# Vaccine Efficacy of a Replication-Competent Interferon-Expressing Porcine Reproductive and Respiratory Syndrome (PRRS) Virus Against NADC-34 Challenge

## TL;DR

A new PRRSV vaccine candidate, IFNmix, was developed to boost immunity by expressing multiple interferons and showed similar or better protection in pigs compared to commercial vaccines.

## Contribution

The novel vaccine candidate IFNmix co-expresses three Type I interferons to enhance antiviral immunity against PRRSV.

## Key findings

- IFNmix showed comparable or lower body temperatures and weight gain in vaccinated pigs compared to commercial vaccines.
- IFNmix demonstrated early viral load reduction compared to commercial vaccines during the first two weeks post-challenge.
- IFNmix provided similar efficacy in controlling PRRSV replication and lung pathology as commercial vaccines.

## Abstract

Background/Objectives: Porcine reproductive and respiratory syndrome virus (PRRSV) significantly impedes swine production due to rapid genetic variation and suppression of antiviral interferon (IFN) responses, leading to ineffective immunity. To address this, we developed IFNmix, a replication-competent PRRSV modified live vaccine (MLV) candidate co-expressing three Type I IFN subclasses (IFNα, IFNβ, IFNδ) to enhance antiviral immunity. Methods: In two independent in vivo experiments, we compared the protection of IFNmix and a commercial PRRSV MLV vaccine during challenge with a virulent PRRSV strain. Clinical signs, antibody and cytokine production, viral replication, and lung pathology in IFNmix-vaccinated pigs were compared to those of commercial PRRSV vaccines and controls. Results: Pigs vaccinated with IFNmix exhibited similar anti-PRRSV antibody development, serum viral loads, lung lesions, and cytokine responses post-challenge with the virulent NADC34 strain, with comparable or lower body temperatures and weight gain, to pigs vaccinated with the commercial vaccines. While IFNmix showed early viral load reduction compared to the commercial vaccine (Days 7–14 post-challenge), it demonstrated similar efficacy in controlling PRRSV replication and lung pathology. Conclusions: These findings suggest that IFNmix, by expressing multiple IFNs, can potentially enhance innate and adaptive immune responses, offering a promising approach to improving PRRSV vaccine efficacy. Further studies are needed to evaluate IFNmix against a broader range of PRRSV strains and to optimize its attenuation and immunogenicity.