Pub Date : 2025-02-01DOI: 10.1016/j.lanmic.2024.101012
Amirhossein Rahmati , Shima Shahbaz , Mohammed Osman , Jan Willen Cohen Tervaert , Shokrollah Elahi
{"title":"Blood transcriptomic analyses do not support SARS-CoV-2 persistence in patients with post-COVID-19 condition with chronic fatigue syndrome","authors":"Amirhossein Rahmati , Shima Shahbaz , Mohammed Osman , Jan Willen Cohen Tervaert , Shokrollah Elahi","doi":"10.1016/j.lanmic.2024.101012","DOIUrl":"10.1016/j.lanmic.2024.101012","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 2","pages":"Article 101012"},"PeriodicalIF":20.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142569821","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.lanmic.2024.07.015
Norbert Heinrich MD PhD , Veronique de Jager MBChB , Julia Dreisbach DVM , Petra Gross-Demel PhD , Susanne Schultz MD , Sina Gerbach PhD , Florian Kloss PhD , Prof Rodney Dawson MD , Kim Narunsky MD , Leoni Matt MD , Leticia Wildner PhD , Prof Timothy D McHugh PhD , Prof Uwe Fuhr MD , Brian H Aldana MPh , Chaima Mouhdad PharmD , Lindsey te Brake PhD , Prof Martin J Boeree MD , Prof Rob E Aarnoutse PharmD PhD , Elin M Svensson PhD , Xue Gong MSc , Madalo Mukoka
<div><h3>Background</h3><div>The broad use of bedaquiline and pretomanid as the mainstay of new regimens to combat tuberculosis is a risk due to increasing bedaquiline resistance. We aimed to assess the safety, bactericidal activity, and pharmacokinetics of BTZ-043, a first-in-class DprE1 inhibitor with strong bactericidal activity in murine models.</div></div><div><h3>Methods</h3><div>This open-label, dose-expansion, randomised, controlled, phase 1b/2a trial was conducted in two specialised tuberculosis sites in Cape Town, South Africa. Adults aged 18–64 years with newly diagnosed pulmonary tuberculosis sensitive to rifampicin and isoniazid, who weighed at least 40 kg, had a positive sputum smear graded at least 1+, were HIV negative, and had no history of hypertension or other substantial comorbidities were admitted to hospital. In stage 1 (multiple-ascending dose phase 1b with an adaptive continual reassessment method), the starting dose of BTZ-043 was 250 mg, with planned dose increments of 250 mg up to 2000 mg, and cohorts of three participants were enrolled sequentially. In stage 2 (phase 2a dose-expansion stage), participants were randomly assigned (3:3:3:2) to receive one of three doses of oral BTZ-043 (decided after stage 1) or standard of care (isoniazid, rifampicin, pyrazinamide, and ethambutol) using sealed opaque envelopes. The BTZ-043 groups also received oral dolutegravir (a third of participants) or a probe drug cocktail (caffeine [probe for CYP1A2], tolbutamide [CYP2C9], dextromethorphan [CYP2D6], midazolam [CYP3A4], and digoxin [P-glycoprotein]; two-thirds of participants). Study staff and participants were not masked, but laboratory staff were masked to treatment assignment. The primary outcome was to assess the safety and tolerability of BTZ-43 over 14 days of dosing by evaluation of adverse events in the safety analysis population. Secondary outcomes were bactericidal activity, measured by time to positivity (TTP) and colony-forming unit (CFU) count; pharmacokinetics (stage 2; including the food effect on BTZ-043); and drug–drug interactions with CYP450 enzymes, P-glycoprotein, and dolutegravir. This study is registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, <span><span>NCT04044001</span><svg><path></path></svg></span> (completed).</div></div><div><h3>Findings</h3><div>In stage 1, 61 patients were assessed for eligibility and 24 were enrolled into seven dose cohorts between Nov 13, 2019, and Aug 13, 2020. Dose escalations were performed safely up to 1750 mg of BTZ-043 with three participants per dose cohort (and two dose cohorts for the highest dose). In stage 2, 151 patients were assessed for eligibility and 54 were enrolled and randomly assigned between Feb 2, 2021, and Feb 9, 2022, to receive 250, 500, and 1000 mg of BTZ-043 or standard of care. 66 (85%) of 78 participants were male and 12 (15%) were female. The most frequently observed adverse events were nausea (12 [8%] of 154), headac
{"title":"Safety, bactericidal activity, and pharmacokinetics of the antituberculosis drug candidate BTZ-043 in South Africa (PanACEA-BTZ-043–02): an open-label, dose-expansion, randomised, controlled, phase 1b/2a trial","authors":"Norbert Heinrich MD PhD , Veronique de Jager MBChB , Julia Dreisbach DVM , Petra Gross-Demel PhD , Susanne Schultz MD , Sina Gerbach PhD , Florian Kloss PhD , Prof Rodney Dawson MD , Kim Narunsky MD , Leoni Matt MD , Leticia Wildner PhD , Prof Timothy D McHugh PhD , Prof Uwe Fuhr MD , Brian H Aldana MPh , Chaima Mouhdad PharmD , Lindsey te Brake PhD , Prof Martin J Boeree MD , Prof Rob E Aarnoutse PharmD PhD , Elin M Svensson PhD , Xue Gong MSc , Madalo Mukoka","doi":"10.1016/j.lanmic.2024.07.015","DOIUrl":"10.1016/j.lanmic.2024.07.015","url":null,"abstract":"<div><h3>Background</h3><div>The broad use of bedaquiline and pretomanid as the mainstay of new regimens to combat tuberculosis is a risk due to increasing bedaquiline resistance. We aimed to assess the safety, bactericidal activity, and pharmacokinetics of BTZ-043, a first-in-class DprE1 inhibitor with strong bactericidal activity in murine models.</div></div><div><h3>Methods</h3><div>This open-label, dose-expansion, randomised, controlled, phase 1b/2a trial was conducted in two specialised tuberculosis sites in Cape Town, South Africa. Adults aged 18–64 years with newly diagnosed pulmonary tuberculosis sensitive to rifampicin and isoniazid, who weighed at least 40 kg, had a positive sputum smear graded at least 1+, were HIV negative, and had no history of hypertension or other substantial comorbidities were admitted to hospital. In stage 1 (multiple-ascending dose phase 1b with an adaptive continual reassessment method), the starting dose of BTZ-043 was 250 mg, with planned dose increments of 250 mg up to 2000 mg, and cohorts of three participants were enrolled sequentially. In stage 2 (phase 2a dose-expansion stage), participants were randomly assigned (3:3:3:2) to receive one of three doses of oral BTZ-043 (decided after stage 1) or standard of care (isoniazid, rifampicin, pyrazinamide, and ethambutol) using sealed opaque envelopes. The BTZ-043 groups also received oral dolutegravir (a third of participants) or a probe drug cocktail (caffeine [probe for CYP1A2], tolbutamide [CYP2C9], dextromethorphan [CYP2D6], midazolam [CYP3A4], and digoxin [P-glycoprotein]; two-thirds of participants). Study staff and participants were not masked, but laboratory staff were masked to treatment assignment. The primary outcome was to assess the safety and tolerability of BTZ-43 over 14 days of dosing by evaluation of adverse events in the safety analysis population. Secondary outcomes were bactericidal activity, measured by time to positivity (TTP) and colony-forming unit (CFU) count; pharmacokinetics (stage 2; including the food effect on BTZ-043); and drug–drug interactions with CYP450 enzymes, P-glycoprotein, and dolutegravir. This study is registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, <span><span>NCT04044001</span><svg><path></path></svg></span> (completed).</div></div><div><h3>Findings</h3><div>In stage 1, 61 patients were assessed for eligibility and 24 were enrolled into seven dose cohorts between Nov 13, 2019, and Aug 13, 2020. Dose escalations were performed safely up to 1750 mg of BTZ-043 with three participants per dose cohort (and two dose cohorts for the highest dose). In stage 2, 151 patients were assessed for eligibility and 54 were enrolled and randomly assigned between Feb 2, 2021, and Feb 9, 2022, to receive 250, 500, and 1000 mg of BTZ-043 or standard of care. 66 (85%) of 78 participants were male and 12 (15%) were female. The most frequently observed adverse events were nausea (12 [8%] of 154), headac","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 2","pages":"Article 100952"},"PeriodicalIF":20.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142967203","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-02-01DOI: 10.1016/j.lanmic.2024.101069
Dennis Nurjadi, Hinrich Schulenburg, Stefan Niemann, Annelies S Zinkernagel, Jan Rupp
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Pub Date : 2025-02-01DOI: 10.1016/j.lanmic.2024.07.014
Lindsay Dahora Hein PhD , Izabella N Castillo BS , Freddy A Medina PhD , Frances Vila BS , Bruno Segovia-Chumbez DDS , Jorge L Muñoz-Jordán PhD , Stephen S Whitehead PhD , Laura E Adams DVM MPH , Gabriela Paz-Bailey MD, PhD , Prof Aravinda M de Silva PhD , Lakshmanane Premkumar PhD
Background
Serology for dengue viruses (DENV) and Zika virus (ZIKV) has been hindered by antibody cross-reactivity, which limits the utility of these tests for surveillance and assessment of sero-status. Our aim was to develop a multiplexed IgG-based assay with increased accuracy to assess the history of previous DENV and ZIKV infections.
Methods
We developed and assessed the analytical performance of a sample-sparing, multiplexed, microsphere-based serological assay using domain III of the envelope protein (EDIII) of DENV serotypes 1–4 and ZIKV, the most variable region between each virus. We used a reference panel of well-characterised serum samples from US-based travellers or residents of southeast Asia, central America, or Puerto Rico, who were naive or immune to either or both DENV and ZIKV, to develop an algorithm for detecting previous exposure to DENV and ZIKV and identify optimal positivity cutoffs to maximise assay performance. To independently confirm the performance of the assay and algorithm, we used a second test set of previously collected samples from healthy children (aged 9–16 years) living in Puerto Rico, whose DENV and ZIKV serostatus had been defined using the gold-standard virus neutralisation assay. We evaluated the performance of the multiplex assay compared with the gold-standard assay by estimating sensitivity and specificity for identification of past exposure to ZIKV and DENV.
Findings
The multiplexed EDIII assay showed reproducible results over different days and a linearity range from μg to pg levels for various EDIII antigens. Using a reference panel of serum samples from individuals who were DENV naive (n=136), DENV immune (n=38), ZIKV naive (n=67), and ZIKV immune (n=28), we optimised the assay and developed a testing algorithm that was 94·9% (95% CI 83·1–99·1) sensitive and 97·1% (92·7–98·9) specific for identifying previous exposure to DENV, and 100% (95% CI 88·0–100) sensitive and 97·0% (89·8–99·5) specific for identifying previous exposure to ZIKV. In an analysis with an independent test set of 389 samples, the assay and algorithm had 94·2% (89·9–97·1) sensitivity and 92·9% (87·3–96·5) specificity for DENV, and 94·1% (88·7–97·4) sensitivity and 95·0% (90·0–98·0) specificity for ZIKV.
Interpretation
The multiplexed EDIII serology assay can accurately identify the history of previous infection with either DENV or ZIKV. This high-throughput and sample-sparing assay is a promising new tool for supporting flavivirus surveillance, epidemiological and clinical studies, and serological testing for dengue vaccine eligibility. Further studies are needed to reduce the cost of the assay, eliminate high background in some samples, and to assess performance in DENV-endemic and ZIKV-endemic countries.
Funding
US National Institutes of Health.
背景：登革热病毒（DENV）和寨卡病毒（ZIKV）的血清学一直受到抗体交叉反应性的阻碍，这限制了这些检测在监测和评估血清状态方面的应用。我们的目的是开发一种基于igg的多重检测方法，提高准确性，以评估以往DENV和ZIKV感染的历史。方法：我们利用DENV血清型1-4和ZIKV的包膜蛋白结构域III （EDIII）开发并评估了一种样本保留、多路、基于微球的血清学分析方法的分析性能，这是每种病毒之间变化最大的区域。我们使用了一个来自美国旅行者或东南亚、中美洲或波多黎各居民的特征良好的血清样本的参考小组，这些人对DENV和ZIKV中的一种或两种都没有免疫或没有免疫，从而开发了一种算法来检测以前接触过DENV和ZIKV并确定最佳阳性截止点，以最大限度地提高分析性能。为了独立确认该检测方法和算法的性能，我们使用了第二组先前从波多黎各健康儿童（9-16岁）收集的样本，这些儿童的DENV和ZIKV血清状态已使用金标准病毒中和试验确定。我们通过评估多重检测与金标准检测的敏感性和特异性来评估多重检测的性能，以确定过去暴露于ZIKV和DENV的情况。结果：多重EDIII检测结果在不同的时间内具有可重复性，并且多种EDIII抗原在μg到pg水平范围内呈线性。利用来自DENV初发（n=136）、DENV免疫（n=38）、ZIKV初发（n=67）和ZIKV免疫（n=28）个体的血清样本的参考小组，我们优化了检测方法，并开发了一种检测算法，该算法在识别DENV既往暴露方面敏感性为94.9% (95% CI 83.1 - 99.1)，特异性为97.1% (95% CI 92.7 - 98.9)，在识别既往暴露方面敏感性为100% (95% CI 88·0-100)，特异性为97.0% （95% CI 89·8- 99.5）。在对389份样本的独立测试集进行分析时，该检测方法和算法对DENV的敏感性为94.8%(89.9 ~ 97.1)，特异性为92.9%(87.3 ~ 99.5)，对ZIKV的敏感性为94.1%(88.7 ~ 97.4)，特异性为99.5%（90.0 ~ 98.0）。多重EDIII血清学检测可准确识别DENV或ZIKV既往感染史。这种高通量和样本保留分析是支持黄病毒监测、流行病学和临床研究以及登革热疫苗资格血清学检测的一种有前景的新工具。需要进一步研究以降低检测成本，消除某些样本中的高背景，并评估登革热病毒流行国家和寨卡病毒流行国家的表现。资助：美国国立卫生研究院。
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Although microbiome signatures have been identified in various contexts (ie, pathogenesis of non-communicable diseases and treatment response), qualified microbiome-based biomarkers are currently not in use in clinical practice. The Human Microbiome Action consortium initiated a Delphi survey to establish a consensus on the needs, challenges, and limitations in developing qualified microbiome-based biomarkers. The questionnaire was developed by a scientific committee via literature review and expert interviews. To ensure broad applicability of the results, 307 experts were invited to participate; 114 of them responded to the first round of the survey, 93 of whom completed the second and final round as well. The survey highlighted the experts’ confidence in the potential of microbiome-based biomarkers for several indications or pathologies. The paucity of validated analytical methods appears to be the principal factor hindering the qualification of these biomarkers. The survey also showed that clinical implementation of these biomarkers would only be possible if kitted and validated molecular assays with simple interpretation are developed. This initiative serves as a foundation for designing and implementing public-private collaborative projects to overcome the challenges and promote clinical application of microbiome-based biomarkers.
{"title":"State of the art and the future of microbiome-based biomarkers: a multidisciplinary Delphi consensus","authors":"Julie Rodriguez PhD , Zahra Hassani PhD , Carolina Alves Costa Silva PhD , Fay Betsou PhD , Federica Carraturo PhD , Prof Alessio Fasano MD , Mads Israelsen PhD , Anandhi Iyappan PhD , Aleksander Krag PhD , Amira Metwaly PhD , Robert Schierwagen PhD , Prof Jonel Trebicka PhD , Prof Hub Zwart PhD , Joel Doré PhD , Magali Cordaillat-Simmons PhD , Celine Druart PhD","doi":"10.1016/j.lanmic.2024.07.011","DOIUrl":"10.1016/j.lanmic.2024.07.011","url":null,"abstract":"<div><div>Although microbiome signatures have been identified in various contexts (ie, pathogenesis of non-communicable diseases and treatment response), qualified microbiome-based biomarkers are currently not in use in clinical practice. The Human Microbiome Action consortium initiated a Delphi survey to establish a consensus on the needs, challenges, and limitations in developing qualified microbiome-based biomarkers. The questionnaire was developed by a scientific committee via literature review and expert interviews. To ensure broad applicability of the results, 307 experts were invited to participate; 114 of them responded to the first round of the survey, 93 of whom completed the second and final round as well. The survey highlighted the experts’ confidence in the potential of microbiome-based biomarkers for several indications or pathologies. The paucity of validated analytical methods appears to be the principal factor hindering the qualification of these biomarkers. The survey also showed that clinical implementation of these biomarkers would only be possible if kitted and validated molecular assays with simple interpretation are developed. This initiative serves as a foundation for designing and implementing public-private collaborative projects to overcome the challenges and promote clinical application of microbiome-based biomarkers.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"6 2","pages":"Article 100948"},"PeriodicalIF":20.9,"publicationDate":"2025-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142146582","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2025-01-30DOI: 10.1016/j.lanmic.2024.101068
Emily Erbelding
{"title":"National Institute of Allergy and Infectious Diseases' commitment to advancing innovative bioinformatics resources.","authors":"Emily Erbelding","doi":"10.1016/j.lanmic.2024.101068","DOIUrl":"https://doi.org/10.1016/j.lanmic.2024.101068","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"101068"},"PeriodicalIF":20.9,"publicationDate":"2025-01-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143081366","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 : 2025-01-27DOI: 10.1016/j.lanmic.2024.100984
Meagan E Deming, Elizabeth R Brown, Monica A McArthur, Stephanie J Schrag, Melissa Arvay, Mike Humphrys, Jacques Ravel, Jeffrey Adelglass, Brandon Essink, David B Musante, Rebecca Maguire, Richard Gorman, Elizabeth Formentini, Robin Mason, Merlin L Robb, Kathleen M Neuzil, Rekha R Rapaka, Peter Wolff, Karen L Kotloff
<p><strong>Background: </strong>Although existing COVID-19 vaccines are known to be highly effective against severe disease and death, data are needed to assess their ability to reduce SARS-CoV-2 infection. We aimed to estimate the efficacy of the NVX-CoV2373 protein subunit vaccine against SARS-CoV-2 infection, regardless of symptoms, among adolescents.</p><p><strong>Methods: </strong>We performed an ancillary observational study (SNIFF) to the phase 3, observer-blinded, randomised, placebo-controlled PREVENT-19 trial that assessed vaccine efficacy against symptomatic COVID-19 in the USA. Participants in the PREVENT-19 trial included healthy adolescents aged 12-17 years and with no history of laboratory-confirmed SARS-CoV-2 infection. They were randomly assigned (2:1) to receive either the NVX-CoV2373 (Novavax, Gaithersburg, MD, USA) vaccine (immediate NVX-CoV2373 group) or placebo (delayed NVX-CoV2373 group) on days 0 and 21 (initial series). After 2 months, in a crossover series, participants received two doses, 21 days apart, of the intervention that they did not receive in their initial series. Participants at 47 of the PREVENT-19 sites were invited to participate in the SNIFF study and self-collect nasal swabs at home twice weekly for SARS-CoV-2 testing to assess vaccine efficacy against SARS-CoV-2 infection. This primary outcome was defined as the first identification of SARS-CoV-2 detected by RT-PCR, regardless of symptoms, with onset within 4 weeks after the second dose of the initial vaccination series until the second dose of the crossover series. Secondary outcomes were vaccine efficacy against asymptomatic and minimally symptomatic SARS-CoV-2 infection, durability of vaccine efficacy against SARS-CoV-2 infection, and durability of vaccine efficacy against asymptomatic and minimally symptomatic infections. Outcomes were analysed in the modified intention-to-treat population, which included all participants without previous SARS-CoV-2 infection and was restricted to participants enrolled within 4 weeks of the second dose of the primary (primary analysis population) or crossover (post-crossover analysis population) series. This study is registered with ClinicalTrials.gov (NCT04611802).</p><p><strong>Findings: </strong>Between June 1 and Dec 17, 2021, 1196 (53·2%) of the 2247 adolescent participants recruited in the PREVENT-19 trial enrolled in the SNIFF study. The primary analysis population included 471 participants in the immediate NVX-CoV2373 group and 220 in the delayed NVX-CoV2373 group. Incidence of SARS-CoV-2 infection was 14·9 cases per 100 person-years (95% CI 7·9-25·5) in the immediate group and 54·2 cases per 100 person-years (33·6-82·9) in the delayed group; vaccine efficacy was 73·5% (95% CI 47·1-86·7; p=0·0002). Incidence of minimally symptomatic or asymptomatic SARS-CoV-2 infection was 10·3 cases per 100 person-years (95% CI 4·7-19·6) in the immediate group and 36·1 cases per 100 person-years (19·8-60·7) in the delayed gr
{"title":"Vaccine efficacy of NVX-CoV2373 against SARS-CoV-2 infection in adolescents in the USA: an ancillary study to a phase 3, observer-blinded, randomised, placebo-controlled trial.","authors":"Meagan E Deming, Elizabeth R Brown, Monica A McArthur, Stephanie J Schrag, Melissa Arvay, Mike Humphrys, Jacques Ravel, Jeffrey Adelglass, Brandon Essink, David B Musante, Rebecca Maguire, Richard Gorman, Elizabeth Formentini, Robin Mason, Merlin L Robb, Kathleen M Neuzil, Rekha R Rapaka, Peter Wolff, Karen L Kotloff","doi":"10.1016/j.lanmic.2024.100984","DOIUrl":"10.1016/j.lanmic.2024.100984","url":null,"abstract":"<p><strong>Background: </strong>Although existing COVID-19 vaccines are known to be highly effective against severe disease and death, data are needed to assess their ability to reduce SARS-CoV-2 infection. We aimed to estimate the efficacy of the NVX-CoV2373 protein subunit vaccine against SARS-CoV-2 infection, regardless of symptoms, among adolescents.</p><p><strong>Methods: </strong>We performed an ancillary observational study (SNIFF) to the phase 3, observer-blinded, randomised, placebo-controlled PREVENT-19 trial that assessed vaccine efficacy against symptomatic COVID-19 in the USA. Participants in the PREVENT-19 trial included healthy adolescents aged 12-17 years and with no history of laboratory-confirmed SARS-CoV-2 infection. They were randomly assigned (2:1) to receive either the NVX-CoV2373 (Novavax, Gaithersburg, MD, USA) vaccine (immediate NVX-CoV2373 group) or placebo (delayed NVX-CoV2373 group) on days 0 and 21 (initial series). After 2 months, in a crossover series, participants received two doses, 21 days apart, of the intervention that they did not receive in their initial series. Participants at 47 of the PREVENT-19 sites were invited to participate in the SNIFF study and self-collect nasal swabs at home twice weekly for SARS-CoV-2 testing to assess vaccine efficacy against SARS-CoV-2 infection. This primary outcome was defined as the first identification of SARS-CoV-2 detected by RT-PCR, regardless of symptoms, with onset within 4 weeks after the second dose of the initial vaccination series until the second dose of the crossover series. Secondary outcomes were vaccine efficacy against asymptomatic and minimally symptomatic SARS-CoV-2 infection, durability of vaccine efficacy against SARS-CoV-2 infection, and durability of vaccine efficacy against asymptomatic and minimally symptomatic infections. Outcomes were analysed in the modified intention-to-treat population, which included all participants without previous SARS-CoV-2 infection and was restricted to participants enrolled within 4 weeks of the second dose of the primary (primary analysis population) or crossover (post-crossover analysis population) series. This study is registered with ClinicalTrials.gov (NCT04611802).</p><p><strong>Findings: </strong>Between June 1 and Dec 17, 2021, 1196 (53·2%) of the 2247 adolescent participants recruited in the PREVENT-19 trial enrolled in the SNIFF study. The primary analysis population included 471 participants in the immediate NVX-CoV2373 group and 220 in the delayed NVX-CoV2373 group. Incidence of SARS-CoV-2 infection was 14·9 cases per 100 person-years (95% CI 7·9-25·5) in the immediate group and 54·2 cases per 100 person-years (33·6-82·9) in the delayed group; vaccine efficacy was 73·5% (95% CI 47·1-86·7; p=0·0002). Incidence of minimally symptomatic or asymptomatic SARS-CoV-2 infection was 10·3 cases per 100 person-years (95% CI 4·7-19·6) in the immediate group and 36·1 cases per 100 person-years (19·8-60·7) in the delayed gr","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"100984"},"PeriodicalIF":20.9,"publicationDate":"2025-01-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143068759","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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