mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant

Wilfredo F. Garcia-Beltran; Kerri J. St. Denis; Angelique Hoelzemer; Evan C. Lam; Adam D. Nitido; Maegan L. Sheehan; Cristhian Berrios; Onosereme Ofoman; Christina C. Chang; Blake M. Hauser; Jared Feldman; Alex L. Roederer; David J. Gregory; Mark C. Poznansky; Aaron G. Schmidt; A. John Iafrate; Vivek Naranbhai; Alejandro B. Balazs

doi:10.1016/j.cell.2021.12.033

mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant

Wilfredo F. Garcia-Beltran
, Kerri J. St. Denis
, Angelique Hoelzemer
, Evan C. Lam
, Adam D. Nitido
, Maegan L. Sheehan
, Cristhian Berrios
, Onosereme Ofoman
, Christina C. Chang
, Blake M. Hauser
, Jared Feldman
, Alex L. Roederer
, David J. Gregory
, Mark C. Poznansky
, Aaron G. Schmidt
, A. John Iafrate
, Vivek Naranbhai
, Alejandro B. Balazs

Infectious Diseases

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

815 Citations (Scopus)

Abstract

Recent surveillance has revealed the emergence of the SARS-CoV-2 Omicron variant (BA.1/B.1.1.529) harboring up to 36 mutations in spike protein, the target of neutralizing antibodies. Given its potential to escape vaccine-induced humoral immunity, we measured the neutralization potency of sera from 88 mRNA-1273, 111 BNT162b, and 40 Ad26.COV2.S vaccine recipients against wild-type, Delta, and Omicron SARS-CoV-2 pseudoviruses. We included individuals that received their primary series recently (<3 months), distantly (6–12 months), or an additional “booster” dose, while accounting for prior SARS-CoV-2 infection. Remarkably, neutralization of Omicron was undetectable in most vaccinees. However, individuals boosted with mRNA vaccines exhibited potent neutralization of Omicron, only 4–6-fold lower than wild type, suggesting enhanced cross-reactivity of neutralizing antibody responses. In addition, we find that Omicron pseudovirus infects more efficiently than other variants tested. Overall, this study highlights the importance of additional mRNA doses to broaden neutralizing antibody responses against highly divergent SARS-CoV-2 variants.

Original language	English
Pages (from-to)	457-466.e4
Number of pages	15
Journal	Cell
Volume	185
Issue number	3
DOIs	https://doi.org/10.1016/j.cell.2021.12.033
Publication status	Published - 3 Feb 2022

UN SDGs

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

SDG 3 Good Health and Well-being

Keywords

breadth
COVID-19
Delta
infectivity
neutralizing antibodies
Omicron
SARS-CoV-2
spike
vaccination
variants

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10.1016/j.cell.2021.12.033

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Garcia-Beltran, W. F., St. Denis, K. J., Hoelzemer, A., Lam, E. C., Nitido, A. D., Sheehan, M. L., Berrios, C., Ofoman, O., Chang, C. C., Hauser, B. M., Feldman, J., Roederer, A. L., Gregory, D. J., Poznansky, M. C., Schmidt, A. G., Iafrate, A. J., Naranbhai, V., & Balazs, A. B. (2022). mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant. Cell, 185(3), 457-466.e4. https://doi.org/10.1016/j.cell.2021.12.033

@article{159a76a5610b4f8c97ecc7c4994d828d,

title = "mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant",

abstract = "Recent surveillance has revealed the emergence of the SARS-CoV-2 Omicron variant (BA.1/B.1.1.529) harboring up to 36 mutations in spike protein, the target of neutralizing antibodies. Given its potential to escape vaccine-induced humoral immunity, we measured the neutralization potency of sera from 88 mRNA-1273, 111 BNT162b, and 40 Ad26.COV2.S vaccine recipients against wild-type, Delta, and Omicron SARS-CoV-2 pseudoviruses. We included individuals that received their primary series recently (<3 months), distantly (6–12 months), or an additional “booster” dose, while accounting for prior SARS-CoV-2 infection. Remarkably, neutralization of Omicron was undetectable in most vaccinees. However, individuals boosted with mRNA vaccines exhibited potent neutralization of Omicron, only 4–6-fold lower than wild type, suggesting enhanced cross-reactivity of neutralizing antibody responses. In addition, we find that Omicron pseudovirus infects more efficiently than other variants tested. Overall, this study highlights the importance of additional mRNA doses to broaden neutralizing antibody responses against highly divergent SARS-CoV-2 variants.",

keywords = "breadth, COVID-19, Delta, infectivity, neutralizing antibodies, Omicron, SARS-CoV-2, spike, vaccination, variants",

author = "Garcia-Beltran, \{Wilfredo F.\} and \{St. Denis\}, \{Kerri J.\} and Angelique Hoelzemer and Lam, \{Evan C.\} and Nitido, \{Adam D.\} and Sheehan, \{Maegan L.\} and Cristhian Berrios and Onosereme Ofoman and Chang, \{Christina C.\} and Hauser, \{Blake M.\} and Jared Feldman and Roederer, \{Alex L.\} and Gregory, \{David J.\} and Poznansky, \{Mark C.\} and Schmidt, \{Aaron G.\} and Iafrate, \{A. John\} and Vivek Naranbhai and Balazs, \{Alejandro B.\}",

note = "Funding Information: We thank Anand Dighe, MD; Andrea Nixon, BS; and the MGH Core Laboratory for excellent assistance with clinical SARS-CoV-2 serology testing. We wish to thank Michael Farzan, PhD, for providing ACE2-expressing 293T cells. A.H. is supported by the DZIF (German Center for Infection Research, TTU 01.709 ; 8009701709 ). B.M.H. is supported by award number T32GM007753 from the National Institute of General Medical Sciences and F30 AI160908 from the National Institute of Allergy and Infectious Diseases . J.F. is supported by T32AI007245 . D.J.G. and M.C.P. were supported by the VIC Innovation Fund . A.G.S. was supported by NIH R01 AI146779 and a Massachusetts Consortium on Pathogenesis Readiness (MassCPR) grant. A.H. is supported by the DZIF (German Center for Infection Research, TTU 01.709 ). This work was supported by the Peter and Ann Lambertus Family Foundation . V.N. received support from a Medscape Young Investigators Lung Cancer Award . A.B.B. was supported by the National Institute on Drug Abuse (NIDA) Avenir New Innovator Award DP2DA040254 , the MGH Transformative Scholars Program , and a Massachusetts Consortium on Pathogenesis Readiness (MassCPR) grant. Publisher Copyright: {\textcopyright} 2021 Elsevier Inc.",

year = "2022",

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doi = "10.1016/j.cell.2021.12.033",

language = "English",

volume = "185",

pages = "457--466.e4",

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Garcia-Beltran, WF, St. Denis, KJ, Hoelzemer, A, Lam, EC, Nitido, AD, Sheehan, ML, Berrios, C, Ofoman, O, Chang, CC, Hauser, BM, Feldman, J, Roederer, AL, Gregory, DJ, Poznansky, MC, Schmidt, AG, Iafrate, AJ, Naranbhai, V & Balazs, AB 2022, 'mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant', Cell, vol. 185, no. 3, pp. 457-466.e4. https://doi.org/10.1016/j.cell.2021.12.033

TY - JOUR

T1 - mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant

AU - Garcia-Beltran, Wilfredo F.

AU - St. Denis, Kerri J.

AU - Hoelzemer, Angelique

AU - Lam, Evan C.

AU - Nitido, Adam D.

AU - Sheehan, Maegan L.

AU - Berrios, Cristhian

AU - Ofoman, Onosereme

AU - Chang, Christina C.

AU - Hauser, Blake M.

AU - Feldman, Jared

AU - Roederer, Alex L.

AU - Gregory, David J.

AU - Poznansky, Mark C.

AU - Schmidt, Aaron G.

AU - Iafrate, A. John

AU - Naranbhai, Vivek

AU - Balazs, Alejandro B.

N1 - Funding Information: We thank Anand Dighe, MD; Andrea Nixon, BS; and the MGH Core Laboratory for excellent assistance with clinical SARS-CoV-2 serology testing. We wish to thank Michael Farzan, PhD, for providing ACE2-expressing 293T cells. A.H. is supported by the DZIF (German Center for Infection Research, TTU 01.709 ; 8009701709 ). B.M.H. is supported by award number T32GM007753 from the National Institute of General Medical Sciences and F30 AI160908 from the National Institute of Allergy and Infectious Diseases . J.F. is supported by T32AI007245 . D.J.G. and M.C.P. were supported by the VIC Innovation Fund . A.G.S. was supported by NIH R01 AI146779 and a Massachusetts Consortium on Pathogenesis Readiness (MassCPR) grant. A.H. is supported by the DZIF (German Center for Infection Research, TTU 01.709 ). This work was supported by the Peter and Ann Lambertus Family Foundation . V.N. received support from a Medscape Young Investigators Lung Cancer Award . A.B.B. was supported by the National Institute on Drug Abuse (NIDA) Avenir New Innovator Award DP2DA040254 , the MGH Transformative Scholars Program , and a Massachusetts Consortium on Pathogenesis Readiness (MassCPR) grant. Publisher Copyright: © 2021 Elsevier Inc.

PY - 2022/2/3

Y1 - 2022/2/3

N2 - Recent surveillance has revealed the emergence of the SARS-CoV-2 Omicron variant (BA.1/B.1.1.529) harboring up to 36 mutations in spike protein, the target of neutralizing antibodies. Given its potential to escape vaccine-induced humoral immunity, we measured the neutralization potency of sera from 88 mRNA-1273, 111 BNT162b, and 40 Ad26.COV2.S vaccine recipients against wild-type, Delta, and Omicron SARS-CoV-2 pseudoviruses. We included individuals that received their primary series recently (<3 months), distantly (6–12 months), or an additional “booster” dose, while accounting for prior SARS-CoV-2 infection. Remarkably, neutralization of Omicron was undetectable in most vaccinees. However, individuals boosted with mRNA vaccines exhibited potent neutralization of Omicron, only 4–6-fold lower than wild type, suggesting enhanced cross-reactivity of neutralizing antibody responses. In addition, we find that Omicron pseudovirus infects more efficiently than other variants tested. Overall, this study highlights the importance of additional mRNA doses to broaden neutralizing antibody responses against highly divergent SARS-CoV-2 variants.

AB - Recent surveillance has revealed the emergence of the SARS-CoV-2 Omicron variant (BA.1/B.1.1.529) harboring up to 36 mutations in spike protein, the target of neutralizing antibodies. Given its potential to escape vaccine-induced humoral immunity, we measured the neutralization potency of sera from 88 mRNA-1273, 111 BNT162b, and 40 Ad26.COV2.S vaccine recipients against wild-type, Delta, and Omicron SARS-CoV-2 pseudoviruses. We included individuals that received their primary series recently (<3 months), distantly (6–12 months), or an additional “booster” dose, while accounting for prior SARS-CoV-2 infection. Remarkably, neutralization of Omicron was undetectable in most vaccinees. However, individuals boosted with mRNA vaccines exhibited potent neutralization of Omicron, only 4–6-fold lower than wild type, suggesting enhanced cross-reactivity of neutralizing antibody responses. In addition, we find that Omicron pseudovirus infects more efficiently than other variants tested. Overall, this study highlights the importance of additional mRNA doses to broaden neutralizing antibody responses against highly divergent SARS-CoV-2 variants.

KW - breadth

KW - COVID-19

KW - Delta

KW - infectivity

KW - neutralizing antibodies

KW - Omicron

KW - SARS-CoV-2

KW - spike

KW - vaccination

KW - variants

UR - https://www.scopus.com/pages/publications/85122456843

U2 - 10.1016/j.cell.2021.12.033

DO - 10.1016/j.cell.2021.12.033

M3 - Article

C2 - 34931201

AN - SCOPUS:85122456843

SN - 0092-8674

VL - 185

SP - 457-466.e4

JO - Cell

JF - Cell

IS - 3

ER -

mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant

Abstract

UN SDGs

Keywords

Access to Document

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