SARS-CoV-2 Omicron has extensive but incomplete escape of Pfizer BNT162b2 elicited neutralization and requires ACE2 for infection
Open accessPreprint — published as 10.1038/s41586-021-04387-1 · Paper page
Abstract
The emergence of SARS-CoV-2 Omicron, first identified in Botswana and South Africa, may compromise vaccine effectiveness and the ability of antibodies triggered by previous infection to protect against re-infection (1). Here we investigated whether Omicron escapes antibody neutralization in South Africans, either previously SARS-CoV-2 infected or uninfected, who were vaccinated with Pfizer BNT162b2. We also investigated if Omicron requires the ACE2 receptor to infect cells. We isolated and sequence confirmed live Omicron virus from an infected person in South Africa and compared plasma neutralization of this virus relative to an ancestral SARS-CoV-2 strain with the D614G mutation, observing that Omicron still required ACE2 to infect. For neutralization, blood samples were taken soon after vaccination, so that vaccine elicited neutralization was close to peak. Neutralization capacity of the D614G virus was much higher in infected and vaccinated versus vaccinated only participants but both groups had 22-fold Omicron escape from vaccine elicited neutralization. Previously infected and vaccinated individuals had residual neutralization predicted to confer 73% protection from symptomatic Omicron infection, while those without previous infection were predicted to retain only about 35%. Both groups were predicted to have substantial protection from severe disease. These data support the notion that high neutralization capacity elicited by a combination of infection and vaccination, and possibly boosting, could maintain reasonable effectiveness against Omicron. A waning neutralization response is likely to decrease vaccine effectiveness below these estimates. However, since protection from severe disease requires lower neutralization levels and involves T cell immunity, such protection may be maintained.
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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 [13]
The Abstract (page not indicated) reports a 22-fold reduction in Omicron neutralization after Pfizer BNT162b2 vaccination and predicts reduced protection against symptomatic infection. The study examines that vaccine, not all approved vaccines, so it does not support the claim that efficacy is reduced for every current vaccine. The call for a new variant-specific analysis is the citing authors’ conclusion. (LLM, conf=0.88)
Experimental — accuracy not yet measuredReinfections and vaccine breakthrough infections accounted for the majority of Omicron BA.1/2 infections, likely attributable to a minority of population remaining naïve prior to the Omicron BA.1/2 wave and to Omicron BA.1/2's immune-escape properties.
“Reinfections and vaccine breakthrough infections accounted for the majority of Omicron BA.1/2 infections, likely attributable to a minority of population remaining naïve prior to the Omicron BA.1/2 wave and to Omicron BA.1/2's immune-escape properties 16,21,22 .”
From Rapidly shifting immunologic landscape and severity of SARS-CoV-2 in the Omicron era in South Africa (2023) · cites this paper as [16]
Many SARS-CoV-2 variants, including Delta and Omicron, have adopted different mutation strategies to evade immune recognition, leading to the failure of neutralizing antibodies and vaccines.
“Many such variants, including Delta and the most recent Omicron, have adopted different mutation strategies to evade immune recognition, leading to the failure of neutralizing antibodies and vaccines (18, 23, 45–48).”
From Deep learning guided optimization of human antibody against SARS-CoV-2 variants with broad neutralization (2022) · cites this paper as [48]
Higher neutralizing activity was observed after a booster dose.
“Higher neutralizing activity was observed after a booster dose.”
From Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern (2021) · cites this paper as [3]
These findings are consistent with neutralization data for the omicron variant.
“These findings are consistent with neutralization data for the omicron variant.”
From Effectiveness of COVID-19 vaccines against the Omicron (B.1.1.529) variant of concern (2021) · cites this paper as [3]
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“Serum neutralizing activity is one of many correlates of protection, and although SARS-CoV-2 variants have been associated with escape of vaccine-induced neutralizing antibodies 36–41 , clinical protection is maintained through vaccine-induced T cell responses and Fc effector functions 42–46 .”
BackgroundBounding the levels of transmissibility & immune evasion of the Omicron variant in South Africa
Pearson, C. A. B., Silal, S. P., Li, M. W. Z., Dushoff, J., Bolker, B. M., Abbott, S., van Schalkwyk, C., Davies, N. G., Barnard, R. C., Edmunds, W. J., et al. (2021) · doi:10.1101/2021.12.19.21268038 · Cited by 44 · see citing works
Sun, K., Tempia, S., Kleynhans, J., von Gottberg, A., McMorrow, M. L., Wolter, N., Bhiman, J. N., Moyes, J., du Plessis, M., Carrim, M., et al. (2022) · Science Translational Medicine · doi:10.1126/scitranslmed.abo7081 · Cited by 52 · see citing works
Self-citationRapidly shifting immunologic landscape and severity of SARS-CoV-2 in the Omicron era in South Africa
Sun, K., Tempia, S., Kleynhans, J., von Gottberg, A., McMorrow, M. L., Wolter, N., Bhiman, J. N., Moyes, J., Carrim, M., Martinson, N. A., et al. (2023) · Nature Communications · doi:10.1038/s41467-022-35652-0 · Cited by 45 · see citing works
Self-citationGuo, Y., Zhang, G., Yang, Q., Xie, X., Lu, Y., Cheng, X., Wang, H., Liang, J., Tang, J., Gao, Y., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-39267-x · Cited by 28 · see citing works
“…34 distinct insertions,deletions, and mutations 6 , along with 15 amino acid mutations located in the receptor-binding domain (RBD), which leads to widespread escape from drugs and vaccines developed based on the ancestral strain in the early stage 7,8 , especially RBD-speci fi c antibodies 6 .”
Meggiolaro, A., Sane Schepisi, M., Farina, S., Castagna, C., Mammone, A., Siddu, A., Stefanelli, P., Boccia, S., & Rezza, G. (2022) · Expert Review of Vaccines · doi:10.1080/14760584.2022.2130773 · Cited by 17 · see citing works
Sitaras, I., Jacobsen, H., Higdon, M. M., Dowling, W. E., Bar-Zeev, N., & Deloria Knoll, M. (2022) · npj Vaccines · doi:10.1038/s41541-022-00565-y · Cited by 17 · see citing works
Gatechompol, S., Kittanamongkolchai, W., Ketloy, C., Prompetchara, E., Thitithanyanont, A., Jongkaewwattana, A., Buranapraditkun, S., Alameh, M.-G., Ubolyam, S., Sophonphan, J., et al. (2022) · Nature Microbiology · doi:10.1038/s41564-022-01271-0 · Cited by 15 · see citing works
Self-citation
- Authors
- Cele, S., Jackson, L., Khoury, D. S., Khan, K., Moyo-Gwete, T., Tegally, H., San, J. E., Cromer, D., Scheepers, C., Amoako, D., Karim, F., Bernstein, M., Lustig, G., Archary, D., Smith, M., Ganga, Y., Jule, Z., Reedoy, K., Hwa, S.-H., Giandhari, J., Blackburn, J. M., Gosnell, B. I., Karim, S. S. A., Hanekom, W., NGS-SA, COMMIT-KZN Team, von Gottberg, A., Bhiman, J., Lessells, R. J., Moosa, M.-Y. S., Davenport, M. P., de Oliveira, T., Moore, P. L., & Sigal, A.
- Affiliations
- Africa Health Research Institute (ZA)
- UNSW Sydney (AU)
- National Health Laboratory Service (ZA)
- Stellenbosch University (ZA)
- Centre for the AIDS Programme of Research in South Africa (ZA)
- University of Cape Town (ZA)
- University of KwaZulu-Natal (ZA)
- University of Washington (US)
- Max Planck Institute for Infection Biology (DE)
- Corresponding author
- Sigal, Alex
- ORCID
- Cele, Sandile
- Jackson, Laurelle
- Khoury, David S.
- Khan, Khadija
- Moyo-Gwete, Thandeka
- Tegally, Houriiyah
- Cromer, Deborah
- Scheepers, Cathrine
- Amoako, Daniel
- Karim, Farina
- Bernstein, Mallory
- Lustig, Gila
- Archary, Derseree
- Smith, Muneerah
- Ganga, Yashica
- Reedoy, Kajal
- Hwa, Shi-Hsia
- Giandhari, Jennifer
- Blackburn, Jonathan M.
- Gosnell, Bernadett I.
- Karim, Salim S. Abdool
- Hanekom, Willem
- Bhiman, Jinal
- Lessells, Richard J.
- Moosa, Mahomed-Yunus S.
- Davenport, Miles P.
- de Oliveira, Tulio
- Moore, Penny L.
- Sigal, Alex
- Venue
- Nature
- Publisher
- openRxiv
- Published
- 2021-12-09
- Volume
- 602
- Issue
- 7898
- Pages
- 654-656
- ISSN
- 0028-0836 (ISSN-L)
- PMC
- PMC8669855
- OpenAlex
- W4220673385
- Cited by
- 1,333
- References
- 37
- Citations by year
- 2026: 40 · 2025: 80 · 2024: 125 · 2023: 302 · 2022: 735 · 2021: 51
- FWCI
- 96.19
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Nature (publishedVersion, cc-by)
- medRxiv (acceptedVersion, cc-by-nd)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (publishedVersion, cc-by)
- UNSWorks (University of New South Wales, Sydney, Australia) (submittedVersion, cc-by-nc-nd)
- PubMed Central (submittedVersion, cc-by-nd)
- Griffith Research Online (submittedVersion, cc-by)
- Funders
- Wellcome Trust (221003/Z/20/Z)
- South African Medical Research Council (98341)
- Foreign, Commonwealth and Development Office
- National Institutes of Health (98341)
- Medical Research Council
- National Health and Medical Research Council
- National Institute of Allergy and Infectious Diseases (R01AI033856, R01AI138546)
- European and Developing Countries Clinical Trials Partnership (TMA2017SF-1960)
- 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 › Biochemistry, Genetics and Molecular Biology › Molecular Biology › vaccines and immunoinformatics approaches
- Keywords
- Omicron variant, SARS-CoV-2, BNT162b2, vaccine escape, neutralizing antibodies, antibody neutralization, ACE2 receptor, prior SARS-CoV-2 infection, South Africa
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