The Journal of Infectious Diseases最新文献_第8页

Safety and Immunogenicity of an Adjuvanted Clostridioides difficile Vaccine Candidate in Healthy Adults: A Randomized Placebo-Controlled Phase 1 Study 健康成年人接种艰难梭菌佐剂疫苗的安全性和免疫原性：随机安慰剂对照 1 期研究

The Journal of Infectious Diseases Pub Date : 2024-10-24 DOI: 10.1093/infdis/jiae466

Isabel Leroux-Roels, Azhar Alhatemi, Magalie Caubet, Fien De Boever, Bertrand de Wergifosse, Mohamed El Idrissi, Guilherme S Ferreira, Bart Jacobs, Axel Lambert, Sandra Morel, Charlotte Servais, Juan Pablo Yarzabal

{"title":"Safety and Immunogenicity of an Adjuvanted Clostridioides difficile Vaccine Candidate in Healthy Adults: A Randomized Placebo-Controlled Phase 1 Study","authors":"Isabel Leroux-Roels, Azhar Alhatemi, Magalie Caubet, Fien De Boever, Bertrand de Wergifosse, Mohamed El Idrissi, Guilherme S Ferreira, Bart Jacobs, Axel Lambert, Sandra Morel, Charlotte Servais, Juan Pablo Yarzabal","doi":"10.1093/infdis/jiae466","DOIUrl":"https://doi.org/10.1093/infdis/jiae466","url":null,"abstract":"Background This study investigated the safety, reactogenicity, and immunogenicity in healthy subjects of a Clostridioides difficile vaccine candidate with/without adjuvant, targeting toxins A and B. Methods In this first-in-human, phase 1, observer-blind study, subjects aged 18–45 years were randomized to receive F2 antigen (n = 10) or placebo (n = 10), and subjects aged 50–70 years to receive F2 antigen plus AS01 adjuvant (n = 45), F2 antigen (n = 45), or placebo (n = 30) in 2 doses 1 month apart. A subcohort (n = 40) received a third dose 15 months later. Solicited adverse events (AEs) were recorded for 7 days and unsolicited AEs for 30 days after each dose. Immunogenicity was assessed at baseline and after each dose. Results Solicited AEs were transient and most frequent in subjects receiving F2 antigen plus AS01. No serious AEs were considered related to study vaccine. Immunogenicity was substantially higher in subjects receiving F2 antigen plus AS01 than subjects receiving F2 antigen alone. A third dose increased the immune response in subjects with baseline neutralization titers below the assay lower limit of quantitation. Conclusions The GSK C. difficile vaccine candidate was immunogenic, especially when given with AS01, and was well tolerated with an acceptable safety profile. Clinical Trial Registration NCT04026009.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"9 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

An Expression Quantitative Trait Locus of Fc Gamma Receptor Genes is Associated with Anti-Malarial IgG Responses and Infection Levels in Burkinabe Families Fc Gamma 受体基因的表达量性状基因座与布基纳法索家庭的抗疟疾 IgG 反应和感染水平有关

The Journal of Infectious Diseases Pub Date : 2024-10-23 DOI: 10.1093/infdis/jiae528

Christelle Dieppois, Mathieu Adjemout, Jules Cretin, Frederic Gallardo, Magali Torres, Christophe Picard, Serge Aimé Sawadogo, Pascal Rihet, Pascale Paul

{"title":"An Expression Quantitative Trait Locus of Fc Gamma Receptor Genes is Associated with Anti-Malarial IgG Responses and Infection Levels in Burkinabe Families","authors":"Christelle Dieppois, Mathieu Adjemout, Jules Cretin, Frederic Gallardo, Magali Torres, Christophe Picard, Serge Aimé Sawadogo, Pascal Rihet, Pascale Paul","doi":"10.1093/infdis/jiae528","DOIUrl":"https://doi.org/10.1093/infdis/jiae528","url":null,"abstract":"Background The interaction between antibodies and Fc gamma receptors (FcγRs) plays a critical role in regulating immune responses to Plasmodium falciparum. Polymorphisms in genes encoding FcγRs influence the host's capacity to control parasite infection. This study investigates whether non-coding variants influencing FcγR expression are associated with anti-malarial immunization and infection traits. Methods We utilized eQTL databases and functional annotations to identify non-coding variants, specifically rs1771575, rs2099684, and rs6700241, within the FCGR gene cluster. In addition, we examined the coding variants rs1801274 (p.His167Arg) and rs1050501 (p.Ile231Thr), which affect the affinity of FcγRIIa and FcγRIIb for IgG. These variants were genotyped in 163 individuals from Burkinabe families. Family-based linear mixed regression and Quantitative Transmission Disequilibrium Tests (QTDT) analyses were performed to assess associations with IgG levels and malaria infection, accounting for relevant covariates. Results Linear mixed models identified rs1771575 as associated with total IgG levels, while both rs1771575 and rs1801274 were linked to IgG2, and rs1050501 to IgG1 levels. A haplotype combining rs2099684 and rs6700241 was positively associated with IgG1. The rs1771575-CC and rs1050501-TT genotypes correlated with higher infection levels in children. QTDT models confirmed the association of rs1771575 with IgG2 and infection in children. Conclusions Our findings suggest that the intergenic variant rs1771575 serves as an independent marker for IgG levels and blood infection in children. This highlights the interplay between regulatory variants and coding mutations in FCGR, which may influence immune function and antibody production. These results underscore the potential for personalized strategies to monitor humoral responses in malaria-endemic regions.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"54 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490543","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Evaluation and real-world experience of a neutralization susceptibility screening assay for broadly neutralizing anti-HIV-1 antibodies. 广泛中和抗 HIV-1 抗体的中和敏感性筛选试验的评估和实际经验。

The Journal of Infectious Diseases Pub Date : 2024-10-23 DOI: 10.1093/infdis/jiae486

Marie Høst Pahus,Yu Zheng,Maxine Olefsky,Jesper Damsgaard Gunst,Pablo Tebas,Babafemi Taiwo,Ole S Søgaard,Michael J Peluso,Yolanda Lie,Jacqueline D Reeves,Christos J Petropoulos,Marina Caskey,Katharine J Bar

{"title":"Evaluation and real-world experience of a neutralization susceptibility screening assay for broadly neutralizing anti-HIV-1 antibodies.","authors":"Marie Høst Pahus,Yu Zheng,Maxine Olefsky,Jesper Damsgaard Gunst,Pablo Tebas,Babafemi Taiwo,Ole S Søgaard,Michael J Peluso,Yolanda Lie,Jacqueline D Reeves,Christos J Petropoulos,Marina Caskey,Katharine J Bar","doi":"10.1093/infdis/jiae486","DOIUrl":"https://doi.org/10.1093/infdis/jiae486","url":null,"abstract":"BACKGROUNDDevelopment of a screening assay for the clinical use of broadly neutralizing antibodies (bnAbs) is a priority for HIV therapy and cure initiatives.METHODSWe assessed the PhenoSense Monoclonal Antibody (mAb) Assay (Labcorp-Monogram Biosciences) which is CLIA-validated and has been used prospectively and retrospectively in multiple recent bnAb clinical trials.RESULTSWhen performed on pre-ART plasma and on-ART longitudinal PBMC samples sourced from a recent clinical trial, the PhenoSense mAb Assay produced robust reproducibility, concordance across sample types, and expected ranges in the susceptibility measures of bnAbs in clinical development. PhenoSense mAb applied retrospectively to baseline samples from three recent studies correlated with published laboratory-based study evaluations, but baseline bnAb susceptibility was not consistently predictive of durable virus suppression. Assessment of the feasibility of the assay in four recent clinical studies provides estimates of assay success rate and processing time.CONCLUSIONSThe PhenoSense mAb Assay provides reproducible bnAb susceptibility measurements across relevant sample types yet was not consistently predictive of virus suppression. Logistical and operational assay requirements can impact timely clinical trial conduct. These results inform bnAb studies in development.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"194 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488190","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Review: Diagnostic Potential for Collaborative Pharyngitis Biomarkers. 评论：咽炎合作生物标志物的诊断潜力。

The Journal of Infectious Diseases Pub Date : 2024-10-23 DOI: 10.1093/infdis/jiae416

Nathan A Ledeboer,Jane M Caldwell,Bobby L Boyanton

引用次数: 0

Review: Current Laboratory and Point-of-Care Pharyngitis Diagnostic Testing and Knowledge Gaps. 回顾：当前实验室和护理点咽炎诊断测试及知识差距。

The Journal of Infectious Diseases Pub Date : 2024-10-23 DOI: 10.1093/infdis/jiae415

Bobby L Boyanton,Jane M Caldwell,Nathan A Ledeboer

引用次数: 0

EDP-938 Has a High Barrier to Resistance in Healthy Adults Experimentally Infected with Respiratory Syncytial Virus. EDP-938 在实验性感染呼吸道合胞病毒的健康成人中具有很高的抗性屏障。

The Journal of Infectious Diseases Pub Date : 2024-10-23 DOI: 10.1093/infdis/jiae471

Rachel Emily Levene,John DeVincenzo,Annie L Conery,Alaa Ahmed,Yat Sun Or,Michael H J Rhodin

{"title":"EDP-938 Has a High Barrier to Resistance in Healthy Adults Experimentally Infected with Respiratory Syncytial Virus.","authors":"Rachel Emily Levene,John DeVincenzo,Annie L Conery,Alaa Ahmed,Yat Sun Or,Michael H J Rhodin","doi":"10.1093/infdis/jiae471","DOIUrl":"https://doi.org/10.1093/infdis/jiae471","url":null,"abstract":"BACKGROUNDEDP-938 is an oral once-daily RSV nucleoprotein (N) inhibitor with potent antiviral activity. In a human RSV challenge trial, EDP-938 significantly reduced viral load and symptom severity. During antiviral development, it is critical to understand the propensity for resistance to develop. In vitro studies of EDP-938 suggest a higher barrier to resistance as compared to RSV fusion inhibitors. We evaluated the development of viral resistance to EDP-938 in a human challenge trial.METHODSA subset of the 124 participants with RSV infection were chosen for genetic analysis; 159 nasal wash samples from 48 participants were analyzed using next-generation sequencing of the N gene of RSV. Of the 48 participant sampled, 37 were from EDP-938-treated and 11 were placebo-treated participants, representing 45% and 26% of the participants, respectively. The effects of treatment-emergent mutations on viral load, EDP-938 efficacy, and viral fitness were evaluated.RESULTSTwo of the 37 EDP-938-treated participants with samples sequenced had treatment-emergent mutations: N:L139I and N:E112G. From in vitro analysis, N:L139I reduced sensitivity to EDP-938 by approximately 10-fold, while N:E112G had no effect. However, N:L139I was associated with a reduction in viral fitness, suggesting clinical resistance is associated with fitness costs. Neither of these variants were associated with reduced viral clearance.CONCLUSIONSIn human RSV infections treated with EDP-938, emergence of RSV variants with reduced sensitivity to EDP-938 occurred in only 1 participant and was associated with reduced viral fitness. EDP-938's high barrier to resistance highlights its robust mechanism of action.CLINICAL TRIALS REGISTRATIONNCT03691623.","PeriodicalId":501010,"journal":{"name":"The Journal of Infectious Diseases","volume":"30 1","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142489794","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

COVID-19 lineages in a minimally vaccinated island population: Genomic epidemiology of SARS-CoV-2 in Haiti. 接种疫苗最少的岛屿人口中的 COVID-19 世系：海地 SARS-CoV-2 基因组流行病学。

The Journal of Infectious Diseases Pub Date : 2024-10-23 DOI: 10.1093/infdis/jiae520

Carla N Mavian,Massimiliano S Tagliamonte,Maclean Bassett,Meer Alam,Melanie N Cash,Matt Hitchings,Rigan Louis,Alberto Riva,Kayvan Zainabadi,Marie Marcelle Deschamps,Bernard Liautaud,Vanessa Rouzier,Daniel W Fitzgerald,Jean William Pape,J Glenn Morris,Marco Salemi

引用次数: 0

Review: Known, Emerging, and Remerging Pharyngitis Pathogens. 回顾：已知、新出现和再次出现的咽炎病原体。

The Journal of Infectious Diseases Pub Date : 2024-10-23 DOI: 10.1093/infdis/jiae391

Jane M Caldwell,Nathan A Ledeboer,Bobby L Boyanton

引用次数: 0

Neutralizing Antibody Responses to Chlamydia trachomatis in Women and Associations with Chlamydia Outcomes 女性沙眼衣原体中和抗体反应及其与衣原体感染结果的关系

The Journal of Infectious Diseases Pub Date : 2024-10-22 DOI: 10.1093/infdis/jiae519

Hong Yu, William M Geisler, Chuanbin Dai, Kanupriya Gupta, Gary Cutter, Robert C Brunham

引用次数: 0

Systems Vaccinology: Navigating the Future of Personalized Immunity and Next Generation Vaccines 系统疫苗学：引领个性化免疫和下一代疫苗的未来

The Journal of Infectious Diseases Pub Date : 2024-10-19 DOI: 10.1093/infdis/jiae505

Serena Maria Dib, Sonia Tandon Wimalasena, Daniel S Graciaa, Nadine Rouphael

引用次数: 0