Pub Date : 2024-12-01Epub Date: 2024-02-29DOI: 10.1080/22221751.2024.2321993
Iolanda Vieira Anahory Monjane, Hernâni Djedje, Esmeralda Tamele, Virgínia Nhabomba, Almiro Rogério Tivane, Zacarias Elias Massicame, Dercília Mudanisse Arone, Ambra Pastori, Alessio Bortolami, Isabella Monne, Timothy Woma, Charles E Lamien, William G Dundon
On 13 October 2023, the National Directorate for Livestock Development in Mozambique was notified of a suspected outbreak of avian influenza in commercial layers. Samples were screened by real-time and conventional RT-PCR and were positive for both H7 and N6. Full genome sequences were obtained for three representative samples. Sequence analysis of the H7 cleavage site confirmed that the viruses were highly pathogenic (i.e. 333- PEPPKGPRFRR/GLF-346). In addition, the H7 and N6 sequences were highly similar (from 99.4-99.5% and 99.6-99.7% for the HA gene and the NA gene, respectively) to the sequences of a H7N6 virus identified in the Republic of South Africa in May 2023 indicating a similar origin of the viruses. The identification of H7N6 HPAIV in Mozambique has important implications for disease management and food security in the region.
{"title":"H7N6 highly pathogenic avian influenza in Mozambique, 2023.","authors":"Iolanda Vieira Anahory Monjane, Hernâni Djedje, Esmeralda Tamele, Virgínia Nhabomba, Almiro Rogério Tivane, Zacarias Elias Massicame, Dercília Mudanisse Arone, Ambra Pastori, Alessio Bortolami, Isabella Monne, Timothy Woma, Charles E Lamien, William G Dundon","doi":"10.1080/22221751.2024.2321993","DOIUrl":"10.1080/22221751.2024.2321993","url":null,"abstract":"<p><p>On 13 October 2023, the National Directorate for Livestock Development in Mozambique was notified of a suspected outbreak of avian influenza in commercial layers. Samples were screened by real-time and conventional RT-PCR and were positive for both H7 and N6. Full genome sequences were obtained for three representative samples. Sequence analysis of the H7 cleavage site confirmed that the viruses were highly pathogenic (i.e. 333- PEPPKGPRFRR/GLF-346). In addition, the H7 and N6 sequences were highly similar (from 99.4-99.5% and 99.6-99.7% for the HA gene and the NA gene, respectively) to the sequences of a H7N6 virus identified in the Republic of South Africa in May 2023 indicating a similar origin of the viruses. The identification of H7N6 HPAIV in Mozambique has important implications for disease management and food security in the region.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"13 1","pages":"2321993"},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10906114/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139995918","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}
Pub Date : 2024-12-01Epub Date: 2024-03-11DOI: 10.1080/22221751.2024.2313849
Evgeny B Pichkur, Mikhail F Vorovitch, Alla L Ivanova, Elena V Protopopova, Valery B Loktev, Dmitry I Osolodkin, Aydar A Ishmukhametov, Valeriya R Samygina
Tick-borne encephalitis virus (TBEV) causes a severe disease, tick-borne encephalitis (TBE), that has a substantial epidemiological importance for Northern Eurasia. Between 10,000 and 15,000 TBE cases are registered annually despite the availability of effective formaldehyde-inactivated full-virion vaccines due to insufficient vaccination coverage, as well as sporadic cases of vaccine breakthrough. The development of improved vaccines would benefit from the atomic resolution structure of the antigen. Here we report the refined single-particle cryo-electron microscopy (cryo-EM) structure of the inactivated mature TBEV vaccine strain Sofjin-Chumakov (Far-Eastern subtype) at a resolution of 3.0 Å. The increase of the resolution with respect to the previously published structures of TBEV strains Hypr and Kuutsalo-14 (European subtype) was reached due to improvement of the virus sample quality achieved by the optimized preparation methods. All the surface epitopes of TBEV were structurally conserved in the inactivated virions. ELISA studies with monoclonal antibodies supported the hypothesis of TBEV protein shell cross-linking upon inactivation with formaldehyde.
{"title":"The structure of inactivated mature tick-borne encephalitis virus at 3.0 Å resolution.","authors":"Evgeny B Pichkur, Mikhail F Vorovitch, Alla L Ivanova, Elena V Protopopova, Valery B Loktev, Dmitry I Osolodkin, Aydar A Ishmukhametov, Valeriya R Samygina","doi":"10.1080/22221751.2024.2313849","DOIUrl":"10.1080/22221751.2024.2313849","url":null,"abstract":"<p><p>Tick-borne encephalitis virus (TBEV) causes a severe disease, tick-borne encephalitis (TBE), that has a substantial epidemiological importance for Northern Eurasia. Between 10,000 and 15,000 TBE cases are registered annually despite the availability of effective formaldehyde-inactivated full-virion vaccines due to insufficient vaccination coverage, as well as sporadic cases of vaccine breakthrough. The development of improved vaccines would benefit from the atomic resolution structure of the antigen. Here we report the refined single-particle cryo-electron microscopy (cryo-EM) structure of the inactivated mature TBEV vaccine strain Sofjin-Chumakov (Far-Eastern subtype) at a resolution of 3.0 Å. The increase of the resolution with respect to the previously published structures of TBEV strains Hypr and Kuutsalo-14 (European subtype) was reached due to improvement of the virus sample quality achieved by the optimized preparation methods. All the surface epitopes of TBEV were structurally conserved in the inactivated virions. ELISA studies with monoclonal antibodies supported the hypothesis of TBEV protein shell cross-linking upon inactivation with formaldehyde.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"13 1","pages":"2313849"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10930109/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093622","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}
Pub Date : 2024-12-01Epub Date: 2024-03-11DOI: 10.1080/22221751.2024.2315960
Bernardo Guerra Tenório, Daniel R Kollath, Lalitha Gade, Anastasia P Litvintseva, Tom Chiller, Jeff S Jenness, Jason E Stajich, Daniel R Matute, Andrew S Hanzlicek, Bridget M Barker, Marcus de Melo Teixeira
ABSTRACTHistoplasmosis is an endemic mycosis in North America frequently reported along the Ohio and Mississippi River Valleys, although autochthonous cases occur in non-endemic areas. In the United States, the disease is provoked by two genetically distinct clades of Histoplasma capsulatum sensu lato, Histoplasma mississippiense (Nam1) and H. ohiense (Nam2). To bridge the molecular epidemiological gap, we genotyped 93 Histoplasma isolates (62 novel genomes) including clinical, environmental, and veterinarian samples from a broader geographical range by whole-genome sequencing, followed by evolutionary and species niche modelling analyses. We show that histoplasmosis is caused by two major lineages, H. ohiense and H. mississippiense; with sporadic cases caused by H. suramericanum in California and Texas. While H. ohiense is prevalent in eastern states, H. mississipiense was found to be prevalent in the central and western portions of the United States, but also geographically overlapping in some areas suggesting that these species might co-occur. Species Niche Modelling revealed that H. ohiense thrives in places with warmer and drier conditions, while H. mississippiense is endemic to areas with cooler temperatures and more precipitation. In addition, we predicted multiple areas of secondary contact zones where the two species co-occur, potentially facilitating gene exchange and hybridization. This study provides the most comprehensive understanding of the genomic epidemiology of histoplasmosis in the USA and lays a blueprint for the study of invasive fungal diseases.
摘要组织胞浆菌病是北美洲的一种地方性真菌病,经常报告发生在俄亥俄河和密西西比河流域,但在非流行地区也有自发病例。在美国,该病是由两种不同基因的荚膜组织胞浆菌(Histoplasma capsulatum sensu lato)引起的,即密西西比荚膜组织胞浆菌(Histoplasma mississippiense,Nam1)和奥希斯荚膜组织胞浆菌(H. ohiense,Nam2)。为了弥补分子流行病学上的差距,我们通过全基因组测序对 93 个组织胞浆菌分离株(62 个新基因组)进行了基因分型,包括来自更广泛地理范围的临床、环境和兽医样本,随后进行了进化和物种生态位建模分析。我们的研究表明,组织胞浆菌病由两个主要菌系引起:H. ohiense 和 H. mississippiense;在加利福尼亚州和得克萨斯州还有由 H. suramericanum 引起的零星病例。H.ohiense主要流行于美国东部各州,而H.mississipiense则主要流行于美国中部和西部地区,但在某些地区也有地理重叠,这表明这些物种可能同时存在。物种生态位建模显示,H. ohiense在温暖干燥的地方生长茂盛,而H. mississippiense则是气温较低、降水较多地区的特有物种。此外,我们还预测了两个物种共存的多个次级接触区,这可能会促进基因交流和杂交。这项研究最全面地了解了美国组织胞浆菌病的基因组流行病学,为研究入侵性真菌疾病奠定了蓝图。
{"title":"Tracing histoplasmosis genomic epidemiology and species occurrence across the USA.","authors":"Bernardo Guerra Tenório, Daniel R Kollath, Lalitha Gade, Anastasia P Litvintseva, Tom Chiller, Jeff S Jenness, Jason E Stajich, Daniel R Matute, Andrew S Hanzlicek, Bridget M Barker, Marcus de Melo Teixeira","doi":"10.1080/22221751.2024.2315960","DOIUrl":"10.1080/22221751.2024.2315960","url":null,"abstract":"<p><p><b>ABSTRACT</b>Histoplasmosis is an endemic mycosis in North America frequently reported along the Ohio and Mississippi River Valleys, although autochthonous cases occur in non-endemic areas. In the United States, the disease is provoked by two genetically distinct clades of <i>Histoplasma capsulatum sensu lato</i>, <i>Histoplasma mississippiense</i> (Nam1) and <i>H. ohiense</i> (Nam2). To bridge the molecular epidemiological gap, we genotyped 93 <i>Histoplasma</i> isolates (62 novel genomes) including clinical, environmental, and veterinarian samples from a broader geographical range by whole-genome sequencing, followed by evolutionary and species niche modelling analyses. We show that histoplasmosis is caused by two major lineages, <i>H. ohiense</i> and <i>H. mississippiense</i>; with sporadic cases caused by <i>H. suramericanum</i> in California and Texas. While <i>H. ohiense</i> is prevalent in eastern states, <i>H. mississipiense</i> was found to be prevalent in the central and western portions of the United States, but also geographically overlapping in some areas suggesting that these species might co-occur. Species Niche Modelling revealed that <i>H. ohiense</i> thrives in places with warmer and drier conditions, while <i>H. mississippiense</i> is endemic to areas with cooler temperatures and more precipitation. In addition, we predicted multiple areas of secondary contact zones where the two species co-occur, potentially facilitating gene exchange and hybridization. This study provides the most comprehensive understanding of the genomic epidemiology of histoplasmosis in the USA and lays a blueprint for the study of invasive fungal diseases.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"13 1","pages":"2315960"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10930103/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140093623","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}
Pub Date : 2024-12-01Epub Date: 2024-09-10DOI: 10.1080/22221751.2024.2399268
Ariful Islam, Michelle Wille, Mohammed Ziaur Rahman, Ashleigh F Porter, Mohammed Enayet Hosaain, Mohammad Mahmudul Hassan, Tahmina Shirin, Jonathan H Epstein, Marcel Klaassen
High pathogenicity avian influenza (HPAI) virus H5N1 first emerged in Bangladesh in 2007. Despite the use of vaccines in chickens since 2012 to control HPAI, HPAI H5Nx viruses have continued to infect poultry, and wild birds, resulting in notable mass mortalities in house crows (Corvus splendens). The first HPAI H5Nx viruses in Bangladesh belonged to clade 2.2.2, followed by clade 2.3.4.2 and 2.3.2.1 viruses in 2011. After the implementation of chicken vaccination in 2012, these viruses were mostly replaced by clade 2.3.2.1a viruses and more recently clade 2.3.4.4b and h viruses. In this study, we reconstruct the phylogenetic history of HPAI H5Nx viruses in Bangladesh to evaluate the role of major host species in the maintenance and evolution of HPAI H5Nx virus in Bangladesh and reveal the role of heavily impacted crows in virus epidemiology. Epizootic waves caused by HPAI H5N1 and H5N6 viruses amongst house crows occurred annually in winter. Bayesian phylodynamic analysis of clade 2.3.2.1a revealed frequent bidirectional viral transitions between domestic ducks, chickens, and house crows that was markedly skewed towards ducks; domestic ducks might be the source, or reservoir, of HPAI H5Nx in Bangladesh, as the number of viral transitions from ducks to chickens and house crows was by far more numerous than the other transitions. Our results suggest viral circulation in domestic birds despite vaccination, with crow epizootics acting as a sentinel. The vaccination strategy needs to be updated to use more effective vaccinations, assess vaccine efficacy, and extension of vaccination to domestic ducks, the key reservoir.
{"title":"Phylodynamics of high pathogenicity avian influenza virus in Bangladesh identifying domestic ducks as the amplifying host reservoir.","authors":"Ariful Islam, Michelle Wille, Mohammed Ziaur Rahman, Ashleigh F Porter, Mohammed Enayet Hosaain, Mohammad Mahmudul Hassan, Tahmina Shirin, Jonathan H Epstein, Marcel Klaassen","doi":"10.1080/22221751.2024.2399268","DOIUrl":"10.1080/22221751.2024.2399268","url":null,"abstract":"<p><p>High pathogenicity avian influenza (HPAI) virus H5N1 first emerged in Bangladesh in 2007. Despite the use of vaccines in chickens since 2012 to control HPAI, HPAI H5Nx viruses have continued to infect poultry, and wild birds, resulting in notable mass mortalities in house crows (<i>Corvus splendens</i>). The first HPAI H5Nx viruses in Bangladesh belonged to clade 2.2.2, followed by clade 2.3.4.2 and 2.3.2.1 viruses in 2011. After the implementation of chicken vaccination in 2012, these viruses were mostly replaced by clade 2.3.2.1a viruses and more recently clade 2.3.4.4b and h viruses. In this study, we reconstruct the phylogenetic history of HPAI H5Nx viruses in Bangladesh to evaluate the role of major host species in the maintenance and evolution of HPAI H5Nx virus in Bangladesh and reveal the role of heavily impacted crows in virus epidemiology. Epizootic waves caused by HPAI H5N1 and H5N6 viruses amongst house crows occurred annually in winter. Bayesian phylodynamic analysis of clade 2.3.2.1a revealed frequent bidirectional viral transitions between domestic ducks, chickens, and house crows that was markedly skewed towards ducks; domestic ducks might be the source, or reservoir, of HPAI H5Nx in Bangladesh, as the number of viral transitions from ducks to chickens and house crows was by far more numerous than the other transitions. Our results suggest viral circulation in domestic birds despite vaccination, with crow epizootics acting as a sentinel. The vaccination strategy needs to be updated to use more effective vaccinations, assess vaccine efficacy, and extension of vaccination to domestic ducks, the key reservoir.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2399268"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11389634/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142105493","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}
The escalation of antibiotic resistance and the diminishing antimicrobial pipeline have emerged as significant threats to public health. The ESKAPE pathogens - Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. - were initially identified as critical multidrug-resistant bacteria, demanding urgently effective therapies. Despite the introduction of various new antibiotics and antibiotic adjuvants, such as innovative β-lactamase inhibitors, these organisms continue to pose substantial therapeutic challenges. People's Republic of China, as a country facing a severe bacterial resistance situation, has undergone a series of changes and findings in recent years in terms of the prevalence, transmission characteristics and resistance mechanisms of antibiotic resistant bacteria. The increasing levels of population mobility have not only shaped the unique characteristics of antibiotic resistance prevalence and transmission within People's Republic of China but have also indirectly reflected global patterns of antibiotic-resistant dissemination. What's more, as a vast nation, People's Republic of China exhibits significant variations in the levels of antibiotic resistance and the prevalence characteristics of antibiotic resistant bacteria across different provinces and regions. In this review, we examine the current epidemiology and characteristics of this important group of bacterial pathogens, delving into relevant mechanisms of resistance to recently introduced antibiotics that impact their clinical utility in China.
{"title":"ESKAPE in China: epidemiology and characteristics of antibiotic resistance.","authors":"Qixia Luo, Ping Lu, Yunbo Chen, Ping Shen, Beiwen Zheng, Jinru Ji, Chaoqun Ying, Zhiying Liu, Yonghong Xiao","doi":"10.1080/22221751.2024.2317915","DOIUrl":"10.1080/22221751.2024.2317915","url":null,"abstract":"<p><p>The escalation of antibiotic resistance and the diminishing antimicrobial pipeline have emerged as significant threats to public health. The ESKAPE pathogens - Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter spp. - were initially identified as critical multidrug-resistant bacteria, demanding urgently effective therapies. Despite the introduction of various new antibiotics and antibiotic adjuvants, such as innovative β-lactamase inhibitors, these organisms continue to pose substantial therapeutic challenges. People's Republic of China, as a country facing a severe bacterial resistance situation, has undergone a series of changes and findings in recent years in terms of the prevalence, transmission characteristics and resistance mechanisms of antibiotic resistant bacteria. The increasing levels of population mobility have not only shaped the unique characteristics of antibiotic resistance prevalence and transmission within People's Republic of China but have also indirectly reflected global patterns of antibiotic-resistant dissemination. What's more, as a vast nation, People's Republic of China exhibits significant variations in the levels of antibiotic resistance and the prevalence characteristics of antibiotic resistant bacteria across different provinces and regions. In this review, we examine the current epidemiology and characteristics of this important group of bacterial pathogens, delving into relevant mechanisms of resistance to recently introduced antibiotics that impact their clinical utility in China.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2317915"},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10896150/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139734726","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}
Pub Date : 2024-12-01Epub Date: 2024-11-08DOI: 10.1080/22221751.2024.2420723
Ann Kathrin Ahrens, Anne Pohlmann, Christian Grund, Martin Beer, Timm C Harder
{"title":"Out of the blue: detection of a unique highly pathogenic avian influenza virus of subtype H7N5 in Germany.","authors":"Ann Kathrin Ahrens, Anne Pohlmann, Christian Grund, Martin Beer, Timm C Harder","doi":"10.1080/22221751.2024.2420723","DOIUrl":"10.1080/22221751.2024.2420723","url":null,"abstract":"","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2420723"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11552254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142460744","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}
Pub Date : 2024-12-01Epub Date: 2024-10-29DOI: 10.1080/22221751.2024.2409350
Shuqin Gu, Libo Tang, Ling Guo, Chunxiu Zhong, Xin Fu, Guofu Ye, Shihong Zhong, Xiaoyi Li, Chunhua Wen, Yang Zhou, Jinling Wei, Haitao Chen, Nikolai Novikov, Simon P Fletcher, M Anthony Moody, Jinlin Hou, Yongyin Li
It is well established that humoral immunity targeting hepatitis B virus surface antigen (HBsAg) plays a critical role in viral clearance and clinical cure. However, the functional changes in HBsAg-specific B cells before and after achieving functional cure remain poorly understood. In this study, we characterized circulating HBsAg-specific B cells and identified functional shifts and B-cell epitopes directly associated with HBsAg loss. The phenotypes and functions of HBV-specific B cells in patients with chronic HBV infection were investigated using a dual staining method and the ELISpot assay. Epitope mapping was performed to identify B cell epitopes associated with functional cure. Hyperactivated HBsAg-specific B cells in patients who achieved HBsAg loss were composed of enriched resting memory and contracted atypical memory fractions, accompanied by sustained co-expression of multiple inhibitory receptors and increased IL-6 secretion. The frequency of HBsAb-secreting B cells was significantly increased after achieving a functional cure. The rHBsAg displayed a weaker immunomodulatory effect on B cells than rHBeAg and rHBcAg in vitro. Notably, sera from patients with HBsAg loss reacted mainly with peptides S60, S61, and S76, suggesting that these are dominant linear B-cell epitopes relevant for functional cure. Intriguingly, patients reactive with S76 showed a higher frequency of the HLA class II DQB1*05:01 allele. Taken together, HBsAg-specific B cells were partially restored in patients after achieving a functional cure. Functional cure-related epitopes may be promising targets for developing therapeutic vaccines to treat HBV infection and promote functional cure.
众所周知,针对乙型肝炎病毒表面抗原(HBsAg)的体液免疫在病毒清除和临床治愈中起着至关重要的作用。然而,人们对实现功能性治愈前后 HBsAg 特异性 B 细胞的功能变化仍然知之甚少。在这项研究中,我们描述了循环中 HBsAg 特异性 B 细胞的特征,并确定了与 HBsAg 缺失直接相关的功能转变和 B 细胞表位。我们使用双重染色法和 ELISpot 检测法研究了慢性 HBV 感染患者 HBV 特异性 B 细胞的表型和功能。通过表位图谱确定了与功能性治愈相关的 B 细胞表位。在HBsAg消失的患者中,超活化的HBsAg特异性B细胞由富集的静息记忆和收缩的非典型记忆部分组成,同时伴有多种抑制受体的持续共表达和IL-6分泌的增加。功能性治愈后,分泌 HBsAb 的 B 细胞频率明显增加。与 rHBeAg 和 rHBcAg 相比,rHBsAg 在体外对 B 细胞的免疫调节作用较弱。值得注意的是,HBsAg 缺失患者的血清主要与肽 S60、S61 和 S76 反应,表明这些是与功能性治愈相关的主要线性 B 细胞表位。耐人寻味的是,对 S76 有反应的患者显示出较高的 HLA II 类 DQB1*05:01 等位基因频率。综上所述,在实现功能性治愈后,患者的 HBsAg 特异性 B 细胞得到了部分恢复。与功能性治愈相关的表位可能是开发治疗性疫苗以治疗 HBV 感染并促进功能性治愈的有希望的靶点。
{"title":"Circulating HBsAg-specific B cells are partially rescued in chronically HBV-infected patients with functional cure.","authors":"Shuqin Gu, Libo Tang, Ling Guo, Chunxiu Zhong, Xin Fu, Guofu Ye, Shihong Zhong, Xiaoyi Li, Chunhua Wen, Yang Zhou, Jinling Wei, Haitao Chen, Nikolai Novikov, Simon P Fletcher, M Anthony Moody, Jinlin Hou, Yongyin Li","doi":"10.1080/22221751.2024.2409350","DOIUrl":"10.1080/22221751.2024.2409350","url":null,"abstract":"<p><p>It is well established that humoral immunity targeting hepatitis B virus surface antigen (HBsAg) plays a critical role in viral clearance and clinical cure. However, the functional changes in HBsAg-specific B cells before and after achieving functional cure remain poorly understood. In this study, we characterized circulating HBsAg-specific B cells and identified functional shifts and B-cell epitopes directly associated with HBsAg loss. The phenotypes and functions of HBV-specific B cells in patients with chronic HBV infection were investigated using a dual staining method and the ELISpot assay. Epitope mapping was performed to identify B cell epitopes associated with functional cure. Hyperactivated HBsAg-specific B cells in patients who achieved HBsAg loss were composed of enriched resting memory and contracted atypical memory fractions, accompanied by sustained co-expression of multiple inhibitory receptors and increased IL-6 secretion. The frequency of HBsAb-secreting B cells was significantly increased after achieving a functional cure. The rHBsAg displayed a weaker immunomodulatory effect on B cells than rHBeAg and rHBcAg <i>in vitro</i>. Notably, sera from patients with HBsAg loss reacted mainly with peptides S60, S61, and S76, suggesting that these are dominant linear B-cell epitopes relevant for functional cure. Intriguingly, patients reactive with S76 showed a higher frequency of the HLA class II DQB1*05:01 allele. Taken together, HBsAg-specific B cells were partially restored in patients after achieving a functional cure. Functional cure-related epitopes may be promising targets for developing therapeutic vaccines to treat HBV infection and promote functional cure.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"13 1","pages":"2409350"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11523254/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142544433","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}
Pub Date : 2024-12-01Epub Date: 2024-11-17DOI: 10.1080/22221751.2024.2420737
Viviane de C Oliveira, Alba Soler-Comas, Amanda C S D Rocha, Cláudia H Silva-Lovato, Evandro Watanabe, Antoni Torres, Laia Fernández-Barat
Although an increased effectiveness has been suggested when phages and antibiotics are combined, this approach has not been tested against a mature biofilm on an endotracheal tube (ETT) surface. This study evaluated the effect of short- and long-term combined phage-antibiotic therapy in a control of a mature biofilm on an ETT surface. Pseudomonas aeruginosa strains, including susceptible and resistant clinical samples, were used to develop the ETT biofilm. Biofilm was treated with 108PFU/mL of phage_2, phage_18 or 5 μg/mL of ceftolozane/tazobactam, alone or in combination with phages. The sequential combination of the two different phages and ceftolozane/tazobactam was also tested. Biofilm viability was assessed after short (2, 4, 24 h) and long-(48, 72 h) term treatment exposure using colony forming unit measurement. For long-term exposition, a new treatment shot was added every 24 h. In the sequential combination, the phage type was switched at 24 h of treatment. Regarding the susceptible strains, the treatments had limited antibiofilm effect after 2, 4 and 24 h. After 48 and 72 h, administering phages alone had no effect on biofilm viability, indicating the emergence of phage-resistant phenotypes. Nonetheless, the combined phage-antibiotic treatment reduced the biofilm viability in about 5-log, whilst antibiotic alone reduced in about 3-log. The sequential combination of phages and antibiotic reduced the biofilm viability in about 6-log. With respect to the resistant strains, no antibiofilm activity was observed regarding the treatment arms. The combination of phages and ceftolozane/tazobactam showed a synergism strain-dependent, being more apparent in susceptible strains.
{"title":"The synergistic effect between phages and Ceftolozane/Tazobactam in <i>Pseudomonas aeruginosa</i> endotracheal tube biofilm.","authors":"Viviane de C Oliveira, Alba Soler-Comas, Amanda C S D Rocha, Cláudia H Silva-Lovato, Evandro Watanabe, Antoni Torres, Laia Fernández-Barat","doi":"10.1080/22221751.2024.2420737","DOIUrl":"10.1080/22221751.2024.2420737","url":null,"abstract":"<p><p>Although an increased effectiveness has been suggested when phages and antibiotics are combined, this approach has not been tested against a mature biofilm on an endotracheal tube (ETT) surface. This study evaluated the effect of short- and long-term combined phage-antibiotic therapy in a control of a mature biofilm on an ETT surface. <i>Pseudomonas aeruginosa</i> strains, including susceptible and resistant clinical samples, were used to develop the ETT biofilm. Biofilm was treated with 10<sup>8</sup>PFU/mL of phage_2, phage_18 or 5 μg/mL of ceftolozane/tazobactam, alone or in combination with phages. The sequential combination of the two different phages and ceftolozane/tazobactam was also tested. Biofilm viability was assessed after short (2, 4, 24 h) and long-(48, 72 h) term treatment exposure using colony forming unit measurement. For long-term exposition, a new treatment shot was added every 24 h. In the sequential combination, the phage type was switched at 24 h of treatment. Regarding the susceptible strains, the treatments had limited antibiofilm effect after 2, 4 and 24 h. After 48 and 72 h, administering phages alone had no effect on biofilm viability, indicating the emergence of phage-resistant phenotypes. Nonetheless, the combined phage-antibiotic treatment reduced the biofilm viability in about 5-log, whilst antibiotic alone reduced in about 3-log. The sequential combination of phages and antibiotic reduced the biofilm viability in about 6-log. With respect to the resistant strains, no antibiofilm activity was observed regarding the treatment arms. The combination of phages and ceftolozane/tazobactam showed a synergism strain-dependent, being more apparent in susceptible strains.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2420737"},"PeriodicalIF":8.4,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11571741/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142616958","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}
Coxsackievirus B4 (CVB4) is associated with a range of acute and chronic diseases such as hand, foot, and mouth disease, myocarditis, meningitis, pancreatitis, and type 1 diabetes, affecting millions of young children annually around the world. However, no vaccine is currently available for preventing CVB4 infection. Here, we report the development of inactivated viral particle vaccines for CVB4. Two types of inactivated CVB4 particles were prepared from CVB4-infected cell cultures as vaccine antigens, including F-particle (also called mature virion) consisting of VP1, VP3, VP2, and VP4 subunit proteins, and E-particle (also called empty capsid) which is made of VP1, VP3, and uncleaved VP0. Both the inactivated CVB4 F-particle and E-particle were able to potently elicit neutralizing antibodies in mice, despite slightly lower neutralizing antibody titres seen with the E-particle vaccine after the third immunization. Importantly, we demonstrated that passive transfer of either anti-F-particle or anti-E-particle sera could completely protect the recipient mice from lethal CVB4 challenge. Our study not only defines the immunogenicity and protective efficacy of inactivated CVB4 F-particle and E-particle but also reveals the central role of neutralizing antibodies in anti-CVB4 protective immunity, thus providing important information that may accelerate the development of inactivated CVB4 vaccines.
摘要ABSTRACTCoxsackievirus B4(CVB4)与手足口病、心肌炎、脑膜炎、胰腺炎和 1 型糖尿病等一系列急性和慢性疾病有关,每年影响着全球数百万幼儿。然而,目前还没有预防 CVB4 感染的疫苗。在此,我们报告了 CVB4 病毒颗粒灭活疫苗的研发情况。我们从CVB4感染的细胞培养物中制备了两种灭活的CVB4颗粒作为疫苗抗原,包括由VP1、VP3、VP2和VP4亚基蛋白组成的F颗粒(又称成熟病毒体)和由VP1、VP3和未分化VP0组成的E颗粒(又称空壳)。灭活的 CVB4 F 颗粒和 E 颗粒都能有效激发小鼠体内的中和抗体,尽管在第三次免疫后,E 颗粒疫苗的中和抗体滴度略低。重要的是,我们证明了被动转移抗 F 粒子或抗 E 粒子血清可完全保护受体小鼠免受致命的 CVB4 挑战。我们的研究不仅确定了 CVB4 F 颗粒和 E 颗粒灭活疫苗的免疫原性和保护效力,还揭示了中和抗体在抗 CVB4 保护性免疫中的核心作用,从而为加速 CVB4 灭活疫苗的开发提供了重要信息。
{"title":"Immunogenicity and protective efficacy of inactivated coxsackievirus B4 viral particles.","authors":"Tingfeng Wang, Chiyuan Wang, Lili Pang, Yujie Zhang, Shuxia Wang, Xiaozhen Liang, Zhong Huang","doi":"10.1080/22221751.2024.2337665","DOIUrl":"10.1080/22221751.2024.2337665","url":null,"abstract":"<p><p>Coxsackievirus B4 (CVB4) is associated with a range of acute and chronic diseases such as hand, foot, and mouth disease, myocarditis, meningitis, pancreatitis, and type 1 diabetes, affecting millions of young children annually around the world. However, no vaccine is currently available for preventing CVB4 infection. Here, we report the development of inactivated viral particle vaccines for CVB4. Two types of inactivated CVB4 particles were prepared from CVB4-infected cell cultures as vaccine antigens, including F-particle (also called mature virion) consisting of VP1, VP3, VP2, and VP4 subunit proteins, and E-particle (also called empty capsid) which is made of VP1, VP3, and uncleaved VP0. Both the inactivated CVB4 F-particle and E-particle were able to potently elicit neutralizing antibodies in mice, despite slightly lower neutralizing antibody titres seen with the E-particle vaccine after the third immunization. Importantly, we demonstrated that passive transfer of either anti-F-particle or anti-E-particle sera could completely protect the recipient mice from lethal CVB4 challenge. Our study not only defines the immunogenicity and protective efficacy of inactivated CVB4 F-particle and E-particle but also reveals the central role of neutralizing antibodies in anti-CVB4 protective immunity, thus providing important information that may accelerate the development of inactivated CVB4 vaccines.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":" ","pages":"2337665"},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11000607/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140318030","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}
The prevalence of listeriosis in China has been increasing in recent years. Listeriosis primarily spreads through contaminated food. However, the resilient causative organism, Listeria monocytogenes, and its extended incubation period pose challenges in identifying risk factors associated with food consumption and food-handling habits. This study aimed to identify the risk factors associated with food consumption and food-handling habits for listeriosis in China. A matched case-control study (1:1 ratio) was conducted, which enrolled all eligible cases of listeriosis between 1 January 2013 and 31 December 2022 in China. Basic information and possible risk factors associated with food consumption and food-handling habits were collected. Overall, 359 patients were enrolled, including 208 perinatal and 151 non-perinatal cases. Univariate and multivariable logistic analyzes were performed for the perinatal group. For the perinatal and non-perinatal groups, ice cream and Chinese cold dishes were the high-risk foods for listeriosis (odds ratio (OR) 2.09 95% confidence interval (CI): 1.23-3.55; OR 3.17 95% CI: 1.29-7.81), respectively; consumption of leftovers and pet ownership were the high-risk food-handling habits (OR 1.92 95% CI: 1.03-3.59; OR 3.00 95% CI: 1.11-8.11), respectively. In both groups, separation of raw and cooked foods was a protective factor (OR 0.27 95% CI: 0.14-0.51; OR 0.35 95% CI: 0.14-0.89), while refrigerator cleaning reduced the infection risk by 64.94-70.41% only in the perinatal group. The identification of high-risk foods and food-handling habits for listeriosis is important for improving food safety guidelines for vulnerable populations.
{"title":"Risk factors associated with food consumption and food-handling habits for sporadic listeriosis: a case-control study in China from 2013 to 2022.","authors":"Yanlin Niu, Weiwei Li, Biyao Xu, Wen Chen, Xiaojuan Qi, Yijing Zhou, Ping Fu, Xiaochen Ma, Yunchang Guo","doi":"10.1080/22221751.2024.2307520","DOIUrl":"10.1080/22221751.2024.2307520","url":null,"abstract":"<p><p>The prevalence of listeriosis in China has been increasing in recent years. Listeriosis primarily spreads through contaminated food. However, the resilient causative organism, <i>Listeria monocytogenes</i>, and its extended incubation period pose challenges in identifying risk factors associated with food consumption and food-handling habits. This study aimed to identify the risk factors associated with food consumption and food-handling habits for listeriosis in China. A matched case-control study (1:1 ratio) was conducted, which enrolled all eligible cases of listeriosis between 1 January 2013 and 31 December 2022 in China. Basic information and possible risk factors associated with food consumption and food-handling habits were collected. Overall, 359 patients were enrolled, including 208 perinatal and 151 non-perinatal cases. Univariate and multivariable logistic analyzes were performed for the perinatal group. For the perinatal and non-perinatal groups, ice cream and Chinese cold dishes were the high-risk foods for listeriosis (odds ratio (OR) 2.09 95% confidence interval (CI): 1.23-3.55; OR 3.17 95% CI: 1.29-7.81), respectively; consumption of leftovers and pet ownership were the high-risk food-handling habits (OR 1.92 95% CI: 1.03-3.59; OR 3.00 95% CI: 1.11-8.11), respectively. In both groups, separation of raw and cooked foods was a protective factor (OR 0.27 95% CI: 0.14-0.51; OR 0.35 95% CI: 0.14-0.89), while refrigerator cleaning reduced the infection risk by 64.94-70.41% only in the perinatal group. The identification of high-risk foods and food-handling habits for listeriosis is important for improving food safety guidelines for vulnerable populations.</p>","PeriodicalId":11602,"journal":{"name":"Emerging Microbes & Infections","volume":"13 1","pages":"2307520"},"PeriodicalIF":13.2,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10860432/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139717429","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}