MGF100 but not MGF300 family is a potential multigene-deleted target for ASFV attenuation and live attenuated vaccine development
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African swine fever is a highly contagious and lethal disease of swine, but there are few therapeutic options available for treatment. Therefore, it is urgent to develop safe and effective vaccines. In this regard, we described the differential effect of deletion of whole MGF100 and MGF300 families from Genotype Ⅱ highly virulent strain on virus replication, virulence and induction of protection. The resulting ASFV-Δ100 and ASFV-Δ300 mutants demonstrated reduced growth kinetics in vitro, with the former displaying aberrant virus morphogenesis. The ASFV-Δ100 was efficiently attenuated, whereas the ASFV-Δ300 still retained virulence. In homologous lethal challenge, two mutants achieved the same protection rate, with the former providing more pathological protection on organs. Mechanically, we found that ASFV-Δ100 was capable of inducing more robust innate immune in vitro and more consistent P30 antibody response in vivo. To conclude, the MGF100 family is a potential multigene-deleted target for ASFV live attenuated vaccine development.