From 2010, novel recombinant lineage 3 of porcine reproductive and respiratory syndrome virus 2 (PRRSV2) has continuously emerged China, which has brought about clinical outbreaks of the disease. Previously, a PRRSV2 strain named ZJnb16-2 was identified as a recombinant virus from lineage 8 and 3. In this study, two modified-live vaccines VR2332 MLV and HuN4-F112, which belong to lineage 5 and 8 respectively, were used for efficacy evaluation against the challenge of ZJnb16-2. Piglets vaccinated with HuN4-F112 exhibited temporary fever, higher average daily weight gain, and mild clinical signs as compared to VR2332 MLV vaccinated and unvaccinated piglets upon ZJnb16-2 challenge. Both vaccines could inhibit virus replication in piglets at 21days post challenge (DPC). Cross-reactivity of interferon (IFN)-γ secreting cells against ZJnb16-2 were detected in both vaccinated piglets. The number of IFN-γ secreting cells against ZJnb16-2 in the vaccination group exhibited sustaining elevation after challenge. Results demonstrated that both vaccines provided partial protection against ZJnb16-2 infection. A cross-neutralization antibody against ZJnb16-2 was not detected in any vaccinated piglet before challenge. A low neutralizing antibody titer against ZJnb16-2 was detected after challenge. Besides, all the vaccinated piglets suffered from different degrees of lung pathological lesions, indicating neither VR2332 MLV nor HuN4-F112 provided full protection against ZJnb16-2. This study provides valuable guidelines to control the recombinant virus from lineage 8 and 3 infection with MLV vaccines in the field.