Evaluation of the Cross-Protective Efficacy of a Chimeric Porcine Reproductive and Respiratory Syndrome Virus Constructed Based on Two Field Strains

Abstract

One of the major hurdles to porcine reproductive and respiratory syndrome (PRRS) vaccinology is the limited or no cross-protection conferred by current vaccines. To overcome this challenge, a PRRS chimeric virus (CV) was constructed using an FL12-based cDNA infectious clone in which open reading frames (ORFs) 3–4 and ORFs 5–6 were replaced with the two Korean field isolates K08-1054 and K07-2273,respectively. This virus was evaluated as a vaccine candidate to provide simultaneous protection against two genetically distinct PRRS virus (PRRSV) strains. Thirty PRRS-negative three-week-old pigs were divided into five groups and vaccinated with CV, K08-1054, K07-2273, VR-2332, or a mock inoculum. At 25 days post-vaccination (dpv), the pigs in each group were divided further into two groups and challenged with either K08-1054 or K07-2273. All of the pigs were observed until 42 dpv and were euthanized for pathological evaluation. Overall, the CV-vaccinated group exhibited higher levels of tumor necrosis factor-alpha (TNF-α), interferon-gamma (IFN-γ), and interleukin-12 (IL-12) expression and of serum virus-neutralizing antibodies compared with the other groups after vaccination and also demonstrated better protection levels against both viruses compared with the challenge control group. Based on these results, it was concluded that CV might be an effective vaccine model that can confer a broader range of cross-protection to various PRRSV strains.

Chimeric HP-PRRSV2 containing an ORF2-6 consensus sequence induces antibodies with broadly neutralizing activity and confers cross protection against virulent NADC30-like isolate

“…A multi-strain vaccine constructed based on five attenuated PRRSV strains was evaluated in pigs, which did not provide an improved cross protection compared with the single-strain vaccine and which might have a safety issue [ 39 ]. A chimeric PRRSV based on two field strains could confer better protection against both viruses but its efficiency against other heterologous strains was not tested [ 40 ]. DNA shuffling of individual envelope encoding genes (ORF3, ORF4, ORF5, ORF6) from multiple strains could generate chimeric viruses with improved cross-neutralizing antibodies [ 20 – 22 ].…”

Evaluation of the Cross-Protective Efficacy of a Chimeric PRRSV Vaccine against Two Genetically Diverse PRRSV2 Field Strains in a Reproductive Model

“…PRRS-modified live vaccines (MLVs) have been used to control PRRSV, providing better homologous protection than killed PRRSV vaccines or recombinant vaccines [25]. However, a major problem in the use of PRRS MLVs is their limited cross-protection [26][27][28]. Additionally, the use of PRRS MLVs has serious safety issues due to quick reversion to virulence of the vaccine strains during serial passages in pigs [29][30][31].…”

Porcine Reproductive and Respiratory Syndrome Virus: Immune Escape and Application of Reverse Genetics in Attenuated Live Vaccine Development

“…Pigs vaccinated with the chimeric virus have higher levels of TNF-α, IFN-γ, IL-12, and serum virus-neutralizing antibodies, and lower levels of IL-10 and viral loads in the lung. The chimeric virus exhibits better protection levels against K08-1054 and K07-2273 [ 135 ].…”