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Three tetravalent vaccine (TV) formulations of previously described monovalent dengue (DEN) virus vaccine candidates were compared to a tetravalent formulation of wild-type DEN viruses (T-wt) for replication in SCID mice transplanted with human liver cells (SCID-HuH-7) or for replication and immunogenicity in rhesus monkeys. TV-1 consists of recombinant(More)
Mutations that restrict replication of dengue virus have been sought for the generation of recombinant live-attenuated dengue virus vaccines. Dengue virus type 4 (DEN4) was previously grown in Vero cells in the presence of 5-fluorouracil, and the characterization of 1248 mutagenized, Vero cell passaged clones identified 20 temperature-sensitive (ts) mutant(More)
Three novel recombinant dengue type 3 (DEN3) virus vaccine candidates have been generated from a DEN3 virus isolated from a mild outbreak of dengue fever in the Sleman area of central Java in Indonesia in 1978. Antigenic chimeric viruses were prepared by replacing the membrane precursor and envelope (ME) proteins of recombinant DEN4 (rDEN4) virus with those(More)
The number of cases of severe dengue disease continues to grow in endemic areas of southeast Asia, Central and South America, and other subtropical regions. Children bear the greatest burden of disease, and the development of an effective vaccine remains a global public health priority. A tetravalent vaccine is urgently needed and must be effective against(More)
The rDEN4Delta30-200,201 is a live attenuated DENV-4 vaccine candidate specifically designed to further attenuate the rDEN4Delta30 parent virus. In the present study, 28 healthy adult volunteers were randomized to receive either 10(5) plaque-forming unit (PFU) of vaccine (20) or placebo (8) as a single subcutaneous injection. Volunteers were evaluated for(More)
BACKGROUND The live attenuated DEN1 vaccine candidate virus rDEN1Delta30 has been evaluated in preclinical animal models and found to be attenuated and immunogenic. These promising preclinical studies have identified rDEN1Delta30 as a candidate DEN1 vaccine virus for further testing in a human Phase I clinical trial. METHODS rDEN1Delta30 at a dose of(More)
rDEN2/4Delta30(ME) is an attenuated chimeric dengue virus in which the prM and E structural proteins of the DEN4 candidate vaccine rDEN4Delta30 have been replaced by those of the prototypic DEN2 NGC virus. rDEN2/4Delta30(ME) was evaluated at a dose of 1,000 PFU in 20 healthy dengue-naïve adult volunteers. Eight volunteers received placebo. Volunteers were(More)
Dengue is an emerging infectious disease that has become the most important arboviral infection worldwide. There are four serotypes of dengue virus, DENV-1, DENV-2, DENV-3, and DENV-4, each capable of causing the full spectrum of disease. rDEN1Δ30 is a live attenuated investigational vaccine for the prevention of DENV-1 illness and is also a component of an(More)
BACKGROUND The live attenuated dengue virus type 4 (DEN-4) vaccine candidate virus rDEN4 Delta 30 was previously found to be safe and immunogenic at a dose of 10(5) plaque-forming units (pfu). METHODS In a follow-up placebo-controlled phase 2 clinical trial, rDEN4 Delta 30 was administered as a single inoculation to 3 separate dose cohorts (10(3) pfu,(More)
We have evaluated the potential of conferring protective immunity to herpes simplex virus type 2 (HSV-2) by selectively inducing an HSV-specific CD8(+) cytotoxic T-lymphocyte (CTL) response directed against a single major histocompatibility complex class I-restricted CTL recognition epitope. We generated a recombinant vaccinia virus (rVV-ES-gB498-505) which(More)