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

Abstract

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 neutralization resistant 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.

SARS-CoV-2 Omicron triggers cross-reactive neutralization and Fc effector functions in previously vaccinated, but not unvaccinated individuals

“…This study confirms this is also true of Omicron breakthrough infections, with a 153-fold increase in titers to D614G in vaccinated compared to unvaccinated individuals, consistent with other studies (Khan et al, 2022;Suryawanshi et al, 2022;Zhou et al, 2022). We also extend our previous study, where we showed ADCC was boosted by breakthrough infection, to include ADCP, confirming that this applies to other Fc effector functions (Kitchin et al, 2022).…”

“…We and others have shown that Fc effector function is largely preserved against VOCs in both convalescent and vaccine-elicited plasma (Kaplonek et al, 2022;Richardson et al, 2022). Also, as with neutralization, we have shown that Fc effector function triggered by Beta is more cross-reactive compared to antibodies elicited by D614G, indicating that the spike sequence of the eliciting immunogen impacts the extent of ADCC cross-reactivity (Moyo-Gwete et al, 2021;Richardson et al, 2022). Here, we show that Omicron infection similarly triggers differential ADCC cross-reactivity, with significantly decreased activity against D614G and Beta, but not Delta.…”

“…Although Fc receptor binding was substantially reduced in antibodies tested against Omicron (Bartsch et al, 2021), functional Fc effector responses have not yet been reported. The ability of antibodies to bind the Omicron spike suggests that cytotoxic effector functions driven by antibodies may also be retained, as for earlier VOCs (Kaplonek et al, 2022;Richardson et al, 2022). This, along with the finding that T cells triggered by infection or vaccination are cross-reactive for Omicron (Gao et al, 2022;Keeton et al, 2022;Tarke et al, 2022), likely contributes to maintained vaccine effectiveness against severe disease following Omicron infection (Collie et al, 2022).…”

“…We and others have shown that humoral function is significantly boosted in individuals with breakthrough infections after vaccination [21][22][23] . This study confirms that this is also true of Omicron breakthrough infections, with a 153-fold increase in titers to D614G in vaccinated compared to unvaccinated individuals, consistent with other studies [23][24][25] .…”

Enhanced immunity after Ad26.COV2.S vaccine breakthrough infection

“…A study by Kitchin, Richardson et al. 10 begins to provide answers to what this impact might be. They measured plasma antibodies in 19 Ad26.COV2.S-vaccinated health care workers (HCWs) in South Africa, 6 of whom experienced mild cases of breakthrough infections 4–5 months later, during a period of time when Delta was the predominant variant in the region.…”