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Article ; Online: Population immunity predicts evolutionary trajectories of SARS-CoV-2.

Meijers, Matthijs / Ruchnewitz, Denis / Eberhardt, Jan / Łuksza, Marta / Lässig, Michael

2023 Volume 186, Issue 23, Page(s) 5151–5164.e13

Abstract: The large-scale evolution of the SARS-CoV-2 virus has been marked by rapid turnover of genetic clades. New variants show intrinsic changes, notably increased transmissibility, and antigenic changes that reduce cross-immunity induced by previous ... ...

Abstract	The large-scale evolution of the SARS-CoV-2 virus has been marked by rapid turnover of genetic clades. New variants show intrinsic changes, notably increased transmissibility, and antigenic changes that reduce cross-immunity induced by previous infections or vaccinations. How this functional variation shapes global evolution has remained unclear. Here, we establish a predictive fitness model for SARS-CoV-2 that integrates antigenic and intrinsic selection. The model is informed by tracking of time-resolved sequence data, epidemiological records, and cross-neutralization data of viral variants. Our inference shows that immune pressure, including contributions of vaccinations and previous infections, has become the dominant force driving the recent evolution of SARS-CoV-2. The fitness model can serve continued surveillance in two ways. First, it successfully predicts the short-term evolution of circulating strains and flags emerging variants likely to displace the previously predominant variant. Second, it predicts likely antigenic profiles of successful escape variants prior to their emergence.
MeSH term(s)	Humans ; COVID-19/epidemiology ; COVID-19/virology ; SARS-CoV-2/genetics ; SARS-CoV-2/physiology ; Vaccination ; Models, Genetic ; Epidemiological Monitoring
Language	English
Publishing date	2023-10-23
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	187009-9
ISSN	1097-4172 ; 0092-8674
ISSN (online)	1097-4172
ISSN	0092-8674
DOI	10.1016/j.cell.2023.09.022
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Article: Is it possible to predict influenza antigenic variants?

Lina, Bruno / Łuksza, Marta

Virologie (Montrouge, France)

2020 Volume 21, Issue 1, Page(s) 5–8

Title translation	Peut-on prédire les variants antigéniques de la grippe ?
Language	English
Publishing date	2020-01-22
Publishing country	France
Document type	Journal Article
ISSN	1267-8694
ISSN	1267-8694
DOI	10.1684/vir.2017.0678
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Article ; Online: Vaccination shapes evolutionary trajectories of SARS-CoV-2

Meijers, Matthijs / Ruchnewitz, Denis / Luksza, Marta / Lässig, Michael

bioRxiv

Abstract: The large-scale evolution of the SARS-CoV-2 virus has been marked by rapid turnover of genetic clades. New variants show intrinsic changes, notably increased transmissibility, as well as antigenic changes that reduce the cross-immunity induced by ... ...

Abstract	The large-scale evolution of the SARS-CoV-2 virus has been marked by rapid turnover of genetic clades. New variants show intrinsic changes, notably increased transmissibility, as well as antigenic changes that reduce the cross-immunity induced by previous infections or vaccinations. How this functional variation shapes the global evolutionary dynamics has remained unclear. Here we show that selection induced by vaccination impacts on the recent antigenic evolution of SARS-CoV-2; other relevant forces include intrinsic selection and antigenic selection induced by previous infections. We obtain these results from a fitness model with intrinsic and antigenic fitness components. To infer model parameters, we combine time-resolved sequence data, epidemiological records, and cross-neutralisation assays. This model accurately captures the large-scale evolutionary dynamics of SARS-CoV-2 in multiple geographical regions. In particular, it quantifies how recent vaccinations and infections affect the speed of frequency shifts between viral variants.Our results show that timely neutralisation data can be harvested to identify hotspots of antigenic selection and to predict the impact of vaccination on viral evolution.
Keywords	covid19
Language	English
Publishing date	2022-07-20
Publisher	Cold Spring Harbor Laboratory
Document type	Article ; Online
DOI	10.1101/2022.07.19.500637
Database	COVID19

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Book ; Online: Vaccination shapes evolutionary trajectories of SARS-CoV-2

Meijers, Matthijs / Ruchnewitz, Denis / Łuksza, Marta / Lässig, Michael

2022

Abstract: The large-scale evolution of the SARS-CoV-2 virus has been marked by rapid turnover of genetic clades. New variants show intrinsic changes, notably increased transmissibility, as well as antigenic changes that reduce the cross-immunity induced by ... ...

Abstract	The large-scale evolution of the SARS-CoV-2 virus has been marked by rapid turnover of genetic clades. New variants show intrinsic changes, notably increased transmissibility, as well as antigenic changes that reduce the cross-immunity induced by previous infections or vaccinations. How this functional variation shapes the global evolutionary dynamics has remained unclear. Here we show that selection induced by vaccination impacts on the recent antigenic evolution of SARS-CoV-2; other relevant forces include intrinsic selection and antigenic selection induced by previous infections. We obtain these results from a fitness model with intrinsic and antigenic fitness components. To infer model parameters, we combine time-resolved sequence data, epidemiological records, and cross-neutralisation assays. This model accurately captures the large-scale evolutionary dynamics of SARS-CoV-2 in multiple geographical regions. In particular, it quantifies how recent vaccinations and infections affect the speed of frequency shifts between viral variants. Our results show that timely neutralisation data can be harvested to identify hotspots of antigenic selection and to predict the impact of vaccination on viral evolution.
Keywords	Quantitative Biology - Populations and Evolution ; Physics - Biological Physics
Subject code	612
Publishing date	2022-07-19
Publishing country	us
Document type	Book ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article ; Online: Can we read the future from a tree?

Lässig, Michael / Łuksza, Marta

eLife

2014 Volume 3

MeSH term(s)	Algorithms ; Evolution, Molecular ; Forecasting ; Humans ; Influenza A Virus, H3N2 Subtype/genetics ; Models, Genetic
Language	English
Publishing date	2014
Publishing country	England
Document type	Comment ; Journal Article
ISSN	2050-084X
ISSN (online)	2050-084X
DOI	10.7554/eLife.05060
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: A predictive fitness model for influenza.

Luksza, Marta / Lässig, Michael

Nature

2014 Volume 507, Issue 7490, Page(s) 57–61

Abstract: The seasonal human influenza A/H3N2 virus undergoes rapid evolution, which produces significant year-to-year sequence turnover in the population of circulating strains. Adaptive mutations respond to human immune challenge and occur primarily in antigenic ...

Abstract	The seasonal human influenza A/H3N2 virus undergoes rapid evolution, which produces significant year-to-year sequence turnover in the population of circulating strains. Adaptive mutations respond to human immune challenge and occur primarily in antigenic epitopes, the antibody-binding domains of the viral surface protein haemagglutinin. Here we develop a fitness model for haemagglutinin that predicts the evolution of the viral population from one year to the next. Two factors are shown to determine the fitness of a strain: adaptive epitope changes and deleterious mutations outside the epitopes. We infer both fitness components for the strains circulating in a given year, using population-genetic data of all previous strains. From fitness and frequency of each strain, we predict the frequency of its descendent strains in the following year. This fitness model maps the adaptive history of influenza A and suggests a principled method for vaccine selection. Our results call for a more comprehensive epidemiology of influenza and other fast-evolving pathogens that integrates antigenic phenotypes with other viral functions coupled by genetic linkage.
MeSH term(s)	Computer Simulation ; Epitopes/genetics ; Epitopes/immunology ; Evolution, Molecular ; Genes, Viral/genetics ; Genetic Fitness/genetics ; Genetic Fitness/immunology ; Genetic Fitness/physiology ; Genetics, Population ; Hemagglutinin Glycoproteins, Influenza Virus/chemistry ; Hemagglutinin Glycoproteins, Influenza Virus/genetics ; Hemagglutinin Glycoproteins, Influenza Virus/immunology ; Humans ; Influenza A Virus, H3N2 Subtype/chemistry ; Influenza A Virus, H3N2 Subtype/classification ; Influenza A Virus, H3N2 Subtype/genetics ; Influenza A Virus, H3N2 Subtype/immunology ; Influenza Vaccines/chemistry ; Influenza Vaccines/genetics ; Influenza Vaccines/immunology ; Influenza, Human/epidemiology ; Influenza, Human/immunology ; Influenza, Human/virology ; Models, Immunological ; Mutation/genetics ; Time Factors
Chemical Substances	Epitopes ; Hemagglutinin Glycoproteins, Influenza Virus ; Influenza Vaccines
Language	English
Publishing date	2014-02-26
Publishing country	England
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	120714-3
ISSN	1476-4687 ; 0028-0836
ISSN (online)	1476-4687
ISSN	0028-0836
DOI	10.1038/nature13087
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Book ; Online ; Thesis: Cluster statistics and gene expression analysis

Łuksza, Marta [Verfasser]

2012

Author's details	Marta Łuksza
Keywords	Naturwissenschaften ; Science
Subject code	sg500
Language	English
Publisher	Freie Universität Berlin
Publishing place	Berlin
Document type	Book ; Online ; Thesis
Database	Digital theses on the web

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Article ; Online: Fierce Selection and Interference in B-Cell Repertoire Response to Chronic HIV-1.

Nourmohammad, Armita / Otwinowski, Jakub / Łuksza, Marta / Mora, Thierry / Walczak, Aleksandra M

Molecular biology and evolution

2019 Volume 36, Issue 10, Page(s) 2184–2194

Abstract: During chronic infection, HIV-1 engages in a rapid coevolutionary arms race with the host's adaptive immune system. While it is clear that HIV exerts strong selection on the adaptive immune system, the characteristics of the somatic evolution that shape ... ...

Abstract	During chronic infection, HIV-1 engages in a rapid coevolutionary arms race with the host's adaptive immune system. While it is clear that HIV exerts strong selection on the adaptive immune system, the characteristics of the somatic evolution that shape the immune response are still unknown. Traditional population genetics methods fail to distinguish chronic immune response from healthy repertoire evolution. Here, we infer the evolutionary modes of B-cell repertoires and identify complex dynamics with a constant production of better B-cell receptor (BCR) mutants that compete, maintaining large clonal diversity and potentially slowing down adaptation. A substantial fraction of mutations that rise to high frequencies in pathogen-engaging CDRs of BCRs are beneficial, in contrast to many such changes in structurally relevant frameworks that are deleterious and circulate by hitchhiking. We identify a pattern where BCRs in patients who experience larger viral expansions undergo stronger selection with a rapid turnover of beneficial mutations due to clonal interference in their CDR3 regions. Using population genetics modeling, we show that the extinction of these beneficial mutations can be attributed to the rise of competing beneficial alleles and clonal interference. The picture is of a dynamic repertoire, where better clones may be outcompeted by new mutants before they fix.
MeSH term(s)	Adaptive Immunity ; HIV Infections/immunology ; HIV-1/immunology ; Humans ; Receptors, Antigen, B-Cell/genetics ; Selection, Genetic
Chemical Substances	Receptors, Antigen, B-Cell
Language	English
Publishing date	2019-06-17
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	998579-7
ISSN	1537-1719 ; 0737-4038
ISSN (online)	1537-1719
ISSN	0737-4038
DOI	10.1093/molbev/msz143
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Article ; Online: Antibodies targeting the neuraminidase active site inhibit influenza H3N2 viruses with an S245N glycosylation site.

Stadlbauer, Daniel / McMahon, Meagan / Turner, Hannah L / Zhu, Xueyong / Wan, Hongquan / Carreño, Juan Manuel / O'Dell, George / Strohmeier, Shirin / Khalil, Zain / Luksza, Marta / van Bakel, Harm / Simon, Viviana / Ellebedy, Ali H / Wilson, Ian A / Ward, Andrew B / Krammer, Florian

Nature communications

2022 Volume 13, Issue 1, Page(s) 7864

Abstract: Contemporary influenza A H3N2 viruses circulating since 2016 have acquired a glycosylation site in the neuraminidase in close proximity to the enzymatic active site. Here, we investigate if this S245N glycosylation site, as a result of antigenic ... ...

Abstract	Contemporary influenza A H3N2 viruses circulating since 2016 have acquired a glycosylation site in the neuraminidase in close proximity to the enzymatic active site. Here, we investigate if this S245N glycosylation site, as a result of antigenic evolution, can impact binding and function of human monoclonal antibodies that target the conserved active site. While we find that a reduction in the inhibitory ability of neuraminidase active site binders is measurable, this class of broadly reactive monoclonal antibodies maintains protective efficacy in vivo.
MeSH term(s)	Humans ; Antibodies, Monoclonal/chemistry ; Antibodies, Monoclonal/immunology ; Antibodies, Viral/chemistry ; Antibodies, Viral/metabolism ; Catalytic Domain/immunology ; Catalytic Domain/physiology ; Glycosylation ; Hemagglutinin Glycoproteins, Influenza Virus ; Influenza A virus ; Influenza A Virus, H3N2 Subtype/immunology ; Influenza A Virus, H3N2 Subtype/metabolism ; Influenza, Human/immunology ; Influenza, Human/metabolism ; Neuraminidase/chemistry ; Neuraminidase/immunology
Chemical Substances	Antibodies, Monoclonal ; Antibodies, Viral ; Hemagglutinin Glycoproteins, Influenza Virus ; Neuraminidase (EC 3.2.1.18)
Language	English
Publishing date	2022-12-21
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural
ZDB-ID	2553671-0
ISSN	2041-1723 ; 2041-1723
ISSN (online)	2041-1723
ISSN	2041-1723
DOI	10.1038/s41467-022-35586-7
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Clinical and molecular features of acquired resistance to immunotherapy in non-small cell lung cancer.

Memon, Danish / Schoenfeld, Adam J / Ye, Darwin / Fromm, George / Rizvi, Hira / Zhang, Xiang / Keddar, Mohamed Reda / Mathew, Divij / Yoo, Kyung Jin / Qiu, Jingya / Lihm, Jayon / Miriyala, Jayalaksmi / Sauter, Jennifer L / Luo, Jia / Chow, Andrew / Bhanot, Umesh K / McCarthy, Caroline / Vanderbilt, Chad M / Liu, Cailian /

Abu-Akeel, Mohsen / Plodkowski, Andrew J / McGranahan, Nicholas / Łuksza, Marta / Greenbaum, Benjamin D / Merghoub, Taha / Achour, Ikbel / Barrett, J Carl / Stewart, Ross / Beltrao, Pedro / Schreiber, Taylor H / Minn, Andy J / Miller, Martin L / Hellmann, Matthew D

Cancer cell

2024 Volume 42, Issue 2, Page(s) 209–224.e9

Abstract: Although immunotherapy with PD-(L)1 blockade is routine for lung cancer, little is known about acquired resistance. Among 1,201 patients with non-small cell lung cancer (NSCLC) treated with PD-(L)1 blockade, acquired resistance is common, occurring in > ... ...

Abstract	Although immunotherapy with PD-(L)1 blockade is routine for lung cancer, little is known about acquired resistance. Among 1,201 patients with non-small cell lung cancer (NSCLC) treated with PD-(L)1 blockade, acquired resistance is common, occurring in >60% of initial responders. Acquired resistance shows differential expression of inflammation and interferon (IFN) signaling. Relapsed tumors can be separated by upregulated or stable expression of IFNγ response genes. Upregulation of IFNγ response genes is associated with putative routes of resistance characterized by signatures of persistent IFN signaling, immune dysfunction, and mutations in antigen presentation genes which can be recapitulated in multiple murine models of acquired resistance to PD-(L)1 blockade after in vitro IFNγ treatment. Acquired resistance to PD-(L)1 blockade in NSCLC is associated with an ongoing, but altered IFN response. The persistently inflamed, rather than excluded or deserted, tumor microenvironment of acquired resistance may inform therapeutic strategies to effectively reprogram and reverse acquired resistance.
MeSH term(s)	Humans ; Animals ; Mice ; Carcinoma, Non-Small-Cell Lung/drug therapy ; Carcinoma, Non-Small-Cell Lung/genetics ; Lung Neoplasms/drug therapy ; Lung Neoplasms/genetics ; Signal Transduction ; Immunotherapy ; Antigen Presentation ; B7-H1 Antigen/metabolism ; Tumor Microenvironment
Chemical Substances	B7-H1 Antigen
Language	English
Publishing date	2024-01-11
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	2078448-X
ISSN	1878-3686 ; 1535-6108
ISSN (online)	1878-3686
ISSN	1535-6108
DOI	10.1016/j.ccell.2023.12.013
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