Engineered Lactococcus lactis for Oral Delivery of Bovine Type I Interferon: A Biotherapeutic Strategy for Mucosal Antiviral Defense

Description

Interferons (IFNs) are key broad-spectrum antiviral cytokines and represent an important complement to conventional vaccination. However, the application of bovine interferons (BoIFNs) is limited by short biological half-life, poor in vivo stability, and inconvenient delivery. In this study, BoIFN-β1, BoIFN-β2, BoIFN-β3, and BoIFN-γ were expressed in Escherichia coli, and four fusion proteins (BoIFN-α-β2, BoIFN-α-γ, BoIFN-β2-γ, and BoIFN-α-β2-γ) were constructed to evaluate potential synergistic antiviral effects. All fusion proteins showed lower antiviral activity than BoIFN-α and BoIFN-β2 monomers. Subsequently, a food-grade pNZ8149/NZ3900 system was used to achieve antibiotic resistance marker-free secretory expression of BoIFN-α and BoIFN-β2 in Lactococcus lactis (L. lactis). Recombinant culture supernatants showed no apparent cytotoxicity toward Madin–Darby bovine kidney (MDBK) cells, effectively inhibited bovine enterovirus (BEV) and vesicular stomatitis virus (VSV) replication, and significantly induced MX1, OAS1, ISG15, and IFITM1 expression. In BALB/c mice, oral administration of recombinant L. lactis increased splenic Oas1 and Isg15 expression and reduced VSV-induced weight loss, tissue viral loads, and pathological lesions, with prophylactic administration showing greater efficacy. These findings establish a food-grade L. lactis-based oral BoIFN delivery strategy for bovine viral disease prevention and control.

Institutions

• Northeast Agricultural University

  Heilongjiang, Harbin

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