Replication-competent recombinant porcine reproductive and respiratory syndrome (PRRS) virus expressing antiviral cytokine interferon-ω5 as a modified live virus vaccine

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.