Pub Date : 2025-02-12DOI: 10.1016/j.lanmic.2024.101000
Melinda J Hamer, James M McCarty, Benjamin C Pierson, Jason A Regules, Jason Mendy, Aaron D Sanborn, Christina L Gardner, Jeannine M Haller, Melissa K Gregory, Dani L Liggett, Pamela J Glass, Neha Ghosh, Sarah Royalty Tredo, Kelly L Warfield, Crystal W Burke, Christine Lee, David Saunders, Lisa Bedell, Jason S Richardson
<p><strong>Background: </strong>Immune responses to alphavirus vaccines might be impaired when heterologous alphavirus vaccines are administered sequentially. We aimed to compare immunogenicity and safety of a chikungunya virus virus-like particle (CHIKV VLP) vaccine in previous recipients of heterologous alphavirus vaccines with alphavirus-naive controls in the USA.</p><p><strong>Methods: </strong>In this open-label, parallel-group, age-matched, sex-matched, phase 2 randomised controlled trial, which was conducted at two clinical study sites in the USA, adults (aged 18-65 years) who had previously received an investigational Venezuelan equine encephalitis virus vaccine (previous alphavirus vaccine recipients; n=30) and sex-matched and age-matched alphavirus vaccine-naive controls (n=30) were intramuscularly administered one 40 μg dose of CHIKV VLP vaccine on day 1. Immunogenicity was based on serum neutralising antibodies assessed by an in-vitro luciferase-based anti-CHIKV NT<sub>80</sub> neutralisation assay. The primary immunogenicity endpoint, which was assessed in the immunogenicity evaluable population (CHIKV VLP-vaccinated participants who had no important protocol deviations, had not received a prohibited medication, and provided evaluable serum sample results for baseline and on day 22), was to compare the proportion of previous alphavirus vaccine recipients with the proportion of alphavirus vaccine-naive controls who reached seroconversion 21 days after vaccination (ie, study day 22) with a single dose of CHIKV VLP vaccine, based on a four-fold increase of CHIKV neutralising antibodies compared with baseline. The significance of the comparison of the two groups was assessed using Fisher's exact test. The proportion with seroconversion in each group is presented with 95% CIs calculated using the Wilson method. The difference and 95% CIs for this difference was calculated based on Newcombe hybrid score method. An ANOVA model was fit with log<sub>10</sub>-transformed titre as the dependent variable, and study arm, age, and sex as predictors. Least squares means, difference, and 95% CIs were back-transformed and reported as geometric mean titres (GMTs). This trial is registered with ClinicalTrials.gov, NCT03992872.</p><p><strong>Findings: </strong>Between Nov 20, 2019, and Jan 19, 2021, 60 participants (20 [33%] female and 40 [67%] male; 40 (67%) White; median age 47·0 years [IQR 13·5]), 30 previous alphavirus vaccine recipients and 30 alphavirus vaccine-naive controls, were enrolled, vaccinated with CHIKV VLP, and completed the trial. The anti-CHIKV neutralising antibody seroconversion rate at day 22 was 100% (95% CI 88·6-100) in both groups. GMTs peaked in previous alphavirus vaccine recipients and alphavirus vaccine-naive controls at day 22 (2032·5 [95% CI 1413·0-2923·6] and 2299·2 [1598·1-3307·8], respectively) and were similar between the groups on day 22 and all subsequent visits. A higher proportion of previous alphavirus vaccine rec
{"title":"Safety and immunogenicity of an adjuvanted chikungunya virus virus-like particle (CHIKV VLP) vaccine in previous recipients of other alphavirus vaccines versus alphavirus vaccine-naive controls: an open-label, parallel-group, age-matched, sex-matched, phase 2 randomised controlled study.","authors":"Melinda J Hamer, James M McCarty, Benjamin C Pierson, Jason A Regules, Jason Mendy, Aaron D Sanborn, Christina L Gardner, Jeannine M Haller, Melissa K Gregory, Dani L Liggett, Pamela J Glass, Neha Ghosh, Sarah Royalty Tredo, Kelly L Warfield, Crystal W Burke, Christine Lee, David Saunders, Lisa Bedell, Jason S Richardson","doi":"10.1016/j.lanmic.2024.101000","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.101000","url":null,"abstract":"<p><strong>Background: </strong>Immune responses to alphavirus vaccines might be impaired when heterologous alphavirus vaccines are administered sequentially. We aimed to compare immunogenicity and safety of a chikungunya virus virus-like particle (CHIKV VLP) vaccine in previous recipients of heterologous alphavirus vaccines with alphavirus-naive controls in the USA.</p><p><strong>Methods: </strong>In this open-label, parallel-group, age-matched, sex-matched, phase 2 randomised controlled trial, which was conducted at two clinical study sites in the USA, adults (aged 18-65 years) who had previously received an investigational Venezuelan equine encephalitis virus vaccine (previous alphavirus vaccine recipients; n=30) and sex-matched and age-matched alphavirus vaccine-naive controls (n=30) were intramuscularly administered one 40 μg dose of CHIKV VLP vaccine on day 1. Immunogenicity was based on serum neutralising antibodies assessed by an in-vitro luciferase-based anti-CHIKV NT<sub>80</sub> neutralisation assay. The primary immunogenicity endpoint, which was assessed in the immunogenicity evaluable population (CHIKV VLP-vaccinated participants who had no important protocol deviations, had not received a prohibited medication, and provided evaluable serum sample results for baseline and on day 22), was to compare the proportion of previous alphavirus vaccine recipients with the proportion of alphavirus vaccine-naive controls who reached seroconversion 21 days after vaccination (ie, study day 22) with a single dose of CHIKV VLP vaccine, based on a four-fold increase of CHIKV neutralising antibodies compared with baseline. The significance of the comparison of the two groups was assessed using Fisher's exact test. The proportion with seroconversion in each group is presented with 95% CIs calculated using the Wilson method. The difference and 95% CIs for this difference was calculated based on Newcombe hybrid score method. An ANOVA model was fit with log<sub>10</sub>-transformed titre as the dependent variable, and study arm, age, and sex as predictors. Least squares means, difference, and 95% CIs were back-transformed and reported as geometric mean titres (GMTs). This trial is registered with ClinicalTrials.gov, NCT03992872.</p><p><strong>Findings: </strong>Between Nov 20, 2019, and Jan 19, 2021, 60 participants (20 [33%] female and 40 [67%] male; 40 (67%) White; median age 47·0 years [IQR 13·5]), 30 previous alphavirus vaccine recipients and 30 alphavirus vaccine-naive controls, were enrolled, vaccinated with CHIKV VLP, and completed the trial. The anti-CHIKV neutralising antibody seroconversion rate at day 22 was 100% (95% CI 88·6-100) in both groups. GMTs peaked in previous alphavirus vaccine recipients and alphavirus vaccine-naive controls at day 22 (2032·5 [95% CI 1413·0-2923·6] and 2299·2 [1598·1-3307·8], respectively) and were similar between the groups on day 22 and all subsequent visits. A higher proportion of previous alphavirus vaccine rec","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101000"},"PeriodicalIF":20.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426322","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-12DOI: 10.1016/j.lanmic.2025.101077
The Lancet Microbe Editors
{"title":"Thank you to The Lancet Microbe statistical and peer reviewers in 2024.","authors":"The Lancet Microbe Editors","doi":"10.1016/j.lanmic.2025.101077","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101077","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101077"},"PeriodicalIF":20.9,"publicationDate":"2025-02-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426324","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-10DOI: 10.1016/j.lanmic.2024.100988
Wontae Hwang, Paeton L Wantuch, Biana Bernshtein, Julia A Zhiteneva, Damien M Slater, Kian Hutt Vater, Sushmita Sridhar, Elizabeth Oliver, David J Roach, Sowmya R Rao, Sarah E Turbett, Cory J Knoot, Christian M Harding, Mohammed Nurul Amin, Alan S Cross, Regina C LaRocque, David A Rosen, Jason B Harris
<p><strong>Background: </strong>Klebsiella pneumoniae is a leading cause of infection-related deaths globally, yet little is known about human antibody responses to invasive K pneumoniae. We sought to determine whether the O-specific polysaccharide antigen is immunogenic in humans with K pneumoniae bloodstream infection. We also sought to define the cross-reactivity of human antibody responses among structurally related K pneumoniae O-specific polysaccharide subtypes and to assess the effect of capsule production on O-specific polysaccharide-targeted antibody binding and function.</p><p><strong>Methods: </strong>In this prospective cohort study, we compared plasma antibody responses to O-specific polysaccharide in a cohort of consecutively enrolled patients with K pneumoniae bloodstream infection with controls, specifically a cohort of healthy individuals and a cohort of individuals with Enterococcus spp bloodstream infection. Patients were enrolled at the Massachusetts General Hospital, a tertiary hospital with affiliated clinics in the USA. We excluded patients whose isolates were not confirmed to be K pneumoniae by whole-genome sequencing. The primary outcome was the measurement of plasma IgG, IgM, and IgA antibody responses. We performed flow cytometry to measure the effects of K pneumoniae capsule production on O-specific polysaccharide antibody binding and O-specific polysaccharide antibody-mediated complement deposition, using patient isolates with variable levels of capsule production and isogenic capsule-deficient strains derived from these isolates.</p><p><strong>Findings: </strong>We enrolled 129 consecutive patients with suspected K pneumoniae bloodstream infection between July 24, 2021, and August 4, 2022, of whom 69 patients (44 [64%] male and 25 [36%] female) with confirmed K pneumoniae bloodstream infection were eligible for immunological evaluation. Common O-specific polysaccharide serotypes (O1, O2, O3, and O5) accounted for 57 (83%) of 69 infections. O-specific polysaccharide was immunogenic in patients with K pneumoniae bloodstream infection, and peak O-specific polysaccharide-IgG antibody responses in patients were ten-fold to 30-fold higher than antibody responses detected in healthy controls, depending on the serotype. There was cross-reactivity among similar O-specific polysaccharide subtypes, including the O1v1 and O1v2, O2v1 and O2v2, and O3 and O3b subtypes, as well as between the O1 and O2 types. Capsule produced by both hyperencapsulated and non-hyperencapsulated K pneumoniae inhibited O-specific polysaccharide-targeted antibody binding and function.</p><p><strong>Interpretation: </strong>O-specific polysaccharide was immunogenic in patients with K pneumoniae bloodstream infection, supporting its potential as a candidate vaccine antigen. The cross-reactivity observed between similar O-specific polysaccharide subtypes in patients with K pneumoniae bloodstream infection suggests that it might not be necessary to include
{"title":"Antibody responses in Klebsiella pneumoniae bloodstream infection: a prospective cohort study.","authors":"Wontae Hwang, Paeton L Wantuch, Biana Bernshtein, Julia A Zhiteneva, Damien M Slater, Kian Hutt Vater, Sushmita Sridhar, Elizabeth Oliver, David J Roach, Sowmya R Rao, Sarah E Turbett, Cory J Knoot, Christian M Harding, Mohammed Nurul Amin, Alan S Cross, Regina C LaRocque, David A Rosen, Jason B Harris","doi":"10.1016/j.lanmic.2024.100988","DOIUrl":"10.1016/j.lanmic.2024.100988","url":null,"abstract":"<p><strong>Background: </strong>Klebsiella pneumoniae is a leading cause of infection-related deaths globally, yet little is known about human antibody responses to invasive K pneumoniae. We sought to determine whether the O-specific polysaccharide antigen is immunogenic in humans with K pneumoniae bloodstream infection. We also sought to define the cross-reactivity of human antibody responses among structurally related K pneumoniae O-specific polysaccharide subtypes and to assess the effect of capsule production on O-specific polysaccharide-targeted antibody binding and function.</p><p><strong>Methods: </strong>In this prospective cohort study, we compared plasma antibody responses to O-specific polysaccharide in a cohort of consecutively enrolled patients with K pneumoniae bloodstream infection with controls, specifically a cohort of healthy individuals and a cohort of individuals with Enterococcus spp bloodstream infection. Patients were enrolled at the Massachusetts General Hospital, a tertiary hospital with affiliated clinics in the USA. We excluded patients whose isolates were not confirmed to be K pneumoniae by whole-genome sequencing. The primary outcome was the measurement of plasma IgG, IgM, and IgA antibody responses. We performed flow cytometry to measure the effects of K pneumoniae capsule production on O-specific polysaccharide antibody binding and O-specific polysaccharide antibody-mediated complement deposition, using patient isolates with variable levels of capsule production and isogenic capsule-deficient strains derived from these isolates.</p><p><strong>Findings: </strong>We enrolled 129 consecutive patients with suspected K pneumoniae bloodstream infection between July 24, 2021, and August 4, 2022, of whom 69 patients (44 [64%] male and 25 [36%] female) with confirmed K pneumoniae bloodstream infection were eligible for immunological evaluation. Common O-specific polysaccharide serotypes (O1, O2, O3, and O5) accounted for 57 (83%) of 69 infections. O-specific polysaccharide was immunogenic in patients with K pneumoniae bloodstream infection, and peak O-specific polysaccharide-IgG antibody responses in patients were ten-fold to 30-fold higher than antibody responses detected in healthy controls, depending on the serotype. There was cross-reactivity among similar O-specific polysaccharide subtypes, including the O1v1 and O1v2, O2v1 and O2v2, and O3 and O3b subtypes, as well as between the O1 and O2 types. Capsule produced by both hyperencapsulated and non-hyperencapsulated K pneumoniae inhibited O-specific polysaccharide-targeted antibody binding and function.</p><p><strong>Interpretation: </strong>O-specific polysaccharide was immunogenic in patients with K pneumoniae bloodstream infection, supporting its potential as a candidate vaccine antigen. The cross-reactivity observed between similar O-specific polysaccharide subtypes in patients with K pneumoniae bloodstream infection suggests that it might not be necessary to include","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"100988"},"PeriodicalIF":20.9,"publicationDate":"2025-02-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143426318","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-06DOI: 10.1016/j.lanmic.2025.101086
Ziyu Huang, Yunyun Liu, Anna Philips, Fen Zhang, Tao Zuo
{"title":"Varied prevalence and asymptomatic carriage of Cryptococcus gattii in the gut of Chinese populations.","authors":"Ziyu Huang, Yunyun Liu, Anna Philips, Fen Zhang, Tao Zuo","doi":"10.1016/j.lanmic.2025.101086","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101086","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101086"},"PeriodicalIF":20.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383747","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-06DOI: 10.1016/j.lanmic.2025.101079
Yichao Pan, Andi Chen, Ling Chen, Zhijian Lin
{"title":"Wastewater surveillance for early warning of COVID-19 outbreaks in long-term care facilities.","authors":"Yichao Pan, Andi Chen, Ling Chen, Zhijian Lin","doi":"10.1016/j.lanmic.2025.101079","DOIUrl":"https://doi.org/10.1016/j.lanmic.2025.101079","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101079"},"PeriodicalIF":20.9,"publicationDate":"2025-02-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143383751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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