| Summary: | Although widespread administration of attenuated porcine reproductive and respiratory syndrome virus (PRRSV) vaccines has been implemented since they first became commercially available two decades ago, PRRSV infection prevalence in swine herds remains high. The limited success of PRRSV vaccines is partly due to the well-established fact that a given vaccine strain confers only partial or no protection against heterologous strains. In our past work, A2MC2-P90, a novel PRRSV vaccine candidate that induced a type I IFNs response in vitro, conferred complete protection against challenge with genetically heterologous PRRSV strains. Here we assessed the ability of the PRRSV vaccine candidate A2MC2-P90 to protect piglets against the HP-PRRSV challenge and compared its efficacy to that of a licensed HP-PRRSV-specific vaccine (TJM-F92) assessed in parallel. A2MC2-P90 provided vaccinated piglets with 100% protection from a lethal challenge with extremely virulent HP-PRRSV-XJA1, while 100% mortality was observed for unvaccinated piglets by day 21 post-challenge. Notably, comparison of partial sequence (GP5) of XJA1 to A2MC2-P90 suggested there was only 88.7% homology. When comparing post-HP-PRRSV challenge responses between piglets administered A2AMC2-P90 versus those immunized with licensed vaccine TJM-F92, A2MC2-P90-vaccinated piglets rapidly developed a stronger protective humoral immune response, as evidenced by much higher titers of neutralizing antibodies, more rapid clearance of viremia and less nasal virus shedding. In conclusion, our data suggest that this novel vaccine candidate A2MC2-P90 has improved protection spectrum against heterologous HP-PRRSV strains.
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