In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies.

In vitro and in vivo functions of SARS-CoV-2 infection-enhancing and neutralizing antibodies.

Cell (2021-07-10)

Dapeng Li, Robert J Edwards, Kartik Manne, David R Martinez, Alexandra Schäfer, S Munir Alam, Kevin Wiehe, Xiaozhi Lu, Robert Parks, Laura L Sutherland, Thomas H Oguin, Charlene McDanal, Lautaro G Perez, Katayoun Mansouri, Sophie M C Gobeil, Katarzyna Janowska, Victoria Stalls, Megan Kopp, Fangping Cai, Esther Lee, Andrew Foulger, Giovanna E Hernandez, Aja Sanzone, Kedamawit Tilahun, Chuancang Jiang, Longping V Tse, Kevin W Bock, Mahnaz Minai, Bianca M Nagata, Kenneth Cronin, Victoria Gee-Lai, Margaret Deyton, Maggie Barr, Tarra Von Holle, Andrew N Macintyre, Erica Stover, Jared Feldman, Blake M Hauser, Timothy M Caradonna, Trevor D Scobey, Wes Rountree, Yunfei Wang, M Anthony Moody, Derek W Cain, C Todd DeMarco, Thomas N Denny, Christopher W Woods, Elizabeth W Petzold, Aaron G Schmidt, I-Ting Teng, Tongqing Zhou, Peter D Kwong, John R Mascola, Barney S Graham, Ian N Moore, Robert Seder, Hanne Andersen, Mark G Lewis, David C Montefiori, Gregory D Sempowski, Ralph S Baric, Priyamvada Acharya, Barton F Haynes, Kevin O Saunders

PMID34242577

ABSTRACT

SARS-CoV-2-neutralizing antibodies (NAbs) protect against COVID-19. A concern regarding SARS-CoV-2 antibodies is whether they mediate disease enhancement. Here, we isolated NAbs against the receptor-binding domain (RBD) or the N-terminal domain (NTD) of SARS-CoV-2 spike from individuals with acute or convalescent SARS-CoV-2 or a history of SARS-CoV infection. Cryo-electron microscopy of RBD and NTD antibodies demonstrated function-specific modes of binding. Select RBD NAbs also demonstrated Fc receptor-γ (FcγR)-mediated enhancement of virus infection in vitro, while five non-neutralizing NTD antibodies mediated FcγR-independent in vitro infection enhancement. However, both types of infection-enhancing antibodies protected from SARS-CoV-2 replication in monkeys and mice. Three of 46 monkeys infused with enhancing antibodies had higher lung inflammation scores compared to controls. One monkey had alveolar edema and elevated bronchoalveolar lavage inflammatory cytokines. Thus, while in vitro antibody-enhanced infection does not necessarily herald enhanced infection in vivo, increased lung inflammation can rarely occur in SARS-CoV-2 antibody-infused macaques.

MATERIALS

Product Number

Brand

Product Description

HPA048982

Sigma-Aldrich

Anti-CD68 antibody produced in rabbit, Prestige Antibodies^® Powered by Atlas Antibodies, affinity isolated antibody, buffered aqueous glycerol solution

PRCYT2MAG40K

Millipore

MILLIPLEX^® Non-Human Primate Cytokine/Chemokine Panel II - Immunology Multiplex Assay, Simultaneously analyze multiple cytokine and chemokine biomarkers with Bead-Based Multiplex Assays using the Luminex technology, in non-human primate serum, plasma and cell culture samples.