Kitchin, DaleRichardson, Simone I.Van der Mescht, Mieke AdriMotlou, ThopisangMzindle, NonkululekoMoyo-Gwete, ThandekaMakhado, ZaneleAyres, FrancesManamela, Nelia P.Spencer, HollyLambson, BronwenOosthuysen, BrentKaldine, HaajiraDu Pisanie, MarizaneMennen, MathildaSkelem, SangoWilliams, NoleenNtusi, Ntobeko A.B.Burgers, Wendy A.Gray, Glenda G.Bekker, Linda-GailBoswell, Michael T.Rossouw, Theresa M.Ueckermann, VeronicaMoore, Penny L.2023-05-102023-05-102022-03-15Kitchin, D., Richardson, S.I., Van der Mescht, M.A. et al. 2022, 'Ad26.COV2.S breakthrough infections induce high titers of neutralizing antibodies against Omicron and other SARS-CoV-2 variants of concern', Cell Host & Microbe, vol. 3, art. 100535, pp. 1-7, doi : 10.1016/j.xcrm.2022.100535.1931-3128 (print)1934-6069 (online)10.1016/j.xcrm.2022.100535http://hdl.handle.net/2263/90615The Janssen (Johnson & Johnson) Ad26.COV2.S non-replicating viral vector vaccine has been widely deployed for COVID-19 vaccination programs in resource-limited settings. Here we confirm that neutralizing and binding antibody responses to Ad26.COV2.S vaccination are stable for 6 months post-vaccination, when tested against multiple SARS-CoV-2 variants. Secondly, using longitudinal samples from individuals who experienced clinically mild breakthrough infections 4 to 5 months after vaccination, we show dramatically boosted binding antibodies, Fc effector function, and neutralization. These high titer responses are of similar magnitude to humoral immune responses measured in convalescent donors who had been hospitalized with severe illness, and are cross-reactive against diverse SARS-CoV-2 variants, including the neutralizationresistant Omicron (B.1.1.529) variant that currently dominates global infections, as well as SARS-CoV-1. These data have implications for population immunity in areas where the Ad26.COV2.S vaccine has been widely deployed, but where ongoing infections continue to occur at high levels.en© 2022 The Author(s). This is an open access article under the CC BY-NC-ND license.Omicron (B.1.1.529) variantAd26.COV2.SVaccineInfectionsSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2)Article