Foot-and-mouth disease virus vaccine with VP1 G-H loop substitution of the Cathay strain broadens antigen spectrum.

Recently, serotype O foot-and-mouth disease viruses (FMDVs) belonging to four lineages (O/ME-SA/PanAsia, O/ME-SA/Ind2001, O/SEA/Mya-98, and O/Cathay) co-circulate in China, and the emergence of new variant viruses belonging to the Cathay lineage renders the existing vaccines less effective, which poses a serious threat to the livestock industries. The surface-exposed G-H loop of the VP1 structural protein of FMDV plays an important role in inducing neutralizing antibodies, generation of antigenic variants, and virus attachment. Here, we generated three recombinant FMDVs in which the G-H loops have been substituted with the corresponding sequences from the circulating strains of the PanAsia, Mya-98, and Cathay lineages based on an infectious cDNA clone of a chimeric FMDV, which carries amino acid substitutions in the leader protein and all surface proteins of FMDV O/XJ/CHA/2017. All mutant viruses exhibited a significantly improved replication capacity in BHK-21 cells and displayed relatively larger plaque morphologies compared with the parental virus. Chemically inactivated vaccines prepared from the parental virus and the mutant viruses all induced protective liquid-phase blocking ELISA (LPBE) antibodies against FMDVs in pigs after 28 days post vaccination (dpv), but only the vaccine with the substitution of the G-H loop of the Cathay strain induced protective neutralizing antibodies against the viruses of four lineages, while other vaccines exhibited excellent immunological cross-reactivity to the viruses of Ind2001, PanAsia, and Mya-98 lineages but did not for the Cathay virus at 28 dpv. Our studies indicated that the G-H loop of the Cathay virus plays a critical role in the antigenic drift of FMDV, which will provide key insights for designing porcinophilic FMDV vaccines in the future. KEY POINTS: • The swapping of the G-H loops of FMDVs notably improved replication capacity of FMDV in BHK-21 cells. • The swapping of the G-H loop of the Cathay virus obviously broadens antigenic coverage of FMDV vaccine. • The study showed that the G-H loop of the Cathay virus plays a critical role in antigenic drift of FMDV.