Transcriptomic Analysis of Liver Indicates Novel Vaccine to Porcine Reproductive and Respiratory Virus Promotes Homeostasis in T-Cell and Inflammatory Immune Responses Compared to Commercial Vaccine in Pigs

One of the largest impediments for commercial swine production is the presence of Porcine Reproductive and Respiratory Syndrome virus (PRRSV), a devastating RNA viral infection that is responsible for over $1 billion in loss in the U.S. annually. The challenge with combating PRRSV is a combination of the effect of an extraordinary rate of mutation, the ability to infect macrophages, and subversion of host immune response through a series of actions leading to both immunomodulation and immune evasion. Currently there are a handful of commercial vaccines on the market that have been shown to be effective against homologous infections, but struggle against heterologous or mixed strain infections. However, vaccination is the current best strategy for combating PRRSV, making research into new vaccine technology key. To address these issues with PRRSV and host antiviral functions a novel modified-live vaccine (MLV) able to stimulate known anti-viral interferons was created and examined for its ability to potentiate effective immunity and better protection. Here, we examine gene expression in the liver of pigs vaccinated with our novel vaccine, given the liver’s large role in anti-viral responses and vaccine metabolism. Our study indicated that pigs administered the novel vaccine experience homeostatic gene expression consistent with less inflammation and T-cell depletion risk than pigs administered the commercial vaccine. Overall design: Liver 3' mRNA single-end profiles of novel vaccine, commercial vaccine, and sham-vaccinated PRRSV challenged pigs at 14 days post infection

商业猪养殖业面临的一大障碍是猪繁殖与呼吸综合征病毒（Porcine Reproductive and Respiratory Syndrome virus，简称PRRSV）的存在，该病毒是一种毁灭性的RNA病毒感染，每年在美国造成的损失超过10亿美元。与PRRSV作斗争的挑战在于其异常的突变速率、感染巨噬细胞的能力以及通过一系列导致免疫调节和免疫逃逸的行为，对宿主免疫反应的颠覆。目前市场上仅有少量商业疫苗被证明对同源感染有效，但在异源或混合菌株感染方面效果不佳。然而，疫苗接种是目前对抗PRRSV的最佳策略，因此研究新型疫苗技术至关重要。为了解决PRRSV和宿主抗病毒功能中的这些问题，我们创建并检验了一种新型活疫苗（Modified-live Vaccine，简称MLV），该疫苗能够刺激已知的抗病毒干扰素。在本研究中，我们考察了接种该新型疫苗的猪肝脏中的基因表达，鉴于肝脏在抗病毒反应和疫苗代谢中扮演的重要角色。我们的研究结果表明，接种新型疫苗的猪表现出与商业疫苗相比更低的炎症和T细胞耗竭风险的稳态基因表达。总体设计：感染PRRSV后第14天，对新型疫苗、商业疫苗和假疫苗接种猪的肝脏3' mRNA单端测序分析。