On the stability of sequences inserted into viral genomes

Willemsen, Anouk; Zwart, Mark P

Live attenuated vaccines for porcine reproductive and respiratory syndrome (PRRSV) have failed to provide effective protection due to the genetic diversity of circulating PRRSV strains. To improve the efficacy of PRRSV vaccination, a recombinant virus expressing porcine Interleukin-4 (a regulator of the immune response) was constructed (Zhijun . This recombinant virus remained stable upon serial passaging in vitro, and induced higher ratios of Interleukin-4 and CD4þCD8þ doublepositive T cells in vivo. Despite the presumably better immune response of the host, the recombinant PRRSV vaccine did not significantly improve protection efficacy (Zhijun . In another attempt, granulocyte-macrophage colony-stimulating factor (GM-CSF) was inserted in a PRRSV vaccine strain. The inserted gene was stably expressed upon serial passaging in vitro, and the presence of GM-CSF led to increased surface expression of MHCIþ, MHCIIþ, and CD80/86þ (Yu et al. 2014) . Although evaluated solely in vitro, this recombinant strain is expected to elicit stronger immune responses and hereby improve vaccine efficacy against PRRSV infection.