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| Open AccessThe hinge-engineered IgG1-IgG3 hybrid subclass IgGh47 potently enhances Fc-mediated function of anti-streptococcal and SARS-CoV-2 antibodies
Here, the authors elongated the hinge structure of IgG1 monoclonal antibodies. The modified IgG1-IgG3 hybrid subclass showed enhanced Fc-mediated function compared to IgG1 in two distinct biological systems, Streptococcus pyogenes and SARS-CoV-2.
- Arman Izadi
- , Yasaman Karami
- & Pontus Nordenfelt
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Article
| Open AccessMucosal prime-boost immunization with live murine pneumonia virus-vectored SARS-CoV-2 vaccine is protective in macaques
Immunization via the respiratory route is predicted to increase the effectiveness of SARS-CoV-2 vaccines. Here, Kaiser et al. describe a murine pneumonia virus vectored vaccine expressing spike protein, and show that intranasal immunization of male rhesus macaques provides good mucosal and systemic immunogenicity and efficacy.
- Jaclyn A. Kaiser
- , Christine E. Nelson
- & Cyril Le Nouën
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Article
| Open AccessBat-borne H9N2 influenza virus evades MxA restriction and exhibits efficient replication and transmission in ferrets
In this study, the authors report that bat H9N2 influenza A virus replicates and transmits in ferrets, efficiently infects human lung explant cultures, evades MxA antiviral activity in mice, and has low antigenic similarity to seasonal N2, meeting pre-pandemic criteria.
- Nico Joel Halwe
- , Lea Hamberger
- & Martin Beer
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Article
| Open AccessLoss of TRIM29 mitigates viral myocarditis by attenuating PERK-driven ER stress response in male mice
Knowledge of pathogenesis mechanisms and effective treatments for viral myocarditis is lacking. Here, Wang et al show that loss of TRIM29 and PERK inhibitor mitigate viral myocarditis by attenuating PERK-driven ER stress and ROS responses in male mice.
- Junying Wang
- , Wenting Lu
- & Junji Xing
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Article
| Open AccessOverlapping Streptococcus pyogenes and Streptococcus dysgalactiae subspecies equisimilis household transmission and mobile genetic element exchange
Streptococcus dysgalactiae subsp. equisimilis is closely related to Streptococcus pyogenes and colonises the same sites in humans. This study examines cross-species transmission interactions and genetic exchange in a high disease burden setting.
- Ouli Xie
- , Cameron Zachreson
- & Steven Y. C. Tong
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Article
| Open AccessA giant virus infecting the amoeboflagellate Naegleria
This is the first report on a virus infecting the amoeboflagellate Naegleria, including the lethal human pathogen N. fowleri. The new virus isolate, Catovirus naegleriensis (Naegleriavirus, NiV), shows hallmarks of giant viruses (Nucleocytoviricota) and unique adaptations to its protist host.
- Patrick Arthofer
- , Florian Panhölzl
- & Matthias Horn
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| Open AccessLong-term monitoring of SARS-CoV-2 seroprevalence and variants in Ethiopia provides prediction for immunity and cross-immunity
Detailed data on SARS-CoV-2 dynamics in Africa remain limited. Here, the authors use longitudinal serology and SARS-CoV-2 sequencing data from Ethiopia between August 2020 and July 2022 to characterise circulating variants, identify infection pathways, and explore cross-immunity properties.
- Simon Merkt
- , Solomon Ali
- & Andreas Wieser
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Article
| Open AccessEstimating the effects of temperature on transmission of the human malaria parasite, Plasmodium falciparum
Malaria transmission is affected by temperature but this relationship is not well characterised. Here, the authors experimentally determine the effect of temperature on parasite development in the mosquito and model how it impacts malaria transmission in Kenya under current and future climate scenarios.
- Eunho Suh
- , Isaac J. Stopard
- & Matthew B. Thomas
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Article
| Open AccessMulti-omics analysis reveals COVID-19 vaccine induced attenuation of inflammatory responses during breakthrough disease
Here, Drury et al study gene, microRNA and protein expression during COVID-19, in a randomised controlled trial of ChAdOx1 nCoV19 vaccine and find that ChAdOx1 nCoV-19 attenuates the inflammatory response, thought to be the basis for severe COVID-19.
- Ruth E. Drury
- , Susana Camara
- & Daniel O’Connor
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Article
| Open AccessMonkeypox virus genomic accordion strategies
The 2023 monkeypox outbreak was caused by a subclade IIb monkeypox virus (MPXV). Here, using advanced sequencing techniques, the authors identify variations on low-complexity regions of the MPXV genome and describe their potential as evolutionary drivers.
- Sara Monzón
- , Sarai Varona
- & Gustavo Palacios
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| Open AccessInflammation and cytomegalovirus viremia during pregnancy drive sex-differentiated differences in mortality and immune development in HIV-exposed infants
HIV exposed but uninfected infants may face an increased risk of serious infection and mortality. In this work, the authors utilise a cohort from rural Zimbabwe to explore the biological mechanisms underlying infant mortality.
- Ceri Evans
- , Kuda Mutasa
- & Andrew J. Prendergast
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Article
| Open AccessImprovement of immune dysregulation in individuals with long COVID at 24-months following SARS-CoV-2 infection
Post-acute sequelae of COVID (PASC) or long-COVID can affect a proportion of those infected but this is not well understood. Here the authors perform a single cell transcriptomics analysis of immune cells from long-COVID patients at 24 months and find that cell changes observed at 3 and 8 months do not persist to 24 months.
- Chansavath Phetsouphanh
- , Brendan Jacka
- & Gail V. Matthews
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Article
| Open AccessEmerging variants develop total escape from potent monoclonal antibodies induced by BA.4/5 infection
Many emerging SARS-CoV-2 variants partially escape the humoral immune response. Here, Liu et al. characterize 28 antibodies from BA.4/5 breakthrough infections and find attrition of neutralization and complete loss of function for variants with Spike mutations at positions 455 and 456.
- Chang Liu
- , Raksha Das
- & Gavin R. Screaton
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| Open AccessUltrasensitive single-step CRISPR detection of monkeypox virus in minutes with a vest-pocket diagnostic device
The recent monkeypox outbreak highlighted the need for rapid and accurate diagnosis of this disease. Here, authors develop an ultrasensitive and streamlined CRISPR assay using miniaturized device, which can detect monkeypox virus in rash fluid swab, oral swab, saliva, and urine within 15 minutes.
- Yunxiang Wang
- , Hong Chen
- & Shengqi Wang
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Article
| Open AccessPerinatal outcomes after admission with COVID-19 in pregnancy: a UK national cohort study
The impacts of maternal SARS-CoV-2 infection on newborns are not well understood. Here, the authors perform a national cohort study using data on births in the UK from March 2020—March 2022 and find that moderate to severe maternal COVID-19 was associated with adverse perinatal outcomes.
- Hilde Marie Engjom
- , Rema Ramakrishnan
- & Marian Knight
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Article
| Open AccessPositive selection underlies repeated knockout of ORF8 in SARS-CoV-2 evolution
SARS-CoV-2 constantly evolves but the roles of resulting mutations are not always clear. In this study, the authors report that ORF8 knockout confers a fitness advantage to SARS-CoV-2 using genomic surveillance data, highlighting how different types of adaptations across the SARS-CoV-2 genome can drive variant fitness.
- Cassia Wagner
- , Kathryn E. Kistler
- & Trevor Bedford
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Article
| Open AccessInfluenza antibody breadth and effector functions are immune correlates from acquisition of pandemic infection of children
In this study, the authors assessed influenza-specific antibody responses in a cohort of seasonally vaccinated children and report that seasonal vaccination is beneficial by enhancing pandemic influenza virus-specific antibodies and cross-reactive effector functions.
- Janice Z. Jia
- , Carolyn A. Cohen
- & Sophie A. Valkenburg
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Article
| Open AccessDeep learning predictions of TCR-epitope interactions reveal epitope-specific chains in dual alpha T cells
Prediction of the specificity of a T cell receptor from amino acid sequence has been performed using different methods and approaches. Here the authors use TCRab sequences with known specificity to develop a deep learning TCR-epitope interaction predictor and use this method to predict specificity of dual alpha chain TCRs and TCRs specific for different antigens.
- Giancarlo Croce
- , Sara Bobisse
- & David Gfeller
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Article
| Open AccessEpidemiological, clinical, and genomic landscape of coccidioidomycosis in northeastern Brazil
Coccidioidomycosis, a WHO-listed mycosis, is neglected in South America. Analysis of 292 cases in Brazil, often tied to armadillo hunting, unveils unique disease patterns, environmental factors and pathogen genetics causing the disease.
- Kelsen Dantas Eulálio
- , Daniel R. Kollath
- & Marcus de Melo Teixeira
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Article
| Open AccessCoPoP liposomes displaying stabilized clade C HIV-1 Env elicit tier 2 multiclade neutralization in rabbits
HIV vaccine candidates often have limited capacity to induce broadly neutralizing antibodies (nAbs). In this study, the authors show that stabilized Clade C HIV-1 Env protein trimers decorated on CoPoP liposomes induce nAbs against 18 of 20 multiclade tier 2 HIV-1 strains in immunized rabbits.
- Annemart Koornneef
- , Kanika Vanshylla
- & Frank Wegmann
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Article
| Open AccessImmunoglobulin G N-glycan markers of accelerated biological aging during chronic HIV infection
In this study, Giron et al. find that people living with chronic HIV experience accelerated aging-associated alterations in antibody glycans. These alterations, attributed to senescence enzymes, predict comorbidities and reduce the antiviral function of antibodies.
- Leila B. Giron
- , Qin Liu
- & Mohamed Abdel-Mohsen
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Article
| Open AccessThe genomic evolutionary dynamics and global circulation patterns of respiratory syncytial virus
This study on respiratory syncytial virus (RSV) reveals global genomic gaps. Using INFORM-RSV data, it uncovers selection’s impact on RSVA and RSVB diversity. Analysing full genomes, it highlights non-neutral epidemic processes. The research emphasises air travel’s influence on global spread, underscoring the need for comprehensive RSV genomic surveillance.
- Annefleur C. Langedijk
- , Bram Vrancken
- & Shabir A. Madhi
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| Open AccessThe recent rapid expansion of multidrug resistant Ural lineage Mycobacterium tuberculosis in Moldova
Chitwood et al. report on the rapid expansion of a Ural-lineage multidrug resistant strain of Mycobacterium tuberculosis in Moldova. This strain has an estimated reproduction number more than two times greater than otherwise similar drug susceptible strains.
- Melanie H. Chitwood
- , Caroline Colijn
- & Benjamin Sobkowiak
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Article
| Open AccessBat species assemblage predicts coronavirus prevalence
Human encroachment into nature alters species communities and can lead to changes in disease dynamics. Here, Meyer et al. find that coronavirus prevalence increased in less diverse bat communities, which were dominated by susceptible host species.
- Magdalena Meyer
- , Dominik W. Melville
- & Simone Sommer
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Article
| Open AccessMonoclonal antibodies targeting sites in respiratory syncytial virus attachment G protein provide protection against RSV-A and RSV-B in mice
Effective antibodies targeting various respiratory syncytial virus (RSV) proteins are needed to address public health burden of RSV. Here the authors shows that in addition to the currently approved F-targeting monoclonal antibodies, anti-G cross-reactive monoclonal antibodies to RSV-A and RSV-B strains can provide cross-protection and prevent from RSV disease.
- Youri Lee
- , Laura Klenow
- & Surender Khurana
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Article
| Open AccessEarly detection of emerging viral variants through analysis of community structure of coordinated substitution networks
Rise of new viral strains is a major public health challenge, demanding advanced detection and forecasting methods. This study shows how examining communities within networks of viral mutations enables early detection of emerging strains.
- Fatemeh Mohebbi
- , Alex Zelikovsky
- & Pavel Skums
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Article
| Open AccessMaternal hybrid immunity and risk of infant COVID-19 hospitalizations: national case-control study in Israel
Maternal anti-SARS-CoV-2 antibodies can provide protection against severe COVID-19 in infants, but the relative protection conferred by maternal infection, vaccination, and hybrid immunity is unknown. Here, the authors use data from Israel and show that infants born to mothers with hybrid immunity had lowest rates of COVID-19 hospitalisation.
- Joshua Guedalia
- , Michal Lipschuetz
- & Ofer Beharier
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Article
| Open AccessIncident allergic diseases in post-COVID-19 condition: multinational cohort studies from South Korea, Japan and the UK
SARS-CoV-2 infection has been linked to various persistent or new-onset health consequences, including disruption of the immune system. Here, the authors investigate the risk of new-onset allergic diseases following SARS-CoV-2 infection using data from South Korea, Japan, and the UK.
- Jiyeon Oh
- , Myeongcheol Lee
- & Dong Keon Yon
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Article
| Open AccessClinically used broad-spectrum antibiotics compromise inflammatory monocyte-dependent antibacterial defense in the lung
Authors utilise a murine model of infection to provide mechanistic insight into how antimicrobial therapy may be a predisposing risk factor for hospital-acquired pneumonia. They show that antibiotic-induced microbiota perturbations compromise inflammatory monocytes and thereby impair antibacterial defence.
- Patrick J. Dörner
- , Harithaa Anandakumar
- & Bastian Opitz
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Article
| Open AccessGasdermin D promotes influenza virus-induced mortality through neutrophil amplification of inflammation
Gasdermin D (GSDMD) is a pore forming protein activated by inflammasome derived caspases. Here the authors characterize the function of GSDMD in mouse influenza virus infection and show that immunopathology is reduced in the absence of GSDMD and involves changes in neutrophil function.
- Samuel Speaks
- , Matthew I. McFadden
- & Jacob S. Yount
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Article
| Open AccessThe SARS-CoV-2 neutralizing antibody response to SD1 and its evasion by BA.2.86
Due to the focus of vaccination on the SARS CoV-2 spike protein, spike has been associated with high levels of viral mutation and subsequent immune escape. Here the authors study a conserved epitope in SARS CoV-2 sub-domain-1 and characterise the neutralising antibody response and evasion in contemporary SARS COV-2 viral strains.
- Daming Zhou
- , Piyada Supasa
- & Gavin R. Screaton
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Article
| Open AccessAutophagy-enhancing ATG16L1 polymorphism is associated with improved clinical outcome and T-cell immunity in chronic HIV-1 infection
T cell dysregulation is a hallmark of chronic HIV-1 infection that is partially restored by antiretroviral therapy. Here the authors show that ATG16L1 rs6861 polymorphism is associated clinically with prolonged control of disease pathogenesis, and functionally with enhanced autophagy and T-cell immunity in chronically HIV-1 infected individuals.
- Renée R. C. E. Schreurs
- , Athanasios Koulis
- & Carla M. S. Ribeiro
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Article
| Open AccessiNOS is necessary for GBP-mediated T. gondii clearance in murine macrophages via vacuole nitration and intravacuolar network collapse
IFNγ-inducible guanylate binding proteins (GBPs) recognize the Toxoplasma gondii vacuole during infection. Here, the authors report that inducible nitric oxide synthase (iNOS) is necessary for efficient parasite clearance by GBPs and that reactive nitrogen species produced by iNOS lead to nitration of the parasite vacuole and collapse of the intravacuolar network space, preventing parasite escape from GBP targeting.
- Xiao-Yu Zhao
- , Samantha L. Lempke
- & Sarah E. Ewald
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Perspective
| Open AccessEcological countermeasures to prevent pathogen spillover and subsequent pandemics
In this Perspective, the authors discuss the importance of preventing zoonotic spillover to prevent pandemics. They highlight mechanisms by which environmental changes can enable spillover, identify ecological interventions for spillover prevention and suggest policy frameworks through which interventions can be implemented.
- Raina K. Plowright
- , Aliyu N. Ahmed
- & Annika T. H. Keeley
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Article
| Open AccessPrior infection with unrelated neurotropic virus exacerbates influenza disease and impairs lung T cell responses
Co-infections are much less studied than single pathogen infections. Here, the authors show that co-infection with two unrelated viruses, neurotropic Semliki Forest virus and influenza A virus, exacerbates influenza-related lung pathology and prolongs lung virus replication in a mouse model.
- Isabelle Jia-Hui Foo
- , Brendon Y. Chua
- & Lukasz Kedzierski
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Article
| Open AccessPredictive evolutionary modelling for influenza virus by site-based dynamics of mutations
Seasonal influenza vaccine effectiveness depends on including virus strains in the vaccine that closely match those circulating in the upcoming season. In this study, the authors develop a computational model of influenza virus evolution to predict future circulating strains and therefore support vaccine strain selection.
- Jingzhi Lou
- , Weiwen Liang
- & Maggie Haitian Wang
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Article
| Open AccessImmunization with V987H-stabilized Spike glycoprotein protects K18-hACE2 mice and golden Syrian hamsters upon SARS-CoV-2 infection
In this study, the authors report a mutation that increases the production of recombinant SARS-CoV-2 Spike and exposure of the RBD. In animal models, a Spike-based vaccine containing the mutation induces strong immunogenicity, provides protection from disease and results in faster tissue viral clearance.
- Carlos Ávila-Nieto
- , Júlia Vergara-Alert
- & Jorge Carrillo
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Article
| Open AccessStrong positive selection biases identity-by-descent-based inferences of recent demography and population structure in Plasmodium falciparum
Identity-by-descent (IBD) is used to infer malaria parasite population demography, but positive selection imposed by drug pressure can bias IBD estimates. This study shows that strong selection distorts IBD distributions impacting downstream inferences and presents an approach to correct these biases.
- Bing Guo
- , Victor Borda
- & Shannon Takala-Harrison
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Article
| Open AccessLong-term effects of Omicron BA.2 breakthrough infection on immunity-metabolism balance: a 6-month prospective study
Here the authors study recovery from mild to moderate Omicron breakthrough infection at six months post infection. Serum proteomics, PBMC single-cell transcriptomics and clinical parameters indicate slow recovery with coagulation abnormalities and an imbalance of the immune response and metabolism remaining.
- Yanhua Li
- , Shijie Qin
- & George Fu Gao
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Article
| Open AccessTargeted metagenomics reveals association between severity and pathogen co-detection in infants with respiratory syncytial virus
The impact of other pathogens on disease outcome was studied in European infants with RSV infection. Additional viruses were commonly co-detected during infection but were weakly linked to severity. However, presence of Haemophilus bacteria strongly associated with severe cases.
- Gu-Lung Lin
- , Simon B. Drysdale
- & Andrew J. Pollard
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Article
| Open AccessGenomic malaria surveillance of antenatal care users detects reduced transmission following elimination interventions in Mozambique
Routine sampling of pregnant women at first antenatal care (ANC) visits could be used for malaria surveillance. Here, the authors compare the genetic structure of Plasmodium falciparum parasite populations between samples from first ANC users and children from the community in Mozambique, and show that it can inform about changes in transmission beyond epidemiological data.
- Nanna Brokhattingen
- , Glória Matambisso
- & Alfredo Mayor
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Article
| Open AccessBeyond the microcirculation: sequestration of infected red blood cells and reduced flow in large draining veins in experimental cerebral malaria
Cerebral malaria can lead to fatal brain swelling. Oelschlegel et al. find infected red blood cells and reduced flow in large draining cerebral veins in mouse model of cerebral malaria, suggesting that impaired venous efflux could cause the swelling.
- A. M. Oelschlegel
- , R. Bhattacharjee
- & G. Nishanth
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Article
| Open AccessClearance of persistent SARS-CoV-2 associates with increased neutralizing antibodies in advanced HIV disease post-ART initiation
There is limited data on immune factors contributing to SARS-CoV-2 viral clearance in people living with HIV. Here, the authors show that re-emergence of the neutralizing antibody response may be key to clearing persistent SARS-CoV-2 infection in ART-mediated recovery from immunosuppression in advanced HIV disease.
- Farina Karim
- , Catherine Riou
- & Alex Sigal
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Article
| Open AccessFilamentous fungus-produced human monoclonal antibody provides protection against SARS-CoV-2 in hamster and non-human primate models
The filamentous fungus expression system Thermothelomyces heterothallica (C1) is a protein expression system that may be useful for large scale antibody production. Here the authors characterise the production of a human monoclonal antibody that neutralises SARS-CoV-2 and compare functional properties in vitro and in animal models to antibodies produced using other methods.
- Franziska K. Kaiser
- , Mariana Gonzalez Hernandez
- & Albert D.M.E. Osterhaus
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Article
| Open AccessThe decline of the 2022 Italian mpox epidemic: Role of behavior changes and control strategies
Mpox cases in Italy rapidly declined following a peak in summer 2022. Here, the authors investigate potential reasons for the decline in cases using an individual-based model of a sexual contact network of men who have sex with men.
- Giorgio Guzzetta
- , Valentina Marziano
- & Stefano Merler
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Article
| Open AccessBacteriophage DNA induces an interrupted immune response during phage therapy in a chicken model
Bacteriophage are potential therapeutics to target bacterial infections, but recent studies suggest that bacteriophage may induce immune responses in eukaryotic cells. Here the authors show that bacteriophage DNA induces interrupted host immunity in a chicken infection model.
- Magdalena Podlacha
- , Lidia Gaffke
- & Alicja Węgrzyn
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Article
| Open AccessTheileria parasites sequester host eIF5A to escape elimination by host-mediated autophagy
Theileria parasites have evolved mechanisms to evade host cell defenses. Here, Villares et al use an anti-parasite drug to show how intracellular parasites sequester host eIF5A to escape elimination by autophagy pathways.
- Marie Villares
- , Nelly Lourenço
- & Jonathan B. Weitzman
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Article
| Open AccessQuantifying how single dose Ad26.COV2.S vaccine efficacy depends on Spike sequence features
SARS-CoV-2 variants with mutations in spike have emerged during the pandemic. Magaret et al. show that in Latin America, efficacy of the Ad26.COV2.S vaccine against moderate to severe–critical COVID-19 varied by sequence features, antibody escape scores, and neutralization impacting features of the SARS-CoV-2 variant.
- Craig A. Magaret
- , Li Li
- & Peter B. Gilbert
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Article
| Open AccessUnderstanding the infection severity and epidemiological characteristics of mpox in the UK
Mpox cases without known travel links to endemic countries began to be detected in the UK in mid-2022. In this study, the authors characterise the severity of mpox cases in the UK and estimate the overall infection hospitalisation risk at ~4%.
- Thomas Ward
- , Christopher E. Overton
- & Martyn Fyles