High-Titer Neutralizing Antibodies against the SARS-CoV-2 Delta Variant Induced by Alhydroxyquim-II-Adjuvanted Trimeric Spike Antigens.
High-Titer Neutralizing Antibodies against the SARS-CoV-2 Delta Variant Induced by Alhydroxyquim-II-Adjuvanted Trimeric Spike Antigens.
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DOI：
10.1128/spectrum.01695-21
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发表时间：
2022-02-23
影响因子：
3.7
通讯作者：
Triccas JA
中科院分区：
文献类型：
--
作者：
Counoupas C;Pino P;Stella AO;Ashley C;Lukeman H;Bhattacharyya ND;Tada T;Anchisi S;Metayer C;Martinis J;Aggarwal A;Dcosta BM;Britton WJ;Kint J;Wurm MJ;Landau NR;Steain M;Turville SG;Wurm FM;David SA;Triccas JA
全球控制COVID-19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。在这份报告中，我们描述了一种含佐剂的亚单位候选疫苗，它在多种动物模型中提供了升高的、持续的和交叉变异的SARS-CoV-2中和抗体（NAbs）。Alhydroxiquim-II是一种Toll样受体（TLR）7/8小分子激动剂，化学吸附在氢氧化铝（Alhydrogel）上。用Alhydroxiquim-II与稳定的三聚体形式的SARS-CoV-2刺突蛋白（称为CoVac-II）组合的疫苗接种导致小鼠中的高滴度NAb，在8个月的时间内应答没有衰减。来自CoVac-II免疫小鼠、马和兔血清的NAb对SARS-CoV-2变体具有广泛中和作用。用来自β变体的佐剂刺突蛋白加强长期CoVac-II免疫小鼠显著增加了针对多种SARS-CoV-2变体的NAb滴度水平;值得注意的是，观察到针对Delta变体的高滴度。这些数据强烈支持Alhydroxiquim-II-佐剂刺突蛋白的临床评估，以防止SARS-CoV-2变异的关注。重要性目前迫切需要安全的下一代COVID-19疫苗，对SARS-CoV-2变种具有高保护效力，并且可以大规模生产。我们描述了一种候选疫苗（CoVac-II），该疫苗基于在优化的、可扩展的和化学定义的生产工艺中生产的稳定的三聚体刺突抗原。CoVac-II在小鼠接种疫苗后表现出强烈和持久的免疫力，并且在多种动物模型中具有高度免疫原性，包括兔和马。我们进一步表明，使用来自β变体的重组刺突抗原可以增强先前的免疫力;重要的是，来自增强小鼠的血浆在体外有效地中和多种SARS-CoV-2变体，包括Delta。CoVac-II的强体液和Th 1偏好免疫原性是通过使用Alhydroxiquim-II（AHQ-II）驱动的，Alhydroxiquim-II是授权疫苗中的第一种佐剂，通过双重Toll样受体（TLR）7和TLR 8途径起作用，作为Covaxin疫苗的一部分。我们的数据表明，AHQ-II/刺突蛋白组合可以构成安全、负担得起且可大规模生产的COVID-19疫苗，用于全球分销。
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 neutralizing antibodies (NAbs) in multiple animal models. Alhydroxiquim-II is a Toll-Like Receptor (TLR) 7/8 small-molecule agonist chemisorbed on aluminum hydroxide (Alhydrogel). Vaccination with Alhydroxiquim-II combined with a stabilized, trimeric form of the SARS-CoV-2 spike protein (termed CoVac-II) resulted in high-titer 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 neutralizing 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 titers against multiple SARS-CoV-2 variants; notably, high titers 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. IMPORTANCE There is an urgent need for next-generation COVID-19 vaccines that are safe, demonstrate high protective efficacy against SARS-CoV-2 variants and can be manufactured at scale. We describe a vaccine candidate (CoVac-II) that is based on stabilized, trimeric spike antigen produced in an optimized, scalable and chemically defined production process. CoVac-II demonstrates strong and persistent immunity after vaccination of mice, and is highly immunogenic in multiple animal models, including rabbits and horses. We further show that prior immunity can be boosted using a recombinant spike antigen from the Beta variant; importantly, plasma from boosted mice effectively neutralize multiple SARS-CoV-2 variants in vitro, including Delta. The strong humoral and Th1-biased immunogenicity of CoVac-II is driven by use of Alhydroxiquim-II (AHQ-II), the first adjuvant in an authorized vaccine that acts through the dual Toll-like receptor (TLR)7 and TLR8 pathways, as part of the Covaxin vaccine. Our data suggest AHQ-II/spike protein combinations could constitute safe, affordable, and mass-manufacturable COVID-19 vaccines for global distribution.
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DOI：
10.1056/nejmoa2109072
发表时间：
2021-10-14
期刊：
The New England journal of medicine
影响因子：
--
作者：
Bergwerk M;Gonen T;Lustig Y;Amit S;Lipsitch M;Cohen C;Mandelboim M;Levin EG;Rubin C;Indenbaum V;Tal I;Zavitan M;Zuckerman N;Bar-Chaim A;Kreiss Y;Regev-Yochay G
通讯作者：
Regev-Yochay G
影响因子：
3.5
作者：
Pino, Paco;Kint, Joeri;Wurm, Florian M.
通讯作者：
Wurm, Florian M.
DOI：
10.1056/nejmoa2102214
发表时间：
2021-05-20
期刊：
The New England journal of medicine
影响因子：
--
作者：
Madhi SA;Baillie V;Cutland CL;Voysey M;Koen AL;Fairlie L;Padayachee SD;Dheda K;Barnabas SL;Bhorat QE;Briner C;Kwatra G;Ahmed K;Aley P;Bhikha S;Bhiman JN;Bhorat AE;du Plessis J;Esmail A;Groenewald M;Horne E;Hwa SH;Jose A;Lambe T;Laubscher M;Malahleha M;Masenya M;Masilela M;McKenzie S;Molapo K;Moultrie A;Oelofse S;Patel F;Pillay S;Rhead S;Rodel H;Rossouw L;Taoushanis C;Tegally H;Thombrayil A;van Eck S;Wibmer CK;Durham NM;Kelly EJ;Villafana TL;Gilbert S;Pollard AJ;de Oliveira T;Moore PL;Sigal A;Izu A;NGS-SA Group;Wits-VIDA COVID Group
通讯作者：
Wits-VIDA COVID Group
影响因子：
7.3
作者：
Agnolon V;Kiseljak D;Wurm MJ;Wurm FM;Foissard C;Gallais F;Wehrle S;Muñoz-Fontela C;Bellanger L;Correia BE;Corradin G;Spertini F
通讯作者：
Spertini F
DOI：
10.1016/s0140-6736(21)00241-5
发表时间：
2021-02-20
期刊：
Lancet (London, England)
影响因子：
--
作者：
Richmond P;Hatchuel L;Dong M;Ma B;Hu B;Smolenov I;Li P;Liang P;Han HH;Liang J;Clemens R
通讯作者：
Clemens R