A prime-boost immunization strategy with DNA and recombinant baculovirus-expressed protein enhances protective immunogenicity of glycoprotein D of equine herpesvirus 1 in naı̈ve and infection-primed mice

Ruitenberg, K. M.; Walker, Clinton; Love, Daria N.; Wellington, J. E.; Whalley, J. M.

doi:10.1016/s0264-410x(99)00400-4

Cited by 38 publications

(15 citation statements)

References 28 publications

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“…In contrast, Th2 cells, which predominantly produce IL-4, IL-5, IL-10 and IL-13, promote the development of eosinophilia as well as the generation of IgG1 and IgE antibody isotypes (Abbas et al, 1996;Mosmann & Coffman, 1989a). Based on the analysis of IgG1 and IgG2a in the immunized mice, our data showed that the pORF2 plasmid and Cap protein induced Th1-and Th2-biased immune responses, respectively, which is similar to reports on other viruses described previously (Ruitenberg et al, 2000;Sin et al, 1999;Tanghe et al, 2001;Zakhartchouk et al, 2005). Histopathological examination and real-time PCR results, particularly in the protection assay, also showed that mice immunized using the pORF2, pORF2/Cap and Cap/pORF2 protocols had milder microscopic lesions and lower serum PCV2 loads than the Cap-immunized mice.…”

Section: Groupsupporting

confidence: 90%

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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Section: Groupsupporting

confidence: 90%

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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“…Furthermore, the Th bias of the response was influenced by the prime-boost strategy. A DNA prime/DNA boost strategy resulted in a strongly Th1-biased response (IgG2a 11 IgG1), as previously reported [55,56]. With the DNA prime/protein boost strategies, responses were more Th1-like when any adjuvant was used with the protein boost than with protein alone, in which case responses were mixed ( fig.…”

Section: Prime/boost Strategiessupporting

confidence: 74%

“…Another optimization approach tested was the use of different prime/boost immunization strategies. Other investigators have demonstrated that DNA-based immunization primes strong humoral and cell-mediated immune responses, which can be further boosted using different immunization strategies including administration of protein antigens or recombinant viral vectors [31,32,55,56,[58][59][60]. Here we have investigated the feasibility of boosting a DNA-primed immune response with a protein boost given IM or IN, alone or with adjuvants.…”

Section: Discussionmentioning

confidence: 99%

Optimization Strategies for DNA Vaccines

et al. 2000

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DNA immunization is a relatively new vaccination strategy that involves the direct introduction into the host of plasmid DNA encoding the desired antigen. The DNA enters host cells and results in immune responses following in vivo expression of the antigen. Although DNA-based immunization works well in animal models for the induction of both humoral and cell-mediated immune responses, its success in humans has been limited. This paper discusses different approaches that have attempted to optimize DNA vaccines, and presents results evaluating some of these approaches in mice.

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“…Previous reports from several laboratories demonstrated that the envelope glycoproteins of EHV-1 are vaccine candidates as they elicit both virus-specific antibody and cytotoxic T-cell responses (20,26,37,41,42,44,(48)(49)(50)(51)55,56). EHV-1 gD, a 55-58-kDa glycoprotein, is a component of the virion envelope, is inserted into the membrane of EHV-1-infected cells, and is required for virus entry and cell-tocell spread (14,16,53).…”

Section: Discussionmentioning

confidence: 99%

Cytokine Profiles and Long-Term Virus-Specific Antibodies Following Immunization of CBA Mice with Equine Herpesvirus 1 and Viral Glycoprotein D

Zhang

Frampton²,

Osterrieder³

et al. 2003

Viral Immunology

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Equine herpesvirus 1 (EHV-1)-specific antibody-secreting cells (ASC) isolated from the lung and spleen of mice at 12 months after immunization with attenuated EHV-1 KyA, heat-killed KyA, or recombinant viral glycoprotein D (rgD) assessed by ELISPOT showed a three- to fivefold increase in three immunoglobulin isotypes at 3 days post-challenge with pathogenic EHV-1 RacL11 as compared to control mice. ELISPOT assays demonstrated a high frequency of cells secreting proinflammatory tumor necrosis factor-alpha (TNF-alpha), interferon gamma (IFN-gamma), and interleukin 4 (IL-4) in the lungs in response to infection with KyA or RacL11 or immunization with rgD. Cytokine production elicited by EHV-1 KyA or RacL11 infection revealed similar frequencies of EHV-1-specific IFN-gamma and IL-4 spot forming cells in the mediastinal lymph nodes and spleen. However, KyA induced significantly greater amounts of IFN-gamma producing cells in the lungs than did RacL11. Intranasal immunization with KyA or rgD induced long-term immunity that provided protection against pathogenic EHV-1 challenge infection at 12 months post-immunization. Overall, the data indicate that immunization with infectious KyA or rgD induces significant levels of cytokines, virus-specific ASC in the lungs and spleen, and long-term virus specific B-cell responses.

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A prime-boost immunization strategy with DNA and recombinant baculovirus-expressed protein enhances protective immunogenicity of glycoprotein D of equine herpesvirus 1 in naı̈ve and infection-primed mice

Cited by 38 publications

References 28 publications

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

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

Optimization Strategies for DNA Vaccines

Cytokine Profiles and Long-Term Virus-Specific Antibodies Following Immunization of CBA Mice with Equine Herpesvirus 1 and Viral Glycoprotein D

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