Spike deep mutational scanning helps predict success of SARS-CoV-2 clades

Nature, Год журнала: 2024, Номер 631(8021), С. 617 - 626

Опубликована: Июль 3, 2024

SARS-CoV-2 variants acquire mutations in the spike protein that promote immune evasion

Язык: Английский

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SARS-CoV-2 evolution on a dynamic immune landscape

Nature, Год журнала: 2025, Номер unknown

Опубликована: Янв. 29, 2025

Abstract Since the onset of pandemic, many SARS-CoV-2 variants have emerged, exhibiting substantial evolution in virus’ spike protein 1 , main target neutralizing antibodies 2 . A plausible hypothesis proposes that virus evolves to evade antibody-mediated neutralization (vaccine- or infection-induced) maximize its ability infect an immunologically experienced population 1,3 Because viral infection induces antibodies, may thus navigate on a dynamic immune landscape is shaped by local history. Here we developed comprehensive mechanistic model, incorporating deep mutational scanning data 4,5 antibody pharmacokinetics and regional genomic surveillance data, predict variant-specific relative number susceptible individuals over time. We show this quantity precisely matched historical variant dynamics, predicted future dynamics explained global differences dynamics. Our work strongly suggests ongoing pandemic continues shape immunity, which determines variant’s transmit, defining fitness. The model can be applied any region utilizing allows contextualizing risk assessment provides information for vaccine design.

Язык: Английский

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Learning the fitness dynamics of pathogens from phylogenies

Nature, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Abstract The dynamics of the genetic diversity pathogens, including emergence lineages with increased fitness, is a foundational concept disease ecology key public-health implications. However, identification such and estimation associated fitness remain challenging, rarely done outside densely sampled systems 1,2 . Here we present phylowave, scalable approach that summarizes changes in population composition phylogenetic trees, enabling automatic detection based on shared evolutionary relationships. We use our broad set viruses bacteria (SARS-CoV-2, influenza A subtype H3N2, Bordetella pertussis Mycobacterium tuberculosis ), which include both well-studied understudied threats to human health. show phylowave recovers main known circulating for each pathogen it can detect specific amino acid linked changes. Furthermore, identifies previously undetected three co-circulating B. lineages. Inference using robust uneven limited observations. This widely applicable provides an avenue monitor evolution real time support action explore fundamental drivers fitness.

Язык: Английский

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Using minor variant genomes and machine learning to study the genome biology of SARS-CoV-2 over time

Nucleic Acids Research, Год журнала: 2025, Номер 53(4)

Опубликована: Фев. 8, 2025

In infected individuals, viruses are present as a population consisting of dominant and minor variant genomes. Most databases contain information on the genome sequence. Since emergence SARS-CoV-2 in late 2019, variants have been selected that more transmissible capable partial immune escape. Currently, models for projecting evolution based using sequences to forecast whether known mutation will be prevalent future. However, novel (and other viruses) driven by evolutionary pressure acting genomes, which then become form potential next wave infection. this study, sequencing data from 96 209 patients, sampled over 3-year period, were used analyse patterns These develop unsupervised machine learning clusters identify amino acids had greater than others Spike protein. Being able may future would better inform design longer-lived medical countermeasures allow risk-based evaluation viral properties, including assessment transmissibility escape, thus providing candidates with early warning signals when new emerges.

Язык: Английский

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Steering and controlling evolution — from bioengineering to fighting pathogens

Nature Reviews Genetics, Год журнала: 2023, Номер 24(12), С. 851 - 867

Опубликована: Июль 3, 2023

Язык: Английский

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Modeling memory B cell responses in a lymphoid organ-chip to evaluate mRNA vaccine boosting

The Journal of Experimental Medicine, Год журнала: 2024, Номер 221(10)

Опубликована: Сен. 6, 2024

Predicting the immunogenicity of candidate vaccines in humans remains a challenge. To address this issue, we developed lymphoid organ-chip (LO chip) model based on microfluidic chip seeded with human PBMC at high density within 3D collagen matrix. Perfusion SARS-CoV-2 spike protein mimicked vaccine boost by inducing massive amplification spike-specific memory B cells, plasmablast differentiation, and antibody secretion. Features tissue, including formation activated CD4+ T cell/B cell clusters emigration matured plasmablasts, were recapitulated LO chip. Importantly, myeloid cells competent capturing expressing mRNA vectored lipid nanoparticles, enabling assessment responses to vaccines. Comparison on-chip Wuhan monovalent Wuhan/Omicron bivalent boosts showed equivalent induction Omicron neutralizing antibodies, pointing immune imprinting as reported vivo. The thus represents versatile platform suited preclinical evaluation vaccine-boosting strategies.

Язык: Английский

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Concepts and methods for predicting viral evolution

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Март 19, 2024

The seasonal human influenza virus undergoes rapid evolution, leading to significant changes in circulating viral strains from year year. These are typically driven by adaptive mutations, particularly the antigenic epitopes, regions of surface protein haemagglutinin targeted antibodies. Here we describe a consistent set methods for data-driven predictive analysis evolution. Our pipeline integrates four types data: (1) sequence data isolates collected on worldwide scale, (2) epidemiological incidences, (3) characterization viruses, and (4) intrinsic phenotypes. From combined these data, obtain estimates relative fitness predictions clade frequencies periods up one Furthermore, comparative protection against future populations candidate vaccine strains, providing basis pre-emptive strain selection. Continuously updated obtained prediction SARS-CoV-2 available website previr.app.

Язык: Английский

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Host heterogeneity and epistasis explain punctuated evolution of SARS-CoV-2

PLoS Computational Biology, Год журнала: 2023, Номер 19(2), С. e1010896 - e1010896

Опубликована: Фев. 15, 2023

Identifying drivers of viral diversity is key to understanding the evolutionary as well epidemiological dynamics COVID-19 pandemic. Using rich genomic data sets, we show that periods steadily rising have been punctuated by sudden, enormous increases followed similarly abrupt collapses diversity. We introduce a mechanistic model saltational evolution with epistasis and demonstrate these features parsimoniously account for observed temporal inter-genomic Our results provide support recent proposals may be signature feature SARS-CoV-2, allowing pathogen more readily evolve highly transmissible variants. These findings lend theoretical heightened awareness biological contexts where increased diversification occur. They also underline power genomics other surveillance streams in clarifying phylodynamics emerging endemic infections. In public health terms, our further importance equitable distribution up-to-date vaccines.

Язык: Английский

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Artificial intelligence‐based prediction of pathogen emergence and evolution in the world of synthetic biology

Microbial Biotechnology, Год журнала: 2024, Номер 17(10)

Опубликована: Окт. 1, 2024

The emergence of new techniques in both microbial biotechnology and artificial intelligence (AI) is opening up a completely field for monitoring sometimes even controlling the evolution pathogens. However, now famous generative AI extracts reorganizes prior knowledge from large datasets, making it poorly suited to predictions an unreliable future. In contrast, unfamiliar perspective can help us identify key issues related technologies, such as those arising synthetic biology, whilst revisiting old views or including generator abduction resource. This could enable dangerous situations that are bound emerge not-too-distant future, prepare ourselves anticipate when where they will occur. Here, we emphasize fact amongst many causes pathogen outbreaks, often driven by explosion human population, laboratory accidents major cause epidemics. review, limited animal pathogens, concludes with discussion potential epidemic origins based on unusual organisms associations have rarely been highlighted studied.

Язык: Английский

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Characterizing fitness and immune escape of SARS-CoV-2 EG.5 sublineage using elderly serum and nasal organoid

iScience, Год журнала: 2024, Номер 27(5), С. 109706 - 109706

Опубликована: Апрель 9, 2024

Язык: Английский

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