Michal Juraska, Angela M Early, Li Li, Stephen F Schaffner, Marc Lievens, Akanksha Khorgade, Brian Simpkins, Nima S Hejazi, David Benkeser, Qi Wang, Laina D Mercer, Samuel Adjei, Tsiri Agbenyega, Scott Anderson, Daniel Ansong, Dennis K Bii, Patrick B Y Buabeng, Sean English, Nicholas Fitzgerald, Jonna Grimsby, Simon K Kariuki, Kephas Otieno, François Roman, Aaron M Samuels, Nelli Westercamp, Christian F Ockenhouse, Opokua Ofori-Anyinam, Cynthia K Lee, Bronwyn L MacInnis, Dyann F Wirth, Peter B Gilbert, Daniel E Neafsey
{"title":"加纳和肯尼亚 5-17 个月儿童接种 RTS,S/AS01E 疟疾疫苗预防寄生虫感染的效力随剂量方案和基线疟疾感染状况而变化的基因型分析：一项纵向 2b 期随机对照试验。","authors":"Michal Juraska, Angela M Early, Li Li, Stephen F Schaffner, Marc Lievens, Akanksha Khorgade, Brian Simpkins, Nima S Hejazi, David Benkeser, Qi Wang, Laina D Mercer, Samuel Adjei, Tsiri Agbenyega, Scott Anderson, Daniel Ansong, Dennis K Bii, Patrick B Y Buabeng, Sean English, Nicholas Fitzgerald, Jonna Grimsby, Simon K Kariuki, Kephas Otieno, François Roman, Aaron M Samuels, Nelli Westercamp, Christian F Ockenhouse, Opokua Ofori-Anyinam, Cynthia K Lee, Bronwyn L MacInnis, Dyann F Wirth, Peter B Gilbert, Daniel E Neafsey","doi":"10.1016/S1473-3099(24)00179-8","DOIUrl":null,"url":null,"abstract":"<p><strong>Background: </strong>The first licensed malaria vaccine, RTS,S/AS01<sub>E</sub>, confers moderate protection against symptomatic disease. Because many malaria infections are asymptomatic, we conducted a large-scale longitudinal parasite genotyping study of samples from a clinical trial exploring how vaccine dosing regimen affects vaccine efficacy.</p><p><strong>Methods: </strong>Between Sept 28, 2017, and Sept 25, 2018, 1500 children aged 5-17 months were randomly assigned (1:1:1:1:1) to receive four different RTS,S/AS01<sub>E</sub> regimens or a rabies control vaccine in a phase 2b open-label clinical trial in Ghana and Kenya. Participants in the four RTS,S groups received two full doses at month 0 and month 1 and either full doses at month 2 and month 20 (group R012-20); full doses at month 2, month 14, month 26, and month 38 (group R012-14); fractional doses at month 2, month 14, month 26, and month 38 (group Fx012-14; early fourth dose); or fractional doses at month 7, month 20, and month 32 (group Fx017-20; delayed third dose). We evaluated the time to the first new genotypically detected infection and the total number of new infections during two follow-up periods (12 months and 20 months) in more than 36 000 dried blood spot specimens from 1500 participants. To study vaccine effects on time to the first new infection, we defined vaccine efficacy as one minus the hazard ratio (HR; RTS,S vs control) of the first new infection. We performed a post-hoc analysis of vaccine efficacy based on malaria infection status at first vaccination and force of infection by month 2. This trial (MAL-095) is registered with ClinicalTrials.gov, NCT03281291.</p><p><strong>Findings: </strong>We observed significant and similar vaccine efficacy (25-43%; 95% CI union 9-53) against first new infection for all four RTS,S/AS01<sub>E</sub> regimens across both follow-up periods (12 months and 20 months). Each RTS,S/AS01<sub>E</sub> regimen significantly reduced the mean number of new infections in the 20-month follow-up period by 1·1-1·6 infections (95% CI union 0·6-2·1). Vaccine efficacy against first new infection was significantly higher in participants who were infected with malaria (68%; 95% CI 50-80) than in those who were uninfected (37%; 23-48) at the first vaccination (p=0·0053).</p><p><strong>Interpretation: </strong>All tested dosing regimens blocked some infections to a similar degree. Improved vaccine efficacy in participants infected during vaccination could suggest new strategies for highly efficacious malaria vaccine development and implementation.</p><p><strong>Funding: </strong>GlaxoSmithKline Biologicals SA, PATH, Bill & Melinda Gates Foundation, and the German Federal Ministry of Education and Research.</p>","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":36.4000,"publicationDate":"2024-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339203/pdf/","citationCount":"0","resultStr":"{\"title\":\"Genotypic analysis of RTS,S/AS01<sub>E</sub> malaria vaccine efficacy against parasite infection as a function of dosage regimen and baseline malaria infection status in children aged 5-17 months in Ghana and Kenya: a longitudinal phase 2b randomised controlled trial.\",\"authors\":\"Michal Juraska, Angela M Early, Li Li, Stephen F Schaffner, Marc Lievens, Akanksha Khorgade, Brian Simpkins, Nima S Hejazi, David Benkeser, Qi Wang, Laina D Mercer, Samuel Adjei, Tsiri Agbenyega, Scott Anderson, Daniel Ansong, Dennis K Bii, Patrick B Y Buabeng, Sean English, Nicholas Fitzgerald, Jonna Grimsby, Simon K Kariuki, Kephas Otieno, François Roman, Aaron M Samuels, Nelli Westercamp, Christian F Ockenhouse, Opokua Ofori-Anyinam, Cynthia K Lee, Bronwyn L MacInnis, Dyann F Wirth, Peter B Gilbert, Daniel E Neafsey\",\"doi\":\"10.1016/S1473-3099(24)00179-8\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Background: </strong>The first licensed malaria vaccine, RTS,S/AS01<sub>E</sub>, confers moderate protection against symptomatic disease. Because many malaria infections are asymptomatic, we conducted a large-scale longitudinal parasite genotyping study of samples from a clinical trial exploring how vaccine dosing regimen affects vaccine efficacy.</p><p><strong>Methods: </strong>Between Sept 28, 2017, and Sept 25, 2018, 1500 children aged 5-17 months were randomly assigned (1:1:1:1:1) to receive four different RTS,S/AS01<sub>E</sub> regimens or a rabies control vaccine in a phase 2b open-label clinical trial in Ghana and Kenya. Participants in the four RTS,S groups received two full doses at month 0 and month 1 and either full doses at month 2 and month 20 (group R012-20); full doses at month 2, month 14, month 26, and month 38 (group R012-14); fractional doses at month 2, month 14, month 26, and month 38 (group Fx012-14; early fourth dose); or fractional doses at month 7, month 20, and month 32 (group Fx017-20; delayed third dose). We evaluated the time to the first new genotypically detected infection and the total number of new infections during two follow-up periods (12 months and 20 months) in more than 36 000 dried blood spot specimens from 1500 participants. To study vaccine effects on time to the first new infection, we defined vaccine efficacy as one minus the hazard ratio (HR; RTS,S vs control) of the first new infection. We performed a post-hoc analysis of vaccine efficacy based on malaria infection status at first vaccination and force of infection by month 2. This trial (MAL-095) is registered with ClinicalTrials.gov, NCT03281291.</p><p><strong>Findings: </strong>We observed significant and similar vaccine efficacy (25-43%; 95% CI union 9-53) against first new infection for all four RTS,S/AS01<sub>E</sub> regimens across both follow-up periods (12 months and 20 months). Each RTS,S/AS01<sub>E</sub> regimen significantly reduced the mean number of new infections in the 20-month follow-up period by 1·1-1·6 infections (95% CI union 0·6-2·1). Vaccine efficacy against first new infection was significantly higher in participants who were infected with malaria (68%; 95% CI 50-80) than in those who were uninfected (37%; 23-48) at the first vaccination (p=0·0053).</p><p><strong>Interpretation: </strong>All tested dosing regimens blocked some infections to a similar degree. Improved vaccine efficacy in participants infected during vaccination could suggest new strategies for highly efficacious malaria vaccine development and implementation.</p><p><strong>Funding: </strong>GlaxoSmithKline Biologicals SA, PATH, Bill & Melinda Gates Foundation, and the German Federal Ministry of Education and Research.</p>\",\"PeriodicalId\":49923,\"journal\":{\"name\":\"Lancet Infectious Diseases\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":36.4000,\"publicationDate\":\"2024-09-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11339203/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Lancet Infectious Diseases\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1016/S1473-3099(24)00179-8\",\"RegionNum\":1,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2024/5/6 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q1\",\"JCRName\":\"INFECTIOUS DISEASES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Lancet Infectious Diseases","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1016/S1473-3099(24)00179-8","RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2024/5/6 0:00:00","PubModel":"Epub","JCR":"Q1","JCRName":"INFECTIOUS DISEASES","Score":null,"Total":0}
Genotypic analysis of RTS,S/AS01E malaria vaccine efficacy against parasite infection as a function of dosage regimen and baseline malaria infection status in children aged 5-17 months in Ghana and Kenya: a longitudinal phase 2b randomised controlled trial.
Background: The first licensed malaria vaccine, RTS,S/AS01E, confers moderate protection against symptomatic disease. Because many malaria infections are asymptomatic, we conducted a large-scale longitudinal parasite genotyping study of samples from a clinical trial exploring how vaccine dosing regimen affects vaccine efficacy.
Methods: Between Sept 28, 2017, and Sept 25, 2018, 1500 children aged 5-17 months were randomly assigned (1:1:1:1:1) to receive four different RTS,S/AS01E regimens or a rabies control vaccine in a phase 2b open-label clinical trial in Ghana and Kenya. Participants in the four RTS,S groups received two full doses at month 0 and month 1 and either full doses at month 2 and month 20 (group R012-20); full doses at month 2, month 14, month 26, and month 38 (group R012-14); fractional doses at month 2, month 14, month 26, and month 38 (group Fx012-14; early fourth dose); or fractional doses at month 7, month 20, and month 32 (group Fx017-20; delayed third dose). We evaluated the time to the first new genotypically detected infection and the total number of new infections during two follow-up periods (12 months and 20 months) in more than 36 000 dried blood spot specimens from 1500 participants. To study vaccine effects on time to the first new infection, we defined vaccine efficacy as one minus the hazard ratio (HR; RTS,S vs control) of the first new infection. We performed a post-hoc analysis of vaccine efficacy based on malaria infection status at first vaccination and force of infection by month 2. This trial (MAL-095) is registered with ClinicalTrials.gov, NCT03281291.
Findings: We observed significant and similar vaccine efficacy (25-43%; 95% CI union 9-53) against first new infection for all four RTS,S/AS01E regimens across both follow-up periods (12 months and 20 months). Each RTS,S/AS01E regimen significantly reduced the mean number of new infections in the 20-month follow-up period by 1·1-1·6 infections (95% CI union 0·6-2·1). Vaccine efficacy against first new infection was significantly higher in participants who were infected with malaria (68%; 95% CI 50-80) than in those who were uninfected (37%; 23-48) at the first vaccination (p=0·0053).
Interpretation: All tested dosing regimens blocked some infections to a similar degree. Improved vaccine efficacy in participants infected during vaccination could suggest new strategies for highly efficacious malaria vaccine development and implementation.
Funding: GlaxoSmithKline Biologicals SA, PATH, Bill & Melinda Gates Foundation, and the German Federal Ministry of Education and Research.
期刊介绍：
The Lancet Infectious Diseases was launched in August, 2001, and is a lively monthly journal of original research, review, opinion, and news covering international issues relevant to clinical infectious diseases specialists worldwide.The infectious diseases journal aims to be a world-leading publication, featuring original research that advocates change or sheds light on clinical practices related to infectious diseases. The journal prioritizes articles with the potential to impact clinical practice or influence perspectives. Content covers a wide range of topics, including anti-infective therapy and immunization, bacterial, viral, fungal, and parasitic infections, emerging infectious diseases, HIV/AIDS, malaria, tuberculosis, mycobacterial infections, infection control, infectious diseases epidemiology, neglected tropical diseases, and travel medicine. Informative reviews on any subject linked to infectious diseases and human health are also welcomed.
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