%0 Journal Article
%T Vaccine candidates derived from a novel infectious cDNA clone of an American genotype dengue virus type 2
%A Joseph E Blaney
%A Christopher T Hanson
%A Kathryn A Hanley
%A Brian R Murphy
%A Stephen S Whitehead
%J BMC Infectious Diseases
%D 2004
%I BioMed Central
%R 10.1186/1471-2334-4-39
%X A full-length cDNA clone was generated from the DEN-2 virus and used to produce recombinant DEN-2 (rDEN-2) and rDEN2¦¤30. Viruses were evaluated for replication in SCID mice transplanted with human hepatoma cells (SCID-HuH-7 mice), in mosquitoes, and in rhesus monkeys. Neutralizing antibody induction and protective efficacy were also assessed in rhesus monkeys.The rDEN2¦¤30 virus was ten-fold reduced in replication in SCID-HuH-7 mice when compared to the parent virus. The rDEN-2 viruses were not infectious for Aedes mosquitoes, but both readily infected Toxorynchites mosquitoes. In rhesus monkeys, rDEN2¦¤30 appeared to be slightly attenuated when compared to the parent virus as measured by duration and peak of viremia and neutralizing antibody induction. A derivative of rDEN2¦¤30, designated rDEN2¦¤30-4995, was generated by incorporation of a point mutation previously identified in the NS3 gene of DEN-4 and was found to be more attenuated than rDEN2¦¤30 in SCID-HuH-7 mice.The rDEN2¦¤30 and rDEN2¦¤30-4995 viruses can be considered for evaluation in humans and for inclusion in a tetravalent dengue vaccine.The increased prevalence of disease caused by the mosquito-borne dengue (DEN) viruses (four serotypes; DEN-1 ¨C DEN-4) has intensified the effort to generate a vaccine that would both confer protection and be economically feasible for use in countries with limited resources for healthcare [1]. Dengue fever and dengue hemorrhagic fever and shock (DHF/DSS) are a severe disease burden for tropical and semitropical countries inhabited by more than 2.5 billion people [2]. Risk factors for the more severe disease, DHF/DSS, include the strain of virus, age and genetic background of the host, and secondary infection by a DEN serotype different from that which caused the primary infection [2]. Increased risk associated with secondary infection by a different DEN serotype is believed to be caused both by increased virus replication resulting from antibody-dependent enhancement and by a
%U http://www.biomedcentral.com/1471-2334/4/39