Lancet MicrobePub Date : 2024-07-01DOI: 10.1016/S2666-5247(24)00038-7
Annika Saukkoriipi PhD , Natalie C Silmon de Monerri PhD , Maija Toropainen PhD , Laura Lindholm MSc , Riitta Veijola MD PhD , Jorma Toppari MD PhD , Mikael Knip MD PhD , David Radley MSc , Emily Gomme PhD , Babalwa Jongihlati MD , Annaliesa S Anderson PhD , Arto A Palmu MD PhD , Raphael Simon PhD
{"title":"Association between anti-capsular IgG levels at birth and risk of invasive group B streptococcus disease in Finnish newborns: a retrospective case–control study","authors":"Annika Saukkoriipi PhD , Natalie C Silmon de Monerri PhD , Maija Toropainen PhD , Laura Lindholm MSc , Riitta Veijola MD PhD , Jorma Toppari MD PhD , Mikael Knip MD PhD , David Radley MSc , Emily Gomme PhD , Babalwa Jongihlati MD , Annaliesa S Anderson PhD , Arto A Palmu MD PhD , Raphael Simon PhD","doi":"10.1016/S2666-5247(24)00038-7","DOIUrl":"10.1016/S2666-5247(24)00038-7","url":null,"abstract":"<div><h3>Background</h3><p>Group B streptococcus is a major cause of neonatal disease. Natural history studies have linked maternally transferred anti-group B streptococcus capsular polysaccharide antibodies with protection against infant group B streptococcus disease. Previous studies of capsular polysaccharide antibody concentration in European populations have used maternal (not infant) sera and a non-standardised assay. This study aimed to evaluate anti-capsular polysaccharide IgG concentrations associated with protection against invasive group B streptococcus disease in Finnish infants.</p></div><div><h3>Methods</h3><p>In this retrospective case–control study, we used cord sera from the Finnish DIPP study repository, which was obtained between Jan 1, 1995, and Dec 31, 2017. We included infants aged 6 months or younger with group B streptococcus infection (cases) and healthy infants (controls). We enrolled infants with invasive neonatal group B streptococcus (55 cases) and matched controls (229 controls) aged 6 months or younger after identification from Finnish health registers. We measured anti-capsular polysaccharide IgG (serotypes Ia–V) concentration using a standardised immunoassay and we estimated its relationship to disease risk using a Bayesian model. We used the derived risk–concentration curve to predict potential efficacy of six-valent group B streptococcus capsular polysaccharide vaccine (GBS6) based on previously reported immunogenicity data.</p></div><div><h3>Findings</h3><p>Most (32 [58%] of 55 cases) group B streptococcus cases were due to serotype III and anti-serotype III streptococcus capsular IgG concentrations were higher in serotype III-matched controls than in cases (p<0·001). 0·120–0·266 μg/mL serotype III-specific IgG was estimated to confer 75–90% risk reduction against serotype III disease. A universal risk–concentration curve, aggregating results across all six serotypes, yielded similar results. Application of this curve to GBS6 immunogenicity data predicted maternal immunisation to be more than 80% efficacious for prevention of infant group B streptococcus disease.</p></div><div><h3>Interpretation</h3><p>Higher neonatal anti-capsular polysaccharide serum IgG concentration at birth correlated with reduced risk of infant group B streptococcus disease in Finland. Based on these results, a maternal group B streptococcus capsular conjugate vaccine currently in development is predicted to be efficacious.</p></div><div><h3>Funding</h3><p>Pfizer.</p></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666524724000387/pdfft?md5=7bd951a4b269070f173e4858a3e8c7ee&pid=1-s2.0-S2666524724000387-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865420","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}
Lancet MicrobePub Date : 2024-07-01DOI: 10.1016/S2666-5247(24)00095-8
Leonardo Pereira de Araújo , Evandro Neves Silva , Patrícia Paiva Corsetti , Leonardo Augusto de Almeida
{"title":"Shared immunogenic epitopes between host entry and exit proteins from monkeypox and Alaskapox viruses","authors":"Leonardo Pereira de Araújo , Evandro Neves Silva , Patrícia Paiva Corsetti , Leonardo Augusto de Almeida","doi":"10.1016/S2666-5247(24)00095-8","DOIUrl":"10.1016/S2666-5247(24)00095-8","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666524724000958/pdfft?md5=c6cd14cf5efcd726207b6a25e42184c7&pid=1-s2.0-S2666524724000958-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140797252","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}
Lancet MicrobePub Date : 2024-07-01DOI: 10.1016/S2666-5247(24)00133-2
Priya Venkatesan
{"title":"New measures to tackle the global cholera surge","authors":"Priya Venkatesan","doi":"10.1016/S2666-5247(24)00133-2","DOIUrl":"10.1016/S2666-5247(24)00133-2","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666524724001332/pdfft?md5=02dae21d80f83fb901e8fbda6ea458d6&pid=1-s2.0-S2666524724001332-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141186958","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}
Lancet MicrobePub Date : 2024-07-01DOI: 10.1016/S2666-5247(24)00041-7
Lucrèce Ahovègbé PharmD , Rajiv Shah MD , Prof Aboudou Raïmi Kpossou MD , Chris Davis PhD , Marc Niebel PhD , Ana Filipe PhD , Emily Goldstein PhD , Khadidjatou S Alassan MD , René Keke MD , Prof Jean Sehonou MD , Prof Nicolas Kodjoh MD , Sossa Edmond Gbedo MD , Prof Surajit Ray PhD , Craig Wilkie PhD , Sreenu Vattipally PhD , Lily Tong PhD , Pakoyo F Kamba PhD , S Judith Gbenoudon PhD , Prof Rory Gunson PhD , Prof Patrick Ogwang PhD , Prof Emma C Thomson PhD FRCP
{"title":"Hepatitis C virus diversity and treatment outcomes in Benin: a prospective cohort study","authors":"Lucrèce Ahovègbé PharmD , Rajiv Shah MD , Prof Aboudou Raïmi Kpossou MD , Chris Davis PhD , Marc Niebel PhD , Ana Filipe PhD , Emily Goldstein PhD , Khadidjatou S Alassan MD , René Keke MD , Prof Jean Sehonou MD , Prof Nicolas Kodjoh MD , Sossa Edmond Gbedo MD , Prof Surajit Ray PhD , Craig Wilkie PhD , Sreenu Vattipally PhD , Lily Tong PhD , Pakoyo F Kamba PhD , S Judith Gbenoudon PhD , Prof Rory Gunson PhD , Prof Patrick Ogwang PhD , Prof Emma C Thomson PhD FRCP","doi":"10.1016/S2666-5247(24)00041-7","DOIUrl":"10.1016/S2666-5247(24)00041-7","url":null,"abstract":"<div><h3>Background</h3><p>10 million people are chronically infected with the hepatitis C virus (HCV) in sub-Saharan Africa. The assessment of viral genotypes and treatment response in this region is necessary to achieve the WHO target of worldwide elimination of viral hepatitis by 2030. We aimed to investigate the prevalence of HCV genotypes and outcomes of treatment with direct-acting antiviral agents in Benin, a country with a national HCV seroprevalence of 4%.</p></div><div><h3>Methods</h3><p>This prospective cohort study was conducted at two referral hospitals in Benin. Individuals were eligible for inclusion if they were seropositive for HCV and willing to consent to participation in the study; exclusion criteria were an inability to give consent or incarceration. Viraemia was confirmed by PCR. The primary outcomes were to identify HCV genotypes and measure sustained virological response rates 12 weeks after completion of treatment (SVR12) with a 12-week course of sofosbuvir–velpatasvir or sofosbuvir–ledipasvir, with or without ribavirin. We conducted phylogenetic and resistance analyses after the next-generation sequencing of samples with a cycle threshold (Ct) value of 30 or fewer cycles. The in-vitro efficacy of NS5A inhibitors was tested using a subgenomic replicon assay.</p></div><div><h3>Findings</h3><p>Between June 2, 2019, and Dec 30, 2020, 148 individuals were screened for eligibility, of whom 100 were recruited prospectively to the study. Plasma samples from 79 (79%) of the 100 participants were positive for HCV by PCR. At the time of the study, 52 (66%) of 79 patients had completed treatment, with an SVR12 rate of 94% (49 of 52). 57 (72%) of 79 samples had a Ct value of 30 or fewer cycles and were suitable for whole-genome sequencing, from which we characterised 29 (51%) samples as genotype 1 and 28 (49%) as genotype 2. Three new genotype 1 subtypes (1q, 1r, and 1s) and one new genotype 2 subtype (2xa) were identified. The most commonly detected subtype was 2d (12 [21%] of 57 samples), followed by 1s (eight [14%]), 1r (five [9%]), 1b (four [7%]), 1q (three [5%]), 2xa (three [5%]), and 2b (two [3%]). 20 samples (11 genotype 2 and nine genotype 1) were unassigned new singleton lineages. 53 (93%) of 57 sequenced samples had at least two resistance-associated substitutions within the <em>NS5A</em> gene. Subtype 2d was associated with a lower-than-expected SVR12 rate (eight [80%] of ten patients). For one patient, with subtype 2b, treatment was not successful.</p></div><div><h3>Interpretation</h3><p>This study revealed a high SVR rate in Benin among individuals treated for HCV with sofosbuvir–velpatasvir, including those with highly diverse viral genotypes. Further studies of treatment effectiveness in genotypes 2d and 2b are indicated.</p></div><div><h3>Funding</h3><p>Medical Research Council, Wellcome, Global Challenges Research Fund, Academy of Medical Sciences, and PHARMBIOTRAC.</p></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666524724000417/pdfft?md5=d6f397699411d57249844adb520a903c&pid=1-s2.0-S2666524724000417-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141411145","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}
Lancet MicrobePub Date : 2024-07-01DOI: 10.1016/S2666-5247(24)00046-6
Edwin P Armitage BMBS , Gabrielle de Crombrugghe MD , Alexander J Keeley BMBS , Elina Senghore BSc , Fatoumata E Camara MSc , Musukoi Jammeh , Amat Bittaye ADN , Haddy Ceesay CHN , Isatou Ceesay RN , Bunja Samateh BSN , Muhammed Manneh TNA , Prof Beate Kampmann , Claire E Turner PhD , Prof Adam Kucharski , Anne Botteaux PhD , Prof Pierre R Smeesters , Prof Thushan I de Silva , Prof Michael Marks
{"title":"Streptococcus pyogenes carriage and infection within households in The Gambia: a longitudinal cohort study","authors":"Edwin P Armitage BMBS , Gabrielle de Crombrugghe MD , Alexander J Keeley BMBS , Elina Senghore BSc , Fatoumata E Camara MSc , Musukoi Jammeh , Amat Bittaye ADN , Haddy Ceesay CHN , Isatou Ceesay RN , Bunja Samateh BSN , Muhammed Manneh TNA , Prof Beate Kampmann , Claire E Turner PhD , Prof Adam Kucharski , Anne Botteaux PhD , Prof Pierre R Smeesters , Prof Thushan I de Silva , Prof Michael Marks","doi":"10.1016/S2666-5247(24)00046-6","DOIUrl":"10.1016/S2666-5247(24)00046-6","url":null,"abstract":"<div><h3>Background</h3><p><em>Streptococcus pyogenes</em> causes more than 500 000 deaths per year globally, which occur disproportionately in low-income and middle-income countries. The roles of <em>S pyogenes</em> skin and pharyngeal carriage in transmission are unclear. We aimed to investigate the clinical epidemiology and household transmission dynamics of both <em>S pyogenes</em> asymptomatic carriage and infection in a high-burden setting.</p></div><div><h3>Methods</h3><p>We did a 1-year prospective, longitudinal, household cohort study, recruiting healthy participants from households in Sukuta, The Gambia. Households were eligible if they comprised at least three members, including one child younger than 18 years, and were excluded if more than half of household members declined to participate. Households were identified by random GPS coordinates derived from census data. At monthly visits, pharyngeal and normal skin swabs were collected for <em>S pyogenes</em> culture, and sociodemographic data were recorded by interview. Incident pharyngitis and pyoderma infections were captured. Cultured isolates underwent <em>emm</em> genotyping. The primary outcome measures were incidence of <em>S pyogenes</em> carriage and disease. Additional outcomes were prevalence of <em>S pyogenes</em> skin and pharyngeal carriage, <em>S pyogenes</em> skin and pharyngeal clearance time, <em>S pyogenes emm</em> type, risk factors for carriage and disease events, household secondary attack rate, and <em>emm</em>-linked household transmission events. The study is registered on ClinicalTrials.gov, <span>NCT05117528</span><svg><path></path></svg>.</p></div><div><h3>Findings</h3><p>Between July 27, 2021, and Sept 28, 2022, 442 participants were enrolled from 44 households. The median age was 15 years (IQR 6–28) and 233 (53%) were female. We identified 17 pharyngitis and 99 pyoderma events and 49 pharyngeal and 39 skin <em>S pyogenes</em> carriage acquisition events. Mean monthly prevalence was 1·4% (95% CI 1·1–1·9) for <em>S pyogenes</em> pharyngeal carriage and 1·2% (0·9–1·6) for <em>S pyogenes</em> skin carriage. Incidence was 120 per 1000 person-years (95% CI 87–166) for <em>S pyogenes</em> pharyngeal carriage, 124 per 1000 person-years (90–170) for <em>S pyogenes</em> skin carriage, 51 per 1000 person-years (31–84) for <em>S pyogenes</em> pharyngitis, and 263 per 1000 person-years (212–327) for <em>S pyogenes</em> pyoderma. Pharyngeal carriage risk was higher during the rainy season (HR 5·67, 95% CI 2·19–14·69) and in larger households (per additional person: 1·03, 1·00–1·05), as was pharyngitis risk (rainy season: 3·00, 1·10–8·22; household size: 1·04, 1·02–1·07). Skin carriage risk was not affected by season or household size, but was lower in female than in male participants (0·45, 0·22–0·92) and highest in children younger than 5 years compared with adults (22·69, 3·08–167·21), with similar findings for pyoderma (female sex: 0·34, 0·19–0·61; age <5 years: 7","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666524724000466/pdfft?md5=bc8389712029b740af2e4fb87875e5e4&pid=1-s2.0-S2666524724000466-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140912984","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}
{"title":"The WHO fungal priority pathogens list: a crucial reappraisal to review the prioritisation","authors":"Giacomo Casalini MD , Andrea Giacomelli MD , Prof Spinello Antinori PhD","doi":"10.1016/S2666-5247(24)00042-9","DOIUrl":"10.1016/S2666-5247(24)00042-9","url":null,"abstract":"<div><p>In October, 2022, WHO published the first fungal priority pathogen list, which categorised 19 fungal entities into three priority groups (critical, high, and medium), for prioritisation of research efforts. The final ranking was determined via multiple criteria decision analysis, considering both research and development needs and perceived public health importance. In this Personal View, we discuss the positioning of the fungal pathogens, namely, Mucorales, <em>Candida</em> spp, <em>Histoplasma</em> spp, <em>Coccidioides</em> and <em>Paracoccidioides</em> spp, <em>Fusarium</em> spp, eumycetoma causative agents, <em>Talaromyces marneffei</em>, and <em>Pneumocystis jirovecii</em>, while expressing concerns about potential disparities between the WHO fungal priority pathogen list ranking and the actual disease burden associated with these pathogens. Finally, we propose a revised prioritisation list that also considers the regional disparities in the burden of fungal diseases.</p></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666524724000429/pdfft?md5=0c9f8fbc91e25678c968c4dbe0f721a0&pid=1-s2.0-S2666524724000429-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140792248","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}
Lancet MicrobePub Date : 2024-07-01DOI: 10.1016/S2666-5247(24)00044-2
Lucia Molinengo MSc , Theodore Estrin-Serlui MBBS , Brian Hanley FRCPath , Prof Michael Osborn FRCPath , Prof Robert Goldin FRCPath
{"title":"Infectious diseases and the role of needle biopsy post-mortem","authors":"Lucia Molinengo MSc , Theodore Estrin-Serlui MBBS , Brian Hanley FRCPath , Prof Michael Osborn FRCPath , Prof Robert Goldin FRCPath","doi":"10.1016/S2666-5247(24)00044-2","DOIUrl":"10.1016/S2666-5247(24)00044-2","url":null,"abstract":"<div><p>Post-mortem examinations continue to play a crucial role in understanding the epidemiology and pathogenesis of infectious diseases. However, the perceived infection risk can preclude traditional, invasive, complete diagnostic autopsy. Post-mortem examination is especially important in emerging infectious diseases with potentially unknown infection risks, but rapid acquisition of good quality tissue samples is needed as part of the scientific and public health response. Needle biopsy post-mortem is a minimally invasive, rapid, closed-body autopsy technique that was originally developed to minimise the infection risk to practitioners. Since its inception, needle biopsy post-mortem has also been used as a technique to support complete diagnostic autopsy provision in poorly resourced regions and to facilitate post-mortem examinations in communities that might have religious or cultural objections to an invasive autopsy. This Review analyses the evolution and applicability of needle biopsy post-mortem in investigating endemic and emerging infectious diseases.</p></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666524724000442/pdfft?md5=4a0cde4ea539d7e4504d1d4c1229f91b&pid=1-s2.0-S2666524724000442-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140757770","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}
Lancet MicrobePub Date : 2024-07-01DOI: 10.1016/S2666-5247(24)00025-9
Susan Jackson MRCP , Julia L Marshall DPhil , Andrew Mawer BMBCh , Raquel Lopez-Ramon MSc , Stephanie A Harris BSc , Iman Satti PhD , Eileen Hughes BSc , Hannah Preston-Jones MSc , Ingrid Cabrera Puig PhD , Stephanie Longet PhD , Tom Tipton PhD , Stephen Laidlaw PhD , Rebecca Powell Doherty PhD , Hazel Morrison MRCP , Robert Mitchell MSc , Rachel Tanner DPhil , Alberta Ateere MSc , Elena Stylianou PhD , Meng-San Wu MRCP , Timothy P W Fredsgaard-Jones MRCP , Gavindren Vuddamalay
{"title":"Safety, tolerability, viral kinetics, and immune correlates of protection in healthy, seropositive UK adults inoculated with SARS-CoV-2: a single-centre, open-label, phase 1 controlled human infection study","authors":"Susan Jackson MRCP , Julia L Marshall DPhil , Andrew Mawer BMBCh , Raquel Lopez-Ramon MSc , Stephanie A Harris BSc , Iman Satti PhD , Eileen Hughes BSc , Hannah Preston-Jones MSc , Ingrid Cabrera Puig PhD , Stephanie Longet PhD , Tom Tipton PhD , Stephen Laidlaw PhD , Rebecca Powell Doherty PhD , Hazel Morrison MRCP , Robert Mitchell MSc , Rachel Tanner DPhil , Alberta Ateere MSc , Elena Stylianou PhD , Meng-San Wu MRCP , Timothy P W Fredsgaard-Jones MRCP , Gavindren Vuddamalay","doi":"10.1016/S2666-5247(24)00025-9","DOIUrl":"10.1016/S2666-5247(24)00025-9","url":null,"abstract":"<div><h3>Background</h3><p>A SARS-CoV-2 controlled human infection model (CHIM) has been successfully established in seronegative individuals using a dose of 1×10<sup>1</sup> 50% tissue culture infectious dose (TCID<sub>50</sub>) pre-alpha SARS-CoV-2 virus. Given the increasing prevalence of seropositivity to SARS-CoV-2, a CHIM that could be used for vaccine development will need to induce infection in those with pre-existing immunity. Our aim was to find a dose of pre-alpha SARS-CoV-2 virus that induced infection in previously infected individuals.</p></div><div><h3>Methods</h3><p>Healthy, UK volunteers aged 18–30 years, with proven (quantitative RT-PCR or lateral flow antigen test) previous SARS-CoV-2 infection (with or without vaccination) were inoculated intranasally in a stepwise dose escalation CHIM with either 1×10<sup>1</sup>, 1×10<sup>2</sup>, 1×10³, 1×10<sup>4</sup>, or 1×10<sup>5</sup> TCID<sub>50</sub> SARS-CoV-2/human/GBR/484861/2020, the same virus used in the seronegative CHIM. Post-inoculation, volunteers were quarantined in functionally negative pressure rooms (Oxford, UK) for 14 days and until 12-hourly combined oropharyngeal–nasal swabs were negative for viable virus by focus-forming assay. Outpatient follow-up continued for 12 months post-enrolment, with additional visits for those who developed community-acquired SARS-CoV-2 infection. The primary objective was to identify a safe, well tolerated dose that induced infection (defined as two consecutive SARS-CoV-2 positive PCRs starting 24 h after inoculation) in 50% of seropositive volunteers. This study is registered with ClinicalTrials.gov (<span>NCT04864548</span><svg><path></path></svg>); enrolment and follow-up to 12 months post-enrolment are complete.</p></div><div><h3>Findings</h3><p>Recruitment commenced on May 6, 2021, with the last volunteer enrolled into the dose escalation cohort on Nov 24, 2022. 36 volunteers were enrolled, with four to eight volunteers inoculated in each dosing group from 1×10<sup>1</sup> to 1×10<sup>5</sup> TCID<sub>50</sub> SARS-CoV-2. All volunteers have completed quarantine, with follow-up to 12 months complete. Despite dose escalation to 1×10<sup>5</sup> TCID<sub>50</sub>, we were unable to induce sustained infection in any volunteers. Five (14%) of 36 volunteers were considered to have transient infection, based on the kinetic of their PCR-positive swabs. Transiently infected volunteers had significantly lower baseline mucosal and systemic SARS-CoV-2-specific antibody titres and significantly lower peripheral IFNγ responses against a CD8<sup>+</sup> T-cell SARS-CoV-2 peptide pool than uninfected volunteers. 14 (39%) of 36 volunteers subsequently developed breakthrough infection with the omicron variant after discharge from quarantine. Most adverse events reported by volunteers in quarantine were mild, with fatigue (16 [44%]) and stuffy nose (16 [44%]) being the most common. There were no serious adverse events.</p></div><div><h3>Interpretatio","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":null,"pages":null},"PeriodicalIF":20.9,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S2666524724000259/pdfft?md5=8d64e946c4adedce34c02dfe630a7574&pid=1-s2.0-S2666524724000259-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140865192","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}