Pub Date : 2026-01-01Epub Date: 2025-08-30DOI: 10.1016/j.lanmic.2025.101225
Xiaoqing Fan , Jingyuan Ning
{"title":"Drug-resistant fungi: the unintended consequence of modern immunosuppression","authors":"Xiaoqing Fan , Jingyuan Ning","doi":"10.1016/j.lanmic.2025.101225","DOIUrl":"10.1016/j.lanmic.2025.101225","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101225"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144973844","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 : 2026-01-01Epub Date: 2025-10-17DOI: 10.1016/j.lanmic.2025.101259
Krishna Prasad Acharya , Sarita Phuyal , Richard Trevor Wilson , Narayan Acharya , Sher Bahadur Pun , Kishor Pandey
{"title":"Why did rabies control fail in low-income and middle-income countries?","authors":"Krishna Prasad Acharya , Sarita Phuyal , Richard Trevor Wilson , Narayan Acharya , Sher Bahadur Pun , Kishor Pandey","doi":"10.1016/j.lanmic.2025.101259","DOIUrl":"10.1016/j.lanmic.2025.101259","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101259"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145337785","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 : 2026-01-01Epub Date: 2026-01-07DOI: 10.1016/j.lanmic.2025.101219
Anja Saso MBBS , Janeri Fröberg PhD , Haddijatou Jobe MSc , Marc Eleveld BSc , Michael Okoye MSc , Ebrima Kanteh BSc , Annemijn Arns BSc , Fred van Opzeeland BSc , Michelle Kumado MSc , Amadou Faal MSc , Elishia Roberts MSc , Modou-Lamin Fofana BSc , Aru-Kumba Baldeh MPH , Karamo Conteh BSc , Bram van Cranenbroek BSc , Sophie Roetynck PhD , Prof Marien de Jonge PhD , Prof Thushan I de Silva PhD , Prof Martijn Huynen PhD , Prof Beate Kampmann MD PhD , Dimitri A Diavatopoulos PhD
<div><h3>Background</h3><div>Mucosal protection against pertussis depends on antibodies and the activation of mucosal-resident memory T cells, both of which are differentially induced by acellular pertussis and whole-cell pertussis vaccines. We aimed to investigate the effect of primary vaccination with these two vaccine types on pertussis-specific mucosal immunity in infants after their mothers received an acellular pertussis-containing vaccine (tetanus–diphtheria–acellular pertussis–inactivated poliovirus; Tdap–IPV) or a tetanus-toxoid (TT)-only vaccine during pregnancy.</div></div><div><h3>Methods</h3><div>This immunological substudy was embedded within the Gambian Pertussis Study (GaPs), a single-centre, randomised, controlled, double-blind, phase 4 trial conducted in The Gambia. In GaPs, healthy, pregnant participants aged 18–40 years were randomly assigned (1:1) to receive a pertussis-containing (Tdap–IPV) vaccine or a TT-only vaccine at 28–34 weeks’ gestation, and their infants were randomly assigned (1:1) to receive a primary immunisation series comprising either a diphtheria–tetanus–whole-cell pertussis (DTwP) vaccine or a diphtheria–tetanus–acellular pertussis (DTaP) vaccine at the ages of 8, 12, and 16 weeks. Nasosorption devices were used to collect nasal mucosal lining fluid (MLF) from infants at the ages of 8, 16, 17, and 20 weeks, and 9 months. The immunological substudy was conducted in a subset of infants in the GaPs trial for whom MLF and paired cord blood and serum samples were available; outcomes were the concentrations of nasal anti-<em>B pertussis</em> IgG and IgA and anti-pertussis toxin IgG, before and after the DTaP or DTwP primary immunisation series at the ages of 8 weeks, 20 weeks, and 9 months, and the concentrations of nasal T-cell-associated cytokines at age 17 weeks. This study is registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, <span><span>NCT03606096</span><svg><path></path></svg></span>.</div></div><div><h3>Findings</h3><div>This substudy included 160 infants enrolled in the main GaPs trial between Feb 13, 2019, and May 17, 2021. At age 8 weeks, before primary vaccination, infants born to mothers who had received the Tdap–IPV vaccine in pregnancy had higher concentrations of maternally derived nasal anti-pertussis toxin IgG (geometric mean ratio 3·84 [95% CI 3·22–4·59]; p<0·0001) and anti-<em>B pertussis</em> IgG (6·45 [5·94–7·01]; p<0·0001), but not IgA, than infants whose mothers received the TT vaccine in pregnancy. After primary vaccination, both groups of infants who received the DTwP vaccine had significantly higher geometric mean concentrations (GMCs) of nasal anti-<em>B pertussis</em> IgG than infants who received the DTaP vaccine (5·42 arbitrary units [AU] per mL [95% CI 3·79–7·75], p=0·0036 for the TT–DTwP group and 4·40 AU/mL [2·99–6·45], p=0·024 for the Tdap–IPV–DTwP group <em>vs</em> 2·16 AU/mL [1·40–3·32] for the Tdap–IPV–DTaP group). Furthermore, DTaP-vac
背景：粘膜对百日咳的保护依赖于抗体和粘膜驻留记忆T细胞的激活，这两者在非细胞百日咳和全细胞百日咳疫苗诱导下是不同的。我们的目的是研究在母亲在怀孕期间接种了无细胞百日咳疫苗（破伤风-白喉-无细胞百日咳-灭活脊髓灰质炎病毒；Tdap-IPV）或破伤风-类毒素（TT）单一疫苗后，首次接种这两种疫苗对婴儿百日咳特异性粘膜免疫的影响。方法：冈比亚百日咳研究（GaPs）是一项在冈比亚进行的单中心、随机、对照、双盲、4期试验。在GaPs中，年龄在18-40岁的健康孕妇被随机分配（1:1）在妊娠28-34周接受含百日咳（Tdap-IPV）疫苗或tt -单纯疫苗，她们的婴儿被随机分配（1:1）接受初级免疫系列，包括白喉-破伤风-全细胞百日咳（DTwP）疫苗或白喉-破伤风-无细胞百日咳（DTaP）疫苗，年龄在8、12和16周。采用鼻吸装置收集8、16、17、20周和9个月婴儿的鼻黏膜衬里液（MLF）。免疫亚研究是在GaPs试验中的一组婴儿中进行的，这些婴儿可以获得MLF和配对脐带血和血清样本；结果是在8周龄、20周龄和9月龄DTaP或DTwP一次免疫系列前后，鼻腔抗b型百日咳IgG、IgA和抗百日咳毒素IgG的浓度，以及17周龄鼻腔t细胞相关细胞因子的浓度。本研究已在ClinicalTrials.gov注册，编号NCT03606096。研究结果：该亚研究包括160名在2019年2月13日至2021年5月17日期间参加主要GaPs试验的婴儿。妊娠期接种Tdap-IPV疫苗的母亲所生的婴儿，在初次接种疫苗前8周时，其母源性鼻腔抗百日咳毒素IgG浓度较高（几何平均比3.84 [95% CI 3.22 - 4.59]）；解释：妊娠期接种Tdap-IPV疫苗可诱导抗体通过胎盘转移至婴儿上呼吸道粘膜，有助于局部保护。尽管母源性抗体调节了婴儿对一次接种百日咳毒素特异性IgG的反应，但与接受DTaP疫苗的婴儿相比，接受DTwP疫苗的婴儿对全细胞B型百日咳始终产生更高的粘膜IgG，并表现出更强的局部细胞激活，证实了从动物研究中发现的DTwP特异性粘膜效应。综上所述，这些发现为怀孕期间免疫接种所赋予的早期生命保护提供了机制支持，并证明了DTwP疫苗接种引起的更广泛的粘膜免疫，为产前疫苗接种规划和婴儿百日咳疫苗接种时间表的政策讨论提供了信息。资助：创新药物倡议联合事业、地平线2020、欧洲制药工业和协会联合会、盖茨基金会、威康信托基金会和BactiVac。
{"title":"Mucosal immune responses to Bordetella pertussis in Gambian infants after maternal and primary vaccination: an immunological substudy of a single-centre, randomised, controlled, double-blind, phase 4 trial","authors":"Anja Saso MBBS , Janeri Fröberg PhD , Haddijatou Jobe MSc , Marc Eleveld BSc , Michael Okoye MSc , Ebrima Kanteh BSc , Annemijn Arns BSc , Fred van Opzeeland BSc , Michelle Kumado MSc , Amadou Faal MSc , Elishia Roberts MSc , Modou-Lamin Fofana BSc , Aru-Kumba Baldeh MPH , Karamo Conteh BSc , Bram van Cranenbroek BSc , Sophie Roetynck PhD , Prof Marien de Jonge PhD , Prof Thushan I de Silva PhD , Prof Martijn Huynen PhD , Prof Beate Kampmann MD PhD , Dimitri A Diavatopoulos PhD","doi":"10.1016/j.lanmic.2025.101219","DOIUrl":"10.1016/j.lanmic.2025.101219","url":null,"abstract":"<div><h3>Background</h3><div>Mucosal protection against pertussis depends on antibodies and the activation of mucosal-resident memory T cells, both of which are differentially induced by acellular pertussis and whole-cell pertussis vaccines. We aimed to investigate the effect of primary vaccination with these two vaccine types on pertussis-specific mucosal immunity in infants after their mothers received an acellular pertussis-containing vaccine (tetanus–diphtheria–acellular pertussis–inactivated poliovirus; Tdap–IPV) or a tetanus-toxoid (TT)-only vaccine during pregnancy.</div></div><div><h3>Methods</h3><div>This immunological substudy was embedded within the Gambian Pertussis Study (GaPs), a single-centre, randomised, controlled, double-blind, phase 4 trial conducted in The Gambia. In GaPs, healthy, pregnant participants aged 18–40 years were randomly assigned (1:1) to receive a pertussis-containing (Tdap–IPV) vaccine or a TT-only vaccine at 28–34 weeks’ gestation, and their infants were randomly assigned (1:1) to receive a primary immunisation series comprising either a diphtheria–tetanus–whole-cell pertussis (DTwP) vaccine or a diphtheria–tetanus–acellular pertussis (DTaP) vaccine at the ages of 8, 12, and 16 weeks. Nasosorption devices were used to collect nasal mucosal lining fluid (MLF) from infants at the ages of 8, 16, 17, and 20 weeks, and 9 months. The immunological substudy was conducted in a subset of infants in the GaPs trial for whom MLF and paired cord blood and serum samples were available; outcomes were the concentrations of nasal anti-<em>B pertussis</em> IgG and IgA and anti-pertussis toxin IgG, before and after the DTaP or DTwP primary immunisation series at the ages of 8 weeks, 20 weeks, and 9 months, and the concentrations of nasal T-cell-associated cytokines at age 17 weeks. This study is registered with <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span>, <span><span>NCT03606096</span><svg><path></path></svg></span>.</div></div><div><h3>Findings</h3><div>This substudy included 160 infants enrolled in the main GaPs trial between Feb 13, 2019, and May 17, 2021. At age 8 weeks, before primary vaccination, infants born to mothers who had received the Tdap–IPV vaccine in pregnancy had higher concentrations of maternally derived nasal anti-pertussis toxin IgG (geometric mean ratio 3·84 [95% CI 3·22–4·59]; p<0·0001) and anti-<em>B pertussis</em> IgG (6·45 [5·94–7·01]; p<0·0001), but not IgA, than infants whose mothers received the TT vaccine in pregnancy. After primary vaccination, both groups of infants who received the DTwP vaccine had significantly higher geometric mean concentrations (GMCs) of nasal anti-<em>B pertussis</em> IgG than infants who received the DTaP vaccine (5·42 arbitrary units [AU] per mL [95% CI 3·79–7·75], p=0·0036 for the TT–DTwP group and 4·40 AU/mL [2·99–6·45], p=0·024 for the Tdap–IPV–DTwP group <em>vs</em> 2·16 AU/mL [1·40–3·32] for the Tdap–IPV–DTaP group). Furthermore, DTaP-vac","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101219"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145949404","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 : 2026-01-01Epub Date: 2026-01-09DOI: 10.1016/j.lanmic.2025.101227
Melisa M Shah MD , Glen R Abedi MPH , Scott Lu MBBS , Miguel Garcia-Knight PhD , Jesus Pineda-Ramirez BA , Sarah A Goldberg MAS , Prof Carlos G Grijalva MD , Prof H Keipp Talbot MD MPH , Jonathan Schmitz MD PhD , Karen Lutrick PhD , Katherine D Ellingson PhD , Prof Melissa S Stockwell MD MPH , Ellen Sano DO , Huong Q Nguyen PhD , Suchitra Rao MBBS , Prof Edwin J Asturias MD , Mehul S Suthar PhD , Alexandra M Mellis PhD , Prof Steven G Deeks MD , Prof Jeffrey N Martin MD , Amethyst Zhang
<div><h3>Background</h3><div>The effect of COVID-19 oral antivirals on the duration of SARS-CoV-2 infectious viral shedding and viral rebound remains uncertain. This study aimed to examine the association of oral antivirals with viral dynamics, shedding of infectious virus, and SARS-CoV-2 rebound.</div></div><div><h3>Methods</h3><div>A prospective case-ascertained household study design was used. Participants were non-hospitalised adults older than 18 years with symptomatic SARS-CoV-2 enrolled in one of two prospective household transmission studies (University of California, San Francisco, FindCOVID and Respiratory Virus Transmission Network–Sentinel [RVTN–S]) conducted in the USA across six states at academic institutions from Jan 1, 2022 to June 10, 2023. We excluded those reporting receipt of multiple COVID-19 outpatient medications, treatment with remdesivir, a treatment duration of more than 6 days, and those from whom fewer than five daily anterior nasal swabs were collected during their illness. Participants were considered to be at high risk of severe COVID-19 (and, therefore, eligible for SARS-CoV-2 oral antiviral treatment) if they were aged 50 years or older or were aged 18 years or older and reporting at least one underlying condition. Study procedures included frequent self-collected nasal swabs (daily for 14 days after symptom onset and then every 3 days until day 28 after symptom onset in FindCOVID and two nasal swabs daily for 10 days from enrolment in RVTN-S) and viral testing by quantitative reverse transcriptase PCR (qRT-PCR), at-home antigen testing, and viral culture. Treatment was defined as self-reported receipt of an oral antiviral (nirmatrelvir–ritonavir or molnupiravir). The primary analysis compared viral detection by qRT-PCR, antigen test positivity, and culture positivity and assessed SARS-CoV-2 viral rebound (viral RNA, antigen, culture, and symptom rebound) in untreated and treated participants at high risk of severe outcomes. We used multivariable Poisson regression to assess associations between treatment, duration of test positivity, and the presence of viral culture rebound, adjusting for age, underlying conditions, and recent immunological events.</div></div><div><h3>Findings</h3><div>Between Jan 1, 2022, and June 10, 2023, 160 individuals with symptomatic COVID-19 and at high risk of severe outcomes were included in FindCOVID and RVTN–S. There was no significant difference in the duration of viral detection between treated and untreated participants at high risk of severe COVID-19 by antigen test positivity (6 days [IQR 5–11] <em>vs</em> 8 days [5–10]; adjusted relative risk [RR] 1·07, 95% CI 0·24–4·81) or viral culture (7 days [4–11] <em>vs</em> 6 days [5–9]; 2·21, 0·45–10·79). Among 122 participants without viral RNA rebound, the last day of antigen test positivity and detection of culturable virus post-symptom onset was earlier in treated participants than in untreated participants (5 days [4–8] <em>vs</em
{"title":"SARS-CoV-2 infectious shedding and rebound among adults with and without oral antiviral use: two case-ascertained prospective household studies","authors":"Melisa M Shah MD , Glen R Abedi MPH , Scott Lu MBBS , Miguel Garcia-Knight PhD , Jesus Pineda-Ramirez BA , Sarah A Goldberg MAS , Prof Carlos G Grijalva MD , Prof H Keipp Talbot MD MPH , Jonathan Schmitz MD PhD , Karen Lutrick PhD , Katherine D Ellingson PhD , Prof Melissa S Stockwell MD MPH , Ellen Sano DO , Huong Q Nguyen PhD , Suchitra Rao MBBS , Prof Edwin J Asturias MD , Mehul S Suthar PhD , Alexandra M Mellis PhD , Prof Steven G Deeks MD , Prof Jeffrey N Martin MD , Amethyst Zhang","doi":"10.1016/j.lanmic.2025.101227","DOIUrl":"10.1016/j.lanmic.2025.101227","url":null,"abstract":"<div><h3>Background</h3><div>The effect of COVID-19 oral antivirals on the duration of SARS-CoV-2 infectious viral shedding and viral rebound remains uncertain. This study aimed to examine the association of oral antivirals with viral dynamics, shedding of infectious virus, and SARS-CoV-2 rebound.</div></div><div><h3>Methods</h3><div>A prospective case-ascertained household study design was used. Participants were non-hospitalised adults older than 18 years with symptomatic SARS-CoV-2 enrolled in one of two prospective household transmission studies (University of California, San Francisco, FindCOVID and Respiratory Virus Transmission Network–Sentinel [RVTN–S]) conducted in the USA across six states at academic institutions from Jan 1, 2022 to June 10, 2023. We excluded those reporting receipt of multiple COVID-19 outpatient medications, treatment with remdesivir, a treatment duration of more than 6 days, and those from whom fewer than five daily anterior nasal swabs were collected during their illness. Participants were considered to be at high risk of severe COVID-19 (and, therefore, eligible for SARS-CoV-2 oral antiviral treatment) if they were aged 50 years or older or were aged 18 years or older and reporting at least one underlying condition. Study procedures included frequent self-collected nasal swabs (daily for 14 days after symptom onset and then every 3 days until day 28 after symptom onset in FindCOVID and two nasal swabs daily for 10 days from enrolment in RVTN-S) and viral testing by quantitative reverse transcriptase PCR (qRT-PCR), at-home antigen testing, and viral culture. Treatment was defined as self-reported receipt of an oral antiviral (nirmatrelvir–ritonavir or molnupiravir). The primary analysis compared viral detection by qRT-PCR, antigen test positivity, and culture positivity and assessed SARS-CoV-2 viral rebound (viral RNA, antigen, culture, and symptom rebound) in untreated and treated participants at high risk of severe outcomes. We used multivariable Poisson regression to assess associations between treatment, duration of test positivity, and the presence of viral culture rebound, adjusting for age, underlying conditions, and recent immunological events.</div></div><div><h3>Findings</h3><div>Between Jan 1, 2022, and June 10, 2023, 160 individuals with symptomatic COVID-19 and at high risk of severe outcomes were included in FindCOVID and RVTN–S. There was no significant difference in the duration of viral detection between treated and untreated participants at high risk of severe COVID-19 by antigen test positivity (6 days [IQR 5–11] <em>vs</em> 8 days [5–10]; adjusted relative risk [RR] 1·07, 95% CI 0·24–4·81) or viral culture (7 days [4–11] <em>vs</em> 6 days [5–9]; 2·21, 0·45–10·79). Among 122 participants without viral RNA rebound, the last day of antigen test positivity and detection of culturable virus post-symptom onset was earlier in treated participants than in untreated participants (5 days [4–8] <em>vs</em","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101227"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145960390","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 : 2026-01-01Epub Date: 2025-12-15DOI: 10.1016/j.lanmic.2025.101230
Lisa Bauer PhD , Lonneke Leijten BSc , Matteo Iervolino MSc , Varun Chopra MSc , Laura van Dijk MSc , Mark Power MSc , Willemijn Rijnink MSc , Mark Pronk BSc , Monique Spronken MSc , Mathis Funk PhD , Rory D de Vries PhD , Mathilde Richard PhD , Prof Thijs Kuiken PhD DVM , Debby van Riel PhD
<div><h3>Background</h3><div>Highly pathogenic avian influenza H5N1 viruses of the A/Goose/Guangdong/1/1996 lineage pose a global threat to wildlife, domestic animals, and humans. Cross-species transmission events to mammals, including humans, in the past 4 years highlight this threat. For influenza A viruses, crucial determinants of cross-species and intraspecies transmission to and among mammals include attachment to and replication in respiratory airway epithelial cells. Although these determinants have been studied for H5N1 viruses in the past, limited studies for clade 2.3.4.4b viruses exist. Therefore, the aim of this study was to determine the ability of recent clade 2.3.4.4b H5N1 viruses to attach to human respiratory tissues, to replicate in human airway epithelial cells and the associated immune response.</div></div><div><h3>Methods</h3><div>In this in-vitro study, we investigated three H5N1 clade 2.3.4.4b viruses (H5N1<sup>Gull2022</sup>, H5N1<sup>Polecat2022</sup>, and H5N1<sup>Bovine2024</sup>) in comparison with previously studied 2.1.3.2 H5N1 (H5N1<sup>2005</sup>) and a seasonal H3N2 virus. First, we compared virus attachment patterns by virus histochemistry. Second, we investigated the infection and replication efficiency, and innate immune responses in infected human respiratory epithelium in vitro. Third, we measured polymerase complex activity using a minigenome assay.</div></div><div><h3>Findings</h3><div>Clade 2.3.4.4b viruses and H5N1<sup>2005</sup> virus differed by five amino acids located near the receptor binding site of the haemagglutinin. All clade 2.3.4.4b viruses attached more efficiently to cells of the human upper and lower respiratory tract compared with H5N1<sup>2005</sup> virus. All clade 2.3.4.4b viruses replicated in human nasal and tracheobronchial respiratory epithelium cultures. In the tracheobronchial respiratory epithelium cultures, H5N1<sup>Gull20</sup><sup>2</sup><sup>2</sup> virus replicated more efficiently than H5N1<sup>2005</sup> virus (p=0·0050) and reached titres similar to H3N2<sup>2003</sup> virus. Polymerase complex activity of H5N1<sup>Gull2022</sup> virus was not significantly different from that of H5N1<sup>2005</sup> and was significantly lower compared with H3N2<sup>2003</sup> virus (p≤0·0001). Infection with H5N1<sup>Gull2022</sup> virus induced a broader antiviral immune response than H5N1<sup>2005</sup> virus.</div></div><div><h3>Interpretation</h3><div>Clade 2.3.4.4b H5N1 viruses have phenotypic characteristics that are different from a clade 2.1.3.2 H5N1<sup>2005</sup> virus. The ability of clade 2.3.4.4b viruses to attach to and replicate in respiratory epithelium likely contributes to an increased risk for both human infection and virus adaptation to humans.</div></div><div><h3>Funding</h3><div>The EU, the Dutch Research Council, the Netherlands Organization for Health Research and Development, and the Dutch Ministries of Agriculture, Fisheries, Food Security and Nature, and Health,
{"title":"Attachment and replication of clade 2.3.4.4b influenza A (H5N1) viruses in human respiratory epithelium: an in-vitro study","authors":"Lisa Bauer PhD , Lonneke Leijten BSc , Matteo Iervolino MSc , Varun Chopra MSc , Laura van Dijk MSc , Mark Power MSc , Willemijn Rijnink MSc , Mark Pronk BSc , Monique Spronken MSc , Mathis Funk PhD , Rory D de Vries PhD , Mathilde Richard PhD , Prof Thijs Kuiken PhD DVM , Debby van Riel PhD","doi":"10.1016/j.lanmic.2025.101230","DOIUrl":"10.1016/j.lanmic.2025.101230","url":null,"abstract":"<div><h3>Background</h3><div>Highly pathogenic avian influenza H5N1 viruses of the A/Goose/Guangdong/1/1996 lineage pose a global threat to wildlife, domestic animals, and humans. Cross-species transmission events to mammals, including humans, in the past 4 years highlight this threat. For influenza A viruses, crucial determinants of cross-species and intraspecies transmission to and among mammals include attachment to and replication in respiratory airway epithelial cells. Although these determinants have been studied for H5N1 viruses in the past, limited studies for clade 2.3.4.4b viruses exist. Therefore, the aim of this study was to determine the ability of recent clade 2.3.4.4b H5N1 viruses to attach to human respiratory tissues, to replicate in human airway epithelial cells and the associated immune response.</div></div><div><h3>Methods</h3><div>In this in-vitro study, we investigated three H5N1 clade 2.3.4.4b viruses (H5N1<sup>Gull2022</sup>, H5N1<sup>Polecat2022</sup>, and H5N1<sup>Bovine2024</sup>) in comparison with previously studied 2.1.3.2 H5N1 (H5N1<sup>2005</sup>) and a seasonal H3N2 virus. First, we compared virus attachment patterns by virus histochemistry. Second, we investigated the infection and replication efficiency, and innate immune responses in infected human respiratory epithelium in vitro. Third, we measured polymerase complex activity using a minigenome assay.</div></div><div><h3>Findings</h3><div>Clade 2.3.4.4b viruses and H5N1<sup>2005</sup> virus differed by five amino acids located near the receptor binding site of the haemagglutinin. All clade 2.3.4.4b viruses attached more efficiently to cells of the human upper and lower respiratory tract compared with H5N1<sup>2005</sup> virus. All clade 2.3.4.4b viruses replicated in human nasal and tracheobronchial respiratory epithelium cultures. In the tracheobronchial respiratory epithelium cultures, H5N1<sup>Gull20</sup><sup>2</sup><sup>2</sup> virus replicated more efficiently than H5N1<sup>2005</sup> virus (p=0·0050) and reached titres similar to H3N2<sup>2003</sup> virus. Polymerase complex activity of H5N1<sup>Gull2022</sup> virus was not significantly different from that of H5N1<sup>2005</sup> and was significantly lower compared with H3N2<sup>2003</sup> virus (p≤0·0001). Infection with H5N1<sup>Gull2022</sup> virus induced a broader antiviral immune response than H5N1<sup>2005</sup> virus.</div></div><div><h3>Interpretation</h3><div>Clade 2.3.4.4b H5N1 viruses have phenotypic characteristics that are different from a clade 2.1.3.2 H5N1<sup>2005</sup> virus. The ability of clade 2.3.4.4b viruses to attach to and replicate in respiratory epithelium likely contributes to an increased risk for both human infection and virus adaptation to humans.</div></div><div><h3>Funding</h3><div>The EU, the Dutch Research Council, the Netherlands Organization for Health Research and Development, and the Dutch Ministries of Agriculture, Fisheries, Food Security and Nature, and Health,","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101230"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145783207","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 : 2026-01-01Epub Date: 2025-09-18DOI: 10.1016/j.lanmic.2025.101243
Seshasailam Venkateswaran , Jessica Mitchell , Marieke Emonts , Mark Bradley , Nichola Hawkins , Andrew C Singer
{"title":"Diagnostics at the frontline: using the Public Accounts Committee report to catalyse the UK’s antimicrobial resistance diagnostics strategy","authors":"Seshasailam Venkateswaran , Jessica Mitchell , Marieke Emonts , Mark Bradley , Nichola Hawkins , Andrew C Singer","doi":"10.1016/j.lanmic.2025.101243","DOIUrl":"10.1016/j.lanmic.2025.101243","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101243"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145114707","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 : 2026-01-01Epub Date: 2025-12-23DOI: 10.1016/j.lanmic.2025.101336
The Lancet Microbe
{"title":"We have the means to beat malaria, do we have the will?","authors":"The Lancet Microbe","doi":"10.1016/j.lanmic.2025.101336","DOIUrl":"10.1016/j.lanmic.2025.101336","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"7 1","pages":"Article 101336"},"PeriodicalIF":20.4,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145844235","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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