H1N2亚型猪流感病毒的灭活稳定性及小鼠免疫原性评价OA

To enhance the inactivation stability and immunogenicity of swine influenza virus(SIV),the HA and NA genes of the H1N2 subtype strain A/Swine/Jiangsu/1281/2019(JS1281)were combined with the six internal genes of A/Puerto Rico/8/1934(PR8)to generate a recombinant virus,designated r1281.Site-directed mutations(K170Q,S174T,D202I,and S174T+Y175F)were introduced into the HA pro-tein of r1281 at amino acid positions associated with viral thermostability.The biological character-istics of r1281 and the mutant recombinant viruses were analyzed,and the protective efficacy of r1281-174T+175F was further evaluated in mice through immunization and challenge experiments.Results showed that,compared with the parental virus r1281,the mutant virus r1281-174T+175F exhibited enhanced replication capacity in MDCK cells and significantly improved inactivation stability after treatment with either formaldehyde or binary ethyleneimine(BEI).Moreover,mice immunized with formaldehyde or BEI-inactivated r1281-174T+175F produced higher hemagglutination inhibition anti-body titers and were effectively protected against pathological damage in their organs.These findings demonstrate that the combined mutations S174T and Y175F are critical for maintaining the inactivation stability of SIV without compromising its immunogenicity,providing a scientific basis for improving the antigen stability of SIV-inactivated vaccines.