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that can cause reproductive disorders in sows and affect the breathing of piglets, seriously endangering pig breeding worldwide. In this study, Lactobacillus plantarum NC8 was used as the expression delivery vector of foreign proteins, and a single-chain antibody was designed based on an mAb-PN9cx3 sequence. Three recombinant strains of Lactobacillus plantarum, namely, NC8\/pSIP409-pgsA\u2018-PN9cx3-scFV(E), NC8\/pSIP409-pgsA\u2019-PN9cx3-HC(E), and NC8\/pSIP409-pgsA\u2018-PN9cx3-LC(E), were successfully constructed. In an in vitro test, the viral load of each experimental group was significantly lower than that of the control group (p &lt; 0.01). In the piglet challenge protection test, the percentage of CD3+CD8+T cells in the blood of piglets given complex lactic acid bacteria was significantly increased before and after the challenge (p &lt; 0.01); the body temperature of piglets in this group was normal, the viral load of each organ was reduced, and the obvious pathological changes in each tissue were alleviated. At the same time, the abundance of Bacteroides, Fusobacterium, and other bacteria in the intestinal tracts of the piglets changed, affecting the metabolism of carbohydrates and amino acids and the differentiation of Th1 and Th2 cells. This experiment provides a feasible strategy and method for the design of a PRRSV vaccine.<\/jats:p>","DOI":"10.3390\/ijms26052257","type":"journal-article","created":{"date-parts":[[2025,3,4]],"date-time":"2025-03-04T03:26:21Z","timestamp":1741058781000},"page":"2257","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Lactobacillus plantae Expressing Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Single-Chain Antibody Can Inhibit PRRSV Replication and Change the Intestinal Flora Structure of Piglets"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0241-8430","authenticated-orcid":false,"given":"Tianming","family":"Niu","sequence":"first","affiliation":[{"name":"College of Veterinary Medicine, Jilin Agricultural University, Changchun 130012, China"},{"name":"Jilin Provincial Engineering Research Center of Animal Probiotics, Jilin Provincial Key Laboratory of 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