Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity

Wilfredo F. Garcia-Beltran; Evan C. Lam; Kerri St. Denis; Adam D. Nitido; Zeidy H. Garcia; Blake M. Hauser; Jared Feldman; Maia N. Pavlovic; David J. Gregory; Mark C. Poznansky; Alex Sigal; Aaron G. Schmidt; A. John Iafrate; Vivek Naranbhai; Alejandro B. Balazs

doi:10.1016/j.cell.2021.03.013

Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity

Wilfredo F. Garcia-Beltran, Evan C. Lam, Kerri St. Denis, Adam D. Nitido, Zeidy H. Garcia, Blake M. Hauser, Jared Feldman, Maia N. Pavlovic, David J. Gregory, Mark C. Poznansky, Alex Sigal, Aaron G. Schmidt, A. John Iafrate, Vivek Naranbhai, Alejandro B. Balazs

Research output: Contribution to journal › Article › Research › peer-review

984 Citations (Scopus)

Abstract

Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence of variants harboring mutations in spike, the main target of neutralizing antibodies. To understand the impact of these variants, we evaluated the neutralization potency of 99 individuals that received one or two doses of either BNT162b2 or mRNA-1273 vaccines against pseudoviruses representing 10 globally circulating strains of SARS-CoV-2. Five of the 10 pseudoviruses, harboring receptor-binding domain mutations, including K417N/T, E484K, and N501Y, were highly resistant to neutralization. Cross-neutralization of B.1.351 variants was comparable to SARS-CoV and bat-derived WIV1-CoV, suggesting that a relatively small number of mutations can mediate potent escape from vaccine responses. While the clinical impact of neutralization resistance remains uncertain, these results highlight the potential for variants to escape from neutralizing humoral immunity and emphasize the need to develop broadly protective interventions against the evolving pandemic.

Original language	English
Pages (from-to)	2372-2383.e9
Number of pages	24
Journal	Cell
Volume	184
Issue number	9
DOIs	https://doi.org/10.1016/j.cell.2021.03.013
Publication status	Published - 29 Apr 2021
Externally published	Yes

Keywords

COVID-19
escape
mRNA vaccines
neutralizing antibodies
RBD
SARS-CoV-2
spike
variants

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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Garcia-Beltran, W. F., Lam, E. C., St. Denis, K., Nitido, A. D., Garcia, Z. H., Hauser, B. M., Feldman, J., Pavlovic, M. N., Gregory, D. J., Poznansky, M. C., Sigal, A., Schmidt, A. G., Iafrate, A. J., Naranbhai, V., & Balazs, A. B. (2021). Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. Cell, 184(9), 2372-2383.e9. https://doi.org/10.1016/j.cell.2021.03.013

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abstract = "Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence of variants harboring mutations in spike, the main target of neutralizing antibodies. To understand the impact of these variants, we evaluated the neutralization potency of 99 individuals that received one or two doses of either BNT162b2 or mRNA-1273 vaccines against pseudoviruses representing 10 globally circulating strains of SARS-CoV-2. Five of the 10 pseudoviruses, harboring receptor-binding domain mutations, including K417N/T, E484K, and N501Y, were highly resistant to neutralization. Cross-neutralization of B.1.351 variants was comparable to SARS-CoV and bat-derived WIV1-CoV, suggesting that a relatively small number of mutations can mediate potent escape from vaccine responses. While the clinical impact of neutralization resistance remains uncertain, these results highlight the potential for variants to escape from neutralizing humoral immunity and emphasize the need to develop broadly protective interventions against the evolving pandemic.",

keywords = "COVID-19, escape, mRNA vaccines, neutralizing antibodies, RBD, SARS-CoV-2, spike, variants",

author = "Garcia-Beltran, {Wilfredo F.} and Lam, {Evan C.} and {St. Denis}, Kerri and Nitido, {Adam D.} and Garcia, {Zeidy H.} and Hauser, {Blake M.} and Jared Feldman and Pavlovic, {Maia N.} and Gregory, {David J.} and Poznansky, {Mark C.} and Alex Sigal and Schmidt, {Aaron G.} and Iafrate, {A. John} and Vivek Naranbhai and Balazs, {Alejandro B.}",

note = "Funding Information: We wish to thank Michael Farzan, PhD for providing ACE2-expressing 293T cells. We also thank Mandakolathur Murali, MD for many useful and insightful discussions. B.M.H. and is supported by award number T32GM007753 from the National Institute of General Medical Sciences . J.F. is supported by T32AI007245 . D.J.G., M.C.P., and M.N.P. were supported by the VIC Innovation fund. A.S. was supported by the Bill and Melinda Gates Investment INV-018944 (A.S.). A.G.S. was supported by NIH R01 AI146779 and a Massachusetts Consortium on Pathogenesis Readiness (MassCPR) grant. A.J.I. is supported by the Lambertus Family Foundation . A.B.B. was supported by the National Institutes for Drug Abuse (NIDA) Avenir New Innovator Award DP2DA040254 , the MGH Transformative Scholars Program as well as funding from the Charles H. Hood Foundation . This independent research was supported by the Gilead Sciences Research Scholars Program in HIV. Publisher Copyright: {\textcopyright} 2021 The Author(s)",

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doi = "10.1016/j.cell.2021.03.013",

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Garcia-Beltran, WF, Lam, EC, St. Denis, K, Nitido, AD, Garcia, ZH, Hauser, BM, Feldman, J, Pavlovic, MN, Gregory, DJ, Poznansky, MC, Sigal, A, Schmidt, AG, Iafrate, AJ, Naranbhai, V & Balazs, AB 2021, 'Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity', Cell, vol. 184, no. 9, pp. 2372-2383.e9. https://doi.org/10.1016/j.cell.2021.03.013

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T1 - Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity

AU - Garcia-Beltran, Wilfredo F.

AU - Lam, Evan C.

AU - St. Denis, Kerri

AU - Nitido, Adam D.

AU - Garcia, Zeidy H.

AU - Hauser, Blake M.

AU - Feldman, Jared

AU - Pavlovic, Maia N.

AU - Gregory, David J.

AU - Poznansky, Mark C.

AU - Sigal, Alex

AU - Schmidt, Aaron G.

AU - Iafrate, A. John

AU - Naranbhai, Vivek

AU - Balazs, Alejandro B.

N1 - Funding Information: We wish to thank Michael Farzan, PhD for providing ACE2-expressing 293T cells. We also thank Mandakolathur Murali, MD for many useful and insightful discussions. B.M.H. and is supported by award number T32GM007753 from the National Institute of General Medical Sciences . J.F. is supported by T32AI007245 . D.J.G., M.C.P., and M.N.P. were supported by the VIC Innovation fund. A.S. was supported by the Bill and Melinda Gates Investment INV-018944 (A.S.). A.G.S. was supported by NIH R01 AI146779 and a Massachusetts Consortium on Pathogenesis Readiness (MassCPR) grant. A.J.I. is supported by the Lambertus Family Foundation . A.B.B. was supported by the National Institutes for Drug Abuse (NIDA) Avenir New Innovator Award DP2DA040254 , the MGH Transformative Scholars Program as well as funding from the Charles H. Hood Foundation . This independent research was supported by the Gilead Sciences Research Scholars Program in HIV. Publisher Copyright: © 2021 The Author(s)

PY - 2021/4/29

Y1 - 2021/4/29

N2 - Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence of variants harboring mutations in spike, the main target of neutralizing antibodies. To understand the impact of these variants, we evaluated the neutralization potency of 99 individuals that received one or two doses of either BNT162b2 or mRNA-1273 vaccines against pseudoviruses representing 10 globally circulating strains of SARS-CoV-2. Five of the 10 pseudoviruses, harboring receptor-binding domain mutations, including K417N/T, E484K, and N501Y, were highly resistant to neutralization. Cross-neutralization of B.1.351 variants was comparable to SARS-CoV and bat-derived WIV1-CoV, suggesting that a relatively small number of mutations can mediate potent escape from vaccine responses. While the clinical impact of neutralization resistance remains uncertain, these results highlight the potential for variants to escape from neutralizing humoral immunity and emphasize the need to develop broadly protective interventions against the evolving pandemic.

AB - Vaccination elicits immune responses capable of potently neutralizing SARS-CoV-2. However, ongoing surveillance has revealed the emergence of variants harboring mutations in spike, the main target of neutralizing antibodies. To understand the impact of these variants, we evaluated the neutralization potency of 99 individuals that received one or two doses of either BNT162b2 or mRNA-1273 vaccines against pseudoviruses representing 10 globally circulating strains of SARS-CoV-2. Five of the 10 pseudoviruses, harboring receptor-binding domain mutations, including K417N/T, E484K, and N501Y, were highly resistant to neutralization. Cross-neutralization of B.1.351 variants was comparable to SARS-CoV and bat-derived WIV1-CoV, suggesting that a relatively small number of mutations can mediate potent escape from vaccine responses. While the clinical impact of neutralization resistance remains uncertain, these results highlight the potential for variants to escape from neutralizing humoral immunity and emphasize the need to develop broadly protective interventions against the evolving pandemic.

KW - COVID-19

KW - escape

KW - mRNA vaccines

KW - neutralizing antibodies

KW - RBD

KW - SARS-CoV-2

KW - spike

KW - variants

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DO - 10.1016/j.cell.2021.03.013

M3 - Article

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AN - SCOPUS:85102763305

SN - 0092-8674

VL - 184

SP - 2372-2383.e9

JO - Cell

JF - Cell

IS - 9

ER -

Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity

Abstract

Keywords

UN SDGs

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Erratum: Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity (Cell (2021) 184(9) (2372–2383.e9), (S0092867421002981), (10.1016/j.cell.2021.03.013))

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