Defining the determinants of protection against SARS-CoV-2 infection and viral control in a dose-down Ad26.CoV2.S vaccine study in nonhuman primates
Name
journal.pbio.3001609.pdf
Description
Published version
Size
3.79 MB
Format
Adobe PDF
Checksum (MD5)
cbb9d853649d09d3c28c45299c8f8c2f
Author(s)
Zhu, Daniel Y
Gorman, Matthew J
Yuan, Dansu
Yu, Jingyou
Mercado, Noe B
McMahan, Katherine
Borducchi, Erica N
Lifton, Michelle
Liu, Jinyan
Nampanya, Felix
Date Issued
2022
Journal
PLoS Biology
Publisher
Public Library of Science (PLoS)
Citation
Zhu, Daniel Y, Gorman, Matthew J, Yuan, Dansu, Yu, Jingyou, Mercado, Noe B et al. 2022. "Defining the determinants of protection against SARS-CoV-2 infection and viral control in a dose-down Ad26.CoV2.S vaccine study in nonhuman primates." PLoS Biology, 20 (5).
Version
Final published version
Abstract
Despite the rapid creation of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) vaccines, the precise correlates of immunity against severe Coronavirus Disease 2019 (COVID-19) are still unknown. Neutralizing antibodies represent a robust surrogate of protection in early Phase III studies, but vaccines provide protection prior to the evolution of neutralization, vaccines provide protection against variants that evade neutralization, and vaccines continue to provide protection against disease severity in the setting of waning neutralizing titers. Thus, in this study, using an Ad26.CoV2.S dose-down approach in nonhuman primates (NHPs), the role of neutralization, Fc effector function, and T-cell immunity were collectively probed against infection as well as against viral control. While dosing-down minimally impacted neutralizing and binding antibody titers, Fc receptor binding and functional antibody levels were induced in a highly dose-dependent manner. Neutralizing antibody and Fc receptor binding titers, but minimally T cells, were linked to the prevention of transmission. Conversely, Fc receptor binding/function and T cells were linked to antiviral control, with a minimal role for neutralization. These data point to dichotomous roles of neutralization and T-cell function in protection against transmission and disease severity and a continuous role for Fc effector function as a correlate of immunity key to halting and controlling SARS-CoV-2 and emerging variants.
MIT Department
Massachusetts Institute of Technology. Department of Biological Engineering
Terms of Use
Creative Commons Attribution 4.0 International license
Persistent DSpace Link
DOI of Published Version
https://doi.org/10.1371/JOURNAL.PBIO.3001609
