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

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

doi:10.3390/vaccines13040413

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

Journal Article · Tue Apr 15 00:00:00 EDT 2025 · Vaccines

DOI:https://doi.org/10.3390/vaccines13040413· OSTI ID:2557540

; Anderson, Sarah J.; ; ; Hasan, Mahamudul; Sarlo Davila, Kaitlyn M.; ; Lager, Kelly M.; ;

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.

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Sponsoring Organization:: USDOE

OSTI ID:: 2557540

Journal Information:: Vaccines, Journal Name: Vaccines Journal Issue: 4 Vol. 13; ISSN VBSABP; ISSN 2076-393X

Publisher:: MDPI AGCopyright Statement

Country of Publication:: Switzerland

Language:: English

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