Sidharth Malhotra, Birendra P. Gupta, Surendra Uranw, Chinmay Kumar Mantri, Abhay P.S. Rathore, Ashley L. St. John
{"title":"登革热在人类中的严重程度因日本脑炎病毒免疫力的减弱而增强","authors":"Sidharth Malhotra, Birendra P. Gupta, Surendra Uranw, Chinmay Kumar Mantri, Abhay P.S. Rathore, Ashley L. St. John","doi":"10.1126/scitranslmed.ads9572","DOIUrl":null,"url":null,"abstract":"<div >Owing to increased global movement, vector-spread permissive climate change, and increased vaccination coverage against certain flaviviruses, the likelihood of being exposed to multiple flaviviruses in a lifetime has increased. Although many Asian countries have routine vaccination campaigns against Japanese encephalitis virus (JEV), the effect of JEV immunity on dengue disease severity is largely unknown. Here, we aimed to understand the effect of preexisting immunity against JEV on subsequent dengue disease outcomes in a prospective human cohort in Nepal, which has a high prevalence of JEV immunity and rapidly rising dengue virus (DENV) infections. A cohort consisting of 546 participants was studied over three dengue seasons and 5 years. Chymase, a serum biomarker of severe dengue across multiple patient cohorts, was assessed alongside clinical outcomes to determine whether there were associations between JEV immunity and dengue severity. We observed that midrange neutralizing antibody titers, approximately a 1:160 serum dilution capable of inhibiting JEV, were associated with heightened biomarkers of dengue disease severity and warning signs of severe disease in this cohort of patients who were mostly experiencing primary dengue infections. These results suggest that waning immunity to JEV could enhance the severity of dengue disease. This highlights the potential of maintaining strong immunity to JEV through vaccine boosters, not only to maintain protection against JEV in endemic regions but also to limit the potential of antibody-mediated enhancement of dengue disease.</div>","PeriodicalId":21580,"journal":{"name":"Science Translational Medicine","volume":"17 814","pages":""},"PeriodicalIF":14.6000,"publicationDate":"2025-09-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Dengue disease severity in humans is augmented by waning Japanese encephalitis virus immunity\",\"authors\":\"Sidharth Malhotra, Birendra P. Gupta, Surendra Uranw, Chinmay Kumar Mantri, Abhay P.S. Rathore, Ashley L. St. John\",\"doi\":\"10.1126/scitranslmed.ads9572\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div >Owing to increased global movement, vector-spread permissive climate change, and increased vaccination coverage against certain flaviviruses, the likelihood of being exposed to multiple flaviviruses in a lifetime has increased. Although many Asian countries have routine vaccination campaigns against Japanese encephalitis virus (JEV), the effect of JEV immunity on dengue disease severity is largely unknown. Here, we aimed to understand the effect of preexisting immunity against JEV on subsequent dengue disease outcomes in a prospective human cohort in Nepal, which has a high prevalence of JEV immunity and rapidly rising dengue virus (DENV) infections. A cohort consisting of 546 participants was studied over three dengue seasons and 5 years. Chymase, a serum biomarker of severe dengue across multiple patient cohorts, was assessed alongside clinical outcomes to determine whether there were associations between JEV immunity and dengue severity. We observed that midrange neutralizing antibody titers, approximately a 1:160 serum dilution capable of inhibiting JEV, were associated with heightened biomarkers of dengue disease severity and warning signs of severe disease in this cohort of patients who were mostly experiencing primary dengue infections. These results suggest that waning immunity to JEV could enhance the severity of dengue disease. This highlights the potential of maintaining strong immunity to JEV through vaccine boosters, not only to maintain protection against JEV in endemic regions but also to limit the potential of antibody-mediated enhancement of dengue disease.</div>\",\"PeriodicalId\":21580,\"journal\":{\"name\":\"Science Translational Medicine\",\"volume\":\"17 814\",\"pages\":\"\"},\"PeriodicalIF\":14.6000,\"publicationDate\":\"2025-09-03\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Science Translational Medicine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.science.org/doi/10.1126/scitranslmed.ads9572\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CELL BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Science Translational Medicine","FirstCategoryId":"3","ListUrlMain":"https://www.science.org/doi/10.1126/scitranslmed.ads9572","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CELL BIOLOGY","Score":null,"Total":0}
Dengue disease severity in humans is augmented by waning Japanese encephalitis virus immunity
Owing to increased global movement, vector-spread permissive climate change, and increased vaccination coverage against certain flaviviruses, the likelihood of being exposed to multiple flaviviruses in a lifetime has increased. Although many Asian countries have routine vaccination campaigns against Japanese encephalitis virus (JEV), the effect of JEV immunity on dengue disease severity is largely unknown. Here, we aimed to understand the effect of preexisting immunity against JEV on subsequent dengue disease outcomes in a prospective human cohort in Nepal, which has a high prevalence of JEV immunity and rapidly rising dengue virus (DENV) infections. A cohort consisting of 546 participants was studied over three dengue seasons and 5 years. Chymase, a serum biomarker of severe dengue across multiple patient cohorts, was assessed alongside clinical outcomes to determine whether there were associations between JEV immunity and dengue severity. We observed that midrange neutralizing antibody titers, approximately a 1:160 serum dilution capable of inhibiting JEV, were associated with heightened biomarkers of dengue disease severity and warning signs of severe disease in this cohort of patients who were mostly experiencing primary dengue infections. These results suggest that waning immunity to JEV could enhance the severity of dengue disease. This highlights the potential of maintaining strong immunity to JEV through vaccine boosters, not only to maintain protection against JEV in endemic regions but also to limit the potential of antibody-mediated enhancement of dengue disease.
期刊介绍:
Science Translational Medicine is an online journal that focuses on publishing research at the intersection of science, engineering, and medicine. The goal of the journal is to promote human health by providing a platform for researchers from various disciplines to communicate their latest advancements in biomedical, translational, and clinical research.
The journal aims to address the slow translation of scientific knowledge into effective treatments and health measures. It publishes articles that fill the knowledge gaps between preclinical research and medical applications, with a focus on accelerating the translation of knowledge into new ways of preventing, diagnosing, and treating human diseases.
The scope of Science Translational Medicine includes various areas such as cardiovascular disease, immunology/vaccines, metabolism/diabetes/obesity, neuroscience/neurology/psychiatry, cancer, infectious diseases, policy, behavior, bioengineering, chemical genomics/drug discovery, imaging, applied physical sciences, medical nanotechnology, drug delivery, biomarkers, gene therapy/regenerative medicine, toxicology and pharmacokinetics, data mining, cell culture, animal and human studies, medical informatics, and other interdisciplinary approaches to medicine.
The target audience of the journal includes researchers and management in academia, government, and the biotechnology and pharmaceutical industries. It is also relevant to physician scientists, regulators, policy makers, investors, business developers, and funding agencies.