RARE DISEASE
Hemorrhagic fever-renal syndrome
Hemorrhagic fever-renal syndrome
Hemorrhagic fever-renal syndrome
Synonyms: Hantavirosis, Hantavirus fever
Synonyms: Hantavirosis, Hantavirus fever
Synonyms: Hantavirosis, Hantavirus fever
Drug discovery
2
drugs
With orphan designations
Overview
Hemorrhagic fever with renal syndrome (HFRS) is a zoonotic disease caused by hantaviruses transmitted through inhalation of aerosolized rodent excreta. It manifests as acute kidney injury, thrombocytopenia, capillary leakage, and coagulopathy, progressing through febrile, hypotensive, oliguric, polyuric, and convalescent phases. Severe cases develop multiorgan failure, shock, or ARDS, with mortality rates ranging from <1% (Puumala virus) to 15% (Hantaan virus) [1][2][12].
Burden
Annual incidence: 60,000–100,000 cases globally, with China reporting >50,000 hospitalizations/year [7][14]
Case fatality: 1–15% depending on viral strain; up to 40% mortality in untreated shock cases [1][12]
Long-term sequelae: Chronic kidney disease, hypertension, and neurological deficits in 5–10% of survivors [1][13]
Therapies
Supportive care: Fluid/electrolyte management, dialysis for AKI (intermittent hemodialysis preferred) [3][13]
Antivirals: Early IV ribavirin reduces mortality; favipiravir shows promise but lacks large-scale validation [6][8][12]
Advanced interventions: Platelet transfusions for severe thrombocytopenia, CRRT for critical cases with multiorgan failure [13][18]
Categories: rare infectious diseases
Research Papers
112 drug discovery papers about Hemorrhagic fever-renal syndrome, with 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
112 drug discovery papers about Hemorrhagic fever-renal syndrome, with 1 next-in-class emerging drug candidate forecasted to outperform the average preclinical success rate. Recent publications:
categories:
Small molecules
small molecules
2026-08-31 | Nucleoside analogues in etiotropic therapy of hantavirus fevers
Hantavirus fevers (HF) are caused by pathogenic orthohantaviruses and are classified into two clinical forms: hemorrhagic fever with renal syndrome (HFRS), reported in Eurasia, and hantavirus pulmonary syndrome (HPS), reported in the Americas. HF are characterised by an acute course with predominant involvement of internal organs: HFRS is mainly associated with kidney damage, while HPS is characterised by severe lung injury. Both diseases may also affect the central nervous and endocrine systems. In addition, hantavirus fevers are marked by severe complications during the acute phase and a prolonged recovery period. Currently, there is neither a WHO-approved vaccine nor any effective etiotropic anti-hantavirus therapy. The development of antiviral treatment strategies focuses on preventing orthohantavirus entry into cells or suppressing their intracellular replication. One of the main directions in the search for effective anti-hantavirus therapy is the low-molecular-weight compounds development and testing, many of which have demonstrated pronounced antiviral activity against orthohantaviruses through direct or indirect effects on viral RNA polymerase function. The review shows that new antiviral nucleoside compounds development and study has promising potential, as well as their combined use for effective etiotropic, pathogenetic and symptomatic treatment of hantavirus fevers.
2026-08-01 | NE01 Panhypopituitarism following hantavirus-induced hemorrhagic fever with renal syndrome: a case report
Abstract Introduction Hemorrhagic fever is a severe infectious disease caused by RNA viruses and represents a serious systemic illness characterized by hemorrhage, a generalized infectious syndrome, and the potential development of shock. The complex nature of this pathological entity may lead to chronic damage of various organ systems, even during the recovery period. One of its prolonged and often occult complications is hypopituitarism. Case presentation We present the case of a 44-year-old male patient who was admitted to the Department of Endocrinology seven months after recovery from hantavirus-induced hemorrhagic fever with renal syndrome (HFRS). The patient was referred for endocrine evaluation due to persistent fatigue during routine daily activities, loss of libido, and reduced body hair growth. Basal hormonal assessment confirmed panhypopituitarism. Magnetic resonance imaging (MRI) of the pituitary gland revealed pituitary atrophy and partial empty sella syndrome. Replacement therapy with hydrocortisone, levothyroxine, and long-acting testosterone depot preparation was initiated. The patient showed clinical improvement and was discharged for further outpatient follow-up. Conclusion In addition to other well-established causes of panhypopituitarism, viral infections should also be considered in the differential diagnosis. Given the endemic occurrence of hantavirus infections in our region and their potential to induce pituitary dysfunction, hormonal status assessment should be included in the long-term follow-up of patients recovering from hemorrhagic fever with renal syndrome.
2026-06-25 | A drug repurposing screen identifies antiviral compounds against Puumala Orthohantavirus
Hantaviruses are zoonotic negative-sense RNA viruses that cause haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), yet no approved antiviral therapies are available. To identify host-directed modulators of hantavirus infection we performed a drug repurposing screen using live Puumala virus (PUUV). We identified and validated 70 drugs with antiviral activity in A549 cells and primary human endothelial cells. Functional clustering confirmed the known infection-inhibitory effect of several groups of compounds, including inhibitors of heat shock proteins, mTOR pathway and nucleotide synthesis. Our screen also identified compounds yet unexplored as antivirals against Hantaviruses, such as certain antibiotics. Our dataset provides a systematic map of host pathways influencing PUUV infection and highlights candidate compounds and cellular processes that can modulate this process.
2026-06-04 | Hantavirus ANDV Glycoprotein Gc: Multi-Site Computational Analysis of Remdesivir Binding Under pH-Dependent Fusion Conditions
Hantaviruses are emerging zoonotic pathogens responsible for hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), diseases associated with substantial mortality and limited antiviral treatment options. Andes virus (ANDV), a highly pathogenic New World hantavirus, utilizes the glycoprotein complex composed of Gn and Gc proteins to mediate host-cell entry and membrane fusion. The Gc glycoprotein undergoes pH-dependent structural rearrangements during endosomal trafficking, making it an attractive therapeutic target. In the present study, a comprehensive molecular docking analysis of Remdesivir against multiple functional regions of the Andes virus glycoprotein Gc was performed using AutoDock Vina under physiologically relevant pH conditions (7.4, 5.5, and 4.6). Five structurally and functionally important regions were investigated, including the fusion-loop pocket (Region 1), Gc homodimer interface (Region 2), pH-sensing interface (Region 3), GnB–Gc stem accommodation interface (Region 4), and conserved aromatic groove stabilization region (Region 5). Remdesivir exhibited strong multi-site binding with affinities ranging from −9.1 to −7.0 kcal/mol. These findings suggest that Remdesivir may interfere with viral fusion machinery through simultaneous constitutive and pH-sensitive mechanisms. The study provides mechanistic insights into hantavirus fusion regulation and highlights the potential value of multi-site antiviral targeting strategies against emerging RNA viruses.
2026-06-02 | <b>Hantavirus Reservoirs in Human-to-Human Transmission: Deep Learning Frameworks for the Identification of Molecular Inhibitors Targeting and Virus Interhuman Pathogenesis</b>
Hantaviruses are serious emerging zoonotic RNA viruses, which are associated with two major diseases (hemorrhagic fever with renal syndrome, HFRS and hantavirus cardiopulmonary syndrome, HCPS) and are maintained mainly in rodent hosts. Of the hantaviruses, Andes virus (ANDV) has been shown to be capable of human-to-human transmission, and is thus of particular public health interest. In the present study, the role of hantavirus reservoirs in Andes virus transmission is explored and Deep Learning computational techniques are used to find molecular inhibitors that inhibit viral pathogenesis. An in-silico research design was used which involves epidemiological analysis, bioinformatics, molecular docking, virtual screening, molecular dynamics simulation, and artificial intelligence supported drug discovery. The glycoproteins (Gn/Gc), nucleocapsid proteins, fusion proteins, and the RNA-dependent RNA polymerase are targeted as therapeutic proteins. The antiviral prediction and compound screening are based on deep learning frameworks like CNN, RNN, GNN and transformer-based models. Results show that transformer-based models and graph neural network models give the maximum prediction accuracy. Several compounds are identified by molecular docking studies that have high binding affinity towards Andes virus proteins. The researchers conclude that AI-enabled computational approaches could greatly enhance the discovery and development of antiviral drugs to treat novel hantavirus infections.
vaccines
2026-07-31 | Epidemiology and changes in age distribution of hemorrhagic fever with renal syndrome in Shaanxi, China, from 2004 to 2023
INTRODUCTION: Hemorrhagic fever with renal syndrome (HFRS) is a serious viral disease in mainland China, and Shaanxi Province is one of the most severely affected areas. In order to reduce HFRS incidence, an inactivated bivalent vaccine against Hantaan virus (HTNV) and Seoul virus (SEOV) infections was developed and used in China since the 1990s. METHODOLOGY: Descriptive epidemiological methods were used to analyze the spatial, temporal, and population distribution of HFRS along with changes in age distribution in Shaanxi Province from January 2004 to December 2023. RESULTS: A total of 34,265 HFRS human cases were reported in Shaanxi Province, including 25,737 males and 8,528 females. HFRS cases were geographically concentrated in the Guanzhong Plain. The local incidence of HFRS fluctuated remarkably over the past 20 years. The primary peak was from October to January. The proportion of HFRS cases in the 15-60 years age group showed a decreasing trend. However, the proportion of HFRS cases among the > 60 years age group increased by 150.94%, rising from 11.68% to 29.31%. CONCLUSIONS: Data from a 20-year surveillance study shows that the proportion of HFRS cases in individuals over 60 years of age has increased significantly, which may potentially be due to vaccine coverage limitations. The results can be used to adjust the prevention and control measures of HFRS and to consider age-expanded vaccination strategies.
2026-01-01 | Immunoinformatics-driven design of a multi-epitope vaccine against Seoul Virus: Structural, dynamic, and immunogenic profiling
• Immunoinformatics-based design of a multi-epitope vaccine against Seoul virus (SEOV). • Designed Vaccine construct V2 showed 95.94% global coverage and strong antigenicity. • Docking and molecular dynamics simulations confirmed stable binding of V2 with the TLR4 receptor. • Immune simulations predicted strong IgG1, IFN-γ, and memory responses of V2. • Codon optimization and in silico cloning confirmed expression feasibility. Seoul Virus (SEOV), a zoonotic hantavirus, is a major cause of Hemorrhagic Fever with Renal Syndrome (HFRS) and represents a global health challenge. With no licensed vaccines or specific antivirals available, this study aimed to design a glycoprotein-based multi-epitope vaccine against SEOV using immunoinformatics approaches. Material s and methods MHC-I and MHC-II epitopes were predicted via the Immune Epitope Database (IEDB) and screened for antigenicity, non-allergenicity, and non-toxicity. Four constructs were designed, with V2 selected as the best candidate. Structural modeling was performed using AlphaFold3 and validated with Ramachandran analysis. Molecular docking with Toll-like receptor-4, molecular dynamics simulations, and immune simulations were conducted to evaluate stability and immunogenicity. The V2 construct demonstrated high antigenicity (0.683) and broad population coverage (95.94%). Structural validation confirmed 95.6% of residues in favored regions. Docking revealed strong binding to Toll-like receptor-4, and dynamics confirmed stability through RMSD, RMSF, Rg, PCA, DCCM, and FEL analysis. Immune simulations predicted robust responses, including high IgG1 titers. Codon optimization (GC content 56.62%) and cloning confirmed expression potential. The V2 construct exhibits stability, strong immunogenicity, and broad population coverage, supporting its potential as a vaccine candidate against SEOV. Experimental validation in vitro and in vivo is required to confirm efficacy and safety.
2026-01-01 | The Use of Artificial Intelligence to Create a Model for the Vaccine Against the Hantavirus
Abstract Background — Hantaviruses are globally distributed zoonotic pathogens responsible for Hemorrhagic Fever with Renal Syndrome (HFRS) and Hantavirus Pulmonary Syndrome (HPS). Maintained in rodent reservoirs and transmitted through aerosolised excreta, they remain a persistent public health threat. Their enveloped structure, incorporating Gn/Gc glycoproteins and ribonucleoprotein complexes, complicates traditional vaccine development. Recent advances in AI driven vaccinology offer new strategies for identifying antigenic determinants and designing safer, more immunogenic constructs. Methods — An integrated AI computational pipeline combined structural modelling, reverse vaccinology, and immunoinformatics. Glycoprotein sequences from representative hantaviruses were modelled to predict conformational features. Deep learning algorithms identified high affinity B cell epitopes and T cell epitopes, which were assembled into a multi epitope construct. Allergenicity, toxicity, and population coverage were computationally screened, and immune simulations assessed predicted host responses. Results — The AI generated construct demonstrated high predicted antigenicity, favourable physicochemical stability, and non allergenic, non toxic profiles. Structural modelling confirmed appropriate folding and solvent exposure of key epitopes. Immune simulations suggested strong induction of humoral and cellular responses, including memory cell formation. Conclusions — AI enabled vaccine design provides a rapid, rational framework for developing next generation hantavirus vaccines. By integrating molecular virology with machine learning, this approach accelerates antigen discovery and construct optimisation. The findings support AI as a transformative tool for emerging pathogen vaccine development and highlight its potential to overcome longstanding barriers in hantavirus prevention.
2025-09-06 | [Analysis of epidemic characteristics and vaccination status of hemorrhagic fever with renal syndrome in Baoji City of Shaanxi Province from 2008 to 2023].
To analyze the epidemic characteristics and vaccination status of hemorrhagic fever with renal syndrome (HFRS) in Baoji City from 2008 to 2023. The descriptive epidemiological method was used to collect the incidence data of HFRS cases in Baoji City from 2008 to 2003 in the Infectious Disease Reporting Information Management System. The epidemic characteristics of HFRS cases were summarized and analyzed. The data on HFRS vaccination from 2008 to 2023 were consulted through the Baoji Hemorrhagic Fever Vaccination Report, and the relationship between vaccination status and reported incidence was analyzed. The results showed that a total of 2 690 cases of HFRS were reported in Baoji City, with an annual average reported incidence rate of 6.94/100 000, 15 cases died and a case fatality rate of 0.41%. The number of reported HFRS cases showed a fluctuating trend, with a peak in 2011-2013. Since 2016, it entered a low-level stable fluctuation period, and the annual mortality rate dropped to below 1% after 2011. From 2008 to 2023, Fufeng County, Meixian County and Chencang District reported a large number of cases, but Linyou County and other counties in the north showed an upward trend in incidence, with obvious seasonal characteristics. Cases were mainly concentrated from October to January of the following year, accounting for 75.91% of the total number of cases. Farmers were the main reported occupations, accounting for 80.19% of the total number of cases. The ratio of male to female reported cases was 3.30∶1. The age group of 35-59 years old accounted for 51.08% of the cases, and the proportion of the age group of 60 years and above showed an upward trend (χ2=331.44, P<0.001). From 2008 to 2023, a total of 1 559 619 people were vaccinated, and the vaccination rate of the target population aged 16-60 years reached 72.23%. With the increase in the vaccination rate, the incidence of HFRS continued to decrease. In summary, with the development of HFRS vaccination work, the epidemic characteristics of HFRS in Baoji City have changed, and the peak incidence has been controlled. The proportion of cases in the age group of 60 years and above continues to increase. HFRS vaccination is still an effective way of prevention and control, and vaccination strategies should be continuously optimized according to the characteristics of HFRS.
2025-06-12 | Genetic and codon usage analyses reveal the evolution of the seoul virus
Seoul virus (Orthohantavirus seoulense, SEOV), a member of the Hantaviridae, causes hemorrhagic fever with renal syndrome (HFRS) through rodent hosts. However, its molecular evolutionary dynamics and codon usage patterns remain poorly understood. This study integrated coding sequences from GenBank and previously acquired SEOV strains to systematically analyze genetic evolution and codon usage bias. It revealed that SEOV evolved seven clades (A-G) with distinct amino acid variation sites and geographic clustering. Recombination events were identified during evolution, alongside purifying and positive selection on specific sites (e.g., codon 259 in the S segment and codon 11 in the M segment). The three viral segments (L, M, and S) exhibited weak codon usage bias, predominantly driven by natural selection, with host adaptation significantly influencing evolutionary trajectories. The S segment demonstrated the strongest pathogenicity due to its closer codon usage alignment with Homo sapiens (H. sapiens) and Rattus norvegicus (R. norvegicus), whereas the L segment showed the lowest host adaptation. Divergent codon preferences among clades highlighted adaptive strategies in host-virus interactions. These findings elucidate the evolutionary mechanisms of SEOV and provide a theoretical foundation for live attenuated vaccine design and region-specific viral control strategies.
antibodies
2026-07-31 | The Changing Landscape of Hantavirus Infections: A Narrative Review of Epidemiology, Pathogenesis, and Countermeasures
Hantaviruses are emerging zoonotic pathogens of increasing global public health significance. Their epidemiological landscape is rapidly changing due to ecological disruption, climate variability, urbanisation, and evolving human-animal interfaces. This narrative review synthesises current knowledge on hantavirus virology, epidemiology, pathogenesis, clinical management, and emerging countermeasures, with a focus on developments from the past 5 years. Traditionally classified into Old World viruses causing haemorrhagic fever with renal syndrome (HFRS) and New World viruses causing hantavirus cardiopulmonary syndrome (HCPS), this dichotomy has become increasingly blurred, with overlapping renal and pulmonary manifestations now recognized. Among the most consequential recent advances is the consolidated evidence for person-to-person transmission of Andes virus, documented among household contacts and during the prodromal phase, with viral shedding in respiratory secretions. Endothelial dysfunction remains the pathological hallmark of severe disease, driven by VEGF sensitisation, Src kinase and RhoA pathway activation, pericyte infection, and dysregulated inflammatory responses including IL-6 trans-signalling. Concurrently, environmental and ecological studies have linked climate change, rodent population dynamics, land-use modification, and urbanisation to increased human disease risk across multiple continents. Diagnostic strategies continue to rely on serology and molecular testing, while management remains predominantly supportive, with extracorporeal membrane oxygenation (ECMO) improving survival in fulminant HCPS. Importantly, recent structural virology advances have enabled the development of broadly neutralising monoclonal antibodies targeting conserved quaternary epitopes, as well as next-generation vaccine platforms including DNA, mRNA, and prefusion-stabilised glycoprotein candidates. Hantaviruses represent a paradigmatic One Health challenge at the intersection of environmental change, viral evolution, and global interconnectedness. Despite major progress in understanding transmission dynamics and endothelial pathogenesis, critical gaps remain regarding determinants of person-to-person spread, long-term post-infection sequelae, and the absence of licenced broadly protective vaccines or specific antiviral therapies. Future preparedness will require integrated surveillance frameworks combining ecological monitoring, genomic epidemiology, and clinical readiness within coordinated international public health strategies.
2026-01-01 | Broadly Neutralizing Antibodies Against Emerging Hantaviruses: Structural Mechanisms, Cross-Protection, and Multi-Scale Immunotherapeutic Perspectives
This repository contains the supplementary data, structural immunoinformatics metrics, and multi-scale systems architecture corresponding to the manuscript: "Broadly Neutralizing Antibodies Against Emerging Hantaviruses: Structural Mechanisms, Cross-Protection, and Multi-Scale Immunotherapeutic Perspectives". Context & Objectives Hantaviruses represent a severe threat to global public health, causing Hantavirus Pulmonary Syndrome (HPS) and Hemorrhagic Fever with Renal Syndrome (HFRS). This dataset supports a comprehensive systematic review (2021–2024) conducted under PRISMA guidelines and formalizes a novel multi-scale control framework for evaluating broadly neutralizing antibodies (bNAbs) targeting the conserved Gn/Gc glycoprotein epitopes. Content of the Repository PRISMA_Flowchart_Metrics.csv/.pdf: Comprehensive screening, inclusion/exclusion matrices, and structural data extracted from recent literature on cross-reactive hantavirus neutralizing antibodies. Systems_Biology_Architecture_Code/: Computational state-space modeling scripts and non-linear dynamic simulation protocols used to formalize neutralization as an emergent property of complex adaptive immune networks (Ashby’s Law of Requisite Variety application). Figure_1_HighRes.png: The multi-scale immunotherapeutic control architecture diagram mapping molecular interactions to systemic immune responses. Methodology Data curation follows strict systems biology protocols, integrating structural structural biology data with control theory principles to transcend single-scale binding affinity models. Keywords Hantavirus Broadly Neutralizing Antibodies Structural Immunology Systems Biology Control Theory State-Space Modeling Emergent Immunity PRISMA Framework
2025-07-26 | Hantavirus Conducted Route from Mice to Human: Potential Dangers and Outcomes of Zoonosis
The hantavirus is associated with deadly illnesses including hemorrhagic fever associated with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), and there are an astounding 200,000 new infections of this virus per year.It is a major concern for world health.Murid rats are the major hosts of these viruses, which operate as silent reservoirs that enable zoonotic transmission to humans via aerosolized faeces.Particularly in endemic regions, the intricate interplay between environmental conditions and human behaviour substantially impacts the transmission of hantavirus infections.This research addresses the complicated biology and pathophysiology of hantaviruses, underlining the crucial need for better immunisation and treatment alternatives.Although numerous promising vaccine candidates are being researched, problems remain in obtaining enduring protection and assuring safety.Also, efforts into neutralizing antigens as prospective therapies give a glimmer of light to better the lives of patients.A comprehensive approach that involves monitoring, public education, and research into innovative vaccines and therapies is required to battle hantavirus infections, decrease public health hazards, and protect vulnerable populations.
2025-05-13 | Urinalysis of a Hantaan virus-infected mouse model of hemorrhagic fever with renal syndrome
Hantaan virus causes hemorrhagic fever with renal syndrome (HFRS), a rodent-borne zoonotic disease. Korean hemorrhagic fever virus (KHFV), a strain of Hantaan virus, showed symptoms in mice similar to those of HFRS patients, including weight loss, renal medullary hemorrhage, hepatitis, and neutrophilia. Therefore, mice inoculated with KHFV were expected to serve as a model for HFRS. However, urinary symptoms characteristic of HFRS, such as proteinuria and hematuria, have not yet been examined. In this study, we attempted to evaluate renal function by analyzing urine. As a result, in mice inoculated with KHFV, oliguria and hematuria accompanied by weight loss were observed at 5-8 days after inoculation, and albuminuria was also observed. In addition, the viral load in the kidney and viral excretion into the urine were observed. When the neutralizing monoclonal antibody HCO2 against Hantaan virus was administered before inoculation, all symptoms were abolished. To clarify the therapeutic effect of HCO2 antibody, it was administered intravenously on days 1, 3, and 5 after infection. Weight loss and renal medullary hemorrhage were suppressed, and histological examination revealed micro renal hemorrhage in mice on day 5 administration. It was found that neutralizing antibody can be expected to alleviate symptoms even if it is administered late, and that early administration is more effective. These results indicate that this mouse model shows symptoms like human HFRS and can be used to evaluate antiviral effects.
2025-05-08 | Puumala orthohantavirus: prevalence, biology, disease, animal models and recent advances in therapeutics development and structural biology
Puumala orthohantavirus (PUUV) is an emerging zoonotic virus that was first discovered in the Puumala region of Finland in the early 1980s and is the primary etiological agent of nephropathia epidemica (NE), a milder form of a life-threatening disease known as hemorrhagic fever with renal syndrome (HFRS). PUUV and other members of the Old World hantaviruses (OWHVs) predominantly circulate in rodents or insectivores across Eurasia, accounting for several thousand of reported HFRS cases every year (with many more unreported/misdiagnosed cases suspected). The rodent reservoir of PUUV is the common bank vole (Myodes (M.) glareolus), and transmission of the virus to humans occurs via inhalation of contagious aerosols and through contact with contaminated droppings or urine. Although PUUV is the subject of extensive research, due to its potential to cause severe disease outcomes in humans and its considerable economic and social impact, neither licensed vaccines nor specific antiviral treatments are available against PUUV. However, many important advancements have been made in terms of PUUV research over the last years. This included the elucidation of its glycoproteins, the discovery of broadly neutralizing hantavirus antibodies as therapeutic candidates and expanded research on the mRNA vaccine technology which will likely enable the development of strong PUUV vaccine candidates in the near future. Currently, there is still a lack of suitable animal models for the preclinical evaluation of experimental vaccines and antivirals, which hampers vaccine and antiviral development. Current attempts to decrease hantavirus-associated human infections rely primarily on prevention and countermeasures for rodent control, including reduced contact to droppings, saliva and urine, and disinfection of areas that are contaminated with rodent excreta. Here, we review these recent advances and other aspects including PUUV prevalence, virus biology, diagnosis and clinical features, and current animal models for vaccine and treatment development.
proteins
2026-08-03 | Angiopoietin-1/Tie2 Activation as a Therapeutic Hypothesis for Hantavirus-Induced Vascular Permeability
Severe hantavirus infection produces extensive vascular leakage, driven by a combination of endothelial dysfunction, dysregulated inflammation, VEGF-mediated hyperpermeability, angiopoietin imbalance, and degradation of the endothelial glycocalyx. This narrative review draws on the peer-reviewed literature, with particular attention to work published between 2016 and 2026, to examine how hantavirus-induced vascular permeability arises in hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), and how Angiopoietin-1 (Ang-1)/Tie2 signaling and glycocalyx injury contribute to endothelial barrier failure. Direct hantavirus evidence shows that Ang-1 inhibits hantavirus-directed endothelial permeability in vitro and that angiopoietin dysregulation tracks with disease severity in patients; findings that Tie2 activation curbs vascular leakage in sepsis and other non-hantavirus models are mechanistically suggestive but remain inferential rather than hantavirus-specific. No hantavirus animal model or clinical trial has yet evaluated Ang-1/Tie2-directed therapy, so this review treats the approach as a testable hypothesis rather than an established or recommended treatment; confirming its therapeutic value will require dedicated hantavirus-specific animal and clinical studies.
2026-05-17 | THE RODENT RECEPTOR CODE: A HOST-ENCODED Β3- INTEGRIN DECOY DOMAIN DICTATES HANTAVIRUS PATHOGENICITY
ABSTRACTHantaviruses cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome(HPS) in humans, with case-fatality rates reaching 10-15% for HFRS and 40-60% for HPS, yet remaincompletely asymptomatic in their reservoir rodent hosts. The molecular basis of this host-specificpathogenicity has remained one of the most enigmatic questions in hantavirology.Here, we demonstrate that a single amino acid polymorphism at position 39 of the β3-integrin plexinsemaphorin-integrin (PSI) domain — Aspartate in humans versus Asparagine in all eight major reservoirspecies — functions as a molecular switch that couples hantavirus glycoprotein binding to downstream propermeability signaling. We cloned β3-integrin PSI domains from all eight reservoir species (Apodemusagrarius, A. flavicollis, Rattus norvegicus, Myodes glareolus, Microtus arvalis, Peromyscus maniculatus,Oligoryzomys longicaudatus, and Homo sapiens) and showed that rodent PSI peptides bind hantavirus Gn/Gc envelope glycoproteins with high affinity but fail to activate the FAK/Src/PI3K/Akt/VEGF-mTORpermeability axis. In contrast, human β3-integrin engagement by Gn/Gc triggers robust signaling, adherensjunction disruption, and vascular leakage.Leveraging this mechanistic insight, we designed soluble "decoy" peptides mimicking the rodent Asn-39PSI domain that competitively inhibit hantavirus entry into human endothelial cells with IC50 values of0.5-1.2 μg/ml and selectivity indices exceeding 500x. In the Syrian hamster model of lethal Andes virus(ANDV) infection, prophylactic administration of Decoy-2 (derived from M. glareolus) conferred 70%survival versus 0% in vehicle controls (p < 0.001), reduced tissue viral loads by >3 log10 copies/g,suppressed cytokine storm, and preserved pulmonary and renal histopathology. These findings identify thefirst host-encoded viral entry decoy, establish the "rodent receptor code" as the mechanistic basis ofreservoir asymptomaticity, and provide a first-in-class hantavirus-specific therapeutic candidate currentlyabsent from the clinical armamentarium.Keywords: hantavirus, β3-integrin, PSI domain, decoy peptide, vascular permeability, host-pathogen evolution,translational therapeutics
2025-05-29 | Dynamic alterations of circulating lymphocytes during the trajectory of Hantaan virus-induced hemorrhagic fever with renal syndrome
Here, we revealed phase-specific immune patterns: CD8+ T, CD8+ Tems, and activated CD8+ T, MAIT and NKT cells peaked during febrile/oliguric phases before declining in polyuria/recovery, while CD4+ T and MAIT cells showed inverse fluctuation patterns. Higher frequencies of CD8+ Tem, B, and CD56dim NK cells during the febrile phase correlated with severe disease, enabling early risk stratification. Lower CD4+ Tcm levels in the oliguric phase marked progression to severe HFRS, indicating potential therapeutic strategies aimed at enhancing CD4+ Tcm generation or inhibiting effector differentiation. Additionally, CD38 and CD161 expression predicted specific lymphocyte subset dynamics, offering novel biomarkers for immunomodulatory strategies. Our study thus provides the first comprehensive atlas of lymphocyte evolution in HTNV-induced HFRS, connecting immune dysregulation with clinical outcomes.
2025-04-09 | Raw data for all figures.
Background Hantavirus causes hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Strong inflammatory responses and vascular leakage are important hallmarks of these often fatal diseases. The mechanism behind pathogenesis is unknown and no specific treatment is available. IL-6 was recently highlighted as a biomarker for HPS/HFRS severity. IL-6 signaling is complex and context dependent: while classical signaling generally provide protective responses, trans-signaling can cause severe pathogenic responses. Here, we investigated a potential role for IL-6 trans-signaling in hantavirus pathogenesis. Methods Effects of IL-6 trans-signaling during in vitro hantavirus infection were assessed using primary human endothelial cells treated with recombinant soluble IL-6 receptor (sIL-6R). Plasma from Puumala orthohantavirus-infected HFRS patients (n=28) were analyzed for IL-6 trans-signaling potential and its associations to severity. Findings In vitro, sIL-6R treatment of infected cells enhanced IL-6 and CCL2 secretion, upregulated ICAM-1, and affected VE-cadherin leading to a disrupted cell barrier integrity. HFRS patients showed altered plasma levels of sIL-6R and soluble gp130 (sgp130) resulting in an increased sIL-6R/sgp130 ratio suggesting enhanced IL-6 trans-signaling potential. Plasma sgp130 levels negatively correlated with number of interventions and positively with albumin levels. Patients receiving oxygen treatment displayed a higher sIL-6R/sgp130 ratio compared to patients that did not. Interpretation IL-6 trans-signaling is linked to hantavirus pathogenesis. Targeting IL-6 trans-signaling might provide a therapeutic strategy for treatment of severe HFRS and perhaps also HPS.
2025-04-09 | IL-6 trans-signaling mediates cytokine secretion and barrier dysfunction in hantavirus-infected cells and correlate to severity in HFRS
Background Hantavirus causes hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Strong inflammatory responses and vascular leakage are important hallmarks of these often fatal diseases. The mechanism behind pathogenesis is unknown and no specific treatment is available. IL-6 was recently highlighted as a biomarker for HPS/HFRS severity. IL-6 signaling is complex and context dependent: while classical signaling generally provide protective responses, trans-signaling can cause severe pathogenic responses. Here, we investigated a potential role for IL-6 trans-signaling in hantavirus pathogenesis. Methods Effects of IL-6 trans-signaling during in vitro hantavirus infection were assessed using primary human endothelial cells treated with recombinant soluble IL-6 receptor (sIL-6R). Plasma from Puumala orthohantavirus-infected HFRS patients (n=28) were analyzed for IL-6 trans-signaling potential and its associations to severity. Findings In vitro , sIL-6R treatment of infected cells enhanced IL-6 and CCL2 secretion, upregulated ICAM-1, and affected VE-cadherin leading to a disrupted cell barrier integrity. HFRS patients showed altered plasma levels of sIL-6R and soluble gp130 (sgp130) resulting in an increased sIL-6R/sgp130 ratio suggesting enhanced IL-6 trans-signaling potential. Plasma sgp130 levels negatively correlated with number of interventions and positively with albumin levels. Patients receiving oxygen treatment displayed a higher sIL-6R/sgp130 ratio compared to patients that did not. Interpretation IL-6 trans-signaling is linked to hantavirus pathogenesis. Targeting IL-6 trans-signaling might provide a therapeutic strategy for treatment of severe HFRS and perhaps also HPS.
other
2026-09-02 | DNA and mRNA Vaccines Against Hantaviruses: Antigen Design, Delivery Strategies and Translational Progress
Hantaviruses are members of the Hantaviridae family, which can cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). At present, no specific antiviral treatment is available for hantavirus infection, while licensed hantavirus vaccines are restricted to a limited number of countries in Asia. This review summarizes recent advances in hantavirus DNA and messenger RNA (mRNA) vaccines, focusing on antigen design, delivery systems, immunogenicity, safety and translational development. Peer-reviewed studies published primarily within the past 10 years were evaluated together with available hantavirus vaccine trials registered in ClinicalTrials.gov, with emphasis on Hantaan virus (HTNV), Puumala virus (PUUV) and Andes virus (ANDV). DNA vaccine candidates have demonstrated immunogenicity in preclinical and early clinical studies, with an acceptable safety profile. mRNA vaccines represent a newer approach with promising preclinical evidence of humoral and cellular immune responses. However, they have not yet been evaluated clinically. Studies have also reported the potential for varying degrees of cross-protection between hantavirus species, although protection remains limited by antigenic diversity. Overall, current evidence supports further development of nucleic acid-based hantavirus vaccines, particularly multivalent strategies, with emphasis on standardized evaluation and clinical efficacy.
2026-03-14 | Prefusion-stabilized Hantaan virus glycoprotein nucleic acid vaccine elicits potent neutralizing antibody responses via germinal center activation
Old World orthohantaviruses, including Hantaan virus (HTNV), cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia. Available inactivated vaccines often induce low neutralizing antibodies and short-term protection. We evaluated nucleic acid vaccines expressing a prefusion-stabilized HTNV glycoprotein in female BALB/c mice. Both DNA and mRNA-LNP versions elicited robust neutralizing antibodies by strongly activating germinal centers, which protected mice against high-dose HTNV challenge. We further tested heterologous prime-boost regimens, where mice primed with inactivated vaccine received different boosters. All boosters increased neutralizing titers, but only the prefusion-stabilized glycoprotein mRNA-LNP vaccine raised titers to the level achieved by its own full primary vaccination course. This demonstrates the immunogen's superiority in developing next-generation vaccines and its unique ability to potently recall memory B cells induced by suboptimal inactivated vaccines. Thus, prefusion-stabilized glycoprotein-based nucleic acid vaccines are promising candidates for advanced orthohantavirus vaccine development.
2025-12-17 | Characterization of minigenome systems for Hantaan and Seoul hantaviruses
Some rodent-borne hantaviruses are known to cause hemorrhagic fever with renal syndrome in Europe and Asia, and hantavirus cardiopulmonary syndrome in the Americas. Despite the significant public health threat caused by hantaviruses, there are no antiviral therapeutics approved to treat hantavirus infections. One of the major limitations to study these viruses is the requirement for biosafety level 3 (BSL-3) containment. To address this concern, we previously generated a Seoul virus (SEOV) minigenome system which could be used to screen antivirals at BSL-2 level. Here, we report the development of a similar minigenome system based on the L segment of the prototype hantavirus, Hantaan virus (HTNV). In addition, we examined the activity of minigenomes based on M and S segments of SEOV and HTNV. Furthermore, we used the new HTNV minigenome system to confirm the activity of a selected group of antiviral compounds targeting the viral polymerase. All tested compounds (2'-deoxy-2'-Fluorocytidine, baloxavir, remdesivir and ribavirin) show potent anti-HTNV activity. The minigenome systems could be useful tools to study replication mechanisms and to screen antiviral compounds against hantaviruses at lower containment laboratories.
2025-02-17 | Achievement and Challenges in Orthohantavirus Vaccines
Orthohantaviruses (also known as hantaviruses) are pathogens that cause two distinct, yet related forms of severe human disease: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). These diseases pose a significant threat to global public health due to their high case fatality rates, which can range from 1% to 50%. In recent years, an increasing number of countries and regions have reported human cases, underscoring the urgent need for improved understanding, prevention, and treatment strategies. Given the severity of these diseases and the lack of specific post-exposure antiviral treatments, preventive measures are critical. For several decades, substantial efforts have been dedicated to developing orthohantavirus vaccines, leading to significant advancements. The first large-scale deployment involved inactivated vaccines, which played a crucial role in reducing HFRS incidence in South Korea and China. Subunit vaccines, viral vector vaccines, and virus-like particle (VLP) vaccines have also been extensively researched. Nucleic acid vaccines, including both mRNA and DNA vaccines, hold the greatest potential for future development due to their rapid design and production cycles, ability to elicit robust immune responses, ease of storage and transportation, and adaptable production platforms. Ongoing advancements in computer technology and artificial intelligence promise to further enhance the development of more effective orthohantavirus vaccines.
2024-03-07 | A Comprehensive Investigation of Glycoprotein-based Nucleic Acid Vaccines for Hantaan Virus
Hemorrhagic fever with renal syndrome (HFRS) occurs throughout Eurasia with considerable morbidity and mortality. Currently, the absence of specific treatments or effective antiviral drugs for hantavirus infection makes developing safe and effective vaccines a high priority. Here, we report the development of three novel nucleic acid vaccine candidates, mRNA, DNA, and DNA encapsulated in lipid nanoparticles, encoding the glycoproteins of the Hantaan virus (HTNV). To comprehensively evaluate the potential of candidate HTNV nucleic acid vaccines in preventing HFRS, we focus on evaluating their immunogenicity and efficacy in mice and comparing them with an inactivated vaccine as the benchmark. Our findings reveal that all candidate vaccines activated instant and sustained immune responses, offering effective in vivo protection. Notably, the nucleic acid vaccines demonstrated distinct advantages over the inactivated vaccine, in both humoral and cellular immunity. These results mark a significant step in developing nucleic acid vaccines for HTNV, suggesting that sequential immunization with DNA and mRNA vaccines could further amplify the advantages of nucleic acid vaccines.
small molecules
2026-08-31 | Nucleoside analogues in etiotropic therapy of hantavirus fevers
Hantavirus fevers (HF) are caused by pathogenic orthohantaviruses and are classified into two clinical forms: hemorrhagic fever with renal syndrome (HFRS), reported in Eurasia, and hantavirus pulmonary syndrome (HPS), reported in the Americas. HF are characterised by an acute course with predominant involvement of internal organs: HFRS is mainly associated with kidney damage, while HPS is characterised by severe lung injury. Both diseases may also affect the central nervous and endocrine systems. In addition, hantavirus fevers are marked by severe complications during the acute phase and a prolonged recovery period. Currently, there is neither a WHO-approved vaccine nor any effective etiotropic anti-hantavirus therapy. The development of antiviral treatment strategies focuses on preventing orthohantavirus entry into cells or suppressing their intracellular replication. One of the main directions in the search for effective anti-hantavirus therapy is the low-molecular-weight compounds development and testing, many of which have demonstrated pronounced antiviral activity against orthohantaviruses through direct or indirect effects on viral RNA polymerase function. The review shows that new antiviral nucleoside compounds development and study has promising potential, as well as their combined use for effective etiotropic, pathogenetic and symptomatic treatment of hantavirus fevers.
2026-08-01 | NE01 Panhypopituitarism following hantavirus-induced hemorrhagic fever with renal syndrome: a case report
Abstract Introduction Hemorrhagic fever is a severe infectious disease caused by RNA viruses and represents a serious systemic illness characterized by hemorrhage, a generalized infectious syndrome, and the potential development of shock. The complex nature of this pathological entity may lead to chronic damage of various organ systems, even during the recovery period. One of its prolonged and often occult complications is hypopituitarism. Case presentation We present the case of a 44-year-old male patient who was admitted to the Department of Endocrinology seven months after recovery from hantavirus-induced hemorrhagic fever with renal syndrome (HFRS). The patient was referred for endocrine evaluation due to persistent fatigue during routine daily activities, loss of libido, and reduced body hair growth. Basal hormonal assessment confirmed panhypopituitarism. Magnetic resonance imaging (MRI) of the pituitary gland revealed pituitary atrophy and partial empty sella syndrome. Replacement therapy with hydrocortisone, levothyroxine, and long-acting testosterone depot preparation was initiated. The patient showed clinical improvement and was discharged for further outpatient follow-up. Conclusion In addition to other well-established causes of panhypopituitarism, viral infections should also be considered in the differential diagnosis. Given the endemic occurrence of hantavirus infections in our region and their potential to induce pituitary dysfunction, hormonal status assessment should be included in the long-term follow-up of patients recovering from hemorrhagic fever with renal syndrome.
2026-06-25 | A drug repurposing screen identifies antiviral compounds against Puumala Orthohantavirus
Hantaviruses are zoonotic negative-sense RNA viruses that cause haemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), yet no approved antiviral therapies are available. To identify host-directed modulators of hantavirus infection we performed a drug repurposing screen using live Puumala virus (PUUV). We identified and validated 70 drugs with antiviral activity in A549 cells and primary human endothelial cells. Functional clustering confirmed the known infection-inhibitory effect of several groups of compounds, including inhibitors of heat shock proteins, mTOR pathway and nucleotide synthesis. Our screen also identified compounds yet unexplored as antivirals against Hantaviruses, such as certain antibiotics. Our dataset provides a systematic map of host pathways influencing PUUV infection and highlights candidate compounds and cellular processes that can modulate this process.
2026-06-04 | Hantavirus ANDV Glycoprotein Gc: Multi-Site Computational Analysis of Remdesivir Binding Under pH-Dependent Fusion Conditions
Hantaviruses are emerging zoonotic pathogens responsible for hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), diseases associated with substantial mortality and limited antiviral treatment options. Andes virus (ANDV), a highly pathogenic New World hantavirus, utilizes the glycoprotein complex composed of Gn and Gc proteins to mediate host-cell entry and membrane fusion. The Gc glycoprotein undergoes pH-dependent structural rearrangements during endosomal trafficking, making it an attractive therapeutic target. In the present study, a comprehensive molecular docking analysis of Remdesivir against multiple functional regions of the Andes virus glycoprotein Gc was performed using AutoDock Vina under physiologically relevant pH conditions (7.4, 5.5, and 4.6). Five structurally and functionally important regions were investigated, including the fusion-loop pocket (Region 1), Gc homodimer interface (Region 2), pH-sensing interface (Region 3), GnB–Gc stem accommodation interface (Region 4), and conserved aromatic groove stabilization region (Region 5). Remdesivir exhibited strong multi-site binding with affinities ranging from −9.1 to −7.0 kcal/mol. These findings suggest that Remdesivir may interfere with viral fusion machinery through simultaneous constitutive and pH-sensitive mechanisms. The study provides mechanistic insights into hantavirus fusion regulation and highlights the potential value of multi-site antiviral targeting strategies against emerging RNA viruses.
2026-06-02 | <b>Hantavirus Reservoirs in Human-to-Human Transmission: Deep Learning Frameworks for the Identification of Molecular Inhibitors Targeting and Virus Interhuman Pathogenesis</b>
Hantaviruses are serious emerging zoonotic RNA viruses, which are associated with two major diseases (hemorrhagic fever with renal syndrome, HFRS and hantavirus cardiopulmonary syndrome, HCPS) and are maintained mainly in rodent hosts. Of the hantaviruses, Andes virus (ANDV) has been shown to be capable of human-to-human transmission, and is thus of particular public health interest. In the present study, the role of hantavirus reservoirs in Andes virus transmission is explored and Deep Learning computational techniques are used to find molecular inhibitors that inhibit viral pathogenesis. An in-silico research design was used which involves epidemiological analysis, bioinformatics, molecular docking, virtual screening, molecular dynamics simulation, and artificial intelligence supported drug discovery. The glycoproteins (Gn/Gc), nucleocapsid proteins, fusion proteins, and the RNA-dependent RNA polymerase are targeted as therapeutic proteins. The antiviral prediction and compound screening are based on deep learning frameworks like CNN, RNN, GNN and transformer-based models. Results show that transformer-based models and graph neural network models give the maximum prediction accuracy. Several compounds are identified by molecular docking studies that have high binding affinity towards Andes virus proteins. The researchers conclude that AI-enabled computational approaches could greatly enhance the discovery and development of antiviral drugs to treat novel hantavirus infections.
vaccines
2026-07-31 | Epidemiology and changes in age distribution of hemorrhagic fever with renal syndrome in Shaanxi, China, from 2004 to 2023
INTRODUCTION: Hemorrhagic fever with renal syndrome (HFRS) is a serious viral disease in mainland China, and Shaanxi Province is one of the most severely affected areas. In order to reduce HFRS incidence, an inactivated bivalent vaccine against Hantaan virus (HTNV) and Seoul virus (SEOV) infections was developed and used in China since the 1990s. METHODOLOGY: Descriptive epidemiological methods were used to analyze the spatial, temporal, and population distribution of HFRS along with changes in age distribution in Shaanxi Province from January 2004 to December 2023. RESULTS: A total of 34,265 HFRS human cases were reported in Shaanxi Province, including 25,737 males and 8,528 females. HFRS cases were geographically concentrated in the Guanzhong Plain. The local incidence of HFRS fluctuated remarkably over the past 20 years. The primary peak was from October to January. The proportion of HFRS cases in the 15-60 years age group showed a decreasing trend. However, the proportion of HFRS cases among the > 60 years age group increased by 150.94%, rising from 11.68% to 29.31%. CONCLUSIONS: Data from a 20-year surveillance study shows that the proportion of HFRS cases in individuals over 60 years of age has increased significantly, which may potentially be due to vaccine coverage limitations. The results can be used to adjust the prevention and control measures of HFRS and to consider age-expanded vaccination strategies.
2026-01-01 | Immunoinformatics-driven design of a multi-epitope vaccine against Seoul Virus: Structural, dynamic, and immunogenic profiling
• Immunoinformatics-based design of a multi-epitope vaccine against Seoul virus (SEOV). • Designed Vaccine construct V2 showed 95.94% global coverage and strong antigenicity. • Docking and molecular dynamics simulations confirmed stable binding of V2 with the TLR4 receptor. • Immune simulations predicted strong IgG1, IFN-γ, and memory responses of V2. • Codon optimization and in silico cloning confirmed expression feasibility. Seoul Virus (SEOV), a zoonotic hantavirus, is a major cause of Hemorrhagic Fever with Renal Syndrome (HFRS) and represents a global health challenge. With no licensed vaccines or specific antivirals available, this study aimed to design a glycoprotein-based multi-epitope vaccine against SEOV using immunoinformatics approaches. Material s and methods MHC-I and MHC-II epitopes were predicted via the Immune Epitope Database (IEDB) and screened for antigenicity, non-allergenicity, and non-toxicity. Four constructs were designed, with V2 selected as the best candidate. Structural modeling was performed using AlphaFold3 and validated with Ramachandran analysis. Molecular docking with Toll-like receptor-4, molecular dynamics simulations, and immune simulations were conducted to evaluate stability and immunogenicity. The V2 construct demonstrated high antigenicity (0.683) and broad population coverage (95.94%). Structural validation confirmed 95.6% of residues in favored regions. Docking revealed strong binding to Toll-like receptor-4, and dynamics confirmed stability through RMSD, RMSF, Rg, PCA, DCCM, and FEL analysis. Immune simulations predicted robust responses, including high IgG1 titers. Codon optimization (GC content 56.62%) and cloning confirmed expression potential. The V2 construct exhibits stability, strong immunogenicity, and broad population coverage, supporting its potential as a vaccine candidate against SEOV. Experimental validation in vitro and in vivo is required to confirm efficacy and safety.
2026-01-01 | The Use of Artificial Intelligence to Create a Model for the Vaccine Against the Hantavirus
Abstract Background — Hantaviruses are globally distributed zoonotic pathogens responsible for Hemorrhagic Fever with Renal Syndrome (HFRS) and Hantavirus Pulmonary Syndrome (HPS). Maintained in rodent reservoirs and transmitted through aerosolised excreta, they remain a persistent public health threat. Their enveloped structure, incorporating Gn/Gc glycoproteins and ribonucleoprotein complexes, complicates traditional vaccine development. Recent advances in AI driven vaccinology offer new strategies for identifying antigenic determinants and designing safer, more immunogenic constructs. Methods — An integrated AI computational pipeline combined structural modelling, reverse vaccinology, and immunoinformatics. Glycoprotein sequences from representative hantaviruses were modelled to predict conformational features. Deep learning algorithms identified high affinity B cell epitopes and T cell epitopes, which were assembled into a multi epitope construct. Allergenicity, toxicity, and population coverage were computationally screened, and immune simulations assessed predicted host responses. Results — The AI generated construct demonstrated high predicted antigenicity, favourable physicochemical stability, and non allergenic, non toxic profiles. Structural modelling confirmed appropriate folding and solvent exposure of key epitopes. Immune simulations suggested strong induction of humoral and cellular responses, including memory cell formation. Conclusions — AI enabled vaccine design provides a rapid, rational framework for developing next generation hantavirus vaccines. By integrating molecular virology with machine learning, this approach accelerates antigen discovery and construct optimisation. The findings support AI as a transformative tool for emerging pathogen vaccine development and highlight its potential to overcome longstanding barriers in hantavirus prevention.
2025-09-06 | [Analysis of epidemic characteristics and vaccination status of hemorrhagic fever with renal syndrome in Baoji City of Shaanxi Province from 2008 to 2023].
To analyze the epidemic characteristics and vaccination status of hemorrhagic fever with renal syndrome (HFRS) in Baoji City from 2008 to 2023. The descriptive epidemiological method was used to collect the incidence data of HFRS cases in Baoji City from 2008 to 2003 in the Infectious Disease Reporting Information Management System. The epidemic characteristics of HFRS cases were summarized and analyzed. The data on HFRS vaccination from 2008 to 2023 were consulted through the Baoji Hemorrhagic Fever Vaccination Report, and the relationship between vaccination status and reported incidence was analyzed. The results showed that a total of 2 690 cases of HFRS were reported in Baoji City, with an annual average reported incidence rate of 6.94/100 000, 15 cases died and a case fatality rate of 0.41%. The number of reported HFRS cases showed a fluctuating trend, with a peak in 2011-2013. Since 2016, it entered a low-level stable fluctuation period, and the annual mortality rate dropped to below 1% after 2011. From 2008 to 2023, Fufeng County, Meixian County and Chencang District reported a large number of cases, but Linyou County and other counties in the north showed an upward trend in incidence, with obvious seasonal characteristics. Cases were mainly concentrated from October to January of the following year, accounting for 75.91% of the total number of cases. Farmers were the main reported occupations, accounting for 80.19% of the total number of cases. The ratio of male to female reported cases was 3.30∶1. The age group of 35-59 years old accounted for 51.08% of the cases, and the proportion of the age group of 60 years and above showed an upward trend (χ2=331.44, P<0.001). From 2008 to 2023, a total of 1 559 619 people were vaccinated, and the vaccination rate of the target population aged 16-60 years reached 72.23%. With the increase in the vaccination rate, the incidence of HFRS continued to decrease. In summary, with the development of HFRS vaccination work, the epidemic characteristics of HFRS in Baoji City have changed, and the peak incidence has been controlled. The proportion of cases in the age group of 60 years and above continues to increase. HFRS vaccination is still an effective way of prevention and control, and vaccination strategies should be continuously optimized according to the characteristics of HFRS.
2025-06-12 | Genetic and codon usage analyses reveal the evolution of the seoul virus
Seoul virus (Orthohantavirus seoulense, SEOV), a member of the Hantaviridae, causes hemorrhagic fever with renal syndrome (HFRS) through rodent hosts. However, its molecular evolutionary dynamics and codon usage patterns remain poorly understood. This study integrated coding sequences from GenBank and previously acquired SEOV strains to systematically analyze genetic evolution and codon usage bias. It revealed that SEOV evolved seven clades (A-G) with distinct amino acid variation sites and geographic clustering. Recombination events were identified during evolution, alongside purifying and positive selection on specific sites (e.g., codon 259 in the S segment and codon 11 in the M segment). The three viral segments (L, M, and S) exhibited weak codon usage bias, predominantly driven by natural selection, with host adaptation significantly influencing evolutionary trajectories. The S segment demonstrated the strongest pathogenicity due to its closer codon usage alignment with Homo sapiens (H. sapiens) and Rattus norvegicus (R. norvegicus), whereas the L segment showed the lowest host adaptation. Divergent codon preferences among clades highlighted adaptive strategies in host-virus interactions. These findings elucidate the evolutionary mechanisms of SEOV and provide a theoretical foundation for live attenuated vaccine design and region-specific viral control strategies.
antibodies
2026-07-31 | The Changing Landscape of Hantavirus Infections: A Narrative Review of Epidemiology, Pathogenesis, and Countermeasures
Hantaviruses are emerging zoonotic pathogens of increasing global public health significance. Their epidemiological landscape is rapidly changing due to ecological disruption, climate variability, urbanisation, and evolving human-animal interfaces. This narrative review synthesises current knowledge on hantavirus virology, epidemiology, pathogenesis, clinical management, and emerging countermeasures, with a focus on developments from the past 5 years. Traditionally classified into Old World viruses causing haemorrhagic fever with renal syndrome (HFRS) and New World viruses causing hantavirus cardiopulmonary syndrome (HCPS), this dichotomy has become increasingly blurred, with overlapping renal and pulmonary manifestations now recognized. Among the most consequential recent advances is the consolidated evidence for person-to-person transmission of Andes virus, documented among household contacts and during the prodromal phase, with viral shedding in respiratory secretions. Endothelial dysfunction remains the pathological hallmark of severe disease, driven by VEGF sensitisation, Src kinase and RhoA pathway activation, pericyte infection, and dysregulated inflammatory responses including IL-6 trans-signalling. Concurrently, environmental and ecological studies have linked climate change, rodent population dynamics, land-use modification, and urbanisation to increased human disease risk across multiple continents. Diagnostic strategies continue to rely on serology and molecular testing, while management remains predominantly supportive, with extracorporeal membrane oxygenation (ECMO) improving survival in fulminant HCPS. Importantly, recent structural virology advances have enabled the development of broadly neutralising monoclonal antibodies targeting conserved quaternary epitopes, as well as next-generation vaccine platforms including DNA, mRNA, and prefusion-stabilised glycoprotein candidates. Hantaviruses represent a paradigmatic One Health challenge at the intersection of environmental change, viral evolution, and global interconnectedness. Despite major progress in understanding transmission dynamics and endothelial pathogenesis, critical gaps remain regarding determinants of person-to-person spread, long-term post-infection sequelae, and the absence of licenced broadly protective vaccines or specific antiviral therapies. Future preparedness will require integrated surveillance frameworks combining ecological monitoring, genomic epidemiology, and clinical readiness within coordinated international public health strategies.
2026-01-01 | Broadly Neutralizing Antibodies Against Emerging Hantaviruses: Structural Mechanisms, Cross-Protection, and Multi-Scale Immunotherapeutic Perspectives
This repository contains the supplementary data, structural immunoinformatics metrics, and multi-scale systems architecture corresponding to the manuscript: "Broadly Neutralizing Antibodies Against Emerging Hantaviruses: Structural Mechanisms, Cross-Protection, and Multi-Scale Immunotherapeutic Perspectives". Context & Objectives Hantaviruses represent a severe threat to global public health, causing Hantavirus Pulmonary Syndrome (HPS) and Hemorrhagic Fever with Renal Syndrome (HFRS). This dataset supports a comprehensive systematic review (2021–2024) conducted under PRISMA guidelines and formalizes a novel multi-scale control framework for evaluating broadly neutralizing antibodies (bNAbs) targeting the conserved Gn/Gc glycoprotein epitopes. Content of the Repository PRISMA_Flowchart_Metrics.csv/.pdf: Comprehensive screening, inclusion/exclusion matrices, and structural data extracted from recent literature on cross-reactive hantavirus neutralizing antibodies. Systems_Biology_Architecture_Code/: Computational state-space modeling scripts and non-linear dynamic simulation protocols used to formalize neutralization as an emergent property of complex adaptive immune networks (Ashby’s Law of Requisite Variety application). Figure_1_HighRes.png: The multi-scale immunotherapeutic control architecture diagram mapping molecular interactions to systemic immune responses. Methodology Data curation follows strict systems biology protocols, integrating structural structural biology data with control theory principles to transcend single-scale binding affinity models. Keywords Hantavirus Broadly Neutralizing Antibodies Structural Immunology Systems Biology Control Theory State-Space Modeling Emergent Immunity PRISMA Framework
2025-07-26 | Hantavirus Conducted Route from Mice to Human: Potential Dangers and Outcomes of Zoonosis
The hantavirus is associated with deadly illnesses including hemorrhagic fever associated with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), and there are an astounding 200,000 new infections of this virus per year.It is a major concern for world health.Murid rats are the major hosts of these viruses, which operate as silent reservoirs that enable zoonotic transmission to humans via aerosolized faeces.Particularly in endemic regions, the intricate interplay between environmental conditions and human behaviour substantially impacts the transmission of hantavirus infections.This research addresses the complicated biology and pathophysiology of hantaviruses, underlining the crucial need for better immunisation and treatment alternatives.Although numerous promising vaccine candidates are being researched, problems remain in obtaining enduring protection and assuring safety.Also, efforts into neutralizing antigens as prospective therapies give a glimmer of light to better the lives of patients.A comprehensive approach that involves monitoring, public education, and research into innovative vaccines and therapies is required to battle hantavirus infections, decrease public health hazards, and protect vulnerable populations.
2025-05-13 | Urinalysis of a Hantaan virus-infected mouse model of hemorrhagic fever with renal syndrome
Hantaan virus causes hemorrhagic fever with renal syndrome (HFRS), a rodent-borne zoonotic disease. Korean hemorrhagic fever virus (KHFV), a strain of Hantaan virus, showed symptoms in mice similar to those of HFRS patients, including weight loss, renal medullary hemorrhage, hepatitis, and neutrophilia. Therefore, mice inoculated with KHFV were expected to serve as a model for HFRS. However, urinary symptoms characteristic of HFRS, such as proteinuria and hematuria, have not yet been examined. In this study, we attempted to evaluate renal function by analyzing urine. As a result, in mice inoculated with KHFV, oliguria and hematuria accompanied by weight loss were observed at 5-8 days after inoculation, and albuminuria was also observed. In addition, the viral load in the kidney and viral excretion into the urine were observed. When the neutralizing monoclonal antibody HCO2 against Hantaan virus was administered before inoculation, all symptoms were abolished. To clarify the therapeutic effect of HCO2 antibody, it was administered intravenously on days 1, 3, and 5 after infection. Weight loss and renal medullary hemorrhage were suppressed, and histological examination revealed micro renal hemorrhage in mice on day 5 administration. It was found that neutralizing antibody can be expected to alleviate symptoms even if it is administered late, and that early administration is more effective. These results indicate that this mouse model shows symptoms like human HFRS and can be used to evaluate antiviral effects.
2025-05-08 | Puumala orthohantavirus: prevalence, biology, disease, animal models and recent advances in therapeutics development and structural biology
Puumala orthohantavirus (PUUV) is an emerging zoonotic virus that was first discovered in the Puumala region of Finland in the early 1980s and is the primary etiological agent of nephropathia epidemica (NE), a milder form of a life-threatening disease known as hemorrhagic fever with renal syndrome (HFRS). PUUV and other members of the Old World hantaviruses (OWHVs) predominantly circulate in rodents or insectivores across Eurasia, accounting for several thousand of reported HFRS cases every year (with many more unreported/misdiagnosed cases suspected). The rodent reservoir of PUUV is the common bank vole (Myodes (M.) glareolus), and transmission of the virus to humans occurs via inhalation of contagious aerosols and through contact with contaminated droppings or urine. Although PUUV is the subject of extensive research, due to its potential to cause severe disease outcomes in humans and its considerable economic and social impact, neither licensed vaccines nor specific antiviral treatments are available against PUUV. However, many important advancements have been made in terms of PUUV research over the last years. This included the elucidation of its glycoproteins, the discovery of broadly neutralizing hantavirus antibodies as therapeutic candidates and expanded research on the mRNA vaccine technology which will likely enable the development of strong PUUV vaccine candidates in the near future. Currently, there is still a lack of suitable animal models for the preclinical evaluation of experimental vaccines and antivirals, which hampers vaccine and antiviral development. Current attempts to decrease hantavirus-associated human infections rely primarily on prevention and countermeasures for rodent control, including reduced contact to droppings, saliva and urine, and disinfection of areas that are contaminated with rodent excreta. Here, we review these recent advances and other aspects including PUUV prevalence, virus biology, diagnosis and clinical features, and current animal models for vaccine and treatment development.
proteins
2026-08-03 | Angiopoietin-1/Tie2 Activation as a Therapeutic Hypothesis for Hantavirus-Induced Vascular Permeability
Severe hantavirus infection produces extensive vascular leakage, driven by a combination of endothelial dysfunction, dysregulated inflammation, VEGF-mediated hyperpermeability, angiopoietin imbalance, and degradation of the endothelial glycocalyx. This narrative review draws on the peer-reviewed literature, with particular attention to work published between 2016 and 2026, to examine how hantavirus-induced vascular permeability arises in hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS), and how Angiopoietin-1 (Ang-1)/Tie2 signaling and glycocalyx injury contribute to endothelial barrier failure. Direct hantavirus evidence shows that Ang-1 inhibits hantavirus-directed endothelial permeability in vitro and that angiopoietin dysregulation tracks with disease severity in patients; findings that Tie2 activation curbs vascular leakage in sepsis and other non-hantavirus models are mechanistically suggestive but remain inferential rather than hantavirus-specific. No hantavirus animal model or clinical trial has yet evaluated Ang-1/Tie2-directed therapy, so this review treats the approach as a testable hypothesis rather than an established or recommended treatment; confirming its therapeutic value will require dedicated hantavirus-specific animal and clinical studies.
2026-05-17 | THE RODENT RECEPTOR CODE: A HOST-ENCODED Β3- INTEGRIN DECOY DOMAIN DICTATES HANTAVIRUS PATHOGENICITY
ABSTRACTHantaviruses cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome(HPS) in humans, with case-fatality rates reaching 10-15% for HFRS and 40-60% for HPS, yet remaincompletely asymptomatic in their reservoir rodent hosts. The molecular basis of this host-specificpathogenicity has remained one of the most enigmatic questions in hantavirology.Here, we demonstrate that a single amino acid polymorphism at position 39 of the β3-integrin plexinsemaphorin-integrin (PSI) domain — Aspartate in humans versus Asparagine in all eight major reservoirspecies — functions as a molecular switch that couples hantavirus glycoprotein binding to downstream propermeability signaling. We cloned β3-integrin PSI domains from all eight reservoir species (Apodemusagrarius, A. flavicollis, Rattus norvegicus, Myodes glareolus, Microtus arvalis, Peromyscus maniculatus,Oligoryzomys longicaudatus, and Homo sapiens) and showed that rodent PSI peptides bind hantavirus Gn/Gc envelope glycoproteins with high affinity but fail to activate the FAK/Src/PI3K/Akt/VEGF-mTORpermeability axis. In contrast, human β3-integrin engagement by Gn/Gc triggers robust signaling, adherensjunction disruption, and vascular leakage.Leveraging this mechanistic insight, we designed soluble "decoy" peptides mimicking the rodent Asn-39PSI domain that competitively inhibit hantavirus entry into human endothelial cells with IC50 values of0.5-1.2 μg/ml and selectivity indices exceeding 500x. In the Syrian hamster model of lethal Andes virus(ANDV) infection, prophylactic administration of Decoy-2 (derived from M. glareolus) conferred 70%survival versus 0% in vehicle controls (p < 0.001), reduced tissue viral loads by >3 log10 copies/g,suppressed cytokine storm, and preserved pulmonary and renal histopathology. These findings identify thefirst host-encoded viral entry decoy, establish the "rodent receptor code" as the mechanistic basis ofreservoir asymptomaticity, and provide a first-in-class hantavirus-specific therapeutic candidate currentlyabsent from the clinical armamentarium.Keywords: hantavirus, β3-integrin, PSI domain, decoy peptide, vascular permeability, host-pathogen evolution,translational therapeutics
2025-05-29 | Dynamic alterations of circulating lymphocytes during the trajectory of Hantaan virus-induced hemorrhagic fever with renal syndrome
Here, we revealed phase-specific immune patterns: CD8+ T, CD8+ Tems, and activated CD8+ T, MAIT and NKT cells peaked during febrile/oliguric phases before declining in polyuria/recovery, while CD4+ T and MAIT cells showed inverse fluctuation patterns. Higher frequencies of CD8+ Tem, B, and CD56dim NK cells during the febrile phase correlated with severe disease, enabling early risk stratification. Lower CD4+ Tcm levels in the oliguric phase marked progression to severe HFRS, indicating potential therapeutic strategies aimed at enhancing CD4+ Tcm generation or inhibiting effector differentiation. Additionally, CD38 and CD161 expression predicted specific lymphocyte subset dynamics, offering novel biomarkers for immunomodulatory strategies. Our study thus provides the first comprehensive atlas of lymphocyte evolution in HTNV-induced HFRS, connecting immune dysregulation with clinical outcomes.
2025-04-09 | Raw data for all figures.
Background Hantavirus causes hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Strong inflammatory responses and vascular leakage are important hallmarks of these often fatal diseases. The mechanism behind pathogenesis is unknown and no specific treatment is available. IL-6 was recently highlighted as a biomarker for HPS/HFRS severity. IL-6 signaling is complex and context dependent: while classical signaling generally provide protective responses, trans-signaling can cause severe pathogenic responses. Here, we investigated a potential role for IL-6 trans-signaling in hantavirus pathogenesis. Methods Effects of IL-6 trans-signaling during in vitro hantavirus infection were assessed using primary human endothelial cells treated with recombinant soluble IL-6 receptor (sIL-6R). Plasma from Puumala orthohantavirus-infected HFRS patients (n=28) were analyzed for IL-6 trans-signaling potential and its associations to severity. Findings In vitro, sIL-6R treatment of infected cells enhanced IL-6 and CCL2 secretion, upregulated ICAM-1, and affected VE-cadherin leading to a disrupted cell barrier integrity. HFRS patients showed altered plasma levels of sIL-6R and soluble gp130 (sgp130) resulting in an increased sIL-6R/sgp130 ratio suggesting enhanced IL-6 trans-signaling potential. Plasma sgp130 levels negatively correlated with number of interventions and positively with albumin levels. Patients receiving oxygen treatment displayed a higher sIL-6R/sgp130 ratio compared to patients that did not. Interpretation IL-6 trans-signaling is linked to hantavirus pathogenesis. Targeting IL-6 trans-signaling might provide a therapeutic strategy for treatment of severe HFRS and perhaps also HPS.
2025-04-09 | IL-6 trans-signaling mediates cytokine secretion and barrier dysfunction in hantavirus-infected cells and correlate to severity in HFRS
Background Hantavirus causes hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). Strong inflammatory responses and vascular leakage are important hallmarks of these often fatal diseases. The mechanism behind pathogenesis is unknown and no specific treatment is available. IL-6 was recently highlighted as a biomarker for HPS/HFRS severity. IL-6 signaling is complex and context dependent: while classical signaling generally provide protective responses, trans-signaling can cause severe pathogenic responses. Here, we investigated a potential role for IL-6 trans-signaling in hantavirus pathogenesis. Methods Effects of IL-6 trans-signaling during in vitro hantavirus infection were assessed using primary human endothelial cells treated with recombinant soluble IL-6 receptor (sIL-6R). Plasma from Puumala orthohantavirus-infected HFRS patients (n=28) were analyzed for IL-6 trans-signaling potential and its associations to severity. Findings In vitro , sIL-6R treatment of infected cells enhanced IL-6 and CCL2 secretion, upregulated ICAM-1, and affected VE-cadherin leading to a disrupted cell barrier integrity. HFRS patients showed altered plasma levels of sIL-6R and soluble gp130 (sgp130) resulting in an increased sIL-6R/sgp130 ratio suggesting enhanced IL-6 trans-signaling potential. Plasma sgp130 levels negatively correlated with number of interventions and positively with albumin levels. Patients receiving oxygen treatment displayed a higher sIL-6R/sgp130 ratio compared to patients that did not. Interpretation IL-6 trans-signaling is linked to hantavirus pathogenesis. Targeting IL-6 trans-signaling might provide a therapeutic strategy for treatment of severe HFRS and perhaps also HPS.
other
2026-09-02 | DNA and mRNA Vaccines Against Hantaviruses: Antigen Design, Delivery Strategies and Translational Progress
Hantaviruses are members of the Hantaviridae family, which can cause hemorrhagic fever with renal syndrome (HFRS) and hantavirus cardiopulmonary syndrome (HCPS). At present, no specific antiviral treatment is available for hantavirus infection, while licensed hantavirus vaccines are restricted to a limited number of countries in Asia. This review summarizes recent advances in hantavirus DNA and messenger RNA (mRNA) vaccines, focusing on antigen design, delivery systems, immunogenicity, safety and translational development. Peer-reviewed studies published primarily within the past 10 years were evaluated together with available hantavirus vaccine trials registered in ClinicalTrials.gov, with emphasis on Hantaan virus (HTNV), Puumala virus (PUUV) and Andes virus (ANDV). DNA vaccine candidates have demonstrated immunogenicity in preclinical and early clinical studies, with an acceptable safety profile. mRNA vaccines represent a newer approach with promising preclinical evidence of humoral and cellular immune responses. However, they have not yet been evaluated clinically. Studies have also reported the potential for varying degrees of cross-protection between hantavirus species, although protection remains limited by antigenic diversity. Overall, current evidence supports further development of nucleic acid-based hantavirus vaccines, particularly multivalent strategies, with emphasis on standardized evaluation and clinical efficacy.
2026-03-14 | Prefusion-stabilized Hantaan virus glycoprotein nucleic acid vaccine elicits potent neutralizing antibody responses via germinal center activation
Old World orthohantaviruses, including Hantaan virus (HTNV), cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia. Available inactivated vaccines often induce low neutralizing antibodies and short-term protection. We evaluated nucleic acid vaccines expressing a prefusion-stabilized HTNV glycoprotein in female BALB/c mice. Both DNA and mRNA-LNP versions elicited robust neutralizing antibodies by strongly activating germinal centers, which protected mice against high-dose HTNV challenge. We further tested heterologous prime-boost regimens, where mice primed with inactivated vaccine received different boosters. All boosters increased neutralizing titers, but only the prefusion-stabilized glycoprotein mRNA-LNP vaccine raised titers to the level achieved by its own full primary vaccination course. This demonstrates the immunogen's superiority in developing next-generation vaccines and its unique ability to potently recall memory B cells induced by suboptimal inactivated vaccines. Thus, prefusion-stabilized glycoprotein-based nucleic acid vaccines are promising candidates for advanced orthohantavirus vaccine development.
2025-12-17 | Characterization of minigenome systems for Hantaan and Seoul hantaviruses
Some rodent-borne hantaviruses are known to cause hemorrhagic fever with renal syndrome in Europe and Asia, and hantavirus cardiopulmonary syndrome in the Americas. Despite the significant public health threat caused by hantaviruses, there are no antiviral therapeutics approved to treat hantavirus infections. One of the major limitations to study these viruses is the requirement for biosafety level 3 (BSL-3) containment. To address this concern, we previously generated a Seoul virus (SEOV) minigenome system which could be used to screen antivirals at BSL-2 level. Here, we report the development of a similar minigenome system based on the L segment of the prototype hantavirus, Hantaan virus (HTNV). In addition, we examined the activity of minigenomes based on M and S segments of SEOV and HTNV. Furthermore, we used the new HTNV minigenome system to confirm the activity of a selected group of antiviral compounds targeting the viral polymerase. All tested compounds (2'-deoxy-2'-Fluorocytidine, baloxavir, remdesivir and ribavirin) show potent anti-HTNV activity. The minigenome systems could be useful tools to study replication mechanisms and to screen antiviral compounds against hantaviruses at lower containment laboratories.
2025-02-17 | Achievement and Challenges in Orthohantavirus Vaccines
Orthohantaviruses (also known as hantaviruses) are pathogens that cause two distinct, yet related forms of severe human disease: hemorrhagic fever with renal syndrome (HFRS) and hantavirus pulmonary syndrome (HPS). These diseases pose a significant threat to global public health due to their high case fatality rates, which can range from 1% to 50%. In recent years, an increasing number of countries and regions have reported human cases, underscoring the urgent need for improved understanding, prevention, and treatment strategies. Given the severity of these diseases and the lack of specific post-exposure antiviral treatments, preventive measures are critical. For several decades, substantial efforts have been dedicated to developing orthohantavirus vaccines, leading to significant advancements. The first large-scale deployment involved inactivated vaccines, which played a crucial role in reducing HFRS incidence in South Korea and China. Subunit vaccines, viral vector vaccines, and virus-like particle (VLP) vaccines have also been extensively researched. Nucleic acid vaccines, including both mRNA and DNA vaccines, hold the greatest potential for future development due to their rapid design and production cycles, ability to elicit robust immune responses, ease of storage and transportation, and adaptable production platforms. Ongoing advancements in computer technology and artificial intelligence promise to further enhance the development of more effective orthohantavirus vaccines.
2024-03-07 | A Comprehensive Investigation of Glycoprotein-based Nucleic Acid Vaccines for Hantaan Virus
Hemorrhagic fever with renal syndrome (HFRS) occurs throughout Eurasia with considerable morbidity and mortality. Currently, the absence of specific treatments or effective antiviral drugs for hantavirus infection makes developing safe and effective vaccines a high priority. Here, we report the development of three novel nucleic acid vaccine candidates, mRNA, DNA, and DNA encapsulated in lipid nanoparticles, encoding the glycoproteins of the Hantaan virus (HTNV). To comprehensively evaluate the potential of candidate HTNV nucleic acid vaccines in preventing HFRS, we focus on evaluating their immunogenicity and efficacy in mice and comparing them with an inactivated vaccine as the benchmark. Our findings reveal that all candidate vaccines activated instant and sustained immune responses, offering effective in vivo protection. Notably, the nucleic acid vaccines demonstrated distinct advantages over the inactivated vaccine, in both humoral and cellular immunity. These results mark a significant step in developing nucleic acid vaccines for HTNV, suggesting that sequential immunization with DNA and mRNA vaccines could further amplify the advantages of nucleic acid vaccines.
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Drug Discovery Landscape
2 orphan drug designations for Hemorrhagic fever-renal syndrome.
2 orphan drug designations for Hemorrhagic fever-renal syndrome.
Drug | Therapy type | Orphan designation | Clinical trial status | Sponsor |
|---|---|---|---|---|
Hantaan virus and Puumala virus DNA vaccines | oligonucleotides | FDA | Surgeon General of the U. S. Army | |
ribavirin | small molecules | FDA | Valeant Pharmaceuticals International |
“Terminated” – programs with discontinued clinical trials, or with no updates reported for 5 years after completion or 12 years after the last trial started.
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