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encoding the prM and E proteins with the corresponding genes from JE SA 14-14-2.(Chambers et al., 1999). The Chimeric cDNA was then reverse transcribed to RNA,which was used to transfect African green monkey kidney (Vero) cells. Thenucleocapsid (C) protein, non-structural proteins, and non-translated terminiresponsible for virus replication remain those of the original YF 17D virus. TheChimeric virus replicates efficiently in vitro and in vivo. Monath et. al., (2002) gavea single subcutaneous injection of the vaccine to four groups of six volunteers, whowere either immune or not immune to YF from previous vaccination. All groupshad same mild symptoms and side effects as those elicited by YFI7D. The vaccineraised high titres of neutralizing antibodies against JE at doses of 10 5 and 10 4 plagueforming units. This vaccine IS itself a live-attenuated virus, sharing with other suchvaccines an ability to replicate in the host and to generate an array of antigens thatprovoke antibody and cell-mediated immune responses that result in exceptionaldurable, long-term immunological memory and usually lifelong protection.Applying this same, methodology, four dengue vaccines have been made byintroducing DEN-I-4 (prM and E genes into the backbone of YFV).Presently a total of six of such vaccines ore in late-stage development forDENs. Four of these vaccines are chimeras, generated by introducing prM and Egenes from DEN into the full-length cDNA of attenuated YF or DENs (panel)(Halstead and Deen, 2002). Passing each of the four DENs in non-human tissuecultures has made additional two vaccines. The first of these vaccines wasdeveloped at Mahidol University, Bangkok, and Licensed to Aventis Pasteur, Lyon,France. In this instance, DEN-I, 2, and 4 were serially passaged in primary dogkidney (PDK) cells while DEN-3 was passaged in African green monkey kidneycells (Bhamarapravati and Yoksan, 1997). When two doses of the resulting vaccineswere given to 130 chidren aged 3-14 years, seroconversion rates for tetravalentneutralizing antibody were observed in 80-90% (Bhamarapravati and Yoksan,2000).. A phase 3 trials in children is being planned (Halstead and Deen, 2002).In a separate effort at the Waiter Reed Army Institute of Research, SilverSpring, MD, USA, all four DENs were serially passaged in PDK cells and candidatevaccines produced by a final passage in fetal lung cells from the rhesus monkey(FRLL). After inoculation in SO adult volunteers, 80-90% developed neutralizingantibodies to all four viruses after two doses (Edelrnan et al., 2003). Phase 1 and 254

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