Advances in immunology, Год журнала: 2022, Номер unknown, С. 1 - 69
Опубликована: Янв. 1, 2022
Язык: Английский
Cell, Год журнала: 2022, Номер 185(5), С. 872 - 880.e3
Опубликована: Янв. 20, 2022
Although infections among vaccinated individuals lead to milder COVID-19 symptoms relative those in unvaccinated subjects, the specificity and durability of antibody responses elicited by breakthrough cases remain unknown. Here, we demonstrate that induce serum-binding -neutralizing are markedly more potent, durable, resilient spike mutations observed variants than subjects who received only 2 doses vaccine. However, show cases, were after infection, three times have serum-neutralizing activity comparable magnitude breadth, indicating an increased number exposures SARS-CoV-2 antigen(s) enhance quality responses. Neutralization SARS-CoV was moderate, however, underscoring importance developing vaccines eliciting broad sarbecovirus immunity for pandemic preparedness.
Язык: Английский
Процитировано
203
Nature, Год журнала: 2023, Номер 621(7979), С. 592 - 601
Опубликована: Авг. 30, 2023
Abstract Currently circulating SARS-CoV-2 variants have acquired convergent mutations at hot spots in the receptor-binding domain 1 (RBD) of spike protein. The effects these on viral infection and transmission efficacy vaccines therapies remains poorly understood. Here we demonstrate that recently emerged BQ.1.1 XBB.1.5 bind host ACE2 with high affinity promote membrane fusion more efficiently than earlier Omicron variants. Structures BQ.1.1, XBB.1 BN.1 RBDs bound to fragment antigen-binding region S309 antibody (the parent for sotrovimab) human explain preservation binding through conformational selection, altered recognition immune evasion. We show sotrovimab binds avidly all variants, promotes Fc-dependent effector functions protects mice challenged hamsters XBB.1.5. Vaccine-elicited plasma antibodies cross-react trigger against current despite a reduced neutralizing activity, suggesting mechanism protection disease, exemplified by S309. Cross-reactive RBD-directed memory B cells remained dominant even after two exposures spikes, underscoring role persistent imprinting.
Язык: Английский
Процитировано
125
Nature, Год журнала: 2022, Номер 612(7941), С. 748 - 757
Опубликована: Дек. 7, 2022
Middle East respiratory syndrome coronavirus (MERS-CoV) and several bat coronaviruses use dipeptidyl peptidase-4 (DPP4) as an entry receptor1-4. However, the receptor for NeoCoV-the closest known MERS-CoV relative found in bats-remains unclear5. Here, using a pseudotype virus assay, we that NeoCoV its close relative, PDF-2180, can efficiently bind to specific angiotensin-converting enzyme 2 (ACE2) orthologues and, less favourably, human ACE2 receptors through their receptor-binding domains (RBDs) on spike (S) proteins. Cryo-electron microscopy analysis revealed RBD-ACE2 binding interface involving protein-glycan interactions, distinct from those of other ACE2-using coronaviruses. We identified residues 337-342 molecular determinant restricting entry, whereas S pseudotyped containing T510F RBD mutation entered cells expressing ACE2. Although polyclonal SARS-CoV-2 antibodies or RBD-specific nanobodies did not cross-neutralize ACE2-specific antibody two broadly neutralizing betacoronavirus inhibited these viruses. describe MERS-CoV-related viruses receptor, underscoring promiscuity potential zoonotic threat.
Язык: Английский
Процитировано
110
Cell Reports Medicine, Год журнала: 2023, Номер 4(4), С. 100991 - 100991
Опубликована: Март 21, 2023
Emerging Omicron sub-variants are causing global concerns, and their immune evasion should be monitored continuously. We previously evaluated the escape of BA.1, BA.1.1, BA.2, BA.3 from an atlas 50 monoclonal antibodies (mAbs), covering seven epitope classes severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD). Here, we update totally 77 mAbs against emerging including BQ.1.1 XBB find that BA.4/5, BQ.1.1, display further evasion. Besides, investigation into correlation binding neutralization reveals important role antigenic conformation in mAb functioning. Moreover, complex structures BA.2 RBD/BD-604/S304 BA.4/5 RBD/BD-604/S304/S309 elucidate molecular mechanism antibody by these sub-variants. By focusing on identified broadly potent mAbs, a general hotspot RBD, which could guide design vaccines calls for new broad-spectrum countermeasures COVID-19.
Язык: Английский
Процитировано
68
eLife, Год журнала: 2023, Номер 12
Опубликована: Март 21, 2023
To address the ongoing SARS-CoV-2 pandemic and prepare for future coronavirus outbreaks, understanding protective potential of epitopes conserved across variants lineages is essential. We describe a highly conserved, conformational S2 domain epitope present only in prefusion core β-coronaviruses: apex residues 980–1006 flexible hinge. Antibody RAY53 binds native hinge MERS-CoV spikes on surface mammalian cells mediates antibody-dependent cellular phagocytosis cytotoxicity against spike vitro. Hinge mutations that ablate antibody binding compromise pseudovirus infectivity, but changes elsewhere affect opening dynamics, including those found Omicron BA.1, occlude may evade pre-existing serum antibodies targeting core. This work defines third class while providing insights into potency limitations targeting.
Язык: Английский
Процитировано
67
Immunity, Год журнала: 2024, Номер 57(4), С. 904 - 911.e4
Опубликована: Март 14, 2024
Immune imprinting describes how the first exposure to a virus shapes immunological outcomes of subsequent exposures antigenically related strains. Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) Omicron breakthrough infections and bivalent COVID-19 vaccination primarily recall cross-reactive memory B cells induced by prior Wuhan-Hu-1 spike mRNA rather than priming Omicron-specific naive cells. These findings indicate that immune occurs after repeated exposures, but whether it can be overcome remains unclear. To understand persistence imprinting, we investigated plasma antibody responses administration updated XBB.1.5 vaccine booster. We showed booster elicited neutralizing against current variants were dominated pre-existing previously spike. Therefore, persists multiple spikes through infection, including post vaccination, which will need considered guide future vaccination.
Язык: Английский
Процитировано
61
Nature, Год журнала: 2024, Номер 631(8021), С. 617 - 626
Опубликована: Июль 3, 2024
SARS-CoV-2 variants acquire mutations in the spike protein that promote immune evasion
Язык: Английский
Процитировано
57
Cell, Год журнала: 2025, Номер unknown
Опубликована: Фев. 1, 2025
Язык: Английский
Процитировано
9
Antiviral Research, Год журнала: 2022, Номер 204, С. 105370 - 105370
Опубликована: Июнь 27, 2022
Язык: Английский
Процитировано
45
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2022, Номер unknown
Опубликована: Март 16, 2022
The SARS-CoV-2 Omicron variant of concern comprises three sublineages designated BA.1, BA.2, and BA.3, with BA.2 steadily replacing the globally dominant BA.1. We show that large number BA.1 spike mutations severely dampen plasma neutralizing activity elicited by infection or seven clinical vaccines, cross-neutralization being consistently more potent than independent vaccine platform doses. Although mRNA vaccines induced greatest magnitude activity, administration a booster based on Wuhan-Hu-1 sequence markedly increased antibody titers breadth against across all evaluated. Our data suggest although evade polyclonal responses, current boosting regimens may provide sufficient protection Omicron-induced disease.
Язык: Английский
Процитировано
42