Miller Laura C, Anderson Sarah J, Buckley Alexandra C, Schirtzinger Erin E, Hasan Mahamudul, Sarlo Davila Kaitlyn M, Fleming Damarius S, Lager Kelly M, Li Jiuyi, Sang Yongming
Diagnostic Medicine and Pathobiology, College of Veterinary Medicine, Kansas State University, 1800 Denison Ave, Manhattan, KS, United States.
Virus and Prion Research Unit, National Animal Disease Center, USDA-ARS, 1920 Dayton Ave, Ames, IA, United States.
Vet Microbiol. 2025 Feb;301:110366. doi: 10.1016/j.vetmic.2025.110366. Epub 2025 Jan 3.
Porcine reproductive and respiratory syndrome (PRRS), caused by the highly variable PRRS virus (PRRSV), presents a significant challenge to the swine industry due to its pathogenic and economic burden. The virus evades host immune responses, particularly interferon (IFN) signaling, through various viral mechanisms. Traditional vaccines have shown variable efficacy in the field, prompting the exploration of novel vaccination strategies. This study investigates a reverse genetics approach to develop a modified live virus (MLV) vaccine expressing the potent antiviral cytokine interferon-ω5 (IFN-ω5) to combat PRRSV. The study utilizes an infectious cDNA clone of PRRSV, incorporating genetic modifications for IFN-ω5 expression. A comparative evaluation, including in vitro and particularly in vivo assessments here, was conducted to determine the vaccine's efficacy. Results indicate that pigs vaccinated with the IFN-ω5 MLV exhibited significant differences compared to the mock group in terms of body temperature, weight gain, antibody response, viral load, cytokine profile, and lung lesions following PRRSV challenge. This study underscores the potential of reverse genetics and IFN-ω5 expression as a promising strategy for developing effective PRRSV vaccines. The findings provide valuable insights into the mechanisms of immune response and viral pathogenesis, highlighting the importance of early immune activation in combating PRRSV infection.
猪繁殖与呼吸综合征(PRRS)由高度可变的猪繁殖与呼吸综合征病毒(PRRSV)引起,因其致病性和经济负担给养猪业带来了重大挑战。该病毒通过多种病毒机制逃避宿主免疫反应,尤其是干扰素(IFN)信号传导。传统疫苗在实际应用中显示出不同的效果,这促使人们探索新的疫苗接种策略。本研究调查了一种反向遗传学方法,以开发一种表达强效抗病毒细胞因子干扰素-ω5(IFN-ω5)的改良活病毒(MLV)疫苗来对抗PRRSV。该研究利用PRRSV的感染性cDNA克隆,并对其进行基因改造以表达IFN-ω5。进行了一项比较评估,包括体外评估,尤其是在此处进行的体内评估,以确定疫苗的效力。结果表明,与假手术组相比,接种IFN-ω5 MLV疫苗的猪在PRRSV攻击后的体温、体重增加、抗体反应、病毒载量、细胞因子谱和肺部病变方面存在显著差异。本研究强调了反向遗传学和IFN-ω5表达作为开发有效PRRSV疫苗的一种有前景策略的潜力。这些发现为免疫反应和病毒发病机制提供了有价值的见解,突出了早期免疫激活在对抗PRRSV感染中的重要性。