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A Novel Vaccine Using Nanoparticle Platform to Present Immunogenic M2e against Avian Influenza Infection

机译:一种新型疫苗使用纳米粒子平台呈现针对禽流感的免疫原性M2e。

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摘要

Using peptide nanoparticle technology, we have designed two novel vaccine constructs representing M2e in monomeric (Mono-M2e) and tetrameric (Tetra-M2e) forms. Groups of specific pathogen free (SPF) chickens were immunized intramuscularly with Mono-M2e or Tetra-M2e with and without an adjuvant. Two weeks after the second boost, chickens were challenged with 107.2 EID50 of H5N2 low pathogenicity avian influenza (LPAI) virus. M2e-specific antibody responses to each of the vaccine constructs were tested by ELISA. Vaccinated chickens exhibited increased M2e-specific IgG responses for each of the constructs as compared to a non-vaccinated group. However, the vaccine construct Tetra-M2e elicited a significantly higher antibody response when it was used with an adjuvant. On the other hand, virus neutralization assays indicated that immune protection is not by way of neutralizing antibodies. The level of protection was evaluated using quantitative real time PCR at 4, 6, and 8 days post-challenge with H5N2 LPAI by measuring virus shedding from trachea and cloaca. The Tetra-M2e with adjuvant offered statistically significant (P < 0.05) protection against subtype H5N2 LPAI by reduction of the AI virus shedding. The results suggest that the self-assembling polypeptide nanoparticle shows promise as a potential platform for a development of a vaccine against AI.
机译:使用肽纳米颗粒技术,我们设计了两种新颖的疫苗构建体,分别代表单体(Mono-M2e)和四聚体(Tetra-M2e)形式的M2e。在有或没有佐剂的情况下,用Mono-M2e或Tetra-M2e肌内免疫各组特定的无病原体(SPF)鸡。第二次加强免疫后两周,用107.2 EID50的H5N2低致病性禽流感(LPAI)病毒攻击鸡。通过ELISA测试对每种疫苗构建体的M2e特异性抗体应答。与未接种疫苗的组相比,接种疫苗的鸡对每种构建体均表现出增强的M2e特异性IgG反应。然而,当与佐剂一起使用时,疫苗构建体Tetra-M2e引起明显更高的抗体应答。另一方面,病毒中和测定表明免疫保护不是通过中和抗体的方式。通过在H4N2 LPAI攻击后第4、6和8天使用定量实时PCR评估保护水平,方法是测量从气管和泄殖腔排出的病毒。带有佐剂的Tetra-M2e通过减少AI病毒的释放提供了针对H5N2 LPAI亚型的统计学显着(P <0.05)保护。结果表明,自组装多肽纳米颗粒显示出有望作为开发抗AI疫苗的潜在平台。

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