University of Washington Vaccine and Treatment Evaluation Unit - DMID 21-0012

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 2019年新冠病毒病（COVID-19）大流行，已感染全球超过1.26亿人，并导致超过100万人死亡。 2.7 100万例死亡，其中美国超过54.8万例（2021年3月27日，世卫组织; www.who.int）。多 SARS-CoV-2疫苗结构的3期有效性试验正在美国进行或长期随访， 这些研究支持了3项COVID疫苗的紧急使用授权（EUA）。的 变异株的出现引起了人们对免疫和保护范围的关注， 目前的疫苗。WHO SAGE和CDC ACIP已经确定了混合疫苗的安全性和免疫原性。 作为一个关键的和直接的研究优先事项，通知政策的使用混合时间表。 了解使用异源平台的加强疫苗的安全性、耐受性和免疫原性， 在EUA初次给药后给予的同源或变体加标谱系是 为公共卫生决策提供所需信息。异源加强策略还将提供一种免疫抑制剂。 有机会彻底评估先天性，细胞和体液免疫反应引起的多重 使用非常相似的免疫原，利用mRNA，腺病毒载体和蛋白质， 基于平台。随着新疫苗的生产出现变异，这些基础数据将是关键 对未来变体和异源初免-加强策略的评估。该1/2期临床试验将 评价不同异源延迟剂量（加强）在以下患者中的安全性和免疫原性： 接受EUA疫苗（在参与本试验之前或作为本试验的一部分）。

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2), causative agent of the coronavirus disease of 2019 (COVID-19) pandemic, has infected over 126 million people worldwide and resulted in over 2.7 million deaths, including > 548,000 in the United States (March 27, 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. 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 boost vaccine using a heterologous platform with the homologous or variant spike lineage administered after an EUA primary dosing is a critical piece of information needed to inform public health decisions. 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 vaccines are manufactured to 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).