Immune Evasion, Infectivity, and Fusogenicity of SARS-CoV-2 Omicron BA.2.86 and FLip Variants

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Сен. 12, 2023

Evolution of SARS-CoV-2 requires the reassessment current vaccine measures. Here, we characterized BA.2.86 and XBB-lineage variant FLip by investigating their neutralization alongside D614G, BA.1, BA.2, BA.4/5, XBB.1.5, EG.5.1 sera from 3-dose vaccinated bivalent healthcare workers, XBB.1.5-wave infected first responders, monoclonal antibody (mAb) S309. We assessed biology Spikes measuring viral infectivity membrane fusogenicity. is less immune evasive compared to other XBB variants, consistent with antigenic distances. Importantly, distinct mAb S309 was unable neutralize BA.2.86, likely due a D339H mutation based on modeling. had relatively high fusogenicity in CaLu-3 cells but low fusion 293T-ACE2 some suggesting potentially differences conformational stability Spike. Overall, our study underscores importance surveillance need for updated COVID-19 vaccines.

Язык: Английский

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Less neutralization evasion of SARS-CoV-2 BA.2.86 than XBB sublineages and CH.1.1

Emerging Microbes & Infections, Год журнала: 2023, Номер 12(2)

Опубликована: Окт. 12, 2023

The highly mutated BA.2.86, with over 30 spike protein mutations in comparison to Omicron BA.2 and XBB.1.5 variants, has raised concerns about its potential evade COVID-19 vaccination or prior SARS-CoV-2 infection-elicited immunity. In this study, we employ a live neutralization assay compare the evasion ability of BA.2.86 other emerged subvariants, including BA.2-derived CH.1.1, Delta-Omicron recombinant XBC.1.6, XBB descendants XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1 FL.1.5.1. Our results show that is less evasive than sublineages. EG.5.1, FL.1.5.1 continue significantly induced by parental mRNA vaccine BA.5 Bivalent booster. Notably, when compared more recent descendants, particularly display increased resistance neutralization. Among all tested CH.1.1 exhibits greatest evasion. contrast, XBC.1.6 shows slight reduction but remains comparably sensitive BA.5. Furthermore, XBB.1.5-breakthrough infection enhances breadth potency cross-neutralization. These findings reinforce expectation upcoming would likely boost currently circulating while also underscoring critical importance ongoing surveillance monitor evolution immune variants.

Язык: Английский

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Preclinical Characterization of the Omicron XBB.1.5-Adapted BNT162b2 COVID-19 Vaccine

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Ноя. 20, 2023

ABSTRACT As SARS-CoV-2 continues to evolve, increasing in its potential for greater transmissibility and immune escape, updated vaccines are needed boost adaptive immunity protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine, which contains same mRNA backbone as original modified incorporation XBB.1.5-specific sequence changes encoded prefusion-stabilized spike protein (S(P2)). Biophysical characterization XBB.1.5 S(P2) demonstrated that it maintains a prefusion conformation adopts flexible predominantly open one-RBD-up state, with high affinity binding human ACE-2 receptor. When administered 4 th dose BNT162b2-experienced mice, vaccine elicited substantially higher serum neutralizing titers pseudotyped viruses XBB.1.5, XBB.1.16, XBB.1.16.1, XBB.2.3, EG.5.1 HV.1 sublineages phylogenetically distant BA.2.86 lineage than bivalent Wild Type + BA.4/5 vaccine. Similar trends were observed XBB sublineage pseudoviruses when was 2-dose primary series naïve mice. Strong S-specific Th1 CD4 IFNγ CD8 T cell responses also observed. These findings, together prior experience variant-adapted preclinical clinical studies, suggest is anticipated confer protective dominant ONE-SENTENCE SUMMARY The encodes immunogen elicits more potent antibody homologous other compared thus demonstrating importance annual strain

Язык: Английский

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Less neutralization evasion of SARS-CoV-2 BA.2.86 than XBB sublineages and CH.1.1

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Сен. 11, 2023

Abstract The highly mutated BA.2.86, with over 30 spike protein mutations in comparison to Omicron BA.2 and XBB.1.5 variants, has raised concerns about its potential evade COVID-19 vaccination or prior SARS-CoV-2 infection-elicited immunity. In this study, we employ a live neutralization assay compare the evasion ability of BA.2.86 other emerged subvariants, including BA.2-derived CH.1.1, Delta-Omicron recombinant XBC.1.6, XBB descendants XBB.1.5, XBB.1.16, XBB.2.3, EG.5.1 FL.1.5.1. Our results show that is less evasive than sublineages. Among all tested CH.1.1 exhibits greatest evasion. more recent descendants, particularly FL.1.5.1, display increased resistance induced by parental mRNA vaccine BA.5-Bivalent-booster. contrast, XBC.1.6 shows slight reduction but remains comparable sensitivity when compared BA.5. Furthermore, XBB.1.5-breakthrough infection significantly enhances breadth potency cross-neutralization. These findings reinforce expectation upcoming would likely boost currently circulating while also underscoring critical importance ongoing surveillance monitor evolution immune variants.

Язык: Английский

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SARS-CoV-2 BA.2.86 (“Pirola”): Is it Pi or Just Another Omicron Sublineage?

Vaccines, Год журнала: 2023, Номер 11(11), С. 1634 - 1634

Опубликована: Окт. 25, 2023

The SARS-CoV-2 sublineage BA [...].

Язык: Английский

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Preclinical characterization of the Omicron XBB.1.5-adapted BNT162b2 COVID-19 vaccine

npj Vaccines, Год журнала: 2024, Номер 9(1)

Опубликована: Ноя. 20, 2024

Abstract As SARS-CoV-2 evolves, increasing in potential for greater transmissibility and immune escape, updated vaccines are needed to boost adaptive immunity protect against COVID-19 caused by circulating strains. Here, we report features of the monovalent Omicron XBB.1.5-adapted BNT162b2 vaccine, which contains XBB.1.5-specific sequence changes, relative original backbone, encoded prefusion-stabilized spike protein (S(P2)). Biophysical characterization XBB.1.5 S(P2) demonstrated that it maintains a prefusion conformation adopts flexible, predominantly open, state, with high affinity human ACE-2 receptor. When administered as 4th dose BNT162b2-experienced mice, vaccine elicited substantially higher serum neutralizing titers pseudotyped viruses XBB.1.5, XBB.1.16, XBB.1.16.1, XBB.2.3, EG.5.1 HV.1 sublineages phylogenetically distant BA.2.86 lineage than bivalent Wild Type + BA.4/5 vaccine. Similar trends were observed XBB sublineage pseudoviruses when was 2-dose series naive mice. Strong S-specific Th1 CD4 IFNγ CD8 T cell responses also observed. These findings, together real world performance suggest preclinical data predictive protective dominant

Язык: Английский

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Evolution and neutralization escape of the SARS-CoV-2 BA.2.86 subvariant

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Сен. 8, 2023

Omicron BA.2.86 subvariant differs from BA.2 as well recently circulating variants by over 30 mutations in the spike protein alone. Here we report on first isolation of live a diagnostic swab collected South Africa which tested for escape neutralizing antibodies and viral replication properties cell culture. did not have significantly more than XBB.1.5 immunity elicited infection subvariants ranging BA.1 to XBB, either alone or breakthrough vaccinated individuals. Neutralization was present relative earlier strains: showed extensive both ancestral virus sera pre-Omicron individuals infected We observe substantial differences culture XBB.1.5. Both produced foci similar size, had cytopathic effect (both lower SARS-CoV-2), dynamics. also investigated relationship sequences found that closest were samples Southern early 2022. These observations suggest is closely related other regions so may evolved there, evolution led scale strains SARS-CoV-2.

Язык: Английский

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Antigenicity and receptor affinity of SARS-CoV-2 BA.2.86 spike

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Сен. 25, 2023

Abstract Although the COVID-19 pandemic has officially ended 1 , SARS-CoV-2 continues to spread and evolve. Recent infections have been dominated by XBB.1.5 EG.5.1 subvariants 2 . A new subvariant designated BA.2.86 just emerged, spreading 21 countries in 5 continents 3 This virus contains 34 spike mutations compared its BA.2 predecessor, thereby raising concerns about propensity evade existing antibodies. We examined antigenicity using human sera monoclonal antibodies (mAbs). Reassuringly, was not more resistant than EG.5.1, indicating that would a growth advantage this regard. Importantly, from patients who had XBB breakthrough infection exhibited robust neutralizing activity against all viruses tested, suggesting upcoming monovalent vaccines could confer added protection. The finding longer genetic distance of did yield larger antigenic partially explained mAb data. While showed greater resistance mAbs subdomain (SD1) receptor-binding domain (RBD) class epitopes, it sensitive 4/1 epitopes “inner face” RBD is exposed only when “up” position. also identified six mediate antibody resistance, including E554K threatens SD1 clinical development. remarkably high receptor affinity. ultimate trajectory variant will soon be revealed continuing surveillance, but worldwide worrisome.

Язык: Английский

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Enhancement of IL-6 Production Induced by SARS-CoV-2 Nucleocapsid Protein and Bangladeshi COVID-19 Patients’ Sera

Viruses, Год журнала: 2023, Номер 15(10), С. 2018 - 2018

Опубликована: Сен. 28, 2023

Coronavirus disease 2019 (COVID-19) is a respiratory tract infection caused by severe acute syndrome coronavirus 2 that can have detrimental effects on multiple organs and accelerate patient mortality. This study, which encompassed 130 confirmed COVID-19 patients who were assessed at three different time points (i.e., 3, 7, 12 days) after the onset of symptoms, investigated interleukin-6 (IL-6) enhancement induced viral nucleocapsid (N) protein from myeloid cell line. Disease severity was categorized as mild, moderate, or severe. The cases characterized having significant elevations in serum IL-6, C-reactive protein, D-dimer, ferritin, creatinine, leukocytes, neutrophil-to-lymphocyte ratio decreased hemoglobin, hematocrit, albumin levels compared with mild moderate cases. To evaluate IL-6-inducing activity, heat-inactivated sera these incubated without N protein. findings showed progressive increase IL-6 production upon stimulation. There strong correlation between anti-N antibodies secreted cells presence sera, indicating crucial role antibody plays inducing production. Uncontrolled played pivotal pathogenesis, exacerbating both Efficiently targeting could potentially be employed therapeutic strategy for regulating immune response alleviating inflammation

Язык: Английский

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Emergence of a second SARS‐CoV‐2 variant with a tremendous genetic leap from its ancestors

Journal of Medical Virology, Год журнала: 2023, Номер 95(10)

Опубликована: Окт. 1, 2023

The on-going emergence of the Omicron BA.2.86 variant is one major events in SARS-CoV-2 genetic evolution that remain enigmatic regarding overall virus mutation rate, together with initial variant, BA.1. Indeed, genomes lineage, an offspring second subvariant, BA.2, harbor 39 additional mutations spike compared to this ancestor. Here we comment on phylogeny BA.2.86, positions, and frequencies other SARS-CoV-2, its spike, structural model protein concentrates most mutations.

Язык: Английский

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