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

Influenza research and treatment Pub Date : 2011-01-01 Epub Date: 2012-01-12 DOI:10.1155/2011/126794
Sankhiros Babapoor, Tobias Neef, Christian Mittelholzer, Theodore Girshick, Antonio Garmendia, Hongwei Shang, Mazhar I Khan, Peter Burkhard
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引用次数: 72

Abstract

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.

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利用纳米颗粒平台制备抗禽流感免疫原性M2e疫苗
利用肽纳米颗粒技术,我们设计了两种新型疫苗结构,分别代表M2e的单体(Mono-M2e)和四聚体(tetrai -M2e)形式。在无特定病原体(SPF)鸡的肌肉内分别注射Mono-M2e或tetrao - m2e佐剂和不注射佐剂。第二次强化后2周,用107.2 EID50的H5N2低致病性禽流感(LPAI)病毒攻毒鸡。采用酶联免疫吸附试验(ELISA)检测对每种疫苗结构的m2e特异性抗体反应。与未接种疫苗的鸡相比,接种疫苗的鸡对每种结构的m2e特异性IgG反应增加。然而,当与佐剂一起使用时,疫苗构建体teat - m2e引起了明显更高的抗体反应。另一方面,病毒中和试验表明免疫保护不是通过中和抗体的方式。采用实时荧光定量PCR技术,在感染H5N2 LPAI后4、6和8天,通过检测病毒从气管和泄殖腔中脱落的情况来评估保护水平。加入佐剂的Tetra-M2e对H5N2亚型LPAI的保护作用有统计学意义(P < 0.05),可以减少AI病毒的脱落。结果表明,自组装多肽纳米颗粒有望成为开发抗AI疫苗的潜在平台。
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