Pub Date : 2024-12-16DOI: 10.1016/s1473-3099(24)00648-0
Ryan K Shields, Lilian M Abbo, Renee Ackley, Samuel L Aitken, Benjamin Albrecht, Ahmed Babiker, Rachel Burgoon, Renzo Cifuentes, Kimberly C Claeys, Brooke N Curry, Kathryn E DeSear, Jason C Gallagher, Esther Y Golnabi, Alan E Gross, Jonathan Hand, Emily L Heil, Krutika M Hornback, Keith S Kaye, Trieu-Vi Khuu, Megan E Klatt, Jason M Pogue
<h3>Background</h3>Ceftolozane–tazobactam and ceftazidime–avibactam are preferred treatment options for multidrug-resistant <em>Pseudomonas aeruginosa</em> infections; however, real-world comparative effectiveness studies are scarce. Pharmacokinetic and pharmacodynamic differences between the agents might affect clinical response rates. We aimed to compare the effectiveness of ceftolozane–tazobactam and ceftazidime–avibactam for treatment of invasive multidrug-resistant <em>P aeruginosa</em> infections.<h3>Methods</h3>This multicentre, retrospective, observational study was conducted at 28 hospitals in the USA between Jan 1, 2016, and Dec 31, 2023. Eligible patients were adults (age ≥18 years old) with microbiologically confirmed multidrug-resistant <em>P aeruginosa</em> pneumonia or bacteraemia treated with ceftolozane–tazobactam or ceftazidime–avibactam for more than 48 h. Patients were matched (1:1) by study site, severity of illness, time to treatment initiation (≤72 h or >72 h), and infection type. The primary outcome was clinical success at day 30, which was defined as survival, resolution of signs and symptoms of infection with the intended treatment course, and the absence of recurrent infection due to <em>P aeruginosa</em>. Secondary outcomes included all-cause mortality and development of resistance to study drug.<h3>Findings</h3>420 eligible patients were included (210 in each treatment group), of whom 350 (83%) had pneumonia and 70 (17%) had bacteraemia. Baseline demographics, comorbidities, and severity of illness indicators were similar between groups. On treatment initiation, 336 (80%) patients were in the intensive care unit, 296 (70%) were receiving mechanical ventilation, and 168 (40%) required vasopressor support. Clinical success was observed in 128 (61%) of 210 patients treated with ceftolozane–tazobactam and 109 (52%) of 210 patients treated with ceftazidime–avibactam. By conditional logistic regression analysis, the adjusted odds ratio (aOR) of success after treatment with ceftolozane–tazobactam compared with ceftazidime–avibactam was 2·07 (95% CI 1·16–3·70). For patients with pneumonia, clinical success was observed in 110 (63%) of 175 patients in the ceftolozane–tazobactam group and 89 (51%) of 175 patients in the ceftazidime–avibactam group (aOR 2·34 [95% CI 1·22–4·47]). Among patients with bacteraemia, rates of clinical success were 51% (18 of 35 patients) for patients treated with ceftolozane–tazobactam and 57% (20 of 35 patients) for those treated with ceftazidime–avibactam (0·76 [0·23–2·57]). There were no significant differences between groups in 30-day or 90-day mortality. Among patients whose baseline isolates were tested for susceptibility, resistance developed in 22% (38 of 173) of patients treated with ceftolozane–tazobactam and 23% (40 of 177) of patients treated with ceftazidime–avibactam.<h3>Interpretation</h3>Treatment with ceftolozane–tazobactam resulted in higher rates of clinical success compared with
{"title":"Effectiveness of ceftazidime–avibactam versus ceftolozane–tazobactam for multidrug-resistant Pseudomonas aeruginosa infections in the USA (CACTUS): a multicentre, retrospective, observational study","authors":"Ryan K Shields, Lilian M Abbo, Renee Ackley, Samuel L Aitken, Benjamin Albrecht, Ahmed Babiker, Rachel Burgoon, Renzo Cifuentes, Kimberly C Claeys, Brooke N Curry, Kathryn E DeSear, Jason C Gallagher, Esther Y Golnabi, Alan E Gross, Jonathan Hand, Emily L Heil, Krutika M Hornback, Keith S Kaye, Trieu-Vi Khuu, Megan E Klatt, Jason M Pogue","doi":"10.1016/s1473-3099(24)00648-0","DOIUrl":"https://doi.org/10.1016/s1473-3099(24)00648-0","url":null,"abstract":"<h3>Background</h3>Ceftolozane–tazobactam and ceftazidime–avibactam are preferred treatment options for multidrug-resistant <em>Pseudomonas aeruginosa</em> infections; however, real-world comparative effectiveness studies are scarce. Pharmacokinetic and pharmacodynamic differences between the agents might affect clinical response rates. We aimed to compare the effectiveness of ceftolozane–tazobactam and ceftazidime–avibactam for treatment of invasive multidrug-resistant <em>P aeruginosa</em> infections.<h3>Methods</h3>This multicentre, retrospective, observational study was conducted at 28 hospitals in the USA between Jan 1, 2016, and Dec 31, 2023. Eligible patients were adults (age ≥18 years old) with microbiologically confirmed multidrug-resistant <em>P aeruginosa</em> pneumonia or bacteraemia treated with ceftolozane–tazobactam or ceftazidime–avibactam for more than 48 h. Patients were matched (1:1) by study site, severity of illness, time to treatment initiation (≤72 h or >72 h), and infection type. The primary outcome was clinical success at day 30, which was defined as survival, resolution of signs and symptoms of infection with the intended treatment course, and the absence of recurrent infection due to <em>P aeruginosa</em>. Secondary outcomes included all-cause mortality and development of resistance to study drug.<h3>Findings</h3>420 eligible patients were included (210 in each treatment group), of whom 350 (83%) had pneumonia and 70 (17%) had bacteraemia. Baseline demographics, comorbidities, and severity of illness indicators were similar between groups. On treatment initiation, 336 (80%) patients were in the intensive care unit, 296 (70%) were receiving mechanical ventilation, and 168 (40%) required vasopressor support. Clinical success was observed in 128 (61%) of 210 patients treated with ceftolozane–tazobactam and 109 (52%) of 210 patients treated with ceftazidime–avibactam. By conditional logistic regression analysis, the adjusted odds ratio (aOR) of success after treatment with ceftolozane–tazobactam compared with ceftazidime–avibactam was 2·07 (95% CI 1·16–3·70). For patients with pneumonia, clinical success was observed in 110 (63%) of 175 patients in the ceftolozane–tazobactam group and 89 (51%) of 175 patients in the ceftazidime–avibactam group (aOR 2·34 [95% CI 1·22–4·47]). Among patients with bacteraemia, rates of clinical success were 51% (18 of 35 patients) for patients treated with ceftolozane–tazobactam and 57% (20 of 35 patients) for those treated with ceftazidime–avibactam (0·76 [0·23–2·57]). There were no significant differences between groups in 30-day or 90-day mortality. Among patients whose baseline isolates were tested for susceptibility, resistance developed in 22% (38 of 173) of patients treated with ceftolozane–tazobactam and 23% (40 of 177) of patients treated with ceftazidime–avibactam.<h3>Interpretation</h3>Treatment with ceftolozane–tazobactam resulted in higher rates of clinical success compared with","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":"201 1","pages":""},"PeriodicalIF":56.3,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142832774","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 : 2024-12-12DOI: 10.1016/s1473-3099(24)00673-x
Amanda Rojek, Joshua Fieggen, Paska Apiyo, Séverine Caluwaerts, Robert A Fowler, Pontiano Kaleebu, Richard Kojan, Marta Lado, Teresa Lambe, Jake Dunning, Peter Horby
The west Africa Ebola disease epidemic (2014–16) marked a historic change of course for patient care during emerging infectious disease outbreaks. The epidemic response was a failure in many ways—a slow, cumbersome, and disjointed effort by a global architecture that was not fit for purpose for a rapidly spreading outbreak. In the most affected countries, health-care workers and other responders felt helpless—dealing with an overwhelming number of patients but with few, if any, tools at their disposal to provide high-quality care. These inadequacies, however, led to attention and innovation. The decade since then has seen remarkable achievements in clinical care for Ebola disease, including the approval of the first vaccines and treatments. In this paper, the first in a two-part Series, we reflect on this progress and provide expert summary of the modern landscape of Ebola disease, highlighting the priorities and ongoing activities aimed at further improving patient survival and wellbeing in the years ahead.
{"title":"Ebola disease: bridging scientific discoveries and clinical application","authors":"Amanda Rojek, Joshua Fieggen, Paska Apiyo, Séverine Caluwaerts, Robert A Fowler, Pontiano Kaleebu, Richard Kojan, Marta Lado, Teresa Lambe, Jake Dunning, Peter Horby","doi":"10.1016/s1473-3099(24)00673-x","DOIUrl":"https://doi.org/10.1016/s1473-3099(24)00673-x","url":null,"abstract":"The west Africa Ebola disease epidemic (2014–16) marked a historic change of course for patient care during emerging infectious disease outbreaks. The epidemic response was a failure in many ways—a slow, cumbersome, and disjointed effort by a global architecture that was not fit for purpose for a rapidly spreading outbreak. In the most affected countries, health-care workers and other responders felt helpless—dealing with an overwhelming number of patients but with few, if any, tools at their disposal to provide high-quality care. These inadequacies, however, led to attention and innovation. The decade since then has seen remarkable achievements in clinical care for Ebola disease, including the approval of the first vaccines and treatments. In this paper, the first in a two-part Series, we reflect on this progress and provide expert summary of the modern landscape of Ebola disease, highlighting the priorities and ongoing activities aimed at further improving patient survival and wellbeing in the years ahead.","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":"10 1","pages":""},"PeriodicalIF":56.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816267","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 : 2024-12-12DOI: 10.1016/s1473-3099(24)00811-9
Narmeen Mallah, Jacobo Pardo-Seco, Olaia Pérez-Martínez, Carmen Durán-Parrondo, Federico Martinón-Torres
No Abstract
{"title":"Full 2023–24 season results of universal prophylaxis with nirsevimab in Galicia, Spain: the NIRSE-GAL study","authors":"Narmeen Mallah, Jacobo Pardo-Seco, Olaia Pérez-Martínez, Carmen Durán-Parrondo, Federico Martinón-Torres","doi":"10.1016/s1473-3099(24)00811-9","DOIUrl":"https://doi.org/10.1016/s1473-3099(24)00811-9","url":null,"abstract":"No Abstract","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":"19 1 1","pages":""},"PeriodicalIF":56.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142809539","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 : 2024-12-12DOI: 10.1016/s1473-3099(24)00727-8
Amanda Rojek, Joshua Fieggen, Amy Paterson, Pauline Byakika-Kibwika, Modet Camara, Kim Comer, Tom E Fletcher, Stephan Günther, Sylvie Jonckheere, Gerald Mwima, Jake Dunning, Peter Horby
A key lesson from the west Africa (2014–16) Ebola disease epidemic was that outbreak responses fail when they respond to patients through a narrow clinical lens without considering the broader community and social context of care. Here, in the second of two Series papers on the modern landscape of Ebola disease, we review progress made in the last decade to improve patient-centred care. Although the biosafety imperatives of treating Ebola disease remain, recent advances show how to mitigate these so that patients are cared for in a safe and dignified manner that encourages early treatment-seeking behaviour and provides support after the return of patients to their communities. We review advances in diagnostics, including faster Ebola disease detection via real-time RT-PCR, and consider design improvements in Ebola disease treatment units that enhance patient safety and dignity. We also review advances in care provision, such as the integration of palliative care and mobile communication into routine care, and address how greater access to research is possible through harmonised clinical trials. Finally, we discuss how strengthened community engagement and psychosocial programmes are addressing stigma and providing holistic support for survivors.
{"title":"Embedding treatment in stronger care systems","authors":"Amanda Rojek, Joshua Fieggen, Amy Paterson, Pauline Byakika-Kibwika, Modet Camara, Kim Comer, Tom E Fletcher, Stephan Günther, Sylvie Jonckheere, Gerald Mwima, Jake Dunning, Peter Horby","doi":"10.1016/s1473-3099(24)00727-8","DOIUrl":"https://doi.org/10.1016/s1473-3099(24)00727-8","url":null,"abstract":"A key lesson from the west Africa (2014–16) Ebola disease epidemic was that outbreak responses fail when they respond to patients through a narrow clinical lens without considering the broader community and social context of care. Here, in the second of two Series papers on the modern landscape of Ebola disease, we review progress made in the last decade to improve patient-centred care. Although the biosafety imperatives of treating Ebola disease remain, recent advances show how to mitigate these so that patients are cared for in a safe and dignified manner that encourages early treatment-seeking behaviour and provides support after the return of patients to their communities. We review advances in diagnostics, including faster Ebola disease detection via real-time RT-PCR, and consider design improvements in Ebola disease treatment units that enhance patient safety and dignity. We also review advances in care provision, such as the integration of palliative care and mobile communication into routine care, and address how greater access to research is possible through harmonised clinical trials. Finally, we discuss how strengthened community engagement and psychosocial programmes are addressing stigma and providing holistic support for survivors.","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":"1 1","pages":""},"PeriodicalIF":56.3,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142816268","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 : 2024-12-10DOI: 10.1016/s1473-3099(24)00752-7
Hamtandi M Natama, Jo Salkeld, Athanase Somé, Seyi Soremekun, Salou Diallo, Ousmane Traoré, Toussaint Rouamba, Florence Ouédraogo, Edouard Ouédraogo, K Carine Sonia Daboné, Nadine A Koné, Z Michael John Compaoré, Miguel Kafando, Massa dit Achille Bonko, Fabé Konaté, Hermann Sorgho, Carolyn M Nielsen, Dimitra Pipini, Ababacar Diouf, Lloyd D W King, Angela M Minassian
<h3>Background</h3>Two pre-erythrocytic vaccines (R21/Matrix-M and RTS,S/AS01) are now approved for <em>Plasmodium falciparum</em> malaria. However, neither induces blood-stage immunity against parasites that break through from the liver. RH5.1/Matrix-M, a blood-stage <em>P falciparum</em> malaria vaccine candidate, was highly immunogenic in Tanzanian adults and children. We therefore assessed the safety and efficacy of RH5.1/Matrix-M in Burkinabe children.<h3>Methods</h3>In this double-blind, randomised, controlled, phase 2b trial, RH5.1/Matrix-M was given to children aged 5–17 months in Nanoro, Burkina Faso, a seasonal malaria transmission setting. Children received either three intramuscular vaccinations with 10 μg RH5.1 protein with 50 μg Matrix-M adjuvant or three doses of rabies control vaccine, Rabivax-S, given either in a delayed third-dose (0, 1, and 5 month) regimen (first cohort) or a 0, 1, and 2 month regimen (second cohort). Vaccinations were completed part way through the malaria season. Children were randomly assigned 2:1 within each cohort to receive RH5.1/Matrix-M or Rabivax-S. Participants were assigned according to a random allocation list generated by an independent statistician using block randomisation with variable block sizes. Participants, their families, and the study teams were masked to group allocation; only pharmacists who prepared the vaccines were unmasked. Vaccine safety, immunogenicity, and efficacy were evaluated. The coprimary outcomes assessed were: first, the safety and reactogenicity of RH5.1/Matrix-M; and second, the protective efficacy of RH5.1/Matrix-M against clinical malaria (measured as time to first episode of clinical malaria, using a Cox regression model) from 14 days to 6 months after the third vaccination in the per-protocol sample. This ongoing trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span> (<span><span>NCT05790889</span><svg aria-label="Opens in new window" focusable="false" height="20" viewbox="0 0 8 8"><path d="M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z"></path></svg></span>).<h3>Findings</h3>From April 6 to 13 and July 3 to 7, 2023, 412 children aged 5–17 months were screened, and 51 were excluded. A total of 361 children were enrolled in this study. In the first cohort, 119 were assigned to the RH5.1/Matrix-M delayed third-dose group, and 62 to the equivalent rabies control group. The second cohort included 120 children in the monthly RH5.1/Matrix-M group and 60 in the equivalent rabies control group. The final vaccination was administered to all groups from Sept 4 to 21, 2023. RH5.1/Matrix-M in both cohorts had a favourable safety profile and was well tolerated. Most adverse events were mild, with the most common being local swe
{"title":"Safety and efficacy of the blood-stage malaria vaccine RH5.1/Matrix-M in Burkina Faso: interim results of a double-blind, randomised, controlled, phase 2b trial in children","authors":"Hamtandi M Natama, Jo Salkeld, Athanase Somé, Seyi Soremekun, Salou Diallo, Ousmane Traoré, Toussaint Rouamba, Florence Ouédraogo, Edouard Ouédraogo, K Carine Sonia Daboné, Nadine A Koné, Z Michael John Compaoré, Miguel Kafando, Massa dit Achille Bonko, Fabé Konaté, Hermann Sorgho, Carolyn M Nielsen, Dimitra Pipini, Ababacar Diouf, Lloyd D W King, Angela M Minassian","doi":"10.1016/s1473-3099(24)00752-7","DOIUrl":"https://doi.org/10.1016/s1473-3099(24)00752-7","url":null,"abstract":"<h3>Background</h3>Two pre-erythrocytic vaccines (R21/Matrix-M and RTS,S/AS01) are now approved for <em>Plasmodium falciparum</em> malaria. However, neither induces blood-stage immunity against parasites that break through from the liver. RH5.1/Matrix-M, a blood-stage <em>P falciparum</em> malaria vaccine candidate, was highly immunogenic in Tanzanian adults and children. We therefore assessed the safety and efficacy of RH5.1/Matrix-M in Burkinabe children.<h3>Methods</h3>In this double-blind, randomised, controlled, phase 2b trial, RH5.1/Matrix-M was given to children aged 5–17 months in Nanoro, Burkina Faso, a seasonal malaria transmission setting. Children received either three intramuscular vaccinations with 10 μg RH5.1 protein with 50 μg Matrix-M adjuvant or three doses of rabies control vaccine, Rabivax-S, given either in a delayed third-dose (0, 1, and 5 month) regimen (first cohort) or a 0, 1, and 2 month regimen (second cohort). Vaccinations were completed part way through the malaria season. Children were randomly assigned 2:1 within each cohort to receive RH5.1/Matrix-M or Rabivax-S. Participants were assigned according to a random allocation list generated by an independent statistician using block randomisation with variable block sizes. Participants, their families, and the study teams were masked to group allocation; only pharmacists who prepared the vaccines were unmasked. Vaccine safety, immunogenicity, and efficacy were evaluated. The coprimary outcomes assessed were: first, the safety and reactogenicity of RH5.1/Matrix-M; and second, the protective efficacy of RH5.1/Matrix-M against clinical malaria (measured as time to first episode of clinical malaria, using a Cox regression model) from 14 days to 6 months after the third vaccination in the per-protocol sample. This ongoing trial is registered with <span><span>ClinicalTrials.gov</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span> (<span><span>NCT05790889</span><svg aria-label=\"Opens in new window\" focusable=\"false\" height=\"20\" viewbox=\"0 0 8 8\"><path d=\"M1.12949 2.1072V1H7V6.85795H5.89111V2.90281L0.784057 8L0 7.21635L5.11902 2.1072H1.12949Z\"></path></svg></span>).<h3>Findings</h3>From April 6 to 13 and July 3 to 7, 2023, 412 children aged 5–17 months were screened, and 51 were excluded. A total of 361 children were enrolled in this study. In the first cohort, 119 were assigned to the RH5.1/Matrix-M delayed third-dose group, and 62 to the equivalent rabies control group. The second cohort included 120 children in the monthly RH5.1/Matrix-M group and 60 in the equivalent rabies control group. The final vaccination was administered to all groups from Sept 4 to 21, 2023. RH5.1/Matrix-M in both cohorts had a favourable safety profile and was well tolerated. Most adverse events were mild, with the most common being local swe","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":"47 1","pages":""},"PeriodicalIF":56.3,"publicationDate":"2024-12-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142804616","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 : 2024-12-05DOI: 10.1016/s1473-3099(24)00667-4
Terry Nolan, Chiranjiwi Bhusal, Jiří Beran, Mark Bloch, Benhur Sirvan Cetin, Ener Cagri Dinleyici, Daniel Dražan, Satu Kokko, Susanna Koski, Outi Laajalahti, Joanne M Langley, Mika Rämet, Peter C Richmond, Peter Silas, Bruce Tapiero, Florence Tiong, Mary Tipton, Benita Ukkonen, Betul Ulukol, Maria Lattanzi, Danielle Morelle
<h3>Background</h3>A multicomponent meningococcal serogroups ABCWY vaccine (MenABCWY) could provide broad protection against disease-causing meningococcal strains and simplify the immunisation schedule. The aim of this trial was to confirm the effect of the licensed meningococcal serogroup B (MenB) vaccine, 4CMenB, against diverse MenB strains, and to assess the breadth of immune response against a panel of 110 MenB strains for MenABCWY containing the antigenic components of 4CMenB and licensed serogroups ACWY vaccine, MenACWY-CRM, the non-inferiority of the immune response with MenABCWY versus 4CMenB and MenACWY-CRM, safety, and MenABCWY lot-to-lot consistency.<h3>Methods</h3>We conducted a phase 3 randomised, controlled, observer-blinded trial of healthy adolescents and young adults (age 10–25 years) across 114 centres in Australia, Canada, Czechia, Estonia, Finland, Türkiye, and the USA. Exclusion criteria included previous vaccination with a MenB vaccine or (within the last 4 years) MenACWY vaccine. Participants were randomly allocated (5:5:3:3:3:1 ratio) via a central randomisation system using a minimisation procedure to receive 4CMenB at months 0, 2, and 6 (referred to as 4CMenB 0–2–6 hereafter); or 4CMenB at months 0 and 6 (referred to as 4CMenB 0–6 hereafter); or MenABCWY (three groups, each receiving one production lot of the MenACWY-CRM component) at months 0 and 6; or MenACWY-CRM at month 0. Demonstration in the per-protocol set of the consistency of three MenACWY-CRM component lots of the MenABCWY vaccine was a primary objective (demonstrated with two-sided 95% CIs for the ratio of human serum bactericidal antibody [hSBA] geometric mean titres against each serogroup within predefined criteria [0·5–2·0]). The primary endpoints (breadth of immune response) for the MenB component of MenABCWY and 4CMenB were measured using the endogenous complement hSBA (enc-hSBA) assay against a panel of 110 diverse MenB invasive disease strains. For each serum sample, 35 strains from the 110 MenB strain panel were randomly selected for testing. The 4CMenB breadth of immune response data have been published separately. For MenABCWY, breadth of immune response was assessed in two analyses: a test-based analysis of the percentage of samples (tests) without bactericidal serum activity against MenB strains 1 month after two MenABCWY doses versus the percentage after one MenACWY-CRM dose in the per-protocol set, and a responder-based analysis of the percentage of participants (responders) whose sera killed 70% or more strains at 1 month after two MenABCWY doses in the full analysis set. A lower limit of two-sided 95% CI above 65% would demonstrate breadth of immune response. Other primary outcomes included non-inferiority (5% margin) of two MenABCWY doses versus two 4CMenB doses by enc-hSBA assay in the per-protocol set, non-inferiority (10% margin) of two MenABCWY doses versus one MenACWY-CRM dose in MenACWY vaccine-naive participants by traditional hSBA as
{"title":"Breadth of immune response, immunogenicity, reactogenicity, and safety for a pentavalent meningococcal ABCWY vaccine in healthy adolescents and young adults: results from a phase 3, randomised, controlled observer-blinded trial","authors":"Terry Nolan, Chiranjiwi Bhusal, Jiří Beran, Mark Bloch, Benhur Sirvan Cetin, Ener Cagri Dinleyici, Daniel Dražan, Satu Kokko, Susanna Koski, Outi Laajalahti, Joanne M Langley, Mika Rämet, Peter C Richmond, Peter Silas, Bruce Tapiero, Florence Tiong, Mary Tipton, Benita Ukkonen, Betul Ulukol, Maria Lattanzi, Danielle Morelle","doi":"10.1016/s1473-3099(24)00667-4","DOIUrl":"https://doi.org/10.1016/s1473-3099(24)00667-4","url":null,"abstract":"<h3>Background</h3>A multicomponent meningococcal serogroups ABCWY vaccine (MenABCWY) could provide broad protection against disease-causing meningococcal strains and simplify the immunisation schedule. The aim of this trial was to confirm the effect of the licensed meningococcal serogroup B (MenB) vaccine, 4CMenB, against diverse MenB strains, and to assess the breadth of immune response against a panel of 110 MenB strains for MenABCWY containing the antigenic components of 4CMenB and licensed serogroups ACWY vaccine, MenACWY-CRM, the non-inferiority of the immune response with MenABCWY versus 4CMenB and MenACWY-CRM, safety, and MenABCWY lot-to-lot consistency.<h3>Methods</h3>We conducted a phase 3 randomised, controlled, observer-blinded trial of healthy adolescents and young adults (age 10–25 years) across 114 centres in Australia, Canada, Czechia, Estonia, Finland, Türkiye, and the USA. Exclusion criteria included previous vaccination with a MenB vaccine or (within the last 4 years) MenACWY vaccine. Participants were randomly allocated (5:5:3:3:3:1 ratio) via a central randomisation system using a minimisation procedure to receive 4CMenB at months 0, 2, and 6 (referred to as 4CMenB 0–2–6 hereafter); or 4CMenB at months 0 and 6 (referred to as 4CMenB 0–6 hereafter); or MenABCWY (three groups, each receiving one production lot of the MenACWY-CRM component) at months 0 and 6; or MenACWY-CRM at month 0. Demonstration in the per-protocol set of the consistency of three MenACWY-CRM component lots of the MenABCWY vaccine was a primary objective (demonstrated with two-sided 95% CIs for the ratio of human serum bactericidal antibody [hSBA] geometric mean titres against each serogroup within predefined criteria [0·5–2·0]). The primary endpoints (breadth of immune response) for the MenB component of MenABCWY and 4CMenB were measured using the endogenous complement hSBA (enc-hSBA) assay against a panel of 110 diverse MenB invasive disease strains. For each serum sample, 35 strains from the 110 MenB strain panel were randomly selected for testing. The 4CMenB breadth of immune response data have been published separately. For MenABCWY, breadth of immune response was assessed in two analyses: a test-based analysis of the percentage of samples (tests) without bactericidal serum activity against MenB strains 1 month after two MenABCWY doses versus the percentage after one MenACWY-CRM dose in the per-protocol set, and a responder-based analysis of the percentage of participants (responders) whose sera killed 70% or more strains at 1 month after two MenABCWY doses in the full analysis set. A lower limit of two-sided 95% CI above 65% would demonstrate breadth of immune response. Other primary outcomes included non-inferiority (5% margin) of two MenABCWY doses versus two 4CMenB doses by enc-hSBA assay in the per-protocol set, non-inferiority (10% margin) of two MenABCWY doses versus one MenACWY-CRM dose in MenACWY vaccine-naive participants by traditional hSBA as","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":"27 1","pages":""},"PeriodicalIF":56.3,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782848","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}
{"title":"Will a new pentavalent meningococcal ABCWY vaccine mark a milestone in protecting all those at risk from invasive meningococcal disease?","authors":"Claudia Nieto-Sánchez, Theresa J Ochoa, Chukwuemeka Onwuchekwa, Raffaella Ravinetto, Kristien Verdonck","doi":"10.1016/s1473-3099(24)00736-9","DOIUrl":"https://doi.org/10.1016/s1473-3099(24)00736-9","url":null,"abstract":"No Abstract","PeriodicalId":49923,"journal":{"name":"Lancet Infectious Diseases","volume":"138 1","pages":""},"PeriodicalIF":56.3,"publicationDate":"2024-12-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142782722","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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