The Gold Nanoparticles-Functionalized with the Synthetic PADRE^S2P6 Peptide Can Be Useful for SARS-CoV-2 Detection

Charline Herrscher, Maroua Ben Haddada, Jessica Andries, Wildriss Viranaicken, Colette Cordonin, Gilles Gadea, Patrick Mavingui, Chaker El-Kalamouni, Anne-Laure Morel, Philippe Desprès
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Abstract

Conjugation of bioactive peptides to nanomaterials is a promising approach for a variety of biomedical uses. Indeed, we assumed that gold nanoparticles (AuNPs) functionalized with synthetic viral peptides represent a promising strategy to elicit antibody response against zoonotic coronavirus SARS-CoV-2 responsible for pandemic COVID-19 disease. Two specific linear B-cell epitopes namely S1P4 and S2P6 have been recently identified in the SARS-CoV-2 spike protein expressed by the COVID-19 mRNA BNT162 vaccine of Pfizer-BioNTech and marketed under the brand name Comirnaty. The present study aimed at investigating the immunogenic potential of AuNPs functionalized with synthetic PADRE^S1P4 and PADRE^S2P6 peptides in a mouse model. The AuNPs were synthesized using an environmentally friendly process. In both synthetic PADRE^S1P4 and PADRE^S2P6 peptides, the SARS-CoV-2 spike antibody epitope is preceded by a polybasic sequence and the T-helper cell response activator PADRE. A thiol-terminated polyethylene glycol was used to decorate AuNP surface with the synthetic peptides. The AuNPs-peptide conjugates were inoculated without any adjuvant to adult BALB/c mice by intramuscular route in a prime-boost schedule. The AuNPs functionalized with the PADRE^S2P6 peptide but not the PADRE^S1P4 peptide were efficient to elicit antibody production of relevant specificity against the SARS-CoV-2 spike protein. The ability of PADRE^S2P6 peptide-reactive antibodies to recognize SARS-CoV-2 variants opens important perspectives for AuNP-peptide conjugates as potential serological tools to support the surveillance of wildlife-origin coronaviruses.
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合成PADRE^S2P6肽功能化的金纳米颗粒可用于SARS-CoV-2检测
生物活性肽与纳米材料的偶联是一种很有前途的方法,可用于各种生物医学用途。事实上,我们假设用合成病毒肽功能化的金纳米颗粒(AuNPs)代表了一种有希望的策略,可以引发针对导致COVID-19大流行疾病的人畜共患冠状病毒SARS-CoV-2的抗体反应。最近在由辉瑞- biontech公司的COVID-19 mRNA BNT162疫苗表达的SARS-CoV-2刺突蛋白中发现了两个特异性线性b细胞表位,即S1P4和S2P6,该疫苗以Comirnaty品牌上市。本研究旨在研究合成PADRE^S1P4和PADRE^S2P6肽功能化的AuNPs在小鼠模型中的免疫原性潜力。采用环境友好的方法合成了aunp。在合成的PADRE^S1P4和PADRE^S2P6肽中,SARS-CoV-2刺突抗体表位之前都有一个多碱基序列和t辅助细胞反应激活剂PADRE。用巯基端聚乙二醇在AuNP表面进行修饰。将aunps -肽偶联物无佐剂接种于成年BALB/c小鼠肌内。与PADRE^S2P6肽功能化的AuNPs而非PADRE^S1P4肽功能化的AuNPs可以有效地诱导产生针对SARS-CoV-2刺突蛋白的相关特异性抗体。PADRE^S2P6肽反应性抗体识别SARS-CoV-2变体的能力为aunp -肽偶联物作为支持野生动物源性冠状病毒监测的潜在血清学工具开辟了重要的前景。
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