Plasma Neutralization of the SARS-CoV-2 Omicron Variant
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Abstract
BACKGROUND: The Omicron SARS-CoV-2 variant has spread internationally and is responsible for rapidly increasing case numbers. The emergence of divergent variants in the context of a heterogeneous and evolving neutralizing antibody response in host populations might compromise protection afforded by vaccines or prior infection. METHODS: We measured neutralizing antibody titers in 169 longitudinally collected plasma samples using pseudotypes bearing the Wuhan-hu-1 or the Omicron variant or a laboratory-designed neutralization-resistant SARS-CoV-2 spike (PMS20). Plasmas were obtained from convalescents who did or did not subsequently receive an mRNA vaccine, or naive individuals who received 3-doses of mRNA or 1-dose Ad26 vaccines. Samples were collected approximately 1, 5-6 and 12 months after initial vaccination or infection. RESULTS: Like PMS20, the Omicron spike protein was substantially resistant to neutralization compared to Wuhan-hu-1. In convalescent plasma the median deficit in neutralizing activity against PMS20 or Omicron was 30- to 60-fold. Plasmas from recipients of 2 mRNA vaccine doses were 30- to 180- fold less potent against PMS20 and Omicron than Wuhan-hu-1. Notably, previously infected or two-mRNA dose vaccinated individuals who received additional mRNA vaccine dose(s) had 38 to 154-fold and 35 to 214-fold increases in neutralizing activity against Omicron and PMS20 respectively. CONCLUSIONS: Omicron exhibits similar distribution of sequence changes and neutralization resistance as does a laboratory-designed neutralization-resistant spike protein, suggesting natural evolutionary pressure to evade the human antibody response. Currently available mRNA vaccine boosters, that may promote antibody affinity maturation, significantly ameliorate SARS-CoV-2 neutralizing antibody titers.
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Due to escape of the Omicron variant from current approved vaccines, the efficacy of all current vaccines is reduced and a new variant-specific analysis is required.
“However, due to escape of the Omicron variant from current approved vaccines, the efficacy of all current vaccines is reduced and a new variant-specific analysis is therefore required [13][14][15] .”
From Safety and immunogenicity of a prefusion non-stabilized spike protein mRNA COVID-19 vaccine: a phase I trial (2022) · cites this paper as [14]
The Results (vaccine-recipient plasma section; page unavailable) show substantially reduced neutralization of Omicron after two mRNA vaccine doses, and the Discussion reports low Omicron-neutralizing titers in some Ad26 recipients. The study measured plasma neutralization, not the clinical efficacy of all approved vaccines. Its Discussion calls for broadly based vaccination strategies, but does not state that a new variant-specific analysis is required. (LLM, conf=0.86)
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- Authors
- Schmidt, F., Muecksch, F., Weisblum, Y., Da Silva, J., Bednarski, E., Cho, A., Wang, Z., Gaebler, C., Caskey, M., Nussenzweig, M. C., Hatziioannou, T., & Bieniasz, P. D.
- Affiliations
- Rockefeller University (US)
- Rockefeller University, New York, NY
- Corresponding author
- Bieniasz, Paul D.
- Venue
- New England Journal of Medicine
- Publisher
- Massachusetts Medical Society
- Published
- 2022-02-10
- Volume
- 386
- Issue
- 6
- Pages
- 599-601
- ISSN
- 0028-4793 (ISSN-L)
- 1533-4406
- PMC
- PMC8687470
- OpenAlex
- W4205145778
- Cited by
- 432
- References
- 22
- Citations by year
- 2026: 9 · 2025: 16 · 2024: 24 · 2023: 68 · 2022: 307 · 2021: 8
- FWCI
- 32.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- New England Journal of Medicine (publishedVersion)
- medRxiv (acceptedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion, cc-by-nc-nd)
- Funders
- Howard Hughes Medical Institute
- National Institutes of Health (2U19AI111825, P01-AI138398-S1, R01AI501111, R01AI78788, R37AI64003)
- National Center for Advancing Translational Sciences (UL1 TR001866)
- Topics
- Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
- Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
- Life Sciences › Agricultural and Biological Sciences › Animal Science and Zoology › Animal Virus Infections Studies
- Keywords
- Omicron variant, neutralizing antibodies, plasma neutralization, spike protein mutations, receptor binding domain, N-terminal domain, antibody escape, Wuhan-Hu-1, COVID-19 recovery, mRNA vaccines, neutralization titers
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