Antigen-adjuvant interactions, stability, and immunogenicity profiles of a SARS-CoV-2 receptor-binding domain (RBD) antigen formulated with aluminum salt and CpG adjuvants.
Antigen-adjuvant interactions, stability, and immunogenicity profiles of a SARS-CoV-2 receptor-binding domain (RBD) antigen formulated with aluminum salt and CpG adjuvants.
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DOI：
10.1080/21645515.2022.2079346
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发表时间：
2022-11-30
影响因子：
4.8
通讯作者：
中科院分区：
文献类型：
--
作者：
低成本、冰箱稳定的新冠肺炎疫苗将促进全球获取，并提高低收入和中等收入国家的疫苗覆盖率。为此，针对SARS-CoV-2刺突蛋白受体结合域(RBD)的基于亚单位的方法仍然具有吸引力。针对RBD的抗体通过阻断病毒与宿主细胞受体ACE2的附着来中和SARS-CoV-2。在这里，酵母生产的重组RBD抗原(RBD-L452K-F490W或RBD-J)由不同的铝盐(Alwater Gel®，AH；AdjuPhos®，AP)和CpG 1018佐剂组合而成。我们评估了抗原-佐剂相互作用对不同RBD-J制剂的稳定性和小鼠免疫原性的影响。当RBD-J对AH和AP分别吸附50%和15%时，CpG的加入使AH结合完全，但对AP的吸附没有改善。对配方RBD-J在不同温度(4，25，37℃)下储存的ACE2竞争ELISA分析表明，AH对RBD-J具有不稳定作用，CpG加剧了这种作用。DSC研究表明，铝盐和CpG佐剂降低了RBD-J的构象稳定性，表明CpG-RBD-J存在直接相互作用。虽然AH+CpG佐剂的RBD-J在体外最不稳定，但在小鼠体内诱导SARS-CoV-2假病毒中和抗体的能力最强。相比之下，用AP+CpG配制的RBD-J表现出最小的抗原-佐剂相互作用，更好的稳定性，但免疫反应不佳。有趣的是，用AH+CpG配制的热应激RBD-J在一次剂量后失去体内效力的情况被助推器废除。我们的发现强调了阐明抗原-佐剂相互作用、储存稳定性和体内性能之间的关键相互关系的重要性，以使稳定和有效的亚单位疫苗的成功配方开发成为可能。
Low-cost, refrigerator-stable COVID-19 vaccines will facilitate global access and improve vaccine coverage in low- and middle-income countries. To this end, subunit-based approaches targeting the receptor-binding domain (RBD) of SARS-CoV-2 Spike protein remain attractive. Antibodies against RBD neutralize SARS-CoV-2 by blocking viral attachment to the host cell receptor, ACE2. Here, a yeast-produced recombinant RBD antigen (RBD-L452K-F490W or RBD-J) was formulated with various combinations of aluminum-salt (Alhydrogel®, AH; AdjuPhos®, AP) and CpG 1018 adjuvants. We assessed the effect of antigen-adjuvant interactions on the stability and mouse immunogenicity of various RBD-J preparations. While RBD-J was 50% adsorbed to AH and <15% to AP, addition of CpG resulted in complete AH binding, yet no improvement in AP adsorption. ACE2 competition ELISA analyses of formulated RBD-J stored at varying temperatures (4, 25, 37°C) revealed that RBD-J was destabilized by AH, an effect exacerbated by CpG. DSC studies demonstrated that aluminum-salt and CpG adjuvants decrease the conformational stability of RBD-J and suggest a direct CpG-RBD-J interaction. Although AH+CpG-adjuvanted RBD-J was the least stable in vitro, the formulation was most potent at eliciting SARS-CoV-2 pseudovirus neutralizing antibodies in mice. In contrast, RBD-J formulated with AP+CpG showed minimal antigen-adjuvant interactions, a better stability profile, but suboptimal immune responses. Interestingly, the loss of in vivo potency associated with heat-stressed RBD-J formulated with AH+CpG after one dose was abrogated by a booster. Our findings highlight the importance of elucidating the key interrelationships between antigen-adjuvant interactions, storage stability, and in vivo performance to enable successful formulation development of stable and efficacious subunit vaccines.
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影响因子：
7.3
作者：
Awate S;Babiuk LA;Mutwiri G
通讯作者：
Mutwiri G
DOI：
10.1073/pnas.2106845118
发表时间：
2021-09-21
影响因子：
11.1
作者：
Dalvie NC;Rodriguez-Aponte SA;Hartwell BL;Tostanoski LH;Biedermann AM;Crowell LE;Kaur K;Kumru OS;Carter L;Yu J;Chang A;McMahan K;Courant T;Lebas C;Lemnios AA;Rodrigues KA;Silva M;Johnston RS;Naranjo CA;Tracey MK;Brady JR;Whittaker CA;Yun D;Brunette N;Wang JY;Walkey C;Fiala B;Kar S;Porto M;Lok M;Andersen H;Lewis MG;Love KR;Camp DL;Silverman JM;Kleanthous H;Joshi SB;Volkin DB;Dubois PM;Collin N;King NP;Barouch DH;Irvine DJ;Love JC
通讯作者：
Love JC
DOI：
10.1177/2051013613480144
发表时间：
2013-05-01
期刊：
Therapeutic advances in vaccines
影响因子：
--
作者：
Fox, Christopher B;Kramer, Ryan M;Vedvick, Thomas S
通讯作者：
Vedvick, Thomas S
影响因子：
13.6
作者：
Dalvie NC;Tostanoski LH;Rodriguez-Aponte SA;Kaur K;Bajoria S;Kumru OS;Martinot AJ;Chandrashekar A;McMahan K;Mercado NB;Yu J;Chang A;Giffin VM;Nampanya F;Patel S;Bowman L;Naranjo CA;Yun D;Flinchbaugh Z;Pessaint L;Brown R;Velasco J;Teow E;Cook A;Andersen H;Lewis MG;Camp DL;Silverman JM;Nagar GS;Rao HD;Lothe RR;Chandrasekharan R;Rajurkar MP;Shaligram US;Kleanthous H;Joshi SB;Volkin DB;Biswas S;Love JC;Barouch DH
通讯作者：
Barouch DH
影响因子：
7.3
作者：
Hogenesch H
通讯作者：
Hogenesch H