Concurrent but consecutive vaccination of modified live PRRSV-1 and PRRSV-2 provides better protection in nursery pigs

Porcine reproductive and respiratory syndrome (PRRS) virus is a severe threat to the global swine industry. Modified live virus vaccines (MLVs) for two PRRSV species (PRRSV-1 and PRRSV-2) are the most widely used approach to control PRRSV-caused diseases. For swine herds influenced by PRRSV-1 and PRRSV-2, how to rationalize MLV immunization strategies for robust and cross-protective immune responses has been a long-lasting need. In this study, we found that the replication of PRRSV-1 is strongly suppressed by co-infection with PRRSV-2 in vitro , especially under concurrent co-infection conditions. We compared the adaptive immune responses between consecutive and concurrent vaccination methods in nursery pigs, vaccinated either 3 days apart (PRRSV-1 MLV followed by PRRSV-2 MLV, consecutive) or together on the same day (concurrent). PRRSV-1 RNAs were mainly detectable in the sera of consecutively vaccinated pigs. In contrast, PRRSV-2 RNAs in sera were not changed in both vaccination strategies. After the homologous PRRSV-1 or PRRSV-2 challenge, we found that consecutive vaccination slightly improved PRRSV-1 viremia clearance and did not attenuate the PRRSV-2 viremia clearance. Both vaccination strategies induced comparable T-helper cell responses against PRRSV-1 and PRRSV-2 in peripheral blood before and after the challenge. Interestingly, consecutive vaccination induced significantly higher PRRSV-1-specific post-challenge T-helper and cytotoxic T cells responses in the tracheobronchial lymph nodes than concurrent vaccination. Furthermore, consecutive vaccination significantly improved neutralizing antibody responses against PRRSV-1 and PRRSV-2 in comparison with concurrent vaccination. In conclusion, consecutive vaccination appears to be better for viral clearance and induction of adaptive immune response, and our study provides a preliminary rationale to optimize PRRS MLV immunization strategy for better dual protection. • Replication of PRRSV-1 is strongly suppressed by co-infection with PRRSV-2 in vitro . • Vaccination strategies for two PRRSV species wereanalyzed in a nursery pig challenge model. • Concurrent MLV vaccination failed to protect pigs against PRRSV-1 but it performed comparably to consecutive vaccination against PRRSV-2. • Consecutive MLV immunization (PRRSV-1 followed by PRRSV-2) provided better protection protection against both species of PRRSV infection.