Implementing Vaccine and Treatment Evaluation Unit (VTEU) Clinical Site: DMID 21-0012 Mix and Match

实施疫苗和治疗评估单位 (VTEU) 临床站点：DMID 21-0012 混合搭配

• 批准号: 10424839
• 负责人: Karen L. Kotloff
• 金额: $ 112.15万
• 依托单位: UNIVERSITY OF MARYLAND BALTIMORE
• 依托单位国家: 美国
• 财政年份: 2021
• 资助国家: 美国
• 起止时间: 2021-08-10 至 2025-11-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10424839
• 关键词: 2019-nCoV; Adenovirus Vector; Adverse event; Antigens; B-Lymphocytes; COVID-19; COVID-19 pandemic; COVID-19 vaccine; Centers for Disease Control and Prevention (U.S.); Cessation of life; Data; Dose; Evaluation; FDA Emergency Use Authorization; Foundations; Future; Immune response; Immunity; Immunize; Knowledge; Logistics; Longevity; Longterm Follow-up; Messenger RNA; Persons; Phase; Phase I/II Clinical Trial; Policies; Population; Proteins; Public Health; Regimen; Research Design; Research Priority; Safety; Sampling; Schedule; Stretching; T cell response; Time; United States; Vaccinated; Vaccination; Vaccines; Variant; base; booster vaccine; clinical research site; cohort; coronavirus disease; efficacy trial; immunogenicity; improved; novel vaccines; pandemic disease; phase 1 designs; prospective; respiratory; vaccine access; vaccine delivery

Summary/Abstract The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), causative agent of the coronavirus disease of 2019 (COVID-19) which was designated as a pandemic respiratory illness (WHO - 2020), has infected over 172 million people worldwide and resulted in over 3.7 million deaths, including > 596,000 in the United States (June 3, 2021, WHO; www.who.int). Multiple Phase 3 efficacy trials of SARS-CoV-2 vaccine constructs are underway or in long-term follow-up in the U.S, and these studies have supported 3 Emergency Use Authorizations (EUAs) for COVID vaccines. However, logistical and manufacturing obstacles are limiting the number of vaccines available at any one time. Further, the emergence of variant strains has raised concerns about the breadth of immunity and protection achieved by the current vaccines. WHO SAGE and CDC ACIP have identified the safety and immunogenicity of mixed schedules as a critical and immediate research priority to inform policy on the use of mixed schedules. Knowledge of the safety, tolerability, and immunogenicity of a delayed boost vaccine incorporating a heterologous platform or variant spike lineage administered following EUA prime dosing regimens may greatly stretch the ability to immunize against SARS-CoV-2 at a population level, induce immunity to variant circulating strains and improve upon the breadth and durability of protection. The heterologous boost strategy will also provide an opportunity to thoroughly evaluate innate, cellular, and humoral immune responses elicited from the multiple prime boost combinations using very similar immunogens, utilizing mRNA, adenovirus- vectored, and protein- based platforms. As new immunogens are manufactured to closely match emerging variants, these foundational data will be key to the evaluation of future variant and heterologous prime- boost strategies. This phase 1/2 clinical trial will evaluate the safety and immunogenicity of different heterologous delayed doses (boosts) in those who received an EUA vaccine (either prior to participation in this trial, or as part of this trial).

摘要/摘要 严重急性呼吸系统综合症冠状病毒 2 (SARS-CoV-2)，冠状病毒的病原体 2019 年疾病 (COVID-19) 被指定为大流行性呼吸道疾病 (WHO - 2020)， 全球感染人数超过 1.72 亿，导致超过 370 万人死亡，其中美国死亡人数超过 596,000 人 美国（2021 年 6 月 3 日，世界卫生组织；www.who.int）。 SARS-CoV-2 疫苗的多项 3 期功效试验 美国正在构建或进行长期随访，这些研究支持了 3 个紧急情况 使用新冠疫苗授权 (EUA)。然而，物流和制造障碍限制了 任一时间可获得的疫苗数量。此外，变异菌株的出现也引发了 对当前疫苗所实现的免疫和保护范围的担忧。世界卫生组织圣贤和 CDC ACIP 已将混合方案的安全性和免疫原性确定为关键且紧迫的问题 研究优先事项，为混合时间表的使用政策提供信息。 了解延迟加强疫苗的安全性、耐受性和免疫原性 EUA 初始给药方案后施用的异源平台或变体尖峰谱系可能 极大地扩展了人群水平上针对 SARS-CoV-2 的免疫能力，诱导对变异体的免疫力 传播菌株并提高保护的广度和持久性。异源增强策略 还将提供彻底评估先天、细胞和体液免疫反应的机会 使用非常相似的免疫原，利用 mRNA，从多重初免加强组合中引发， 腺病毒载体和基于蛋白质的平台。随着新的免疫原被制造出来以紧密匹配 新兴变异，这些基础数据将是评估未来变异和异源的关键 启动-促进策略。本次1/2期临床试验将评估不同药物的安全性和免疫原性 接受 EUA 疫苗的人（在参加疫苗接种之前）进行异源延迟剂量（加强） 本试验，或作为本试验的一部分）。