Vaccination with recombinant 4 x M2e.HSP70c fusion protein as a universal vaccine candidate enhances both humoral and cell-mediated immune responses and decreases viral shedding against experimental challenge of H9N2 influenza in chickens
Vaccination with recombinant 4 x M2e.HSP70c fusion protein as a universal vaccine candidate enhances both humoral and cell-mediated immune responses and decreases viral shedding against experimental challenge of H9N2 influenza in chickens
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DOI：
10.1016/j.vetmic.2014.09.009
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发表时间：
2014-11-07
影响因子：
3.3
通讯作者：
Ebrahimi, Seyyed Mahmoud
中科院分区：
文献类型：
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作者：
Dabaghian, Mehran;Latify, Ali Mohammad;Ebrahimi, Seyyed Mahmoud
由于细胞免疫对于病毒清除是必不可少的，因此通常认为所有可用的基于HA的灭活流感疫苗都不能实现足够的细胞免疫。迫切需要一种改进的流感疫苗来诱导体液和细胞介导的免疫应答，以控制家禽养殖场中LPAI H9 N2的爆发。的疫苗已被提出并开发为新一代抗甲型流感感染的通用候选疫苗。我们先前的研究表明，与常规的基于HA的流感疫苗相比，重组4 × M2e.HSP70c（r4 M2 e/H70 c）融合蛋白的加强施用在小鼠中提供了针对致死剂量的甲型流感病毒的完全保护。在本研究中，检测了（r4 M2 e/H70 c）在鸡中的免疫原性和保护效力，本文报道的数据显示，与注射以MF 59为佐剂的常规HA基流感疫苗或不含HSP 70 c的重组4 x M2 e（r4 M2 e）相比，注射r4 M2 e/H70 c在鸡中对H9 N2病毒攻击的保护显著增加。在攻毒后2天，在所有r4 M2 e/H70 c疫苗接种的鸡中检测到病毒的口咽和泄殖腔脱落，但滴度较低，并在攻毒后7天迅速下降至不可检测的水平。此外，r4 M2 e/H70 c肌肉注射免疫的禽类对LPAI H9 N2的保护效力的比较可能代表了基于M2 e的疫苗提供针对异亚型H9 N2攻击的交叉保护的能力，并且还允许宿主免疫系统诱导针对H9 N2攻击的HA-同型亚型中和抗体。这种保护性免疫可能归因于增强的细胞介导的免疫，这被解释为淋巴细胞增殖增加，Th 1型（IFN-γ）和Th 2型（IL-4）细胞因子的产生以及增加的CD 4（+）与CD 8（+）比率，由注射与C-融合的保守流感基质蛋白M2的胞外域的四个串联重复序列（4 × M2 e）引起，结核分枝杆菌HSP 70末端（mHSP 70 c）。(C)2014爱思唯尔有限公司版权所有。
As cellular immunity is essential for virus clearance, it is commonly accepted that no adequate cellular immunity is achieved by all available inactivated HA-based influenza vaccines.Thus, an improved influenza vaccine to induce both humoral and cell-mediated immune responses is urgently required to control LPAI H9N2 outbreaks in poultry farms.M2e-based vaccines have been suggested and developed as a new generation of universal vaccine candidate against influenza A infection.Our previous study have shown that a prime-boost administration of recombinant 4 x M2e.HSP70c (r4M2e/H70c) fusion protein compared to conventional HA-based influenza vaccines provided full protection against lethal dose of influenza A viruses in mice. In the present study, the immunogenicity and protective efficacy of (r4M2e/H70c) was examined in chickens.The data reported herein show that protection against H9N2 viral challenge was significantly increased in chickens by injection of r4M2e/H70c compared with injection of conventional HA-based influenza vaccine adjuvanted with MF59 or recombinant 4 x M2e (r4M2e) without HSP70c. Oropharyngeal and cloacal shedding of the virus was detected in all of the r4M2e/H70c vaccinated birds at 2 days after challenge, but the titer was low and decreased rapidly to reach undetectable levels at 7 days after challenge. Moreover, comparison of protective efficacy against LPAI H9N2 in birds intramuscularly immunized with r4M2e/H70c likely represented the ability of the M2e-based vaccine in providing cross-protection against heterosubtypic H9N2 challenge and also allowed the host immune system to induce HA-homosubtype neutralizing antibody against H9N2 challenge.This protective immunity might be attributed to enhanced cell-mediated immunity, which is interpreted as increased lymphocytes proliferation, increased levels of Th1-type (IFN-gamma) and Th2-type (IL-4) cytokines production and increased CD4(+) to CD8(+) ratios, resulting from the injection of four tandem repeats of the ectodomain of the conserved influenza matrix protein M2 (4 x M2e) genetically fused to C-terminus of Mycobacterium tuberculosis HSP70 (mHSP70c). (C) 2014 Elsevier B.V. All rights reserved.