Omicron BA.4/BA.5 escape neutralizing immunity elicited by BA.1 infection

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: Aug. 10, 2022

SARS-CoV-2 Omicron (B.1.1.529) BA.4 and BA.5 sub-lineages, first detected in South Africa, have changes relative to BA.1 including substitutions the spike receptor binding domain. Here we isolated live viruses measured BA.4/BA.5 neutralization elicited by infection either absence or presence of previous vaccination as well from without infection. In BA.1-infected unvaccinated individuals, declines 7.6-fold for 7.5-fold BA.5. vaccinated individuals with subsequent infection, decreases 3.2-fold 2.6-fold The fold-drop versus ancestral virus this group is 4.0-fold BA.1, 12.9-fold BA.4, 10.3-fold contrast, escape similar immunity: 19.8-fold 19.6-fold 20.9-fold These results show considerable immunity which moderated may indicate that strongest selective advantage evading unvaccinated, infected individuals.

Language: Английский

---

SARS-CoV-2 Omicron BA.5: Evolving tropism and evasion of potent humoral responses and resistance to clinical immunotherapeutics relative to viral variants of concern

EBioMedicine, Journal Year: 2022, Volume and Issue: 84, P. 104270 - 104270

Published: Sept. 18, 2022

BackgroundGenetically distinct viral variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have been recorded since January 2020. The introduction global vaccine programs has contributed to lower COVID-19 hospitalisation and mortality rates, particularly in developed countries. In late 2021, Omicron BA.1 emerged, with substantially altered genetic differences clinical effects from other concern. Shortly after dominating spread early 2022, was supplanted by the genetically lineage BA.2. A sub-lineage BA.2, designated BA.5, presently an outgrowth advantage over BA.2 sub-lineages. Here we study neutralisation BA.1, BA.5 pre-Omicron using a range convalescent sera therapeutic monoclonal antibodies live virus assay. Using primary nasopharyngeal swabs, also tested relative fitness compared lineages their ability use ACE2-TMPRSS2 pathway.MethodsUsing low passage isolates Clade A.2.2, Beta, Delta, determined humoral vitro vaccinated cohorts, concentrated human IgG pooled thousands plasma donors, licensed antibody therapies. We then infectivity particle ratios samples expanded engineered ACE2/TMPRSS2 cell line presence absence TMPRSS2 inhibitor Nafamostat.FindingsPeak responses 3 doses BNT162b2 were associated 9-fold reduction for BA.5. Concentrated donors vaccination breakthrough infections greater breadth neutralisation, although potency still reduced 7-fold across all lineages. Testing grade revealed 14.3-fold Evusheld 16.8-fold Sotrovimab Whilst attenuated entry, observed be equivalent that 2020 circulating clade had sensitivity Nafamostat.InterpretationObservations support significantly escape neutralising and/or responses. Potency is differs key difference sub-variants reversion tropism back well-known pathway, utilised efficiently Monitoring if these changes influence transmission disease severity will ongoing tracking management waves globally.FundingThis work primarily supported Australian Medical Foundation research grants MRF2005760 (ST, GM & WDR), MRF2001684 (ADK ST) Research Future Fund Antiviral Development Call grant (WDR), (MRFF2001684, ADK SGT) New South Wales Health Grants Round (SGT).

Language: Английский

---

Risk of reinfection, vaccine protection, and severity of infection with the BA.5 omicron subvariant: a nation-wide population-based study in Denmark

The Lancet Infectious Diseases, Journal Year: 2022, Volume and Issue: 23(2), P. 167 - 176

Published: Oct. 18, 2022

Language: Английский

---

Characterization of SARS-CoV-2 Omicron BA.4 and BA.5 isolates in rodents

Nature, Journal Year: 2022, Volume and Issue: 612(7940), P. 540 - 545

Published: Nov. 2, 2022

Language: Английский

---

A 30-day follow-up study on the prevalence of SARS-COV-2 genetic markers in wastewater from the residence of COVID-19 patient and comparison with clinical positivity

The Science of The Total Environment, Journal Year: 2022, Volume and Issue: 858, P. 159350 - 159350

Published: Oct. 18, 2022

Wastewater based epidemiology (WBE) is an important tool to fight against COVID-19 as it provides insights into the health status of targeted population from a small single house large municipality in cost-effective, rapid, and non-invasive way. The implementation wastewater surveillance (WBS) could reduce burden on public system, management pandemics, help make informed decisions, protect health. In this study, with patients was for monitoring prevalence SARS-CoV-2 genetic markers samples (WS) clinical specimens (CS) period 30 days. RT-qPCR technique employed target nonstructural (ORF1ab) structural-nucleocapsid (N) protein genes SARS-CoV-2, according validated experimental protocol. Physiological, environmental, biological parameters were also measured following American Public Health Association (APHA) standard protocols. viral shedding peaked when highest number cases clinically diagnosed. Throughout study period, 7450 23,000 gene copies/1000 mL detected, where we identified 47 % (57/120) positive WS 35 (128/360) CS. When patient lowest (2), CT value (39.4; i.e., copy number) WS. On other hand, (6), (25.2 numbers) obtained An advance signal increased load found earlier than Using customized primer sets traditional PCR approach, confirmed that all variants both CS Delta (B.1.617.2). To our knowledge, first follow-up determine temporal relationship between their discharge RNA including family members sampling developing country (Bangladesh), proper sewage system lacking. salient findings indicate virus identify cases, which reduces during pandemics.

Language: Английский

---

Interactions of angiotensin-converting enzyme-2 (ACE2) and SARS-CoV-2 spike receptor-binding domain (RBD): a structural perspective

Molecular Biology Reports, Journal Year: 2022, Volume and Issue: 50(3), P. 2713 - 2721

Published: Dec. 23, 2022

Language: Английский

---

A Review of the Currently Available Antibody Therapy for the Treatment of Coronavirus Disease 2019 (COVID-19)

Antibodies, Journal Year: 2023, Volume and Issue: 12(1), P. 5 - 5

Published: Jan. 11, 2023

Monoclonal antibodies are a promising treatment for COVID-19. However, the emergence of SARS-CoV-2 variants raised concerns about these therapies’ efficacy and long-term viability. Studies reported several antibodies, that received authorization COVID-19 treatment, not effective against new or subvariants SARS-CoV-2, hence their distribution has to be paused. Here, authors reviewed status currently available monoclonal potential as therapeutic agent, challenges ahead. To address issues, presented general information on how work SARS-CoV-2. The then focus have been deployed current status, well evidence supporting an early intervention Lastly, discussed some leading obstacles hinder development administration

Language: Английский

---

SARS-CoV-2 Omicron Subvariants Do Not Differ Much in Binding Affinity to Human ACE2: A Molecular Dynamics Study

The Journal of Physical Chemistry B, Journal Year: 2024, Volume and Issue: 128(14), P. 3340 - 3349

Published: April 2, 2024

The emergence of the variant concern Omicron (B.1.1.529) severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) exacerbates COVID-19 pandemic due to its high contagious ability. Studies have shown that binds human ACE2 more strongly than wild type. prevalence in new cases promotes novel lineages with improved receptor binding affinity and immune evasion. To shed light on this open problem, work, we investigated free energy domain BA.2, BA.2.3.20, BA.3, BA4/BA5, BA.2.75, BA.2.75.2, BA.4.6, XBB.1, XBB.1.5, BJ.1, BN.1, BQ.1.1, CH.1.1 using all-atom molecular dynamics simulation mechanics Poisson–Boltzmann surface area method. results show these increased compared BA.1 lineage, BA.2.75 BA.2.75.2 subvariants bind others. However, general, affinities do not differ significantly from each other. electrostatic force dominates over van der Waals interaction between cells. Based our results, argue viral evolution does further improve SARS-CoV-2 for but may increase

Language: Английский

---

SARS-CoV-2 B.1.1.529 (Omicron) Variant Causes an Unprecedented Surge in Children Hospitalizations and Distinct Clinical Presentation Compared to the SARS-CoV-2 B.1.617.2 (Delta) Variant

Frontiers in Pediatrics, Journal Year: 2022, Volume and Issue: 10

Published: June 27, 2022

Background In the midst of successive waves SARS-CoV-2 variants, B.1.1.529 (omicron) variant has recently caused a surge in pediatric infections and hospitalizations. This study aimed to describe compare symptoms, explorations, treatment evolution COVID-19 hospitalized children during B.1.617.2 (delta) waves. Methods observational was performed Pediatric Pulmonology Department University Hospital Paris, France. All aged between 0 18 years who tested positive for using reverse transcription polymerase chain reaction (RT-PCR) nasopharyngeal swabs from July 15th December 2021 (delta wave), February 28th 2022 (omicron wave) were included. Results total, 53 included, 14 (26.4%) delta wave 39 (73.6%) omicron (almost three times as many hospitalizations half time latter wave). During wave, patients mostly < 5 (90 vs. 71% all waves, respectively), tended have fewer underlying conditions (56 79% respectively, p = 0.20). The also responsible different clinical presentation when compared variant, with significantly higher often poorly tolerated temperatures ( 0.03) increased digestive symptoms 0.01). None older than 12 fully vaccinated. Conclusion dramatic increase hospitalization modification latest require pediatricians remain vigilant. It should encourage caregivers ensure vaccination years, whom BNT162b2 vaccine been deemed safe, immunogenic, effective.

Language: Английский

---

Suppressing Mesenchymal Stromal Cell Ferroptosis Via Targeting a Metabolism‐Epigenetics Axis Corrects their Poor Retention and Insufficient Healing Benefits in the Injured Liver Milieu

Advanced Science, Journal Year: 2023, Volume and Issue: 10(13)

Published: Feb. 19, 2023

Abstract Mesenchymal stromal cell (MSC) implantation is a promising option for liver repair, but their poor retention in the injured milieu critically blunts therapeutic effects. The aim to clarify mechanisms underlying massive MSC loss post‐implantation and establish corresponding improvement strategies. primarily occurs within initial hours after into or under reactive oxygen species (ROS) stress. Surprisingly, ferroptosis identified as culprit rapid depletion. In ferroptosis‐ ROS‐provoking MSCs, branched‐chain amino acid transaminase‐1 (BCAT1) dramatically decreased, its downregulation renders susceptible via suppressing transcription of glutathione peroxidase‐4 (GPX4), vital defensing enzyme. BCAT1 impedes GPX4 rapid‐responsive metabolism‐epigenetics coordinating mechanism, involving α ‐ketoglutarate accumulation, histone 3 lysine 9 trimethylation loss, early growth response protein‐1 upregulation. Approaches suppress (e.g., incorporating inhibitors injection solvent overexpressing BCAT1) significantly improve liver‐protective effects post‐implantation. This study provides first evidence indicating that excessive nonnegligible depletion insufficient efficacy milieu. Strategies are conducive optimizing MSC‐based therapy.

Language: Английский

---