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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.
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http://dx.doi.org/10.1016/j.cell.2021.06.021 | DOI Listing |
Virus Res
September 2025
Center for Molecular Diagnosis and Precision Medicine, The First Affiliated Hospital, Jiangxi Medical College, Nanchang University, 1519 Dongyue Dadao, Nanchang 330209, China; Jiangxi Provincial Center for Advanced Diagnostic Technology and Precision Medicine, The First Affiliated Hospital, Jiangxi
The ongoing mutation and evolution of SARS-CoV-2 have posed a severe threat to global health, and their functional impact remains to be further characterized. Here, we analyzed the selection pressure from 49 Omicron sub-strains at the gene and amino acid levels. We also examined the impact of mutations on the binding affinity between the receptor binding domain (RBD) and angiotensin-Converting Enzyme 2 (ACE2) and evaluated the immune escape ability of RBD responding to the monoclonal antibodies (mAbs) through molecular dynamics simulation on eight representative Omicron sub-variants (B.
View Article and Find Full Text PDFEnviron Toxicol
September 2025
Institute of Reproductive and Child Health/National Health Commission Key Laboratory of Reproductive Health, Department of Epidemiology and Biostatistics, School of Public Health, Peking University Health Science Centre, Beijing, China.
Despite widespread human exposure to tin, its health effects remain poorly understood. This study examined the role of tin in neural tube defects (NTDs) through a case-control study and animal experiments. Tin levels in maternal serum and placentas were analyzed in 200 NTD cases and 400 controls to explore potential associations.
View Article and Find Full Text PDFmBio
August 2025
Viral Diseases Program, Walter Reed Army Institute of Research, Silver Spring, Maryland, USA.
Unlabelled: Monoclonal antibodies to SARS-CoV-2 can offer prophylactic and therapeutic protection against severe disease, with particular utility for immunosuppressed and vulnerable populations. With the constant emergence of new variants, understanding the neutralizing potency of monoclonal antibodies to dynamic spike protein epitopes is crucial. We show that a set of VH1-24-derived N-terminal domain (NTD)-directed antibodies, isolated from a convalescent donor early in the pandemic, displayed remarkable neutralization resilience against many Omicron SARS-CoV-2 variants, including BA.
View Article and Find Full Text PDFProc Natl Acad Sci U S A
September 2025
State Key Laboratory of Vaccines for Infectious Diseases, Xiang An Biomedicine Laboratory, School of Life Sciences, School of Public Health, Xiamen University, Xiamen 361102, China.
severeacute respiratory syndrome coronavirus 2 (SARS-CoV-2) bivalent vaccines show potential against variants but lack a full understanding of the immunological mechanisms that drive broadly neutralizing antibodies (bnAbs). This study explored the immunogenicity of a bivalent vaccine in rhesus macaques, containing spike (S) proteins from the prototype (S) and chimeric S protein (S). The vaccine induced bnAbs against multiple variants, including challenging subvariants like EG.
View Article and Find Full Text PDFJ Mol Biol
August 2025
Department of Biochemistry and Pharmacology, Bio21 Molecular Science and Biotechnology Institute, University of Melbourne, Parkville, Victoria 3010, Australia. Electronic address:
Apolipoprotein A-I (apoA-I) plays important roles in clearing cholesterol and phospholipids from peripheral tissues, forming high-density lipoprotein (HDL). However, despite this important function, apoA-I has a propensity to form amyloid fibrils implicated in atherosclerosis and hereditary amyloidosis. Historically, structural determination of lipid-free or lipid-poor apoA-I has been difficult.
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