Recombinant BCG-based SARS-CoV-2 vaccine

总结 2019冠状病毒病大流行造成的人道主义和经济影响规模之大， 制定预防和治疗对策，以更好地控制SARS-CoV-2感染。之间 NIAID战略计划中列出的COVID-19研究的优先事项是需要采取多种战略 开发一种在整个生命周期内有效的COVID-19疫苗，包括老年人。 最近的流行病学研究强调了牛分枝杆菌BCG（唯一批准的 预防结核病的疫苗），以通过非特异性免疫减轻结核病的流行和严重程度。 COVID-19的症状事实上，自20世纪60年代以来，已知BCG疫苗接种可以非特异性地改善 对一些病毒病原体的免疫力，从而降低新生儿、儿童 和老年人。BCG的其他独特属性使其成为重组疫苗的首选疫苗平台 异源抗原的表达包括它可以产生持久的CD 4+和CD 8 + T细胞 反应，其天然佐剂特性，其显着的安全记录（迄今为止给予超过50亿剂量）和 事实上，它是容易和廉价的大规模生产。 该项目的目标是利用科罗拉多州立大学正在进行的COVID-19研究工作， 制备表达SARS-CoV-2免疫原的重组BCG（rBCG）菌株（Aim 1），并评估 重组卡介苗免疫原性及对SARS-CoV-2感染动物保护作用 感染（目标2）。 我们假设，诱导针对SARS-CoV-2的非特异性免疫与适应性免疫相结合， 由经验证的SARS-CoV-2抗原的重组表达引发的免疫应答将产生rBCG-1， 基于COVID-19的疫苗，为所有年龄段的人提供持久的保护性免疫力。胜任这 这种方法可以迅速提供廉价、安全和可在全球部署的疫苗。

Summary The scale of the humanitarian and economic impact of the COVID-19 pandemic places a high priority on the development of prophylactic and therapeutic countermeasures to better control SARS-CoV-2 infections. Among the priorities listed in the NIAID Strategic Plan for COVID-19 research is the need to pursue multiple strategies to develop a COVID-19 vaccine efficacious across the lifespan, including in the elderly. Recent epidemiologic studies have highlighted the potential for Mycobacterium bovis BCG (the only approved vaccine for TB prevention) to mitigate through non-specific immunity the prevalence and severity of the symptoms of COVID-19. Indeed, BCG vaccination has been known since the 1960s to non-specifically improve immunity against a number of viral pathogens resulting in reduced morbidity and mortality in neonates, children and the elderly. Other unique attributes of BCG that make it a vaccine platform of choice for the recombinant expression of heterologous antigens include the fact that it can produce long-lasting CD4+ and CD8+ T cell responses, its natural adjuvant properties, its remarkable safety record (> 5 billion doses given to date) and the fact that it is easy and inexpensive to mass-produce. The goal of this project is to leverage ongoing COVID-19 research efforts at Colorado State University to generate recombinant BCG (rBCG) strains expressing SARS-CoV-2 immunogens (Aim 1) and to assess the immunogenicity and protective efficacy of rBCG in an established animal challenge model of SARS-CoV-2 infection (Aim 2). We hypothesize that the induction of non-specific immunity against SARS-CoV-2 combined with the adaptive immune responses elicited by the recombinant expression of validated SARS-CoV-2 antigens will yield rBCG- based COVID-19 vaccines conferring long-lasting protective immunity in people of all ages. Success in this approach could rapidly deliver an inexpensive, safe and globally deployable vaccine.