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

A Novel Vaccine Using Nanoparticle Platform to Present Immunogenic M2e against Avian Influenza Infection.
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DOI:
10.1155/2011/126794
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发表时间:
2011
期刊:
Influenza research and treatment
影响因子:
--
通讯作者:
Burkhard P
Burkhard P
中科院分区:
其他
文献类型:
--
作者:
Babapoor S;Neef T;Mittelholzer C;Girshick T;Garmendia A;Shang H;Khan MI;Burkhard P

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使用肽纳米颗粒技术,我们设计了两种新型疫苗构建体,代表单体(Mono-M2 e)和四聚体(Tetra-M2 e)形式的M2 e。用Mono-M2 e或Tetra-M2 e在有和没有佐剂的情况下肌内免疫无特定病原体(SPF)鸡组。在第二次加强后两周,用107.2EID50的H5 N2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M2 e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表现出增加的M2 e特异性IgG应答。然而,当疫苗构建体Tetra-M2 e与佐剂一起使用时,其引发显著更高的抗体应答。另一方面,病毒中和试验表明,免疫保护不是通过中和抗体。在用H5 N2 LPAI攻击后4、6和8天,通过测量从气管和泄殖腔的病毒脱落,使用定量真实的时间PCR评估保护水平。具有佐剂的Tetra-M2 e通过减少AI病毒脱落而提供针对亚型H5 N2 LPAI的统计学显著(P < 0.05)保护。结果表明,自组装多肽纳米颗粒显示出作为开发针对AI的疫苗的潜在平台的希望。
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.