Pub Date : 2026-12-01Epub Date: 2026-02-16DOI: 10.1080/22221751.2026.2627067
Shixing Chen, Tao Liu, Jing Chen, Shengxia Yin, Jinqiu Ran, Wen Zhang, Wanying Zhang, Juan Zhang, Chen Li, Xun Wang, Pengfei Wang, Chao Wu, Fan Yang, Yuxin Chen
Older adults remain highly vulnerable to severe SARS-CoV-2 outcomes despite multiple vaccinations, yet age-associated differences in immune responses to updated COVID-19 booster vaccines remain incompletely characterized. Here, we administered an XBB.1.5 trivalent recombinant protein booster (WSK-V102C) to 22 individuals (<38 years) and 20 individuals (≥73 years), all of whom had previously received 2-3 doses of inactivated COVID-19 vaccines. Neutralizing antibody responses against multiple SARS-CoV-2 variants were quantified and compared between age groups. Meanwhile, single-cell RNA sequencing was also performed on peripheral blood mononuclear cells (PBMCs) collected at baseline and 28 days post-vaccination to profile age-associated immune features following boosting. Following booster immunization, both age groups achieved significantly elevated antibody titres against all tested strains. Nevertheless, the magnitude of antibody fold increase was consistently lower in elderly individuals than in younger adults. Single-cell analyses revealed age-associated differences in post-vaccination immune organization. In elderly individuals, B-cell state transitions were characterized by transcriptional signatures consistent with memory B cell-to-plasmablast differentiation, whereas younger individuals predominantly exhibited transitions from naïve B cells. CD4+ T cells from elderly individuals displayed altered transcriptional trajectories and reduced T-cell receptor diversity relative to younger adults. In contrast, younger individuals showed coordinated B- and T-cell-associated transcriptional programmes, including enrichment of transcription factors such as KLF7, CEBPB, CEBPD, and MAFB. Collectively, our study describes age-associated differences in immune coordination and cellular response patterns following XBB.1.5 booster vaccination. Further longitudinal and functional studies will be required to clarify the mechanistic basis and clinical implications of these observations.
{"title":"Age-associated differences in XBB.1.5 trivalent booster vaccine-induced adaptive responses revealed by single-cell RNA sequencing.","authors":"Shixing Chen, Tao Liu, Jing Chen, Shengxia Yin, Jinqiu Ran, Wen Zhang, Wanying Zhang, Juan Zhang, Chen Li, Xun Wang, Pengfei Wang, Chao Wu, Fan Yang, Yuxin Chen","doi":"10.1080/22221751.2026.2627067","DOIUrl":"10.1080/22221751.2026.2627067","url":null,"abstract":"<p><p>Older adults remain highly vulnerable to severe SARS-CoV-2 outcomes despite multiple vaccinations, yet age-associated differences in immune responses to updated COVID-19 booster vaccines remain incompletely characterized. Here, we administered an XBB.1.5 trivalent recombinant protein booster (WSK-V102C) to 22 individuals (<38 years) and 20 individuals (≥73 years), all of whom had previously received 2-3 doses of inactivated COVID-19 vaccines. Neutralizing antibody responses against multiple SARS-CoV-2 variants were quantified and compared between age groups. Meanwhile, single-cell RNA sequencing was also performed on peripheral blood mononuclear cells (PBMCs) collected at baseline and 28 days post-vaccination to profile age-associated immune features following boosting. Following booster immunization, both age groups achieved significantly elevated antibody titres against all tested strains. Nevertheless, the magnitude of antibody fold increase was consistently lower in elderly individuals than in younger adults. Single-cell analyses revealed age-associated differences in post-vaccination immune organization. In elderly individuals, B-cell state transitions were characterized by transcriptional signatures consistent with memory B cell-to-plasmablast differentiation, whereas younger individuals predominantly exhibited transitions from naïve B cells. CD4+ T cells from elderly individuals displayed altered transcriptional trajectories and reduced T-cell receptor diversity relative to younger adults. In contrast, younger individuals showed coordinated B- and T-cell-associated transcriptional programmes, including enrichment of transcription factors such as KLF7, CEBPB, CEBPD, and MAFB. Collectively, our study describes age-associated differences in immune coordination and cellular response patterns following XBB.1.5 booster vaccination. Further longitudinal and functional studies will be required to clarify the mechanistic basis and clinical implications of these observations.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2627067"},"PeriodicalIF":7.5,"publicationDate":"2026-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12912223/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146112620","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Multiple influenza virus subtypes actively circulate in nature, and assessing their transmissibility provides crucial information for predicting their pandemic potential and for pandemic preparedness. Here, we evaluated the receptor-binding preferences, replication, and transmission of five different influenza viruses (i.e., CA/07-H1N1, GX/18-H1N1, CK/S2283-H3N8, CK/SD007-H9N2, and DK/35-H5N1) in Syrian hamsters. Receptor-binding analysis using biolayer interferometry revealed that four of these viruses preferentially bound α2,6-linked sialic acid receptors, whereas the H5N1 virus bound to α2,3-linked and α2,6-linked sialic acid receptors similarly. All five viruses replicated well in the respiratory tissues of Syrian hamsters, but did not cause obvious symptoms or death, indicating that Syrian hamsters can tolerate influenza virus infection and are not suitable for influenza virus pathogenicity studies. The four viruses that bound to α2,6-linked sialic acid receptors with higher affinity than to α2,3-linked sialic acid receptors were transmissible between Syrian hamsters via direct contact or respiratory droplets; however, the H5N1 virus was not transmissible through respiratory droplets, consistent with previously reported transmission characteristics observed for these viruses in guinea pigs and ferrets. Given that Syrian hamsters and humans have similar receptor expression patterns in their nasal mucosa, our findings suggests that Syrian hamsters can be used as a suitable animal model for evaluating the transmissibility of influenza viruses that preferentially bind to α2,6-linked sialic acid receptors.
{"title":"Syrian hamster is an ideal animal model for evaluating the transmissibility of emerging influenza viruses.","authors":"Jiongjie Li, Dongxue Wang, Bin Li, Jinming Ma, Xinwen He, Lei Chen, Huihui Kong, Guohua Deng, Pengfei Cui, Huanliang Yang, Fei Meng, Xianying Zeng, Guobin Tian, Jianzhong Shi, Hualan Chen","doi":"10.1080/22221751.2026.2629629","DOIUrl":"https://doi.org/10.1080/22221751.2026.2629629","url":null,"abstract":"<p><p>Multiple influenza virus subtypes actively circulate in nature, and assessing their transmissibility provides crucial information for predicting their pandemic potential and for pandemic preparedness. Here, we evaluated the receptor-binding preferences, replication, and transmission of five different influenza viruses (i.e., CA/07-H1N1, GX/18-H1N1, CK/S2283-H3N8, CK/SD007-H9N2, and DK/35-H5N1) in Syrian hamsters. Receptor-binding analysis using biolayer interferometry revealed that four of these viruses preferentially bound α2,6-linked sialic acid receptors, whereas the H5N1 virus bound to α2,3-linked and α2,6-linked sialic acid receptors similarly. All five viruses replicated well in the respiratory tissues of Syrian hamsters, but did not cause obvious symptoms or death, indicating that Syrian hamsters can tolerate influenza virus infection and are not suitable for influenza virus pathogenicity studies. The four viruses that bound to α2,6-linked sialic acid receptors with higher affinity than to α2,3-linked sialic acid receptors were transmissible between Syrian hamsters via direct contact or respiratory droplets; however, the H5N1 virus was not transmissible through respiratory droplets, consistent with previously reported transmission characteristics observed for these viruses in guinea pigs and ferrets. Given that Syrian hamsters and humans have similar receptor expression patterns in their nasal mucosa, our findings suggests that Syrian hamsters can be used as a suitable animal model for evaluating the transmissibility of influenza viruses that preferentially bind to α2,6-linked sialic acid receptors.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2629629"},"PeriodicalIF":7.5,"publicationDate":"2026-02-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146141306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pertussis remains a leading cause of infant mortality globally, with rising cases in China post-COVID-19. Despite vaccination, waning immunity from acellular pertussis vaccines has driven resurgence. We evaluated a novel diphtheria, tetanus and pertussis (acellular, three components) combined vaccine, adsorbed (DTcP), China's first genetically engineered three-component pertussis vaccine, administered under two primary schedules (2/3/4 vs. 2/4/6 months) compared to licensed DTaP-IPV-Hib (Pentaxim). In this randomized, blinded, phase III clinical trial, 1380 healthy 2-month-old infants from Henan, China, received DTcP-1 (2/3/4 months) or DTcP-2 (2/4/6 months) or DTaP-IPV-Hib (2/3/4 months). The primary safety endpoints were the incidence of adverse reactions within 0∼30 days after primary vaccination. The primary immunogenicity endpoints were to evaluate the non-inferiority and superiority of seroconversion rates and geometric mean concentrations (GMCs) of anti-pertussis toxoid (PT), filamentous hemagglutinin (FHA), pertactin (PRN), diphtheria toxoid (DT), tetanus toxoid (TT), antibodies 30 days after primary vaccination. Immunogenicity was assessed via Luminex-based multiplex immunoassay. Both DTcP-1 and DTcP-2 schedules demonstrated non-inferior safety to DTaP-IPV-Hib (total adverse reactions: 14.52/16.59% vs. 16.91%, P = 0.183), with DTcP-2 (2/4/6 months) showing lower swelling (2.59% vs. 4.83%, P = 0.008) and irritability (0.07% vs. 1.02/1.40%, P < 0.001). DTcP-2 elicited higher GMCs against pertussis antigens (PT: 84.23 vs. 65.35; FHA: 132.16 vs. 102.13, both P < 0.001) and comparable DT/TT responses. DTcP exhibited favorable safety and superior pertussis immunogenicity, particularly with the 2/4/6-month schedule. Its genetically engineered three-component design offers a promising strategy to combat pertussis amid global resurgence.
百日咳仍然是全球婴儿死亡的主要原因，在2019冠状病毒病后，中国的百日咳病例有所上升。尽管接种了疫苗，但无细胞百日咳疫苗的免疫力下降导致了死灰复燃。我们评估了一种新型白喉、破伤风和百日咳（无细胞、三组分）吸附联合疫苗（DTcP），这是中国首个基因工程百日咳三组分疫苗，与许可的dtap - ipvv - hib （Pentaxim）相比，分两个主要时间表（2/3/4和2/4/6个月）施用。在这项随机、盲法的III期临床试验中，来自中国河南的1380名2个月大的健康婴儿接受了DTcP-1（2/3/4个月）或DTcP-2（2/4/6个月）或dtap - ipvv - hib（2/3/4个月）。主要安全终点是初次接种后0 ~ 30天内不良反应的发生率。主要免疫原性终点是评价初次接种后30天抗百日咳类毒素（PT）、丝状血凝素（FHA）、perpern、白喉类毒素（DT）、破伤风类毒素（TT）抗体的血清转化率和几何平均浓度（GMCs）的非劣效性和优越性。通过基于luminex的多重免疫分析法评估免疫原性。DTcP-1和DTcP-2方案的安全性均优于dtap - ipvv - hib方案（总不良反应：14.52/16.59% vs. 16.91%, P = 0.183）， DTcP-2方案（2/4/6个月）肿胀（2.59% vs. 4.83%, P = 0.008）和易怒（0.07% vs. 1.02/1.40%, P < 0.001）较低。DTcP-2对百日咳抗原诱导较高的gmc （PT: 84.23 vs. 65.35; FHA: 132.16 vs. 102.13， P均< 0.001）和可比较的DT/TT反应。DTcP表现出良好的安全性和优越的百日咳免疫原性，特别是在2/4/6个月的时间表上。它的基因工程三组分设计提供了一个有希望的策略，以对抗百日咳在全球复苏。
{"title":"Safety and Immunogenicity of Diphtheria, Tetanus and Pertussis (Acellular, Three Components) Combined Vaccine, Adsorbed after three-dose priming in 2 Months Age Infants: A Randomized, Blinded, Controlled Phase III Clinical Trial in China.","authors":"Wei Zhang,Chen Wei,Peng Wan,Guangwei Feng,Feiyu Wang,Lichan Wang,Jiebing Tan,Xuewen Wang,Xue Wang,Xiuwen Sui,Wangyang You,Jinbo Gou,Liyong Yuan,Tao Zhu,Haitao Huang,Xiao Ma,Yanxia Wang","doi":"10.1080/22221751.2026.2625556","DOIUrl":"https://doi.org/10.1080/22221751.2026.2625556","url":null,"abstract":"Pertussis remains a leading cause of infant mortality globally, with rising cases in China post-COVID-19. Despite vaccination, waning immunity from acellular pertussis vaccines has driven resurgence. We evaluated a novel diphtheria, tetanus and pertussis (acellular, three components) combined vaccine, adsorbed (DTcP), China's first genetically engineered three-component pertussis vaccine, administered under two primary schedules (2/3/4 vs. 2/4/6 months) compared to licensed DTaP-IPV-Hib (Pentaxim). In this randomized, blinded, phase III clinical trial, 1380 healthy 2-month-old infants from Henan, China, received DTcP-1 (2/3/4 months) or DTcP-2 (2/4/6 months) or DTaP-IPV-Hib (2/3/4 months). The primary safety endpoints were the incidence of adverse reactions within 0∼30 days after primary vaccination. The primary immunogenicity endpoints were to evaluate the non-inferiority and superiority of seroconversion rates and geometric mean concentrations (GMCs) of anti-pertussis toxoid (PT), filamentous hemagglutinin (FHA), pertactin (PRN), diphtheria toxoid (DT), tetanus toxoid (TT), antibodies 30 days after primary vaccination. Immunogenicity was assessed via Luminex-based multiplex immunoassay. Both DTcP-1 and DTcP-2 schedules demonstrated non-inferior safety to DTaP-IPV-Hib (total adverse reactions: 14.52/16.59% vs. 16.91%, P = 0.183), with DTcP-2 (2/4/6 months) showing lower swelling (2.59% vs. 4.83%, P = 0.008) and irritability (0.07% vs. 1.02/1.40%, P < 0.001). DTcP-2 elicited higher GMCs against pertussis antigens (PT: 84.23 vs. 65.35; FHA: 132.16 vs. 102.13, both P < 0.001) and comparable DT/TT responses. DTcP exhibited favorable safety and superior pertussis immunogenicity, particularly with the 2/4/6-month schedule. Its genetically engineered three-component design offers a promising strategy to combat pertussis amid global resurgence.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"1 1","pages":"2625556"},"PeriodicalIF":13.2,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146088896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-30DOI: 10.1080/22221751.2026.2616944
Lianne Presley,Jimena Pérez-Vargas,Anaïs Saintigny,Iván Villanueva,Michelle Ho,Jessica Fone,Lara Brinsden,Nidhi Kaushik,Syan Olver,Connor A H Thompson,Diana Bautista-Sánchez,Siobhan Ennis,Mike Chen,Matthew McCallum,Jack T Brown,Sára Ferková,Brian Hetrick,David Veesler,Richard Leduc,Masahiro Niikura,Pierre-Luc Boudreault,Bryce Warner,François Jean
Human TMPRSS2 is a type II transmembrane serine protease and an essential host factor for SARS-CoV-2 and influenza A virus (IAV H1N1) infections. It facilitates the cleavage of viral surface glycoproteins, which are required for membrane fusion. This importance makes it an attractive target for host-directed antiviral therapies. We previously identified N-0385 and N-0920 as nanomolar TMPRSS2 inhibitors and demonstrated their antiviral potency against several SARS-CoV-2 variants. Here, we screened another twelve N-0385/N-0920 analogs with improved pharmacokinetics. Compounds 9 and 10 showed strong inhibition of TMPRSS2 activity and viral entry: they blocked pseudoviruses and authentic SARS-CoV-2 JN.1 and IAV H1N1 in Calu-3 cells. Compound 9 displayed a synergistic effect with baloxavir during IAV H1N1 infection. Both compounds highly reduced H1N1 infection in air-liquid interface cultures and mouse models, thus highlighting their broad antiviral potential. The discovery of broad-spectrum, host-directed antivirals against current and emerging human viruses is critical in preparing for future pandemics.
{"title":"TMPRSS2 inhibitors with broad-spectrum efficacy against SARS-CoV-2 (JN.1) and influenza A (H1N1) viruses protect mice from influenza A infection.","authors":"Lianne Presley,Jimena Pérez-Vargas,Anaïs Saintigny,Iván Villanueva,Michelle Ho,Jessica Fone,Lara Brinsden,Nidhi Kaushik,Syan Olver,Connor A H Thompson,Diana Bautista-Sánchez,Siobhan Ennis,Mike Chen,Matthew McCallum,Jack T Brown,Sára Ferková,Brian Hetrick,David Veesler,Richard Leduc,Masahiro Niikura,Pierre-Luc Boudreault,Bryce Warner,François Jean","doi":"10.1080/22221751.2026.2616944","DOIUrl":"https://doi.org/10.1080/22221751.2026.2616944","url":null,"abstract":"Human TMPRSS2 is a type II transmembrane serine protease and an essential host factor for SARS-CoV-2 and influenza A virus (IAV H1N1) infections. It facilitates the cleavage of viral surface glycoproteins, which are required for membrane fusion. This importance makes it an attractive target for host-directed antiviral therapies. We previously identified N-0385 and N-0920 as nanomolar TMPRSS2 inhibitors and demonstrated their antiviral potency against several SARS-CoV-2 variants. Here, we screened another twelve N-0385/N-0920 analogs with improved pharmacokinetics. Compounds 9 and 10 showed strong inhibition of TMPRSS2 activity and viral entry: they blocked pseudoviruses and authentic SARS-CoV-2 JN.1 and IAV H1N1 in Calu-3 cells. Compound 9 displayed a synergistic effect with baloxavir during IAV H1N1 infection. Both compounds highly reduced H1N1 infection in air-liquid interface cultures and mouse models, thus highlighting their broad antiviral potential. The discovery of broad-spectrum, host-directed antivirals against current and emerging human viruses is critical in preparing for future pandemics.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"30 1","pages":"2616944"},"PeriodicalIF":13.2,"publicationDate":"2026-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146072949","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
In humans, Borealpox virus (BRPV) is commonly associated with mild, self-limiting infections. However, in immunosuppressed individuals, infection can be severe and fatal. Due to a limited number of laboratory-confirmed cases and a lack of described animal models, little data on antiviral effectiveness against BRPV are available. Here we developed both immunocompetent and immunodeficient mouse models for the study of BRPV. In immunocompetent mice, BRPV infection resulted in high viral titers with organ-specific gross pathological abnormalities and route-dependant lethality. In immunodeficient mice, BRPV was uniformly lethal with varying times to lethal disease which appeared to coincide with viral replication. Notably, extensive fluid retention was also observed in these mice. Further assessment of cidofovir, brincidofovir, and tecovirimat therapy against BRPV infection demonstrated that all three compounds resulted in improved clinical condition and significant reductions in BRPV titers.
{"title":"Assessment of three antiviral compounds against Borealpox virus infection in a mouse model.","authors":"Jérémie Prévost,Nikesh Tailor,Angela Sloan,Kathleen Fulton,Sarah J Medina,Jonathan Audet,Geoff Soule,David Safronetz","doi":"10.1080/22221751.2026.2623694","DOIUrl":"https://doi.org/10.1080/22221751.2026.2623694","url":null,"abstract":"In humans, Borealpox virus (BRPV) is commonly associated with mild, self-limiting infections. However, in immunosuppressed individuals, infection can be severe and fatal. Due to a limited number of laboratory-confirmed cases and a lack of described animal models, little data on antiviral effectiveness against BRPV are available. Here we developed both immunocompetent and immunodeficient mouse models for the study of BRPV. In immunocompetent mice, BRPV infection resulted in high viral titers with organ-specific gross pathological abnormalities and route-dependant lethality. In immunodeficient mice, BRPV was uniformly lethal with varying times to lethal disease which appeared to coincide with viral replication. Notably, extensive fluid retention was also observed in these mice. Further assessment of cidofovir, brincidofovir, and tecovirimat therapy against BRPV infection demonstrated that all three compounds resulted in improved clinical condition and significant reductions in BRPV titers.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"43 1","pages":"2623694"},"PeriodicalIF":13.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056551","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2026-01-27DOI: 10.1080/22221751.2026.2623695
Cesar Cantero,Cynthia Vazquez,Sandra Gonzalez,Analia Rojas,Fatima Fleitas,Julio Barrios,Andrea Gomez de la Fuente,Shirley Villalba,Martha Torales,Andrea Ijeda,Vagner Fonseca,Luiz Carlos Junior Alcantara,Marta Giovanetti
We report the re-emergence of dengue virus serotype 3 (DENV-3) in Paraguay after 15 years of absence. Twelve laboratory-confirmed cases were detected in early 2025 in the Asunción metropolitan region. Genomic sequencing identified DENV-3 genotype III, lineage B.3.2, indicating a new introduction of an emerging lineage rather than renewed local transmission. Phylogenetic analyses support recent introduction events, underscoring the importance of strengthened genomic surveillance to enable early detection, track viral introductions, and inform public health responses in settings with intense dengue transmission.
{"title":"Re-emergence of DENV-3 in Paraguay After Two Decades: A Genomic and Epidemiological Investigation.","authors":"Cesar Cantero,Cynthia Vazquez,Sandra Gonzalez,Analia Rojas,Fatima Fleitas,Julio Barrios,Andrea Gomez de la Fuente,Shirley Villalba,Martha Torales,Andrea Ijeda,Vagner Fonseca,Luiz Carlos Junior Alcantara,Marta Giovanetti","doi":"10.1080/22221751.2026.2623695","DOIUrl":"https://doi.org/10.1080/22221751.2026.2623695","url":null,"abstract":"We report the re-emergence of dengue virus serotype 3 (DENV-3) in Paraguay after 15 years of absence. Twelve laboratory-confirmed cases were detected in early 2025 in the Asunción metropolitan region. Genomic sequencing identified DENV-3 genotype III, lineage B.3.2, indicating a new introduction of an emerging lineage rather than renewed local transmission. Phylogenetic analyses support recent introduction events, underscoring the importance of strengthened genomic surveillance to enable early detection, track viral introductions, and inform public health responses in settings with intense dengue transmission.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"64 1","pages":"2623695"},"PeriodicalIF":13.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056552","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
OBJECTIVEThis study evaluated the economic and health benefits of hepatitis E (HEV) screening and vaccination in both outbreak and sporadic settings in China.METHODSDecision-analytic Markov models were used to evaluate the population impact and cost-effectiveness of HEV screening and vaccination for people with chronic hepatitis B (CHB), older adults, pregnant women, and women of childbearing age. Simulations projected outcomes over six months for outbreak settings and lifetime horizons for sporadic settings. Incremental cost-effectiveness ratios (ICERs) were derived from a health system perspective with costs in 2023 US$. Robustness was examined through sensitivity analyses.RESULTSPreventive universal screening combined with standard 3-dose HEV 239 vaccine was cost-effective only for people with CHB (Incremental cost-effectiveness ratio [ICER]: $25.38 thousand per Quality-Adjusted Life Year [QALY] gained), reducing symptomatic infections by 58.16% and HEV-related deaths by 57.51% in sporadic settings. This strategy may be economically viable for other vulnerable populations if the vaccine price is below $21 per dose. In outbreak settings, reactive universal screening combined with emergency 2-dose vaccination yielded cost-effective for older adults, pregnant women, and people with CHB (ICERs of $8.80, $26.26, and $31.81 thousand per QALY gained), reducing symptomatic infections and HEV-related deaths by over 70% within six months.CONCLUSIONSIn China, where sporadic settings are more common, preventive universal HEV screening combined with standard 3-dose vaccination is cost-effective only for people with CHB. High vaccine costs render this strategy economically unfeasible for older adults, pregnant women, and women of childbearing age.
{"title":"Cost-effectiveness Analysis of Hepatitis E Screening and Vaccination: Targeting Vulnerable Populations in Outbreak and Sporadic Settings in China.","authors":"Hanting Liu,Gang Chen,Yusheng Jie,Yong Jiang,Yao Huang,Xu Wang,Chun Hao,Jing Gu,Lei Zhang,Jinghua Li","doi":"10.1080/22221751.2026.2623707","DOIUrl":"https://doi.org/10.1080/22221751.2026.2623707","url":null,"abstract":"OBJECTIVEThis study evaluated the economic and health benefits of hepatitis E (HEV) screening and vaccination in both outbreak and sporadic settings in China.METHODSDecision-analytic Markov models were used to evaluate the population impact and cost-effectiveness of HEV screening and vaccination for people with chronic hepatitis B (CHB), older adults, pregnant women, and women of childbearing age. Simulations projected outcomes over six months for outbreak settings and lifetime horizons for sporadic settings. Incremental cost-effectiveness ratios (ICERs) were derived from a health system perspective with costs in 2023 US$. Robustness was examined through sensitivity analyses.RESULTSPreventive universal screening combined with standard 3-dose HEV 239 vaccine was cost-effective only for people with CHB (Incremental cost-effectiveness ratio [ICER]: $25.38 thousand per Quality-Adjusted Life Year [QALY] gained), reducing symptomatic infections by 58.16% and HEV-related deaths by 57.51% in sporadic settings. This strategy may be economically viable for other vulnerable populations if the vaccine price is below $21 per dose. In outbreak settings, reactive universal screening combined with emergency 2-dose vaccination yielded cost-effective for older adults, pregnant women, and people with CHB (ICERs of $8.80, $26.26, and $31.81 thousand per QALY gained), reducing symptomatic infections and HEV-related deaths by over 70% within six months.CONCLUSIONSIn China, where sporadic settings are more common, preventive universal HEV screening combined with standard 3-dose vaccination is cost-effective only for people with CHB. High vaccine costs render this strategy economically unfeasible for older adults, pregnant women, and women of childbearing age.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"164 1","pages":"2623707"},"PeriodicalIF":13.2,"publicationDate":"2026-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146056525","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
African Swine Fever virus (ASFV) causes a contagious and fatal disease in domestic pigs and Eurasian wild boars, representing a serious threat to the global pig industry, since no antivirals are available and vaccine use is currently restricted to Vietnam. Notably, ASFV encodes for an E2 ubiquitin-conjugating enzyme (ASFV-pI215L) which is essential for viral replication and evasion from immune interferon type I responses, suggesting that its functional impairment could lead to a live attenuated vaccine. In this study, we showed that ASFV-pI215L is highly conserved among 222 ASFV isolates, including the emerging ones, emphasizing its value as a target for vaccine design. Furthermore, our mutagenic studies revealed that single- and multiple-residue substitutions comprising the R11-E15 and D130-S134 residues reduced ASFV-pI215L E2 ubiquitin-conjugating activity. In parallel, a strong immunodominant B-cell epitope was mapped and mutated between P61 and F69 resides, reducing or abolishing both IgG and IgM recognition, and ASFV-pI215L E2 activity. In sum, this study highlights that rational targeted mutagenesis can reduce E2 ubiquitin-conjugating activity and immune recognition of ASFV-pI215L, providing a strategy to develop an attenuated vaccine able to differentiate infected from vaccinated animals.
{"title":"Multiple directed mutagenesis reduces enzymatic activity and antibody recognition of the African Swine Fever Virus E2 ubiquitin-conjugating protein (ASFV-pI215L).","authors":"Nuno Jordão,Ana Catarina Urbano,Fernando Boinas,Carlos Martins,Fernando Ferreira","doi":"10.1080/22221751.2026.2622218","DOIUrl":"https://doi.org/10.1080/22221751.2026.2622218","url":null,"abstract":"African Swine Fever virus (ASFV) causes a contagious and fatal disease in domestic pigs and Eurasian wild boars, representing a serious threat to the global pig industry, since no antivirals are available and vaccine use is currently restricted to Vietnam. Notably, ASFV encodes for an E2 ubiquitin-conjugating enzyme (ASFV-pI215L) which is essential for viral replication and evasion from immune interferon type I responses, suggesting that its functional impairment could lead to a live attenuated vaccine. In this study, we showed that ASFV-pI215L is highly conserved among 222 ASFV isolates, including the emerging ones, emphasizing its value as a target for vaccine design. Furthermore, our mutagenic studies revealed that single- and multiple-residue substitutions comprising the R11-E15 and D130-S134 residues reduced ASFV-pI215L E2 ubiquitin-conjugating activity. In parallel, a strong immunodominant B-cell epitope was mapped and mutated between P61 and F69 resides, reducing or abolishing both IgG and IgM recognition, and ASFV-pI215L E2 activity. In sum, this study highlights that rational targeted mutagenesis can reduce E2 ubiquitin-conjugating activity and immune recognition of ASFV-pI215L, providing a strategy to develop an attenuated vaccine able to differentiate infected from vaccinated animals.","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"17 1","pages":"2622218"},"PeriodicalIF":13.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146033832","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Dengue infection is a global health issue with significantly increased incidence and overall burden, especially since 2024. Specifically, epidemiological trends show a rising median age of affected individuals over 65 years/old. Older individuals face increased risks of severe disease, extended hospital stays, healthcare-associated infections, and higher mortality rates, mainly due to a decline in immune function, and multimorbidity. Antibody-dependent enhancement, cytokine dysregulation, and endothelial dysfunction exacerbate disease severity. Moreover, in older patients, dengue diagnosis can be difficult, due to atypical symptoms. To date, there are no specific prognostic markers and no specific antiviral drugs. Management requires age-specific considerations. Evidence on immunomodulatory and antiviral therapies is emerging, and vaccine efficacy and safety data in older adults remain limited, despite growing interest. With an aging global population, dengue represents an urgent clinical challenge: there is an unmet and increasing need for comprehensive, practical guidelines to help clinicians in the diagnosis, treatment, prevention, and control of dengue infection in older patients.Trial registration: ClinicalTrials.gov identifier: NCT05611710..Trial registration: ClinicalTrials.gov identifier: NCT06579755..
{"title":"Dengue and Aging: Challenges and Opportunities in Prevention and Care. A narrative review.","authors":"Alessia Beccacece,Laura Ponzetta,Maria Princiotto,Maria Elsa Gambuzza,Alessandra D'Abramo,Luca Soraci,Fabiola Olivieri,Fabrizia Lattanzio,Enrico Girardi,Leonardo Biscetti,Emanuele Nicastri","doi":"10.1080/22221751.2026.2622217","DOIUrl":"https://doi.org/10.1080/22221751.2026.2622217","url":null,"abstract":"Dengue infection is a global health issue with significantly increased incidence and overall burden, especially since 2024. Specifically, epidemiological trends show a rising median age of affected individuals over 65 years/old. Older individuals face increased risks of severe disease, extended hospital stays, healthcare-associated infections, and higher mortality rates, mainly due to a decline in immune function, and multimorbidity. Antibody-dependent enhancement, cytokine dysregulation, and endothelial dysfunction exacerbate disease severity. Moreover, in older patients, dengue diagnosis can be difficult, due to atypical symptoms. To date, there are no specific prognostic markers and no specific antiviral drugs. Management requires age-specific considerations. Evidence on immunomodulatory and antiviral therapies is emerging, and vaccine efficacy and safety data in older adults remain limited, despite growing interest. With an aging global population, dengue represents an urgent clinical challenge: there is an unmet and increasing need for comprehensive, practical guidelines to help clinicians in the diagnosis, treatment, prevention, and control of dengue infection in older patients.Trial registration: ClinicalTrials.gov identifier: NCT05611710..Trial registration: ClinicalTrials.gov identifier: NCT06579755..","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"17 1","pages":"2622217"},"PeriodicalIF":13.2,"publicationDate":"2026-01-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146021509","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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