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 严重的急性呼吸综合征冠状病毒2（SARS-COV-2），冠状病毒的病毒药物 被指定为大流行呼吸道疾病（WHO -2020）的2019年疾病（Covid -19）已有 全世界感染了超过1.72亿人，并导致超过370万人死亡，其中包括596,000人 美国（2021年6月3日，谁； www.who.int）。 SARS-COV-2疫苗的多阶段3疗效试验 在美国，建筑正在进行或长期随访中，这些研究支持了3个紧急情况 使用授权（EUAS）进行疫苗。但是，后勤和制造障碍是限制的 任何一次可用的疫苗数量。此外，变异菌株的出现已经增加 人们对当前疫苗实现的免疫力和保护广度的担忧。谁圣人和 CDC ACIP已将混合时间表的安全性和免疫原性确定为关键而直接的 研究优先级以告知有关使用混合时间表的政策。 了解延迟增强疫苗的安全性，耐受性和免疫原性 EUA Prime剂量方案后给予的异源平台或变体尖峰谱系可能 大大扩展了在人群水平上对SARS-COV-2免疫的能力 循环应变并提高保护的宽度和耐用性。异源提升策略 还将提供一个彻底评估先天，细胞和体液免疫反应的机会 使用非常相似的免疫原子从多个素数提升组合引起，利用mRNA， 腺病毒量和基于蛋白质的平台。由于新的免疫原生产以密切匹配 新兴的变体，这些基本数据将是评估未来变体和异源的关键 促进策略。该阶段1/2临床试验将评估不同的安全性和免疫原性 接受EUA疫苗的人的异源延迟剂量（增强）（要么在参与之前 该试验，或作为此试验的一部分）。