@article{578ac1ed52f9491e930f8ca4f67a9802,
title = "BNT162b2-induced neutralizing and non-neutralizing antibody functions against SARS-CoV-2 diminish with age",
abstract = "Each severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant renews concerns about decreased vaccine neutralization weakening efficacy. However, while prevention of infection varies, protection from disease remains and implicates immunity beyond neutralization in vaccine efficacy. Polyclonal antibodies function through Fab domains that neutralize virus and Fc domains that induce non-neutralizing responses via engagement of Fc receptors on immune cells. To understand how vaccines promote protection, we leverage sera from 51 SARS-CoV-2 uninfected individuals after two doses of the BNT162b2 mRNA vaccine. We show that neutralizing activities against clinical isolates of wild-type and five SARS-CoV-2 variants, including Omicron BA.2, link to FcγRIIIa/CD16 non-neutralizing effector functions. This is associated with post-translational afucosylation and sialylation of vaccine-specific antibodies. Further, polyfunctional neutralizing and non-neutralizing breadth, magnitude, and coordination diminish with age. Thus, studying Fc functions in addition to Fab-mediated neutralization provides greater insight into vaccine efficacy for vulnerable populations, such as the elderly, against SARS-CoV-2 and novel variants.",
keywords = "antibody glycosylation, COVID-19, CP: Immunology, Fc effector functions, Fc receptor, neutralization, Omicron, SARS-CoV-2, vaccine",
author = "Bates, {Timothy A.} and Pei Lu and Kang, {Ye Jin} and Devin Schoen and Micah Thornton and McBride, {Savannah K.} and Chanhee Park and Daehwan Kim and Messer, {William B.} and Curlin, {Marcel E.} and Tafesse, {Fikadu G.} and Lu, {Lenette L.}",
note = "Funding Information: This study was funded by a grant from the M. J. Murdock Charitable Trust (to M.E.C.); an unrestricted grant from the OHSU Foundation (to M.E.C.); NIH training grant T32HL083808 (to T.A.B.); NIH grant R011R01AI141549-01A1 (to F.G.T.); OHSU Innovative IDEA grant 1018784 (to F.G.T.); NIH grant R01AI145835 (to W.B.M.); Burroughs Wellcome Fund UT Southwestern Training Resident Doctors as Innovators in Science (to Y.J.K.); and a pilot project grant from the UT Southwestern Department of Internal Medicine and Disease Oriented Scholars Award (to L.L.L.). We gratefully acknowledge the OHSU workforce members who participated in this study; the OHSU COVID-19 serology study team and the OHSU occupational health department for their efforts in recruitment and sample acquisition; and the OHSU clinical laboratory under the direction of Donna Hansel and Xuan Qin for SARS-CoV-2 testing and reporting. We thank UTSW healthy volunteers who donated their blood for neutrophil studies; Dawn Wetzel for efforts in recruitment; Gabrielle Lessen for phlebotomy assistance; and Ann McDonald, Gabrielle Lessen, and Joshua Miles for graphical assistance. We are grateful for the support of the M.J. Murdock Charitable Trust and the OHSU Foundation. The funders of the study had no role in study design, execution, analysis, interpretation, or writing of this manuscript. Publisher Copyright: {\textcopyright} 2022 The Author(s)",
year = "2022",
month = oct,
day = "25",
doi = "10.1016/j.celrep.2022.111544",
language = "English (US)",
volume = "41",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "4",
}