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

The SARS-CoV-2 Omicron variant largely escapes neutralizing antibodies elicited by vaccines or infection. However, whether Omicron triggers humoral responses that are cross-reactive to other variants of concern (VOCs) remains largely unknown. We use plasma from 20 unvaccinated and seven vaccinated individuals infected during the Omicron wave in South Africa to test binding, antibody-dependent cellular cytotoxicity (ADCC), antibody-dependent cellular phagocytosis (ADCP) and neutralization against VOCs. In unvaccinated individuals, Fc effector function and binding antibodies target Omicron and other VOCs at comparable levels. However, Omicron-triggered neutralization is not extensively cross-reactive to VOCs, with 20 to 43-fold reductions in titer. In contrast, vaccination followed by breakthrough Omicron infection improved cross-neutralization of VOCs, with titers exceeding 1:2,900. This has important implications for the vulnerability of unvaccinated Omicron-infected individuals to reinfection by circulating and emerging VOCs. Further, while Omicron-based immunogens may be adequate boosters, they are unlikely to be superior to existing vaccines for priming in SARS-CoV-2 naive individuals.

Ad26.COV2.S breakthrough infections induce high titers of antibodies capable of neutralizing variants of concern (preprint)

The Janssen (Johnson & Johnson) Ad26.COV2.S non-replicating viral vector vaccine, which requires only a single dose and conventional cold chain storage, is a valuable tool for COVID-19 vaccination programs in resource-limited settings. Here we show that neutralizing and binding responses to Ad26.COV2.S vaccination are stable for 6 months post-vaccination, with responses highest against the ancestral vaccine-similar D614G variant. Secondly, using longitudinal samples from individuals who experienced clinically mild breakthrough infections 3-4 months after vaccination, we show dramatically boosted binding antibodies, Fc effector function and neutralization. These responses, which are cross-reactive against diverse SARS-CoV-2 variants and SARS-CoV-1, are of similar magnitude to humoral immune responses measured in severely ill, hospitalized donors. These data highlight the significant priming capacity of Ad26.COV2.S, and have implications for population immunity in areas where the single dose Ad26.COV2.S vaccine has been deployed.

SARS-CoV-2 501Y.V2 (B.1.351) elicits cross-reactive neutralizing antibodies (preprint)

Neutralization escape by SARS-CoV-2 variants, as has been observed in the 501Y.V2 (B.1.351) variant, has impacted the efficacy of first generation COVID-19 vaccines. Here, the antibody response to the 501Y.V2 variant was examined in a cohort of patients hospitalized with COVID-19 in early 2021 - when over 90% of infections in South Africa were attributed to 501Y.V2. Robust binding and neutralizing antibody titers to the 501Y.V2 variant were detected and these binding antibodies showed high levels of cross-reactivity for the original variant, from the first wave. In contrast to an earlier study where sera from individuals infected with the original variant showed dramatically reduced potency against 501Y.V2, sera from 501Y.V2-infected patients maintained good cross-reactivity against viruses from the first wave. Furthermore, sera from 501Y.V2-infected patients also neutralized the 501Y.V3 (P.1) variant first described in Brazil, and now circulating globally. Collectively these data suggest that the antibody response in patients infected with 501Y.V2 has a broad specificity and that vaccines designed with the 501Y.V2 sequence may elicit more cross-reactive responses.