Effect of priming interval on reactogenicity, peak immunological response, and waning after homologous and heterologous COVID-19 vaccine schedules: exploratory analyses of Com-COV, a randomised control trial,The Lancet Respiratory Medicine

当前位置： X-MOL 学术 › Lancet Respir. Med. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Effect of priming interval on reactogenicity, peak immunological response, and waning after homologous and heterologous COVID-19 vaccine schedules: exploratory analyses of Com-COV, a randomised control trial
The Lancet Respiratory Medicine ( IF 38.7 ) Pub Date : 2022-06-09 , DOI: 10.1016/s2213-2600(22)00163-1
Robert H Shaw ₁ , Xinxue Liu ₂ , Arabella S V Stuart ₁ , Melanie Greenland ₂ , Parvinder K Aley ₂ , Nick J Andrews ₃ , J Claire Cameron ₄ , Sue Charlton ₅ , Elizabeth A Clutterbuck ₂ , Andrea M Collins ₆ , Wanwisa Dejnirattisai ₇ , Tanya Dinesh ₂ , Saul N Faust ₈ , Daniela M Ferreira ₆ , Adam Finn ₉ , Christopher A Green ₁₀ , Bassam Hallis ₅ , Paul T Heath ₁₁ , Helen Hill ₆ , Teresa Lambe ₁₂ , Rajeka Lazarus ₁₃ , Vincenzo Libri ₁₄ , Fei Long ₂ , Yama F Mujadidi ₂ , Emma L Plested ₂ , Ella R Morey ₂ , Samuel Provstgaard-Morys ₂ , Maheshi N Ramasamy ₁ , Mary Ramsay ₁₅ , Robert C Read ₈ , Hannah Robinson ₂ , Gavin R Screaton ₁₆ , Nisha Singh ₂ , David P J Turner ₁₇ , Paul J Turner ₁₈ , Iason Vichos ₂ , Laura L Walker ₂ , Rachel White ₂ , Jonathan S Nguyen-Van-Tam ₁₉ , Matthew D Snape ₂₀ ,

Affiliation

Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Department of Infection, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK.
Immunisation and Countermeasures Division, National Infection Service, UK Health Security Agency, London, UK; 3Statistics, Modelling and Economics Department, UK Health Security Agency, London, UK.
Public Health Scotland, Glasgow-Edinburgh, Scotland, UK.
UK Health Security Agency, Porton Down, Salisbury, UK.
Liverpool Vaccine Group, Department of Clinical Sciences, Liverpool School of Tropical Medicine, Liverpool, UK.
Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK.
NIHR Southampton Clinical Research Facility and Biomedical Research Centre, University Hospital Southampton NHS Foundation Trust, Southampton, UK; Faculty of Medicine and Institute for Life Sciences, University of Southampton, Southampton, UK.
Bristol Vaccine Centre, Schools of Population Health Sciences and Cellular and Molecular Medicine, University of Bristol, Bristol, UK.
NIHR-Wellcome Trust Clinical Research Facility, University Hospitals Birmingham NHS Foundation Trust, Birmingham, UK.
The Vaccine Institute, St George's University of London, London, UK.
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Chinese Academy of Medical Science Oxford Institute, University of Oxford, Oxford, UK.
North Bristol NHS Trust, Bristol, UK.
NIHR UCLH Clinical Research Facility and NIHR UCLH Biomedical Research Centre, University College London Hospitals NHS Foundation Trust, London, UK.
Immunisation and Countermeasures Division, National Infection Service, UK Health Security Agency, London, UK.
Wellcome Centre for Human Genetics, Nuffield Department of Medicine, University of Oxford, Oxford, UK; Chinese Academy of Medical Science Oxford Institute, University of Oxford, Oxford, UK.
School of Life Sciences, University of Nottingham, and Department of Microbiology, Nottingham University Hospitals NHS Trust, Nottingham, UK.
National Heart & Lung Institute, Imperial College London, London, UK.
Division of Epidemiology and Public Health, University of Nottingham School of Medicine, Nottingham, UK.
Oxford Vaccine Group, Department of Paediatrics, University of Oxford, Oxford, UK; Oxford NIHR-Biomedical Research Centre, Oxford University Hospitals NHS Foundation Trust, Oxford, UK.

Background

Priming COVID-19 vaccine schedules have been deployed at variable intervals globally, which might influence immune persistence and the relative importance of third-dose booster programmes. Here, we report exploratory analyses from the Com-COV trial, assessing the effect of 4-week versus 12-week priming intervals on reactogenicity and the persistence of immune response up to 6 months after homologous and heterologous priming schedules using the vaccines BNT162b2 (tozinameran, Pfizer/BioNTech) and ChAdOx1 nCoV-19 (AstraZeneca).

Methods

Com-COV was a participant-masked, randomised immunogenicity trial. For these exploratory analyses, we used the trial's general cohort, in which adults aged 50 years or older were randomly assigned to four homologous and four heterologous vaccine schedules using BNT162b2 and ChAdOx1 nCoV-19 with 4-week or 12-week priming intervals (eight groups in total). Immunogenicity analyses were done on the intention-to-treat (ITT) population, comprising participants with no evidence of SARS-CoV-2 infection at baseline or for the trial duration, to assess the effect of priming interval on humoral and cellular immune response 28 days and 6 months post-second dose, in addition to the effects on reactogenicity and safety. The Com-COV trial is registered with the ISRCTN registry, 69254139 (EudraCT 2020–005085–33).

Findings

Between Feb 11 and 26, 2021, 730 participants were randomly assigned in the general cohort, with 77–89 per group in the ITT analysis. At 28 days and 6 months post-second dose, the geometric mean concentration of anti-SARS-CoV-2 spike IgG was significantly higher in the 12-week interval groups than in the 4-week groups for homologous schedules. In heterologous schedule groups, we observed a significant difference between intervals only for the BNT162b2–ChAdOx1 nCoV-19 group at 28 days. Pseudotyped virus neutralisation titres were significantly higher in all 12-week interval groups versus 4-week groups, 28 days post-second dose, with geometric mean ratios of 1·4 (95% CI 1·1–1·8) for homologous BNT162b2, 1·5 (1·2–1·9) for ChAdOx1 nCoV-19–BNT162b2, 1·6 (1·3–2·1) for BNT162b2–ChAdOx1 nCoV-19, and 2·4 (1·7–3·2) for homologous ChAdOx1 nCoV-19. At 6 months post-second dose, anti-spike IgG geometric mean concentrations fell to 0·17–0·24 of the 28-day post-second dose value across all eight study groups, with only homologous BNT162b2 showing a slightly slower decay for the 12-week versus 4-week interval in the adjusted analysis. The rank order of schedules by humoral response was unaffected by interval, with homologous BNT162b2 remaining the most immunogenic by antibody response. T-cell responses were reduced in all 12-week priming intervals compared with their 4-week counterparts. 12-week schedules for homologous BNT162b2 and ChAdOx1 nCoV-19–BNT162b2 were up to 80% less reactogenic than 4-week schedules.

Interpretation

These data support flexibility in priming interval in all studied COVID-19 vaccine schedules. Longer priming intervals might result in lower reactogenicity in schedules with BNT162b2 as a second dose and higher humoral immunogenicity in homologous schedules, but overall lower T-cell responses across all schedules. Future vaccines using these novel platforms might benefit from schedules with long intervals.

Funding

UK Vaccine Taskforce and National Institute for Health and Care Research.

中文翻译：

同源和异源 COVID-19 疫苗接种后引发间隔对反应原性、峰值免疫反应和减弱的影响：Com-COV 的探索性分析，一项随机对照试验

背景

全球范围内以不同的时间间隔部署了 COVID-19 初免疫苗计划，这可能会影响免疫持久性和第三剂加强计划的相对重要性。在这里，我们报告了 Com-COV 试验的探索性分析，评估了使用疫苗 BNT162b2（tozinameran , Pfizer/BioNTech) 和 ChAdOx1 nCoV-19 (AstraZeneca)。

方法

Com-COV 是一项参与者设盲的随机免疫原性试验。对于这些探索性分析，我们使用了该试验的一般队列，其中 50 岁或以上的成年人被随机分配到四种同源和四种异源疫苗接种方案，使用 BNT162b2 和 ChAdOx1 nCoV-19，启动间隔为 4 周或 12 周（八组总数）。对意向治疗 (ITT) 人群进行了免疫原性分析，包括在基线或试验期间没有 SARS-CoV-2 感染证据的参与者，以评估启动间隔对体液和细胞免疫反应的影响 28第二次给药后的天数和 6 个月，以及对反应原性和安全性的影响。Com-COV 试验已在 ISRCTN 注册中心注册，注册号为 69254139 (EudraCT 2020–005085–33)。

发现

2021 年 2 月 11 日至 26 日期间，730 名参与者被随机分配到一般队列中，在 ITT 分析中每组 77-89 人。在第二次给药后 28 天和 6 个月时，12 周间隔组中抗 SARS-CoV-2 刺突 IgG 的几何平均浓度显着高于同源给药 4 周组。在异源计划组中，我们观察到仅 BNT162b2–ChAdOx1 nCoV-19 组在 28 天时的间隔之间存在显着差异。在第二次给药后 28 天，所有 12 周间隔组的假型病毒中和滴度均显着高于 4 周组，同源 BNT162b2 的几何平均比率为 1·4 (95% CI 1·1–1·8) , 1·5 (1·2–1·9) 对于 ChAdOx1 nCoV-19–BNT162b2, 1·6 (1·3–2·1) 对于 BNT162b2–ChAdOx1 nCoV-19, 2·4 (1·7– 3·2) 对于同源的 ChAdOx1 nCoV-19。在第二次给药后 6 个月，所有八个研究组的抗尖峰 IgG 几何平均浓度均降至第二次给药后 28 天值的 0·17–0·24，只有同源 BNT162b2 显示出略微较慢的衰减调整后分析中的 12 周与 4 周间隔。体液反应的时间表排序不受间隔的影响，同源 BNT162b2 仍然是抗体反应最具免疫原性的。与 4 周对应物相比，所有 12 周启动间隔的 T 细胞反应均有所降低。同源 BNT162b2 和 ChAdOx1 nCoV-19–BNT162b2 的 12 周计划比 4 周计划的反应原性低 80%。在调整后的分析中，只有同源 BNT162b2 在 12 周和 4 周的时间间隔内显示出稍慢的衰减。体液反应的时间表排序不受间隔的影响，同源 BNT162b2 仍然是抗体反应最具免疫原性的。与 4 周对应物相比，所有 12 周启动间隔的 T 细胞反应均有所降低。同源 BNT162b2 和 ChAdOx1 nCoV-19–BNT162b2 的 12 周计划比 4 周计划的反应原性低 80%。在调整后的分析中，只有同源 BNT162b2 在 12 周和 4 周的时间间隔内显示出稍慢的衰减。体液反应的时间表排序不受间隔的影响，同源 BNT162b2 仍然是抗体反应最具免疫原性的。与 4 周对应物相比，所有 12 周启动间隔的 T 细胞反应均有所降低。同源 BNT162b2 和 ChAdOx1 nCoV-19–BNT162b2 的 12 周计划比 4 周计划的反应原性低 80%。