Counoupas Claudio, Johansen Matt D, Stella Alberto O, Nguyen Duc H, Ferguson Angela L, Aggarwal Anupriya, Bhattacharyya Nayan D, Grey Alice, Hutchings Owen, Patel Karishma, Siddiquee Rezwan, Stewart Erica L, Feng Carl G, Hansbro Nicole G, Palendira Umaimainthan, Steain Megan C, Saunders Bernadette M, Low Jason K K, Mackay Joel P, Kelleher Anthony D, Britton Warwick J, Turville Stuart G, Hansbro Philip M, Triccas James A
School of Medical Sciences, Faculty of Medicine and Health, The University of Sydney, Camperdown, NSW, Australia.
Tuberculosis Research Program at the Centenary Institute, The University of Sydney, Sydney, NSW, Australia.
NPJ Vaccines. 2021 Nov 30;6(1):143. doi: 10.1038/s41541-021-00406-4.
Global control of COVID-19 requires broadly accessible vaccines that are effective against SARS-CoV-2 variants. In this report, we exploit the immunostimulatory properties of bacille Calmette-Guérin (BCG), the existing tuberculosis vaccine, to deliver a vaccination regimen with potent SARS-CoV-2-specific protective immunity. Combination of BCG with a stabilised, trimeric form of SARS-CoV-2 spike antigen promoted rapid development of virus-specific IgG antibodies in the blood of vaccinated mice, that was further augmented by the addition of alum. This vaccine formulation, BCG:CoVac, induced high-titre SARS-CoV-2 neutralising antibodies (NAbs) and Th1-biased cytokine release by vaccine-specific T cells, which correlated with the early emergence of T follicular helper cells in local lymph nodes and heightened levels of antigen-specific plasma B cells after vaccination. Vaccination of K18-hACE2 mice with a single dose of BCG:CoVac almost completely abrogated disease after SARS-CoV-2 challenge, with minimal inflammation and no detectable virus in the lungs of infected animals. Boosting BCG:CoVac-primed mice with a heterologous vaccine further increased SARS-CoV-2-specific antibody responses, which effectively neutralised B.1.1.7 and B.1.351 SARS-CoV-2 variants of concern. These findings demonstrate the potential for BCG-based vaccination to protect against major SARS-CoV-2 variants circulating globally.
全球控制新冠病毒需要广泛可得且对新冠病毒变异株有效的疫苗。在本报告中，我们利用现有的结核病疫苗卡介苗（BCG）的免疫刺激特性，来提供一种具有强大的新冠病毒特异性保护性免疫的疫苗接种方案。卡介苗与稳定的三聚体形式的新冠病毒刺突抗原相结合，促进了接种疫苗小鼠血液中病毒特异性IgG抗体的快速产生，添加明矾后这种产生进一步增强。这种疫苗配方，即卡介苗：CoVac，诱导了高滴度的新冠病毒中和抗体（NAbs）以及疫苗特异性T细胞偏向Th1的细胞因子释放，这与局部淋巴结中T滤泡辅助细胞的早期出现以及接种疫苗后抗原特异性浆B细胞水平的提高相关。用单剂量的卡介苗：CoVac对K18-hACE2小鼠进行接种，在新冠病毒攻击后几乎完全消除了疾病，感染动物的肺部炎症轻微且未检测到病毒。用异源疫苗加强接种卡介苗：CoVac初免的小鼠，进一步增加了新冠病毒特异性抗体反应，这种反应有效地中和了值得关注的B.1.1.7和B.1.351新冠病毒变异株。这些发现证明了基于卡介苗的疫苗接种对全球流行的主要新冠病毒变异株具有保护作用的潜力。
