Chimeric dengue type 2 (vaccine strain PDK-53)/dengue type 1 virus as a potential candidate dengue type 1 virus vaccine

We constructed chimeric dengue type 2/type 1 (DEN-2/DEN-1) viruses containi ng the nonstructural genes of DEN-2 16681 virus or its vaccine derivative, strain PDK-53, and the structural genes (encoding capsid protein, premembra ne protein, and envelope glycoprotein) of DEN-I 16007 virus or its vaccine derivative, strain PDK-13, We previously reported that attenuation markers of DEN-2 PDK-53 virus were encoded by genetic loci located outside the stru ctural gene region of the PDK-53 virus genome. Chimeric viruses containing the nonstructural genes of DEN-2 PDK-53 virus and the structural genes of t he parental DEN-1 16007 virus retained the attenuation markers of small pla que size and temperature sensitivity in LLC-MK2 cells, less efficient repli cation in C6/36 cells, and attenuation for mice. These chimeric viruses eli cited higher mouse neutralizing antibody titers against DEN-I virus than di d the candidate DEN-I PDK-13 vaccine virus or chimeric DEN-2/DEN-1 viruses containing the structural genes of the PDK-13 virus. Mutations in the envel ope protein of DEN-I PDK-13 virus affected in vitro phenotype and immunogen icity in mice. The current PDK-13 vaccine is the least efficient of the fou r Mahidol candidate DEN virus vaccines in human trials. The chimeric DEN-2/ DEN-1 virus might be a potential DEN-1 virus vaccine candidate. This study indicated that the infectious clones derived from the candidate DEN-2 PDK-5 3 vaccine are promising attenuated vectors for development of chimeric flav ivirus vaccines.