Neutralising antibodies against the SARS-CoV-2 Delta variant induced by Alhydroxyquim-II-adjuvanted trimeric spike antigens
Neutralising antibodies against the SARS-CoV-2 Delta variant induced by Alhydroxyquim-II-adjuvanted trimeric spike antigens
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Aloxyquim-II 佐剂三聚刺突抗原诱导的针对 SARS-CoV-2 Delta 变体的中和抗体
DOI：
10.1101/2021.08.18.456891
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发表时间：
2021
期刊：
影响因子：
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通讯作者：
J. Triccas
中科院分区：
文献类型：
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作者：
C. Counoupas;P. Pino;A. Stella;C. Ashley;H. Lukeman;Nayan D. Bhattacharyya;Takuya Tada;Stéphanie Anchisi;Charles Metayer;Jacopo Martinis;A. Aggarwal;Belinda M. Dcosta;J. Kint;Maria J. Wurm;N. Landau;M. Steain;S. Turville;F. Wurm;S. David;J. Triccas
COVID-19的全球控制将需要部署能够诱导针对SARS-CoV-2变体的长期保护性免疫的疫苗。在本报告中，我们描述了一种佐剂亚基候选疫苗，可在多种动物模型中提供升高、持续和交叉变异的SARS-CoV-2中和抗体（nab）。Alhydroxiquim-II是一种化学吸附在氢氧化铝上的TLR7/8小分子激动剂。用alhydroxiquin - ii与稳定的三聚体形式的SARS-CoV-2刺突蛋白（称为CoVac-II）联合接种疫苗，在小鼠中产生高滴度的抗体，在8个月的时间内反应没有衰减。covac - ii免疫小鼠、马和兔血清中的nab对SARS-CoV-2变体具有广泛的中和作用。用β变异的佐剂刺突蛋白刺激长期免疫covac - ii的小鼠，可显著提高针对多种SARS-CoV-2变异的NAb滴度水平；观察到对Delta变异的显著高滴度。这些数据有力地支持了alhydroxiquin - ii佐剂刺突蛋白对SARS-CoV-2变体的临床评估。
Global control of COVID-19 will require the deployment of vaccines capable of inducing long-term protective immunity against SARS-CoV-2 variants. In this report, we describe an adjuvanted subunit candidate vaccine that affords elevated, sustained and cross-variant SARS-CoV-2 neutralising antibodies (NAbs) in multiple animal models. Alhydroxiquim-II is a TLR7/8 small-molecule agonist chemisorbed on aluminium hydroxide. Vaccination with Alhydroxiquim-II combined with a stabilized, trimeric form of the SARS-CoV-2 spike protein (termed CoVac-II) resulted in high-titre NAbs in mice, with no decay in responses over an 8-month period. NAbs from sera of CoVac-II-immunized mice, horses and rabbits were broadly neutralising against SARS-CoV-2 variants. Boosting long-term CoVac-II-immunized mice with adjuvanted spike protein from the Beta variant markedly increased levels of NAb titres against multiple SARS-CoV-2 variants; notably high titres against the Delta variant were observed. These data strongly support the clinical assessment of Alhydroxiquim-II-adjuvanted spike proteins to protect against SARS-CoV-2 variants of concern.