Ad26.COV2.S booster dose. We assessed longitudinal spike-specific antibody and T cell responses in individuals who had never had SARS-CoV-2 infection, compared to those who were infected with either the D614G or Beta variants prior to vaccination. Antibody and T cell responses elicited by the primary dose were durable against several variants of concern over the 6 month follow-up period, regardless of infection history. However, at 6 months after first vaccination, antibody binding, neutralization and ADCC were as much as 33-fold higher in individuals with hybrid immunity compared to those with no prior infection. Antibody cross-reactivity profiles of the previously infected groups were similar at 6 months, unlike at earlier time points suggesting that the effect of immune imprinting diminishes by 6 months. Importantly, an Ad26.COV2.S booster dose increased the magnitude of the antibody response in individuals with no prior infection to similar levels as those with previous infection. The magnitude of spike T cell responses and proportion of T cell responders remained stable after homologous boosting, concomitant with a significant increase in long-lived early differentiated CD4 memory T cells. Thus, these data highlight that multiple antigen exposures, whether through infection and vaccination or vaccination alone, result in similar boosts after Ad26.COV2.S vaccination. {\\#}{\\#}{\\#} 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 (DSI), 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 Wellcome Trust (203135/Z/16/Z and 222574). We acknowledge funding from the Bill and Melinda Gates Foundation, through the Global Immunology and Immune Sequencing for Epidemic Response (GIISER) program. PLM is supported by the South African Research Chairs Initiative of the Department of Science and Innovation and National Research Foundation of South Africa (NRF 9834), the SA Medical Research Council SHIP program, the Centre for the AIDS Programme of Research in South Africa (CAPRISA). TMG is funded by a South African Medical Research Council Self-Initiated Research Grant. SIR is funded by the Poliomyelitis Research Foundation. WAB and CR are supported by the EDCTP2 programme of the European Union Horizon 2020 programme (TMA2017SF-1951-TB-SPEC to C.R. and TMA2016SF-1535-CaTCH-22 to WAB) and the Wellcome Trust (226137/Z/22/ Z). CR is supported by the National Institutes of Health (NIH) (R21AI148027). NABN acknowledges funding from the SA MRC, MRC UK, NRF and the Lily and Ernst Hausmann Trust. {\\#}{\\#}{\\#} 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 (Ethics number: HREC 190/2020 and 209/2020) and the University of the Witwatersrand Human Research Medical Ethics Committee (Ethics number: M210429). Written informed consent was obtained from all participants. 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, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes All data are readily available upon request to the corresponding authors.},\r\nauthor = {Moyo-Gwete, Thandeka and Richardson, Simone I and Keeton, Roanne and Hermanus, Tandile and Spencer, Holly and Manamela, Nelia P and Ayres, Frances and Makhado, Zanele and Motlou, Thopisang and Tincho, Marius B and Benede, Ntombi and Ngomti, Amkele and Baguma, Richard and Chauke, Masego V and Mennen, Mathilda and Adriaanse, Marguerite and Skelem, Sango and Goga, Ameena and Garrett, Nigel and Bekker, Linda-Gail and Gray, Glenda and Ntusi, Ntobeko A B and Riou, Catherine and Burgers, Wendy A and Moore, Penny L},\r\ndoi = {10.1101/2023.03.15.23287288},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Moyo-Gwete et al. - 2023 - Homologous Ad26.COV2.S vaccination results in reduced boosting of humoral responses in hybrid immunity, but e.pdf:pdf},\r\njournal = {medRxiv},\r\nkeywords = {ADCC,Ad26COV2S vaccine,OA,SARS-CoV-2,T cells,antibodies,fund{\\_}ack,genomics{\\_}fund{\\_}ack,hybrid immunity,memory differentiation,neutralization,original},\r\nmendeley-tags = {OA,fund{\\_}ack,genomics{\\_}fund{\\_}ack,original},\r\nmonth = {mar},\r\npages = {2023.03.15.23287288},\r\npublisher = {Cold Spring Harbor Laboratory Press},\r\ntitle = {{Homologous Ad26.COV2.S vaccination results in reduced boosting of humoral responses in hybrid immunity, but elicits antibodies of similar magnitude regardless of prior infection}},\r\nurl = {https://www.medrxiv.org/content/10.1101/2023.03.15.23287288v1 https://www.medrxiv.org/content/10.1101/2023.03.15.23287288v1.abstract},\r\nvolume = {10},\r\nyear = {2023}\r\n}\r\n","author_short":["Moyo-Gwete, T.","Richardson, S. 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