| Autor: |
Li D, Edwards RJ, Manne K, Martinez DR, Schäfer A, Alam SM, Wiehe K, Lu X, Parks R, Sutherland LL, Oguin TH, McDanal C, Perez LG, Mansouri K, Gobeil SMC, Janowska K, Stalls V, Kopp M, Cai F, Lee E, Foulger A, Hernandez GE, Sanzone A, Tilahun K, Jiang C, Tse LV, Bock KW, Minai M, Nagata BM, Cronin K, Gee-Lai V, Deyton M, Barr M, Holle TV, Macintyre AN, Stover E, Feldman J, Hauser BM, Caradonna TM, Scobey TD, Rountree W, Wang Y, Moody MA, Cain DW, DeMarco CT, Denny T, Woods CW, Petzold EW, Schmidt AG, Teng IT, Zhou T, Kwong PD, Mascola JR, Graham BS, Moore IN, Seder R, Andersen H, Lewis MG, Montefiori DC, Sempowski GD, Baric RS, Acharya P, Haynes BF, Saunders KO |
| Jazyk: |
angličtina |
| Zdroj: |
BioRxiv : the preprint server for biology [bioRxiv] 2021 Feb 18. Date of Electronic Publication: 2021 Feb 18. |
| DOI: |
10.1101/2020.12.31.424729 |
| Abstrakt: |
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) and 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-1 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. Nonetheless, three of 31 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 occur in SARS-CoV-2 antibody-infused macaques. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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