EBioMedicine最新文献

{"title":"Cilgavimab and tixagevimab as pre-exposure prophylaxis in vaccine non-responder kidney transplant recipients during a period of prevalent SARS-CoV-2 BA.2 and BA.4/5 variants-a prospective cohort study (RESCUE-TX).","authors":"Roman Reindl-Schwaighofer, Andreas Heinzel, Lukas Raab, Robert Strassl, Carsten T Herz, Florina Regele, Konstantin Doberer, Oliver Helk, Paul Spechtl, Constantin Aschauer, Karin Hu, Rahel Jagoditsch, Bianca Reiskopf, Georg A Böhmig, Bernhard Benka, Benedikt Mahr, Karin Stiasny, Lukas Weseslindtner, Michael Kammer, Thomas Wekerle, Rainer Oberbauer","doi":"10.1016/j.ebiom.2024.105417","DOIUrl":"10.1016/j.ebiom.2024.105417","url":null,"abstract":"<p><strong>Background: </strong>The response to severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) vaccination is severely impaired in patients on maintenance immunosuppression after kidney transplantation.</p><p><strong>Methods: </strong>We conducted a prospective cohort study of 194 kidney transplant recipients (KTR) who exhibited no response to SARS-CoV-2 vaccinations (i.e., SARS-CoV-2 spike protein antibodies ≤264 U/mL) and had no prior documented infection. Patients received 300 mg of cilgavimab/tixagevimab as SARS-CoV-2 pre-exposure prophylaxis (PrEP) between March 4, 2022, and May 3, 2022 and were contrasted to a matched cohort of 186 KTRs also without immunization again defined as SARS-CoV-2 spike protein antibodies ≤264 U/mL and no documented prior infection. The primary outcome was the serum kinetics of cilgavimab/tixagevimab, the secondary endpoints were time to SARS-CoV-2 breakthrough infection, severity of disease and variant specific live viral in vitro neutralization tests of patient sera.</p><p><strong>Findings: </strong>Longitudinal serum level monitoring showed a half-life of 91 days for both antibodies (95% CI 86-95 days for cilgavimab and 85-96 days for tixagevimab) in KTRs. In vitro neutralization tests showed effectiveness against the BA.2 omicron subvariant but not BA.5. The cumulative incidence of SARS-CoV-2 infections until May 15, 2022, (BA.2 dominance) was 15/194 vs 36/186 in the PrEP and control group respectively (OR = 0.35, 95% CI 0.18-0.66) but was not different thereafter (BA.4/5 dominance). The number of severe infections during the BA.2 period was lower in the prophylaxis than in the control group (OR = 0.37, 95% CI 0.17-0.79).</p><p><strong>Interpretation: </strong>This study showed that SARS-CoV-2 PrEP with cilgavimab/tixagevimab demonstrated clinical effectiveness against variants that are neutralised (BA.2) but not against BA.4/5.</p><p><strong>Funding: </strong>This study was funded by the Medical University of Vienna and an unrestricted grant from AstraZeneca (ESR-21-21585).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"109 ","pages":"105417"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11539723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497077","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Detection and staging of Alzheimer's disease by plasma pTau217 on a high throughput immunoassay platform.","authors":"Azadeh Feizpour, James David Doecke, Vincent Doré, Natasha Krishnadas, Kun Huang, Pierrick Bourgeat, Simon Matthew Laws, Christopher Fowler, Joanne Robertson, Lucy Mackintosh, Scott Ayton, Ralph Martins, Stephanie Ruth Rainey-Smith, Kevin Taddei, Larry Ward, Eddie Stage, Anthony Wilson Bannon, Colin Louis Masters, Jurgen Fripp, Victor Luis Villemagne, Christopher Cleon Rowe","doi":"10.1016/j.ebiom.2024.105405","DOIUrl":"10.1016/j.ebiom.2024.105405","url":null,"abstract":"<p><strong>Background: </strong>Plasma phospho-tau 217 (pTau217) assays can accurately detect Alzheimer's disease (AD) pathology, but clinical application is limited by the need for specialised equipment. This study tests the performance of a plasma pTau217 assay performed on the Lumipulse-G® platform, that is in widespread clinical use, for selecting patients for therapy based on β-amyloid (Aβ) status and tau staging.</p><p><strong>Methods: </strong>Participants included 388 individuals with ¹⁸F-NAV4694 Aβ-PET and ¹⁸F-MK6240 tau-PET. Association of pTau217 with PET was examined using Spearman's correlation. Discriminative performance for Aβ and tau PET status as well as tau staging was assessed using Receiver Operating Characteristic analysis.</p><p><strong>Findings: </strong>Plasma pTau217 had a high correlation with both Aβ Centiloid (r = 0.76) and tau SUVR_{meta-temporal} (r = 0.78). Area under curve (AUC) was 0.93 for Aβ- vs Aβ+ and 0.94 for tau- vs tau+. Applying one threshold (Youden's index), pTau217 was 87% accurate in classification of participants to Aβ- vs Aβ+. Applying two thresholds to classify participants into Low, Indeterminate, and High zones, 17.8% had Indeterminate results and among Low/High zone participants, 92% were correctly classified as Aβ- or Aβ+. The assay accurately discriminated moderate/high neocortical tau from no tau or tau limited to mesial-temporal lobe (AUC 0.97) and high neocortical tau from all others (AUC 0.94).</p><p><strong>Interpretation: </strong>Plasma pTau217, measured by the widely-available, fully-automated Lumipulse®, was a strong predictor of both Aβ and tau PET status and demonstrated strong predictive power in identifying individuals likely to benefit the most from anti-Aβ treatments.</p><p><strong>Funding: </strong>NHMRC grants 1132604, 1140853, 1152623 and AbbVie.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"109 ","pages":"105405"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11536028/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142497078","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Loss of heterozygosity exploited for collateral lethality-based cancer therapy.","authors":"Hai Fang","doi":"10.1016/j.ebiom.2024.105388","DOIUrl":"10.1016/j.ebiom.2024.105388","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"109 ","pages":"105388"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11490889/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388826","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intermittent preventive treatment for malaria in pregnancy and infant growth: a mediation analysis of a randomised trial.","authors":"Yanwei Tong, Kalani Ratnasiri, Suhi Hanif, Anna T Nguyen, Michelle E Roh, Grant Dorsey, Abel Kakuru, Prasanna Jagannathan, Jade Benjamin-Chung","doi":"10.1016/j.ebiom.2024.105397","DOIUrl":"10.1016/j.ebiom.2024.105397","url":null,"abstract":"<p><strong>Background: </strong>Intermittent preventive treatment for malaria in pregnancy (IPTp) can improve birth outcomes, but whether it confers benefits to postnatal growth is unclear. We investigated the effect of IPTp on infant growth in Uganda and its pathways of effects using causal mediation analyses.</p><p><strong>Methods: </strong>We analysed data from 633 infants born to mothers enrolled in a randomised trial of monthly IPTp with dihydroartemisinin-piperaquine (DP) vs. sulfadoxine-pyrimethamine (SP) (NCT02793622). Weight and length were measured from 0 to 12 months of age. Using generalised linear models, we estimated effects of DP vs. SP on gravidity-stratified mean length-for-age (LAZ) and weight-for-length Z-scores (WLZ). We investigated mediation by placental malaria, gestational weight change, maternal anaemia, maternal inflammation-related proteins, preterm birth, birth length, and birth weight. Mediation models adjusted for infant sex, gravidity, gestational age at enrolment, maternal age, maternal parasitaemia at enrolment, education, and wealth.</p><p><strong>Findings: </strong>SP increased mean LAZ by 0.18-0.28 Z from birth through age 4 months compared to DP, while DP increased mean WLZ by 0.11-0.28 Z from 2 to 8 months compared to SP among infants of multigravidae; at these ages, confidence intervals for mean differences excluded 0. We did not observe differences among primigravida. Mediators of SP included birth weight, birth length, maternal stem cell factor, and DNER. Mediators of DP included placental malaria and birth length, maternal IL-18, CDCP1, and CD6 at delivery.</p><p><strong>Interpretation: </strong>In high malaria transmission settings, this exploratory study suggests different IPTp regimens may influence infant growth among multigravidae, potentially through distinct pathways, in the exclusive breastfeeding period, when few other interventions are available.</p><p><strong>Funding: </strong>Stanford Center for Innovation in Global Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development, Bill & Melinda Gates Foundation.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"109 ","pages":"105397"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11530852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460714","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Induction of IGHV3-53 public antibodies with broadly neutralising activity against SARS-CoV-2 including Omicron subvariants in a Delta breakthrough infection case.","authors":"Takeo Kuwata, Yu Kaku, Shashwata Biswas, Kaho Matsumoto, Mikiko Shimizu, Yoko Kawanami, Ryuta Uraki, Kyo Okazaki, Rumi Minami, Yoji Nagasaki, Mami Nagashima, Isao Yoshida, Kenji Sadamasu, Kazuhisa Yoshimura, Mutsumi Ito, Maki Kiso, Seiya Yamayoshi, Masaki Imai, Terumasa Ikeda, Kei Sato, Mako Toyoda, Takamasa Ueno, Takako Inoue, Yasuhito Tanaka, Kanako Tarakado Kimura, Takao Hashiguchi, Yukihiko Sugita, Takeshi Noda, Hiroshi Morioka, Yoshihiro Kawaoka, Shuzo Matsushita","doi":"10.1016/j.ebiom.2024.105439","DOIUrl":"10.1016/j.ebiom.2024.105439","url":null,"abstract":"<p><strong>Background: </strong>Emergence of SARS-CoV-2 variants that escape neutralising antibodies hampers the development of vaccines and therapeutic antibodies against SARS-CoV-2. IGHV3-53/3-66-derived public antibodies, which are generally specific to the prototype virus and are frequently induced in infected or vaccinated individuals, show minimal affinity maturation and high potency against prototype SARS-CoV-2.</p><p><strong>Methods: </strong>Monoclonal antibodies isolated from a Delta breakthrough infection case were analysed for cross-neutralising activities against SARS-CoV-2 variants. The broadly neutralising antibody K4-66 was further analysed in a hamster model, and the effect of somatic hypermutations was assessed using the inferred germline precursor.</p><p><strong>Findings: </strong>Antibodies derived from IGHV3-53/3-66 showed broader neutralising activity than antibodies derived from IGHV1-69 and other IGHV genes. IGHV3-53/3-66 antibodies neutralised the Delta variant better than the IGHV1-69 antibodies, suggesting that the IGHV3-53/3-66 antibodies were further maturated by Delta breakthrough infection. One IGHV3-53/3-66 antibody, K4-66, neutralised all Omicron subvariants tested, including EG.5.1, BA.2.86, and JN.1, and decreased the viral load in the lungs of hamsters infected with Omicron subvariant XBB.1.5. The importance of somatic hypermutations was demonstrated by the loss of neutralising activity of the inferred germline precursor of K4-66 against Beta and Omicron variants.</p><p><strong>Interpretation: </strong>Broadly neutralising IGHV3-53/3-66 antibodies have potential as a target for the development of effective vaccines and therapeutic antibodies against newly emerging SARS-CoV-2 variants.</p><p><strong>Funding: </strong>This work was supported by grants from AMED (JP23ym0126048, JP22ym0126048, JP21ym0126048, JP23wm0125002, JP233fa627001, JP223fa627009, JP24jf0126002, and JP22fk0108572), and the JSPS (JP21H02970, JK23K20041, and JPJSCCA20240006).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"110 ","pages":"105439"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11565539/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142563978","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correlation between evoked neurotransmitter release and adaptive functions in SYT1-associated neurodevelopmental disorder.","authors":"Paul Yangho Park, Lauren Elizabeth Bleakley, Nadia Saraya, Reem Al-Jawahiri, Josefine Eck, Marc Anthony Aloi, Holly Melland, Kate Baker, Sarah Louise Gordon","doi":"10.1016/j.ebiom.2024.105416","DOIUrl":"10.1016/j.ebiom.2024.105416","url":null,"abstract":"<p><strong>Background: </strong>Pathogenic missense variants in the essential synaptic vesicle protein synaptotagmin-1 (SYT1) cause a neurodevelopmental disorder characterised by motor delay and intellectual disability, hyperkinetic movement disorder, episodic agitation, and visual impairments. SYT1 is the presynaptic calcium sensor that triggers synchronous neurotransmitter release. We have previously shown that pathogenic variants around the calcium-sensing region of the critical C2B domain decrease synaptic vesicle exocytosis in neurons.</p><p><strong>Methods: </strong>Here, we have used cultured hippocampal neurons transfected with SYT1-pHluorin to examine how variants within the C2A and C2B domain of SYT1 impact evoked exocytosis.</p><p><strong>Findings: </strong>We show that recently identified variants within the facilitatory C2A domain of the protein (L159R, T196K, E209K, E219Q), as well as additional variants in the C2B domain (M303V, S309P, Y365C, G369D), share an underlying pathogenic mechanism, causing a graded and variant-dependent dominant-negative impairment in exocytosis. We establish that the extent of evoked exocytosis observed in vitro in the presence of SYT1 variants correlates with neurodevelopmental impacts of this disorder. Specifically, the severity of motor and communication impairments exhibited by individuals harbouring these variants correlates with multiple measures of exocytic efficiency.</p><p><strong>Interpretation: </strong>Together, this suggests that there is a genotype-function-phenotype relationship in SYT1-associated neurodevelopmental disorder, centring impaired evoked neurotransmitter release as a common pathogenic driver. Moreover, this points toward a direct link between control of neurotransmitter release and development of adaptive functions, providing a tractable target for therapeutic amelioration.</p><p><strong>Funding: </strong>Australian National Health and Medical Research Council, UK Medical Research Council, Great Ormond Street Hospital Children's Charity, University of Melbourne.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"109 ","pages":"105416"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11564929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142557420","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A decade of discovery: bridging science and clinical practice in biomedical research.","authors":"eBioMedicine","doi":"10.1016/j.ebiom.2024.105469","DOIUrl":"https://doi.org/10.1016/j.ebiom.2024.105469","url":null,"abstract":"","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"109 ","pages":"105469"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142638434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Predictive genomic and transcriptomic analysis on endoscopic ultrasound-guided fine needle aspiration materials from primary pancreatic adenocarcinoma: a prospective multicentre study.","authors":"Rémy Nicolle, Cindy Canivet, Laurent Palazzo, Bertrand Napoléon, Mira Ayadi, Camille Pignolet, Jérôme Cros, Sophie Gourgou, Janick Selves, Jérôme Torrisani, Nelson Dusetti, Pierre Cordelier, Louis Buscail, Barbara Bournet","doi":"10.1016/j.ebiom.2024.105373","DOIUrl":"10.1016/j.ebiom.2024.105373","url":null,"abstract":"<p><strong>Background: </strong>We apply endoscopic ultrasound-guided fine needle aspiration biopsy to cytopathologically diagnose and sample nucleic acids from primary tumours regardless of the disease stage.</p><p><strong>Methods: </strong>397 patients with proven pancreatic adenocarcinoma were included and followed up in a multicentre prospective study. DNA and mRNA were extracted from materials of primary tumours obtained by endoscopic ultrasound-guided fine needle aspiration biopsy and analysed using targeted deep sequencing and RNAseq respectively.</p><p><strong>Findings: </strong>The variant allele frequency of the KRAS mutation was used to evaluate the tumour cellularity, ranging from 15 to 20% in all cells, regardless of the tumour stage. The molecular profile of metastatic primary tumours significantly differed from other types of tumours, more frequently having TP53 mutations (p = 0.0002), less frequently having RNF43 mutations, and possessing more basal-like mRNA component (p = 0.001). Molecular markers associated with improved overall survival were: mutations in homologous recombination deficiency genes in patients who received first-line platinum-based chemotherapy (p = 0.025) and wild-type TP53 gene in patients with locally advanced tumours who received radio-chemotherapy (p = 0.01). The GemPred transcriptomic profile was associated with a significantly better overall survival in patients with locally advanced or metastatic pancreatic cancer who received a gemcitabine-based first-line treatment (p = 0.019).</p><p><strong>Interpretation: </strong>The combination of genomic and transcriptomic analyses of primary pancreatic tumours enables us to distinguish metastatic tumours from other tumour types. Our molecular strategy may assist in predicting overall survival outcomes for platinum or gemcitabine-based chemotherapies, as well as radio-chemotherapy.</p><p><strong>Funding: </strong>Institut National Du Cancer (BCB INCa_7294), CHU of Toulouse, Inserm and Ligue Nationale Contre le Cancer (CIT program).</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"109 ","pages":"105373"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11497430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142388828","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 antigen rapid detection tests: test performance during the COVID-19 pandemic and the impact of COVID-19 vaccination.","authors":"Isabell Wagenhäuser, Kerstin Knies, Tamara Pscheidl, Michael Eisenmann, Sven Flemming, Nils Petri, Miriam McDonogh, Agmal Scherzad, Daniel Zeller, Anja Gesierich, Anna Katharina Seitz, Regina Taurines, Ralf-Ingo Ernestus, Johannes Forster, Dirk Weismann, Benedikt Weißbrich, Johannes Liese, Christoph Härtel, Oliver Kurzai, Lars Dölken, Alexander Gabel, Manuel Krone","doi":"10.1016/j.ebiom.2024.105394","DOIUrl":"10.1016/j.ebiom.2024.105394","url":null,"abstract":"<p><strong>Background: </strong>SARS-CoV-2 antigen rapid detection tests (RDTs) emerged as point-of-care diagnostics alongside reverse transcription polymerase chain reaction (RT-qPCR) as reference.</p><p><strong>Methods: </strong>In a prospective performance assessment from 12 November 2020 to 30 June 2023 at a single centre tertiary care hospital, the sensitivity and specificity (primary endpoints) of RDTs from three manufacturers (NADAL®, Panbio™, MEDsan®) were compared to RT-qPCR as reference standard among patients, accompanying persons and staff aged ≥ six month in large-scale, clinical screening use. Regression models were used to assess influencing factors on RDT performance (secondary endpoints).</p><p><strong>Findings: </strong>Among 78,798 paired RDT/RT-qPCR results analysed, overall RDT sensitivity was 34.5% (695/2016; 95% CI 32.4-36.6%), specificity 99.6% (76,503/76,782; 95% CI 99.6-99.7%). Over the pandemic course, sensitivity decreased in line with a lower rate of individuals showing typical COVID-19 symptoms. The lasso regression model showed that a higher viral load and typical COVID-19 symptoms were directly significantly correlated with the likelihood of a positive RDT result in SARS-CoV-2 infection, whereas age, sex, vaccination status, and the Omicron VOC were not.</p><p><strong>Interpretation: </strong>The decline in RDT sensitivity throughout the pandemic can primarily be attributed to the reduced prevalence of symptomatic infections among vaccinated individuals and individuals infected with Omicron VOC. RDTs remain valuable for detecting SARS-CoV-2 in symptomatic individuals and offer potential for detecting other respiratory pathogens in the post-pandemic era, underscoring their importance in infection control efforts.</p><p><strong>Funding: </strong>German Federal Ministry of Education and Research (BMBF), Free State of Bavaria, Bavarian State Ministry of Health and Care.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"109 ","pages":"105394"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142399757","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Single-chain A35R-M1R-B6R trivalent mRNA vaccines protect mice against both mpox virus and vaccinia virus.","authors":"Tianxiang Kong, Pei Du, Renyi Ma, Han Wang, Xuehui Ma, Jian Lu, Zhengrong Gao, Hai Qi, Ruiqi Li, Hao Zhang, Fei Xia, Yuanlang Liu, Ruyu Wang, Kai Duan, Zejun Wang, Qihui Wang, George F Gao","doi":"10.1016/j.ebiom.2024.105392","DOIUrl":"10.1016/j.ebiom.2024.105392","url":null,"abstract":"<p><strong>Background: </strong>Mpox has spread to many countries around the world. While the existing live attenuated mpox vaccines are effective, advances in 21st century technologies now enable the development of vaccines with more specific antigens, clearer mechanisms, and more controllable side effects.</p><p><strong>Methods: </strong>We systematically evaluated the immunogenicity and protective efficacy of the A35R, M1R and B6R antigens of the mpox virus (MPXV). With these findings, we designed three single-chain trivalent mRNA vaccines (AMAB-wt, AMAB-C140S and AMB-C140S) by integrating the soluble regions of these antigens into single mRNA-encoded polypeptides based on their protein structures. Then, the immunogenicity and protective efficacy of these single-chain mRNA vaccines were evaluated in mice models against both VACV and MPXV.</p><p><strong>Findings: </strong>The three single-chain vaccines elicited neutralising antibodies that effectively neutralised both VACV and MPXV. The single-chain vaccines or cocktail vaccine containing mRNAs encoding soluble antigen (sA35R + sM1R + sB6R) exhibited 100% or 80% protection against a lethal dose of VACV challenge, while the cocktail of full-length antigens (A35 + M1 + B6) and the live attenuated vaccine, VACV Tian Tan (VACV-VTT), completely failed to protect mice. Moreover, the single-chain vaccines significantly reduced viral load in the lungs and ovaries of MPXV-challenged mice.</p><p><strong>Interpretation: </strong>Compared with the cocktail vaccines, our single-chain designs demonstrated similar or superior immunogenicity and protective efficacy. Importantly, the simplicity of the single-chain vaccines enhances both the controllability and accessibility of mpox vaccines. We believe these single-chain vaccines qualify as the next-generation mpox vaccines.</p><p><strong>Funding: </strong>National Natural Science Foundation of China and Youth Innovation Promotion Association of the CAS.</p>","PeriodicalId":11494,"journal":{"name":"EBioMedicine","volume":"109 ","pages":"105392"},"PeriodicalIF":9.7,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11513793/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460720","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}