Alternative codon usage of PRRS virus ORF5 gene increases eucaryotic expression of GP5 glycoprotein and improves immune response in challenged pigs

Kheyar, Ali; Jabrane, Ahmed; Zhu, Chengru; Cléroux, Patrick; Massie, Bernard; Dea, S.; Gagnon, Carl A.

doi:10.1016/j.vaccine.2005.03.012

Cited by 27 publications

(14 citation statements)

References 38 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The present study demonstrated that the deglycosylation of GP5 also successfully improved the immunogenicity of an inactivated virus that was incapable of viral replication and endogenous viral protein synthesis to a level similar to that of a live virus. In previous studies, enhanced developments of SN antibodies have not always been associated with blocking viremia [48,49]. However, Osorio et al [50] previously demonstrated that the SN antibody response is relatively correlated with protective immunity in PRRSV infection, particularly regarding the clearance of viremia; our results are in agreement with their findings [50].…”

Section: Discussionsupporting

confidence: 91%

Protective humoral immune response induced by an inactivated porcine reproductive and respiratory syndrome virus expressing the hypo-glycosylated glycoprotein 5

Lee¹,

Kwon²,

Osorio³

et al. 2014

Vaccine

View full text Add to dashboard Cite

Porcine reproductive and respiratory syndrome (PRRS) causes significant economic losses to the swine industry worldwide. Although inactivated and live vaccines are commercially available for the control of PRRS, both types of vaccine have not always proven successful in terms of generating a protective immune response, particularly in the case of inactivated vaccines. In this study, we tested whether an inactivated vaccine could induce a humoral immune response to PRRS during a homologous challenge. Amino acid substitutions were introduced into glycoprotein (GP) 5 of the FL12 strain of the PRRS virus (PRRSV) using site-directed mutagenesis with a pFL12 infectious clone. The substitutions led to double deglycosylation in the putative glycosylation moieties on GP5. The mutant virus was subsequently inactivated with binary ethylenimine. The efficacy of the inactivated mutant virus was compared with that of the inactivated wild-type PRRSV. Only the inactivated mutant PRRSV induced serum neutralizing antibodies at six weeks post-vaccination. The group that was administered the inactivated mutant virus twice exhibited a significantly increased neutralizing antibody titer after a challenge with the virulent homologous strain and exhibited more rapid clearing of viremia compared to other groups, including the groups that were administered either the inactivated mutant or wild-type virus only once and the group that was administered the inactivated wild-type virus twice. Histopathological examination of lung tissue sections revealed that the group that was administered the inactivated mutant virus twice exhibited significantly thinner alveolar septa, whereas the thickness of the alveolar septa of the other groups were markedly increased due to lymphocyte infiltration. These results indicated that the deglycosylation of GP5 enhanced the immunogenicity of the inactivated mutant PRRSV and that twice administrations of the inactivated mutant virus conferred better protection against the homologous challenge. These findings suggest that the inactivated PRRSV that expresses a hypo-glycosylated GP5 is a potential inactivated vaccine candidate and a valuable tool for controlling PRRS for the swine industry.

show abstract

Section: Discussionsupporting

confidence: 91%

Protective humoral immune response induced by an inactivated porcine reproductive and respiratory syndrome virus expressing the hypo-glycosylated glycoprotein 5

Lee¹,

Kwon²,

Osorio³

et al. 2014

Vaccine

View full text Add to dashboard Cite

show abstract

“…GP5 and M protein are present as disulfide-linked heterodimers [6] and are the major components of virus envelope. Any of GP5, M, and GP5/M heterodimer is known to have good immunogenicity and associate with protection against PRRSV infection [10][11][12][13][14][15], but little is known about that of the minor envelope proteins [16].…”

Section: Introductionmentioning

confidence: 99%

Analysis of immunogenicity of minor envelope protein GP3 of porcine reproductive and respiratory syndrome virus in mice

Jiang

et al. 2007

Virus Genes

View full text Add to dashboard Cite

Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically significant viral diseases in swine industry. Though the minor envelope protein GP3 is associated with protective immunity, its immunogenicity and protective mechanism are poorly known. In this study, two recombinant adenoviruses, rAd-GP3 expressing complete GP3 and rAd-tGP3 expressing truncated GP3 in which aa2-64 were deleted, were constructed and the immunogenicity were tested in a mouse model. Four groups of BALB/c mice were immunized subcutaneously twice at 2-week internals with the recombinants rAd-GP3 and rAd-tGP3 or with wild type adenovirus (wtAd) and PBS as control. The results showed that the mice immunized with recombinant adenoviruses developed PRRSV-specific neutralizing antibodies and cellular immune response, including T-cell proliferation responses and cytotoxic T responses, by 2 weeks post-primary immunization. Moreover, the levels of immune responses of mice immunized with rAd-tGP3 were significantly higher than that of mice with rAd-GP3. It indicated that the first 64aa fragment of GP3 might affect the conformation of the antigen structures of GP3 protein. GP3 protein should be one of candidate molecules for developing a new safer effective vaccine.

show abstract

“…This result is not surprising since it has been reported that virus-like particles composed of PRRSV GP5 and M protein were capable of eliciting neutralizing antibodies during mice immunization [30]. However, whether the phenotype observed in our mice model would be able to translate into porcine vaccine development is still questionable as PRRSV GP5-based vaccines only induce unsatisfactory neutralization antibodies and confer limited protection upon challenge [31–33]. Similarly, although the E2 recombinant virus successfully induces neutralizing antibodies against the CSFV C-strain in our mouse system, further investigations have to be performed to evaluate its protective immune response induction in a pig model.…”

Section: Discussionmentioning

confidence: 65%

Recombinant Encephalomyocarditis Viruses Elicit Neutralizing Antibodies against PRRSV and CSFV in Mice

et al. 2015

View full text Add to dashboard Cite

Encephalomyocarditis virus (EMCV) is capable of infecting a wide range of species and the infection can cause myocarditis and reproductive failure in pigs as well as febrile illness in human beings. In this study, we introduced the entire ORF5 of the porcine reproductive and respiratory syndrome virus (PRRSV) or the neutralization epitope regions in the E2 gene of the classical swine fever virus (CSFV), into the genome of a stably attenuated EMCV strain, T1100I. The resultant viable recombinant viruses, CvBJC3m/I-ΔGP5 and CvBJC3m/I-E2, respectively expressed partial PRRSV envelope protein GP5 or CSFV neutralization epitope A1A2 along with EMCV proteins. These heterologous proteins fused to the N-terminal of the nonstructural leader protein could be recognized by anti-GP5 or anti-E2 antibody. We also tested the immunogenicity of these fusion proteins by immunizing BALB/c mice with the recombinant viruses. The immunized animals elicited neutralizing antibodies against PRRSV and CSFV. Our results suggest that EMCV can be engineered as an expression vector and serve as a tool in the development of novel live vaccines in various animal species.

show abstract

Alternative codon usage of PRRS virus ORF5 gene increases eucaryotic expression of GP5 glycoprotein and improves immune response in challenged pigs

Cited by 27 publications

References 38 publications

Protective humoral immune response induced by an inactivated porcine reproductive and respiratory syndrome virus expressing the hypo-glycosylated glycoprotein 5

Protective humoral immune response induced by an inactivated porcine reproductive and respiratory syndrome virus expressing the hypo-glycosylated glycoprotein 5

Analysis of immunogenicity of minor envelope protein GP3 of porcine reproductive and respiratory syndrome virus in mice

Recombinant Encephalomyocarditis Viruses Elicit Neutralizing Antibodies against PRRSV and CSFV in Mice

Contact Info

Product

Resources

About