Induction of adaptive immune responses against respiratory viruses using in ovo delivered toll-like receptor (TLR) ligands

由鸡传染性支气管炎病毒(IBV)和传染性喉气管炎病毒(ILTV)引起的呼吸道病毒感染在加拿大和全球范围内普遍存在，给家禽养殖业造成了数十亿美元的损失。实验室减弱的病毒被用作控制这些病毒感染的疫苗。由于两个主要原因，这些呼吸道病毒感染的暴发发生在接种疫苗的鸡身上。首先，疫苗中使用的IBV和ILTV等病毒可以通过在禽群中传播来重新获得致病能力。其次，IBV的野外毒株可以在疫苗接种施加的压力下发生变异。因此，开发针对这些病毒感染的新的、更可持续的控制措施至关重要。潜在的方法之一是使用免疫刺激剂来诱导自然抵抗力，从而对遇到的病原体产生长期免疫。为了建立这种控制手段，我们将研究：(1)已知的刺激自然免疫的免疫刺激剂诱导对IBV和ILTV感染的长期免疫的能力，(2)这些免疫刺激剂建立对这些病毒感染的长期抵抗力的机制，以及(3)当使用IBV和ILTV病毒的种子感染模型模拟田间条件时，诱导的长期抵抗力是否有效。拟议的研究将导致制定新的控制策略，防止鸡的呼吸道病毒感染，使加拿大家禽研究理事会受益，从而使加拿大家禽生产者受益。

Respiratory viral infections caused by infectious bronchitis virus (IBV) and infectious laryngotracheitis virus (ILTV) in chickens are prevalent in Canada and globally leading to losses that amount to billions of dollars to the poultry industry. Laboratory weakened viruses are used as vaccines for the control of these viral infections. For two major reasons, outbreaks of these respiratory viral infections occur in vaccinated chickens. Firstly, the virus such as IBV and ILTV used in vaccines can regain the ability to cause diseases by spreading through the flock. Secondly, the field strains of IBV can mutate against the pressure imposed by vaccination. Therefore it is critical to develop novel and more sustainable control measures against these viral infections. One of the potential ways is the use of immune stimulants to induce natural resistance leading to long-term immunity against encountered pathogens. In order to establish this means of control, we will study: (1) the ability of immune stimulants that are known to stimulate natural immunity to induce long-term immunity against IBV and ILTV infections, (2) the mechanisms by which these immune stimulants establish long-term resistance against these viral infections and (3) whether the induced long-term resistance is effective when seeder infection models of IBV and ILTV viruses are used mimicking the field conditions. The proposed studies will lead to the formulation of novel control strategies against respiratory viral infections in chickens benefiting the Canadian Poultry Research Council thus the Canadian poultry producers.