dPreS1-TLR2 激动剂纳米疫苗对乙型肝炎病毒的强烈和持久的中

StephenW

dPreS1-TLR2 激动剂纳米疫苗对乙型肝炎病毒的强烈和持久的中和免疫反应的诱导
Myriam Lamrayah 1、Fanny Charriaud 2、Manon Desmares 3、Céline Coiffier 2、Simon Megy 4、Evelyne Colomb 2、Raphaël Terreux 4、Julie Lucifora 3、David Durantel 3、Bernard Verrier 2
隶属关系
隶属关系

     1个
     Colloidal Vectors and Therapeutic Targeted Engineering, UMR5305, LBTI, Institut de Biologie et Chimie des Protéines, Université Lyon 1, 7 Passage du Vercors, 69367, Lyon Cedex 07, France。 电子地址：[email protected]。
     2个
     Colloidal Vectors and Therapeutic Targeted Engineering, UMR5305, LBTI, Institut de Biologie et Chimie des Protéines, Université Lyon 1, 7 Passage du Vercors, 69367, Lyon Cedex 07, France。
     3个
     HepVir 团队，国际传染病研究中心 (CIRI)，INSERM U1111，CNRS UMR_5308，里昂大学 (UCBL1)，里昂，法国。
     4个
     ECMO Team, UMR5305, LBTI, Institut de Biologie et Chimie des Protéines, Université Lyon 1, 7 Passage du Vercors, 69367, Lyon Cedex 07, France。

     PMID：36496142 DOI：10.1016/j.antiviral.2022.105483

抽象的

由于疾病进展为严重并发症（肝硬化、肝细胞癌），乙型肝炎病毒仍然是一个主要的医疗负担，全世界每年有超过 2.5 亿慢性感染患者和 900,000 人死亡。 尽管可以使用预防性疫苗，但这种感染在西太平洋和非洲地区仍然大流行，那里约有 6% 的成年人口受到感染。 在新型抗 HBV 策略中，已经研究了创新的药物递送系统，例如递送疫苗抗原或治疗分子的纳米颗粒平台。 在这里，我们开发了基于聚乳酸的可生物降解纳米粒子作为一种创新高效的疫苗。 它们通过 (i) 包埋 Pam3CSK4（一种免疫调节剂和 Toll 样受体 1/2 的配体）和 (ii) 从 HBV 表面抗原中吸附/包被豆蔻酰化 (2-48) 衍生的 PreS1 进行两次功能化 ，确定为肝细胞上的主要病毒附着位点。 我们证明，此类制剂通过免疫系统的有效肽识别来模拟 HBV 病毒粒子，并在至少一年内在幼稚小鼠中引发有效且持久的抗体反应。 我们还表明，使用 NP-Pam3CSK4-dPreS1 血清观察到最有效的体外病毒中和。 衍生的 HBV 抗原的免疫原性由 dPreS1 包被的纳米载体和佐剂部分的可能协同作用调节。 这种制剂代表了一种有前途的疫苗替代品来对抗 HBV 感染。

关键词：乙型肝炎病毒； 纳米粒子； 中和抗体； PreS1肽； TLR激动剂； 聚（乳酸）。

版权所有 © 2022。由 Elsevier B.V. 出版。
利益冲突声明

竞争利益声明 作者声明，他们没有已知的可能影响本文报告的工作的竞争经济利益或个人关系。

StephenW

Induction of a strong and long-lasting neutralizing immune response by dPreS1-TLR2 agonist nanovaccine against hepatitis B virus
Myriam Lamrayah  1 , Fanny Charriaud  2 , Manon Desmares  3 , Céline Coiffier  2 , Simon Megy  4 , Evelyne Colomb  2 , Raphaël Terreux  4 , Julie Lucifora  3 , David Durantel  3 , Bernard Verrier  2
Affiliations
Affiliations

    1
    Colloidal Vectors and Therapeutic Targeted Engineering, UMR5305, LBTI, Institut de Biologie et Chimie des Protéines, Université Lyon 1, 7 Passage du Vercors, 69367, Lyon Cedex 07, France. Electronic address: [email protected].
    2
    Colloidal Vectors and Therapeutic Targeted Engineering, UMR5305, LBTI, Institut de Biologie et Chimie des Protéines, Université Lyon 1, 7 Passage du Vercors, 69367, Lyon Cedex 07, France.
    3
    HepVir Team, Centre International de Recherche en Infectiologie (CIRI), INSERM U1111, CNRS UMR_5308, University of Lyon (UCBL1), Lyon, France.
    4
    ECMO Team, UMR5305, LBTI, Institut de Biologie et Chimie des Protéines, Université Lyon 1, 7 Passage du Vercors, 69367, Lyon Cedex 07, France.

    PMID: 36496142 DOI: 10.1016/j.antiviral.2022.105483

Abstract

Hepatitis B virus remains a major medical burden with more than 250 million chronically infected patients worldwide and 900,000 deaths each year, due to the disease progression towards severe complications (cirrhosis, hepatocellular carcinoma). Despite the availability of a prophylactic vaccine, this infection is still pandemic in Western Pacific and African regions, where around 6% of the adult population is infected. Among novel anti-HBV strategies, innovative drug delivery systems, such as nanoparticle platforms to deliver vaccine antigens or therapeutic molecules have been investigated. Here, we developed polylactic acid-based biodegradable nanoparticles as an innovative and efficient vaccine. They are twice functionalized by (i) the entrapment of Pam3CSK4, an immunomodulator and ligand to Toll-Like-Receptor 1/2, and by (ii) the adsorption/coating of myristoylated (2-48) derived PreS1 from the HBV surface antigen, identified as the major viral attachment site on hepatocytes. We demonstrate that such formulations mimic HBV virion with an efficient peptide recognition by the immune system, and elicit potent and durable antibody responses in naive mice during at least one year. We also show that the most efficient in vitro viral neutralization was observed with NP-Pam3CSK4-dPreS1 sera. The immunogenicity of the derived HBV antigen is modulated by the likely synergistic action of both the dPreS1 coated nanovector and the adjuvant moiety. This formulation represents a promising vaccine alternative to fight HBV infection.

Keywords: Hepatitis B virus; Nanoparticle; Neutralizing antibodies; PreS1 peptide; TLR agonist; poly(lactic acid).

Copyright © 2022. Published by Elsevier B.V.
Conflict of interest statement

Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.