Characterization of antibody responses to combinations of a dengue-2 DNA and dengue-2 recombinant subunit vaccine.

Simmons, Monika; Murphy, Gerald S.; Kochel, Tadeusz J.; Raviprakash, Kanakatte; Hayes, Curtis G.

doi:10.4269/ajtmh.2001.65.420

Cited by 70 publications

(47 citation statements)

References 35 publications

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“…Therefore, it is reasonable to suggest that VN antibody against PCV2 is composed mainly of IgG2a antibody against Cap protein, and that this Cap-specific neutralizing IgG2a antibody plays an important role in protecting against PCV2 infection. In fact, VN antibodies against dengue virus (Simmons et al, 2001) and herpes simplex virus type 1 (McKendall & Woo, 1988) have also been shown to comprise primarily IgG2a antibody in mice. A recent study reported that recombinant adenovirus expressing the Cap protein generated VN antibody titres ranging from 1 : 8 to 1 : 17 in mice (Wang et al, 2006), and all plasmids encoding Cap protein with different subcellular localizations induced VN antibody titres of ,1 : 10 in mice (Fan et al, 2008).…”

Section: Groupmentioning

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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Section: Groupmentioning

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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“…A vaccine which achieves this is expected to provide uniform protection against all serotypes and a low risk of ADE. A variety of vaccine approaches have been undertaken, including empirically derived and cDNA-derived live attenuated viruses, recombinant subunit vaccines, inactivated virus, and DNA vaccines (2,3,5,13,19,20,24,25,28,31,32,45,47,48,(52)(53)(54). Although some candidates have progressed to clinical trials, there have been problems with immunogenicity and reactogenicity of certain vaccines, and it is not yet known which modality will be most suitable for use in humans.…”

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confidence: 99%

Yellow Fever Virus/Dengue-2 Virus and Yellow Fever Virus/Dengue-4 Virus Chimeras: Biological Characterization, Immunogenicity, and Protection against Dengue Encephalitis in the Mouse Model

Chambers

Liang

Droll

et al. 2003

J Virol

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Two yellow fever virus (YFV)/dengue virus chimeras which encode the prM and E proteins of either dengue virus serotype 2 (dengue-2 virus) or dengue-4 virus within the genome of the YFV 17D strain (YF5.2iv infectious clone) were constructed and characterized for their properties in cell culture and as experimental vaccines in mice. The prM and E proteins appeared to be properly processed and glycosylated, and in plaque reduction neutralization tests and other assays of antigenic specificity, the E proteins exhibited profiles which resembled those of the homologous dengue virus serotypes. Both chimeric viruses replicated in cell lines of vertebrate and mosquito origin to levels comparable to those of homologous dengue viruses but less efficiently than the YF5.2iv parent. YFV/dengue-4 virus, but not YFV/dengue-2 virus, was neurovirulent for 3-week-old mice by intracerebral inoculation; however, both viruses were attenuated when administered by the intraperitoneal route in mice of that age. Single-dose inoculation of either chimeric virus at a dose of 10 5 PFU by the intraperitoneal route induced detectable levels of neutralizing antibodies against the homologous dengue virus strains. Mice which had been immunized in this manner were fully protected from challenge with homologous neurovirulent dengue viruses by intracerebral inoculation compared to unimmunized mice. Protection was associated with significant increases in geometric mean titers of neutralizing antibody compared to those for unimmunized mice. These data indicate that YFV/dengue virus chimeras elicit antibodies which represent protective memory responses in the mouse model of dengue encephalitis. The levels of neurovirulence and immunogenicity of the chimeric viruses in mice correlate with the degree of adaptation of the dengue virus strain to mice. This study supports ongoing investigations concerning the use of this technology for development of a live attenuated viral vaccine against dengue viruses.

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“…Another molecular approach being utilized is the creation of four separate infectious chimeric flaviviruses, each of which contains the pre-M and E genes of one of the four DENV serotypes in a single "backbone" containing the C and NS proteins of an attenuated flavivirus, either the yellow fever vaccine strain or an attenuated DENV strain (21,22). DNA vaccines consisting of plasmids expressing one or a few proteins from each DENV serotype are in an earlier stage of development, as are subunit vaccines based on purified recombinant DENV proteins (23,24). Several of these approaches have demonstrated protective efficacy in animal models of DENV infection, and a few have shown safety and immunogenicity in early phase clinical studies (14,18,25,26).…”

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Dengue: defining protective versus pathologic immunity

Rothman¹

2004

J. Clin. Invest.

303

216

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Nonstandard abbreviations used: antibody-dependent enhancement of infection (ADE); core (C); dengue fever (DF); dengue hemorrhagic fever (DHF); dengue virus (DENV); envelope (E); membrane (M); nonstructural (NS). Conflict of interest:The author has declared that no conflict of interest exists. Among scientists in the developed world, there has been a recent resurgence of interest in exotic diseases, with the aim of protecting the global population from emerging infectious disease threats. The renewed commitment of effort and resources has welcome implications for the developing world, whose population faces the greatest part of these threats. Among the biological threats considered most serious are the viral hemorrhagic fevers. Although this term usually brings to mind the deadly outbreaks of Ebola virus, in reality over 99% of the cases of viral hemorrhagic fever reported worldwide are related instead to dengue hemorrhagic fever (DHF) (1).DHF is caused by the dengue viruses (DENVs), members of the Flaviviridae family of small enveloped viruses (2). The flaviviruses carry a single-stranded RNA genome of relatively simple organization. A single open reading frame in the RNA directs the synthesis of a long polyprotein that is processed by viral and host cell proteases to produce the ten viral proteins, including three structural proteins (core [C]; membrane [M], produced as a precursor protein; and envelope [E]) and seven nonstructural (NS) proteins (Figure 1). The DENV complex encompasses four closely related serotypes: DENV-1, DENV-2, DENV-3, and DENV-4. All four DENV serotypes are transmitted between humans in nature by mosquitoes of the genus Aedes, principally Aedes aegypti, which is highly domesticated and has a preference for biting humans.It has been estimated that over 50 million DENV infections occur globally each year (3). Most of these infections are clinically inapparent. Among symptomatic cases, the majority of subjects experience uncomplicated dengue fever (DF), an acute febrile illness typically lasting 3-7 days, accompanied by headache, myalgias, and, less often, a maculopapular rash. The headache and myalgias may be quite debilitating, which originated the name "break-bone fever" that was recorded prior to the 1900s (4). Laboratory findings in patients with DF include leukopenia thrombocytopenia, and mild elevations in serum hepatic transaminases (5). Fatigue may be prolonged for months after resolution of fever, but patients eventually recover without sequelae. None of these features is sufficiently specific for accurate clinical diagnosis of DF. Laboratory support for detection of IgM antibody or virus (by RT-PCR or virus isolation) is therefore important for recognition of outbreaks.DHF represents the severe clinical manifestation of DENV infection, which occurs in no more than 3% of infected individuals (6). Fever, headache, and myalgias are prominent symptoms in DHF, as they are in DF. DHF is distinguished from DF on clinical grounds, with the three primary criteria being the occurrence of a...

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Characterization of antibody responses to combinations of a dengue-2 DNA and dengue-2 recombinant subunit vaccine.

Cited by 70 publications

References 35 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

Yellow Fever Virus/Dengue-2 Virus and Yellow Fever Virus/Dengue-4 Virus Chimeras: Biological Characterization, Immunogenicity, and Protection against Dengue Encephalitis in the Mouse Model

Dengue: defining protective versus pathologic immunity

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