Pub Date : 2026-02-11DOI: 10.1038/s41591-026-04224-w
{"title":"Extracorporeal cross-circulation with genetically modified pig livers in a human decedent model.","authors":"","doi":"10.1038/s41591-026-04224-w","DOIUrl":"https://doi.org/10.1038/s41591-026-04224-w","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165346","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}
Pub Date : 2026-02-11DOI: 10.1038/s41591-026-04216-w
Capillary blood sampling for the Alzheimer’s disease biomarkers p-tau217, NfL and GFAP correlates with venous measures for the same biomarkers. As capillary p-tau217 accurately classified amyloid burden, it might support remote assessment in large-scale epidemiology to estimate the prevalence of Alzheimer’s disease and enable triage into clinical services and trials.
{"title":"Capillary blood sampling for detecting biomarkers of Alzheimer’s disease","authors":"","doi":"10.1038/s41591-026-04216-w","DOIUrl":"10.1038/s41591-026-04216-w","url":null,"abstract":"Capillary blood sampling for the Alzheimer’s disease biomarkers p-tau217, NfL and GFAP correlates with venous measures for the same biomarkers. As capillary p-tau217 accurately classified amyloid burden, it might support remote assessment in large-scale epidemiology to estimate the prevalence of Alzheimer’s disease and enable triage into clinical services and trials.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"32 2","pages":"429-430"},"PeriodicalIF":50.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165278","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}
Pub Date : 2026-02-11DOI: 10.1038/s41591-025-04178-5
Dian Zeng, Lorainne Tudor Car, Kamlesh Khunti, Yuanli Liu, Till Bärnighausen, Niels H Chavannes, Pearse A Keane, Holger Kunz, Lan Xue, Joseph J Y Sung, Yih Chung Tham, Lorenzo Righetto, Rupa Sarker, Samuel Yeung Shan Wong, Donald Boudreau, Qionghai Dai, Weiping Jia, Yang Liu, Dinggang Shen, Jia Liu, Weixing Shen, John S Ji, Zhong Wang, Zhiyi Wang, Haibo Wang, Shenglan Tang, Chenyang Pei, Zehua Jiang, Zihao Zou, Yiming Qin, Huating Li, Yasha Wang, Dinesh Visva Gunasekeran, Sabrina Wong, Dong Xu, Ryan Urbanowicz, Liliana Laranjo, Ana Luisa Neves, Nan Liu, Yulan He, Phuoc Van Le, Neil Bressler, Rifat Atun, David C Klonoff, Bin Sheng, Nigam Shah, Josip Car, Tien Yin Wong
{"title":"PRIMARY-AI: outcomes-based standards to safeguard primary care in the AI era.","authors":"Dian Zeng, Lorainne Tudor Car, Kamlesh Khunti, Yuanli Liu, Till Bärnighausen, Niels H Chavannes, Pearse A Keane, Holger Kunz, Lan Xue, Joseph J Y Sung, Yih Chung Tham, Lorenzo Righetto, Rupa Sarker, Samuel Yeung Shan Wong, Donald Boudreau, Qionghai Dai, Weiping Jia, Yang Liu, Dinggang Shen, Jia Liu, Weixing Shen, John S Ji, Zhong Wang, Zhiyi Wang, Haibo Wang, Shenglan Tang, Chenyang Pei, Zehua Jiang, Zihao Zou, Yiming Qin, Huating Li, Yasha Wang, Dinesh Visva Gunasekeran, Sabrina Wong, Dong Xu, Ryan Urbanowicz, Liliana Laranjo, Ana Luisa Neves, Nan Liu, Yulan He, Phuoc Van Le, Neil Bressler, Rifat Atun, David C Klonoff, Bin Sheng, Nigam Shah, Josip Car, Tien Yin Wong","doi":"10.1038/s41591-025-04178-5","DOIUrl":"https://doi.org/10.1038/s41591-025-04178-5","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2026-02-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146165314","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}
Pub Date : 2026-02-10DOI: 10.1038/s41591-026-04261-5
Douglas A Simonetto, David Rushlow, Kan Liu, Alberto Calleri, Blake A Kassmeyer, Ryan J Lennon, Puru Rattan, Matthew E Bernard, Gagandeep Singh, Mark E Deyo-Svendsen, Graham King, Stephen K Stacey, Amy Olofson, Alina Allen, Joseph C Ahn, Paul A Friedman, Patrick S Kamath, Zachi I Attia, Peter A Noseworthy, Vijay H Shah
{"title":"Author Correction: Detection of undiagnosed liver cirrhosis via AI-enabled electrocardiogram: a pragmatic, cluster-randomized clinical trial.","authors":"Douglas A Simonetto, David Rushlow, Kan Liu, Alberto Calleri, Blake A Kassmeyer, Ryan J Lennon, Puru Rattan, Matthew E Bernard, Gagandeep Singh, Mark E Deyo-Svendsen, Graham King, Stephen K Stacey, Amy Olofson, Alina Allen, Joseph C Ahn, Paul A Friedman, Patrick S Kamath, Zachi I Attia, Peter A Noseworthy, Vijay H Shah","doi":"10.1038/s41591-026-04261-5","DOIUrl":"https://doi.org/10.1038/s41591-026-04261-5","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2026-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146157831","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}
Pub Date : 2026-02-09DOI: 10.1038/s41591-025-04074-y
Andrew M. Bean, Rebecca Elizabeth Payne, Guy Parsons, Hannah Rose Kirk, Juan Ciro, Rafael Mosquera-Gómez, Sara Hincapié M, Aruna S. Ekanayaka, Lionel Tarassenko, Luc Rocher, Adam Mahdi
Global healthcare providers are exploring the use of large language models (LLMs) to provide medical advice to the public. LLMs now achieve nearly perfect scores on medical licensing exams, but this does not necessarily translate to accurate performance in real-world settings. We tested whether LLMs can assist members of the public in identifying underlying conditions and choosing a course of action (disposition) in ten medical scenarios in a controlled study with 1,298 participants. Participants were randomly assigned to receive assistance from an LLM (GPT-4o, Llama 3, Command R+) or a source of their choice (control). Tested alone, LLMs complete the scenarios accurately, correctly identifying conditions in 94.9% of cases and disposition in 56.3% on average. However, participants using the same LLMs identified relevant conditions in fewer than 34.5% of cases and disposition in fewer than 44.2%, both no better than the control group. We identify user interactions as a challenge to the deployment of LLMs for medical advice. Standard benchmarks for medical knowledge and simulated patient interactions do not predict the failures we find with human participants. Moving forward, we recommend systematic human user testing to evaluate interactive capabilities before public deployments in healthcare. In a randomized controlled study involving 1,298 participants from a general sample, performance of humans when assisted by a large language model (LLM) was sensibly inferior to that of the LLM alone when assessing ten medical scenarios leading to disease identification and recommendations for treatment.
{"title":"Reliability of LLMs as medical assistants for the general public: a randomized preregistered study","authors":"Andrew M. Bean, Rebecca Elizabeth Payne, Guy Parsons, Hannah Rose Kirk, Juan Ciro, Rafael Mosquera-Gómez, Sara Hincapié M, Aruna S. Ekanayaka, Lionel Tarassenko, Luc Rocher, Adam Mahdi","doi":"10.1038/s41591-025-04074-y","DOIUrl":"10.1038/s41591-025-04074-y","url":null,"abstract":"Global healthcare providers are exploring the use of large language models (LLMs) to provide medical advice to the public. LLMs now achieve nearly perfect scores on medical licensing exams, but this does not necessarily translate to accurate performance in real-world settings. We tested whether LLMs can assist members of the public in identifying underlying conditions and choosing a course of action (disposition) in ten medical scenarios in a controlled study with 1,298 participants. Participants were randomly assigned to receive assistance from an LLM (GPT-4o, Llama 3, Command R+) or a source of their choice (control). Tested alone, LLMs complete the scenarios accurately, correctly identifying conditions in 94.9% of cases and disposition in 56.3% on average. However, participants using the same LLMs identified relevant conditions in fewer than 34.5% of cases and disposition in fewer than 44.2%, both no better than the control group. We identify user interactions as a challenge to the deployment of LLMs for medical advice. Standard benchmarks for medical knowledge and simulated patient interactions do not predict the failures we find with human participants. Moving forward, we recommend systematic human user testing to evaluate interactive capabilities before public deployments in healthcare. In a randomized controlled study involving 1,298 participants from a general sample, performance of humans when assisted by a large language model (LLM) was sensibly inferior to that of the LLM alone when assessing ten medical scenarios leading to disease identification and recommendations for treatment.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"32 2","pages":"609-615"},"PeriodicalIF":50.0,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.nature.comhttps://www.nature.com/articles/s41591-025-04074-y.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149740","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}
Pub Date : 2026-02-09DOI: 10.1038/s41591-025-04196-3
Abraham Shaked, Alex Sagar, Kim M Olthoff, Peter L Abt, Emily A Vail, Niels D Martin, Charles S Abrams, Rick D Hasz, Christine Radolovic, Shannon Kaminski, Bao-Li Loza, James F Markmann, Susan C Low, Mike Curtis, Leanne Lanieri, Kirsten G Swenson, Gregory T Everson, David A Wagner, Mohamed A Elzawahry, John I Fallon, Syed Hussain Abbas, Danielle Fortuna, Emma E Furth, K Rajender Reddy, Peter P Reese, Peter Friend
Extracorporeal liver cross-circulation (ELC) using genetically modified pig livers may address an unmet need for temporary liver support in patients with acute or acute-on-chronic liver failure. This study used the ELC platform to evaluate early immune responses and assess xenogeneic liver physiological support in a human decedent model. Four human decedents underwent ELC using pig livers with a triple glycan knockout; insertion of seven human transgenes and inactivation of pig endogenous retroviruses. Intravenous methylprednisolone was administered for immunosuppression. In the case of decedents 1-3, ELC was performed for 72-84 h with the native livers of the decedents remaining in situ. In the case of decedent 4, hepatectomy was performed, followed by 48 h of xenogeneic liver support exclusively using ELC. Biopsies of xenogeneic livers demonstrated preserved parenchymal architecture, mild immune infiltration and IgM deposition. Xenogeneic livers produced bile and supplemented native hepatocellular function. In decedent 4, xenogeneic liver-only support after hepatectomy maintained hemodynamic stability, normal pH, lactate, ammonia, international normalized ratio and sustained metabolic function. This study shows that ELC is feasible using xenogeneic livers with minimal immunosuppression and can provide effective liver support.
{"title":"Extracorporeal liver cross-circulation using transgenic xenogeneic pig livers with brain-dead human decedents.","authors":"Abraham Shaked, Alex Sagar, Kim M Olthoff, Peter L Abt, Emily A Vail, Niels D Martin, Charles S Abrams, Rick D Hasz, Christine Radolovic, Shannon Kaminski, Bao-Li Loza, James F Markmann, Susan C Low, Mike Curtis, Leanne Lanieri, Kirsten G Swenson, Gregory T Everson, David A Wagner, Mohamed A Elzawahry, John I Fallon, Syed Hussain Abbas, Danielle Fortuna, Emma E Furth, K Rajender Reddy, Peter P Reese, Peter Friend","doi":"10.1038/s41591-025-04196-3","DOIUrl":"10.1038/s41591-025-04196-3","url":null,"abstract":"<p><p>Extracorporeal liver cross-circulation (ELC) using genetically modified pig livers may address an unmet need for temporary liver support in patients with acute or acute-on-chronic liver failure. This study used the ELC platform to evaluate early immune responses and assess xenogeneic liver physiological support in a human decedent model. Four human decedents underwent ELC using pig livers with a triple glycan knockout; insertion of seven human transgenes and inactivation of pig endogenous retroviruses. Intravenous methylprednisolone was administered for immunosuppression. In the case of decedents 1-3, ELC was performed for 72-84 h with the native livers of the decedents remaining in situ. In the case of decedent 4, hepatectomy was performed, followed by 48 h of xenogeneic liver support exclusively using ELC. Biopsies of xenogeneic livers demonstrated preserved parenchymal architecture, mild immune infiltration and IgM deposition. Xenogeneic livers produced bile and supplemented native hepatocellular function. In decedent 4, xenogeneic liver-only support after hepatectomy maintained hemodynamic stability, normal pH, lactate, ammonia, international normalized ratio and sustained metabolic function. This study shows that ELC is feasible using xenogeneic livers with minimal immunosuppression and can provide effective liver support.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146149446","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}
Pub Date : 2026-02-06DOI: 10.1038/s41591-026-04227-7
Annesa Flentje, Brian Mustanski
{"title":"Surviving as a health equity researcher amidst a shifting political climate.","authors":"Annesa Flentje, Brian Mustanski","doi":"10.1038/s41591-026-04227-7","DOIUrl":"https://doi.org/10.1038/s41591-026-04227-7","url":null,"abstract":"","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132495","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}
Pub Date : 2026-02-06DOI: 10.1038/s41591-026-04246-4
Vivek Y Reddy, Edward P Gerstenfeld, Stavros E Mountantonakis, Chinmay Patel, Kenneth A Ellenbogen, John D Harding, Douglas N Gibson, Andrea Natale, Jonathan W Waks, Hugh Calkins, Sanjaya K Gupta, Christopher E Woods, William Whang, Marcos Daccarett, Frank A Cuoco, David B Delurgio, Elizabeth Richards, Matthew D Martens, Brad Sutton, Moussa Mansour
Pulsed field ablation (PFA) has proven to be a safe and effective non-thermal ablation modality for the treatment of atrial fibrillation (AF), but little outcome data beyond 1 year has been reported. Here, we present results from the ADVENT-LTO study, which provides extended follow-up of the ADVENT trial, the first randomized trial comparing PFA with conventional thermal ablation. In ADVENT-LTO, 364 paroxysmal AF patients (183 PFA, 181 thermal; 237 men, 127 women) participated, and were followed for 1,332±147 days. For the primary endpoint of four-year treatment success, PFA demonstrated preserved effectiveness compared to thermal ablation (72.8% PFA, 64.1% thermal; P=0.12). Moreover, there was a trend favoring PFA as compared to thermal ablation for the pre-specified outcome of freedom from hospital-based arrhythmia intervention (85.6% PFA, 78.6% thermal; HR 0.64, 95%CI 0.38, 1.05), including fewer repeat ablations (10.4% PFA, 17.7% thermal; P=0.04), as well as a trend favoring PFA as compared to thermal ablation for the pre-specified outcome of progression to persistent AF (2.6% PFA, 4.6% thermal; HR 0.55, 95%CI 0.16, 1.88). Taken together, these data demonstrate that the favorable outcomes of PFA are maintained over the course of four years. Coupled with the safety advantages of PFA over thermal ablation, these long-term data support widespread adoption of PFA for the treatment of AF. Clinical Trial Registration: NCT06526546.
{"title":"Pulsed Field versus Conventional Thermal Ablation for Paroxysmal Atrial Fibrillation: 4-Year Outcomes in the ADVENT-LTO Study.","authors":"Vivek Y Reddy, Edward P Gerstenfeld, Stavros E Mountantonakis, Chinmay Patel, Kenneth A Ellenbogen, John D Harding, Douglas N Gibson, Andrea Natale, Jonathan W Waks, Hugh Calkins, Sanjaya K Gupta, Christopher E Woods, William Whang, Marcos Daccarett, Frank A Cuoco, David B Delurgio, Elizabeth Richards, Matthew D Martens, Brad Sutton, Moussa Mansour","doi":"10.1038/s41591-026-04246-4","DOIUrl":"https://doi.org/10.1038/s41591-026-04246-4","url":null,"abstract":"<p><p>Pulsed field ablation (PFA) has proven to be a safe and effective non-thermal ablation modality for the treatment of atrial fibrillation (AF), but little outcome data beyond 1 year has been reported. Here, we present results from the ADVENT-LTO study, which provides extended follow-up of the ADVENT trial, the first randomized trial comparing PFA with conventional thermal ablation. In ADVENT-LTO, 364 paroxysmal AF patients (183 PFA, 181 thermal; 237 men, 127 women) participated, and were followed for 1,332±147 days. For the primary endpoint of four-year treatment success, PFA demonstrated preserved effectiveness compared to thermal ablation (72.8% PFA, 64.1% thermal; P=0.12). Moreover, there was a trend favoring PFA as compared to thermal ablation for the pre-specified outcome of freedom from hospital-based arrhythmia intervention (85.6% PFA, 78.6% thermal; HR 0.64, 95%CI 0.38, 1.05), including fewer repeat ablations (10.4% PFA, 17.7% thermal; P=0.04), as well as a trend favoring PFA as compared to thermal ablation for the pre-specified outcome of progression to persistent AF (2.6% PFA, 4.6% thermal; HR 0.55, 95%CI 0.16, 1.88). Taken together, these data demonstrate that the favorable outcomes of PFA are maintained over the course of four years. Coupled with the safety advantages of PFA over thermal ablation, these long-term data support widespread adoption of PFA for the treatment of AF. Clinical Trial Registration: NCT06526546.</p>","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":" ","pages":""},"PeriodicalIF":50.0,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132412","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}
Pub Date : 2026-02-06DOI: 10.1038/s41591-026-04205-z
Nerys Astbury, Elizabeth Morris
Data suggest that primary care practices could help deliver effective weight management — but only with robust implementation strategies that acknowledge the realities and pressures of primary care settings.
{"title":"Practical solutions to weight management in primary care","authors":"Nerys Astbury, Elizabeth Morris","doi":"10.1038/s41591-026-04205-z","DOIUrl":"10.1038/s41591-026-04205-z","url":null,"abstract":"Data suggest that primary care practices could help deliver effective weight management — but only with robust implementation strategies that acknowledge the realities and pressures of primary care settings.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"32 2","pages":"418-419"},"PeriodicalIF":50.0,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132401","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}
Pub Date : 2026-02-06DOI: 10.1038/s41591-025-04197-2
Petronela Weisová, Susanne Scheiblauer, Jacqueline Ecker, Martina Schneider, Romana Hochreiter, Annegret Bitzer, Karin Kosulin, Petra Schoengrundner, Ulrike Fuchs, Luz Rodeles, Sonia Mazara, Yeycy Donastorg, Silvia Rivera, Nina Wressnigg, Katrin Dubischar, Vera Buerger, Susanne Eder-Lingelbach, Juan Carlos Jaramillo
Currently, no licensed vaccine is available against chikungunya virus (CHIKV) in children aged less than 12 years. In this phase 2, observer-blind, randomized, dose–response trial we evaluated the tolerability (solicited adverse events (AEs)), safety (unsolicited AEs) and immunogenicity of a live-attenuated CHIKV vaccine (VLA1553) in healthy children aged 1–11 years in endemic countries. Here we provide a prespecified interim analysis to 28 days after vaccination. Participants (n = 304) received either a half dose (n = 119) or a full dose (n = 124) of VLA1553, or active control meningococcal vaccine (Nimenrix) (n = 61). The primary endpoint was the incidence and severity of solicited AEs within 14 days after vaccination. Secondary endpoints included unsolicited AEs, medically attended AEs, serious AEs, AEs of special interest and immunogenicity through 28 days after vaccination. For the primary endpoint, there were no statistically significant differences between the VLA1553 groups and control for each age group nor between age groups (1–2, 3–6 and 7–11 years). Overall, the most frequently reported solicited injection site AEs were tenderness (10.9%) and pain (8.6% of participants); the most frequently reported solicited systemic AEs were fever (12.5%) and headache (11.5%; participants aged 7–11 years and 3–6 years only, (headache was not solicited in participants aged 1–2 years)). For the secondary safety endpoints, the most common unsolicited AEs were infections and infestations (10.0–20.5%) and the most common medically attended AE overall was fever (2.6%), with no differences for unsolicited AEs or medically attended AEs regardless of vaccine and age group (serious AEs and AEs of special interest were too infrequent for meaningful comparisons). Anti-CHIKV neutralizing antibody titers were higher in the full-dose than the half-dose group at days 14 and 28 after vaccination. The trial met its prespecified endpoints and supported the selection of full-dose VLA1553 in future clinical trials in this population, addressing a critical unmet medical need. ClinicalTrials.gov registration: NCT06106581 . In a phase 2 randomized, controlled, dose–response trial, the live-attenuated chikungunya vaccine (VLA1553) was given in full and half doses to children under the age of 12 in Honduras and the Dominican Republic and was found to be safe and immunogenic, with the results supporting selection of the full-dose VLA1553 in future clinical trials in this population.
{"title":"Live-attenuated chikungunya vaccine in children: a randomized phase 2 trial","authors":"Petronela Weisová, Susanne Scheiblauer, Jacqueline Ecker, Martina Schneider, Romana Hochreiter, Annegret Bitzer, Karin Kosulin, Petra Schoengrundner, Ulrike Fuchs, Luz Rodeles, Sonia Mazara, Yeycy Donastorg, Silvia Rivera, Nina Wressnigg, Katrin Dubischar, Vera Buerger, Susanne Eder-Lingelbach, Juan Carlos Jaramillo","doi":"10.1038/s41591-025-04197-2","DOIUrl":"10.1038/s41591-025-04197-2","url":null,"abstract":"Currently, no licensed vaccine is available against chikungunya virus (CHIKV) in children aged less than 12 years. In this phase 2, observer-blind, randomized, dose–response trial we evaluated the tolerability (solicited adverse events (AEs)), safety (unsolicited AEs) and immunogenicity of a live-attenuated CHIKV vaccine (VLA1553) in healthy children aged 1–11 years in endemic countries. Here we provide a prespecified interim analysis to 28 days after vaccination. Participants (n = 304) received either a half dose (n = 119) or a full dose (n = 124) of VLA1553, or active control meningococcal vaccine (Nimenrix) (n = 61). The primary endpoint was the incidence and severity of solicited AEs within 14 days after vaccination. Secondary endpoints included unsolicited AEs, medically attended AEs, serious AEs, AEs of special interest and immunogenicity through 28 days after vaccination. For the primary endpoint, there were no statistically significant differences between the VLA1553 groups and control for each age group nor between age groups (1–2, 3–6 and 7–11 years). Overall, the most frequently reported solicited injection site AEs were tenderness (10.9%) and pain (8.6% of participants); the most frequently reported solicited systemic AEs were fever (12.5%) and headache (11.5%; participants aged 7–11 years and 3–6 years only, (headache was not solicited in participants aged 1–2 years)). For the secondary safety endpoints, the most common unsolicited AEs were infections and infestations (10.0–20.5%) and the most common medically attended AE overall was fever (2.6%), with no differences for unsolicited AEs or medically attended AEs regardless of vaccine and age group (serious AEs and AEs of special interest were too infrequent for meaningful comparisons). Anti-CHIKV neutralizing antibody titers were higher in the full-dose than the half-dose group at days 14 and 28 after vaccination. The trial met its prespecified endpoints and supported the selection of full-dose VLA1553 in future clinical trials in this population, addressing a critical unmet medical need. ClinicalTrials.gov registration: NCT06106581 . In a phase 2 randomized, controlled, dose–response trial, the live-attenuated chikungunya vaccine (VLA1553) was given in full and half doses to children under the age of 12 in Honduras and the Dominican Republic and was found to be safe and immunogenic, with the results supporting selection of the full-dose VLA1553 in future clinical trials in this population.","PeriodicalId":19037,"journal":{"name":"Nature Medicine","volume":"32 2","pages":"561-571"},"PeriodicalIF":50.0,"publicationDate":"2026-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146132417","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}
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