@article{8f82ab0c82374f3abb496eeab39b8670,
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",
note = "Funding Information: We thank Nancy Zimmerman, Mark and Lisa Schwartz, an anonymous donor (financial support), Terry and Susan Ragon, and the SAMANA Kay MGH Research Scholars award for their support. We acknowledge the support from the Ragon Institute of MGH, MIT, and Harvard , the Massachusetts Consortium on Pathogen Readiness (MassCPR), the NIH ( 3R37AI080289-11S1 , R01AI146785 , U19AI42790-01 , U19AI135995-02 , U19AI42790-01 , 1U01CA260476 – 01 , and CIVIC75N93019C00052 ), and the Gates Foundation Global . This study was also supported by Health Vaccine Accelerator Platform funding ( OPP1146996 and INV-001650 ), Translational Research Institute for Space Health through NASA Cooperative Agreement ( NNX16AO69A ), and the Musk Foundation . This work used samples from the phase 1 mRNA-1273 study ( NCT04283461 ; doi: 10.1056/NEJMoa2022483). The mRNA-1273 phase 1 study was sponsored and primarily funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institutes of Health (NIH), Bethesda, MD. This trial has been partially funded with federal funds from the NIAID under grant awards UM1AI148373 to Kaiser Washington; UM1AI148576 , UM1AI148684 , and NIH P51 OD011132 to Emory University; and NIH AID AI149644 and contract award HHSN272201500002C to Emmes. Funding for the manufacture of mRNA-1273 phase 1 material was provided by the Coalition for Epidemic Preparedness Innovation . Funding Information: We thank Nancy Zimmerman, Mark and Lisa Schwartz, an anonymous donor (financial support), Terry and Susan Ragon, and the SAMANA Kay MGH Research Scholars award for their support. We acknowledge the support from the Ragon Institute of MGH, MIT, and Harvard, the Massachusetts Consortium on Pathogen Readiness (MassCPR), the NIH (3R37AI080289-11S1, R01AI146785, U19AI42790-01, U19AI135995-02, U19AI42790-01, 1U01CA260476 – 01, and CIVIC75N93019C00052), and the Gates Foundation Global. This study was also supported by Health Vaccine Accelerator Platform funding (OPP1146996 and INV-001650), Translational Research Institute for Space Health through NASA Cooperative Agreement (NNX16AO69A), and the Musk Foundation. This work used samples from the phase 1 mRNA-1273 study (NCT04283461; doi: 10.1056/NEJMoa2022483). The mRNA-1273 phase 1 study was sponsored and primarily funded by the National Institute of Allergy and Infectious Diseases (NIAID) and the National Institutes of Health (NIH), Bethesda, MD. This trial has been partially funded with federal funds from the NIAID under grant awards UM1AI148373 to Kaiser Washington; UM1AI148576, UM1AI148684, and NIH P51 OD011132 to Emory University; and NIH AID AI149644 and contract award HHSN272201500002C to Emmes. Funding for the manufacture of mRNA-1273 phase 1 material was provided by the Coalition for Epidemic Preparedness Innovation. P.K. B.J. and G.A. analyzed and interpreted the data. P.K. S.F. Y.C.B. J.K. J.S.B. and S.A.S. performed experiments. P.K. S.F. and D.C. performed the analysis. D.D. P.M. A.S.M. E.J.N. and E.R.M. managed samples and data collection for the community-acquired COVID-19 cohort. C.M. F.A. F.K. and E.O.S. produced SARS-CoV-2 S antigens. A.C. collected the samples and supervised and managed the clinical data for the Moderna mRNA-1273-vaccinated cohort. G.A. supervised the project. P.K. and G.A. drafted the manuscript. All authors critically reviewed the manuscript. G.A. is the founder of Seromyx Systems Inc. A.C. is an employee of Moderna Inc. D.D. P.M. A.S.M. and E.R.M. are employees of Space Exploration Technologies Corp. All other authors have declared no competing interests. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = feb,
day = "8",
doi = "10.1016/j.immuni.2022.01.001",
language = "English",
volume = "55",
pages = "355--365.e4",
journal = "Immunity",
issn = "1074-7613",
publisher = "Cell Press",
number = "2",
}