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血凝素蛋白中的突变及其对高致病性禽流感(HPAI)H5N1病毒在疫苗接种效果欠佳的鸡只中传播的影响。

Mutations in the haemagglutinin protein and their effect in transmission of highly pathogenic avian influenza (HPAI) H5N1 virus in sub-optimally vaccinated chickens.

作者信息

Sitaras Ioannis, Rousou Xanthoula, Peeters Ben, de Jong Mart C M

机构信息

Quantitative Veterinary Epidemiology, Department of Animal Sciences, Wageningen University, Radix Building 107, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands; Department of Virology, Central Veterinary Institute of Wageningen University and Research Centre, Houtribweg 39, 8221 RA Lelystad, The Netherlands.

Quantitative Veterinary Epidemiology, Department of Animal Sciences, Wageningen University, Radix Building 107, Droevendaalsesteeg 1, 6708 PB Wageningen, The Netherlands.

出版信息

Vaccine. 2016 Nov 4;34(46):5512-5518. doi: 10.1016/j.vaccine.2016.10.002. Epub 2016 Oct 8.

Abstract

BACKGROUND

Transmission of highly pathogenic avian influenza (HPAI) viruses in poultry flocks is associated with huge economic losses, culling of millions of birds, as well as human infections and deaths. In the cases where vaccination against avian influenza is used as a control measure, it has been found to be ineffective in preventing transmission of field strains. Reports suggest that one of the reasons for this is the use of vaccine doses much lower than the ones recommended by the manufacturer, resulting in very low levels of immunity. In a previous study, we selected for immune escape mutants using homologous polyclonal sera and used them as vaccines in transmission experiments. We concluded that provided a threshold of immunity is reached, antigenic distance between vaccine and challenge strains due to selection need not result in vaccine escape. Here, we evaluate the effect that the mutations in the haemagglutinin protein of our most antigenically-distant mutant may have in the transmission efficiency of this mutant to chickens vaccinated against the parent strain, under sub-optimal vaccination conditions resembling those often found in the field.

METHODS

In this study we employed reverse genetics techniques and transmission experiments to examine if the HA mutations of our most antigenically-distant mutant affect its efficiency to transmit to vaccinated chickens. In addition, we simulated sub-optimal vaccination conditions in the field, by using a very low vaccine dose.

RESULTS

We find that the mutations in the HA protein of our most antigenically-distant mutant are not enough to allow it to evade even low levels of vaccination-induced immunity.

DISCUSSION

Our results suggest that - for the antigenic distances we investigated - vaccination can reduce transmission of an antigenically-distant strain compared to the unvaccinated groups, even when low vaccine doses are used, resulting in low levels of immunity.

摘要

背景

高致病性禽流感(HPAI)病毒在家禽群体中的传播会带来巨大经济损失、数百万只禽类被扑杀,以及人类感染和死亡。在将禽流感疫苗接种用作控制措施的情况下,已发现其在预防野毒株传播方面无效。报告表明,其中一个原因是使用的疫苗剂量远低于制造商推荐的剂量,导致免疫力水平极低。在先前的一项研究中,我们使用同源多克隆血清筛选出免疫逃逸突变体,并在传播实验中将它们用作疫苗。我们得出的结论是,只要达到一定的免疫阈值,因筛选导致的疫苗株与攻击株之间的抗原距离不一定会导致疫苗逃逸。在此,我们评估在类似于实际中常见的次优疫苗接种条件下,我们抗原性差异最大的突变体的血凝素蛋白突变对该突变体传播给接种了亲本毒株疫苗的鸡的传播效率可能产生的影响。

方法

在本研究中,我们采用反向遗传学技术和传播实验来检查我们抗原性差异最大的突变体的血凝素(HA)突变是否会影响其传播给接种疫苗的鸡的效率。此外,我们通过使用极低的疫苗剂量来模拟实际中的次优疫苗接种条件。

结果

我们发现,我们抗原性差异最大的突变体的血凝素蛋白突变不足以使其逃避即使是低水平的疫苗诱导免疫。

讨论

我们的结果表明,对于我们研究的抗原距离,与未接种疫苗的组相比,即使使用低剂量疫苗导致免疫力水平较低,疫苗接种仍可降低抗原性差异较大毒株的传播。

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