Persistent immune imprinting after XBB.1.5 COVID vaccination in humans DOI Creative Commons
M. Alejandra Tortorici, Amin Addetia,

Albert J. Seo

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2023, Volume and Issue: unknown

Published: Nov. 30, 2023

Immune imprinting - also known as ‘original antigenic sin’ describes how the first exposure to a virus shapes immunological outcome of subsequent exposures antigenically related strains. SARS-CoV-2 Omicron breakthrough infections and bivalent COVID-19 vaccination were shown primarily recall cross-reactive memory B cells antibodies induced by prior mRNA with Wuhan-Hu-1 spike rather than priming naive that recognize Omicron-specific epitopes. These findings underscored strong immune resulting from repeated exposures. To understand if can be overcome, we investigated plasma antibody responses after administration updated XBB.1.5 COVID vaccine booster. Our data show booster elicits neutralizing against current variants are dominated pre-existing previously spike. results indicate persists even multiple spikes through infection, including post vaccination, which will need considered guide design future boosters.

Language: Английский

SARS-CoV-2 breakthrough infections elicit potent, broad, and durable neutralizing antibody responses DOI Creative Commons
Alexandra C. Walls, Kaitlin R. Sprouse, John E. Bowen

et al.

Cell, Journal Year: 2022, Volume and Issue: 185(5), P. 872 - 880.e3

Published: Jan. 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.

Language: Английский

Citations

198
Neutralization, effector function and immune imprinting of Omicron variants DOI Creative Commons
Amin Addetia, Luca Piccoli, James Brett Case

et al.

Nature, Journal Year: 2023, Volume and Issue: 621(7979), P. 592 - 601

Published: Aug. 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.

Language: Английский

Citations

117
Close relatives of MERS-CoV in bats use ACE2 as their functional receptors DOI Creative Commons
Qing Xiong, Lei Cao,

Chengbao Ma

et al.

Nature, Journal Year: 2022, Volume and Issue: 612(7941), P. 748 - 757

Published: Dec. 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.

Language: Английский

Citations

104
An updated atlas of antibody evasion by SARS-CoV-2 Omicron sub-variants including BQ.1.1 and XBB DOI Creative Commons

Qingwen He,

Lili Wu, Zepeng Xu

et al.

Cell Reports Medicine, Journal Year: 2023, Volume and Issue: 4(4), P. 100991 - 100991

Published: March 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.

Language: Английский

Citations

67
Identification of a conserved S2 epitope present on spike proteins from all highly pathogenic coronaviruses DOI Creative Commons

Rui P. Silva,

Yimin Huang, Annalee W. Nguyen

et al.

eLife, Journal Year: 2023, Volume and Issue: 12

Published: March 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.

Language: Английский

Citations

66
Persistent immune imprinting occurs after vaccination with the COVID-19 XBB.1.5 mRNA booster in humans DOI Creative Commons
M. Alejandra Tortorici, Amin Addetia,

Albert J. Seo

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(4), P. 904 - 911.e4

Published: March 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.

Language: Английский

Citations

57
Spike deep mutational scanning helps predict success of SARS-CoV-2 clades DOI Creative Commons
Bernadeta Dadonaite,

Jack Brown,

Teagan McMahon

et al.

Nature, Journal Year: 2024, Volume and Issue: 631(8021), P. 617 - 626

Published: July 3, 2024

SARS-CoV-2 variants acquire mutations in the spike protein that promote immune evasion

Language: Английский

Citations

47
Molecular basis of convergent evolution of ACE2 receptor utilization among HKU5 coronaviruses DOI
Young‐Jun Park, Chen Liu, Jimin Lee

et al.

Cell, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 1, 2025

Language: Английский

Citations

5
A circular mRNA vaccine prototype producing VFLIP-X spike confers a broad neutralization of SARS-CoV-2 variants by mouse sera DOI Open Access
Chotiwat Seephetdee, Kanit Bhukhai,

Nattawut Buasri

et al.

Antiviral Research, Journal Year: 2022, Volume and Issue: 204, P. 105370 - 105370

Published: June 27, 2022

Language: Английский

Citations

44
Omicron BA.1 and BA.2 neutralizing activity elicited by a comprehensive panel of human vaccines DOI Creative Commons
John E. Bowen, Kaitlin R. Sprouse, Alexandra C. Walls

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: March 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.

Language: Английский

Citations

42