Purified dengue 2 virus envelope glycoprotein aggregates produced by baculovirus are immunogenic in mice

Kelly, Eileen P.; Greene, James J.; King, Alan D.; Innis, Bruce L.

doi:10.1016/s0264-410x(00)00032-3

Cited by 71 publications

(40 citation statements)

References 48 publications

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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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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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“…Sequential infection in areas of hyperendemicity (where multiple serotypes cocirculate) has the potential to trigger life-threatening disease widely believed to be mediated by an antibody-dependent enhancement mechanism (33). This has prompted the view that a dengue vaccine must be tetravalent; that is, it must afford solid and long-lasting protection against all four dengue virus serotypes.Several laboratories worldwide are exploring multiple approaches towards developing dengue virus vaccines based on live attenuated viruses (1, 21, 36), inactivated viruses (35), infectious clone-derived intertypic (18, 26) and chimeric (5, 13, 14, 43) viruses, antigen-encoding plasmids (23, 24), recombinant proteins expressed in heterologous systems (2,22,38,40), and live vaccinia virus vectors encoding antigen genes (9, 31, 32). However, the major focus is on the live, empirically attenuated (1, 21, 36), and infectious clone-derived ChimeriVax vaccines based on the attenuated YF17D yellow fever vaccine vector (13,14).…”

mentioning

confidence: 99%

“…Several laboratories worldwide are exploring multiple approaches towards developing dengue virus vaccines based on live attenuated viruses (1,21,36), inactivated viruses (35), infectious clone-derived intertypic (18,26) and chimeric (5,13,14,43) viruses, antigen-encoding plasmids (23,24), recombinant proteins expressed in heterologous systems (2,22,38,40), and live vaccinia virus vectors encoding antigen genes (9,31,32). However, the major focus is on the live, empirically attenuated (1,21,36), and infectious clone-derived ChimeriVax vaccines based on the attenuated YF17D yellow fever vaccine vector (13,14).…”

mentioning

confidence: 99%

Replication-Defective Adenoviral Vaccine Vector for the Induction of Immune Responses to Dengue Virus Type 2

Jaiswal

Khanna

Swaminathan

2003

J Virol

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A recombinant replication-defective adenovirus vector that can overexpress the ectodomain of the envelope protein of dengue virus type 2 (NGC strain) has been constructed. This virus was immunogenic in mice and elicited dengue virus type 2 specific B-and T-cell responses. Sera from immunized mice contained neutralizing antibodies that could specifically recognize dengue virus type 2 and neutralize its infectivity in vitro, indicating that this approach has the potential to confer protective immunity. In vitro stimulation of splenocytes (from immunized mice) with dengue virus type 2 resulted in a significant proliferative response accompanied by the production of high levels of gamma interferon but did not show significant changes in interleukin-4 levels. This is suggestive of a Th1-like response (considered to be important in the maturation of cytotoxic T lymphocytes that are essential for the elimination of virus-infected cells). The data show that adenovirus vectors offer a promising alternative strategy for the development of dengue virus vaccines.Dengue viruses, which are members of the Flaviviridae family, are mosquito-borne human pathogens with a worldwide prevalence (12). There are four antigenically distinct serotypes of dengue viruses (28). There is neither an effective antiviral therapy for the treatment of dengue virus infections nor a licensed vaccine for their prevention (12,27). Infection with any one dengue virus serotype provides lifelong homologous immunity with only transient cross-protection against the remaining three serotypes (19). Sequential infection in areas of hyperendemicity (where multiple serotypes cocirculate) has the potential to trigger life-threatening disease widely believed to be mediated by an antibody-dependent enhancement mechanism (33). This has prompted the view that a dengue vaccine must be tetravalent; that is, it must afford solid and long-lasting protection against all four dengue virus serotypes.Several laboratories worldwide are exploring multiple approaches towards developing dengue virus vaccines based on live attenuated viruses (1, 21, 36), inactivated viruses (35), infectious clone-derived intertypic (18, 26) and chimeric (5, 13, 14, 43) viruses, antigen-encoding plasmids (23, 24), recombinant proteins expressed in heterologous systems (2,22,38,40), and live vaccinia virus vectors encoding antigen genes (9, 31, 32). However, the major focus is on the live, empirically attenuated (1, 21, 36), and infectious clone-derived ChimeriVax vaccines based on the attenuated YF17D yellow fever vaccine vector (13,14). Alternative attenuated vector backbones based on dengue type 1 (DEN-1) (29, 45), DEN-2 (18), and DEN-4 (8) viruses are being developed in parallel. All these strategies rely on the creation of monovalent vaccine viruses, which are mixed together to generate tetravalent formulations.Recent studies in which the tetravalent live attenuated (21) and ChimeriVax (13) vaccines were tested in humans and nonhuman primates, respectively, revealed that the tetravalent form...

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“…Both systems have been successfully used in BTV recombinant protein production before (16,35,49) and are practical for vaccine application because of their availability, affordability, and potential capability to produce large quantities of functional protein (50). In addition to the subunit vaccine design presented here, other approaches, including reverse genetics technologies, are also increasingly practical for BTV vaccine designs, since they demonstrate DIVA potential (51) and show promising early success against multiple serotypes (52).…”

Section: Discussionmentioning

confidence: 99%

Purification, Stability, and Immunogenicity Analyses of Five Bluetongue Virus Proteins for Use in Development of a Subunit Vaccine That Allows Differentiation of Infected from Vaccinated Animals

Anderson

Bréard

Bengtsson

et al. 2014

Clin. Vaccine Immunol.

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e Bluetongue virus (BTV) causes bluetongue disease, a vector-borne disease of ruminants. The recent northerly spread of BTV serotype 8 in Europe resulted in outbreaks characterized by clinical signs in cattle, including unusual teratogenic effects. Vaccination has been shown to be crucial for controlling the spread of vector-borne diseases such as BTV. With the aim of developing a novel subunit vaccine targeting BTV-8 that allows differentiation of infected from vaccinated animals, five His-tagged recombinant proteins, VP2 and VP5 of BTV-8 and NS1, NS2, and NS3 of BTV-2, were expressed in baculovirus or Escherichia coli expression systems for further study. Optimized purification protocols were determined for VP2, NS1, NS2, and NS3, which remained stable for detection for at least 560 to 610 days of storage at ؉4°C or ؊80°C, and Western blotting using sera from vaccinated or experimentally infected cattle indicated that VP2 and NS2 were recognized by BTV-specific antibodies. To characterize murine immune responses to the four proteins, mice were subcutaneously immunized twice at a 4-week interval with one of three protein combinations plus immunostimulating complex ISCOM-Matrix adjuvant or with ISCOM-Matrix alone (n ‫؍‬ 6 per group). Significantly higher serum IgG antibody titers specific for VP2 and NS2 were detected in immunized mice than were detected in controls. VP2, NS1, and NS2 but not NS3 induced specific lymphocyte proliferative responses upon restimulation of spleen cells from immunized mice. The data suggest that these recombinant purified proteins, VP2, NS1, and NS2, could be an important part of a novel vaccine design against BTV-8.

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Purified dengue 2 virus envelope glycoprotein aggregates produced by baculovirus are immunogenic in mice

Cited by 71 publications

References 48 publications

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

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

Replication-Defective Adenoviral Vaccine Vector for the Induction of Immune Responses to Dengue Virus Type 2

Purification, Stability, and Immunogenicity Analyses of Five Bluetongue Virus Proteins for Use in Development of a Subunit Vaccine That Allows Differentiation of Infected from Vaccinated Animals

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