Immunisation against PCV2 structural protein by DNA vaccination of mice

Kamstrup, Søren; Barfoed, Annette Malene; Frimann, Tine Holland; Ladekjær-Mikkelsen, A.-S.; Bøtner, Anette

doi:10.1016/j.vaccine.2004.01.032

Cited by 60 publications

(38 citation statements)

References 22 publications

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“…It is conceivable that the delay in replication translates into attenuation in vivo, leading to a virus strain with vaccine potential. For PCV2, ORF2 protein has been considered as a major immunogenic capsid protein (9,30,31) and could stimulate a protective response in pigs inoculated with baculovirus-expressed recombinant ORF2 (5) or injected with DNA vaccine from ORF2 (5,19). Chimeric PCV1-2 virus with the ORF2 gene of PCV2 cloned into the nonpathogenic PCV1 genomic backbone could also induce a strong immune response against PCV2 while it is mildly pathogenic (15), suggesting that the ORF2 protein of PCV2 is a good host-protective immunogen.…”

Section: Discussionmentioning

confidence: 99%

Characterization of a Previously Unidentified Viral Protein in Porcine Circovirus Type 2-Infected Cells and Its Role in Virus-Induced Apoptosis

Liu

Chen

Kwang

2005

J Virol

275

258

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Porcine circovirus type 2 (PCV2) is the causative agent of postweaning multisystemic wasting syndrome in pigs. In this study, transcription and translation of a novel viral gene (termed ORF3 here) was detected during productive infection of PCV2 in PK15 cells. The results of infection with ORF3-deficient PCV2 by site-directed mutagenesis indicated that the protein is not essential for viral replication. To investigate the underlying mechanism of cell death caused by replication of PCV2, apoptosis characterized by chromosomal condensation and fragmentation, formation of apoptotic bodies, and significant increase in hypodiploids were detected in infected cells. We further demonstrated that PCV2-induced apoptosis required the activation of caspase-8 but not caspase-9. The activation of caspase-8 results in the activation of caspase-3 as shown by an increase in the cleavage of the caspase substrate in the infected cells. To determine whether ORF3 protein could trigger apoptosis, ORF3 as well as ORF1 and ORF2 genes were transiently expressed in PK15 and Cos-7 cells for apoptotic activity assay. Transfection of cells with the ORF3 alone induced apoptosis using a pathway similar to that described in the context of viral infection. This is further confirmed by a significant decrease in apoptotic activity of infected cells in the absence of the ORF3 expression, suggesting that the protein plays a major role in the induction of virus-induced apoptosis. Altogether, these results indicate that ORF3 is a novel PCV2 protein that is not essential for viral replication in cultured cells but is involved in PCV2-induced apoptosis by activating caspase-8 and caspase-3 pathways.

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Section: Discussionmentioning

confidence: 99%

Characterization of a Previously Unidentified Viral Protein in Porcine Circovirus Type 2-Infected Cells and Its Role in Virus-Induced Apoptosis

Liu

Chen

Kwang

2005

J Virol

275

258

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“…15 A BALB/c mouse model has also been used to test a plasmid PCV2 DNA coated onto gold particles. 53 Commercial PCV2 vaccines for use in growing pigs and breeding-age animals became available in North America in 2006 (Table 6). Evidence to date indicates that the commercial vaccines are a remarkably effective tool to reduce losses in herds and production systems experiencing PCVAD in growing pigs.…”

Section: Control Of Coinfectionsmentioning

confidence: 99%

Porcine Circovirus Type 2–Associated Disease: Update on Current Terminology, Clinical Manifestations, Pathogenesis, Diagnosis, and Intervention Strategies

2007

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Abstract. Porcine circovirus type 2 (PCV2)-associated disease (PCVAD) continues to be an important differential diagnosis on pig farms in the United States and worldwide. Case trend analyses indicate that the incidence of PCVAD is on the rise in the United States. Accurate diagnosis is important in order to implement appropriate intervention strategies. PCVAD can manifest as a systemic disease, as part of the respiratory disease complex, as an enteric disease, as porcine dermatitis and nephropathy syndrome, or as reproductive problems. PCVAD may be only a sporadic individual animal diagnosis; however, PCVAD may also manifest as a severe herd problem accelerated and enhanced by concurrent virus or bacterial infections. This article is intended to discuss the most common disease manifestations, pathogenesis, diagnostic approaches, and intervention strategies associated with PCVAD in North America.

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“…tested (mean log PCV2 load±SD) at the following weeks p.c. 2004; Ju et al, 2005;Kamstrup et al, 2004;Song et al, 2007;Wang et al, 2006Wang et al, , 2007. In the present study, we investigated the Cap-specific lymphoproliferative activity and splenocyte phenotypes induced by different immunization protocols.…”

Section: Groupmentioning

confidence: 99%

“…Based on comparison of the immunogenicity of the PCV2 Cap and Rep proteins, Blanchard et al (2003) demonstrated that the ORF2-encoded Cap protein was the major immunogen, whilst the ORF1-encoded Rep protein was only weakly immunogenic. Kamstrup et al (2004) subsequently investigated the potential of a DNA vaccine encoding the PCV2 Cap protein in mice and demonstrated the production of antibody. On the other hand, Fenaux et al (2003Fenaux et al ( , 2004 focused on a chimeric PCV1-PCV2, which was shown to induce specific antibody responses and protection against PCV2 in pigs.…”

Section: Introductionmentioning

confidence: 99%

Protective immunity against porcine circovirus 2 by vaccination with ORF2-based DNA and subunit vaccines in mice

Shen

Zhou

Huang

et al. 2008

Journal of General Virology

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The protective immune response against porcine circovirus 2 (PCV2) infection in mice was characterized using flow cytometric analysis (FCM), assays of antibody (of different IgG isotypes) and viraemia, and histopathological examination. An open reading frame 2 plasmid (pORF2) and the capsid protein (Cap) of PCV2 were used as DNA and subunit vaccines, respectively. In FCM analysis, although pORF2 and Cap alone showed comparable efficacy in eliciting lymphoproliferative responses and Cap-specific CD4 + T cells, pORF2 was superior to the Cap protein in triggering CD8 + T cells. A virus neutralization assay showed that pORF2 evoked stronger recall virus-neutralizing (VN) antibody responses than the Cap protein on PCV2 challenge. Correspondingly, VN antibody kinetics coincided with those of Cap-specific IgG2a, but not with the kinetics of IgG and IgG1. Following virus challenge, real-time PCR and histopathological analysis confirmed that only low viral DNA loads and mild microscopic lesions appeared in pORF2-immunized mice. These findings indicate that CD8 + T cells and VN antibody responses correlating mainly with Cap-specific IgG2a play crucial roles in protecting against PCV2 infection, and that the protective immunity induced by the pORF2 plasmid is superior to that induced by the PCV2 Cap protein. INTRODUCTIONPost-weaning multisystemic wasting syndrome (PMWS), first recorded in pigs in Western Canada in 1991, has been described in pigs from many regions of the world (Allan et al., 1998b;Allan & Ellis, 2000;Clark, 1997;Wen et al., 2005;Zhou et al., 2006). PMWS affects pigs of 5-12 weeks of age, with a morbidity of 5-30 %; it is characterized by weight loss, dyspnoea and jaundice. Field and experimental evidence has revealed that PMWS-affected pigs may develop severe immunosuppression (Segales et al., 2004).Porcine circovirus 2 (PCV2) has been identified as the primary aetiological agent of PMWS (Allan et al., 1998a, b;Allan & Ellis, 2000;Ellis et al., 1998;Fenaux et al., 2002;Meehan et al., 1998). PCV2 is a non-enveloped, singlestranded, circular DNA virus with a diameter of 17 nm (Tischer et al., 1982). The PCV2 genome comprises 1767 or 1768 nt and is assumed to have 11 potential open reading frames (ORF1-11;Hamel et al., 1998;Zhou et al., 2006). Previous studies have demonstrated that ORF1, -2 and -3 encode a 35.7 kDa replication (Rep) protein involved in virus replication (Mankertz et al., 1998), a 27.8 kDa capsid (Cap) protein involved in PCV2 immunogenicity (Mahe et al., 2000; Nawagitgul et al., 2000;Truong et al., 2001;Zhou et al., 2005a) and a protein involved in PCV2-induced apoptosis , respectively.Immunization against PCV2 has been studied intensely and found to be the most effective strategy for protecting pigs against PCV2 infection. Based on comparison of the immunogenicity of the PCV2 Cap and Rep proteins, Blanchard et al. (2003) demonstrated that the ORF2-encoded Cap protein was the major immunogen, whilst the ORF1-encoded Rep protein was only weakly immunogenic. Kamstrup et al. (2004) subsequently...

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Immunisation against PCV2 structural protein by DNA vaccination of mice

Cited by 60 publications

References 22 publications

Characterization of a Previously Unidentified Viral Protein in Porcine Circovirus Type 2-Infected Cells and Its Role in Virus-Induced Apoptosis

Characterization of a Previously Unidentified Viral Protein in Porcine Circovirus Type 2-Infected Cells and Its Role in Virus-Induced Apoptosis

Porcine Circovirus Type 2–Associated Disease: Update on Current Terminology, Clinical Manifestations, Pathogenesis, Diagnosis, and Intervention Strategies

Protective immunity against porcine circovirus 2 by vaccination with ORF2-based DNA and subunit vaccines in mice

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