Substitution of Wild‐Type Yellow Fever Asibi Sequences for 17D Vaccine Sequencesin ChimeriVax–Dengue 4 Does Not Enhance Infection of<i>Aedes aegypti</i>Mosquitoes

McGee, Charles E.; Tsetsarkin, Konstantin A.; Vanlandingham, Dana L.; McElroy, Kate L.; Lang, Jean; Guy, Bruno; Decelle, Thierry; Higgs, Stephen

doi:10.1086/527328

Cited by 40 publications

(27 citation statements)

References 37 publications

(70 reference statements)

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“…These results are consistent with the previous observations that chimeras exhibited growth characteristics similar to those of the viruses contributing structural protein genes (5,41), indicating that the reduction in plaque size and replication efficiency for ChinDENV compared to JEV are likely to be determined partly by the donor prM-E genes. In addition, the chimerization itself has been proved to contribute to the attenuation of chimeras (10,(42)(43)(44)(45)(46)(47)(48)(49)(50). Notably, the chimeric virus ChinDENV replicated efficiently in Vero and PHK cells, both of which are certified for vaccine production.…”

Section: Discussionmentioning

confidence: 99%

A Chimeric Dengue Virus Vaccine using Japanese Encephalitis Virus Vaccine Strain SA14-14-2 as Backbone Is Immunogenic and Protective against Either Parental Virus in Mice and Nonhuman Primates

Deng

Yang

et al. 2013

J Virol

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The development of a safe and efficient dengue vaccine represents a global challenge in public health. Chimeric dengue viruses (DENV) based on an attenuated flavivirus have been well developed as vaccine candidates by using reverse genetics. In this study, based on the full-length infectious cDNA clone of the well-known Japanese encephalitis virus live vaccine strain SA14-14-2 as a backbone, a novel chimeric dengue virus (named ChinDENV) was rationally designed and constructed by replacement with the premembrane and envelope genes of dengue 2 virus. The recovered chimeric virus showed growth and plaque properties similar to those of the parental DENV in mammalian and mosquito cells. ChinDENV was highly attenuated in mice, and no viremia was induced in rhesus monkeys upon subcutaneous inoculation. ChinDENV retained its genetic stability and attenuation phenotype after serial 15 passages in cultured cells. A single immunization with various doses of ChinDENV elicited strong neutralizing antibodies in a dose-dependent manner. When vaccinated monkeys were challenged with wild-type DENV, all animals except one that received the lower dose were protected against the development of viremia. Furthermore, immunization with Chin-DENV conferred efficient cross protection against lethal JEV challenge in mice in association with robust cellular immunity induced by the replicating nonstructural proteins. Taken together, the results of this preclinical study well demonstrate the great potential of ChinDENV for further development as a dengue vaccine candidate, and this kind of chimeric flavivirus based on JE vaccine virus represents a powerful tool to deliver foreign antigens.

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Section: Discussionmentioning

confidence: 99%

A Chimeric Dengue Virus Vaccine using Japanese Encephalitis Virus Vaccine Strain SA14-14-2 as Backbone Is Immunogenic and Protective against Either Parental Virus in Mice and Nonhuman Primates

Deng

Yang

et al. 2013

J Virol

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“…All observations of replication and transmission in mosquitoes, as well as outcomes in NHPs showed that these recombinants were attenuated compared with the parental wt viruses. 28,29 These studies also suggested that the chimerization process itself contributed to the attenuation of these viruses. Thus, not only is the recombination of the CYD vaccine viruses with a wt flavivirus extremely unlikely, any recombinant would be unlikely to cause disease or be disseminated.…”

Section: Environmental Risk Assessmentmentioning

confidence: 92%

Development of sanofi pasteur tetravalent dengue vaccine

Guy

Saville²,

Lang³

2010

Human Vaccines

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113

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The Sanofi Pasteur tetravalent dengue vaccine candidate is composed of four recombinant live attenuated vaccines based on a yellow fever vaccine 17D (YFv 17D) backbone, each expressing the prM and envelope genes of one of the four dengue virus serotypes. Pre-clinical studies have demonstrated that the Tv dengue vaccine is genetically and phenotypically stable, non-hepatotropic, less neurovirulent than YFv 17D and does not infect mosquitoes by the oral route. in vitro and in vivo preclinical studies also showed that the Tv dengue vaccine induced controlled stimulation in human dendritic cells and significant immune responses in monkeys. Tv dengue vaccine reactogenicity, viramia induction and antibody responses were investigated in three Phase i trials in the USA, the Philippines and Mexico, in a two or three-dose regimen over a 12 month period. results showed that the majority of adverse events were mild to moderate and transient in nature. viremia was transient and low, and was not increased after initial dengue Tv administration, even in the case of incomplete responses. fSeropositivity (≥10 in a PrNT 50 assay) was 100% for all four serotypes in flavivirus-naive adults injected with 3 doses of Tv dengue vaccine in the USA. Similarly, seropositivity was 88-100% following three administrations in flavivirus-naive Mexican children aged 2-5 years. Furthermore, the proportion of seropositive subjects increased with each dengue Tv injection in the Philippines where baseline flavivirus immunity was high. responses were also monitored at the cellular level in humans, and their level and nature were in good agreement with the observed safety and the immunogenicity of the vaccine. Finally, the challenges inherent to the development of such Tv dengue vaccines will also be discussed in the last part of this review.in conclusion, preclinical and clinical results support the favorable immunogenicity and short-term safety of the dengue Tv vaccine. An extensive clinical development program for dengue Tv is underway including completion of the enrollment of 4,000 4-11 years old children in an efficacy trial in Thailand, in an area of high dengue incidence. Assuming continued successful outcomes, initial submissions to regulatory authorities are envisaged within a 5-year period.

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“…aegypti , which originated from Rexville, Puerto Rico, was used. [9][10][11] Viruses. Three strains of YFV that had been characterized previously in mosquitoes were used for the experiments.…”

Section: Introductionmentioning

confidence: 99%

“…Viral antigen in mosquito samples and the blood/virus mixture titrations was detected using a modification of the indirect immunofluorescence assay described previously. 9,12 The YFV NS1-reactive monoclonal antibody 863 was used as the primary antibody, 16 and Alexa Fluor 488-conjugated goat anti-mouse IgG (Invitrogen, Eugene, OR) was used as the secondary antibody. Samples were scored using an Olympus IX70 inverted epifluorescence microscope (Olympus, Tokyo, Japan) fitted with a fluorescein filter.…”

Section: Introductionmentioning

confidence: 99%

Vector Competence of Australian Mosquitoes for Yellow Fever Virus

Hurk¹,

McElroy²,

Pyke³

et al. 2011

The American Society of Tropical Medicine and Hygiene

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The vector competence of Australian mosquitoes for yellow fever virus (YFV) was evaluated. Infection and transmission rates in Cairns and Townsville populations of Aedes aegypti and a Brisbane strain of Ae. notoscriptus were not significantly different from a well-characterized YFV-susceptible strain of Ae. aegypti. After exposure to 107.2 tissue culture infectious dose (TCID50)/mL of an African strain of YFV, > 70% of Ae. aegypti and Ae. notoscriptus became infected, and > 50% transmitted the virus. When exposed to 106.7 TCID50/mL of a South American strain of YFV, the highest infection (64%) and transmission (56%) rates were observed in Ae. notoscriptus. The infection and transmission rates in the Cairns Ae. aegypti were both 24%, and they were 36% and 28%, respectively, for the Townsville population. Because competent vectors are present, the limited number of travelers from endemic areas and strict vaccination requirements will influence whether YFV transmission occurs in Australia.

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Substitution of Wild‐Type Yellow Fever Asibi Sequences for 17D Vaccine Sequencesin ChimeriVax–Dengue 4 Does Not Enhance Infection ofAedes aegyptiMosquitoes

Cited by 40 publications

References 37 publications

A Chimeric Dengue Virus Vaccine using Japanese Encephalitis Virus Vaccine Strain SA14-14-2 as Backbone Is Immunogenic and Protective against Either Parental Virus in Mice and Nonhuman Primates

A Chimeric Dengue Virus Vaccine using Japanese Encephalitis Virus Vaccine Strain SA14-14-2 as Backbone Is Immunogenic and Protective against Either Parental Virus in Mice and Nonhuman Primates

Development of sanofi pasteur tetravalent dengue vaccine

Vector Competence of Australian Mosquitoes for Yellow Fever Virus

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