Immune response to Fc tagged GP5 glycoproteins of porcine reproductive and respiratory syndrome virus.

Porcine reproductive and respiratory syndrome virus (PRRSV) glycoprotein 5 (GP5) is the most abundant envelope glycoprotein and a key target for neutralizing antibodies. Previous studies have demonstrated that the native GP5 glycoprotein is poorly immunogenic and not able to induce robust protective responses, probably due to the presence of a non-neutralizing decoy epitope and shielding N-linked glycans close to its neutralizing epitope. In the present report, two Fc tagged GP5 proteins (GP5-Fc containing a truncated GP5 with the deletion of its signal peptide and transmembrane regions, and GP5N-Fc containing only the ectodomain of GP5) were designed based on the sequences of a highly pathogenic PRRSV strain and produced using a baculovirus/insect cell expression system. Immunization studies showed that both GP5-Fc and GP5N-Fc elicited strong serum responses in the absence of adjuvant to the native GP5 present on the surface of purified PRRSV virons. Although GP5N-Fc failed in inducing significant titer of neutralizing antibodies in mice, GP5-Fc was shown as an effective inducer of neutralizing antibodies specific to PRRSV. Our results suggest that the modified GP5 glycoprotein with Fc tag has the potential to be a candidate for the future development of new generation vaccine against PRRSV infection.

[1]  W. Feng,et al.  Recombinant Kluyveromyces lactis expressing highly pathogenic porcine reproductive and respiratory syndrome virus GP5 elicits mucosal and cell-mediated immune responses in mice , 2014, Journal of veterinary science.

[2]  M. Murtaugh,et al.  Immune response to ORF5a protein immunization is not protective against porcine reproductive and respiratory syndrome virus infection. , 2013, Veterinary microbiology.

[3]  C. Gagnon,et al.  Immunogenic and protective properties of GP5 and M structural proteins of porcine reproductive and respiratory syndrome virus expressed from replicating but nondisseminating adenovectors , 2013, Veterinary Research.

[4]  Yongchang Cao,et al.  Production and immunogenicity of chimeric virus-like particles containing porcine reproductive and respiratory syndrome virus GP5 protein. , 2012, Vaccine.

[5]  D. Tong,et al.  Baculovirus as a PRRSV and PCV2 bivalent vaccine vector: baculovirus virions displaying simultaneously GP5 glycoprotein of PRRSV and capsid protein of PCV2. , 2012, Journal of virological methods.

[6]  M. Murtaugh,et al.  Novel structural protein in porcine reproductive and respiratory syndrome virus encoded by an alternative ORF5 present in all arteriviruses , 2011, The Journal of general virology.

[7]  J. F. Atkins,et al.  Discovery of a small arterivirus gene that overlaps the GP5 coding sequence and is important for virus production , 2011, The Journal of general virology.

[8]  C. Colaco,et al.  Adjuvant-Free Immunization with Hemagglutinin-Fc Fusion Proteins as an Approach to Influenza Vaccines , 2010, Journal of Virology.

[9]  Chun-Ming Lin,et al.  The immunogenicity of DNA constructs co-expressing GP5 and M proteins of porcine reproductive and respiratory syndrome virus conjugated by GPGP linker in pigs. , 2010, Veterinary microbiology.

[10]  Lai-Xi Wang,et al.  Expression, glycoform characterization, and antibody-binding of HIV-1 V3 glycopeptide domain fused with human IgG1-Fc. , 2010, Bioconjugate chemistry.

[11]  Yudong Ren,et al.  Heterologous expression of fused genes encoding the glycoprotein 5 from PRRSV: A way for producing functional protein in prokaryotic microorganism , 2010, Journal of Biotechnology.

[12]  J. Ciacci-Zanella,et al.  Vaccine efficacy of porcine reproductive and respiratory syndrome virus chimeras. , 2010, Vaccine.

[13]  H. Nauwynck,et al.  The M/GP5 Glycoprotein Complex of Porcine Reproductive and Respiratory Syndrome Virus Binds the Sialoadhesin Receptor in a Sialic Acid-Dependent Manner , 2010, PLoS pathogens.

[14]  T. Kimman,et al.  Challenges for porcine reproductive and respiratory syndrome virus (PRRSV) vaccinology. , 2009, Vaccine.

[15]  S. Xiao,et al.  Immunogenicity of the highly pathogenic porcine reproductive and respiratory syndrome virus GP5 protein encoded by a synthetic ORF5 gene. , 2009, Vaccine.

[16]  R. Ptak,et al.  Cross-reactive HIV-1-neutralizing activity of serum IgG from a rabbit immunized with gp41 fused to IgG1 Fc: possible role of the prolonged half-life of the immunogen. , 2009, Vaccine.

[17]  Yanjun Zhou,et al.  A recombinant plasmid co-expressing swine ubiquitin and the GP5 encoding-gene of porcine reproductive and respiratory syndrome virus induces protective immunity in piglets. , 2008, Vaccine.

[18]  Bin Zhou,et al.  Co-expressing GP5 and M proteins under different promoters in recombinant modified vaccinia virus ankara (rMVA)-based vaccine vector enhanced the humoral and cellular immune responses of porcine reproductive and respiratory syndrome virus (PRRSV) , 2007, Virus Genes.

[19]  I. Jones,et al.  Immunogenicity of the outer domain of a HIV-1 clade C gp120 , 2007, Retrovirology.

[20]  F. Osorio,et al.  Protection against Porcine Reproductive and Respiratory Syndrome Virus (PRRSV) Infection through Passive Transfer of PRRSV-Neutralizing Antibodies Is Dose Dependent , 2007, Clinical and Vaccine Immunology.

[21]  M. Torremorell,et al.  Neutralizing antibody responses of pigs infected with natural GP5 N-glycan mutants of porcine reproductive and respiratory syndrome virus. , 2006, Viral immunology.

[22]  F. Osorio,et al.  Influence of N-Linked Glycosylation of Porcine Reproductive and Respiratory Syndrome Virus GP5 on Virus Infectivity, Antigenicity, and Ability To Induce Neutralizing Antibodies , 2006, Journal of Virology.

[23]  S. Xiao,et al.  Enhanced immunogenicity of the modified GP5 of porcine reproductive and respiratory syndrome virus , 2006, Virus Genes.

[24]  M. Murtaugh,et al.  Comparison of the structural protein coding sequences of the VR-2332 and Lelystad virus strains of the PRRS virus , 1995, Archives of Virology.

[25]  F. Osorio,et al.  Role of neutralizing antibodies in PRRSV protective immunity. , 2004, Veterinary immunology and immunopathology.

[26]  F. Osorio,et al.  Immune response of pigs inoculated with Mycobacterium bovis BCG expressing a truncated form of GP5 and M protein of porcine reproductive and respiratory syndrome virus. , 2004, Vaccine.

[27]  Alicia Urniza,et al.  Baculovirus Expression of Proteins of Porcine Reproductive and Respiratory Syndrome Virus Strain Olot/91. Involvement of ORF3 and ORF5 Proteins in Protection , 2004, Virus Genes.

[28]  P. Rottier,et al.  The major envelope protein, GP5, of a European porcine reproductive and respiratory syndrome virus contains a neutralization epitope in its N-terminal ectodomain. , 2003, The Journal of general virology.

[29]  I. Jones,et al.  Improving baculovirus recombination. , 2003, Nucleic acids research.

[30]  R. Rowland,et al.  The primary neutralization epitope of porcine respiratory and reproductive syndrome virus strain VR-2332 is located in the middle of the GP5 ectodomain , 2002, Archives of Virology.

[31]  M. Ostrowski,et al.  Identification of Neutralizing and Nonneutralizing Epitopes in the Porcine Reproductive and Respiratory Syndrome Virus GP5 Ectodomain , 2002, Journal of Virology.

[32]  J. J. Meulenberg.  PRRSV, the virus. , 2000, Veterinary research.

[33]  K. Conzelmann,et al.  Monoclonal antibodies to the GP5 of porcine reproductive and respiratory syndrome virus are more effective in virus neutralization than monoclonal antibodies to the GP4. , 1999, Veterinary microbiology.

[34]  M. Murtaugh,et al.  Porcine Reproductive and Respiratory Syndrome Virus Comparison: Divergent Evolution on Two Continents , 1999, Journal of Virology.

[35]  C. Gagnon,et al.  Seroneutralization of Porcine Reproductive and Respiratory Syndrome Virus Correlates with Antibody Response to the GP5 Major Envelope Glycoprotein , 1999, Journal of veterinary diagnostic investigation : official publication of the American Association of Veterinary Laboratory Diagnosticians, Inc.

[36]  P. Wallace,et al.  Increased potency of Fc-receptor-targeted antigens , 1997, Cancer Immunology, Immunotherapy.

[37]  S. Dea,et al.  Monoclonal antibodies to the ORF5 product of porcine reproductive and respiratory syndrome virus define linear neutralizing determinants. , 1997, The Journal of general virology.

[38]  J. Meulenberg,et al.  Molecular characterization of Lelystad virus , 1997, Veterinary Microbiology.

[39]  F. Wagenaar,et al.  Lelystad virus, the cause of porcine epidemic abortion and respiratory syndrome: a review of mystery swine disease research at Lelystad. , 1992, Veterinary microbiology.