Intranasal vaccination with an NDV-vectored SARS-CoV-2 vaccine protects against Delta and Omicron challenges DOI Creative Commons
Bryce M. Warner,

Jacob G. E. Yates,

Robert Vendramelli

et al.

npj Vaccines, Journal Year: 2024, Volume and Issue: 9(1)

Published: May 23, 2024

Abstract The rapid development and deployment of vaccines following the emergence severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been estimated to have saved millions lives. Despite their immense success, there remains a need for next-generation vaccination approaches SARS-CoV-2 future emerging coronaviruses other viruses. Here we utilized Newcastle Disease virus (NDV) vectored vaccine expressing ancestral spike protein in pre-fusion stabilized chimeric conformation (NDV-PFS). When delivered intranasally, NDV-PFS protected both Syrian hamsters K18 mice against Delta Omicron variants concern. Additionally, intranasal induced robust, durable protection that was extended 6 months post-vaccination. Overall, our data provide evidence NDV-vectored represent viable mucosal approach.

Language: Английский

Convergent evolution of SARS-CoV-2 XBB lineages on receptor-binding domain 455–456 synergistically enhances antibody evasion and ACE2 binding DOI Creative Commons
Fanchong Jian, Leilei Feng, Sijie Yang

et al.

PLoS Pathogens, Journal Year: 2023, Volume and Issue: 19(12), P. e1011868 - e1011868

Published: Dec. 20, 2023

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) XBB lineages have achieved dominance worldwide and keep on evolving. Convergent evolution of the receptor-binding domain (RBD) L455F F456L is observed, resulting in variants with substantial growth advantages, such as EG.5, FL.1.5.1, XBB.1.5.70, HK.3. Here, we show that neutralizing antibody (NAb) evasion drives convergent F456L, while epistatic shift caused by enables subsequent convergence through ACE2 binding enhancement further immune evasion. evade RBD-targeting Class 1 public NAbs, reducing neutralization efficacy breakthrough infection (BTI) reinfection convalescent plasma. Importantly, single substitution significantly dampens receptor binding; however, combination forms an adjacent residue flipping, which leads to enhanced NAbs resistance affinity. The perturbed mode exceptional NAb evasion, revealed structural analyses. Our results indicate flexibility contributed epistasis cannot be underestimated, potential SARS-CoV-2 RBD remains high.

Language: Английский

Citations

70
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
Immunological imprinting shapes the specificity of human antibody responses against SARS-CoV-2 variants DOI
Timothy S. Johnston,

Shuk Hang Li,

Mark M. Painter

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(4), P. 912 - 925.e4

Published: March 14, 2024

Language: Английский

Citations

34
Imprinting of serum neutralizing antibodies by Wuhan-1 mRNA vaccines DOI
Chieh-Yu Liang, Saravanan Raju, Zhuoming Liu

et al.

Nature, Journal Year: 2024, Volume and Issue: 630(8018), P. 950 - 960

Published: May 15, 2024

Language: Английский

Citations

33
Distinct patterns of SARS-CoV-2 BA.2.87.1 and JN.1 variants in immune evasion, antigenicity, and cell-cell fusion DOI Creative Commons

Pei Li,

Yajie Liu, Julia N. Faraone

et al.

mBio, Journal Year: 2024, Volume and Issue: 15(5)

Published: April 9, 2024

The rapid evolution of SARS-CoV-2 variants presents a constant challenge to the global vaccination effort. In this study, we conducted comprehensive investigation into two newly emerged variants, BA.2.87.1 and JN.1, focusing on their neutralization resistance, infectivity, antigenicity, cell-cell fusion, spike processing. Neutralizing antibody (nAb) titers were assessed in diverse cohorts, including individuals who received bivalent mRNA vaccine booster, patients infected during BA.2.86/JN.1-wave, hamsters vaccinated with XBB.1.5-monovalent vaccine. We found that shows much less nAb escape from WT-BA.4/5 JN.1-wave breakthrough infection sera compared JN.1 XBB.1.5. Interestingly, is more resistant by XBB.1.5-monovalent-vaccinated hamster than BA.2.86/JN.1 XBB.1.5, but efficiently neutralized class III monoclonal S309, which largely fails neutralize BA.2.86/JN.1. Importantly, exhibits higher levels fusion activity, furin cleavage efficiency Antigenically, closer ancestral BA.2 other recently Omicron subvariants Altogether, these results highlight immune properties as well biology new underscore importance continuous surveillance informed decision-making development effective vaccines.

Language: Английский

Citations

30
Evolving antibody response to SARS-CoV-2 antigenic shift from XBB to JN.1 DOI Creative Commons
Fanchong Jian, Jing Wang, Ayijiang Yisimayi

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: April 22, 2024

Abstract The continuous evolution of SARS-CoV-2, particularly the emergence BA.2.86/JN.1 lineage replacing XBB lineages, necessitates re-evaluation current vaccine compositions. Here, we provide a comprehensive analysis humoral immune response to and JN.1 human exposures, emphasizing need for JN.1-lineage-based boosters. We demonstrate antigenic distinctiveness lineages in SARS-CoV-2-naive individuals but not those with prior vaccinations or infections, infection elicits superior plasma neutralization titers against its subvariants. highlight strong evasion receptor binding capability KP.3, supporting foreseeable prevalence. Extensive BCR repertoire, isolating ∼2000 RBD-specific monoclonal antibodies (mAbs) their targeting epitopes characterized by deep mutational scanning (DMS), underscores systematic superiority JN.1-elicited memory B cells (MBCs). Notably, Class 1 IGHV3-53/3-66-derived neutralizing (NAbs) contribute majorly within wildtype (WT)-reactive NAbs JN.1. However, KP.2 KP.3 evade substantial subset them, even induced JN.1, advocating booster updates optimized enrichment. JN.1-induced Omicron-specific also high potency across all Omicron lineages. Escape hotspots these have mainly been mutated RBD, resulting higher barrier escape, considering probable recovery previously escaped NAbs. Additionally, prevalence broadly reactive IGHV3-53/3-66- encoding MBCs, competing suggests inhibitory role on de novo activation naive cells, potentially explaining heavy imprinting mRNA-vaccinated individuals. These findings delineate evolving antibody shift from importance developing lineage, especially KP.3-based boosters, enhance immunity future SARS-CoV-2 variants.

Language: Английский

Citations

20
Opposing effects of pre-existing antibody and memory T cell help on the dynamics of recall germinal centers DOI
Ariën Schiepers,

Marije F.L. van’t Wout,

Alvaro Hobbs

et al.

Immunity, Journal Year: 2024, Volume and Issue: 57(7), P. 1618 - 1628.e4

Published: June 5, 2024

Language: Английский

Citations

18
SARS-CoV-2 evolution on a dynamic immune landscape DOI Creative Commons
N. Alexia Raharinirina, Nils Gubela, Daniela Börnigen

et al.

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

Published: Jan. 29, 2025

Abstract Since the onset of pandemic, many SARS-CoV-2 variants have emerged, exhibiting substantial evolution in virus’ spike protein 1 , main target neutralizing antibodies 2 . A plausible hypothesis proposes that virus evolves to evade antibody-mediated neutralization (vaccine- or infection-induced) maximize its ability infect an immunologically experienced population 1,3 Because viral infection induces antibodies, may thus navigate on a dynamic immune landscape is shaped by local history. Here we developed comprehensive mechanistic model, incorporating deep mutational scanning data 4,5 antibody pharmacokinetics and regional genomic surveillance data, predict variant-specific relative number susceptible individuals over time. We show this quantity precisely matched historical variant dynamics, predicted future dynamics explained global differences dynamics. Our work strongly suggests ongoing pandemic continues shape immunity, which determines variant’s transmit, defining fitness. The model can be applied any region utilizing allows contextualizing risk assessment provides information for vaccine design.

Language: Английский

Citations

3
A unified evolution-driven deep learning framework for virus variation driver prediction DOI
Zhiwei Nie, Xudong Liu, Jie Chen

et al.

Nature Machine Intelligence, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 17, 2025

Language: Английский

Citations

2
Waning immunity and IgG4 responses following bivalent mRNA boosting DOI Creative Commons
Ninaad Lasrado, Ai‐ris Y. Collier, Jessica Miller

et al.

Science Advances, Journal Year: 2024, Volume and Issue: 10(8)

Published: Feb. 23, 2024

Messenger RNA (mRNA) vaccines were highly effective against the ancestral SARS-CoV-2 strain, but efficacy of bivalent mRNA boosters XBB variants was substantially lower. Here, we show limited durability neutralizing antibody (NAb) responses and isotype switching to immunoglobulin G4 (IgG4) following boosting. Bivalent boosting elicited modest XBB.1-, XBB.1.5-, XBB.1.16-specific NAbs that waned rapidly within 3 months. In contrast, induced more robust sustained WA1/2020 suggesting immune imprinting. Following boosting, serum primarily IgG2 IgG4 with poor Fc functional activity. a third monovalent immunization boosted all isotypes including IgG1 IgG3 These data substantial imprinting for spike important implications future booster designs strategies.

Language: Английский

Citations

15