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).

总结/摘要 严重急性呼吸道综合征冠状病毒2（SARS-CoV-2），冠状病毒的病原体 被指定为大流行性呼吸道疾病（WHO - 2020）的2019年疾病（COVID-19）， 全世界感染了1.72亿多人，导致370多万人死亡，其中包括超过596，000人， 美国（2021年6月3日，WHO; www.who.int）。SARS-CoV-2疫苗的多项3期有效性试验 在美国，这些结构正在进行或处于长期随访中，这些研究支持了3种紧急情况， COVID疫苗的使用授权（EUA）。然而，物流和制造障碍是有限的 在任何时候都可以获得的疫苗数量。此外，变异株的出现提高了 对目前疫苗所实现的免疫和保护广度的关切。WHO SAGE和 CDC ACIP已经确定了混合方案的安全性和免疫原性， 研究优先事项，为使用混合时间表的政策提供信息。 了解包含以下物质的延迟加强疫苗的安全性、耐受性和免疫原性： 在EUA初始给药方案后施用的异源平台或变体刺突谱系可 极大地扩展了在群体水平上对SARS-CoV-2免疫的能力，诱导对变异株的免疫， 循环应变和改善的广度和持久性的保护。异源加强策略 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， 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， 新出现的变异，这些基础数据将是评估未来变异和异源的关键。 prime-boost策略。这项1/2期临床试验将评估不同的免疫抑制剂的安全性和免疫原性。 在接受EUA疫苗的受试者中，异源延迟剂量（加强）（在参与 或作为本试验的一部分）。