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Heterosubtypic protection against avian influenza virus by live attenuated and chimeric norovirus P-particle-M2e vaccines in chickens

机译:鸡的活病毒和嵌合诺维病毒P粒子-M2E疫苗对禽流感病毒的异质术保护

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Avian influenza in poultry continues to be a great concern worldwide, and the currently licensed inactivated influenza vaccines are not effective against the novel strains of influenza virus that continue to emerge in the field. This warrants the development of more broadly protective influenza vaccines or vaccination regimens. Live attenuated influenza vaccines (LAIVs) and subunit vaccines derived from viral peptides, such as the highly conserved ectodomain of influenza virus matrix protein 2 (M2e), can offer a more broadly reactive immune response. In chickens, we previously showed that a chimeric norovirus P particle containing M2e (M2eP) could provide partial but broad immunity, when administered as a standalone vaccine, and also enhanced the protective efficacy of inactivated vaccine when used in a combination regimen. We also demonstrated that a naturally-selected NS1-truncated H7N3 LAIV (pc4-LAIV) was highly efficacious against antigenically distant heterologous H7N2 low pathogenicity avian influenza virus challenge, especially when used as the priming vaccine in a prime-boost vaccination regimen. In this study, we investigated the cross-subtype protective efficacy of pc4-LAIV in conjunction with M2eP using single vaccination, combined treatment, and prime-boost approaches. Chickens vaccinated with pc4-LAIV showed significant reduction of tracheal shedding of a low pathogenicity H5N2 challenge virus. This cross-subtype protective efficacy was further enhanced, during the initial stages of challenge virus replication, in chickens that received a vaccination regimen consisting of priming with pc4-LAIV at 1 day of age and boosting with M2eP. Further, H5N2-specific serum IgG and pc4-LAIV-specific hemagglutination-inhibition antibody titers were enhanced in LAIV-primed and M2eP boostvaccinated chickens. Taken together, our data point to the need of further investigation into the benefits of combined and prime-boost vaccination schemes utilizing LAIV and epitope-based vaccines, to develop more broadly protective vaccination regimens. (C) 2019 Elsevier Ltd. All rights reserved.
机译:家禽中的禽流感继续是全球范围内的一个巨大关注,目前许可的灭活流感疫苗对继续涌现在该领域的新型流感病毒的新菌株无效。这保证了更广泛保护的流感疫苗或疫苗接种方案的发展。生物减毒的流感疫苗(Laivs)和源自病毒肽的亚基疫苗,例如流感病毒基质2(M2E)的高度保守的外胚瘤菌,可以提供更广泛的活性免疫应答。在鸡中,我们以前表明,当施用独立疫苗时,含有M2E(M2EP)的嵌合诺维病毒P粒子可以提供部分但宽的免疫力,并且在组合方案中使用时也增强了灭活疫苗的保护效果。我们还证明了一种天然选择的NS1截短的H7N3 Laiv(PC4-Laiv)非常有效地针对抗原性远处的异源H7N2低致病性禽流感病毒攻击,特别是当用作初始疫苗接种方案中的灌注疫苗时。在这项研究中,我们研究了使用单次疫苗接种,结合治疗和素质 - 升压方法与M2EP结合CP4-Laiv的交叉亚型保护效果。用PC4-LAIV接种疫苗的鸡显示出低致病性H5N2攻击病毒的气管脱落的显着减少。在攻击病毒复制的初始阶段,这种杂交亚型保护效果进一步增强了患有在1天的PC4-Laiv的疫苗接种方案,并用M2EP提高疫苗接种方案。此外,在Laiv-inved和M2EP Boostvaccated鸡中增强了H5N2特异性血清IgG和PC4-Laiv特异性血凝抑制抗体滴度。我们的数据指出,需要进一步调查利用Laiv和基于表位的疫苗的合并和初级促进疫苗接种方案的益处,以发展更广泛的保护性疫苗接种方案。 (c)2019 Elsevier Ltd.保留所有权利。

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