Pub Date : 2024-10-28DOI: 10.1016/s1473-3099(24)00595-4
Nathan C Lo, David G Addiss, Dora Buonfrate, Arancha Amor, Melaku Anegagrie, Zeno Bisoffi, Richard S Bradbury, Jennifer Keiser, Stella Kepha, Virak Khieu, Alejandro Krolewiecki, Jean B Mbonigaba, Jose Muñoz, Francisca Mutapi, Valdemiro Novela, Susana Vaz Nery, Luc E Coffeng, Sake J de Vlas, Jessica Bartoszko, Lorenzo Moja, Antonio Montresor
Strongyloidiasis is a soil-transmitted helminthiasis that is estimated to affect 300–600 million people across Asia, Africa, South and central America, and the Pacific. This neglected parasitic disease is most known for its ability to persist as a lifelong infection due to autoinfection and its risk of hyperinfection and disseminated disease during immunosuppression, which has a more than 60% case fatality. Despite the large global burden of strongyloidiasis, there have been no large-scale public health programmes or WHO guidelines directed towards its control and elimination. However, over the past decade, key scientific and policy changes along with requests from endemic countries have led to WHO incorporating strongyloidiasis into its 2021–30 roadmap and public health targets for control and elimination of neglected tropical diseases. In 2024, WHO published its first guideline on public health control of strongyloidiasis with a single recommendation: in endemic settings with a Strongyloides stercoralis infection prevalence of 5% or higher (measured either with Baermann or agar plate culture from stool specimens), WHO conditionally recommends mass drug administration with single-dose ivermectin (200 μg/kg; oral therapy) in all age groups from 5 years and older to reduce strongyloidiasis. This Review, written by the 2023–24 strongyloidiasis guidelines development group along with WHO colleagues and international experts, presents a summary of the recently published WHO guideline recommendation for strongyloidiasis, and the supporting evidence, considerations for public health implementation, and future research needs.
{"title":"Review of the WHO guideline on preventive chemotherapy for public health control of strongyloidiasis","authors":"Nathan C Lo, David G Addiss, Dora Buonfrate, Arancha Amor, Melaku Anegagrie, Zeno Bisoffi, Richard S Bradbury, Jennifer Keiser, Stella Kepha, Virak Khieu, Alejandro Krolewiecki, Jean B Mbonigaba, Jose Muñoz, Francisca Mutapi, Valdemiro Novela, Susana Vaz Nery, Luc E Coffeng, Sake J de Vlas, Jessica Bartoszko, Lorenzo Moja, Antonio Montresor","doi":"10.1016/s1473-3099(24)00595-4","DOIUrl":"https://doi.org/10.1016/s1473-3099(24)00595-4","url":null,"abstract":"Strongyloidiasis is a soil-transmitted helminthiasis that is estimated to affect 300–600 million people across Asia, Africa, South and central America, and the Pacific. This neglected parasitic disease is most known for its ability to persist as a lifelong infection due to autoinfection and its risk of hyperinfection and disseminated disease during immunosuppression, which has a more than 60% case fatality. Despite the large global burden of strongyloidiasis, there have been no large-scale public health programmes or WHO guidelines directed towards its control and elimination. However, over the past decade, key scientific and policy changes along with requests from endemic countries have led to WHO incorporating strongyloidiasis into its 2021–30 roadmap and public health targets for control and elimination of neglected tropical diseases. In 2024, WHO published its first guideline on public health control of strongyloidiasis with a single recommendation: in endemic settings with a <em>Strongyloides stercoralis</em> infection prevalence of 5% or higher (measured either with Baermann or agar plate culture from stool specimens), WHO conditionally recommends mass drug administration with single-dose ivermectin (200 μg/kg; oral therapy) in all age groups from 5 years and older to reduce strongyloidiasis. This Review, written by the 2023–24 strongyloidiasis guidelines development group along with WHO colleagues and international experts, presents a summary of the recently published WHO guideline recommendation for strongyloidiasis, and the supporting evidence, considerations for public health implementation, and future research needs.","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":"111 1","pages":""},"PeriodicalIF":56.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520019","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-28DOI: 10.1016/s1473-3099(24)00733-3
Cahal McQuillan
No Abstract
无摘要
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Pub Date : 2024-10-28DOI: 10.1016/s1473-3099(24)00598-x
William Burman, C Robert Horsburgh, James Johnston
No Abstract
无摘要
{"title":"Predictable excess hepatotoxicity in the SimpliciTB trial","authors":"William Burman, C Robert Horsburgh, James Johnston","doi":"10.1016/s1473-3099(24)00598-x","DOIUrl":"https://doi.org/10.1016/s1473-3099(24)00598-x","url":null,"abstract":"No Abstract","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":"102 1","pages":""},"PeriodicalIF":56.3,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142520021","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-25DOI: 10.1016/s1473-3099(24)00566-8
Sandra Bos, José Victor Zambrana, Elias Duarte, Aaron L Graber, Julia Huffaker, Carlos Montenegro, Lakshmanane Premkumar, Aubree Gordon, Guillermina Kuan, Angel Balmaseda, Eva Harris
Background
Dengue is the most prevalent mosquito-borne viral disease and a major public health problem worldwide. Most primary infections with the four dengue virus serotypes (DENV1–4) are inapparent; nonetheless, whether the distribution of symptomatic versus inapparent infections by serotype varies remains unknown. Here, we present (1) the evaluation of a DENV1–4 envelope domain III multiplex microsphere-based assay (EDIII-MMBA) to serotype inapparent primary infections and (2) its application leveraging 17 years of prospective sample collection from the Nicaraguan Pediatric Dengue Cohort Study (PDCS).
Methods
We analysed primary DENV infections in the PDCS from 2004 to 2022 detected by inhibition ELISA (iELISA) or RT-PCR. First, we evaluated the performance of the EDIII-MMBA for serotyping with samples characterised by RT-PCR or focus reduction neutralisation test. Next, we analysed a subset of inapparent primary DENV infections in the PDCS with the EDIII-MMBA to evaluate the epidemiology of inapparent infections. Remaining infections were inferred using stochastic imputation, taking year and neighbourhood into account. Infection incidence and percentage of inapparent, symptomatic, and severe infections were analysed by serotype.
Findings
Between Aug 30, 2004, and March 10, 2022, a total of 5931 DENV-naive participants were followed in the PDCS. There were 1626 primary infections (382 symptomatic, 1244 inapparent) detected by iELISA or RT-PCR over the study period. The EDIII-MMBA demonstrated excellent overall accuracy (100%, 95% CI 95·8–100) for serotyping inapparent primary DENV infections when evaluated against gold-standard serotyping methods. Of the 1244 inapparent infections, we analysed 574 (46%) using the EDIII-MMBA. We found that the majority of primary infections were inapparent, with DENV3 exhibiting the highest likelihood of symptomatic (pooled odds ratio compared with DENV1: 2·13, 95% CI 1·28–3·56) and severe (6·75, 2·01–22·62) primary infections, whereas DENV2 was similar to DENV1 in both analyses. Considerable within-year and between-year variation in serotype distribution between symptomatic and inapparent infections and circulation of serotypes undetected in symptomatic cases were observed in multiple years.
Interpretation
Our study indicates that case surveillance skews the perceived epidemiological footprint of DENV. We reveal a more complex and intricate pattern of serotype distribution in inapparent infections. The substantial differences in infection outcomes by serotype emphasises the need for vaccines with balanced immunogenicity and efficacy across serotypes.
Funding
National Institute of Allergy and Infectious Diseases (National Institutes of Health) and Bill & Melinda Gates Foundation.
Translation
For the Spanish translation of the abstract see Supplementary Materials section.
背景登革热是最流行的蚊媒病毒性疾病，也是全球主要的公共卫生问题。四种登革热病毒血清型（DENV1-4）的大多数原发感染是不明显的；然而，有症状感染与不明显感染的分布是否因血清型而异仍是未知数。在此，我们介绍了：（1）对基于微球的 DENV1-4 包膜域 III 多重检测法（EDIII-MMBA）进行评估，以确定不明显的原发性感染血清型；（2）利用尼加拉瓜儿科登革热队列研究（PDCS）17 年的前瞻性样本收集对该检测法进行应用。首先，我们评估了 EDIII-MMBA 通过 RT-PCR 或病灶还原中和试验对样本进行血清分型的性能。接着，我们用EDIII-MMBA分析了PDCS中不明显的原发性DENV感染，以评估不明显感染的流行病学。剩余的感染病例采用随机估算法进行推断，并将年份和邻近地区考虑在内。研究结果2004年8月30日至2022年3月10日期间，PDCS共对5931名未感染过DENV的参与者进行了随访。在研究期间，通过iELISA或RT-PCR检测到1626例原发性感染（382例有症状，1244例无症状）。与金标准血清分型方法相比，EDIII-MMBA在对不明显的原发性DENV感染进行血清分型时表现出了极高的总体准确性（100%，95% CI 95-8-100）。在 1244 例不明显的感染中，我们使用 EDIII-MMBA 分析了 574 例（46%）。我们发现，大多数原发性感染都是不明显的，其中 DENV3 出现无症状（与 DENV1 相比的汇总几率比：2-13，95% CI 1-28-3-56）和严重（6-75，2-01-22-62）原发性感染的可能性最大，而 DENV2 在这两项分析中的表现与 DENV1 相似。我们的研究表明，病例监测歪曲了人们对 DENV 流行病学足迹的认识。我们揭示了隐性感染中血清型分布更为复杂和错综复杂的模式。不同血清型的感染结果存在巨大差异，这强调了我们需要在不同血清型之间平衡免疫原性和有效性的疫苗。
{"title":"Serotype-specific epidemiological patterns of inapparent versus symptomatic primary dengue virus infections: a 17-year cohort study in Nicaragua","authors":"Sandra Bos, José Victor Zambrana, Elias Duarte, Aaron L Graber, Julia Huffaker, Carlos Montenegro, Lakshmanane Premkumar, Aubree Gordon, Guillermina Kuan, Angel Balmaseda, Eva Harris","doi":"10.1016/s1473-3099(24)00566-8","DOIUrl":"https://doi.org/10.1016/s1473-3099(24)00566-8","url":null,"abstract":"<h3>Background</h3>Dengue is the most prevalent mosquito-borne viral disease and a major public health problem worldwide. Most primary infections with the four dengue virus serotypes (DENV1–4) are inapparent; nonetheless, whether the distribution of symptomatic versus inapparent infections by serotype varies remains unknown. Here, we present (1) the evaluation of a DENV1–4 envelope domain III multiplex microsphere-based assay (EDIII-MMBA) to serotype inapparent primary infections and (2) its application leveraging 17 years of prospective sample collection from the Nicaraguan Pediatric Dengue Cohort Study (PDCS).<h3>Methods</h3>We analysed primary DENV infections in the PDCS from 2004 to 2022 detected by inhibition ELISA (iELISA) or RT-PCR. First, we evaluated the performance of the EDIII-MMBA for serotyping with samples characterised by RT-PCR or focus reduction neutralisation test. Next, we analysed a subset of inapparent primary DENV infections in the PDCS with the EDIII-MMBA to evaluate the epidemiology of inapparent infections. Remaining infections were inferred using stochastic imputation, taking year and neighbourhood into account. Infection incidence and percentage of inapparent, symptomatic, and severe infections were analysed by serotype.<h3>Findings</h3>Between Aug 30, 2004, and March 10, 2022, a total of 5931 DENV-naive participants were followed in the PDCS. There were 1626 primary infections (382 symptomatic, 1244 inapparent) detected by iELISA or RT-PCR over the study period. The EDIII-MMBA demonstrated excellent overall accuracy (100%, 95% CI 95·8–100) for serotyping inapparent primary DENV infections when evaluated against gold-standard serotyping methods. Of the 1244 inapparent infections, we analysed 574 (46%) using the EDIII-MMBA. We found that the majority of primary infections were inapparent, with DENV3 exhibiting the highest likelihood of symptomatic (pooled odds ratio compared with DENV1: 2·13, 95% CI 1·28–3·56) and severe (6·75, 2·01–22·62) primary infections, whereas DENV2 was similar to DENV1 in both analyses. Considerable within-year and between-year variation in serotype distribution between symptomatic and inapparent infections and circulation of serotypes undetected in symptomatic cases were observed in multiple years.<h3>Interpretation</h3>Our study indicates that case surveillance skews the perceived epidemiological footprint of DENV. We reveal a more complex and intricate pattern of serotype distribution in inapparent infections. The substantial differences in infection outcomes by serotype emphasises the need for vaccines with balanced immunogenicity and efficacy across serotypes.<h3>Funding</h3>National Institute of Allergy and Infectious Diseases (National Institutes of Health) and Bill & Melinda Gates Foundation.<h3>Translation</h3>For the Spanish translation of the abstract see Supplementary Materials section.","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":"149 1","pages":""},"PeriodicalIF":56.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-25DOI: 10.1016/s1473-3099(24)00599-1
Patrícia Brasil, Jan Felix Drexler
No Abstract
无摘要
{"title":"Vaccine and surveillance implications of dengue underdetection","authors":"Patrícia Brasil, Jan Felix Drexler","doi":"10.1016/s1473-3099(24)00599-1","DOIUrl":"https://doi.org/10.1016/s1473-3099(24)00599-1","url":null,"abstract":"No Abstract","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":"25 1","pages":""},"PeriodicalIF":56.3,"publicationDate":"2024-10-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142490168","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-23DOI: 10.1016/s1473-3099(24)00527-9
Dídac Macià, Joseph J Campo, Chenjerai Jairoce, Maximilian Mpina, Hermann Sorgho, David Dosoo, Selidji Todagbe Agnandji, Kwadwo Asamoah Kusi, Luis M Molinos-Albert, Simon Kariuki, Claudia Daubenberger, Benjamin Mordmüller, Gemma Moncunill, Carlota Dobaño
<h3>Background</h3>The RTS,S/AS01<sub>E</sub> malaria vaccine showed lower antibody response and protective efficacy in infants aged 6–12 weeks compared with children aged 5–17 months (for whom this vaccine is recommended). We aimed to study the effect of previous <em>Plasmodium falciparum</em> exposure on the antibody responses to RTS,S/AS01<sub>E</sub> vaccination in infants and children, and the mediating effect of baseline (including maternal) anti-circumsporozoite protein (CSP) antibodies.<h3>Methods</h3>In this observational study, we included children and infants from six African countries (Burkina Faso, Gabon, Ghana, Kenya, Mozambique, and Tanzania) enrolled in the MAL067 immunology ancillary study of the RTS,S/AS01<sub>E</sub> phase 3 clinical trial from March 27, 2009, to Jan 21, 2011. We used comparator-vaccinated infants and children to identify antibody-based signatures of previous <em>P falciparum</em> exposure, which were later applied to RTS,S/AS01<sub>E</sub>-vaccinated infants and children. In these participants, we explored the relationship between vaccine antibody immunoglobulin G (IgG) responses measured by ELISA and pre-vaccination serological markers of malaria exposure by assessing the IgG levels against 1000 <em>P falciparum</em> antigens using partial proteome microarrays.<h3>Findings</h3>We included 718 comparator-vaccinated infants (348 [48%]) and children (370 [52%]) and 606 RTS,S/AS01<sub>E</sub>-vaccinated infants (329 [54%]) and children (277 [46%]). Anti-CSP IgG responses to primary vaccination did not correlate with a baseline signature of previous exposure in children, suggesting that prior <em>P falciparum</em> exposure does not significantly affect antibody immunogenicity in children (Pearson's <em>r</em>=–0·02 [95% CI –0·13 to 0·10]). By contrast, high <em>P falciparum</em> exposure signature levels at the time of vaccination in infants, presumably driven by maternally transferred antibodies and declining within the initial 6–12 months of life, correlated with reduced RTS,S/AS01<sub>E</sub> responses (<em>r</em>=–0·17 [–0·27 to –0·06]). This negative correlation was stronger for anti-CSP IgG than for the exposure signature or any other more immunogenic blood stage <em>P falciparum</em> antigens (<em>r</em>=–0·42 [–0·50 to –0·33]), persisted after adjustment by baseline levels of the exposure signature (semi-partial correlation r=–0·44 [–0·55 to –0·33]), and involved antibodies to the central NANP region (<em>r</em>=–0·39 [–0·49 to –0·28]) but not the C-terminal region (<em>r</em>=0·02 [–0·10 to 0·15]) of CSP. The negative effect of maternal anti-CSP IgG in infants did not appear to be confounded by other malaria transmission-dependent variables.<h3>Interpretation</h3>Interference between passive immunity and vaccine response is clinically significant and might affect the implementation of next-generation CSP-based vaccines for young infants and mothers as well as passive immunisation with human monoclonal ant
背景RTS,S/AS01E疟疾疫苗在6-12周大婴儿中的抗体反应和保护效力低于5-17个月大（推荐接种该疫苗）的儿童。我们的目的是研究既往恶性疟原虫暴露对婴幼儿接种 RTS,S/AS01E 疫苗后抗体反应的影响，以及基线（包括母体）抗圆孢子虫蛋白 (CSP) 抗体的中介作用。方法在这项观察性研究中，我们纳入了 2009 年 3 月 27 日至 2011 年 1 月 21 日期间参加 RTS,S/AS01E 3 期临床试验 MAL067 免疫学辅助研究的六个非洲国家（布基纳法索、加蓬、加纳、肯尼亚、莫桑比克和坦桑尼亚）的儿童和婴儿。我们利用接种过对比疫苗的婴儿和儿童来确定先前恶性疟原虫暴露的抗体特征，随后将其应用于接种过 RTS,S/AS01E 疫苗的婴儿和儿童。在这些参与者中，我们使用部分蛋白质组芯片评估了针对 1000 种恶性疟原虫抗原的 IgG 水平，从而探讨了通过 ELISA 测量的疫苗抗体免疫球蛋白 G (IgG) 反应与接种前疟疾暴露血清学标记物之间的关系。研究结果我们纳入了 718 名接种过对比疫苗的婴儿（348 [48%]）和儿童（370 [52%]），以及 606 名接种过 RTS,S/AS01E 疫苗的婴儿（329 [54%]）和儿童（277 [46%]）。儿童对初次接种的抗 CSP IgG 反应与先前暴露的基线特征无关，这表明先前的恶性疟原虫暴露不会显著影响儿童的抗体免疫原性（Pearson's r=-0-02 [95% CI -0-13 to 0-10]）。相比之下，婴儿接种疫苗时的恶性疟原虫暴露特征水平较高，可能是受母体转移抗体的影响，并在出生后的最初 6-12 个月内下降，这与 RTS,S/AS01E 反应的降低有关（r=-0-17 [-0-27 to -0-06]）。抗 CSP IgG 的这种负相关性比暴露特征或任何其他免疫原性更强的血期恶性疟原虫抗原更强（r=-0-42 [-0-50 to -0-33]）、在根据暴露特征的基线水平进行调整后，抗 CSP IgG 的负作用仍然存在（半相关性 r=-0-44 [-0-55 to -0-33]），并且涉及 CSP 的 NANP 中心区抗体（r=-0-39 [-0-49 to -0-28]）而非 C 端区抗体（r=0-02 [-0-10 to 0-15]）。解释被动免疫和疫苗反应之间的干扰具有重要的临床意义，可能会影响为婴儿和母亲接种基于CSP的下一代疫苗以及使用人类单克隆抗体进行被动免疫。资金来源美国国立卫生研究院、国立过敏与传染病研究所、PATH-疟疾疫苗计划、西班牙经济与竞争部（卡洛斯三世健康研究所）、欧洲区域发展基金和欧洲社会基金、拉蒙-阿雷斯基金会、西班牙科学与创新部和加泰罗尼亚自治区（CERCA 计划）。
{"title":"The effect of Plasmodium falciparum exposure and maternal anti-circumsporozoite protein antibodies on responses to RTS,S/AS01E vaccination in infants and children: an ancillary observational immunological study to a phase 3, randomised clinical trial","authors":"Dídac Macià, Joseph J Campo, Chenjerai Jairoce, Maximilian Mpina, Hermann Sorgho, David Dosoo, Selidji Todagbe Agnandji, Kwadwo Asamoah Kusi, Luis M Molinos-Albert, Simon Kariuki, Claudia Daubenberger, Benjamin Mordmüller, Gemma Moncunill, Carlota Dobaño","doi":"10.1016/s1473-3099(24)00527-9","DOIUrl":"https://doi.org/10.1016/s1473-3099(24)00527-9","url":null,"abstract":"<h3>Background</h3>The RTS,S/AS01<sub>E</sub> malaria vaccine showed lower antibody response and protective efficacy in infants aged 6–12 weeks compared with children aged 5–17 months (for whom this vaccine is recommended). We aimed to study the effect of previous <em>Plasmodium falciparum</em> exposure on the antibody responses to RTS,S/AS01<sub>E</sub> vaccination in infants and children, and the mediating effect of baseline (including maternal) anti-circumsporozoite protein (CSP) antibodies.<h3>Methods</h3>In this observational study, we included children and infants from six African countries (Burkina Faso, Gabon, Ghana, Kenya, Mozambique, and Tanzania) enrolled in the MAL067 immunology ancillary study of the RTS,S/AS01<sub>E</sub> phase 3 clinical trial from March 27, 2009, to Jan 21, 2011. We used comparator-vaccinated infants and children to identify antibody-based signatures of previous <em>P falciparum</em> exposure, which were later applied to RTS,S/AS01<sub>E</sub>-vaccinated infants and children. In these participants, we explored the relationship between vaccine antibody immunoglobulin G (IgG) responses measured by ELISA and pre-vaccination serological markers of malaria exposure by assessing the IgG levels against 1000 <em>P falciparum</em> antigens using partial proteome microarrays.<h3>Findings</h3>We included 718 comparator-vaccinated infants (348 [48%]) and children (370 [52%]) and 606 RTS,S/AS01<sub>E</sub>-vaccinated infants (329 [54%]) and children (277 [46%]). Anti-CSP IgG responses to primary vaccination did not correlate with a baseline signature of previous exposure in children, suggesting that prior <em>P falciparum</em> exposure does not significantly affect antibody immunogenicity in children (Pearson's <em>r</em>=–0·02 [95% CI –0·13 to 0·10]). By contrast, high <em>P falciparum</em> exposure signature levels at the time of vaccination in infants, presumably driven by maternally transferred antibodies and declining within the initial 6–12 months of life, correlated with reduced RTS,S/AS01<sub>E</sub> responses (<em>r</em>=–0·17 [–0·27 to –0·06]). This negative correlation was stronger for anti-CSP IgG than for the exposure signature or any other more immunogenic blood stage <em>P falciparum</em> antigens (<em>r</em>=–0·42 [–0·50 to –0·33]), persisted after adjustment by baseline levels of the exposure signature (semi-partial correlation r=–0·44 [–0·55 to –0·33]), and involved antibodies to the central NANP region (<em>r</em>=–0·39 [–0·49 to –0·28]) but not the C-terminal region (<em>r</em>=0·02 [–0·10 to 0·15]) of CSP. The negative effect of maternal anti-CSP IgG in infants did not appear to be confounded by other malaria transmission-dependent variables.<h3>Interpretation</h3>Interference between passive immunity and vaccine response is clinically significant and might affect the implementation of next-generation CSP-based vaccines for young infants and mothers as well as passive immunisation with human monoclonal ant","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":"4 1","pages":""},"PeriodicalIF":56.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488052","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pub Date : 2024-10-23DOI: 10.1016/s1473-3099(24)00565-6
Yusuke Okada, Yuji Kumagai, Iori Okura, Mako Otsuki, Natsuki Ishida, Yasuhiro Iwama, Takeshi Minamida, Yukihiro Yagi, Toru Kurosawa, Josephine van Boxmeer, Ye Zhang, Igor Smolenov, Judd L Walson
<h3>Background</h3>We previously showed that ARCT-154, a self-amplifying mRNA COVID-19 vaccine, had improved immunogenicity and antibody persistence compared with conventional mRNA or adenovirus vector vaccines. In this study, we compared ARCT-2301, a bivalent self-amplifying mRNA vaccine (Asp614Gly and omicron BA.4/5 variant), with the bivalent Comirnaty omicron BA.4-5 vaccine, to determine whether this improved response persisted in bivalent formulations against different SARS-CoV-2 variants.<h3>Methods</h3>This randomised, multicentre, phase 3, observer-masked, active-controlled comparative study was done at nine hospitals in Japan. Eligible participants were healthy Japanese adults, aged at least 18 years, who had previously received a full immunisation series of three to five doses of mRNA COVID-19 vaccines (Comirnaty or Spikevax [Moderna]), with the last dose received at least 3 months before screening for this trial. Participants were randomly assigned (1:1) to either ARCT-2301 or Comirnaty BA.4-5 mRNA vaccine using interactive computer-generated randomisation with a block size of four. Randomisation was stratified by gender (men <em>vs</em> women), age group (<65 years <em>vs</em> ≥65 years), type of vaccine used for last vaccination (bivalent omicron BA.1 <em>vs</em> bivalent omicron BA.4/5), and time since last COVID-19 vaccination (<5 months <em>vs</em> ≥5 months). ARCT-2301 was supplied in vials containing 100 μg lyophilised mRNA, 50 μg mRNA each coding for the full-length spike proteins of the ancestral Asp614Gly SARS-CoV-2 strain and omicron BA.4/5 variant. Immediately before use, each vial was reconstituted with 10 mL saline. The comparator original omicron BA.4/5 mRNA vaccine (Comirnaty BA.4-5) was supplied in ready-to-use vials containing a single dose of 30 μg mRNA in 0·3 mL volume. Both vaccines were administered by intramuscular injection in the deltoid of the non-dominant arm. The primary outcome of the study was to show non-inferiority of immunogenicity of ARCT-2301 versus Comirnaty BA.4-5 at day 29 as neutralising antibody geometric mean titres (GMT) and seroresponse rates against omicron BA.4/5. Primary analyses were done in a per-protocol manner. The trial is registered with the Japan Registry for Clinical Trials, jRCT2031230340.<h3>Findings</h3>Between Sept 29 and Nov 18, 2023, we enrolled 930 participants (451 men and 479 women) to receive a booster dose of ARCT-2301 (n=465) or Comirnaty BA.4-5 (n=465). The primary immunogenicity outcome to show that the antibody response at day 29 against omicron BA.4/5 elicited by ARCT-2301 was non-inferior to that elicited with Comirnaty BA.4-5 was achieved, both by GMT ratio (1·49, 95% CI 1·26–1·76) and difference in seroresponse rate (7·2%, 95% CI 0·6–13·7). Furthermore, the differences in antibody response between the groups showed superiority for ARCT-2301 against Wuhan-Hu-1 using both criteria, with a GMT ratio of 1·45 (95% CI 1·28–1·63) and a difference in seroresponse ra
{"title":"Immunogenicity of a booster dose of a bivalent (Asp614Gly and omicron BA.4/5 variant) self-amplifying mRNA SARS-CoV-2 booster vaccine versus the BNT162b2 omicron BA.4/5 mRNA vaccine: a randomised phase 3 trial","authors":"Yusuke Okada, Yuji Kumagai, Iori Okura, Mako Otsuki, Natsuki Ishida, Yasuhiro Iwama, Takeshi Minamida, Yukihiro Yagi, Toru Kurosawa, Josephine van Boxmeer, Ye Zhang, Igor Smolenov, Judd L Walson","doi":"10.1016/s1473-3099(24)00565-6","DOIUrl":"https://doi.org/10.1016/s1473-3099(24)00565-6","url":null,"abstract":"<h3>Background</h3>We previously showed that ARCT-154, a self-amplifying mRNA COVID-19 vaccine, had improved immunogenicity and antibody persistence compared with conventional mRNA or adenovirus vector vaccines. In this study, we compared ARCT-2301, a bivalent self-amplifying mRNA vaccine (Asp614Gly and omicron BA.4/5 variant), with the bivalent Comirnaty omicron BA.4-5 vaccine, to determine whether this improved response persisted in bivalent formulations against different SARS-CoV-2 variants.<h3>Methods</h3>This randomised, multicentre, phase 3, observer-masked, active-controlled comparative study was done at nine hospitals in Japan. Eligible participants were healthy Japanese adults, aged at least 18 years, who had previously received a full immunisation series of three to five doses of mRNA COVID-19 vaccines (Comirnaty or Spikevax [Moderna]), with the last dose received at least 3 months before screening for this trial. Participants were randomly assigned (1:1) to either ARCT-2301 or Comirnaty BA.4-5 mRNA vaccine using interactive computer-generated randomisation with a block size of four. Randomisation was stratified by gender (men <em>vs</em> women), age group (<65 years <em>vs</em> ≥65 years), type of vaccine used for last vaccination (bivalent omicron BA.1 <em>vs</em> bivalent omicron BA.4/5), and time since last COVID-19 vaccination (<5 months <em>vs</em> ≥5 months). ARCT-2301 was supplied in vials containing 100 μg lyophilised mRNA, 50 μg mRNA each coding for the full-length spike proteins of the ancestral Asp614Gly SARS-CoV-2 strain and omicron BA.4/5 variant. Immediately before use, each vial was reconstituted with 10 mL saline. The comparator original omicron BA.4/5 mRNA vaccine (Comirnaty BA.4-5) was supplied in ready-to-use vials containing a single dose of 30 μg mRNA in 0·3 mL volume. Both vaccines were administered by intramuscular injection in the deltoid of the non-dominant arm. The primary outcome of the study was to show non-inferiority of immunogenicity of ARCT-2301 versus Comirnaty BA.4-5 at day 29 as neutralising antibody geometric mean titres (GMT) and seroresponse rates against omicron BA.4/5. Primary analyses were done in a per-protocol manner. The trial is registered with the Japan Registry for Clinical Trials, jRCT2031230340.<h3>Findings</h3>Between Sept 29 and Nov 18, 2023, we enrolled 930 participants (451 men and 479 women) to receive a booster dose of ARCT-2301 (n=465) or Comirnaty BA.4-5 (n=465). The primary immunogenicity outcome to show that the antibody response at day 29 against omicron BA.4/5 elicited by ARCT-2301 was non-inferior to that elicited with Comirnaty BA.4-5 was achieved, both by GMT ratio (1·49, 95% CI 1·26–1·76) and difference in seroresponse rate (7·2%, 95% CI 0·6–13·7). Furthermore, the differences in antibody response between the groups showed superiority for ARCT-2301 against Wuhan-Hu-1 using both criteria, with a GMT ratio of 1·45 (95% CI 1·28–1·63) and a difference in seroresponse ra","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":"31 1","pages":""},"PeriodicalIF":56.3,"publicationDate":"2024-10-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142488056","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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