A Live-Attenuated Chimeric Vaccine Candidate Against the Emerging NADC34-Like PRRSV.

NADC34-like porcine reproductive and respiratory syndrome virus (PRRSV) has been circulating in China for several years, causing substantial economic losses to the local pig industry. Current commercial vaccines have failed to provide complete protection against NADC34-like PRRSV infection. Additionally, the poor adaptation of NADC34-like strains to Marc-145 cells presents a considerable challenge for developing effective vaccines against these strains. This study addresses these challenges by developing a novel vaccine candidate against NADC34-like PRRSV. We engineered a recombinant PRRSV, rNADC34-CHSps, by replacing the structural protein region of the JS2021NADC34 strain with that of the CHR6 strain to improve its adaptation to Marc-145 cells. The rescued strain could proliferate well in Marc-145 cells, maintaining high titers and stable growth kinetics even at high passage numbers. Piglets were vaccinated with rNADC34-CHSps at passage 80 and then challenged with the virulent NADC34-like PRRSV strain, JS2021NADC34, at 28 days post-vaccination. All vaccinated piglets developed specific antibodies against PRRSV at 14 dpv and showed no significant clinical symptoms, even after exposure to PRRSV JS2021NADC34. Furthermore, the vaccinated piglets gained significantly more weight, displayed much less severe pathological lesions, and reduced viremia compared to the challenge control piglets. These results indicate that rNADC34-CHSps is a promising vaccine candidate against NADC34-like PRRSV infection, highlighting the potential of targeted genomic modifications to enhance vaccine efficacy.