An intranasal influenza virus-vectored vaccine prevents SARS-CoV-2 replication in respiratory tissues of mice and hamsters DOI Creative Commons
Shaofeng Deng, Ying Liu, Rachel Chun-Yee Tam

и другие.

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Апрель 12, 2023

Abstract Current available vaccines for COVID-19 are effective in reducing severe diseases and deaths caused by SARS-CoV-2 infection but less optimal preventing infection. Next-generation which able to induce mucosal immunity the upper respiratory prevent or reduce infections highly transmissible variants of urgently needed. We have developed an intranasal vaccine candidate based on a live attenuated influenza virus (LAIV) with deleted NS1 gene that encodes cell surface expression receptor-binding-domain (RBD) spike protein, designated DelNS1-RBD4N-DAF. Immune responses protection against challenge following administration DelNS1-RBD4N-DAF were analyzed mice compared intramuscular injection BioNTech BNT162b2 mRNA hamsters. LAIVs induced high levels neutralizing antibodies various hamsters stimulated robust T mice. Notably, vaccination LAIVs, not mRNA, prevented replication variants, including Delta Omicron BA.2, tissues animals. The LAIV system warrants further evaluation humans control transmission and, more significantly, creating dual function both use annual strategies.

Язык: Английский

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway DOI Creative Commons
Brian J. Willett, Joe Grove, Oscar A. MacLean

и другие.

Nature Microbiology, Год журнала: 2022, Номер 7(8), С. 1161 - 1179

Опубликована: Июль 7, 2022

Vaccines based on the spike protein of SARS-CoV-2 are a cornerstone public health response to COVID-19. The emergence hypermutated, increasingly transmissible variants concern (VOCs) threaten this strategy. Omicron (B.1.1.529), fifth VOC be described, harbours multiple amino acid mutations in spike, half which lie within receptor-binding domain. Here we demonstrate substantial evasion neutralization by BA.1 and BA.2 vitro using sera from individuals vaccinated with ChAdOx1, BNT162b2 mRNA-1273. These data were mirrored reduction real-world vaccine effectiveness that was partially restored booster vaccination. did not induce cell syncytia favoured TMPRSS2-independent endosomal entry pathway, these phenotypes mapping distinct regions protein. Impaired fusion determined domain, while mapped S2 Such marked changes antigenicity replicative biology may underlie rapid global spread altered pathogenicity variant.

Язык: Английский

Процитировано

548
Evolution of the SARS‐CoV‐2 omicron variants BA.1 to BA.5: Implications for immune escape and transmission DOI
Lok Bahadur Shrestha, Charles S. P. Foster, William D. Rawlinson

и другие.

Reviews in Medical Virology, Год журнала: 2022, Номер 32(5)

Опубликована: Июль 20, 2022

Abstract The first dominant SARS‐CoV‐2 Omicron variant BA.1 harbours 35 mutations in its Spike protein from the original that emerged late 2019. Soon after discovery, rapidly to become worldwide and has since evolved into several variants. is of major public health concern owing high infectivity antibody evasion. This review article examines theories have been proposed on evolution including zoonotic spillage, infection immunocompromised individuals cryptic spread community without being diagnosed. Added complexity Omicron's are multiple reports recombination events occurring between co‐circulating variants with Delta other such as XE. Current literature suggests combination novel resulted having higher than Wuhan‐Hu‐1 variant. However, severity believed be less reduced syncytia formation lower multiplication human lung tissue. Perhaps most challenging studies indicate efficacy available vaccines against (8–127 times reduction) compared administration booster vaccine, however, compensates reduction improves by 12–35 fold. Concerningly though, broadly neutralising monoclonal antibodies, those approved FDA for therapeutic use previous variants, mostly ineffective exception Sotrovimab recent suggest BA.2 also resistant Sotrovimab. Currently two new BA.4 BA.5 emerging reported more transmissible immunity generated antibodies. As will likely continue emerge it important evolution, biological consequences mutations, existing well understood.

Язык: Английский

Процитировано

414
Virological characteristics of the SARS-CoV-2 Omicron BA.2 subvariants, including BA.4 and BA.5 DOI Creative Commons

Izumi Kimura,

Daichi Yamasoba,

Tomokazu Tamura

и другие.

Cell, Год журнала: 2022, Номер 185(21), С. 3992 - 4007.e16

Опубликована: Сен. 14, 2022

After the global spread of SARS-CoV-2 Omicron BA.2, some BA.2 subvariants, including BA.2.9.1, BA.2.11, BA.2.12.1, BA.4, and BA.5, emerged in multiple countries. Our statistical analysis showed that effective reproduction numbers these subvariants are greater than original BA.2. Neutralization experiments revealed immunity induced by BA.1/2 infections is less against BA.4/5. Cell culture BA.2.12.1 BA.4/5 replicate more efficiently human alveolar epithelial cells particularly, fusogenic We further provided structure spike receptor-binding domain binds to ACE2 considered how substitutions play roles binding immune evasion. Moreover, using hamsters suggested pathogenic multiscale investigations suggest risk particularly BA.4/5, health

Язык: Английский

Процитировано

242
Monoclonal antibody therapies against SARS-CoV-2 DOI Open Access
Daniele Focosi, Scott A. McConnell, Arturo Casadevall

и другие.

The Lancet Infectious Diseases, Год журнала: 2022, Номер 22(11), С. e311 - e326

Опубликована: Июль 5, 2022

Язык: Английский

Процитировано

211
Omicron: What Makes the Latest SARS-CoV-2 Variant of Concern So Concerning? DOI
Christoph Jung, Dorota Kmieć, Lennart Koepke

и другие.

Journal of Virology, Год журнала: 2022, Номер 96(6)

Опубликована: Фев. 28, 2022

Emerging strains of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent disease 2019 (COVID-19) pandemic, that show increased transmission fitness and/or immune evasion are classified as "variants concern" (VOCs). Recently, a SARS-CoV-2 variant first identified in November 2021 South Africa has been recognized fifth VOC, termed "Omicron." What makes this VOC so alarming is high number changes, especially viral Spike protein, and accumulating evidence for efficiency escape from neutralizing antibodies. In an amazingly short time, Omicron outcompeted previously dominating Delta VOC. However, it seems overall less pathogenic than other VOCs. Here, we provide overview mutations genome resulting changes proteins compared to discuss their potential functional consequences.

Язык: Английский

Процитировано

203
Determinants of Spike infectivity, processing, and neutralization in SARS-CoV-2 Omicron subvariants BA.1 and BA.2 DOI Creative Commons
Chiara Pastorio, Fabian Zech, Sabrina Noettger

и другие.

Cell Host & Microbe, Год журнала: 2022, Номер 30(9), С. 1255 - 1268.e5

Опубликована: Июль 18, 2022

SARS-CoV-2 Omicron rapidly outcompeted other variants and currently dominates the COVID-19 pandemic. Its enhanced transmission immune evasion are thought to be driven by numerous mutations in Spike protein. Here, we systematically introduced BA.1 and/or BA.2 into ancestral protein examined impacts on function, processing, susceptibility neutralization. Individual of S371F/L, S375F, T376A ACE2-receptor-binding domain as well Q954H N969K hinge region 1 impaired infectivity, while changes G339D, D614G, N764K, L981F moderately it. Most N-terminal receptor-binding reduced sensitivity neutralization sera from individuals vaccinated with BNT162b2 vaccine therapeutic antibodies. Our results represent a systematic functional analysis adaptations that have allowed this variant dominate current

Язык: Английский

Процитировано

78
Susceptibility of SARS-CoV-2 Omicron Variants to Therapeutic Monoclonal Antibodies: Systematic Review and Meta-analysis DOI Creative Commons
Kaiming Tao, Philip L. Tzou, Sergei L. Kosakovsky Pond

и другие.

Microbiology Spectrum, Год журнала: 2022, Номер 10(4)

Опубликована: Июнь 14, 2022

SARS-CoV-2 Omicron variants contain many mutations in its spike receptor-binding domain, the target of all authorized monoclonal antibodies (MAbs). Determining extent to which reduced MAb susceptibility is critical preventing and treating COVID-19. We systematically reviewed PubMed three preprint servers, last updated 11 April 2022, for vitro activity MAbs against variants. Fifty-one studies were eligible, including 50 containing BA.1 data 17 BA.2 data. The first two combinations, bamlanivimab/etesevimab casirivimab/imdevimab, largely inactive In 34 studies, sotrovimab displayed a median 4.0-fold (interquartile range [IQR]: 2.6 6.9) reduction BA.1, 12 it 17-fold (IQR: 13 30) BA.2. 15 combination cilgavimab/tixagevimab 86-fold 27 151) six 5.4-fold 3.7 eight BA.2, bebtelovimab no activity. Disparate results between assays common. For MAbs, 51/268 (19.0%) wild-type control 78/348 (22.4%) more than 4-fold below or above result that MAb. Highly disparate published indicate need improved test standardization interassay calibration. IMPORTANCE Monoclonal (MAbs) targeting protein are among most effective measures However, their domains, MAbs. Therefore, determining identified 51 reported main therapeutic advanced clinical development, individual combinations. estimated degree different marked loss underscores importance developing conserved regions spike. standardization.

Язык: Английский

Процитировано

76
Bench-to-bedside: Innovation of small molecule anti-SARS-CoV-2 drugs in China DOI Open Access
Liyan Yang, Zhonglei Wang

European Journal of Medicinal Chemistry, Год журнала: 2023, Номер 257, С. 115503 - 115503

Опубликована: Май 18, 2023

Язык: Английский

Процитировано

63
Emergence and antibody evasion of BQ, BA.2.75 and SARS-CoV-2 recombinant sub-lineages in the face of maturing antibody breadth at the population level DOI Creative Commons
Anouschka Akerman, Vanessa Milogiannakis,

Tyra Jean

и другие.

EBioMedicine, Год журнала: 2023, Номер 90, С. 104545 - 104545

Опубликована: Март 30, 2023

Язык: Английский

Процитировано

44
Improvement of immune dysregulation in individuals with long COVID at 24-months following SARS-CoV-2 infection DOI Creative Commons
Chansavath Phetsouphanh, Brendan Jacka, Sara Ballouz

и другие.

Nature Communications, Год журнала: 2024, Номер 15(1)

Опубликована: Апрель 17, 2024

Abstract This study investigates the humoral and cellular immune responses health-related quality of life measures in individuals with mild to moderate long COVID (LC) compared age gender matched recovered COVID-19 controls (MC) over 24 months. LC participants show elevated nucleocapsid IgG levels at 3 months, higher neutralizing capacity up 8 months post-infection. Increased spike-specific nucleocapsid-specific CD4 + T cells, PD-1, TIM-3 expression on CD8 cells were observed but these differences do not persist Some had detectable IFN-γ IFN-β, that was attributed reinfection antigen re-exposure. Single-cell RNA sequencing month timepoint shows similar cell proportions reconstitution naïve B subsets MC. No significant exhaustion scores or antigen-specific clones are observed. These findings suggest resolution activation return comparable between MC time. Improvement self-reported also evident majority (62%). PTX3, CRP platelet count associated improvements life.

Язык: Английский

Процитировано

17