The XBB.1.5 mRNA booster vaccine does not significantly increase the percentage of XBB.1.5 mono-reactive T cells DOI Creative Commons

Joel Sop,

A. Mercado,

Alexis Figueroa

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 12, 2025

Recent efforts in vaccine development have targeted spike proteins from evolving SARS-CoV-2 variants. In this study, we analyzed T cell responses to the XBB.1.5 and BA.2.86 subvariants individuals who previously received bivalent vaccines containing mRNA for ancestral BA.5 proteins. cell-mediated cytokine both variants were largely preserved. To determine mechanism of preserved recognition, utilized functional expansion specific cells (FEST) assay distinguish between presence that cross-recognized variant epitopes versus distinct populations mono-reactive or epitopes. We found majority spike-specific subvariants, with less than 10% being either variant. Interestingly, immunization monovalent booster did not significantly increase percentage cells. Our results suggest a potential limitation induction by variant-specific vaccines.

Language: Английский

XBB.1.5 monovalent mRNA vaccine booster elicits robust neutralizing antibodies against XBB subvariants and JN.1 DOI Creative Commons
Qian Wang, Yicheng Guo, Anthony Bowen

et al.

Cell Host & Microbe, Journal Year: 2024, Volume and Issue: 32(3), P. 315 - 321.e3

Published: Feb. 19, 2024

COVID-19 vaccines have recently been updated to specifically encode or contain the spike protein of SARS-CoV-2 XBB.1.5 subvariant, but their immunogenicity in humans has yet be fully evaluated and reported, particularly against emergent viruses that are rapidly expanding. We now report administration an monovalent mRNA vaccine booster (XBB.1.5 MV) previously uninfected individuals boosted serum virus-neutralizing antibodies significantly not only (27.0-fold increase) EG.5.1 (27.6-fold also key emerging such as HV.1, HK.3, JD.1.1, JN.1 (13.3- 27.4-fold increase). Individuals infected by Omicron subvariant had highest overall neutralizing titers (ID

Language: Английский

Citations

111
Antibody neutralisation of emerging SARS-CoV-2 subvariants: EG.5.1 and XBC.1.6 DOI
Qian Wang, Yicheng Guo,

Richard M. Zhang

et al.

The Lancet Infectious Diseases, Journal Year: 2023, Volume and Issue: 23(10), P. e397 - e398

Published: Sept. 11, 2023

Language: Английский

Citations

72
Immune evasion and membrane fusion of SARS-CoV-2 XBB subvariants EG.5.1 and XBB.2.3 DOI Creative Commons
Julia N. Faraone, Panke Qu,

Negin Goodarzi

et al.

Emerging Microbes & Infections, Journal Year: 2023, Volume and Issue: 12(2)

Published: Oct. 11, 2023

Immune evasion by SARS-CoV-2 paired with immune imprinting from monovalent mRNA vaccines has resulted in attenuated neutralizing antibody responses against Omicron subvariants. In this study, we characterized two new XBB variants rising circulation - EG.5.1 and XBB.2.3, for their neutralization syncytia formation. We determined the titers sera of individuals that received a bivalent vaccine booster, BA.4/5-wave infection, or XBB.1.5-wave infection. Bivalent vaccination-induced antibodies neutralized ancestral D614G efficiently, but to much less extent, XBB.2.3 variants. fact, enhanced escape appeared be driven its key defining mutation XBB.1.5-F456L. Notably, infection BA.4/5 XBB.1.5 afforded little, if any, EG.5.1, previous especially unvaccinated individuals, average near limit detection. Additionally, investigated infectivity, fusion activity, processing variant spikes HEK293T-ACE2 CaLu-3 cells found no significant differences compared earlier Overall, our findings highlight continued subvariants and, more importantly, need reformulate include better protection.

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
Population immunity predicts evolutionary trajectories of SARS-CoV-2 DOI Creative Commons
Matthijs Meijers, Denis Ruchnewitz,

Jan Eberhardt

et al.

Cell, Journal Year: 2023, Volume and Issue: 186(23), P. 5151 - 5164.e13

Published: Oct. 23, 2023

The large-scale evolution of the SARS-CoV-2 virus has been marked by rapid turnover genetic clades. New variants show intrinsic changes, notably increased transmissibility, and antigenic changes that reduce cross-immunity induced previous infections or vaccinations. How this functional variation shapes global remained unclear. Here, we establish a predictive fitness model for integrates selection. is informed tracking time-resolved sequence data, epidemiological records, cross-neutralization data viral variants. Our inference shows immune pressure, including contributions vaccinations infections, become dominant force driving recent SARS-CoV-2. can serve continued surveillance in two ways. First, it successfully predicts short-term circulating strains flags emerging likely to displace previously predominant variant. Second, profiles successful escape prior their emergence.

Language: Английский

Citations

50
XBB.1.5 spike protein COVID-19 vaccine induces broadly neutralizing and cellular immune responses against EG.5.1 and emerging XBB variants DOI Creative Commons
Nita Patel, Jessica F. Trost,

Mimi Guebre‐Xabier

et al.

Scientific Reports, Journal Year: 2023, Volume and Issue: 13(1)

Published: Nov. 6, 2023

Monovalent SARS-CoV-2 Prototype (Wuhan-Hu-1) and bivalent (Prototype + BA.4/5) COVID-19 vaccines have demonstrated a waning of vaccine-mediated immunity highlighted by lower neutralizing antibody responses against Omicron XBB sub-variants. The reduction humoral due to the rapid evolution has signaled need for an update vaccine composition. A strain change all authorized/approved monovalent composition with subvariant XBB.1.5 been supported WHO, EMA, FDA. Here, we demonstrate that immunization recombinant spike protein (Novavax, Inc.) based on induces antibodies XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1, XBB.1.16.6 subvariants, promotes higher pseudovirus titers than XBB.1.5) vaccine, spike-specific Th1-biased CD4 T-cell robustly boosts in mice nonhuman primates primed variety vaccines. Together, these data support updating Novavax formulation 2023-2024 vaccination campaign.

Language: Английский

Citations

47
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
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
XBB.1.5 monovalent booster improves antibody binding and neutralization against emerging SARS-CoV-2 Omicron variants DOI Open Access
Shilpi Jain, Sanjeev Kumar, Lilin Lai

et al.

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

Published: Feb. 5, 2024

Abstract The rapid emergence of divergent SARS-CoV-2 variants has led to an update the COVID-19 booster vaccine a monovalent version containing XBB.1.5 spike. To determine neutralization breadth following immunization, we collected blood samples from 24 individuals pre- and post-XBB.1.5 mRNA vaccination (∼1 month). improved both neutralizing activity against ancestral strain (WA1) circulating Omicron variants, including EG.5.1, HK.3, HV.1, JN.1. Relative pre-boost titers, induced greater total IgG subclass binding, particular IgG4, spike as compared WA1 We evaluated antigen-specific memory B cells (MBCs) using either or receptor binding domain (RBD) probes found that largely increases non-RBD cross-reactive MBCs. These data suggest induces antibodies neutralize related variants.

Language: Английский

Citations

11
Hybrid immunity to SARS-CoV-2 arises from serological recall of IgG antibodies distinctly imprinted by infection or vaccination DOI Creative Commons
William N. Voss,

Michael L. Mallory,

Patrick O. Byrne

et al.

Cell Reports Medicine, Journal Year: 2024, Volume and Issue: 5(8), P. 101668 - 101668

Published: Aug. 1, 2024

We describe the molecular-level composition of polyclonal immunoglobulin G (IgG) anti-spike antibodies from ancestral severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection, vaccination, or their combination ("hybrid immunity") at monoclonal resolution. Infection primarily triggers S2/N-terminal domain (NTD)-reactive antibodies, whereas vaccination mainly induces anti-receptor-binding (RBD) antibodies. This imprint persists after secondary exposures wherein >60% ensuing hybrid immunity derives original IgG pool. Monoclonal constituents pool can increase breadth, affinity, and prevalence upon exposures, as exemplified by plasma antibody SC27. Following a breakthrough vaccine-induced SC27 gained neutralization breadth potency against SARS-CoV-2 variants zoonotic viruses (half-maximal inhibitory concentration [IC

Language: Английский

Citations

9