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Ad26.COV2.S breakthrough infections induce high titers of neutralizing antibodies against Omicron and other SARS-CoV-2 variants of concern
The 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.