SARS-CoV-2 receptor binding domain displayed on HBsAg virus-like particles elicits protective immunity in macaques.

SARS-CoV-2 receptor binding domain displayed on HBsAg virus-like particles elicits protective immunity in macaques.
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乙型肝炎表面抗原病毒样颗粒上显示的SARS-CoV-2受体结合域在猕猴中引发保护性免疫。

DOI:
10.1126/sciadv.abl6015
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发表时间:
2022-03-18
期刊:
影响因子:
13.6
通讯作者:
Barouch DH
Barouch DH
中科院分区:
综合性期刊1区
文献类型:
--
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

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由于供应不足、成本高和储存要求,在低收入和中等收入国家获得的SARS-CoV-2授权疫苗仍然较少。全球免疫力仍然可以受益于使用广泛可用的安全佐剂的新疫苗,例如明矾和蛋白质亚单位,适合在现有制造设施中进行低成本生产。在这里,包含SARS-CoV-2受体结合域-乙肝表面抗原病毒样颗粒的临床阶段疫苗候选在食蟹猴中诱导保护性免疫。该候选疫苗在非人类灵长类动物中诱导的中和抗体(>104)效价高于其他已获许可的疫苗的保护范围。包括CpG1018在内的CpG1018不能显著改善免疫应答。与假对照组相比,SARS-CoV-2免疫动物的支气管肺泡灌洗液(~3.4log10)和鼻黏膜(~2.9log10)病毒载量的中位数降低。这些数据支持这一设计的潜在好处,即为SARS-CoV-2和其他令人关注的变种或贝塔冠状病毒提供低成本模块化疫苗平台。一种在酵母中生产的模块化蛋白质亚单位候选疫苗在非人类灵长类动物中提供了对SARS-CoV-2的保护。
Authorized vaccines against SARS-CoV-2 remain less available in low- and middle-income countries due to insufficient supply, high costs, and storage requirements. Global immunity could still benefit from new vaccines using widely available, safe adjuvants, such as alum and protein subunits, suited to low-cost production in existing manufacturing facilities. Here, a clinical-stage vaccine candidate comprising a SARS-CoV-2 receptor binding domain–hepatitis B surface antigen virus–like particle elicited protective immunity in cynomolgus macaques. Titers of neutralizing antibodies (>104) induced by this candidate were above the range of protection for other licensed vaccines in nonhuman primates. Including CpG 1018 did not significantly improve the immunological responses. Vaccinated animals challenged with SARS-CoV-2 showed reduced median viral loads in bronchoalveolar lavage (~3.4 log10) and nasal mucosa (~2.9 log10) versus sham controls. These data support the potential benefit of this design for a low-cost modular vaccine platform for SARS-CoV-2 and other variants of concern or betacoronaviruses. A modular protein subunit vaccine candidate produced in yeast confers protection against SARS-CoV-2 in nonhuman primates.
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