SARS-CoV-2 Omicron triggers cross-reactive neutralization and Fc effector functions in previously vaccinated, but not unvaccinated, individuals
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Abstract
The SARS-CoV-2 Omicron variant escapes neutralizing antibodies elicited by vaccines or infection. However, whether Omicron triggers cross-reactive humoral responses to other variants of concern (VOCs) remains unknown. We used plasma from 20 unvaccinated and 7 vaccinated individuals infected by Omicron BA.1 to test binding, Fc effector function, and neutralization against VOCs. In unvaccinated individuals, Fc effector function and binding antibodies targeted Omicron and other VOCs at comparable levels. However, Omicron BA.1-triggered neutralization was not extensively cross-reactive for VOCs (14- to 31-fold titer reduction), and we observed 4-fold decreased titers against Omicron BA.2. In contrast, vaccination followed by breakthrough Omicron infection associated with improved cross-neutralization of VOCs with titers exceeding 1:2,100. This has important implications for the vulnerability of unvaccinated Omicron-infected individuals to reinfection by circulating and emerging VOCs. Although Omicron-based immunogens might be adequate boosters, they are unlikely to be superior to existing vaccines for priming in SARS-CoV-2-naive individuals.
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Prior work has demonstrated Omicron BA.1/2's significant immune escape properties.
“Prior work has demonstrated Omicron BA. 1/2's significant immune escape properties [13][14][15][16][17] .”
From Rapidly shifting immunologic landscape and severity of SARS-CoV-2 in the Omicron era in South Africa (2023) · cites this paper as [15]
Over reliance on immune memory may impact the breadth and strength of antibody and B-cell immunity as new antigenically drifted variants arise.
“Over reliance on immune memory may impact the breadth and strength of antibody and B-cell immunity as new antigenically drifted variants arise 15,21,32,33 .”
From Rapidly shifting immunologic landscape and severity of SARS-CoV-2 in the Omicron era in South Africa (2023) · cites this paper as [15]
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- Authors
- Richardson, S. I., Madzorera, V. S., Spencer, H., Manamela, N. P., van der Mescht, M. A., Lambson, B. E., Oosthuysen, B., Ayres, F., Makhado, Z., Moyo-Gwete, T., Mzindle, N., Motlou, T., Strydom, A., Mendes, A., Tegally, H., de Beer, Z., Roma de Villiers, T., Bodenstein, A., van den Berg, G., Venter, M., de Oliviera, T., Ueckermann, V., Rossouw, T. M., Boswell, M. T., & Moore, P. L.
- Affiliations
- National Health Laboratory Service (ZA)
- University of Pretoria (ZA)
- Stellenbosch University (ZA)
- Steve Biko Hospital (ZA)
- Corresponding author
- Moore, Penny L.
- ORCID
- Venue
- Cell Host & Microbe
- Publisher
- Elsevier BV
- Published
- 2022-06
- Volume
- 30
- Issue
- 6
- Pages
- 880-886.e4
- ISSN
- 1931-3128 (ISSN-L)
- PMC
- PMC8947963
- OpenAlex
- W4226065542
- Cited by
- 119
- References
- 36
- Citations by year
- 2026: 8 · 2025: 12 · 2024: 22 · 2023: 29 · 2022: 47
- FWCI
- 13.44
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell Host & Microbe (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- UpSpace Institutional Repository (University of Pretoria) (submittedVersion, cc-by)
- Funders
- International AIDS Vaccine Initiative
- National Research Foundation
- South African Medical Research Council
- Bill & Melinda Gates Foundation
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- Omicron variant, Omicron BA.1, Omicron BA.2, Fc effector functions, vaccine escape, breakthrough infection, variants of concern, humoral immunity, COVID-19 vaccination, reinfection
- MeSH terms
- COVID-19, SARS-CoV-2, Antibodies, Viral, Humans, Neutralization Tests, Antibodies, Neutralizing
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