mRNA booster immunization elicits potent neutralizing serum activity against the SARS-CoV-2 Omicron variant
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Abstract
The Omicron variant of SARS-CoV-2 is causing a rapid increase in infections across the globe. This new variant of concern carries an unusually high number of mutations in key epitopes of neutralizing antibodies on the viral spike glycoprotein, suggesting potential immune evasion. Here we assessed serum neutralizing capacity in longitudinal cohorts of vaccinated and convalescent individuals, as well as monoclonal antibody activity against Omicron using pseudovirus neutralization assays. We report a near-complete lack of neutralizing activity against Omicron in polyclonal sera from individuals vaccinated with two doses of the BNT162b2 COVID-19 vaccine and from convalescent individuals, as well as resistance to different monoclonal antibodies in clinical use. However, mRNA booster immunizations in vaccinated and convalescent individuals resulted in a significant increase of serum neutralizing activity against Omicron. This study demonstrates that booster immunizations can critically improve the humoral immune response against the Omicron variant.
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Repeated immunization extends neutralization to non-homologous variants, possibly through affinity maturation of memory B cell populations.
“Recent studies have revealed that repeated immunization extends neutralization to non-homologous variants, possibly through affinity maturation of memory B cell populations12,25.”
From Efficacy of an unmodified bivalent mRNA vaccine against SARS-CoV-2 variants in female small animal models (2023) · cites this paper as [25]
The Main section reports that a BNT162b2 booster substantially increased serum neutralization against Omicron and speculates that ongoing affinity maturation may explain the response. It does not identify memory B cell populations as the mechanism or establish the effect across multiple non-homologous variants; the measured booster response here is to Omicron. No page number is provided in our copy. (LLM, conf=0.85)
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- Authors
- Gruell, H., Vanshylla, K., Tober-Lau, P., Hillus, D., Schommers, P., Lehmann, C., Kurth, F., Sander, L. E., & Klein, F.
- Affiliations
- University of Cologne (DE)
- Humboldt-Universität zu Berlin (DE)
- Corresponding author
- Klein, Florian
- ORCID
- Venue
- Nature Medicine
- Published
- 2022-01-19
- Volume
- 28
- Issue
- 3
- Pages
- 477-480
- ISSN
- 1078-8956 (ISSN-L)
- 1546-170X
- PMC
- PMC8767537
- OpenAlex
- W4225386205
- Cited by
- 410
- References
- 38
- Citations by year
- 2026: 11 · 2025: 20 · 2024: 40 · 2023: 87 · 2022: 246 · 2021: 6
- FWCI
- 48.03
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Locations
- Nature Medicine (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- Research Square (acceptedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Kölner Universitäts PublikationsServer (Universität zu Köln) (publishedVersion)
- Funders
- Deutsches Zentrum für Infektionsforschung
- Deutsche Forschungsgemeinschaft (CRC1310)
- Bundesministerium für Bildung und Forschung (01KX2021)
- Bundesinstitut für Arzneimittel und Medizinprodukte (Federal Institute for Drugs and Medical Devices)
- 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
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Keywords
- Omicron variant, neutralizing antibodies, BNT162b2, humoral immune response, monoclonal antibody resistance, convalescent sera, spike protein mutations, immune evasion, COVID-19 vaccination
- MeSH terms
- COVID-19, SARS-CoV-2, COVID-19 Vaccines, BNT162 Vaccine, Antibodies, Viral, Humans, Immunization, Secondary, RNA, Messenger, Antibodies, Neutralizing
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