mRNA-1273 vaccine-induced antibodies maintain Fc effector functions across SARS-CoV-2 variants of concern

Paulina Kaplonek; Stephanie Fischinger; Deniz Cizmeci; Yannic C. Bartsch; Jaewon Kang; John S. Burke; Sally A. Shin; Diana Dayal; Patrick Martin; Colin Mann; Fatima Amanat; Boris Julg; Eric J. Nilles; Elon R. Musk; Anil S. Menon; Florian Krammer; Erica Ollman Saphire; Carfi Andrea Carfi; Galit Alter

doi:10.1016/j.immuni.2022.01.001

mRNA-1273 vaccine-induced antibodies maintain Fc effector functions across SARS-CoV-2 variants of concern

Paulina Kaplonek, Stephanie Fischinger, Deniz Cizmeci, Yannic C. Bartsch, Jaewon Kang, John S. Burke, Sally A. Shin, Diana Dayal, Patrick Martin, Colin Mann, Fatima Amanat, Boris Julg, Eric J. Nilles, Elon R. Musk, Anil S. Menon, Florian Krammer, Erica Ollman Saphire, Carfi Andrea Carfi, Galit Alter

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

71 Scopus citations

Abstract

SARS-CoV-2 mRNA vaccines confer robust protection against COVID-19, but the emergence of variants has generated concerns regarding the protective efficacy of the currently approved vaccines, which lose neutralizing potency against some variants. Emerging data suggest that antibody functions beyond neutralization may contribute to protection from the disease, but little is known about SARS-CoV-2 antibody effector functions. Here, we profiled the binding and functional capacity of convalescent antibodies and Moderna mRNA-1273 COVID-19 vaccine-induced antibodies across SARS-CoV-2 variants of concern (VOCs). Although the neutralizing responses to VOCs decreased in both groups, the Fc-mediated responses were distinct. In convalescent individuals, although antibodies exhibited robust binding to VOCs, they showed compromised interactions with Fc-receptors. Conversely, vaccine-induced antibodies also bound robustly to VOCs but continued to interact with Fc-receptors and mediate antibody effector functions. These data point to a resilience in the mRNA-vaccine-induced humoral immune response that may continue to offer protection from SARS-CoV-2 VOCs independent of neutralization.

Original language	English
Pages (from-to)	355-365.e4
Journal	Immunity
Volume	55
Issue number	2
DOIs	https://doi.org/10.1016/j.immuni.2022.01.001
State	Published - 8 Feb 2022

Keywords

COVID-19
Fc effector function
SARS-CoV-2
mRNA-1273 vaccination
vaccines
variants of concern

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10.1016/j.immuni.2022.01.001

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Kaplonek, P., Fischinger, S., Cizmeci, D., Bartsch, Y. C., Kang, J., Burke, J. S., Shin, S. A., Dayal, D., Martin, P., Mann, C., Amanat, F., Julg, B., Nilles, E. J., Musk, E. R., Menon, A. S., Krammer, F., Saphire, E. O., Andrea Carfi, C., & Alter, G. (2022). mRNA-1273 vaccine-induced antibodies maintain Fc effector functions across SARS-CoV-2 variants of concern. Immunity, 55(2), 355-365.e4. https://doi.org/10.1016/j.immuni.2022.01.001

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title = "mRNA-1273 vaccine-induced antibodies maintain Fc effector functions across SARS-CoV-2 variants of concern",

abstract = "SARS-CoV-2 mRNA vaccines confer robust protection against COVID-19, but the emergence of variants has generated concerns regarding the protective efficacy of the currently approved vaccines, which lose neutralizing potency against some variants. Emerging data suggest that antibody functions beyond neutralization may contribute to protection from the disease, but little is known about SARS-CoV-2 antibody effector functions. Here, we profiled the binding and functional capacity of convalescent antibodies and Moderna mRNA-1273 COVID-19 vaccine-induced antibodies across SARS-CoV-2 variants of concern (VOCs). Although the neutralizing responses to VOCs decreased in both groups, the Fc-mediated responses were distinct. In convalescent individuals, although antibodies exhibited robust binding to VOCs, they showed compromised interactions with Fc-receptors. Conversely, vaccine-induced antibodies also bound robustly to VOCs but continued to interact with Fc-receptors and mediate antibody effector functions. These data point to a resilience in the mRNA-vaccine-induced humoral immune response that may continue to offer protection from SARS-CoV-2 VOCs independent of neutralization.",

keywords = "COVID-19, Fc effector function, SARS-CoV-2, mRNA-1273 vaccination, vaccines, variants of concern",

author = "Paulina Kaplonek and Stephanie Fischinger and Deniz Cizmeci and Bartsch, {Yannic C.} and Jaewon Kang and Burke, {John S.} and Shin, {Sally A.} and Diana Dayal and Patrick Martin and Colin Mann and Fatima Amanat and Boris Julg and Nilles, {Eric J.} and Musk, {Elon R.} and Menon, {Anil S.} and Florian Krammer and Saphire, {Erica Ollman} and {Andrea Carfi}, Carfi and Galit Alter",

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year = "2022",

month = feb,

day = "8",

doi = "10.1016/j.immuni.2022.01.001",

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Kaplonek, P, Fischinger, S, Cizmeci, D, Bartsch, YC, Kang, J, Burke, JS, Shin, SA, Dayal, D, Martin, P, Mann, C, Amanat, F, Julg, B, Nilles, EJ, Musk, ER, Menon, AS, Krammer, F, Saphire, EO, Andrea Carfi, C & Alter, G 2022, 'mRNA-1273 vaccine-induced antibodies maintain Fc effector functions across SARS-CoV-2 variants of concern', Immunity, vol. 55, no. 2, pp. 355-365.e4. https://doi.org/10.1016/j.immuni.2022.01.001

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T1 - mRNA-1273 vaccine-induced antibodies maintain Fc effector functions across SARS-CoV-2 variants of concern

AU - Kaplonek, Paulina

AU - Fischinger, Stephanie

AU - Cizmeci, Deniz

AU - Bartsch, Yannic C.

AU - Kang, Jaewon

AU - Burke, John S.

AU - Shin, Sally A.

AU - Dayal, Diana

AU - Martin, Patrick

AU - Mann, Colin

AU - Amanat, Fatima

AU - Julg, Boris

AU - Nilles, Eric J.

AU - Musk, Elon R.

AU - Menon, Anil S.

AU - Krammer, Florian

AU - Saphire, Erica Ollman

AU - Andrea Carfi, Carfi

AU - Alter, Galit

PY - 2022/2/8

Y1 - 2022/2/8

N2 - SARS-CoV-2 mRNA vaccines confer robust protection against COVID-19, but the emergence of variants has generated concerns regarding the protective efficacy of the currently approved vaccines, which lose neutralizing potency against some variants. Emerging data suggest that antibody functions beyond neutralization may contribute to protection from the disease, but little is known about SARS-CoV-2 antibody effector functions. Here, we profiled the binding and functional capacity of convalescent antibodies and Moderna mRNA-1273 COVID-19 vaccine-induced antibodies across SARS-CoV-2 variants of concern (VOCs). Although the neutralizing responses to VOCs decreased in both groups, the Fc-mediated responses were distinct. In convalescent individuals, although antibodies exhibited robust binding to VOCs, they showed compromised interactions with Fc-receptors. Conversely, vaccine-induced antibodies also bound robustly to VOCs but continued to interact with Fc-receptors and mediate antibody effector functions. These data point to a resilience in the mRNA-vaccine-induced humoral immune response that may continue to offer protection from SARS-CoV-2 VOCs independent of neutralization.

AB - SARS-CoV-2 mRNA vaccines confer robust protection against COVID-19, but the emergence of variants has generated concerns regarding the protective efficacy of the currently approved vaccines, which lose neutralizing potency against some variants. Emerging data suggest that antibody functions beyond neutralization may contribute to protection from the disease, but little is known about SARS-CoV-2 antibody effector functions. Here, we profiled the binding and functional capacity of convalescent antibodies and Moderna mRNA-1273 COVID-19 vaccine-induced antibodies across SARS-CoV-2 variants of concern (VOCs). Although the neutralizing responses to VOCs decreased in both groups, the Fc-mediated responses were distinct. In convalescent individuals, although antibodies exhibited robust binding to VOCs, they showed compromised interactions with Fc-receptors. Conversely, vaccine-induced antibodies also bound robustly to VOCs but continued to interact with Fc-receptors and mediate antibody effector functions. These data point to a resilience in the mRNA-vaccine-induced humoral immune response that may continue to offer protection from SARS-CoV-2 VOCs independent of neutralization.

KW - COVID-19

KW - Fc effector function

KW - SARS-CoV-2

KW - mRNA-1273 vaccination

KW - vaccines

KW - variants of concern

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U2 - 10.1016/j.immuni.2022.01.001

DO - 10.1016/j.immuni.2022.01.001

M3 - Article

C2 - 35090580

AN - SCOPUS:85123696260

SN - 1074-7613

VL - 55

SP - 355-365.e4

JO - Immunity

JF - Immunity

IS - 2

ER -

mRNA-1273 vaccine-induced antibodies maintain Fc effector functions across SARS-CoV-2 variants of concern

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Keywords

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