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Neutralization of viruses with European, South African, and United States SARS-CoV-2 variant spike proteins by convalescent sera and BNT162b2 mRNA vaccine-elicited antibodies
Open accessAbstract
The increasing prevalence of SARS-CoV-2 variants with mutations in the spike protein has raised concerns that recovered individuals may not be protected from reinfection and that current vaccines will become less effective. The B.1.1.7 isolate identified in the United Kingdom and B.1.351 isolate identified in the Republic of South Africa encode spike proteins with multiple mutations in the S1 and S2 subunits. In addition, variants have been identified in Columbus, Ohio (COH.20G/677H), Europe (20A.EU2) and in domesticated minks. Analysis by antibody neutralization of pseudotyped viruses showed that convalescent sera from patients infected prior to the emergence of the variant viruses neutralized viruses with the B.1.1.7, B.1.351, COH.20G/677H Columbus Ohio, 20A.EU2 Europe and mink cluster 5 spike proteins with only a minor decrease in titer compared to that of the earlier D614G spike protein. Serum specimens from individuals vaccinated with the BNT162b2 mRNA vaccine neutralized D614G virus with titers that were on average 7-fold greater than convalescent sera. Vaccine elicited antibodies neutralized virus with the B.1.1.7 spike protein with titers similar to D614G virus and neutralized virus with the B.1.351 spike with, on average, a 3-fold reduction in titer (1:500), a titer that was still higher than the average titer with which convalescent sera neutralized D614G (1:139). The reduction in titer was attributable to the E484K mutation in the RBD. The B.1.1.7 and B.1.351 viruses were not more infectious than D614G on ACE2.293T cells in vitro but N501Y, an ACE2 contacting residue present in the B.1.1.7, B.1.351 and COH.20G/677H spike proteins caused higher affinity binding to ACE2, likely contributing to their increased transmissibility. These findings suggest that antibodies elicited by primary infection and by the BNT162b2 mRNA vaccine are likely to maintain protective efficacy against B.1.1.7 and most other variants but that the partial resistance of virus with the B.1.351 spike protein could render some individuals less well protected, supporting a rationale for the development of modified vaccines containing E484K.
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“On the other hand, the loss in activity by 10.3-12.4-foldagainst B.1.351 is larger than results that were reported using mutant pseudoviruses 34,42,43 .”
From Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7 (2021) · cites this paper as [43]
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“The E484K mutation appears to result in a lower neutralising ability of mRNA vaccine sera.48”
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“The neutralization data reported here are in line with previous reports ( 42 , 47 – 49 ).”
Metadata
- Authors
- Tada, T., Dcosta, B. M., Samanovic-Golden, M., Herati, R. S., Cornelius, A., Mulligan, M. J., & Landau, N. R.
- Affiliations
- New York University (US)
- Corresponding author
- Landau, Nathaniel R.
- Venue
- mBio
- Publisher
- openRxiv
- Published
- 2021-02-07
- Volume
- 12
- Issue
- 3
- Pages
- e0069621-e0069621
- ISSN
- 2150-7511 (ISSN-L)
- PMC
- PMC7872356
- OpenAlex
- W3164611210
- Cited by
- 153
- References
- 35
- Citations by year
- 2025: 4 · 2024: 5 · 2023: 11 · 2022: 45 · 2021: 88
- FWCI
- 11.88
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- mBio (publishedVersion, cc-by)
- bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- PubMed Central (submittedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- National Institutes of Health (AI122390)
- National Institute on Drug Abuse (DP1DA046100)
- National Institute of Allergy and Infectious Diseases (K08AI120898, R21AI122390, U01AI047996, R33AI122390, UM1AI148574)
- Common Fund (AI122390, AI120898, DA046100, UM1AI148574)
- 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
- SARS-CoV-2 variants, neutralizing antibodies, convalescent sera, vaccine-elicited antibodies, B.1.351 variant, anti-spike antibodies, antibody escape, combination therapy, vaccine effectiveness, variant surveillance
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