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Substantial genetic variation among PRRSV strains represents a major obstacle for the development of a broadly protective vaccine. We describe here a novel approach to generate a PRRSV vaccine strain that could confer broad cross-protection against divergent PRRSV isolates.
We had initially obtained a set of 60 non-redundant, full-genome sequences of type-II PRRSV. After that, we generated the consensus genome (designated as PRRSV-CON) by aligning the 60 PRRSV full-genome sequences, followed by selecting the most common nucleotide found at each position of the alignment. Our analysis demonstrates that the PRRSV-CON has the highest degree of sequence identity to the PRRSV field-isolates when compared to any current PRRS vaccine strains, both at the full-genome level and the individual gene level. Next, we chemically synthesized the PRRSV-CON genome and assembled it into a bacterial plasmid under the control of the T7 promoter. The resulting PRRSV-CON cDNA clone is fully infectious. Viable virus is consistently produced after MARC-145 cells are transfected with the RNA transcript produced from the PRRSV-CON cDNA clone. Moreover, the PRRSV-CON virus replicates as efficiently as our prototype PRRSV strain FL12, both in vitro and in vivo. Importantly, primary infection of pigs with PRRSV-CON virus confers significantly broader protection than the prototype PRRSV strain FL12 when tested upon subsequent challenge with a third unrelated heterologous PRRSV strain.
Collectively, our data demonstrate that the PRRSV-CON virus can serve as a potential vaccine candidate for the development of a novel PRRS vaccine with broader cross-protection.
H. Vu, F. Ma, W. Laegreid, A. Pattnaik, F. Osorio. Development of a synthetic porcine reproductive and respiratory syndrome virus strain that confers broader cross-protection. 2014 North American PRRS Symposium.
