Low levels of neutralizing antibodies against XBB Omicron subvariants after BA.5 infection

Signal Transduction and Targeted Therapy, Год журнала: 2023, Номер 8(1)

Опубликована: Июнь 19, 2023

Abstract The COVID-19 response strategies in Chinese mainland were recently adjusted due to the reduced pathogenicity and enhanced infectivity of Omicron subvariants. In Chengdu, China, an infection wave was predominantly induced by BA.5 subvariant. It is crucial determine whether hybrid anti-SARS-CoV-2 immunity following infection, coupled with a variety immune background, sufficient shape responses against newly emerged subvariants, especially for XBB lineages. To investigate this, we collected serum nasal swab samples from 108 participants who had been infected this wave, evaluated neutralization pseudoviruses. Our results showed that convalescent sera individuals, regardless vaccination history, remarkably compromised capacities XBB.1.5 Although post-vaccination breakthrough slightly elevated plasma neutralizing antibodies part pseudoviruses, activities impaired Furthermore, analyzed impacts number vaccinations, age, sex on humoral cellular after infection. findings suggest lineages elicited current are remained at low levels, indicating urgent need development next-generation vaccines designed based sub-lineages other future variants.

Язык: Английский

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A recombinant protein vaccine induces protective immunity against SARS-CoV-2 JN.1 and XBB-lineage subvariants

Signal Transduction and Targeted Therapy, Год журнала: 2025, Номер 10(1)

Опубликована: Фев. 25, 2025

Abstract The emergence of XBB- and JN.1-lineages with remarkable immune evasion characteristics have led to rises in breakthrough infections within populations. In addition, the unfavorable impacts imprinting, stemming from continuous exposure antigens circulated viruses, been observed incline response against earlier lineages, thereby declining neutralization newly emerged Omicron subvariants. this, advancement next-generation vaccines COVID-19 targeting components new subvariants such as XBB-lineage is imperative. current study, a self-assembled trimeric recombinant protein (RBD XBB.1.5 -HR) was generated by concatenating sequences receptor binding domain (RBD) derived heptad-repeat 1 (HR1) HR2 spike S2 subunit. Adjuvanted-RBD -HR induced robust humoral cellular responses, characterized elevated JN.1-inculuded substantial population antigen-specific T memory cells. Protective immunity conferred RBD vaccine preserved post-immunization, evidenced germinal center B (GC B) follicular helper (Tfh) sustained potency, an increase cells (MBCs) long-lived plasma (LLPCs). showed favorable boosting effect when administered heterologously after three doses inactivated virus (IV) mRNA vaccines. Significantly, it provided protection live EG.5.1 viruses vivo. monovalent safety immunogenicity, neutralizing antibodies JN.1- individuals prior vaccinations. These findings highlight its clinical potential safeguarding circulating

Язык: Английский

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Temperature-dependent Spike-ACE2 interaction of Omicron subvariants is associated with viral transmission

mBio, Год журнала: 2024, Номер 15(8)

Опубликована: Июль 2, 2024

The continued evolution of severe acute respiratory syndrome 2 (SARS-CoV-2) requires persistent monitoring its subvariants. Omicron subvariants are responsible for the vast majority SARS-CoV-2 infections worldwide, with XBB and BA.2.86 sublineages representing more than 90% circulating strains as January 2024. To better understand parameters involved in viral transmission, we characterized functional properties Spike glycoproteins from BA.2.75, CH.1.1, DV.7.1, BA.4/5, BQ.1.1, XBB, XBB.1, XBB.1.16, XBB.1.5, FD.1.1, EG.5.1, HK.3, JN.1. We tested their capacity to evade plasma-mediated recognition neutralization, binding angiotensin-converting enzyme (ACE2), susceptibility cold inactivation, processing, well impact temperature on Spike-ACE2 interaction. found that compared early wild-type (D614G) strain, most subvariants' evolved escape neutralization by plasma individuals who received a fifth dose bivalent (BA.1 or BA.4/5) mRNA vaccine improve ACE2 binding, particularly at low temperatures. Moreover, had best affinity all temperatures tested. processing is associated inactivation. Intriguingly, was significantly growth rates humans. Overall, report Spikes newly emerged relatively stable resistant present improved which associated, temperatures, rates.IMPORTANCEThe gave rise wide range variants harboring new mutations glycoproteins. Several factors have been transmission fitness such plasma-neutralization whether additional could be importance variants' characterize several glycoprotein presents an further temperature. interaction strongly rate, such, represent another parameter affecting transmission.

Язык: Английский

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Early 2022 breakthrough infection sera from India target the conserved cryptic class 5 epitope to counteract immune escape by SARS-CoV-2 variants

Journal of Virology, Год журнала: 2025, Номер unknown

Опубликована: Март 26, 2025

ABSTRACT During the coronavirus disease 2019 (COVID-19) pandemic, vast majority of epitope mapping studies have focused on sera from mRNA-vaccinated populations high-income countries. In contrast, here, we report an analysis 164 serum samples isolated patients with breakthrough infection in India during early 2022 who received two doses ChAdOx viral vector vaccine. Sera were screened for neutralization breadth against wild-type (WT), Kappa, Delta, and Omicron BA.1 viruses. Three highest potency selected mapping, using charged scanning mutagenesis coupled yeast surface display next-generation sequencing. The mapped primarily targeted recently identified class 5 cryptic and, to a lesser extent, 1 4 epitopes. is completely conserved across all severe acute respiratory syndrome 2 (SARS-CoV-2) variants most sarbecoviruses. Based these observations, additional 26 characterized, showed broad neutralizing activity, including XBB.1.5. This contrast results obtained individuals receiving multiple original updated mRNA vaccines, where impaired XBB later concern (VOCs) observed. Our study demonstrates that vaccine highly exposed population sufficient drive substantial emerging upcoming concern. These data highlight important role hybrid immunity conferring protection inform future strategies protect rapidly mutating IMPORTANCE Worldwide implementation vaccines parallel emergence newer shaped humoral immune response population-specific manner. While characterizing this monitoring progression at level, it also imperative developing effective countermeasures form novel therapeutics. has implemented world’s second largest COVID-19 vaccination encountered large number post-vaccination “breakthrough” infections. From cohort infection, whose broadly different SARS-CoV-2 variants. Interestingly, target epitope, which was not previous population-level conducted Western rare remains variants, emerged ones SARS-like coronaviruses may cause outbreaks, thus representing potential vaccines.

Язык: Английский

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Genomic Surveillance and Mutation Analysis of SARS-CoV-2 Variants among Patients in Saudi Arabia

Microorganisms, Год журнала: 2024, Номер 12(3), С. 467 - 467

Опубликована: Фев. 26, 2024

The genome of severe acute respiratory coronavirus-2 (SARS-CoV-2), the virus responsible for coronavirus disease 2019 (COVID-19), has undergone a rapid evolution, resulting in emergence multiple SARS-CoV-2 variants with amino acid changes. This study aimed to sequence whole and detect present specimens from Saudi Arabia. Furthermore, we sought analyze characterize changes various proteins identified variants. A total 1161 samples patients diagnosed COVID-19 Arabia, between 1 April 2021 31 July 2023, were analyzed. Whole sequencing was employed variant identification mutation analysis. statistical analysis performed using Statistical Analytical Software SAS, version 9.4, GraphPad, 9.0. twenty-three subvariants within population, Omicron BA.1 (21K) (37.0%) Delta (21J) (12%) being most frequently detected. Notably, exhibited higher mean rate. Amino mutations observed twelve proteins. Among these, spike (S), ORF1a, nucleocapsid (N), ORF1b showed frequency compared other viral S protein highest incidence (47.6%). Conversely, ORF3a, ORF8, ORF7a, ORF6, ORF7b appeared more conserved, demonstrating lowest percentage mutations. investigation structural regions revealed N-terminal S1 subunit harbor mutations, while domain envelope (E) displayed frequency. provides insights into genetic diversity SARS-CoV-2, underscoring need further research comprehend its evolution occurrence These findings are pertinent development testing approaches, therapeutics, vaccine strategies.

Язык: Английский

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Epidemiological characteristics and antibody kinetics of elderly population with booster vaccination following both Omicron BA.5 and XBB waves in China

Journal of Medical Virology, Год журнала: 2024, Номер 96(5)

Опубликована: Май 1, 2024

Abstract After the termination of zero‐COVID‐19 policy, populace in China has experienced both Omicron BA.5 and XBB waves. Considering poor antibody responses severe outcomes observed among elderly following infection, we conducted a longitudinal investigation to examine epidemiological characteristics kinetics 107 boosted participants We that 96 (89.7%) were infected with BA.5, while 59 (55.1%) XBB. Notably, 52 (48.6%) dual infections The proportion symptomatic cases appeared decrease wave (18.6%) compared after (59.3%). breakthrough infection induced lower neutralizing titers against XBB.1.5, BA.2.86, JN.1, reinfection broadened all measured subvariants may alleviate wild type‐vaccination immune imprinting. Boosted vaccination type comorbidities significant factors associated responses. Updated vaccines based on emerging acute respiratory syndrome coronavirus 2 variants are needed control Coronavirus Disease 2019 pandemic elderly.

Язык: Английский

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Humoral and cellular immune responses following Omicron BA.2.2 breakthrough infection and Omicron BA.5 reinfection

iScience, Год журнала: 2024, Номер 27(7), С. 110283 - 110283

Опубликована: Июнь 15, 2024

The emergence of novel Omicron subvariants has raised concerns regarding the efficacy immunity induced by prior breakthrough infection (BTI) or reinfection against current circulating subvariants. Here, we prospectively investigated durability antibody and T cell responses in individuals post BA.2.2 BTI, with without subsequent BA.5 reinfection. Our findings reveal that emerging subvariants, including CH.1.1, XBB, JN.1, exhibit extensive immune evasion previous infections. Notably, level IgG neutralizing antibodies were found to correlate Fortunately, recognizing both BA.2 CH.1.1 peptides observed. Furthermore, may alleviate imprinting WT-vaccination, bolster virus-specific ICS

Язык: Английский

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Systematical assessment of the impact of single spike mutations of SARS-CoV-2 Omicron sub-variants on the neutralization capacity of post-vaccination sera

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Ноя. 10, 2023

Introduction The evolution of novel SARS-CoV-2 variants significantly affects vaccine effectiveness. While these effects can only be studied retrospectively, neutralizing antibody titers are most used as correlates protection. However, studies assessing often show heterogeneous data. Methods To address this, we investigated assay variance and identified virus infection time dose factors affecting robustness. We next measured neutralization against Omicron sub-variants in cohorts with hybrid or induced immunity, identifying a gradient immune escape potential. evaluate the effect individual mutations on this potential variants, systematically assessed each mutation specific to BA.1, BA.2, BA.2.12.1, BA.4/5. Results cloned library pseudo-viruses expressing spikes single point mutations, subjected it pooled sera from vaccinated hosts, thereby multiple that independently affect potency. Discussion These data might help predict antigenic features viral carrying support development broad monoclonal antibodies.

Язык: Английский

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Efficacy, immunogenicity, and safety of a monovalent mRNA vaccine, ABO1020, in adults: A randomized, double-blind, placebo-controlled, phase 3 trial

Med, Год журнала: 2024, Номер 5(10), С. 1282 - 1292.e3

Опубликована: Июль 17, 2024

ABO1020 is a monovalent COVID-19 mRNA vaccine. Results from phase 1 trial showed was safe and well tolerated, 3 trials to evaluate the efficacy, immunogenicity, safety of in healthy adults are urgently needed.

Язык: Английский

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STAR SIGN study: Evaluation of COVID‐19 vaccine efficacy against the SARS‐CoV‐2 variants BQ.1.1 and XBB.1.5 in patients with inflammatory bowel disease

Alimentary Pharmacology & Therapeutics, Год журнала: 2023, Номер 58(7), С. 678 - 691

Опубликована: Авг. 12, 2023

Vaccine-elicited immune responses are impaired in patients with inflammatory bowel disease (IBD) treated anti-TNF biologics.To assess vaccination efficacy against the novel omicron sublineages BQ.1.1 and XBB.1.5 immunosuppressed IBD.This prospective multicentre case-control study included 98 biologic-treated IBD 48 healthy controls. Anti-spike IgG concentrations surrogate neutralisation SARS-CoV-2 wild-type, BA.1, BA.5, BQ.1.1, were measured at two different time points (2-16 weeks 22-40 weeks) following third dose vaccination. Surrogate was based on antibody-mediated blockage of ACE2-spike protein-protein interaction. Primary outcome tested sublineages. Secondary outcomes proportions participants insufficient neutralisation, impact breakthrough infection, correlation anti-spike concentration.Surrogate all reduced who biologics compared to non-anti-TNF controls (each p ≤ 0.001) visit 1. Anti-TNF therapy (odds ratio 0.29 [95% CI 0.19-0.46]) since (0.85 [0.72-1.00]) associated low, mRNA-1273 (1.86 [1.12-3.08]) high wild-type a β-regression model. Accordingly, higher had 1 0.015). decreased over but increased by infection. correlated neutralisation.Patients show may benefit from prioritisation for future variant-adapted vaccines.

Язык: Английский

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