A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection.

A single dose, BCG-adjuvanted COVID-19 vaccine provides sterilising immunity against SARS-CoV-2 infection.
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DOI:
10.1038/s41541-021-00406-4
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发表时间:
2021-11-30
期刊:
影响因子:
9.2
通讯作者:
Triccas JA
Triccas JA
中科院分区:
医学1区
文献类型:
--
作者:
Counoupas C;Johansen MD;Stella AO;Nguyen DH;Ferguson AL;Aggarwal A;Bhattacharyya ND;Grey A;Hutchings O;Patel K;Siddiquee R;Stewart EL;Feng CG;Hansbro NG;Palendira U;Steain MC;Saunders BM;Low JKK;Mackay JP;Kelleher AD;Britton WJ;Turville SG;Hansbro PM;Triccas JA

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要在全球范围内控制COVID-19,就需要能够广泛获得有效对抗SARS-CoV-2变异体的疫苗。在这份报告中,我们利用现有结核病疫苗卡介苗(BCG)的免疫刺激特性,提供一种具有有效SARS-CoV-2特异性保护性免疫的疫苗接种方案。BCG与稳定的三聚体形式的SARS-CoV-2刺突抗原的组合促进了接种小鼠血液中病毒特异性IgG抗体的快速发展,通过添加明矾进一步增强。该疫苗制剂BCG:CoVac诱导高滴度SARS-CoV-2中和抗体(NAbs)和疫苗特异性T细胞的Th 1偏向性细胞因子释放,这与局部淋巴结中T滤泡辅助细胞的早期出现和疫苗接种后抗原特异性血浆B细胞水平升高相关。K18-hACE 2小鼠接种单剂量BCG:CoVac疫苗后,SARS-CoV-2攻击几乎完全消除了疾病,感染动物的肺部炎症最小,检测不到病毒。加强BCG:用异源疫苗接种CoVac-primed小鼠进一步增加了SARS-CoV-2特异性抗体应答,有效地中和了B.1.1.7和B.1.351 SARS-CoV-2变异体。这些发现证明了基于BCG的疫苗接种在预防全球流行的主要SARS-CoV-2变异方面的潜力。
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.
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影响因子: 32.4
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