Recombinant BCG-based SARS-CoV-2 vaccine

摘要 新冠肺炎大流行造成的人道主义和经济影响的规模将高度优先放在 制定预防和治疗对策，以更好地控制SARS-CoV-2感染。其中 NIAID新冠肺炎研究战略规划中列出的优先事项是需要推行多种战略 开发一种对包括老年人在内的终身有效的新冠肺炎疫苗。 最近的流行病学研究强调了牛分枝杆菌卡介苗(唯一被批准的 结核病预防疫苗)，通过非特异性免疫缓解结核病的流行和严重程度 新冠肺炎的症状。事实上，自20世纪60年代以来，卡介苗接种一直被认为是非特指的改善 对多种病毒病原体的免疫降低了新生儿、儿童的发病率和死亡率 还有老年人。卡介苗的其他独特特性使其成为重组疫苗的首选平台 异源抗原的表达包括它能产生长时间的CD4+和CD8+T细胞 反应，其天然佐剂特性，其显著的安全性记录(迄今已给予50亿剂)和 这是一个事实，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新冠肺炎研究努力，以 制备表达SARS-CoV-2免疫原的重组卡介苗(RBCG)(Aim 1)，并对重组卡介苗(RBCG) 重组卡介苗在SARS-CoV-2攻击动物模型中的免疫原性和保护作用 感染(目标2)。 我们推测，SARS-CoV-2非特异性免疫的诱导与适应性 经验证的SARS-CoV-2抗原的重组表达诱导的免疫应答将产生rBCG- 基于新冠肺炎的疫苗在所有年龄段的人中都具有持久的保护性免疫力。在这方面取得了成功 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.