Compartment-specific antibody correlates of protection to SARS-CoV-2 Omicron in macaques

Xin Tong; Qixin Wang; Wonyeong Jung; Taras M. Chicz; Ross Blanc; Lily J. Parker; Dan H. Barouch; Ryan P. McNamara

iScience (Sep 2024)

Compartment-specific antibody correlates of protection to SARS-CoV-2 Omicron in macaques

Xin Tong,
Qixin Wang,
Wonyeong Jung,
Taras M. Chicz,
Ross Blanc,
Lily J. Parker,
Dan H. Barouch,
Ryan P. McNamara

Affiliations

Xin Tong: Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA
Qixin Wang: Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA
Wonyeong Jung: Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA
Taras M. Chicz: Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA
Ross Blanc: Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA
Lily J. Parker: Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA
Dan H. Barouch: Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215, USA; Corresponding author
Ryan P. McNamara: Ragon Institute of Mass General, MIT, and Harvard, Cambridge, MA 02139, USA; Corresponding author

Journal volume & issue: Vol. 27, no. 9
p. 110174

Abstract

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Summary: Antibodies represent a primary mediator of protection against respiratory viruses. Serum neutralizing antibodies (NAbs) are often considered a primary correlate of protection. However, detailed antibody profiles including characterization of antibody functions in different anatomic compartments are poorly understood. Here we show that antibody correlates of protection against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) challenge are different in systemic versus mucosal compartments in rhesus macaques. In serum, NAbs were the strongest correlate of protection and linked to spike-specific binding antibodies and other extra-NAb functions that create a larger protective network. In bronchiolar lavage (BAL), antibody-dependent cellular phagocytosis (ADCP) proved the strongest correlate of protection rather than NAbs. Within BAL, ADCP was linked to mucosal spike-specific immunoglobulin (Ig)G, IgA/secretory IgA, and Fcγ-receptor binding antibodies. Our results support a model in which antibodies with different functions mediate protection at different anatomic sites.

Published in iScience

ISSN: 2589-0042 (Online)
Publisher: Elsevier
Country of publisher: United States
LCC subjects: Science
Website: http://www.cell.com/iscience/home

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