@article{Riou2023a,
abstract = {Background. We report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4{\%} showing evidence of previous SARS-CoV-2 infection. Methods. A total of 286 adults (with or without HIV) were enrolled {\textgreater}4 months after an Ad26.COV2.S prime and randomized 1:1:1:1 to receive either a full or half-dose booster of Ad26.COV2.S or BNT162b2 vaccine. B cell responses (binding, neutralization and antibody dependent cellular cytotoxicity-ADCC), and spike-specific T-cell responses were evaluated at baseline, 2, 12 and 24 weeks post-boost. Antibody and T-cell immunity targeting the Ad26 vector was also evaluated. Results. No vaccine-associated serious adverse events were recorded. The full- and half-dose BNT162b2 boosted anti-SARS-CoV-2 binding antibody levels (3.9- and 4.5-fold, respectively) and neutralizing antibody levels (4.4- and 10-fold). Binding and neutralizing antibodies following half-dose Ad26.COV2.S were not significantly boosted. Full-dose Ad26.COV2.S did not boost binding antibodies but slightly enhanced neutralizing antibodies (2.1-fold). ADCC was marginally increased only after a full-dose BNT162b2. T-cell responses followed a similar pattern to neutralizing antibodies. Six months post-boost, antibody and T-cell responses had waned to baseline levels. While we detected strong anti-vector immunity, there was no correlation between anti-vector immunity in Ad26.COV2.S recipients and spike-specific neutralizing antibody or T-cell responses post-Ad26.COV2.S boosting. Conclusion. In the context of hybrid immunity, boosting with heterologous full- or half-dose BNT162b2 mRNA vaccine demonstrated superior immunogenicity 2 weeks post-vaccination compared to homologous Ad26.COV2.S, though rapid waning occurred by 12 weeks post-boost. Trial Registration: South African National Clinical Trial Registry (SANCR): DOH-27-012022-7841; Funding: South African Medical Research Council (SAMRC) and South African Department of Health (SA DoH). {\#}{\#}{\#} Competing Interest Statement I have read the journal's policy and the authors of this manuscript have the following competing interests: A.Se. is a consultant for AstraZeneca Pharmaceuticals, Calyptus Pharmaceuticals, Inc, Darwin Health, EmerVax, EUROIMMUN, F. Hoffman-La Roche Ltd, Fortress Biotech, Gilead Sciences, Granite bio., Gritstone Oncology, Guggenheim Securities, Moderna, Pfizer, RiverVest Venture Partners, and Turnstone Biologics. A.G. is a consultant for Pfizer. LJI has filed for patent protection for various aspects of T cell epitope and vaccine design work. All other authors declare no competing interests {\#}{\#}{\#} Clinical Trial The study has been registered to the South African National Clinical Trial Registry (SANCR): DOH-27-012022-7841. {\#}{\#}{\#} Funding Statement yes This study was funded by the South African Medical research Council (SAMRC), the Bill and Melinda Gates Foundation, through the Global Immunology and Immune Sequencing for Epidemic Response (GIISER) program (INV-030570) and the Wellcome Trust (226137/Z/22/Z). P.L.M is supported by the SAMRC (96833) and is an Department of Science and Innovation-National Research Foundation South African Research Chair (98341). A.Si. is supported by the Bill and Melinda Gates foundation (INV-046743) and the SAMRC (D2112300-01). W.A.B. is supported by the EDCTP2 program of the European Union's Horizon 2020 programme (TMA2016SF-1535-CaTCH-22) and the EU-Africa Concerted Action on SARS-CoV-2 Virus Variant and Immunological Surveillance (COVICIS), funded through the EU's Horizon Europe Research and Innovation Programme (101046041). C.R. is supported by the EDCTP2 program (TMA2017SF-1951-TB-SPEC). This project has also been funded in part by the National Institute of Allergy and Infectious Diseases, NIH, Department of Health and Human Services, under Contract No. 75N93021C00016 to A.G. and 75N93019C00065 to A.Se. The Wits RHI site received grant funding from Janssen to conduct the following clinical trials: Ensemble study (3UM1 AI068614-14SI), the Sisonke 1 study (96833), the Sherpa Study (96867) as well as Pfizer for the Pfizer C4591015 study (C4591015), Horizon 1 (VAC31518COV2004) and Horizon 2 (VAC31518COV3006). For the purposes of open access, the authors have applied a CC-BY public copyright license to any author-accepted version. {\#}{\#}{\#} 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: This study has been approved by the South African Health Products Regulatory Authority (SAHPRA) and all site-specific Human Research Ethics Committees (HREC numbers: Wits 211001B, UKZN: BREC/00003487/2021, UCT 680/2021 SAHPRA: 20210423). All participants provided written informed consent. 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 Data underlying the findings described in this manuscript may be obtained from the lead authors upon request.},
author = {Riou, Catherine and Bhiman, Jinal N and Ganga, Yashica and Sawry, Shobna and Ayres, Frances and Baguma, Richard and Balla, Sashkia R and Benede, Ntombi and Bernstein, Mallory and Besethi, Asiphe S and Cele, Sandile and Crowther, Carol and Dhar, Mrinmayee and Geyer, Sohair and Gill, Katherine and Grifoni, Alba and Hermanus, Tandile and Kaldine, Haajira and Keeton, Roanne S and Kgagudi, Prudence and Khan, Khadija and Lazarus, Erica and Roux, Jean Le and Lustig, Gila and Madzivhandila, Mashudu and Magugu, Siyabulela FJ and Makhado, Zanele and Manamela, Nelia P and Mkhize, Qiniso and Mosala, Paballo and Motlou, Thopisang P and Mutavhatsindi, Hygon and Mzindle, Nonkululeko B and Nana, Anusha and Nesamari, Rofhiwa and Ngomti, Amkele and Nkayi, Anathi A and Nkosi, Thandeka P and Omondi, Millicent A and Panchia, Ravindre and Patel, Faeezah and Sette, Alessandro and Singh, Upasna and van Graan, Strauss and Venter, Elizabeth M. and Walters, Avril and Moyo-Gwete, Thandeka and Richardson, Simone I. and Garrett, Nigel and Rees, Helen and Bekker, Linda-Gail and Gray, Glenda and Burgers, Wendy A. and Sigal, Alex and Moore, Penny L and Fairlie, Lee},
doi = {10.1101/2023.11.20.23298785},
file = {:C$\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Riou et al. - 2023 - Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-.pdf:pdf},
journal = {medRxiv},
keywords = {OA,OA{\_}PMC,fund{\_}not{\_}ack,original},
mendeley-tags = {OA,OA{\_}PMC,fund{\_}not{\_}ack,original},
month = {nov},
pages = {2023.11.20.23298785},
pmid = {38045321},
publisher = {Cold Spring Harbor Laboratory Press},
title = {{Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-vaccinated participants}},
url = {https://www.medrxiv.org/content/10.1101/2023.11.20.23298785v1 https://www.medrxiv.org/content/10.1101/2023.11.20.23298785v1.abstract},
year = {2023}
}

{"_id":"TAJtHhSsE2cfKd48w","bibbaseid":"riou-bhiman-ganga-sawry-ayres-baguma-balla-benede-etal-safetyandimmunogenicityofboostervaccinationandfractionaldosingwithad26cov2sorbnt162b2inad26cov2svaccinatedparticipants-2023","author_short":["Riou, C.","Bhiman, J. N","Ganga, Y.","Sawry, S.","Ayres, F.","Baguma, R.","Balla, S. R","Benede, N.","Bernstein, M.","Besethi, A. S","Cele, S.","Crowther, C.","Dhar, M.","Geyer, S.","Gill, K.","Grifoni, A.","Hermanus, T.","Kaldine, H.","Keeton, R. S","Kgagudi, P.","Khan, K.","Lazarus, E.","Roux, J. L.","Lustig, G.","Madzivhandila, M.","Magugu, S. F.","Makhado, Z.","Manamela, N. P","Mkhize, Q.","Mosala, P.","Motlou, T. P","Mutavhatsindi, H.","Mzindle, N. B","Nana, A.","Nesamari, R.","Ngomti, A.","Nkayi, A. A","Nkosi, T. P","Omondi, M. A","Panchia, R.","Patel, F.","Sette, A.","Singh, U.","van Graan, S.","Venter, E. M.","Walters, A.","Moyo-Gwete, T.","Richardson, S. I.","Garrett, N.","Rees, H.","Bekker, L.","Gray, G.","Burgers, W. A.","Sigal, A.","Moore, P. L","Fairlie, L."],"bibdata":{"bibtype":"article","type":"article","abstract":"Background. We report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4% showing evidence of previous SARS-CoV-2 infection. Methods. A total of 286 adults (with or without HIV) were enrolled \\textgreater4 months after an Ad26.COV2.S prime and randomized 1:1:1:1 to receive either a full or half-dose booster of Ad26.COV2.S or BNT162b2 vaccine. B cell responses (binding, neutralization and antibody dependent cellular cytotoxicity-ADCC), and spike-specific T-cell responses were evaluated at baseline, 2, 12 and 24 weeks post-boost. Antibody and T-cell immunity targeting the Ad26 vector was also evaluated. Results. No vaccine-associated serious adverse events were recorded. The full- and half-dose BNT162b2 boosted anti-SARS-CoV-2 binding antibody levels (3.9- and 4.5-fold, respectively) and neutralizing antibody levels (4.4- and 10-fold). Binding and neutralizing antibodies following half-dose Ad26.COV2.S were not significantly boosted. Full-dose Ad26.COV2.S did not boost binding antibodies but slightly enhanced neutralizing antibodies (2.1-fold). ADCC was marginally increased only after a full-dose BNT162b2. T-cell responses followed a similar pattern to neutralizing antibodies. Six months post-boost, antibody and T-cell responses had waned to baseline levels. While we detected strong anti-vector immunity, there was no correlation between anti-vector immunity in Ad26.COV2.S recipients and spike-specific neutralizing antibody or T-cell responses post-Ad26.COV2.S boosting. Conclusion. In the context of hybrid immunity, boosting with heterologous full- or half-dose BNT162b2 mRNA vaccine demonstrated superior immunogenicity 2 weeks post-vaccination compared to homologous Ad26.COV2.S, though rapid waning occurred by 12 weeks post-boost. Trial Registration: South African National Clinical Trial Registry (SANCR): DOH-27-012022-7841; Funding: South African Medical Research Council (SAMRC) and South African Department of Health (SA DoH). ### Competing Interest Statement I have read the journal's policy and the authors of this manuscript have the following competing interests: A.Se. is a consultant for AstraZeneca Pharmaceuticals, Calyptus Pharmaceuticals, Inc, Darwin Health, EmerVax, EUROIMMUN, F. Hoffman-La Roche Ltd, Fortress Biotech, Gilead Sciences, Granite bio., Gritstone Oncology, Guggenheim Securities, Moderna, Pfizer, RiverVest Venture Partners, and Turnstone Biologics. A.G. is a consultant for Pfizer. LJI has filed for patent protection for various aspects of T cell epitope and vaccine design work. All other authors declare no competing interests ### Clinical Trial The study has been registered to the South African National Clinical Trial Registry (SANCR): DOH-27-012022-7841. ### Funding Statement yes This study was funded by the South African Medical research Council (SAMRC), the Bill and Melinda Gates Foundation, through the Global Immunology and Immune Sequencing for Epidemic Response (GIISER) program (INV-030570) and the Wellcome Trust (226137/Z/22/Z). P.L.M is supported by the SAMRC (96833) and is an Department of Science and Innovation-National Research Foundation South African Research Chair (98341). A.Si. is supported by the Bill and Melinda Gates foundation (INV-046743) and the SAMRC (D2112300-01). W.A.B. is supported by the EDCTP2 program of the European Union's Horizon 2020 programme (TMA2016SF-1535-CaTCH-22) and the EU-Africa Concerted Action on SARS-CoV-2 Virus Variant and Immunological Surveillance (COVICIS), funded through the EU's Horizon Europe Research and Innovation Programme (101046041). C.R. is supported by the EDCTP2 program (TMA2017SF-1951-TB-SPEC). This project has also been funded in part by the National Institute of Allergy and Infectious Diseases, NIH, Department of Health and Human Services, under Contract No. 75N93021C00016 to A.G. and 75N93019C00065 to A.Se. The Wits RHI site received grant funding from Janssen to conduct the following clinical trials: Ensemble study (3UM1 AI068614-14SI), the Sisonke 1 study (96833), the Sherpa Study (96867) as well as Pfizer for the Pfizer C4591015 study (C4591015), Horizon 1 (VAC31518COV2004) and Horizon 2 (VAC31518COV3006). For the purposes of open access, the authors have applied a CC-BY public copyright license to any author-accepted version. ### 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: This study has been approved by the South African Health Products Regulatory Authority (SAHPRA) and all site-specific Human Research Ethics Committees (HREC numbers: Wits 211001B, UKZN: BREC/00003487/2021, UCT 680/2021 SAHPRA: 20210423). All participants provided written informed consent. 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 Data underlying the findings described in this manuscript may be obtained from the lead authors upon request.","author":[{"propositions":[],"lastnames":["Riou"],"firstnames":["Catherine"],"suffixes":[]},{"propositions":[],"lastnames":["Bhiman"],"firstnames":["Jinal","N"],"suffixes":[]},{"propositions":[],"lastnames":["Ganga"],"firstnames":["Yashica"],"suffixes":[]},{"propositions":[],"lastnames":["Sawry"],"firstnames":["Shobna"],"suffixes":[]},{"propositions":[],"lastnames":["Ayres"],"firstnames":["Frances"],"suffixes":[]},{"propositions":[],"lastnames":["Baguma"],"firstnames":["Richard"],"suffixes":[]},{"propositions":[],"lastnames":["Balla"],"firstnames":["Sashkia","R"],"suffixes":[]},{"propositions":[],"lastnames":["Benede"],"firstnames":["Ntombi"],"suffixes":[]},{"propositions":[],"lastnames":["Bernstein"],"firstnames":["Mallory"],"suffixes":[]},{"propositions":[],"lastnames":["Besethi"],"firstnames":["Asiphe","S"],"suffixes":[]},{"propositions":[],"lastnames":["Cele"],"firstnames":["Sandile"],"suffixes":[]},{"propositions":[],"lastnames":["Crowther"],"firstnames":["Carol"],"suffixes":[]},{"propositions":[],"lastnames":["Dhar"],"firstnames":["Mrinmayee"],"suffixes":[]},{"propositions":[],"lastnames":["Geyer"],"firstnames":["Sohair"],"suffixes":[]},{"propositions":[],"lastnames":["Gill"],"firstnames":["Katherine"],"suffixes":[]},{"propositions":[],"lastnames":["Grifoni"],"firstnames":["Alba"],"suffixes":[]},{"propositions":[],"lastnames":["Hermanus"],"firstnames":["Tandile"],"suffixes":[]},{"propositions":[],"lastnames":["Kaldine"],"firstnames":["Haajira"],"suffixes":[]},{"propositions":[],"lastnames":["Keeton"],"firstnames":["Roanne","S"],"suffixes":[]},{"propositions":[],"lastnames":["Kgagudi"],"firstnames":["Prudence"],"suffixes":[]},{"propositions":[],"lastnames":["Khan"],"firstnames":["Khadija"],"suffixes":[]},{"propositions":[],"lastnames":["Lazarus"],"firstnames":["Erica"],"suffixes":[]},{"propositions":[],"lastnames":["Roux"],"firstnames":["Jean","Le"],"suffixes":[]},{"propositions":[],"lastnames":["Lustig"],"firstnames":["Gila"],"suffixes":[]},{"propositions":[],"lastnames":["Madzivhandila"],"firstnames":["Mashudu"],"suffixes":[]},{"propositions":[],"lastnames":["Magugu"],"firstnames":["Siyabulela","FJ"],"suffixes":[]},{"propositions":[],"lastnames":["Makhado"],"firstnames":["Zanele"],"suffixes":[]},{"propositions":[],"lastnames":["Manamela"],"firstnames":["Nelia","P"],"suffixes":[]},{"propositions":[],"lastnames":["Mkhize"],"firstnames":["Qiniso"],"suffixes":[]},{"propositions":[],"lastnames":["Mosala"],"firstnames":["Paballo"],"suffixes":[]},{"propositions":[],"lastnames":["Motlou"],"firstnames":["Thopisang","P"],"suffixes":[]},{"propositions":[],"lastnames":["Mutavhatsindi"],"firstnames":["Hygon"],"suffixes":[]},{"propositions":[],"lastnames":["Mzindle"],"firstnames":["Nonkululeko","B"],"suffixes":[]},{"propositions":[],"lastnames":["Nana"],"firstnames":["Anusha"],"suffixes":[]},{"propositions":[],"lastnames":["Nesamari"],"firstnames":["Rofhiwa"],"suffixes":[]},{"propositions":[],"lastnames":["Ngomti"],"firstnames":["Amkele"],"suffixes":[]},{"propositions":[],"lastnames":["Nkayi"],"firstnames":["Anathi","A"],"suffixes":[]},{"propositions":[],"lastnames":["Nkosi"],"firstnames":["Thandeka","P"],"suffixes":[]},{"propositions":[],"lastnames":["Omondi"],"firstnames":["Millicent","A"],"suffixes":[]},{"propositions":[],"lastnames":["Panchia"],"firstnames":["Ravindre"],"suffixes":[]},{"propositions":[],"lastnames":["Patel"],"firstnames":["Faeezah"],"suffixes":[]},{"propositions":[],"lastnames":["Sette"],"firstnames":["Alessandro"],"suffixes":[]},{"propositions":[],"lastnames":["Singh"],"firstnames":["Upasna"],"suffixes":[]},{"propositions":["van"],"lastnames":["Graan"],"firstnames":["Strauss"],"suffixes":[]},{"propositions":[],"lastnames":["Venter"],"firstnames":["Elizabeth","M."],"suffixes":[]},{"propositions":[],"lastnames":["Walters"],"firstnames":["Avril"],"suffixes":[]},{"propositions":[],"lastnames":["Moyo-Gwete"],"firstnames":["Thandeka"],"suffixes":[]},{"propositions":[],"lastnames":["Richardson"],"firstnames":["Simone","I."],"suffixes":[]},{"propositions":[],"lastnames":["Garrett"],"firstnames":["Nigel"],"suffixes":[]},{"propositions":[],"lastnames":["Rees"],"firstnames":["Helen"],"suffixes":[]},{"propositions":[],"lastnames":["Bekker"],"firstnames":["Linda-Gail"],"suffixes":[]},{"propositions":[],"lastnames":["Gray"],"firstnames":["Glenda"],"suffixes":[]},{"propositions":[],"lastnames":["Burgers"],"firstnames":["Wendy","A."],"suffixes":[]},{"propositions":[],"lastnames":["Sigal"],"firstnames":["Alex"],"suffixes":[]},{"propositions":[],"lastnames":["Moore"],"firstnames":["Penny","L"],"suffixes":[]},{"propositions":[],"lastnames":["Fairlie"],"firstnames":["Lee"],"suffixes":[]}],"doi":"10.1101/2023.11.20.23298785","file":":C$\\$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Riou et al. - 2023 - Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-.pdf:pdf","journal":"medRxiv","keywords":"OA,OA_PMC,fund_not_ack,original","mendeley-tags":"OA,OA_PMC,fund_not_ack,original","month":"nov","pages":"2023.11.20.23298785","pmid":"38045321","publisher":"Cold Spring Harbor Laboratory Press","title":"Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-vaccinated participants","url":"https://www.medrxiv.org/content/10.1101/2023.11.20.23298785v1 https://www.medrxiv.org/content/10.1101/2023.11.20.23298785v1.abstract","year":"2023","bibtex":"@article{Riou2023a,\r\nabstract = {Background. We report the safety and immunogenicity of fractional and full dose Ad26.COV2.S and BNT162b2 in an open label phase 2 trial of participants previously vaccinated with a single dose of Ad26.COV2.S, with 91.4{\\%} showing evidence of previous SARS-CoV-2 infection. Methods. A total of 286 adults (with or without HIV) were enrolled {\\textgreater}4 months after an Ad26.COV2.S prime and randomized 1:1:1:1 to receive either a full or half-dose booster of Ad26.COV2.S or BNT162b2 vaccine. B cell responses (binding, neutralization and antibody dependent cellular cytotoxicity-ADCC), and spike-specific T-cell responses were evaluated at baseline, 2, 12 and 24 weeks post-boost. Antibody and T-cell immunity targeting the Ad26 vector was also evaluated. Results. No vaccine-associated serious adverse events were recorded. The full- and half-dose BNT162b2 boosted anti-SARS-CoV-2 binding antibody levels (3.9- and 4.5-fold, respectively) and neutralizing antibody levels (4.4- and 10-fold). Binding and neutralizing antibodies following half-dose Ad26.COV2.S were not significantly boosted. Full-dose Ad26.COV2.S did not boost binding antibodies but slightly enhanced neutralizing antibodies (2.1-fold). ADCC was marginally increased only after a full-dose BNT162b2. T-cell responses followed a similar pattern to neutralizing antibodies. Six months post-boost, antibody and T-cell responses had waned to baseline levels. While we detected strong anti-vector immunity, there was no correlation between anti-vector immunity in Ad26.COV2.S recipients and spike-specific neutralizing antibody or T-cell responses post-Ad26.COV2.S boosting. Conclusion. In the context of hybrid immunity, boosting with heterologous full- or half-dose BNT162b2 mRNA vaccine demonstrated superior immunogenicity 2 weeks post-vaccination compared to homologous Ad26.COV2.S, though rapid waning occurred by 12 weeks post-boost. Trial Registration: South African National Clinical Trial Registry (SANCR): DOH-27-012022-7841; Funding: South African Medical Research Council (SAMRC) and South African Department of Health (SA DoH). {\\#}{\\#}{\\#} Competing Interest Statement I have read the journal's policy and the authors of this manuscript have the following competing interests: A.Se. is a consultant for AstraZeneca Pharmaceuticals, Calyptus Pharmaceuticals, Inc, Darwin Health, EmerVax, EUROIMMUN, F. Hoffman-La Roche Ltd, Fortress Biotech, Gilead Sciences, Granite bio., Gritstone Oncology, Guggenheim Securities, Moderna, Pfizer, RiverVest Venture Partners, and Turnstone Biologics. A.G. is a consultant for Pfizer. LJI has filed for patent protection for various aspects of T cell epitope and vaccine design work. All other authors declare no competing interests {\\#}{\\#}{\\#} Clinical Trial The study has been registered to the South African National Clinical Trial Registry (SANCR): DOH-27-012022-7841. {\\#}{\\#}{\\#} Funding Statement yes This study was funded by the South African Medical research Council (SAMRC), the Bill and Melinda Gates Foundation, through the Global Immunology and Immune Sequencing for Epidemic Response (GIISER) program (INV-030570) and the Wellcome Trust (226137/Z/22/Z). P.L.M is supported by the SAMRC (96833) and is an Department of Science and Innovation-National Research Foundation South African Research Chair (98341). A.Si. is supported by the Bill and Melinda Gates foundation (INV-046743) and the SAMRC (D2112300-01). W.A.B. is supported by the EDCTP2 program of the European Union's Horizon 2020 programme (TMA2016SF-1535-CaTCH-22) and the EU-Africa Concerted Action on SARS-CoV-2 Virus Variant and Immunological Surveillance (COVICIS), funded through the EU's Horizon Europe Research and Innovation Programme (101046041). C.R. is supported by the EDCTP2 program (TMA2017SF-1951-TB-SPEC). This project has also been funded in part by the National Institute of Allergy and Infectious Diseases, NIH, Department of Health and Human Services, under Contract No. 75N93021C00016 to A.G. and 75N93019C00065 to A.Se. The Wits RHI site received grant funding from Janssen to conduct the following clinical trials: Ensemble study (3UM1 AI068614-14SI), the Sisonke 1 study (96833), the Sherpa Study (96867) as well as Pfizer for the Pfizer C4591015 study (C4591015), Horizon 1 (VAC31518COV2004) and Horizon 2 (VAC31518COV3006). For the purposes of open access, the authors have applied a CC-BY public copyright license to any author-accepted version. {\\#}{\\#}{\\#} 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: This study has been approved by the South African Health Products Regulatory Authority (SAHPRA) and all site-specific Human Research Ethics Committees (HREC numbers: Wits 211001B, UKZN: BREC/00003487/2021, UCT 680/2021 SAHPRA: 20210423). All participants provided written informed consent. 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 Data underlying the findings described in this manuscript may be obtained from the lead authors upon request.},\r\nauthor = {Riou, Catherine and Bhiman, Jinal N and Ganga, Yashica and Sawry, Shobna and Ayres, Frances and Baguma, Richard and Balla, Sashkia R and Benede, Ntombi and Bernstein, Mallory and Besethi, Asiphe S and Cele, Sandile and Crowther, Carol and Dhar, Mrinmayee and Geyer, Sohair and Gill, Katherine and Grifoni, Alba and Hermanus, Tandile and Kaldine, Haajira and Keeton, Roanne S and Kgagudi, Prudence and Khan, Khadija and Lazarus, Erica and Roux, Jean Le and Lustig, Gila and Madzivhandila, Mashudu and Magugu, Siyabulela FJ and Makhado, Zanele and Manamela, Nelia P and Mkhize, Qiniso and Mosala, Paballo and Motlou, Thopisang P and Mutavhatsindi, Hygon and Mzindle, Nonkululeko B and Nana, Anusha and Nesamari, Rofhiwa and Ngomti, Amkele and Nkayi, Anathi A and Nkosi, Thandeka P and Omondi, Millicent A and Panchia, Ravindre and Patel, Faeezah and Sette, Alessandro and Singh, Upasna and van Graan, Strauss and Venter, Elizabeth M. and Walters, Avril and Moyo-Gwete, Thandeka and Richardson, Simone I. and Garrett, Nigel and Rees, Helen and Bekker, Linda-Gail and Gray, Glenda and Burgers, Wendy A. and Sigal, Alex and Moore, Penny L and Fairlie, Lee},\r\ndoi = {10.1101/2023.11.20.23298785},\r\nfile = {:C$\\backslash$:/Users/01462563/AppData/Local/Mendeley Ltd./Mendeley Desktop/Downloaded/Riou et al. - 2023 - Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-.pdf:pdf},\r\njournal = {medRxiv},\r\nkeywords = {OA,OA{\\_}PMC,fund{\\_}not{\\_}ack,original},\r\nmendeley-tags = {OA,OA{\\_}PMC,fund{\\_}not{\\_}ack,original},\r\nmonth = {nov},\r\npages = {2023.11.20.23298785},\r\npmid = {38045321},\r\npublisher = {Cold Spring Harbor Laboratory Press},\r\ntitle = {{Safety and immunogenicity of booster vaccination and fractional dosing with Ad26.COV2.S or BNT162b2 in Ad26.COV2.S-vaccinated participants}},\r\nurl = {https://www.medrxiv.org/content/10.1101/2023.11.20.23298785v1 https://www.medrxiv.org/content/10.1101/2023.11.20.23298785v1.abstract},\r\nyear = {2023}\r\n}\r\n","author_short":["Riou, C.","Bhiman, J. N","Ganga, Y.","Sawry, S.","Ayres, F.","Baguma, R.","Balla, S. R","Benede, N.","Bernstein, M.","Besethi, A. S","Cele, S.","Crowther, C.","Dhar, M.","Geyer, S.","Gill, K.","Grifoni, A.","Hermanus, T.","Kaldine, H.","Keeton, R. S","Kgagudi, P.","Khan, K.","Lazarus, E.","Roux, J. L.","Lustig, G.","Madzivhandila, M.","Magugu, S. F.","Makhado, Z.","Manamela, N. P","Mkhize, Q.","Mosala, P.","Motlou, T. P","Mutavhatsindi, H.","Mzindle, N. B","Nana, A.","Nesamari, R.","Ngomti, A.","Nkayi, A. A","Nkosi, T. P","Omondi, M. A","Panchia, R.","Patel, F.","Sette, A.","Singh, U.","van Graan, S.","Venter, E. M.","Walters, A.","Moyo-Gwete, T.","Richardson, S. I.","Garrett, N.","Rees, H.","Bekker, L.","Gray, G.","Burgers, W. A.","Sigal, A.","Moore, P. 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