{"title":"不同剂量水平的 Ad26.RSV.preF/RSV preF 蛋白疫苗对 60 岁及以上成人的免疫原性和安全性:一项随机、双盲、安慰剂对照的 2a 期研究","authors":"","doi":"10.1016/j.vaccine.2024.126273","DOIUrl":null,"url":null,"abstract":"<div><h3>Background</h3><p>Respiratory syncytial virus (RSV) can cause severe illness in older adults. A combination vaccine containing Ad26.RSV.preF and purified recombinant RSV preF protein has previously demonstrated efficacy and tolerability in older adults. We report results of a dose-ranging study to determine immunogenicity and safety of different doses of the Ad26.RSV.preF component in the combined Ad26.RSV.preF/RSV preF protein vaccine to support Ad26.RSV.preF drug product release and stability specifications.</p></div><div><h3>Methods</h3><p>In this randomized, double-blind, placebo-controlled, phase 2a study, adults aged ≥60 years in good or stable health were randomly assigned within 1 of 3 cohorts to receive either placebo or Ad26.RSV.preF/RSV preF protein, composed of different doses of Ad26.RSV.preF with a fixed dose of RSV preF protein (150 μg). Ad26.RSV.preF doses in Cohort 1 (4 dose-down groups) ranged from 3.7 × 10<sup>9</sup> to 1.0 × 10<sup>11</sup> viral particles (vp). Doses in Cohorts 2 and 3 (2 dose-up groups, each) ranged from 1.0 to 1.6 × 10<sup>11</sup> vp. Primary endpoints were immunogenicity (RSV preF protein antibody titers) for Cohort 1 and safety (solicited local and systemic adverse events [AEs] and unsolicited AEs) for Cohorts 2 and 3. Immunogenicity analyses (RSV preF protein antibody titers, RSV A2 neutralizing antibodies, and RSV-F–specific interferon-γ enzyme-linked immunosorbent spot) were performed on the day of vaccination and 14 days, 3 months, and 6 months postvaccination. Safety was monitored from vaccination until study end.</p></div><div><h3>Results</h3><p>Overall, 454 participants were enrolled and received 1 dose of study vaccine or placebo (Cohort 1, <em>n</em> = 226; Cohort 2, <em>n</em> = 124; Cohort 3, <em>n</em> = 104). No substantial differences in measured immune responses were observed between lower or higher Ad26.RSV.preF doses compared with Ad26.RSV.preF 1.0 × 10<sup>11</sup> vp across all postvaccination time points. All Ad26.RSV.preF doses between 3.7 × 10<sup>9</sup> vp and 1.6 × 10<sup>11</sup> vp were well tolerated, with no safety issues identified.</p></div><div><h3>Conclusions</h3><p>Results of this dose-ranging study may be used to inform the refinement of Ad26.RSV.preF drug product release and stability specifications.</p><p><strong>Clinical Trial Registration:</strong> <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> Identifier: <span><span>NCT04453202</span><svg><path></path></svg></span></p></div>","PeriodicalId":23491,"journal":{"name":"Vaccine","volume":null,"pages":null},"PeriodicalIF":4.5000,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0264410X24009551/pdfft?md5=197b57c1fb3d7e4b12fe489543013453&pid=1-s2.0-S0264410X24009551-main.pdf","citationCount":"0","resultStr":"{\"title\":\"Immunogenicity and safety of different dose levels of Ad26.RSV.preF/RSV preF protein vaccine in adults aged 60 years and older: A randomized, double-blind, placebo-controlled, phase 2a study\",\"authors\":\"\",\"doi\":\"10.1016/j.vaccine.2024.126273\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><h3>Background</h3><p>Respiratory syncytial virus (RSV) can cause severe illness in older adults. A combination vaccine containing Ad26.RSV.preF and purified recombinant RSV preF protein has previously demonstrated efficacy and tolerability in older adults. We report results of a dose-ranging study to determine immunogenicity and safety of different doses of the Ad26.RSV.preF component in the combined Ad26.RSV.preF/RSV preF protein vaccine to support Ad26.RSV.preF drug product release and stability specifications.</p></div><div><h3>Methods</h3><p>In this randomized, double-blind, placebo-controlled, phase 2a study, adults aged ≥60 years in good or stable health were randomly assigned within 1 of 3 cohorts to receive either placebo or Ad26.RSV.preF/RSV preF protein, composed of different doses of Ad26.RSV.preF with a fixed dose of RSV preF protein (150 μg). Ad26.RSV.preF doses in Cohort 1 (4 dose-down groups) ranged from 3.7 × 10<sup>9</sup> to 1.0 × 10<sup>11</sup> viral particles (vp). Doses in Cohorts 2 and 3 (2 dose-up groups, each) ranged from 1.0 to 1.6 × 10<sup>11</sup> vp. Primary endpoints were immunogenicity (RSV preF protein antibody titers) for Cohort 1 and safety (solicited local and systemic adverse events [AEs] and unsolicited AEs) for Cohorts 2 and 3. Immunogenicity analyses (RSV preF protein antibody titers, RSV A2 neutralizing antibodies, and RSV-F–specific interferon-γ enzyme-linked immunosorbent spot) were performed on the day of vaccination and 14 days, 3 months, and 6 months postvaccination. Safety was monitored from vaccination until study end.</p></div><div><h3>Results</h3><p>Overall, 454 participants were enrolled and received 1 dose of study vaccine or placebo (Cohort 1, <em>n</em> = 226; Cohort 2, <em>n</em> = 124; Cohort 3, <em>n</em> = 104). No substantial differences in measured immune responses were observed between lower or higher Ad26.RSV.preF doses compared with Ad26.RSV.preF 1.0 × 10<sup>11</sup> vp across all postvaccination time points. All Ad26.RSV.preF doses between 3.7 × 10<sup>9</sup> vp and 1.6 × 10<sup>11</sup> vp were well tolerated, with no safety issues identified.</p></div><div><h3>Conclusions</h3><p>Results of this dose-ranging study may be used to inform the refinement of Ad26.RSV.preF drug product release and stability specifications.</p><p><strong>Clinical Trial Registration:</strong> <span><span>ClinicalTrials.gov</span><svg><path></path></svg></span> Identifier: <span><span>NCT04453202</span><svg><path></path></svg></span></p></div>\",\"PeriodicalId\":23491,\"journal\":{\"name\":\"Vaccine\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.5000,\"publicationDate\":\"2024-09-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.sciencedirect.com/science/article/pii/S0264410X24009551/pdfft?md5=197b57c1fb3d7e4b12fe489543013453&pid=1-s2.0-S0264410X24009551-main.pdf\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Vaccine\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0264410X24009551\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"IMMUNOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Vaccine","FirstCategoryId":"3","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0264410X24009551","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"IMMUNOLOGY","Score":null,"Total":0}
Immunogenicity and safety of different dose levels of Ad26.RSV.preF/RSV preF protein vaccine in adults aged 60 years and older: A randomized, double-blind, placebo-controlled, phase 2a study
Background
Respiratory syncytial virus (RSV) can cause severe illness in older adults. A combination vaccine containing Ad26.RSV.preF and purified recombinant RSV preF protein has previously demonstrated efficacy and tolerability in older adults. We report results of a dose-ranging study to determine immunogenicity and safety of different doses of the Ad26.RSV.preF component in the combined Ad26.RSV.preF/RSV preF protein vaccine to support Ad26.RSV.preF drug product release and stability specifications.
Methods
In this randomized, double-blind, placebo-controlled, phase 2a study, adults aged ≥60 years in good or stable health were randomly assigned within 1 of 3 cohorts to receive either placebo or Ad26.RSV.preF/RSV preF protein, composed of different doses of Ad26.RSV.preF with a fixed dose of RSV preF protein (150 μg). Ad26.RSV.preF doses in Cohort 1 (4 dose-down groups) ranged from 3.7 × 109 to 1.0 × 1011 viral particles (vp). Doses in Cohorts 2 and 3 (2 dose-up groups, each) ranged from 1.0 to 1.6 × 1011 vp. Primary endpoints were immunogenicity (RSV preF protein antibody titers) for Cohort 1 and safety (solicited local and systemic adverse events [AEs] and unsolicited AEs) for Cohorts 2 and 3. Immunogenicity analyses (RSV preF protein antibody titers, RSV A2 neutralizing antibodies, and RSV-F–specific interferon-γ enzyme-linked immunosorbent spot) were performed on the day of vaccination and 14 days, 3 months, and 6 months postvaccination. Safety was monitored from vaccination until study end.
Results
Overall, 454 participants were enrolled and received 1 dose of study vaccine or placebo (Cohort 1, n = 226; Cohort 2, n = 124; Cohort 3, n = 104). No substantial differences in measured immune responses were observed between lower or higher Ad26.RSV.preF doses compared with Ad26.RSV.preF 1.0 × 1011 vp across all postvaccination time points. All Ad26.RSV.preF doses between 3.7 × 109 vp and 1.6 × 1011 vp were well tolerated, with no safety issues identified.
Conclusions
Results of this dose-ranging study may be used to inform the refinement of Ad26.RSV.preF drug product release and stability specifications.
期刊介绍:
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