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1.
Sci Adv ; 9(24): eadf0661, 2023 06 16.
Artigo em Inglês | MEDLINE | ID: mdl-37315144

RESUMO

Severe acute respiratory syndrome coronavirus 2-neutralizing antibodies primarily target the spike receptor binding domain (RBD). However, B cell antigen receptors (BCRs) on RBD-binding memory B (Bmem) cells have variation in the neutralizing activities. Here, by combining single Bmem cell profiling with antibody functional assessment, we dissected the phenotype of Bmem cell harboring the potently neutralizing antibodies in coronavirus disease 2019 (COVID-19)-convalescent individuals. The neutralizing subset was marked by an elevated CD62L expression and characterized by distinct epitope preference and usage of convergent VH (variable region of immunoglobulin heavy chain) genes, accounting for the neutralizing activities. Concordantly, the correlation was observed between neutralizing antibody titers in blood and CD62L+ subset, despite the equivalent RBD binding of CD62L+ and CD62L- subset. Furthermore, the kinetics of CD62L+ subset differed between the patients who recovered from different COVID-19 severities. Our Bmem cell profiling reveals the unique phenotype of Bmem cell subset that harbors potently neutralizing BCRs, advancing our understanding of humoral protection.


Assuntos
Subpopulações de Linfócitos B , COVID-19 , Selectina L , Humanos , Anticorpos Neutralizantes , Anticorpos Antivirais , Epitopos , SARS-CoV-2
2.
Sci Immunol ; 7(70): eabn8590, 2022 04 22.
Artigo em Inglês | MEDLINE | ID: mdl-35113654

RESUMO

Multiple SARS-CoV-2 variants have mutations in the spike receptor binding domain (RBD) with potential to evade neutralizing antibody. In particular, the Beta and Omicron variants escape from antibody neutralizing activity in those who received two doses of BNT162b2 mRNA vaccine. Nonetheless, boosting with a third vaccine dose or by breakthrough infection improves the overall breadth of the neutralizing antibodies, but the mechanism remains unclear. Here, we longitudinally profiled the cellular composition of RBD-binding memory B cell subsets and their antibody binding and neutralizing activity against SARS-CoV-2 variants after the second dose of mRNA vaccine. Two doses of the mRNA vaccine elicited plasma neutralizing antibodies with a limited activity against Beta and Omicron but induced an expanded antibody breadth overtime, up to 4.9 months after vaccination. In contrast, more than one-third of RBD-binding IgG+ memory B cells with a resting phenotype initially bound the Beta and Omicron variants and steadily increased the B cell receptor breadth overtime. As a result, a fraction of the resting memory B cell subset secreted Beta and Omicron-neutralizing antibody when stimulated in vitro. The neutralizing breadth of the resting memory B cell subset helps us understand the prominent recall of Omicron-neutralizing antibodies after an additional booster or breakthrough infection in fully vaccinated individuals.


Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , Vacina BNT162 , COVID-19/prevenção & controle , Vacinas contra COVID-19 , Humanos , Células B de Memória , Vacinas Sintéticas , Vacinas de mRNA
3.
Dalton Trans ; 47(25): 8229-8239, 2018 Jun 25.
Artigo em Inglês | MEDLINE | ID: mdl-29756141

RESUMO

The synthesis and photoluminescence properties of three-coordinate Au(i) complexes with rigid diphosphine ligands LMe {1,2-bis[bis(2-methylphenyl)phosphino]benzene}, LEt {1,2-bis[bis(2-ethylphenyl)phosphino]benzene}, and LiPr {1,2-bis[bis(2-isopropylphenyl)phosphino]benzene} are investigated. The LMe and LEt ligands afford two types of complexes: dinuclear complexes [µ-LMe(AuCl)2] (1d) and [µ-LEt(AuCl)2] (2d) with an Au(i)-Au(i) bond and mononuclear three-coordinate Au(i) complexes LMeAuCl (1) and LEtAuCl (2). On the other hand, the bulkiest ligand, LiPr, affords three-coordinate Au(i) complexes, LiPrAuCl (3) and LiPrAuI (4), but no dinuclear complexes. X-ray analysis suggests that both 3 and 4 possess a highly distorted trigonal planar geometry. Moreover, luminescence data reveal that at room temperature, 3 and 4 exhibit yellow-green thermally activated delayed fluorescence in the crystalline state with maximum emission wavelengths at 558 and 549 nm, respectively. The emission yields are close to unity. Quantum chemical calculations suggest that the emission of 4 originates from the (σ + X) → π* excited state that possesses strong intraligand charge-transfer character. The luminescent properties of four-coordinate Au(i) complex (5) possessing a tetrahedral geometry are discussed on the basis of the emission spectra and decay times measured in a temperature range of 309-77 K.

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