Field porcine reproductive and respiratory syndrome viruses (PRRSV) attenuated by codon pair deoptimization (CPD) in NSP1 protected pigs from heterologous challenge

Two type 2 field porcine reproductive and respiratory syndrome viruses (PRRSV) isolated from PRRS-affected swine farms were attenuated by de-optimization of codon pair bias in NSP1. In 3-week-old pigs infection, the attenuated viruses showed significantly lower replication ability than the original viruses without distinct clinical sign and pathological lesions, which were observed in pig infected with the original viruses. Regarding induction of PRRSV specific immunity, the level of the neutralizing antibodies as well as secretion of IFN-γ-SCs in PBMCs was not different between the attenuated viruses and the original viruses. More importantly, pigs infected with the attenuated viruses exhibited significant reduction in respiratory scores, viremia, macroscopic and microscopic lung lesion scores, and PRRSV-antigen with interstitial pneumonia against a heterologous challenge with a type 2 virulent strain. Conclusively, the viruses attenuated by CPD in this study demonstrated potential usefulness as vaccine strains to provide protective immunity against diverse virulent PRRSVs.