TY - JOUR
T1 - Enhancing heterologous protection in pigs vaccinated with chimeric porcine reproductive and respiratory syndrome virus containing the full-length sequences of shuffled structural genes of multiple heterologous strains
AU - Tian, Debin
AU - Cao, Dianjun
AU - Lynn Heffron, C.
AU - Yugo, Danielle M.
AU - Rogers, Adam J.
AU - Overend, Christopher
AU - Matzinger, Shannon R.
AU - Subramaniam, Sakthivel
AU - Opriessnig, Tanja
AU - Leroith, Tanya
AU - Meng, Xiang-jin
PY - 2017/4/25
Y1 - 2017/4/25
N2 - Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of arguably the most economically important global swine disease. The extensive genetic variation of PRRSV strains is a major obstacle for heterologous protection of current vaccines. Previously, we constructed a panel of chimeric viruses containing only the ectodomain sequences of DNA-shuffled structural genes of different PRRSV strains in the backbone of a commercial vaccine, and found that one chimeric virus had an improved cross-protection efficacy. In this present study, to further enhance the cross-protective efficacy against heterologous strains, we constructed a novel chimeric virus VR2385-S3456 containing the full-length sequences of shuffled structural genes (ORFs 3-6) from 6 heterologous PRRSV strains in the backbone of PRRSV strain VR2385. We showed that the chimeric virus VR2385-S3456 induced a high level of neutralizing antibodies in pigs against two heterologous strains. A subsequent vaccination and challenge study in 48 pigs revealed that the chimeric virus VR2385-S3456 conferred an enhanced cross-protection when challenged with heterologous virus strain NADC20 or a contemporary heterologous strain RFLP 1-7-4. The results suggest that the chimera VR2385-S3456 may be a good PRRSV vaccine candidate for further development to confer heterologous protection.
AB - Porcine reproductive and respiratory syndrome virus (PRRSV) is the causative agent of arguably the most economically important global swine disease. The extensive genetic variation of PRRSV strains is a major obstacle for heterologous protection of current vaccines. Previously, we constructed a panel of chimeric viruses containing only the ectodomain sequences of DNA-shuffled structural genes of different PRRSV strains in the backbone of a commercial vaccine, and found that one chimeric virus had an improved cross-protection efficacy. In this present study, to further enhance the cross-protective efficacy against heterologous strains, we constructed a novel chimeric virus VR2385-S3456 containing the full-length sequences of shuffled structural genes (ORFs 3-6) from 6 heterologous PRRSV strains in the backbone of PRRSV strain VR2385. We showed that the chimeric virus VR2385-S3456 induced a high level of neutralizing antibodies in pigs against two heterologous strains. A subsequent vaccination and challenge study in 48 pigs revealed that the chimeric virus VR2385-S3456 conferred an enhanced cross-protection when challenged with heterologous virus strain NADC20 or a contemporary heterologous strain RFLP 1-7-4. The results suggest that the chimera VR2385-S3456 may be a good PRRSV vaccine candidate for further development to confer heterologous protection.
KW - Porcine reproductive and respiratory syndrome virus (PRRSV)
KW - Vaccine
KW - DNA shuffling
KW - Cross-protection
KW - Heterologous strains
KW - RFLP 1-7-4
U2 - 10.1016/j.vaccine.2017.03.046
DO - 10.1016/j.vaccine.2017.03.046
M3 - Article
SN - 0264-410X
VL - 35
SP - 2427
EP - 2434
JO - Vaccine
JF - Vaccine
IS - 18
ER -