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Nano-multilamellar lipid vesicles loaded with a recombinant form of the chikungunya virus E2 protein improve the induction of virus-neutralizing antibodies
Nanomedicine: Nanotechnology, Biology and Medicine ( IF 4.2 ) Pub Date : 2021-07-22 , DOI: 10.1016/j.nano.2021.102445
Aléxia Adrianne Venceslau-Carvalho 1 , Marianna Teixeira de Pinho Favaro 1 , Lennon Ramos Pereira 1 , Mônica Josiane Rodrigues-Jesus 1 , Samuel Santos Pereira 1 , Robert Andreata-Santos 1 , Rúbens Prince Dos Santos Alves 1 , Maria Fernanda Castro-Amarante 1 , Karine Bitencourt Rodrigues 1 , Jamile Ramos da Silva 1 , Rafael Rahal Guaragna Machado 2 , Marielton Dos Passos Cunha 3 , Paolo Marinho de Andrade Zanotto 3 , Wesley Luzetti Fotoran 4 , Gerhard Wunderlich 4 , Edison Luiz Durigon 2 , Luís Carlos de Souza Ferreira 1
Affiliation  

Chikungunya virus (CHIKV) is responsible for a self-limited illness that can evolve into long-lasting painful joint inflammation. In this study, we report a novel experimental CHIKV vaccine formulation of lipid nanoparticles loaded with a recombinant protein derived from the E2 structural protein. This antigen fragment, designated ∆E2.1, maintained the antigenicity of the native viral protein and was specifically recognized by antibodies induced in CHIKV-infected patients. The antigen has been formulated into nanoparticles consisting of nano-multilamellar vesicles (NMVs) combined with the adjuvant monophosphoryl lipid A (MPLA). The vaccine formulation demonstrated a depot effect, leading to controlled antigen release, and induced strong antibody responses significantly higher than in mice immunized with the purified protein combined with the adjuvant. More relevantly, E2-specific antibodies raised in mice immunized with ∆E2.1-loaded NMV-MPLA neutralized CHIKV under in vitro conditions. Taken together, the results demonstrated that the new nanoparticle-based vaccine formulation represents a promising approach for the development of effective anti-CHIKV vaccines.



中文翻译:

载有基孔肯雅病毒 E2 蛋白重组形式的纳米多层脂质囊泡可改善病毒中和抗体的诱导

基孔肯雅病毒 (CHIKV) 是一种自限性疾病,可演变为长期疼痛的关节炎症。在这项研究中,我们报告了一种新的实验性 CHIKV 疫苗制剂,该制剂是脂质纳米颗粒,该脂质纳米颗粒装载了一种源自 E2 结构蛋白的重组蛋白。该抗原片段,命名为 ΔE2.1,保持天然病毒蛋白的抗原性,并被 CHIKV 感染患者诱导的抗体特异性识别。该抗原已被配制成由纳米多层囊泡 (NMV) 和佐剂单磷酰脂质 A (MPLA) 组成的纳米颗粒。疫苗制剂表现出贮库效应,导致受控抗原释放,并且诱导的强烈抗体反应明显高于用纯化蛋白与佐剂联合免疫的小鼠。更相关的是,在用载有 ∆E2.1 的 NMV-MPLA 免疫的小鼠中产生的 E2 特异性抗体中和了 CHIKV体外条件。总之,结果表明,新的基于纳米颗粒的疫苗制剂代表了开发有效抗 CHIKV 疫苗的有希望的方法。

更新日期:2021-08-19
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