Pub Date : 2024-10-01DOI: 10.1016/S2666-5247(24)00140-X
{"title":"Need for high-resolution observational cohort studies to understand the natural history of tuberculosis","authors":"","doi":"10.1016/S2666-5247(24)00140-X","DOIUrl":"10.1016/S2666-5247(24)00140-X","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 10","pages":"Article 100908"},"PeriodicalIF":20.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141545388","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 : 2024-10-01DOI: 10.1016/S2666-5247(24)00116-2
Neta S Zuckerman PhD , Efrat Bucris PhD , Hagar Morad-Eliyahu BSc , Leah Weiss BSc , Rinat Vasserman MSc , Ilana S Fratty PhD , Ira Aguvaev BSc , Zvi Cohen-Said BSc , Rua Matar BSc , Oran Erster PhD , Prof Lester M Shulman PhD , Ruth Yishai PhD , Lior Hecht-Sagie MD , Sharon Alroy-Preis MD , Prof Ella Mendelson PhD , Yaniv Lustig PhD , Danit Sofer PhD , Itay Bar-Or PhD , Merav Weil PhD
<div><h3>Background</h3><div>Similarly to wild poliovirus, vaccine-derived poliovirus (VDPV) strains can cause acute flaccid paralysis, posing a considerable challenge to public health and the eradication of poliovirus. VDPV outbreaks, particularly VDPV type 2 (VDPV2), are increasing worldwide, including in high-income countries with high vaccine coverage. We aimed to conduct a comprehensive analysis of the molecular epidemiology of a widespread VDPV2 outbreak in Israel in 2022–23 using conventional polio identification techniques and whole-genome sequencing.</div></div><div><h3>Methods</h3><div>In this genomic epidemiology study, we monitored and identified poliovirus type 2 (PV2) through the surveillance of stool samples from individuals with acute flaccid paralysis and related contacts, as well as environmental surveillance of sewage samples. Environmental surveillance involved 15 routine surveillance sites and an additional 30 sites dedicated to monitoring this outbreak, covering approximately 70% of Israel's population between April 1, 2022, and June 30, 2023. Additionally, we performed phylogenetic and mutation analyses using whole-genome, next-generation sequencing of PV2 isolates to identify recombination events, characterise VDPV2 lineages according to the capsid region, and establish the geographical distribution and linkage of PV2 isolates.</div></div><div><h3>Findings</h3><div>We detected 256 genetically linked samples from environmental surveillance, as well as one case of acute flaccid paralysis and four positive contacts associated with the Sabin type 2 oral vaccine strain. Most affected locations showed a high-density population of Jewish Ultra-Orthodox communities. Through high-resolution genomic characterisation and phylogenetic analysis of 202 representative sequences with complete capsid coverage, including isolates from both environmental surveillance and the case of acute flaccid paralysis, a conclusive linkage was established among all detections, confirming them to be part of a single VDPV2 outbreak. This strategy enabled the characterisation of three distinct lineages and established connections between different locations in Israel, including linking the case of acute flaccid paralysis and nearby environmental surveillance detections from the northern region with detections in the geographically distant central region.</div></div><div><h3>Interpretation</h3><div>This study highlights the role of environmental surveillance in the early detection and monitoring of poliovirus circulation, enabling a prompt public health response involving enhanced surveillance and a catch-up campaign with inactivated polio vaccine. Whole-genome sequencing offered valuable insights into the origins of the outbreak, linkage across detections, and the geographical distribution of the virus, with higher resolution than would have been possible with the standard analysis of the <em>VP1</em> gene alone.</div></div><div><h3>Funding</h3><div>None.<
{"title":"Environmental surveillance of a circulating vaccine-derived poliovirus type 2 outbreak in Israel between 2022 and 2023: a genomic epidemiology study","authors":"Neta S Zuckerman PhD , Efrat Bucris PhD , Hagar Morad-Eliyahu BSc , Leah Weiss BSc , Rinat Vasserman MSc , Ilana S Fratty PhD , Ira Aguvaev BSc , Zvi Cohen-Said BSc , Rua Matar BSc , Oran Erster PhD , Prof Lester M Shulman PhD , Ruth Yishai PhD , Lior Hecht-Sagie MD , Sharon Alroy-Preis MD , Prof Ella Mendelson PhD , Yaniv Lustig PhD , Danit Sofer PhD , Itay Bar-Or PhD , Merav Weil PhD","doi":"10.1016/S2666-5247(24)00116-2","DOIUrl":"10.1016/S2666-5247(24)00116-2","url":null,"abstract":"<div><h3>Background</h3><div>Similarly to wild poliovirus, vaccine-derived poliovirus (VDPV) strains can cause acute flaccid paralysis, posing a considerable challenge to public health and the eradication of poliovirus. VDPV outbreaks, particularly VDPV type 2 (VDPV2), are increasing worldwide, including in high-income countries with high vaccine coverage. We aimed to conduct a comprehensive analysis of the molecular epidemiology of a widespread VDPV2 outbreak in Israel in 2022–23 using conventional polio identification techniques and whole-genome sequencing.</div></div><div><h3>Methods</h3><div>In this genomic epidemiology study, we monitored and identified poliovirus type 2 (PV2) through the surveillance of stool samples from individuals with acute flaccid paralysis and related contacts, as well as environmental surveillance of sewage samples. Environmental surveillance involved 15 routine surveillance sites and an additional 30 sites dedicated to monitoring this outbreak, covering approximately 70% of Israel's population between April 1, 2022, and June 30, 2023. Additionally, we performed phylogenetic and mutation analyses using whole-genome, next-generation sequencing of PV2 isolates to identify recombination events, characterise VDPV2 lineages according to the capsid region, and establish the geographical distribution and linkage of PV2 isolates.</div></div><div><h3>Findings</h3><div>We detected 256 genetically linked samples from environmental surveillance, as well as one case of acute flaccid paralysis and four positive contacts associated with the Sabin type 2 oral vaccine strain. Most affected locations showed a high-density population of Jewish Ultra-Orthodox communities. Through high-resolution genomic characterisation and phylogenetic analysis of 202 representative sequences with complete capsid coverage, including isolates from both environmental surveillance and the case of acute flaccid paralysis, a conclusive linkage was established among all detections, confirming them to be part of a single VDPV2 outbreak. This strategy enabled the characterisation of three distinct lineages and established connections between different locations in Israel, including linking the case of acute flaccid paralysis and nearby environmental surveillance detections from the northern region with detections in the geographically distant central region.</div></div><div><h3>Interpretation</h3><div>This study highlights the role of environmental surveillance in the early detection and monitoring of poliovirus circulation, enabling a prompt public health response involving enhanced surveillance and a catch-up campaign with inactivated polio vaccine. Whole-genome sequencing offered valuable insights into the origins of the outbreak, linkage across detections, and the geographical distribution of the virus, with higher resolution than would have been possible with the standard analysis of the <em>VP1</em> gene alone.</div></div><div><h3>Funding</h3><div>None.<","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 10","pages":"Article 100893"},"PeriodicalIF":20.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142298319","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 : 2024-10-01DOI: 10.1016/S2666-5247(24)00105-8
{"title":"A rapid test using a single drop of blood to screen for schistosomiasis in non-endemic countries","authors":"","doi":"10.1016/S2666-5247(24)00105-8","DOIUrl":"10.1016/S2666-5247(24)00105-8","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 10","pages":"Article 100882"},"PeriodicalIF":20.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141026135","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 : 2024-10-01DOI: 10.1016/S2666-5247(24)00127-7
Tuberculosis is a leading cause of death from an infectious agent globally. Infectious subclinical tuberculosis accounts for almost half of all tuberculosis cases in national tuberculosis prevalence surveys, and possibly contributes to transmission and might be associated with morbidity. Modelling studies suggest that new tuberculosis vaccines could have substantial health and economic effects, partly based on the assumptions made regarding subclinical tuberculosis. Evaluating the efficacy of prevention of disease tuberculosis vaccines intended for preventing both clinical and subclinical tuberculosis is a priority. Incorporation of subclinical tuberculosis as a composite endpoint in tuberculosis vaccine trials can help to reduce the sample size and duration of follow-up and to evaluate the efficacy of tuberculosis vaccines in preventing clinical and subclinical tuberculosis. Several design options with various benefits, limitations, and ethical considerations are possible in this regard, which would allow for the generation of the evidence needed to estimate the positive global effects of tuberculosis vaccine trials, in addition to informing policy and vaccination strategies.
{"title":"Implications of subclinical tuberculosis for vaccine trial design and global effect","authors":"","doi":"10.1016/S2666-5247(24)00127-7","DOIUrl":"10.1016/S2666-5247(24)00127-7","url":null,"abstract":"<div><div>Tuberculosis is a leading cause of death from an infectious agent globally. Infectious subclinical tuberculosis accounts for almost half of all tuberculosis cases in national tuberculosis prevalence surveys, and possibly contributes to transmission and might be associated with morbidity. Modelling studies suggest that new tuberculosis vaccines could have substantial health and economic effects, partly based on the assumptions made regarding subclinical tuberculosis. Evaluating the efficacy of prevention of disease tuberculosis vaccines intended for preventing both clinical and subclinical tuberculosis is a priority. Incorporation of subclinical tuberculosis as a composite endpoint in tuberculosis vaccine trials can help to reduce the sample size and duration of follow-up and to evaluate the efficacy of tuberculosis vaccines in preventing clinical and subclinical tuberculosis. Several design options with various benefits, limitations, and ethical considerations are possible in this regard, which would allow for the generation of the evidence needed to estimate the positive global effects of tuberculosis vaccine trials, in addition to informing policy and vaccination strategies.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 10","pages":"Article 100895"},"PeriodicalIF":20.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11464400/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141535652","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 : 2024-10-01DOI: 10.1016/j.lanmic.2024.100998
Robert Dyrdak, Sofia Stamouli, Shambhu Ganeshappa Aralaguppe, Martin Ekman, Hamzah Safari, Carlo Berg, Elin Movert, Neus Latorre-Margalef, Emmi Andersson, Magnus Gisslén, Joanna Nederby-Öhd, Åsa Sjödin Leufvén, Josette Schoenmakers, Sandra Broddesson, Ben Murrell, Jan Albert
{"title":"A novel SARS-CoV-2 recombinant transmitted from a patient with an acute co-infection.","authors":"Robert Dyrdak, Sofia Stamouli, Shambhu Ganeshappa Aralaguppe, Martin Ekman, Hamzah Safari, Carlo Berg, Elin Movert, Neus Latorre-Margalef, Emmi Andersson, Magnus Gisslén, Joanna Nederby-Öhd, Åsa Sjödin Leufvén, Josette Schoenmakers, Sandra Broddesson, Ben Murrell, Jan Albert","doi":"10.1016/j.lanmic.2024.100998","DOIUrl":"10.1016/j.lanmic.2024.100998","url":null,"abstract":"","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":" ","pages":"100998"},"PeriodicalIF":20.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142376165","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 : 2024-10-01DOI: 10.1016/j.lanmic.2024.100972
Maria Jesus Pinazo PhD , Prof Emilio Malchiodi PhD , Jean-Robert Ioset PhD , Prof Augusto Bivona PhD , Kenneth J Gollob PhD , Prof Walderez O Dutra PhD
Chagas disease, caused by the protozoan parasite Trypanosoma cruzi, presents a substantial global health burden, affecting millions of individuals worldwide and posing a continual risk of infection. Despite the high mortality and morbidity rates, effective vaccines to prevent infection by the parasite remain elusive, and the drugs currently available are suboptimal. Understanding the intricate dynamics of parasite–host interactions and the resulting immune responses, which contribute to both protection and pathology, is crucial for the development of effective vaccines and therapies against Chagas disease. In this Series paper, we discuss the challenges associated with discovering and translating prophylactic and therapeutic strategies from the laboratory bench to clinical application. We highlight ongoing efforts in vaccine and new drug development, with a focus on more advanced candidates for vaccines and drugs. We also discuss potential solutions, emphasising the importance of collaborative research efforts, sustained funding, and a comprehensive understanding of host–parasite interactions and immunopathology to advance the development of new vaccines and therapies against Chagas disease.
{"title":"Challenges and advancements in the development of vaccines and therapies against Chagas disease","authors":"Maria Jesus Pinazo PhD , Prof Emilio Malchiodi PhD , Jean-Robert Ioset PhD , Prof Augusto Bivona PhD , Kenneth J Gollob PhD , Prof Walderez O Dutra PhD","doi":"10.1016/j.lanmic.2024.100972","DOIUrl":"10.1016/j.lanmic.2024.100972","url":null,"abstract":"<div><div>Chagas disease, caused by the protozoan parasite <em>Trypanosoma cruzi</em>, presents a substantial global health burden, affecting millions of individuals worldwide and posing a continual risk of infection. Despite the high mortality and morbidity rates, effective vaccines to prevent infection by the parasite remain elusive, and the drugs currently available are suboptimal. Understanding the intricate dynamics of parasite–host interactions and the resulting immune responses, which contribute to both protection and pathology, is crucial for the development of effective vaccines and therapies against Chagas disease. In this Series paper, we discuss the challenges associated with discovering and translating prophylactic and therapeutic strategies from the laboratory bench to clinical application. We highlight ongoing efforts in vaccine and new drug development, with a focus on more advanced candidates for vaccines and drugs. We also discuss potential solutions, emphasising the importance of collaborative research efforts, sustained funding, and a comprehensive understanding of host–parasite interactions and immunopathology to advance the development of new vaccines and therapies against Chagas disease.</div></div>","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 10","pages":"Article 100972"},"PeriodicalIF":20.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142298396","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 : 2024-10-01DOI: 10.1016/S2666-5247(24)00112-5
Biana Bernshtein PhD , Meagan Kelly AB , Deniz Cizmeci PhD , Julia A Zhiteneva BS , Ryan Macvicar BA , Mohammad Kamruzzaman MSc , Taufiqur R Bhuiyan PhD , Fahima Chowdhury MBBS PhD , Ashraful Islam Khan MBBS , Firdausi Qadri PhD , Richelle C Charles MD , Peng Xu PhD , Pavol Kováč PhD , Kristen A Clarkson PhD , Robert W Kaminski PhD , Prof Galit Alter PhD , Prof Edward T Ryan MD
<div><h3>Background</h3><div><em>Shigella</em> is the third leading global cause of moderate or severe diarrhoea among children younger than 5 years globally, and is the leading cause in children aged 24–59 months. The mechanism of protection against <em>Shigella</em> infection and disease in endemic areas is uncertain. We aimed to compare the <em>Shigella</em>-specific antibody responses in individuals living in <em>Shigella</em>-endemic and non-endemic areas, and to identify correlates of protection in a <em>Shigella</em>-endemic location.</div></div><div><h3>Methods</h3><div>We applied a systems approach to retrospectively analyse serological responses to <em>Shigella</em> across endemic and non-endemic populations. We profiled serum samples collected from 44 individuals from the USA without previous exposure to <em>Shigella</em> and who were experimentally challenged with <em>Shigella sonnei</em> (non-endemic setting), and serum samples collected from 55 Peruvian army recruits (endemic setting). In the endemic setting, a subset of 37 samples collected from individuals infected with culture-confirmed <em>Shigella flexneri</em> 2a were divided into two groups: susceptible, which included individuals infected within 90 days of entering the camp (n=29); or resistant, which included individuals infected later than 90 days after entering the camp (n=8). We analysed <em>Shigella</em>-specific antibody isotype, subclass, and Fc receptor binding profiles across IpaB, IpaC, IpaD, and lipopolysaccharide from <em>S flexneri</em> 2a, 3a, and 6, and <em>S sonnei</em>, and O-specific polysaccharide (OSP) from <em>S flexneri</em> 2a and 3a and <em>S sonnei.</em> We also evaluated antibody-mediated complement deposition and innate immune cell activation. The main outcome of interest was the detection of antibody markers and functionality associated with protection against shigellosis in a high-burden endemic setting.</div></div><div><h3>Findings</h3><div>Adults with endemic exposure to <em>Shigella</em> possessed broad and functional antibody responses across polysaccharide, glycolipid, and protein antigens compared with individuals from non-endemic regions. In a setting with high <em>Shigella</em> burden, elevated levels of OSP-specific Fcα receptor (FcαR) binding antibodies were associated with resistance to shigellosis, whereas total OSP-specific IgA was not, suggesting a potentially unique functionality. OSP-specific FcαR binding IgA found in resistant individuals activated bactericidal neutrophil functions including phagocytosis, degranulation, and production of reactive oxygen species. Moreover, IgA depletion from resistant serum significantly reduced binding of OSP-specific antibodies to FcαR and antibody-mediated activation of neutrophils and monocytes.</div></div><div><h3>Interpretation</h3><div>Our findings suggest that OSP-specific functional IgA responses contribute to protective immunity against <em>Shigella</em> infection in a high-burden settin
背景：志贺氏菌是导致全球 5 岁以下儿童中度或重度腹泻的第三大原因，也是导致 24-59 个月儿童腹泻的主要原因。在志贺氏杆菌流行地区，预防志贺氏杆菌感染和疾病的机制尚不确定。我们的目的是比较生活在志贺氏杆菌流行地区和非流行地区的人的志贺氏杆菌特异性抗体反应，并确定在志贺氏杆菌流行地区保护的相关因素：我们采用了一种系统方法，对志贺氏杆菌流行区和非流行区人群的血清反应进行了回顾性分析。我们分析了从美国 44 名以前未接触过志贺氏杆菌、但在实验中感染了松内志贺氏菌（非地方病）的人身上采集的血清样本，以及从 55 名秘鲁新兵（地方病）身上采集的血清样本。在地方病环境中，从感染了经培养证实的柔性志贺氏菌 2a 的个体中采集的 37 份样本被分为两组：易感组，包括进入营地后 90 天内感染的个体（29 人）；耐受组，包括进入营地后 90 天后感染的个体（8 人）。我们分析了志贺氏杆菌特异性抗体的同型、亚类和 Fc 受体结合情况，包括 IpaB、IpaC、IpaD 和来自 S flexneri 2a、3a 和 6 以及 S sonnei 的脂多糖，以及来自 S flexneri 2a 和 3a 以及 S sonnei 的 O 特异性多糖 (OSP)。我们还评估了抗体介导的补体沉积和先天性免疫细胞活化。我们感兴趣的主要结果是，在高负担地方病环境中检测与志贺氏杆菌病保护相关的抗体标记物和功能：研究结果：与来自非志贺氏杆菌流行地区的个体相比，接触过志贺氏杆菌的成年人对多糖、糖脂和蛋白质抗原具有广泛的功能性抗体反应。在志贺氏杆菌负担较重的环境中，OSP特异性Fcα受体（FcαR）结合抗体水平的升高与志贺氏杆菌病的抵抗力有关，而OSP特异性IgA总量却与之无关，这表明OSP特异性IgA可能具有独特的功能。在耐药个体中发现的 OSP 特异性 FcαR 结合 IgA 激活了中性粒细胞的杀菌功能，包括吞噬、脱颗粒和产生活性氧。此外，从耐药血清中清除 IgA 能显著减少 OSP 特异性抗体与 FcαR 的结合以及抗体介导的中性粒细胞和单核细胞活化：我们的研究结果表明，OSP特异性功能性IgA反应有助于在高负担环境中对志贺氏杆菌感染产生保护性免疫。这些发现将有助于志贺氏杆菌疫苗的开发和评估：美国国立卫生研究院。
{"title":"Determinants of immune responses predictive of protection against shigellosis in an endemic zone: a systems analysis of antibody profiles and function","authors":"Biana Bernshtein PhD , Meagan Kelly AB , Deniz Cizmeci PhD , Julia A Zhiteneva BS , Ryan Macvicar BA , Mohammad Kamruzzaman MSc , Taufiqur R Bhuiyan PhD , Fahima Chowdhury MBBS PhD , Ashraful Islam Khan MBBS , Firdausi Qadri PhD , Richelle C Charles MD , Peng Xu PhD , Pavol Kováč PhD , Kristen A Clarkson PhD , Robert W Kaminski PhD , Prof Galit Alter PhD , Prof Edward T Ryan MD","doi":"10.1016/S2666-5247(24)00112-5","DOIUrl":"10.1016/S2666-5247(24)00112-5","url":null,"abstract":"<div><h3>Background</h3><div><em>Shigella</em> is the third leading global cause of moderate or severe diarrhoea among children younger than 5 years globally, and is the leading cause in children aged 24–59 months. The mechanism of protection against <em>Shigella</em> infection and disease in endemic areas is uncertain. We aimed to compare the <em>Shigella</em>-specific antibody responses in individuals living in <em>Shigella</em>-endemic and non-endemic areas, and to identify correlates of protection in a <em>Shigella</em>-endemic location.</div></div><div><h3>Methods</h3><div>We applied a systems approach to retrospectively analyse serological responses to <em>Shigella</em> across endemic and non-endemic populations. We profiled serum samples collected from 44 individuals from the USA without previous exposure to <em>Shigella</em> and who were experimentally challenged with <em>Shigella sonnei</em> (non-endemic setting), and serum samples collected from 55 Peruvian army recruits (endemic setting). In the endemic setting, a subset of 37 samples collected from individuals infected with culture-confirmed <em>Shigella flexneri</em> 2a were divided into two groups: susceptible, which included individuals infected within 90 days of entering the camp (n=29); or resistant, which included individuals infected later than 90 days after entering the camp (n=8). We analysed <em>Shigella</em>-specific antibody isotype, subclass, and Fc receptor binding profiles across IpaB, IpaC, IpaD, and lipopolysaccharide from <em>S flexneri</em> 2a, 3a, and 6, and <em>S sonnei</em>, and O-specific polysaccharide (OSP) from <em>S flexneri</em> 2a and 3a and <em>S sonnei.</em> We also evaluated antibody-mediated complement deposition and innate immune cell activation. The main outcome of interest was the detection of antibody markers and functionality associated with protection against shigellosis in a high-burden endemic setting.</div></div><div><h3>Findings</h3><div>Adults with endemic exposure to <em>Shigella</em> possessed broad and functional antibody responses across polysaccharide, glycolipid, and protein antigens compared with individuals from non-endemic regions. In a setting with high <em>Shigella</em> burden, elevated levels of OSP-specific Fcα receptor (FcαR) binding antibodies were associated with resistance to shigellosis, whereas total OSP-specific IgA was not, suggesting a potentially unique functionality. OSP-specific FcαR binding IgA found in resistant individuals activated bactericidal neutrophil functions including phagocytosis, degranulation, and production of reactive oxygen species. Moreover, IgA depletion from resistant serum significantly reduced binding of OSP-specific antibodies to FcαR and antibody-mediated activation of neutrophils and monocytes.</div></div><div><h3>Interpretation</h3><div>Our findings suggest that OSP-specific functional IgA responses contribute to protective immunity against <em>Shigella</em> infection in a high-burden settin","PeriodicalId":46633,"journal":{"name":"Lancet Microbe","volume":"5 10","pages":"Article 100889"},"PeriodicalIF":20.9,"publicationDate":"2024-10-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141907970","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}
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