Abstract
The ORF5-encoded major envelope glycoprotein (GP5) is one of the key immunogenic proteins of the porcine reproductive and respiratory syndrome virus (PRRSV) and is the leading target for the development of the new generation of vaccines against PRRS. However, weak and tardy neutralizing antibodies have been elicited in several developed experimental vaccines expressing PRRSV GP5. More recent evidence has demonstrated a non-neutralizing decoy epitope upstream of the neutralizing epitope of GP5, which might prevent the development of a strong neutralizing antibody response against PRRSV. In the present study, we modified the ORF5 gene by inserting a Pan DR T-helper cell epitope (PADRE) between the neutralizing epitope and the decoy epitope to minimize or eliminate the decoy effect of the non-neutralizing epitope. The immunogenicity of the modified GP5 was further evaluated using DNA vaccination. The results showed that significantly enhanced neutralizing antibodies were elicited in mice immunized with the DNA construct expressing the modified GP5 compared with the native GP5. Slightly increased levels of GP5-specific ELISA antibodies and T-cell proliferative activities were also observed. These results indicate that the high immunogenicity of the modified GP5 might facilitate the development of improved PRRS vaccines in the future.
Similar content being viewed by others
References
K.K. Keffaber, Am. Assoc. Swine Pract. Newslett. 1, 1–10 (1989)
G. Wensvoort, C. Terpstra, J.M. Pol, E.A. ter Laak, M. Bloemraad, E.P. de Kluyver, C. Kragten, L. van Buiten, A. den Besten, F. Wagenaar, Vet. Q 13, 21–30 (1991)
J.J. Meulenberg, Vet. Res. 31, 11–21 (2000)
S. Dea, C.A. Gagnon, H. Mardassi, B. Pirzadeh, D. Rogan, Arch Viral 145, 659–688 (2000)
X.J. Meng, Vet. Microbiol. 74, 309–329 (2000)
A. Botner, B. Strandbygaard, K.J. Sorensen, P. Have, K.G. Madsen, E.S. Madsen, S. Alexandersen, Vet. Rec. 141, 497–499 (1997)
K.G. Madsen, C.M. Hansen, E.S. Madsen, B. Strandbygaard, A. Botner, K.J. Sorensen, Arch. Virol. 143, 1683–1700 (1998)
A.M. Botner, M. Blixenkrone-Moller, M.H. Jensen, A. Botner, S. Kamstrup, Vaccine 22, 3628–3641 (2004)
R.G. Bastos, O.A. Dellagostin, R.G. Barletta, A.R. Doster, E. Nelson, F.A. Osorio, Vaccine 21, 21–29 (2002)
R.G. Bastos, O.A. Dellagostm, R.G. Barletta, A.R. Doster, E. Nelson, F. Zuekermann, F.A. Osorio, Vaccine 22, 467–474 (2004)
C.A. Gagnon, G. Lachapelle, Y. Langelier, B. Massie, S. Dea, Arch. Viral. 148, 951–972 (2003)
H.S. Jung, I.W. Hwang, S.M. Kim., C.J. Kim, K.S. Shin, H.S. Kim, J. Vet. Sci. 3, 13–18 (2002)
J. Kwang, F. Zuckermann, G. Ross, S. Yang, F. Osorio, W. Liu, S. Low, Res. Vet. Sci. 67, 199–201 (1999)
B. Pirzadeh, S. Dea, J. Gen. Viral. 79, 989–999 (1998)
J. Plana Duran, I. Climent, J. Sarraseca, A. Urniza, E. Cortes, C. Vela, J.I. Casal, Virus. Gene. 14, 19–29 (1997)
M. Ostrowski, J.A. Galeota, A.M. Jar, K.B. Platt, F.A. Osorio, O.J. Lopez, J. Virol. 76, 4241–4250 (2002)
R.R. Garrity, G. Rimmelzwaan, A. Minassian, w.P. Tsai, G. Lin, J.J. de Jong, J. Goudsmit, P.L. Nara, Immunol. 159, 279–289 (1997)
B.K. Chakrabarti, W.P. Kong, B.Y. Wu, Z.Y. Yang, J. Friborg, X. Ling, S.R. King, D.C. Montefiori, G.J. Nabel, J. Virol. 76, 5357–5368 (2002)
L.A. Novotny, L.O. Bakaletz, J. Immunol. 171, 1978–1983 (2003)
J. Alexander, J. Fikes, S. Hoffman, E. Franke, J. Sacci, E. Appella, F.V. Chisari, L.G. Guidotti, R.W. Chesnut, B. Livingston, A. Sette, Immunol. Res. 18, 79–92 (1998)
L.R. Fang, Doctoral thesis, 2003
H.S. Kim, J. Kwang, I.J. Yoon, H.S. Joo, M.L. Frey, Arch. Virol. 133, 477–483 (1993)
J. Alexander, J. Sidney, S. Southwood, J. Ruppert, C. Oseroff, A. Maewal, K. Snoke, H.M. Serra, R.T. Kubo, A. Sette, Immunity 1, 751–61 (1994)
D.I. Bounous, R.P. Campagnoli, J. Brown, Avian. Dis. 36, 1022–1027 (1992)
I.J. Yoon, H.S. Joo, S.M. Goyal, T.W. Molitor, J. Vet. Diagn. Invest. 6, 289–292 (1994)
S.M. Cleveland, E. Buratti, T.D. Jones, P. North, F. Baralle, L. McLain, T. McInerney, Z. Durrani, N.J. Dimmock, Virology 266, 66–78 (2000)
I. Kiszka, K.D. Kmiecia, J. Gzyl, T. Naito, E. Bolesta, A. Sieron, S.P. Singh, A. Srinivasan, G. Trinchieri, Y. Kaneko, D. Kozbor, J. Virol. 76, 4222–4232 (2002)
M.P. Murtaugh, Z. Xiao, F. Zuckermann, Viral. immunol. 15, 533–547 (2002)
F.A. Osorio, J.A. Galeota, E. Nelson, B. Brodersen, A. Doster, R. Wills, F. Zuckermann, W.W. Laegreid, Virology 302, 9–20 (2002)
K.J. Yoon, L.L. Wu, J.J. Zimmerman, H.T. Hill, K.B. Platt, Viral. Immunol. 9, 51–63 (1996)
J. Alexander, M.F. del Guercio, A. Maewal, L. Qiao, J. Fikes, R.W. Chesnut, J. Paulson, D.R. Bundle, S. DeFrees, A. Sette, J. Immunol. 164, 1625–1633 (2000)
M.F. del Guercio, J. Alexander, R.T. Kubo, T. Arrhenius, A. Maewal, E. Appella, S.L. Hoffman, T. Jones, D. Valmori, K. Sakaguchi, H.M. Grey, A. Sette, Vaccine 15, 441–448 (1997)
P. Pamonsinlapatham, N. Decroix, L. Mihaila-Amrouche, A. Bouvet, J.P. Bouvet, Scand J. Immunol. 59, 504–510 (2004)
I.S. Soares, M.M. Rodrigues, Parasitology 124, 237–246 (2002)
J.J. Meulenberg, J.N. Bos-de Ruijter, R. van de Graaf, G. Wensvoort, R.J. Moormann, J. Virol. 72, 380–387 (1998)
F.S. Nielsen, G. Liu, J. Nielsen, M.B. Oleksiewicz, A. Botner, T. Storgaard, K.S. Faaberg, J. Viral. 77, 3702–3711 (2003)
Acknowledgements
We are grateful to Dr R. Zhou for critical reading of the manuscript. This study was supported by grants from the National Natural Science Foundation of China (30300257, 30571385), The National Basic Research Program (973) of China (2005CB523200), and the Youth Scientist Project of Wuhan City (No. 20025001041).
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Fang, L., Jiang, Y., Xiao, S. et al. Enhanced immunogenicity of the modified GP5 of porcine reproductive and respiratory syndrome virus. Virus Genes 32, 5–11 (2006). https://doi.org/10.1007/s11262-005-5839-y
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/s11262-005-5839-y