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However, the efficacy of monomeric IFN is limited, and its administration relies solely on injection. To address this issue, we successfully expressed and purified a recombinant porcine IFN\u03b1 and IFN\u03b3 fusion protein (rPoIFN\u03b1\/\u03b3). Furthermore, we developed a pH-triggered humic acid hydrogel delivery system that effectively protects rPoIFN\u03b1\/\u03b3 from gastric acid degradation, enhancing its oral bioavailability. Neither the humic acid hydrogel nor rPoIFN\u03b1\/\u03b3 exhibited cytotoxic effects on porcine kidney-15 (PK-15) cells in vitro. The replication of vesicular stomatitis virus and pseudorabies virus (PRV) was effectively inhibited by rPoIFN\u03b1\/\u03b3, resulting in an antiviral activity of approximately 10\n                    <jats:sup>4<\/jats:sup>\n                    \u00a0U\/mL. Scanning electron microscopy revealed that the humic acid hydrogel had a loose and porous honeycomb structure. The IFN\u03b1\/\u03b3@PAM\n                    <jats:sup>gel<\/jats:sup>\n                    hydrogel effectively adsorbed rPoIFN\u03b1\/\u03b3, as confirmed by Fourier transform infrared spectroscopy analysis, demonstrating a favourable IFN-loading capacity. In vitro experiments revealed that IFN\u03b1\/\u03b3@PAM\n                    <jats:sup>gel<\/jats:sup>\n                    swelled and released IFN\u03b1\/\u03b3 rapidly at pH 7.4 but not at pH 1.2. The oral administration of IFN\u03b1\/\u03b3@PAM\n                    <jats:sup>gel<\/jats:sup>\n                    in mice enhanced the proliferation and differentiation of CD4\n                    <jats:sup>+<\/jats:sup>\n                    and CD8\n                    <jats:sup>+<\/jats:sup>\n                    cells. Additionally, mice infected with PRV and treated with IFN\u03b1\/\u03b3@PAM\n                    <jats:sup>gel<\/jats:sup>\n                    presented increased transcription levels of interferon-stimulated genes in the serum, reduced mortality rates, lower viral loads in various tissues, and decreased levels of organ damage. In conclusion, this study demonstrates that orally administered IFN\u03b1\/\u03b3@PAM\n                    <jats:sup>gel<\/jats:sup>\n                    has antiviral and immunomodulatory effects, highlighting its potential as a therapeutic agent against PRV infection.\n                  <\/jats:p>","DOI":"10.1186\/s13567-024-01411-w","type":"journal-article","created":{"date-parts":[[2024,11,20]],"date-time":"2024-11-20T09:12:14Z","timestamp":1732093934000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["A pH-triggered self-releasing humic acid hydrogel loaded with porcine interferon \u03b1\/\u03b3 achieves anti-pseudorabies virus effects by oral administration"],"prefix":"10.1186","volume":"55","author":[{"given":"Maoyuan","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongli","family":"Shi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baishi","family":"Lei","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wuchao","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingjing","family":"Feng","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shenghu","family":"Ge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wanzhe","family":"Yuan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5158-741X","authenticated-orcid":false,"given":"Kuan","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,11,20]]},"reference":[{"key":"1411_CR1","doi-asserted-by":"publisher","first-page":"540","DOI":"10.1016\/j.actbio.2023.06.039","volume":"168","author":"X Liao","year":"2023","unstructured":"Liao X, Nie J, Yuan X, Feng Z, Cui E, Wu Y, Li Y, Scherman D, Liu Y (2023) Carbopol dispersed PAA-modified UIO-66 with high colloidal stability as a combination nano-adjuvant boosts immune response and protection against pseudorabies virus in mice and pigs. 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