Immunogenic and Protective Response in Mice Immunized with a Purified, Inactivated, Dengue-2 Virus Vaccine Prototype Made in Fetal Rhesus Lung Cells

Putnak, Robert; Cassidy, K.F.; Conforti, Nadia; Lee, Raymond; Sollazzo, Domenic; Truong, Tran; Ing, Esther; Dubois, Doria R.; Sparkuhl, Joachim; Gastle, William; Hoke, Charles H.

doi:10.4269/ajtmh.1996.55.504

Cited by 48 publications

(23 citation statements)

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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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mentioning

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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“…Given their structure, these polymers have specific molecular anchor sites that are expected to be exploited to induce antigenic specificity to the conserved regions of dengue virus. Several authors report that the E protein produces immunity and confers protection against infection in mice with low levels of neutralizing antibodies [33][34][35]. Because of the dual role of its receptors as well as the cell entry through membrane fusion, the E protein, apart from being the most exposed protein, is the main target against which the neutralizing antibodies are produced to inhibit its functions.…”

Section: Biopolymers As Potential Adjuvants Carriersmentioning

confidence: 99%

Protein-Protein and Protein-Ligand Docking

Hernández-Santoyo¹,

Tenorio-Barajas²,

VictorAltuzar³

et al. 2013

Protein Engineering - Technology and Application

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“…The WRAIR has developed a purified inactivated virus (PIV) dengue vaccine candidate. [141][142][143] The approach uses high titer DENV grown on VERO cells followed by formalin inactivation. NHP studies of monovalent preparations have demonstrated moderate immunogenicity and protection from wild-type DENV challenge.…”

Section: Candidates In Clinical Developmentmentioning

confidence: 99%