Spike-Dependent Opsonization Indicates Both Dose-Dependent Inhibition of Phagocytosis and That Non-Neutralizing Antibodies Can Confer Protection to SARS-CoV-2

Wael Bahnan,Anna Söderlund Strand,Johannes Kumra Ahnlide,Elisabeth Elder,Mats Ohlin,Lotta Happonen,Anna Bläckberg,Thomas Hellmark,Urban Höglund,Hamed Khakzad,Oscar André,Maria Walle,Sebastian Wrighton,Martin Sundwall,Vidar Wendel-Hansen,Magnus Rasmussen,Lars Malmström,Pontus Nordenfelt,Magdalena Godzwon,Olivia Larsson,Robert P A Wallin ,Johan Malmström

doi:10.3389/fimmu.2021.808932

Abstract

Spike-specific antibodies are central to effective COVID19 immunity. Research efforts have focused on antibodies that neutralize the ACE2-Spike interaction but not on non-neutralizing antibodies. Antibody-dependent phagocytosis is an immune mechanism enhanced by opsonization, where typically, more bound antibodies trigger a stronger phagocyte response. Here, we show that Spike-specific antibodies, dependent on concentration, can either enhance or reduce Spike-bead phagocytosis by monocytes independently of the antibody neutralization potential. Surprisingly, we find that both convalescent patient plasma and patient-derived monoclonal antibodies lead to maximum opsonization already at low levels of bound antibodies and is reduced as antibody binding to Spike protein increases. Moreover, we show that this Spike-dependent modulation of opsonization correlate with the outcome in an experimental SARS-CoV-2 infection model. These results suggest that the levels of anti-Spike antibodies could influence monocyte-mediated immune functions and propose that non-neutralizing antibodies could confer protection to SARS-CoV-2 infection by mediating phagocytosis.

Highlights

COVID19, caused by the SARS-CoV-2 virus, has since the end of 2019 resulted in millions of deaths and serious societal health effects
Blood plasma was obtained from 20 COVID19 convalescent patients (Supplementary Table 1)
The results show that the five antibodies can bind to the Spike protein, but they do not appear to compete with the binding site of human Angiotensin-Converting Enzyme 2 (ACE2) directly

Summary

Introduction

COVID19, caused by the SARS-CoV-2 virus, has since the end of 2019 resulted in millions of deaths and serious societal health effects. Trials showed that antibody cocktails reduced symptoms, hospitalization, and mortality associated with COVID19 for early-stage infections. Studies regarding their use for treating severe COVID19 showed no clinical benefit [6]. Through virion or cellular phagocytosis, phagocytic cells help reduce the viral load by eliminating infection sources. In this context, we were interested in whether or not Spike antibodies might mediate phagocytosis as has been previously seen with influenza [13,14,15]

Methods

Results

Conclusion